BACKGROUND Calculus bovis(CB),used in traditional Chinese medicine,exhibits anti-tumor effects in various cancer models.It also constitutes an integral component of a compound formulation known as Pien Tze Huang,which...BACKGROUND Calculus bovis(CB),used in traditional Chinese medicine,exhibits anti-tumor effects in various cancer models.It also constitutes an integral component of a compound formulation known as Pien Tze Huang,which is indicated for the treatment of liver cancer.However,its impact on the liver cancer tumor microenvironment,particularly on tumor-associated macrophages(TAMs),is not well understood.AIM To elucidate the anti-liver cancer effect of CB by inhibiting M2-TAM polarization via Wnt/β-catenin pathway modulation.METHODS This study identified the active components of CB using UPLC-Q-TOF-MS,evaluated its anti-neoplastic effects in a nude mouse model,and elucidated the underlying mechanisms via network pharmacology,transcriptomics,and molecular docking.In vitro assays were used to investigate the effects of CB-containing serum on HepG2 cells and M2-TAMs,and Wnt pathway modulation was validated by real-time reverse transcriptase-polymerase chain reaction and Western blot analysis.RESULTS This study identified 22 active components in CB,11 of which were detected in the bloodstream.Preclinical investigations have demonstrated the ability of CB to effectively inhibit liver tumor growth.An integrated approach employing network pharmacology,transcriptomics,and molecular docking implicated the Wnt signaling pathway as a target of the antineoplastic activity of CB by suppressing M2-TAM polarization.In vitro and in vivo experiments further confirmed that CB significantly hinders M2-TAM polarization and suppresses Wnt/β-catenin pathway activation.The inhibitory effect of CB on M2-TAMs was reversed when treated with the Wnt agonist SKL2001,confirming its pathway specificity.CONCLUSION This study demonstrated that CB mediates inhibition of M2-TAM polarization through the Wnt/β-catenin pathway,contributing to the suppression of liver cancer growth.展开更多
Tibetan singing bowls emit low-frequency sounds and produce perceptible harmonic tones and vibrations through manual tapping.The sounds the singing bowls produce have been shown to enhance relaxation and reduce anxiet...Tibetan singing bowls emit low-frequency sounds and produce perceptible harmonic tones and vibrations through manual tapping.The sounds the singing bowls produce have been shown to enhance relaxation and reduce anxiety.However,the underlying mechanism remains unclear.In this study,we used chronic restraint stress or sleep deprivation to establish mouse models of anxiety that exhibit anxiety-like behaviors.We then supplied treatment with singing bowls in a bottomless cage placed on the top of a cushion.We found that unlike in humans,the combination of harmonic tones and vibrations did not improve anxietylike behaviors in mice,while individual vibration components did.Additionally,the vibration of singing bowls increased the level of N-methyl-D-aspartate receptor 1 in the somatosensory cortex and prefrontal cortex of the mice,decreased the level ofγ-aminobutyric acid A(GABA)receptorα1 subtype,reduced the level of CaMKII in the prefrontal cortex,and increased the number of GABAergic interneurons.At the same time,electrophysiological tests showed that the vibration of singing bowls significantly reduced the abnormal low-frequency gamma oscillation peak frequency in the medial prefrontal cortex caused by stress restraint pressure and sleep deprivation.Results from this study indicate that the vibration of singing bowls can alleviate anxiety-like behaviors by reducing abnormal molecular and electrophysiological events in somatosensory and medial prefrontal cortex.展开更多
BACKGROUND Hormone replacement therapy is an effective treatment strategy for the management of symptoms in naturally menopausal women.However,some patients report experiencing adverse effects.AIM To analyze the effec...BACKGROUND Hormone replacement therapy is an effective treatment strategy for the management of symptoms in naturally menopausal women.However,some patients report experiencing adverse effects.AIM To analyze the effects of hormone replacement therapy in menopausal female patients.METHODS A total of 152 menopausal female patients admitted to the Gynecology Department of the Ganzhou Maternal and Child Health Hospital between January 2021 and December 2023 were divided into the observation group(n=76,conventional treatment+hormone replacement therapy)and the control group(n=76,conventional treatment only)via random casting.The improvement observed in the following items were compared between the groups:Kupperman menopausal index(KMI),emotional state[The Positive and Negative Affect Scale(PANAS)],sleep quality[Self-Rating Scale of Sleep(SRSS)],treatment effectiveness,and treatment safety.RESULTS The modified KMI and SRSS scores of the observation group were lower than those of the control group after three rounds of treatment.The improvement in the PANAS score observed in the observation group was greater than that observed in the control group(P<0.05).The total treatment effectivity rate in the observation group was higher than that in the control group(86.84%vs 96.05%,χ2=4.121,P=0.042).The incidence rate of adverse reactions in the two groups was comparable(6.58%vs 9.21%,χ2=0.361,P=0.547).CONCLUSION Hormone replacement therapy effectively improved the clinical symptoms,actively channeled negative emotions,and improved the quality of sleep in menopausal patients,indicating its effectiveness and safety.展开更多
The rice planthopper,Sogatella furcifera,is a piercing-sucking insect pest of rice,Oryza sativa.It is responsible for significant crop yield losses,and has developed moderate to high resistance to several commonly use...The rice planthopper,Sogatella furcifera,is a piercing-sucking insect pest of rice,Oryza sativa.It is responsible for significant crop yield losses,and has developed moderate to high resistance to several commonly used chemical insecticides.We investigated the effects of the insect fungal pathogen Isaria javanica,alone and in combination with the chemical insecticide dinotefuran,on S.furcifera under both laboratory and field conditions.Our results show that I.javanica displays high infection efficiency and mortality for different stages of S.furcifera,reducing adult survival,female oviposition and ovary development.Laboratory bioassays showed that the combined use of I.javanica with a low dose(4-16 mg L^(-1))of dinotefuran resulted in higher mortality in S.furcifera than the use of I.javanica or dinotefuran alone.The combined treatment also had more significant effects on several host enzymes,including superoxide dismutase,catalase,peroxidase,and prophenol oxidase activities.In field trials,I.javanica effectively suppressed populations of rice planthoppers to low levels(22-64%of the level in untreated plots).Additional field experiments showed synergistic effects,i.e.,enhanced efficiency,for the control of S.furcifera populations using the combination of a low dose of I.javanica(1×10^(4) conidia mL^(-1))and a low dose of dinotefuran(~4.8-19.2%of normal field use levels),with control effects of>90%and a population level under 50 insects per 100 hills at 3-14 days post-treatment.Our findings indicate that the entomogenous fungus I.javanica offers an attractive biological control addition as part of the integrated pest management(IPM)practices for the control of rice plant pests.展开更多
Chemical-looping oxidative dehydrogenation(CL-ODH)is a process designed for the conversion of alkanes into olefins through cyclic redox reactions,eliminating the need for gaseous O_(2).In this work,we investigated the...Chemical-looping oxidative dehydrogenation(CL-ODH)is a process designed for the conversion of alkanes into olefins through cyclic redox reactions,eliminating the need for gaseous O_(2).In this work,we investigated the use of Ca_(2)MnO_(4)-layered perovskites modified with NaNO_(3) dopants,serving as redox catalysts(also known as oxygen carriers),for the CL-ODH of ethane within a temperature range of 700-780℃.Our findings revealed that the incorporation of NaNO_(3) as a modifier significantly-nhanced the selectivity for-thylene generation from Ca_(2)MnO_(4).At 750℃and a gas hourly space velocity of 1300 h^(-1),we achieved an-thane conversion up to 68.17%,accompanied by a corresponding-thylene yield of 57.39%.X-ray photoelectron spectroscopy analysis unveiled that the doping NaNO_(3) onto Ca_(2)MnO_(4) not only played a role in reducing the oxidation state of Mn ions but also increased the lattice oxygen content of the redox catalyst.Furthermore,formation of NaNO_(3) shell on the surface of Ca_(2)MnO_(4) led to a reduction in the concentration of manganese sites and modulated the oxygen-releasing behavior in a step-wise manner.This modulation contributed significantly to the enhanced selectivity for ethylene of the NaNO_(3)-doped Ca_(2)MnO_(4) catalyst.These findings provide compelling evidence for the potential of Ca_(2)MnO_(4)-layered perovskites as promising redox catalysts in the context of CL-ODH reactions.展开更多
Genetic manipulation(either restraint or enhancement)of the biosynthesis pathway ofα-linolenic acid(ALA)in seed oil is an important goal in Brassica napus breeding.B.napus is a tetraploid plant whose genome often har...Genetic manipulation(either restraint or enhancement)of the biosynthesis pathway ofα-linolenic acid(ALA)in seed oil is an important goal in Brassica napus breeding.B.napus is a tetraploid plant whose genome often har-bors four and six homologous copies,respectively,of the two fatty acid desaturases FAD2 and FAD3,which con-trol the last two steps of ALA biosynthesis during seed oil accumulation.In this study,we compared their promoters,coding sequences,and expression levels in three high-ALA inbred lines 2006L,R8Q10,and YH25005,a low-ALA line A28,a low-ALA/high-oleic-acid accession SW,and the wildtype ZS11.The expression levels of most FAD2 and FAD3 homologs in the three high-ALA accessions were higher than those in ZS11 and much higher than those in A28 and SW.The three high-ALA accessions shared similar sequences with the pro-moters and CDSs of BnFAD3.C4 and BnFAD3.A3.In A28 and SW,substitution of three amino acid residues in BnFAD2.A5 and BnFAD2.C5,an absence of BnFAD2.C1 locus,and a 549 bp long deletion on the BnFAD3.A3 promoter were detected.The profile of BnFAD2 mutation in the two low-ALA accessions A28 and SW is different from that reported in previous studies.The mutations in BnFAD3 in the high-ALA accessions are reported for thefirst time.In identifying the sites of these mutations,we provide detailed information to aid the design of mole-cular markers for accelerated breeding schemes.展开更多
The progress in medical imaging technology highlights the importance of image quality for effective diagnosis and treatment.Yet,noise during capture and transmission can compromise image accuracy and reliability,compl...The progress in medical imaging technology highlights the importance of image quality for effective diagnosis and treatment.Yet,noise during capture and transmission can compromise image accuracy and reliability,complicating clinical decisions.The rising interest in diffusion models has led to their exploration of denoising images.We present Be-FOI(Better Fluoro Images),a weakly supervised model that uses cine images to denoise fluoroscopic images,both DR types.Trained through precise noise estimation and simulation,BeFOI employs Markov chains to denoise using only the fluoroscopic image as guidance.Our tests show that BeFOI outperforms other methods,reducing noise and enhancing clar-ity and diagnostic utility,making it an effective post-processing tool for medical images.展开更多
BACKGROUND The phosphoinositide 3-kinase/protein kinase-B/mechanistic target of rapamycin(PI3K/Akt/mTOR) signalling pathway is crucial for cell survival, differentiation, apoptosis and metabolism. Xihuang pills(XHP) a...BACKGROUND The phosphoinositide 3-kinase/protein kinase-B/mechanistic target of rapamycin(PI3K/Akt/mTOR) signalling pathway is crucial for cell survival, differentiation, apoptosis and metabolism. Xihuang pills(XHP) are a traditional Chinese preparation with antitumour properties. They inhibit the growth of breast cancer, glioma, and other tumours by regulating the PI3K/Akt/mTOR signalling pathway. However, the effects and mechanisms of action of XHP in hepatocellular carcinoma(HCC) remain unclear. Regulation of the PI3K/Akt/mTOR signalling pathway effectively inhibits the progression of HCC. However, no study has focused on the XHPassociated PI3K/Akt/mTOR signalling pathway. Therefore, we hypothesized that XHP might play a role in inhibiting HCC through the PI3K/Akt/mTOR signalling pathway.AIM To confirm the effect of XHP on HCC and the possible mechanisms involved.METHODS The chemical constituents and active components of XHP were analysed using ultra-performance liquid chromatography-quadrupole time of flight mass spectrometry(UPLC-Q-TOF-MS). Cellbased experiments and in vivo xenograft tumour experiments were utilized to evaluate the effect of XHP on HCC tumorigenesis. First, SMMC-7721 cells were incubated with different concentrations of XHP(0, 0.3125, 0.625, 1.25, and 2.5 mg/mL) for 12 h, 24 h and 48 h. Cell viability was assessed using the CCK-8 assay, followed by an assessment of cell migration using a wound healing assay.Second, the effect of XHP on the apoptosis of SMMC-7721 cells was evaluated. SMMC-7721 cells were stained with fluorescein isothiocyanate and annexin V/propidium iodide. The number of apoptotic cells and cell cycle distribution were measured using flow cytometry. The cleaved protein and mRNA expression levels of caspase-3 and caspase-9 were detected using Western blotting and quantitative reverse-transcription polymerase chain reaction(RT-qPCR), respectively.Third, Western blotting and RT–qPCR were performed to confirm the effects of XHP on the protein and mRNA expression of components of the PI3K/Akt/mTOR signalling pathway.Finally, the effects of XHP on the tumorigenesis of subcutaneous hepatocellular tumours in nude mice were assessed.RESULTS The following 12 compounds were identified in XHP using high-resolution mass spectrometry:Valine, 4-gingerol, myrrhone, ricinoleic acid, glycocholic acid, curzerenone, 11-keto-β-boswellic acid, oleic acid, germacrone, 3-acetyl-9,11-dehydro-β-boswellic acid, 5β-androstane-3,17-dione, and 3-acetyl-11-keto-β-boswellic acid. The cell viability assay results showed that treatment with 0.625mg/mL XHP extract decreased HCC cell viability after 12 h, and the effects were dose-and timedependent. The results of the cell scratch assay showed that the migration of HCC cells was significantly inhibited in a time-dependent manner by the administration of XHP extract(0.625mg/mL). Moreover, XHP significantly inhibited cell migration and resulted in cell cycle arrest and apoptosis. Furthermore, XHP downregulated the PI3K/Akt/mTOR signalling pathway, which activated apoptosis executioner proteins(e.g., caspase-9 and caspase-3). The inhibitory effects of XHP on HCC cell growth were determined in vivo by analysing the tumour xenograft volumes and weights.CONCLUSION XHP inhibited HCC cell growth and migration by stimulating apoptosis via the downregulation of the PI3K/Akt/mTOR signalling pathway, followed by the activation of caspase-9 and caspase-3.Our findings clarified that the antitumour effects of XHP on HCC cells are mediated by the PI3K/Akt/mTOR signalling pathway, revealing that XHP may be a potential complementary therapy for HCC.展开更多
BACKGROUND Centipedes have been used to treat tumors for hundreds of years in China.However,current studies focus on antimicrobial and anticoagulation agents rather than tumors.The molecular identities of antihepatoma...BACKGROUND Centipedes have been used to treat tumors for hundreds of years in China.However,current studies focus on antimicrobial and anticoagulation agents rather than tumors.The molecular identities of antihepatoma bioactive components in centipedes have not yet been extensively investigated.It is a challenge to isolate and characterize the effective components of centipedes due to limited peptide purification technologies for animal-derived medicines.AIM To purify,characterize,and synthesize the bioactive components with the strongest antihepatoma activity from centipedes and determine the antihepatoma mechanism.METHODS An antihepatoma peptide(scolopentide)was isolated and identified from the centipede scolopendra subspinipes mutilans using a combination of enzymatic hydrolysis,a Sephadex G-25 column,and two steps of high-performance liquid chromatography(HPLC).Additionally,the CCK8 assay was used to select the extracted fraction with the strongest antihepatoma activity.The molecular weight of the extracted scolopentide was characterized by quadrupole time of flight mass spectrometry(QTOF MS),and the sequence was matched by using the Mascot search engine.Based on the sequence and molecular weight,scolopentide was synthesized using solid-phase peptide synthesis methods.The synthetic scolopentide was confirmed by MS and HPLC.The antineoplastic effect of extracted scolopentide was confirmed by CCK8 assay and morphological changes again in vitro.The antihepatoma effect of synthetic scolopentide was assessed by the CCK8 assay and Hoechst staining in vitro and tumor volume and tumor weight in vivo.In the tumor xenograft experiments,qualified model mice(male 5-week-old BALB/c nude mice)were randomly divided into 2 groups(n=6):The scolopentide group(0.15 mL/d,via intraperitoneal injection of synthetic scolopentide,500 mg/kg/d)and the vehicle group(0.15 mL/d,via intraperitoneal injection of normal saline).The mice were euthanized by cervical dislocation after 14 d of continuous treatment.Mechanistically,flow cytometry was conducted to evaluate the apoptosis rate of HepG2 cells after treatment with extracted scolopentide in vitro.A Hoechst staining assay was also used to observe apoptosis in HepG2 cells after treatment with synthetic scolopentide in vitro.CCK8 assays and morphological changes were used to compare the cytotoxicity of synthetic scolopentide to liver cancer cells and normal liver cells in vitro.Molecular docking was performed to clarify whether scolopentide tightly bound to death receptor 4(DR4)and DR5.qRT-PCR was used to measure the mRNA expression of DR4,DR5,fas-associated death domain protein(FADD),Caspase-8,Caspase-3,cytochrome c(Cyto-C),B-cell lymphoma-2(Bcl-2),Bcl-2-associated X protein(Bax),x-chromosome linked inhibitor-of-apoptosis protein and Cellular fas-associated death domain-like interleukin-1βconverting enzyme inhibitory protein in hepatocarcinoma subcutaneous xenograft tumors from mice.Western blot assays were used to measure the protein expression of DR4,DR5,FADD,Caspase-8,Caspase-3,and Cyto-C in the tumor tissues.The reactive oxygen species(ROS)of tumor tissues were tested.RESULTS In the process of purification,characterization and synthesis of scolopentide,the optimal enzymatic hydrolysis conditions(extract ratio:5.86%,IC_(50):0.310 mg/mL)were as follows:Trypsin at 0.1 g(300 U/g,centipede-trypsin ratio of 20:1),enzymolysis temperature of 46°C,and enzymolysis time of 4 h,which was superior to freeze-thawing with liquid nitrogen(IC_(50):3.07 mg/mL).A peptide with the strongest antihepatoma activity(scolopentide)was further purified through a Sephadex G-25 column(obtained A2)and two steps of HPLC(obtained B5 and C3).The molecular weight of the extracted scolopentide was 1018.997 Da,and the peptide sequence was RAQNHYCK,as characterized by QTOF MS and Mascot.Scolopentide was synthesized in vitro with a qualified molecular weight(1018.8 Da)and purity(98.014%),which was characterized by MS and HPLC.Extracted scolopentide still had an antineoplastic effect in vitro,which inhibited the proliferation of Eca-109(IC_(50):76.27μg/mL),HepG2(IC_(50):22.06μg/mL),and A549(IC_(50):35.13μg/mL)cells,especially HepG2 cells.Synthetic scolopentide inhibited the proliferation of HepG2 cells(treated 6,12,and 24 h)in a concentration-dependent manner in vitro,and the inhibitory effects were the strongest at 12 h(IC_(50):208.11μg/mL).Synthetic scolopentide also inhibited the tumor volume(Vehicle vs Scolopentide,P=0.0003)and weight(Vehicle vs Scolopentide,P=0.0022)in the tumor xenograft experiment.Mechanistically,flow cytometry suggested that the apoptosis ratios of HepG2 cells after treatment with extracted scolopentide were 5.01%(0μg/mL),12.13%(10μg/mL),16.52%(20μg/mL),and 23.20%(40μg/mL).Hoechst staining revealed apoptosis in HepG2 cells after treatment with synthetic scolopentide in vitro.The CCK8 assay and morphological changes indicated that synthetic scolopentide was cytotoxic and was significantly stronger in HepG2 cells than in L02 cells.Molecular docking suggested that scolopentide tightly bound to DR4 and DR5,and the binding free energies were-10.4 kcal/mol and-7.1 kcal/mol,respectively.In subcutaneous xenograft tumors from mice,quantitative real-time polymerase chain reaction and western blotting suggested that scolopentide activated DR4 and DR5 and induced apoptosis in SMMC-7721 Liver cancer cells by promoting the expression of FADD,caspase-8 and caspase-3 through a mitochondria-independent pathway.CONCLUSION Scolopentide,an antihepatoma peptide purified from centipedes,may inspire new antihepatoma agents.Scolopentide activates DR4 and DR5 and induces apoptosis in liver cancer cells through a mitochondria-independent pathway.展开更多
Gas drainage is an efective technology for gas control in coal mines.A high borehole-sealing quality is the fundamental precondition for efcient gas drainage.The expansibilities of cement pastes used in borehole-seali...Gas drainage is an efective technology for gas control in coal mines.A high borehole-sealing quality is the fundamental precondition for efcient gas drainage.The expansibilities of cement pastes used in borehole-sealing processes are critical for the borehole-sealing efect.Nanosized magnesia expansive agents are used to improve the expansibilities of cement pastes and improve the borehole-sealing efect.Nuclear magnetic resonance spectrometry and scanning electron microscopy were adopted to study the efects of nanosized magnesia on the hydration of borehole-sealing cements used with diferent preparation methods.The results showed that an increase in the mass fraction of the nanosized magnesia promoted cement hydration,and the mass fraction was positively correlated with the promotion efect.The use of diferent preparation methods did not change the water-phase distribution in the cement.When using the wet-mixing preparation method,nanosized magnesia promoted the induction,acceleration,and deceleration periods of hydration;when using the dry-mixing preparation method,the nanosized magnesia promoted the induction period of cement hydration,and the promotion efect was less obvious than that seen when using the wet-mixing method.When using the wet-mixing preparation method,the nanosized magnesia was uniformly dispersed,thus enlarging the surface area of the reaction,which provided more nucleation sites for the hydration products of the cement and therefore accelerated the hydration reaction.When using the dry-mixing preparation method,the nanosized magnesia powders were dispersed nonuniformly and aggregated.Under these conditions,only a few nanosized magnesia particles on the surfaces of the aggregated clusters took part in hydration,so only a small number of nucleation sites were provided for the hydration products of cement.This led to inconsistent hydration of cement pastes prepared using the dry-mixing method.The surface porosity of the cement prepared with the wet-mixing preparation method frst decreased and then increased with increases in the mass fraction of the nanosized magnesia.The cement surface exhibited compact hydration products and few pores,and the surface was relatively smooth.In comparison,the surface porosity of the cement prepared using the dry-mixing method fuctuated with increasing mass fraction of the nanosized magnesia,resulting in a rough cement surface and microfractures on some surfaces.The two preparation methods both reduced the surface porosity of the cement.The wet-mixing preparation was more efective and consistent in improving the compactness of the cement than the dry-mixing preparation.These results provide important guidance on the addition of nanosized magnesia in borehole-sealing engineering and the selection of cement preparation methods,and they also lay a solid foundation for realizing safe and efcient gas drainage.展开更多
AIM:To assess the long-term outcomes of treating macular edema(ME)associated with central retinal vein occlusion(CRVO)with a regimen of“5+pro re nata(PRN)”.METHODS:This retrospective study included 27 eyes of 27 pat...AIM:To assess the long-term outcomes of treating macular edema(ME)associated with central retinal vein occlusion(CRVO)with a regimen of“5+pro re nata(PRN)”.METHODS:This retrospective study included 27 eyes of 27 patients with ME associated with non-ischemic CRVO(non-iCRVO group,n=15)and ischemic CRVO(iCRVO group,n=12).The eyes were treated with five consecutive intravitreal injections of conbercept or ranibizumab,followed by reinjections as needed or PRN.Retinal laser photocoagulation or intravitreal dexamethasone implants(DEX)were implemented in both groups when necessary.The best-corrected visual acuity(BCVA,logMAR)and central retinal thickness(CRT)were recorded at baseline,at 1,2,3,4,5,6,and 12mo,and at the final visit.The efficacy rates of BCVA and CRT before and after treatment were calculated.The number of injections at each visit and the incidence of adverse events were also recorded.RESULTS:The patients,aged 59.4±15.1y,were followed up for 24.7±8.8mo(range:15-42mo).After treatment,BCVA improved significantly from 1.04±0.56 logMAR at baseline to 0.59±0.36 logMAR(P=0.038)at the final visit in all patients.Both the non-iCRVO and the iCRVO groups achieved improved BCVA compared to the baseline at all visit points,but there was no statistical significance(P=0.197 and 0.33,respectively).The mean CRT was statistically reduced compared to baseline at all visit points in all the eyes and in both groups(all P<0.001).The apparent effective rate was 22.22% for BCVA and 37.04% for CRT after the first injection,48.15%for BCVA and 62.96% for CRT after 5 consecutive injections,and 74.08% for BCVA and 100% for CRT at the end of follow up.The average number of injections in all patients was 9.0±2.4 at 12mo and 14.9±8.1 finally with no statistical significance between both groups(P>0.05).Laser treatment was applied to all eyes in the iCRVO group,while only 5 patients in the noniCRVO group.Six patients in the non-iCRVO group and 3 patients in the iCRVO group had a drug switch.DEX was applied to 4 eyes in the non-iCRVO group and 5 eyes in the iCRVO group.CONCLUSION:The 5+PRN anti-vascular endothelial growth factor(VEGF)regimen is found to be safe and effective for both iCRVO and non-iCRVO,especially in the iCRVO group.The best regimen for such patients needs to be further investigated.Adjuvant laser therapy and DEX are necessary in some cases.展开更多
Targeted muscle reinnervation has been proposed for reconstruction of neuromuscular function in amputees.However,it is unknown whether performing delayed targeted muscle reinnervation after nerve injury will affect re...Targeted muscle reinnervation has been proposed for reconstruction of neuromuscular function in amputees.However,it is unknown whether performing delayed targeted muscle reinnervation after nerve injury will affect restoration of function.In this rat nerve injury study,the median and musculocutaneous nerves of the forelimb were transected.The proximal median nerve stump was sutured to the distal musculocutaneous nerve stump immediately and 2 and 4 weeks after surgery to reinnervate the biceps brachii.After targeted muscle reinnervation,intramuscular myoelectric signals from the biceps brachii were recorded.Signal amplitude gradually increased with time.Biceps brachii myoelectric signals and muscle fiber morphology and grooming behavior did not significantly differ among rats subjected to delayed target muscle innervation for different periods.Targeted muscle reinnervation delayed for 4 weeks can acquire the same nerve function restoration effect as that of immediate reinnervation.展开更多
During June-July 2020,the strongest recorded mei-yu rainfall occurred in the middle and lower reaches of the Yangtze River.The rainfall processes exhibited an obvious quasi-biweekly(biweekly in brief)variability,and t...During June-July 2020,the strongest recorded mei-yu rainfall occurred in the middle and lower reaches of the Yangtze River.The rainfall processes exhibited an obvious quasi-biweekly(biweekly in brief)variability,and there are altogether five cycles.It is found that the biweekly rainfall cycle mainly arises from the collaborative effects of biweekly variabilities from both the tropics and extratropics.As for the tropics,the biweekly meridional march and retreat of the western Pacific subtropical high(WPSH)is particularly evident.As for the extratropics,geopotential height anomalies near Lake Baikal are active.The former is attributed to the intensified biweekly activity of the southwest-northeast oriented EastAsian Pacific wave train(EAP)originating from the tropical western Pacific,while the latter is associated with the biweekly activities of the eastward propagating Eurasia mid-high latitudinal wave train and the westward propagating North Pacific wave train.Why the biweekly activities of these wave trains intensified is further diagnosed from the perspective of thermodynamical forcing and also from the modulation of interannual background on intraseasonal variability.It is found that the strongest recorded convection anchoring over the tropical western Indian Ocean(IO)triggers anomalous descent over the tropical western Pacific,which modulates the biweekly activity of the EAP.Meanwhile,the anomalous diabatic heating over the IO causes changes of the meridional thermodynamic contrast across the IO to the high latitudes,which modulates the extratropical wave trains.A further diagnosis of barotropic kinetic energy conversion suggests that the active occurrence of two extratropical biweekly wave trains is attributed to the increased efficiency of energy conversion from basic flow.The westward propagation of the extratropical North Pacific wave train is attributed to the weakened and northshifted upper-level westerly,which is caused by the SST warmth near the Kuroshio extension.展开更多
目的比较单孔胸腔镜手术(uniportal VATS)与单操作孔胸腔镜手术(single utility port VATS)治疗自发性气胸的疗效。方法回顾性收集2013年1月-2015年12月收治自发性气胸行uniportal VATS治疗的53例患者作为实验组,对照同期53例行single u...目的比较单孔胸腔镜手术(uniportal VATS)与单操作孔胸腔镜手术(single utility port VATS)治疗自发性气胸的疗效。方法回顾性收集2013年1月-2015年12月收治自发性气胸行uniportal VATS治疗的53例患者作为实验组,对照同期53例行single utility port VATS治疗的患者作为对照组,比较两组的手术时间、术中出血量、胸管放置时间、术后住院时间、术后疼痛、术后并发症及远期复发等临床指标。结果 106例患者均顺利完成手术,无死亡及严重并发症发生。实验组和对照组比较,术后24 h疼痛视觉模拟评分(VAS)为(2.60±0.71)vs(3.38±0.84),术后72 h VAS为(1.30±0.51)vs(1.58±0.62),实验组较对照组术后24和72 h疼痛减轻(P<0.05)。两组患者手术时间、术中出血、胸管引流时间、术后住院时间、手术费用和术后并发症的差异均无统计学意义(P>0.05)。随访时间5~36个月,平均19个月,术后无气胸复发。结论单孔胸腔镜治疗自发性气胸与单操作孔两种方法同样安全有效,但单孔法术后疼痛程度更轻,近期疗效满意,值得进一步临床推广。展开更多
Objective: To compare the two skeletal muscle mass index (SMI) algorithms. One is SMM [SMM(%) = total skeletal muscle mass (kg)/body weight mass (kg) × 100%];and the other is SMH [SMH (kg/m<sup>2</sup>...Objective: To compare the two skeletal muscle mass index (SMI) algorithms. One is SMM [SMM(%) = total skeletal muscle mass (kg)/body weight mass (kg) × 100%];and the other is SMH [SMH (kg/m<sup>2</sup>) = total skeletal muscle mass (kg)/height (m)<sup>2</sup>]. Methods: Body composition, body mass index (BMI) and body fat percentage (BFP) were estimated using a bioelectrical impedance analyzer. SMI was calculated by the two algorithms described above, and measurement parameters were stratified by age, BMI and levels of physical activity. Results: Levels of BMI, BFP, SMM and SMH differed significantly between the sexes. BMI and BFP were positively associated with age, while SMM was negatively associated with age (β = −0.2294, P < 0.001). Furthermore, SMM was determined to have a negative association with BMI (β = −0.5340, P < 0.001), while a positive association between SMH and BMI (β = 0.7930, P β = −0.9849, P β = −0.0642, P < 0.001) were negatively associated with BFP. In both men and women, SMM maintained the analogous correlation with other indicators. In the general population, SMM showed a gradual downward trend from low body weight to grade III obesity (F = 9528.32, P < 0.001), but SMH (F = 34395.46, P F = 9706.20, P < 0.001) had a reciprocal association. BMI, BFP and SMM differences were observed based on levels of physical activity (P < 0.001). However, there was no significant difference in SMH based on exercise (P > 0.05). Conclusions: SMM may be a more ideal and accurate clinical algorithm for SMI because it is more tightly associated with other body composition indices, as compared with SMH.展开更多
Objective: Anti-angiogenic drugs are an emerging treatment option against malignant tumors. The aim of this study was to determine whether the addition of perioperative rh-endostatin to chemotherapy could improve the ...Objective: Anti-angiogenic drugs are an emerging treatment option against malignant tumors. The aim of this study was to determine whether the addition of perioperative rh-endostatin to chemotherapy could improve the probability of distant metastasis-free survival(DMFS) and overall survival(OS) in patients newly diagnosed with non-metastatic conventional osteosarcoma.Methods: This was a controlled non-randomized clinical study that included 388 patients without clinically detectable metastatic disease enrolled from January 2008 to April 2012. The control treatment group had 272 patients; 180 were male and 92, female,with a median age of 17 years. The treatment group had 58 patients; 36 were male and 22, female, with a median age of 16 years.The control group received preoperative chemotherapy followed by surgery and postoperative chemotherapy. The treatment group received 4 cycles of rh-endostatin perioperatively in addition to chemotherapy as per the control group. Patients were followed up from 6-101 months with a median follow-up period of 50.2 months.Results: The 5-year DMFS of the control group(61%) was significantly lower than that of the rh-endostatin group(79%)(P = 0.013). The 5-year OS of the control group(74%) was significantly lower than that of the rh-endostatin treatment group(87%)(P = 0.029). No difference in adverse drug reactions was found between these 2 groups.Conclusions: The addition of perioperative rh-endostatin to chemotherapy could significantly improve the DMFS and OS of patients with non-metastatic osteosarcoma.展开更多
In this study,uniaxial and triaxial compression acoustic emission(AE)tests were implemented to investigate the AE effect and failure characteristics of sandstone under different confining pressures(σ3).The evolution ...In this study,uniaxial and triaxial compression acoustic emission(AE)tests were implemented to investigate the AE effect and failure characteristics of sandstone under different confining pressures(σ3).The evolution of AE parameters in the rock failure process and fracture fractal dimension characteristics after failure were analyzed.The results revealed that the activity of the AE signal is strongly related toσ3.The evolution of the Ib value can be divided into the I-fluctuation,II-stability,and III-decrease stages.In the first stage,the Ib value of the AE was relatively high,and the AE energy was low.Then,the Ib value tended to be stable;however,the fluctuation amplitude decreased,and the AE energy rapidly increased.In the stage of decrease,the AE energy sharply increased before the load approached the peak value,and the Ib value significantly decreased and dropped to the lowest point before the peak value.Asσ3 increased,the rock’s failure mode changed from tensile failure to shear failure and became more coordinated.As the confining pressure increased,the shape dimension decreased,and the order degree of rock failure increased.The confining pressure exerted a certain control effect on the rock failure.展开更多
基金Supported by National Natural Science Foundation of China,No.82074450Education Department of Hunan Province,No.21A0243,No.21B0374,No.22B0397,and No.22B0392+2 种基金Research Project of"Academician Liu Liang Workstation"of Hunan University of Traditional Chinese Medicine,No.21YS003Hunan Administration of Traditional Chinese Medicine,No.B2023001 and No.B2023009Hunan Provincial Natural Science Foundation of China,No.2023JJ40481。
文摘BACKGROUND Calculus bovis(CB),used in traditional Chinese medicine,exhibits anti-tumor effects in various cancer models.It also constitutes an integral component of a compound formulation known as Pien Tze Huang,which is indicated for the treatment of liver cancer.However,its impact on the liver cancer tumor microenvironment,particularly on tumor-associated macrophages(TAMs),is not well understood.AIM To elucidate the anti-liver cancer effect of CB by inhibiting M2-TAM polarization via Wnt/β-catenin pathway modulation.METHODS This study identified the active components of CB using UPLC-Q-TOF-MS,evaluated its anti-neoplastic effects in a nude mouse model,and elucidated the underlying mechanisms via network pharmacology,transcriptomics,and molecular docking.In vitro assays were used to investigate the effects of CB-containing serum on HepG2 cells and M2-TAMs,and Wnt pathway modulation was validated by real-time reverse transcriptase-polymerase chain reaction and Western blot analysis.RESULTS This study identified 22 active components in CB,11 of which were detected in the bloodstream.Preclinical investigations have demonstrated the ability of CB to effectively inhibit liver tumor growth.An integrated approach employing network pharmacology,transcriptomics,and molecular docking implicated the Wnt signaling pathway as a target of the antineoplastic activity of CB by suppressing M2-TAM polarization.In vitro and in vivo experiments further confirmed that CB significantly hinders M2-TAM polarization and suppresses Wnt/β-catenin pathway activation.The inhibitory effect of CB on M2-TAMs was reversed when treated with the Wnt agonist SKL2001,confirming its pathway specificity.CONCLUSION This study demonstrated that CB mediates inhibition of M2-TAM polarization through the Wnt/β-catenin pathway,contributing to the suppression of liver cancer growth.
基金supported by the National Natural Science Foundation of ChinaNos.32170950(to LY),31970915(to LY),31871170(to CL)+4 种基金the Natural Science Foundation of Guangdong Province for Major Cultivation ProjectNo.2018B030336001(to LY)the Natural Science Foundation of Guangdong Province,Nos.2021A1515010804(to CL),2023A1515010899(to CL)the Guangdong Grant‘Key Technologies for Treatment of Brain Disorders’No.2018B030332001(to CL)。
文摘Tibetan singing bowls emit low-frequency sounds and produce perceptible harmonic tones and vibrations through manual tapping.The sounds the singing bowls produce have been shown to enhance relaxation and reduce anxiety.However,the underlying mechanism remains unclear.In this study,we used chronic restraint stress or sleep deprivation to establish mouse models of anxiety that exhibit anxiety-like behaviors.We then supplied treatment with singing bowls in a bottomless cage placed on the top of a cushion.We found that unlike in humans,the combination of harmonic tones and vibrations did not improve anxietylike behaviors in mice,while individual vibration components did.Additionally,the vibration of singing bowls increased the level of N-methyl-D-aspartate receptor 1 in the somatosensory cortex and prefrontal cortex of the mice,decreased the level ofγ-aminobutyric acid A(GABA)receptorα1 subtype,reduced the level of CaMKII in the prefrontal cortex,and increased the number of GABAergic interneurons.At the same time,electrophysiological tests showed that the vibration of singing bowls significantly reduced the abnormal low-frequency gamma oscillation peak frequency in the medial prefrontal cortex caused by stress restraint pressure and sleep deprivation.Results from this study indicate that the vibration of singing bowls can alleviate anxiety-like behaviors by reducing abnormal molecular and electrophysiological events in somatosensory and medial prefrontal cortex.
文摘BACKGROUND Hormone replacement therapy is an effective treatment strategy for the management of symptoms in naturally menopausal women.However,some patients report experiencing adverse effects.AIM To analyze the effects of hormone replacement therapy in menopausal female patients.METHODS A total of 152 menopausal female patients admitted to the Gynecology Department of the Ganzhou Maternal and Child Health Hospital between January 2021 and December 2023 were divided into the observation group(n=76,conventional treatment+hormone replacement therapy)and the control group(n=76,conventional treatment only)via random casting.The improvement observed in the following items were compared between the groups:Kupperman menopausal index(KMI),emotional state[The Positive and Negative Affect Scale(PANAS)],sleep quality[Self-Rating Scale of Sleep(SRSS)],treatment effectiveness,and treatment safety.RESULTS The modified KMI and SRSS scores of the observation group were lower than those of the control group after three rounds of treatment.The improvement in the PANAS score observed in the observation group was greater than that observed in the control group(P<0.05).The total treatment effectivity rate in the observation group was higher than that in the control group(86.84%vs 96.05%,χ2=4.121,P=0.042).The incidence rate of adverse reactions in the two groups was comparable(6.58%vs 9.21%,χ2=0.361,P=0.547).CONCLUSION Hormone replacement therapy effectively improved the clinical symptoms,actively channeled negative emotions,and improved the quality of sleep in menopausal patients,indicating its effectiveness and safety.
基金funded by grants from the Science and Technology Planning Project of Guangzhou,China(202002020029)the Science and Technology Planning Project of Guangdong Province,China(2019B020217003)+1 种基金the National Key R&D Program of China(2018YFD02003)the National Key Technology Support Program of China(201303019-02)。
文摘The rice planthopper,Sogatella furcifera,is a piercing-sucking insect pest of rice,Oryza sativa.It is responsible for significant crop yield losses,and has developed moderate to high resistance to several commonly used chemical insecticides.We investigated the effects of the insect fungal pathogen Isaria javanica,alone and in combination with the chemical insecticide dinotefuran,on S.furcifera under both laboratory and field conditions.Our results show that I.javanica displays high infection efficiency and mortality for different stages of S.furcifera,reducing adult survival,female oviposition and ovary development.Laboratory bioassays showed that the combined use of I.javanica with a low dose(4-16 mg L^(-1))of dinotefuran resulted in higher mortality in S.furcifera than the use of I.javanica or dinotefuran alone.The combined treatment also had more significant effects on several host enzymes,including superoxide dismutase,catalase,peroxidase,and prophenol oxidase activities.In field trials,I.javanica effectively suppressed populations of rice planthoppers to low levels(22-64%of the level in untreated plots).Additional field experiments showed synergistic effects,i.e.,enhanced efficiency,for the control of S.furcifera populations using the combination of a low dose of I.javanica(1×10^(4) conidia mL^(-1))and a low dose of dinotefuran(~4.8-19.2%of normal field use levels),with control effects of>90%and a population level under 50 insects per 100 hills at 3-14 days post-treatment.Our findings indicate that the entomogenous fungus I.javanica offers an attractive biological control addition as part of the integrated pest management(IPM)practices for the control of rice plant pests.
基金support of National Natural Science Foundation of China(22179027)gratefully acknowledged.This work was also supported by the Natural Science Foundation of Guangxi Province(2021GXNSFAA075063,2018GXNSFDA281005)+1 种基金the National Key Research and Development Program of China(2017YFE0105500)Science&Technology Research Project of Guangdong Province(2017A020216009).
文摘Chemical-looping oxidative dehydrogenation(CL-ODH)is a process designed for the conversion of alkanes into olefins through cyclic redox reactions,eliminating the need for gaseous O_(2).In this work,we investigated the use of Ca_(2)MnO_(4)-layered perovskites modified with NaNO_(3) dopants,serving as redox catalysts(also known as oxygen carriers),for the CL-ODH of ethane within a temperature range of 700-780℃.Our findings revealed that the incorporation of NaNO_(3) as a modifier significantly-nhanced the selectivity for-thylene generation from Ca_(2)MnO_(4).At 750℃and a gas hourly space velocity of 1300 h^(-1),we achieved an-thane conversion up to 68.17%,accompanied by a corresponding-thylene yield of 57.39%.X-ray photoelectron spectroscopy analysis unveiled that the doping NaNO_(3) onto Ca_(2)MnO_(4) not only played a role in reducing the oxidation state of Mn ions but also increased the lattice oxygen content of the redox catalyst.Furthermore,formation of NaNO_(3) shell on the surface of Ca_(2)MnO_(4) led to a reduction in the concentration of manganese sites and modulated the oxygen-releasing behavior in a step-wise manner.This modulation contributed significantly to the enhanced selectivity for ethylene of the NaNO_(3)-doped Ca_(2)MnO_(4) catalyst.These findings provide compelling evidence for the potential of Ca_(2)MnO_(4)-layered perovskites as promising redox catalysts in the context of CL-ODH reactions.
基金The study was financially supported by Projects from Shaanxi Province(2021LLRH-07-03-01 and 2023-ZDLNY-07)Yangling Seed Industry Innovation(YLzy-yc2021-01).The funders had no role in study design,data collection and analysis,decision to publish,or preparation of the manuscript.
文摘Genetic manipulation(either restraint or enhancement)of the biosynthesis pathway ofα-linolenic acid(ALA)in seed oil is an important goal in Brassica napus breeding.B.napus is a tetraploid plant whose genome often har-bors four and six homologous copies,respectively,of the two fatty acid desaturases FAD2 and FAD3,which con-trol the last two steps of ALA biosynthesis during seed oil accumulation.In this study,we compared their promoters,coding sequences,and expression levels in three high-ALA inbred lines 2006L,R8Q10,and YH25005,a low-ALA line A28,a low-ALA/high-oleic-acid accession SW,and the wildtype ZS11.The expression levels of most FAD2 and FAD3 homologs in the three high-ALA accessions were higher than those in ZS11 and much higher than those in A28 and SW.The three high-ALA accessions shared similar sequences with the pro-moters and CDSs of BnFAD3.C4 and BnFAD3.A3.In A28 and SW,substitution of three amino acid residues in BnFAD2.A5 and BnFAD2.C5,an absence of BnFAD2.C1 locus,and a 549 bp long deletion on the BnFAD3.A3 promoter were detected.The profile of BnFAD2 mutation in the two low-ALA accessions A28 and SW is different from that reported in previous studies.The mutations in BnFAD3 in the high-ALA accessions are reported for thefirst time.In identifying the sites of these mutations,we provide detailed information to aid the design of mole-cular markers for accelerated breeding schemes.
文摘The progress in medical imaging technology highlights the importance of image quality for effective diagnosis and treatment.Yet,noise during capture and transmission can compromise image accuracy and reliability,complicating clinical decisions.The rising interest in diffusion models has led to their exploration of denoising images.We present Be-FOI(Better Fluoro Images),a weakly supervised model that uses cine images to denoise fluoroscopic images,both DR types.Trained through precise noise estimation and simulation,BeFOI employs Markov chains to denoise using only the fluoroscopic image as guidance.Our tests show that BeFOI outperforms other methods,reducing noise and enhancing clar-ity and diagnostic utility,making it an effective post-processing tool for medical images.
基金Supported by National Natural Science Foundation of China, No. U20A20408 and No. 82074450Natural Science Foundation of Hunan Province, No. 2020JJ4066+4 种基金Hunan Province"Domestic First-class Cultivation Discipline"Integrated Traditional Chinese and Western Medicine Open Fund Project, No. 2020ZXYJH34 and No. 2020ZXYJH35Hunan Graduate Scientific Research Innovation Project, No. QL20210173 and No. CX20210730Hunan Province Science and Technology Innovation Talents Plan College Students Science and Technology Innovation and Entrepreneurship Project, No. 2020RC1004Guangzhou Health Science and Technology Project, No. 20221A011102Hunan Traditional Chinese Medicine Scientific Research Project, No. 202101
文摘BACKGROUND The phosphoinositide 3-kinase/protein kinase-B/mechanistic target of rapamycin(PI3K/Akt/mTOR) signalling pathway is crucial for cell survival, differentiation, apoptosis and metabolism. Xihuang pills(XHP) are a traditional Chinese preparation with antitumour properties. They inhibit the growth of breast cancer, glioma, and other tumours by regulating the PI3K/Akt/mTOR signalling pathway. However, the effects and mechanisms of action of XHP in hepatocellular carcinoma(HCC) remain unclear. Regulation of the PI3K/Akt/mTOR signalling pathway effectively inhibits the progression of HCC. However, no study has focused on the XHPassociated PI3K/Akt/mTOR signalling pathway. Therefore, we hypothesized that XHP might play a role in inhibiting HCC through the PI3K/Akt/mTOR signalling pathway.AIM To confirm the effect of XHP on HCC and the possible mechanisms involved.METHODS The chemical constituents and active components of XHP were analysed using ultra-performance liquid chromatography-quadrupole time of flight mass spectrometry(UPLC-Q-TOF-MS). Cellbased experiments and in vivo xenograft tumour experiments were utilized to evaluate the effect of XHP on HCC tumorigenesis. First, SMMC-7721 cells were incubated with different concentrations of XHP(0, 0.3125, 0.625, 1.25, and 2.5 mg/mL) for 12 h, 24 h and 48 h. Cell viability was assessed using the CCK-8 assay, followed by an assessment of cell migration using a wound healing assay.Second, the effect of XHP on the apoptosis of SMMC-7721 cells was evaluated. SMMC-7721 cells were stained with fluorescein isothiocyanate and annexin V/propidium iodide. The number of apoptotic cells and cell cycle distribution were measured using flow cytometry. The cleaved protein and mRNA expression levels of caspase-3 and caspase-9 were detected using Western blotting and quantitative reverse-transcription polymerase chain reaction(RT-qPCR), respectively.Third, Western blotting and RT–qPCR were performed to confirm the effects of XHP on the protein and mRNA expression of components of the PI3K/Akt/mTOR signalling pathway.Finally, the effects of XHP on the tumorigenesis of subcutaneous hepatocellular tumours in nude mice were assessed.RESULTS The following 12 compounds were identified in XHP using high-resolution mass spectrometry:Valine, 4-gingerol, myrrhone, ricinoleic acid, glycocholic acid, curzerenone, 11-keto-β-boswellic acid, oleic acid, germacrone, 3-acetyl-9,11-dehydro-β-boswellic acid, 5β-androstane-3,17-dione, and 3-acetyl-11-keto-β-boswellic acid. The cell viability assay results showed that treatment with 0.625mg/mL XHP extract decreased HCC cell viability after 12 h, and the effects were dose-and timedependent. The results of the cell scratch assay showed that the migration of HCC cells was significantly inhibited in a time-dependent manner by the administration of XHP extract(0.625mg/mL). Moreover, XHP significantly inhibited cell migration and resulted in cell cycle arrest and apoptosis. Furthermore, XHP downregulated the PI3K/Akt/mTOR signalling pathway, which activated apoptosis executioner proteins(e.g., caspase-9 and caspase-3). The inhibitory effects of XHP on HCC cell growth were determined in vivo by analysing the tumour xenograft volumes and weights.CONCLUSION XHP inhibited HCC cell growth and migration by stimulating apoptosis via the downregulation of the PI3K/Akt/mTOR signalling pathway, followed by the activation of caspase-9 and caspase-3.Our findings clarified that the antitumour effects of XHP on HCC cells are mediated by the PI3K/Akt/mTOR signalling pathway, revealing that XHP may be a potential complementary therapy for HCC.
基金Supported by the National Natural Science Foundation of China,No.U20A20408 and No.82074450Natural Science Foundation of Hunan Province,No.2020JJ4066 and No.2021JJ40405+1 种基金Key scientific research project of Hunan Education Department,No.21A0243Key project of academician workstation guidance project,No.21YSZQ007.
文摘BACKGROUND Centipedes have been used to treat tumors for hundreds of years in China.However,current studies focus on antimicrobial and anticoagulation agents rather than tumors.The molecular identities of antihepatoma bioactive components in centipedes have not yet been extensively investigated.It is a challenge to isolate and characterize the effective components of centipedes due to limited peptide purification technologies for animal-derived medicines.AIM To purify,characterize,and synthesize the bioactive components with the strongest antihepatoma activity from centipedes and determine the antihepatoma mechanism.METHODS An antihepatoma peptide(scolopentide)was isolated and identified from the centipede scolopendra subspinipes mutilans using a combination of enzymatic hydrolysis,a Sephadex G-25 column,and two steps of high-performance liquid chromatography(HPLC).Additionally,the CCK8 assay was used to select the extracted fraction with the strongest antihepatoma activity.The molecular weight of the extracted scolopentide was characterized by quadrupole time of flight mass spectrometry(QTOF MS),and the sequence was matched by using the Mascot search engine.Based on the sequence and molecular weight,scolopentide was synthesized using solid-phase peptide synthesis methods.The synthetic scolopentide was confirmed by MS and HPLC.The antineoplastic effect of extracted scolopentide was confirmed by CCK8 assay and morphological changes again in vitro.The antihepatoma effect of synthetic scolopentide was assessed by the CCK8 assay and Hoechst staining in vitro and tumor volume and tumor weight in vivo.In the tumor xenograft experiments,qualified model mice(male 5-week-old BALB/c nude mice)were randomly divided into 2 groups(n=6):The scolopentide group(0.15 mL/d,via intraperitoneal injection of synthetic scolopentide,500 mg/kg/d)and the vehicle group(0.15 mL/d,via intraperitoneal injection of normal saline).The mice were euthanized by cervical dislocation after 14 d of continuous treatment.Mechanistically,flow cytometry was conducted to evaluate the apoptosis rate of HepG2 cells after treatment with extracted scolopentide in vitro.A Hoechst staining assay was also used to observe apoptosis in HepG2 cells after treatment with synthetic scolopentide in vitro.CCK8 assays and morphological changes were used to compare the cytotoxicity of synthetic scolopentide to liver cancer cells and normal liver cells in vitro.Molecular docking was performed to clarify whether scolopentide tightly bound to death receptor 4(DR4)and DR5.qRT-PCR was used to measure the mRNA expression of DR4,DR5,fas-associated death domain protein(FADD),Caspase-8,Caspase-3,cytochrome c(Cyto-C),B-cell lymphoma-2(Bcl-2),Bcl-2-associated X protein(Bax),x-chromosome linked inhibitor-of-apoptosis protein and Cellular fas-associated death domain-like interleukin-1βconverting enzyme inhibitory protein in hepatocarcinoma subcutaneous xenograft tumors from mice.Western blot assays were used to measure the protein expression of DR4,DR5,FADD,Caspase-8,Caspase-3,and Cyto-C in the tumor tissues.The reactive oxygen species(ROS)of tumor tissues were tested.RESULTS In the process of purification,characterization and synthesis of scolopentide,the optimal enzymatic hydrolysis conditions(extract ratio:5.86%,IC_(50):0.310 mg/mL)were as follows:Trypsin at 0.1 g(300 U/g,centipede-trypsin ratio of 20:1),enzymolysis temperature of 46°C,and enzymolysis time of 4 h,which was superior to freeze-thawing with liquid nitrogen(IC_(50):3.07 mg/mL).A peptide with the strongest antihepatoma activity(scolopentide)was further purified through a Sephadex G-25 column(obtained A2)and two steps of HPLC(obtained B5 and C3).The molecular weight of the extracted scolopentide was 1018.997 Da,and the peptide sequence was RAQNHYCK,as characterized by QTOF MS and Mascot.Scolopentide was synthesized in vitro with a qualified molecular weight(1018.8 Da)and purity(98.014%),which was characterized by MS and HPLC.Extracted scolopentide still had an antineoplastic effect in vitro,which inhibited the proliferation of Eca-109(IC_(50):76.27μg/mL),HepG2(IC_(50):22.06μg/mL),and A549(IC_(50):35.13μg/mL)cells,especially HepG2 cells.Synthetic scolopentide inhibited the proliferation of HepG2 cells(treated 6,12,and 24 h)in a concentration-dependent manner in vitro,and the inhibitory effects were the strongest at 12 h(IC_(50):208.11μg/mL).Synthetic scolopentide also inhibited the tumor volume(Vehicle vs Scolopentide,P=0.0003)and weight(Vehicle vs Scolopentide,P=0.0022)in the tumor xenograft experiment.Mechanistically,flow cytometry suggested that the apoptosis ratios of HepG2 cells after treatment with extracted scolopentide were 5.01%(0μg/mL),12.13%(10μg/mL),16.52%(20μg/mL),and 23.20%(40μg/mL).Hoechst staining revealed apoptosis in HepG2 cells after treatment with synthetic scolopentide in vitro.The CCK8 assay and morphological changes indicated that synthetic scolopentide was cytotoxic and was significantly stronger in HepG2 cells than in L02 cells.Molecular docking suggested that scolopentide tightly bound to DR4 and DR5,and the binding free energies were-10.4 kcal/mol and-7.1 kcal/mol,respectively.In subcutaneous xenograft tumors from mice,quantitative real-time polymerase chain reaction and western blotting suggested that scolopentide activated DR4 and DR5 and induced apoptosis in SMMC-7721 Liver cancer cells by promoting the expression of FADD,caspase-8 and caspase-3 through a mitochondria-independent pathway.CONCLUSION Scolopentide,an antihepatoma peptide purified from centipedes,may inspire new antihepatoma agents.Scolopentide activates DR4 and DR5 and induces apoptosis in liver cancer cells through a mitochondria-independent pathway.
基金supported by“Overall Rationing System”Project of Chongqing Talent Program(cstc2022ycjh-bgzxm0077)the National Natural Science Foundation of China(52074041)+1 种基金Natural Science Foundation of Chongqing,China(cstc2020jcyj-msxmX0836)Fundamental Research Funds for the Central Universities(2020CDJ-LHZZ-002),which are gratefully acknowledged.
文摘Gas drainage is an efective technology for gas control in coal mines.A high borehole-sealing quality is the fundamental precondition for efcient gas drainage.The expansibilities of cement pastes used in borehole-sealing processes are critical for the borehole-sealing efect.Nanosized magnesia expansive agents are used to improve the expansibilities of cement pastes and improve the borehole-sealing efect.Nuclear magnetic resonance spectrometry and scanning electron microscopy were adopted to study the efects of nanosized magnesia on the hydration of borehole-sealing cements used with diferent preparation methods.The results showed that an increase in the mass fraction of the nanosized magnesia promoted cement hydration,and the mass fraction was positively correlated with the promotion efect.The use of diferent preparation methods did not change the water-phase distribution in the cement.When using the wet-mixing preparation method,nanosized magnesia promoted the induction,acceleration,and deceleration periods of hydration;when using the dry-mixing preparation method,the nanosized magnesia promoted the induction period of cement hydration,and the promotion efect was less obvious than that seen when using the wet-mixing method.When using the wet-mixing preparation method,the nanosized magnesia was uniformly dispersed,thus enlarging the surface area of the reaction,which provided more nucleation sites for the hydration products of the cement and therefore accelerated the hydration reaction.When using the dry-mixing preparation method,the nanosized magnesia powders were dispersed nonuniformly and aggregated.Under these conditions,only a few nanosized magnesia particles on the surfaces of the aggregated clusters took part in hydration,so only a small number of nucleation sites were provided for the hydration products of cement.This led to inconsistent hydration of cement pastes prepared using the dry-mixing method.The surface porosity of the cement prepared with the wet-mixing preparation method frst decreased and then increased with increases in the mass fraction of the nanosized magnesia.The cement surface exhibited compact hydration products and few pores,and the surface was relatively smooth.In comparison,the surface porosity of the cement prepared using the dry-mixing method fuctuated with increasing mass fraction of the nanosized magnesia,resulting in a rough cement surface and microfractures on some surfaces.The two preparation methods both reduced the surface porosity of the cement.The wet-mixing preparation was more efective and consistent in improving the compactness of the cement than the dry-mixing preparation.These results provide important guidance on the addition of nanosized magnesia in borehole-sealing engineering and the selection of cement preparation methods,and they also lay a solid foundation for realizing safe and efcient gas drainage.
文摘AIM:To assess the long-term outcomes of treating macular edema(ME)associated with central retinal vein occlusion(CRVO)with a regimen of“5+pro re nata(PRN)”.METHODS:This retrospective study included 27 eyes of 27 patients with ME associated with non-ischemic CRVO(non-iCRVO group,n=15)and ischemic CRVO(iCRVO group,n=12).The eyes were treated with five consecutive intravitreal injections of conbercept or ranibizumab,followed by reinjections as needed or PRN.Retinal laser photocoagulation or intravitreal dexamethasone implants(DEX)were implemented in both groups when necessary.The best-corrected visual acuity(BCVA,logMAR)and central retinal thickness(CRT)were recorded at baseline,at 1,2,3,4,5,6,and 12mo,and at the final visit.The efficacy rates of BCVA and CRT before and after treatment were calculated.The number of injections at each visit and the incidence of adverse events were also recorded.RESULTS:The patients,aged 59.4±15.1y,were followed up for 24.7±8.8mo(range:15-42mo).After treatment,BCVA improved significantly from 1.04±0.56 logMAR at baseline to 0.59±0.36 logMAR(P=0.038)at the final visit in all patients.Both the non-iCRVO and the iCRVO groups achieved improved BCVA compared to the baseline at all visit points,but there was no statistical significance(P=0.197 and 0.33,respectively).The mean CRT was statistically reduced compared to baseline at all visit points in all the eyes and in both groups(all P<0.001).The apparent effective rate was 22.22% for BCVA and 37.04% for CRT after the first injection,48.15%for BCVA and 62.96% for CRT after 5 consecutive injections,and 74.08% for BCVA and 100% for CRT at the end of follow up.The average number of injections in all patients was 9.0±2.4 at 12mo and 14.9±8.1 finally with no statistical significance between both groups(P>0.05).Laser treatment was applied to all eyes in the iCRVO group,while only 5 patients in the noniCRVO group.Six patients in the non-iCRVO group and 3 patients in the iCRVO group had a drug switch.DEX was applied to 4 eyes in the non-iCRVO group and 5 eyes in the iCRVO group.CONCLUSION:The 5+PRN anti-vascular endothelial growth factor(VEGF)regimen is found to be safe and effective for both iCRVO and non-iCRVO,especially in the iCRVO group.The best regimen for such patients needs to be further investigated.Adjuvant laser therapy and DEX are necessary in some cases.
基金supported in part by the National Natural Science Foundation of China,Nos.U1913601,81927804the Key-Area Research and Development Program of Guangdong Province,No.2020B0909020004(GL)the National Natural Science Foundation of China,Nos.81960419,82260456(both to LY)。
文摘Targeted muscle reinnervation has been proposed for reconstruction of neuromuscular function in amputees.However,it is unknown whether performing delayed targeted muscle reinnervation after nerve injury will affect restoration of function.In this rat nerve injury study,the median and musculocutaneous nerves of the forelimb were transected.The proximal median nerve stump was sutured to the distal musculocutaneous nerve stump immediately and 2 and 4 weeks after surgery to reinnervate the biceps brachii.After targeted muscle reinnervation,intramuscular myoelectric signals from the biceps brachii were recorded.Signal amplitude gradually increased with time.Biceps brachii myoelectric signals and muscle fiber morphology and grooming behavior did not significantly differ among rats subjected to delayed target muscle innervation for different periods.Targeted muscle reinnervation delayed for 4 weeks can acquire the same nerve function restoration effect as that of immediate reinnervation.
基金jointly supported by the National Key Research and Development Program of China(Grant No.2018YFA0606403)the National Natural Science Foundation of China(Grant Nos.41731177 and 41790473)。
文摘During June-July 2020,the strongest recorded mei-yu rainfall occurred in the middle and lower reaches of the Yangtze River.The rainfall processes exhibited an obvious quasi-biweekly(biweekly in brief)variability,and there are altogether five cycles.It is found that the biweekly rainfall cycle mainly arises from the collaborative effects of biweekly variabilities from both the tropics and extratropics.As for the tropics,the biweekly meridional march and retreat of the western Pacific subtropical high(WPSH)is particularly evident.As for the extratropics,geopotential height anomalies near Lake Baikal are active.The former is attributed to the intensified biweekly activity of the southwest-northeast oriented EastAsian Pacific wave train(EAP)originating from the tropical western Pacific,while the latter is associated with the biweekly activities of the eastward propagating Eurasia mid-high latitudinal wave train and the westward propagating North Pacific wave train.Why the biweekly activities of these wave trains intensified is further diagnosed from the perspective of thermodynamical forcing and also from the modulation of interannual background on intraseasonal variability.It is found that the strongest recorded convection anchoring over the tropical western Indian Ocean(IO)triggers anomalous descent over the tropical western Pacific,which modulates the biweekly activity of the EAP.Meanwhile,the anomalous diabatic heating over the IO causes changes of the meridional thermodynamic contrast across the IO to the high latitudes,which modulates the extratropical wave trains.A further diagnosis of barotropic kinetic energy conversion suggests that the active occurrence of two extratropical biweekly wave trains is attributed to the increased efficiency of energy conversion from basic flow.The westward propagation of the extratropical North Pacific wave train is attributed to the weakened and northshifted upper-level westerly,which is caused by the SST warmth near the Kuroshio extension.
文摘目的比较单孔胸腔镜手术(uniportal VATS)与单操作孔胸腔镜手术(single utility port VATS)治疗自发性气胸的疗效。方法回顾性收集2013年1月-2015年12月收治自发性气胸行uniportal VATS治疗的53例患者作为实验组,对照同期53例行single utility port VATS治疗的患者作为对照组,比较两组的手术时间、术中出血量、胸管放置时间、术后住院时间、术后疼痛、术后并发症及远期复发等临床指标。结果 106例患者均顺利完成手术,无死亡及严重并发症发生。实验组和对照组比较,术后24 h疼痛视觉模拟评分(VAS)为(2.60±0.71)vs(3.38±0.84),术后72 h VAS为(1.30±0.51)vs(1.58±0.62),实验组较对照组术后24和72 h疼痛减轻(P<0.05)。两组患者手术时间、术中出血、胸管引流时间、术后住院时间、手术费用和术后并发症的差异均无统计学意义(P>0.05)。随访时间5~36个月,平均19个月,术后无气胸复发。结论单孔胸腔镜治疗自发性气胸与单操作孔两种方法同样安全有效,但单孔法术后疼痛程度更轻,近期疗效满意,值得进一步临床推广。
文摘Objective: To compare the two skeletal muscle mass index (SMI) algorithms. One is SMM [SMM(%) = total skeletal muscle mass (kg)/body weight mass (kg) × 100%];and the other is SMH [SMH (kg/m<sup>2</sup>) = total skeletal muscle mass (kg)/height (m)<sup>2</sup>]. Methods: Body composition, body mass index (BMI) and body fat percentage (BFP) were estimated using a bioelectrical impedance analyzer. SMI was calculated by the two algorithms described above, and measurement parameters were stratified by age, BMI and levels of physical activity. Results: Levels of BMI, BFP, SMM and SMH differed significantly between the sexes. BMI and BFP were positively associated with age, while SMM was negatively associated with age (β = −0.2294, P < 0.001). Furthermore, SMM was determined to have a negative association with BMI (β = −0.5340, P < 0.001), while a positive association between SMH and BMI (β = 0.7930, P β = −0.9849, P β = −0.0642, P < 0.001) were negatively associated with BFP. In both men and women, SMM maintained the analogous correlation with other indicators. In the general population, SMM showed a gradual downward trend from low body weight to grade III obesity (F = 9528.32, P < 0.001), but SMH (F = 34395.46, P F = 9706.20, P < 0.001) had a reciprocal association. BMI, BFP and SMM differences were observed based on levels of physical activity (P < 0.001). However, there was no significant difference in SMH based on exercise (P > 0.05). Conclusions: SMM may be a more ideal and accurate clinical algorithm for SMI because it is more tightly associated with other body composition indices, as compared with SMH.
基金Ministry of Human Resources and Social Security of the People's Republic of China (MOHRSS) (Grant No. 2017199)
文摘Objective: Anti-angiogenic drugs are an emerging treatment option against malignant tumors. The aim of this study was to determine whether the addition of perioperative rh-endostatin to chemotherapy could improve the probability of distant metastasis-free survival(DMFS) and overall survival(OS) in patients newly diagnosed with non-metastatic conventional osteosarcoma.Methods: This was a controlled non-randomized clinical study that included 388 patients without clinically detectable metastatic disease enrolled from January 2008 to April 2012. The control treatment group had 272 patients; 180 were male and 92, female,with a median age of 17 years. The treatment group had 58 patients; 36 were male and 22, female, with a median age of 16 years.The control group received preoperative chemotherapy followed by surgery and postoperative chemotherapy. The treatment group received 4 cycles of rh-endostatin perioperatively in addition to chemotherapy as per the control group. Patients were followed up from 6-101 months with a median follow-up period of 50.2 months.Results: The 5-year DMFS of the control group(61%) was significantly lower than that of the rh-endostatin group(79%)(P = 0.013). The 5-year OS of the control group(74%) was significantly lower than that of the rh-endostatin treatment group(87%)(P = 0.029). No difference in adverse drug reactions was found between these 2 groups.Conclusions: The addition of perioperative rh-endostatin to chemotherapy could significantly improve the DMFS and OS of patients with non-metastatic osteosarcoma.
基金the financial s upport from the National Natural Science Foundation of China(No.41702326)the Jiangxi Provincial Natural Science Foundation(No.20202ACB214006)+2 种基金the Innovative Experts,Long-term Program of Jiangxi Province(jxsq2018106049)the Supported by Program of Qingjiang Excellent Young Talents,Jiangxi University of Science and Technologythe Innovation Fund Designated for Graduate Students of Jiangxi Province(YC2020-S451)。
文摘In this study,uniaxial and triaxial compression acoustic emission(AE)tests were implemented to investigate the AE effect and failure characteristics of sandstone under different confining pressures(σ3).The evolution of AE parameters in the rock failure process and fracture fractal dimension characteristics after failure were analyzed.The results revealed that the activity of the AE signal is strongly related toσ3.The evolution of the Ib value can be divided into the I-fluctuation,II-stability,and III-decrease stages.In the first stage,the Ib value of the AE was relatively high,and the AE energy was low.Then,the Ib value tended to be stable;however,the fluctuation amplitude decreased,and the AE energy rapidly increased.In the stage of decrease,the AE energy sharply increased before the load approached the peak value,and the Ib value significantly decreased and dropped to the lowest point before the peak value.Asσ3 increased,the rock’s failure mode changed from tensile failure to shear failure and became more coordinated.As the confining pressure increased,the shape dimension decreased,and the order degree of rock failure increased.The confining pressure exerted a certain control effect on the rock failure.