The ultrashort lasers working in pulse-burst mode reveal great machining performance in recent years. The number of pulses in bursts effects greatly on the removal rate and roughness. To generate a more equal amplitud...The ultrashort lasers working in pulse-burst mode reveal great machining performance in recent years. The number of pulses in bursts effects greatly on the removal rate and roughness. To generate a more equal amplitude of pulses in burst with linear polarization output and time gap adjustable, we propose a new method by the harmonic beam combining(HBC).The beam combining is commonly used in adding pulses into the output beam while maintaining the pulse waveform and beam quality. In the HBC, dichroic mirrors are used to combine laser pulses of fundamental wave(FW) into harmonic wave(HW), and nonlinear crystals are used to convert the FW into HW. Therefore, HBC can add arbitrarily more HW pulses to generate pulse-burst in linear polarization with simple structure. The amplitude of each pulse in bursts can be adjusted the same to increase the stability of the burst, the time gap of each pulse can be adjusted precisely by proper time delay. Because HBC adds pulses sequentially, the peak power density of the burst is the same as each pulse, pulses can be combined without concern of back-conversion which often occurs in high peak power density. In the demonstration, the extendibility of HBC was verified by combining two beams with a third beam. The combined efficiency rates were larger than 99%, and the beam quality of each beam was maintained at M^(2)≈1.4.展开更多
Background As the most widely cultivated fiber crop,cotton production depends on hybridization to unlock the yield potential of current varieties.A deep understanding of genetic dissection is crucial for the cultivati...Background As the most widely cultivated fiber crop,cotton production depends on hybridization to unlock the yield potential of current varieties.A deep understanding of genetic dissection is crucial for the cultivation of enhanced hybrid plants with desired traits,such as high yield and fine fiber quality.In this study,the general combining ability(GCA)and specific combining ability(SCA)of yield and fiber quality of nine cotton parents(six lines and three testers)and eighteen F1 crosses produced using a line×tester mating design were analyzed.Results The results revealed significant effects of genotypes,parents,crosses,and interactions between parents and crosses for most of the studied traits.Moreover,the effects of both additive and non-additive gene actions played a notably significant role in the inheritance of most of the yield and fiber quality attributes.The F1 hybrids of(Giza 90×Aust)×Giza 86,Uzbekistan 1×Giza 97,and Giza 96×Giza 97 demonstrated superior performance due to their favorable integration of high yield attributes and premium fiber quality characteristics.Path analysis revealed that lint yield has the highest positive direct effect on seed cotton yield,while lint percentage showed the highest negative direct effect on seed cotton yield.Principal component analysis identified specific parents and hybrids associated with higher cotton yield,fiber quality,and other agronomic traits.Conclusion This study provides insights into identifying potential single-and three-way cross hybrids with superior cotton yield and fiber quality characteristics,laying a foundation for future research on improving fiber quality in cotton.展开更多
BACKGROUND Pancreatic cancer is a leading cause of cancer-related deaths.Increased activity of the epidermal growth factor receptor(EGFR)is often observed in pancreatic cancer,and the small molecule EGFR inhibitor erl...BACKGROUND Pancreatic cancer is a leading cause of cancer-related deaths.Increased activity of the epidermal growth factor receptor(EGFR)is often observed in pancreatic cancer,and the small molecule EGFR inhibitor erlotinib has been approved for pancreatic cancer therapy by the food and drug administration.Nevertheless,erlotinib alone is ineffective and should be combined with other drugs to improve therapeutic outcomes.We previously showed that certain receptor tyrosine kinase inhibitors can increase mitochondrial membrane potential(Δψm),facilitate tumor cell uptake ofΔψm-sensitive agents,disrupt mitochondrial homeostasis,and subsequently trigger tumor cell death.Erlotinib has not been tested for this effect.AIM To determine whether erlotinib can elevateΔψm and increase tumor cell uptake ofΔψm-sensitive agents,subsequently triggering tumor cell death.METHODSΔψm-sensitive fluorescent dye was used to determine how erlotinib affectsΔψm in pancreatic adenocarcinoma(PDAC)cell lines.The viability of conventional and patient-derived primary PDAC cell lines in 2D-and 3D cultures was measured after treating cells sequentially with erlotinib and mitochondria-targeted ubiquinone(MitoQ),aΔψm-sensitive MitoQ.The synergy between erlotinib and MitoQ was then analyzed using SynergyFinder 2.0.The preclinical efficacy of the twodrug combination was determined using immune-compromised nude mice bearing PDAC cell line xenografts.RESULTS Erlotinib elevatedΔψm in PDAC cells,facilitating tumor cell uptake and mitochondrial enrichment ofΔψm-sensitive agents.MitoQ triggered caspase-dependent apoptosis in PDAC cells in culture if used at high doses,while erlotinib pretreatment potentiated low doses of MitoQ.SynergyFinder suggested that these drugs synergistically induced tumor cell lethality.Consistent with in vitro data,erlotinib and MitoQ combination suppressed human PDAC cell line xenografts in mice more effectively than single treatments of each agent.CONCLUSION Our findings suggest that a combination of erlotinib and MitoQ has the potential to suppress pancreatic tumor cell viability effectively.展开更多
Mangroves play a pivotal role in tropical and subtropical coastal ecosystem,yet they are highly vulnerable to the effects of climate change,particularly the accelerated global sea level rise(SLR)and stronger tropical ...Mangroves play a pivotal role in tropical and subtropical coastal ecosystem,yet they are highly vulnerable to the effects of climate change,particularly the accelerated global sea level rise(SLR)and stronger tropical cyclones(TCs).However,there is a lack of research addressing future simultaneous combined impacts of the slow-onset of SLR and rapid-onset of TCs on China's mangroves.In order to develop a comprehensive risk assessment method considering the superimposed effects of these two factors and analyze risk for mangroves in Dongzhaigang,Hainan Island,China,we used observational and climate model data to assess the risks to mangroves under low,intermediate,and very high greenhouse gas(GHG)emission scenarios(such as SSP1-2.6,SSP2-4.5,and SSP5-8.5)in 2030,2050,and 2100,and compiled a risk assessment scheme for mangroves in Dongzhaigang,China.The results showed that the combined risks from SLR and TCs will continue to rise;however,SLRs will increase in intensity,and TCs will decrease.The comprehensive risk of the Dongzhaigang mangroves posed by climate change will remain low under SSP1-2.6 and SSP2-4.5 scenarios by 2030,but it will increase substantially by 2100.While under SSP5-8.5 scenario,the risks to mangroves in Dongzhaigang are projected to increase considerably by 2050,and approximately 68.8%of mangroves will be at very high risk by 2100.The risk to the Dongzhaigang mangroves is not only influenced by the hazards but also closely linked to their exposure and vulnerability.We therefore propose climate resilience developmental responses for mangroves to address the effects of climate change.This study for the combined impact of TCs and SLR on mangroves in Dongzhaigang,China can enrich the method system of mangrove risk assessment and provide references for scientific management.展开更多
Objective:To analyze the importance of general practitioner residents using the combined teaching method(BOPPPS+mind maps).Methods:From September 2023 to August 2024,a study was conducted with 6 control group particip...Objective:To analyze the importance of general practitioner residents using the combined teaching method(BOPPPS+mind maps).Methods:From September 2023 to August 2024,a study was conducted with 6 control group participants receiving traditional teaching and 6 observation group participants receiving the combined teaching method(BOPPPS+mind maps).The study analyzed various indicators between the two groups(including mind map scores and assessment results).Results:Compared with the control group,the assessment scores of the observation group were significantly higher(P<0.05).Conclusion:The application of the combined teaching method(BOPPPS+mind maps)by general practitioner residents can significantly improve their comprehensive abilities.展开更多
Radix Bupleuri(RB)is commonly used to treat depression,but it can also lead to hepatotoxicity after longterm use.In many anti-depression prescriptions,RB is often used in combination with Radix Paeoniae Alba(RPA)as an...Radix Bupleuri(RB)is commonly used to treat depression,but it can also lead to hepatotoxicity after longterm use.In many anti-depression prescriptions,RB is often used in combination with Radix Paeoniae Alba(RPA)as an herb pair.However,whether RPA can alleviate RB-induced hepatotoxicity remain unclear.In this work,the results confirmed that RB had a dose-dependent antidepressant effect,but the optimal antidepressant dose caused hepatotoxicity.Notably,RPA effectively reversed RB-induced hepatotoxicity.Afterward,the mechanism of RB-induced hepatotoxicity was confirmed.The results showed that saikosaponin A and saikosaponin D could inhibit GSH synthase(GSS)activity in the liver,and further cause liver injury through oxidative stress and nuclear factor kappa B(NF-kB)/NOD-like receptor thermal protein domain associated protein 3(NLRP3)pathway.Furthermore,the mechanisms by which RPA attenuates RBinduced hepatotoxicity were investigated.The results demonstrated that RPA increased the abundance of intestinal bacteria with glycosidase activity,thereby promoting the conversion of saikosaponins to saikogenins in vivo.Different from saikosaponin A and saikosaponin D,which are directly combined with GSS as an inhibitor,their deglycosylation conversion products saikogenin F and saikogenin G exhibited no GSS binding activity.Based on this,RPA can alleviate the inhibitory effect of saikosaponins on GSS activity to reshape the liver redox balance and further reverse the RB-induced liver inflammatory response by the NFkB/NLRP3 pathway.In conclusion,the present study suggests that promoting the conversion of saikosaponins by modulating gut microbiota to attenuate the inhibition of GSS is the potential mechanism by which RPA prevents RB-induced hepatotoxicity.展开更多
AIM:To evaluate the postoperative refractive prediction error(PE)and determine the factors that af fect the refractive outcomes of combined pars plana vitrectomy(PPV)or silicone oil removal(SOR)with cataract surgery.M...AIM:To evaluate the postoperative refractive prediction error(PE)and determine the factors that af fect the refractive outcomes of combined pars plana vitrectomy(PPV)or silicone oil removal(SOR)with cataract surgery.METHODS:The study is a retrospective,case-series study.Totally 301 eyes of 301 patients undergoing combined PPV/SOR with cataract surgery were enrolled.Eligible individuals were separated into four groups according to their preoperative diagnoses:silicone oil-filled eyes after PPV(group 1),epiretinal membrane(group 2),macular hole(group 3),and primary retinal detachment(RD;group 4).The variables af fecting postoperative refractive outcomes were analyzed,including age,gender,preoperative best-corrected visual acuity(BCVA),axial length(AL),keratometry average,anterior chamber depth(ACD),intraocular tamponade,and vitreoretinal pathology.The outcome measurements include the mean refractive PE and the proportions of eyes with a PE within±0.50 diopter(D)and±1.00 D.RESULTS:For all patients,the mean PE was-0.04±1.17 D,and 50.17%of patients(eyes)had a PE within±0.50 D.There was a significant difference in refractive outcomes among the four groups(P=0.028),with RD(group 4)showing the least favorable refractive outcome.In multivariate regression analysis,only AL,vitreoretinal pathology,and ACD were strongly associated with PE(all P<0.01).Univariate analysis revealed that longer eyes(AL>26 mm)and a deeper ACD were correlated with hyperopic PE,and shorter eyes(AL<26 mm)and a shallower ACD were correlated with myopic PE.CONCLUSION:RD patients have the least favorable refractive outcome.AL,vitreoretinal pathology,and ACD are strongly associated with PE in the combined surgery.These three factors affect refractive outcomes and thus can be used to predict a better postoperative refractive outcome in clinical practice.展开更多
BACKGROUND Gastric ulcer(GU)is a common digestive tract disease,and medical records of GU combined with depression are increasingly common.Currently,the risk factors and pathogenesis of GU complicated with depression ...BACKGROUND Gastric ulcer(GU)is a common digestive tract disease,and medical records of GU combined with depression are increasingly common.Currently,the risk factors and pathogenesis of GU complicated with depression remain unclear.Low immune function and gastrointestinal hormone levels may also be significant risk factors.Therefore,this study explored the immune function and gastrointestinal hormone levels in patients with GU combined with depression.AIM To explore the immune function,gastrointestinal hormone level,and clinical significance of patients with GU combined with depression.METHODS A retrospective analysis was conducted on 300 patients with GU combined with depression admitted to Guizhou Provincial People’s Hospital from January 2021 to June 2022 as the study subjects.According to the Hamilton Depression Scale(HAMD)score,patients were divided into mild-to-moderate(n=210)and heavy(n=90)groups.Basic data,immune function indices[immunoglobulin A(IgA),IgM,IgG,serum CD4+and CD8+percentage,and CD4+/CD8+ratio],and gastrointestinal hormone indices[serum gastrin(GAS),cholecystokinin(CCK),and motilin(MTL)levels]were collected.The basic data of the two groups were compared,and the immune function and gastrointestinal hormone indices were analyzed.Multivariate logistic regression was used to analyze the factors influencing the severity of GU complicated with depression.The receiver operating characteristic(ROC)curve and area under the ROC curve(AUC)were used to analyze the value of the immune function index,gastrointestinal hormone index,and combined index in predicting the severity of GU complicated with depression.RESULTS There were no marked differences in sex,age,body mass index,abdominal distension,abdominal pain,belching,nausea,vomiting,or sleep disorders between the heavy and mild-to-moderate groups(P>0.05).There was a marked difference in the family history of depression between the heavy and mild-to-moderate groups(P<0.05).There were significant differences in serum IgA and IgM levels and serum CD4+,CD8+,and CD4+/CD8+ratios between the heavy and mild-to-moderate groups(P<0.05).Multivariate analysis showed that IgA,IgM,GAS,and CCK serum levels influenced the severity of GU with depression(P<0.05).The AUC of the ROC curve for serum IgA level predicting GU with depression severity was 0.808[95%confidence interval(CI):0.760-0.857],the AUC of the serum IgM level was 0.757(95%CI:0.700-0.814),the AUC of the serum GAS level was 0.853(95%CI:0.810-0.897),the AUC of the serum CCK level was 0.762(95%CI:0.709-0.822),the AUC of immune function(IgA,IgM)and gastrointestinal hormone levels(GAS,CCK)for the prediction of GU with depression severity was 0.958(95%CI:0.933-0.976).CONCLUSION Important factors influencing GU complicated with depression are serum IgA,IgM,GAS,and CCK indicators.They can be used as indicators to predict the severity of GU complicated with depression.展开更多
The generation of terahertz(THz) waves by focusing a femtosecond pulsed laser beam at a distance is able to overcome the strong absorption properties of air and has rapidly attracted the attention of industry. However...The generation of terahertz(THz) waves by focusing a femtosecond pulsed laser beam at a distance is able to overcome the strong absorption properties of air and has rapidly attracted the attention of industry. However, the poor directionality of the THz wave radiation generated by this method is not conducive to THz wave applications. By controlling the morphology of the ultrafast laser-excited plasma filament and its electron density distribution through coherent beam combining technology, we achieve direct THz beam shaping and are able to obtain THz wave radiation of Gaussian or arbitrary transverse distribution. The novel experimental approach proposed in this paper opens up the research field of direct THz wave shaping using plasma. Moreover, it innovates multi-parameter convergence algorithms and, by doing so, has the potential to find beam patterns with higher energy conversion efficiency and break the energy limit of THz waves emitted by lasers at high power.展开更多
Background For the purpose of utilising hybrid vigour to produce possible hybrids with a suitable level of stability,the knowledge of gene activity and combining ability is a crucial prerequisite before choosing desir...Background For the purpose of utilising hybrid vigour to produce possible hybrids with a suitable level of stability,the knowledge of gene activity and combining ability is a crucial prerequisite before choosing desirable parents.The present study was carried out with six parents crossed in full diallel fashion and generated 30 F1 hybrids.These hybrids were evaluated in two replications in Randomized Block Design at Department of Cotton,TNAU for combining ability and gene action.Diallel analysis was carried out according to Griffing’s method-I(parents + F_(1) + reciprocals) and model-I and Hayman’s graphical approach by using INDOSTAT software.Results Analysis of variance for combining ability indicated that mean square values of GCA,SCA and reciprocals were highly significant for all the traits except for the uniformity index.RG763 and K12 showed highly positively significant GCA effects for most of the yield traits while PA838 and K12 for fibre quality traits,so they were found as best general combiners.PAIG379 × K12 and PDB29 × K12 for yield traits,and PDB29 × PA838,RG763 × PA838,and CNA1007 × RG763 cross combinations for fibre quality traits could be recommended for future breeding programms.Conclusion The results of both Griffing’s and Hayman’s approaches showed that non-additive gene action predominates as SCA variance was bigger than GCA variance,so heterosis breeding is thought to be a more fruitful option for enhancing GCA of many traits.展开更多
Nanomaterials and low-salinity water(LSW)are two popular enhanced oil recovery(EOR)methods that have been widely studied in recent years.The former is used for in-depth conformance improvement and the latter for micro...Nanomaterials and low-salinity water(LSW)are two popular enhanced oil recovery(EOR)methods that have been widely studied in recent years.The former is used for in-depth conformance improvement and the latter for microscopic oil displacement(by altering the potential and contact angle).However,there are few literature on combining them to achieve synergistic effects,especially for tight sandstone res-ervoirs.Based on the reservoir conditions of the Jimusar Oilfield,this study investigated the oil recovery mechanism of the combined imbibition system,which was composed of black nanosheet(BN)and LSW.Its performances including decreasing interfacial tension,emulsification,and wettability alterations were evaluated.The imbibition differences between the single system of BN and LSW and the combined BN-LsW imbibition system were then compared.Results showed that the combined imbibition system had a better emulsification effect on the crude oil and could also alter the wettability of the core surface.Moreover,the combined system could increase both the imbibition rate and the ultimate oil recovery.The nuclear magnetic T2 spectrum also indicated that the addition of black nanosheets could divert more fluid into small pores and thus improve the microscopic sweep efficiency.展开更多
The treatment of patients with inflammatory bowel disease(IBD),especially those with severe or refractory disease,represents an important challenge for the clinical gastroenterologist.It seems to be no exaggeration to...The treatment of patients with inflammatory bowel disease(IBD),especially those with severe or refractory disease,represents an important challenge for the clinical gastroenterologist.It seems to be no exaggeration to say that in these patients,not only the scientific background of the gastroenterologist is tested,but also the abundance of“gifts”that he should possess(insight,intuition,determ-ination,ability to take initiative,etc.)for the successful outcome of the treatment.In daily clinical practice,depending on the severity of the attack,IBD is treated with one or a combination of two or more pharmaceutical agents.These combin-ations include not only the first-line drugs(e.g.,mesalazine,corticosteroids,antibiotics,etc)but also second-and third-line drugs(immunosuppressants and biologic agents).It is a fact that despite the significant therapeutic advances there is still a significant percentage of patients who do not satisfactorily respond to the treatment applied.Therefore,a part of these patients are going to surgery.In recent years,several small-size clinical studies,reviews,and case reports have been published combining not only biological agents with other drugs(e.g.,immunosuppressants or corticosteroids)but also the combination of two biologi-cal agents simultaneously,especially in severe cases.In our opinion,it is at least a strange(and largely unexplained)fact that we often use combinations of drugs in a given patient although studies comparing the simultaneous administration of two or more drugs with monotherapy are very few.As mentioned above,there is a timid tendency in the literature to combine two biological agents in severe cases unresponsive to the applied treatment or patients with severe extraintestinal manifestations.The appropriate dosage,the duration of the administration,the suitable timing for checking the clinical and laboratory outcome,as well as the treatment side-effects,should be the subject of intense clinical research shortly.In this editorial,we attempt to summarize the existing data regarding the already applied combination therapies and to humbly formulate thoughts and suggestions for the future application of the combination treatment of biological agents in a well-defined category of patients.We suggest that the application of biomarkers and artificial intelligence could help in establishing new forms of treatment using the available modern drugs in patients with IBD resistant to treatment.展开更多
The reversible and precise temporal and spatial regulation of histone lysine methyltransferases(KMTs)is essential for epigenome homeostasis.The dysregulation of KMTs is associated with tumor initiation,metastasis,chem...The reversible and precise temporal and spatial regulation of histone lysine methyltransferases(KMTs)is essential for epigenome homeostasis.The dysregulation of KMTs is associated with tumor initiation,metastasis,chemoresistance,invasiveness,and the immune microenvironment.Therapeutically,their promising effects are being evaluated in diversified preclinical and clinical trials,demonstrating encouraging outcomes in multiple malignancies.In this review,we have updated recent understandings of KMTs'functions and the development of their targeted inhibitors.First,we provide an updated overview of the regulatory roles of several KMT activities in oncogenesis,tumor suppression,and immune regulation.In addition,we summarize the current targeting strategies in different cancer types and multiple ongoing clinical trials of combination therapies with KMT inhibitors.In summary,we endeavor to depict the regulation of KMT-mediated epigenetic landscape and provide potential epigenetic targets in the treatment of cancers.展开更多
The clustered regularly interspaced short palindromic repeats(CRISPR)–CRISPR-associated protein(Cas) system has been widely used for genome editing. In this system, the cytosine base editor(CBE) and adenine base edit...The clustered regularly interspaced short palindromic repeats(CRISPR)–CRISPR-associated protein(Cas) system has been widely used for genome editing. In this system, the cytosine base editor(CBE) and adenine base editor(ABE) allow generating precise and irreversible base mutations in a programmable manner and have been used in many different types of cells and organisms. However, their applications are limited by low editing efficiency at certain genomic target sites or at specific target cytosine(C) or adenine(A) residues. Using a strategy of combining optimized synergistic core components, we developed a new multiplex super-assembled ABE(sABE) in rice that showed higher base-editing efficiency than previously developed ABEs. We also designed a new type of nuclear localization signal(NLS) comprising a FLAG epitope tag with four copies of a codon-optimized NLS(F4NLS^(r2)) to generate another ABE named F4NLS-sABE. This new NLS increased editing efficiency or edited additional A at several target sites. A new multiplex super-assembled CBE(sCBE) and F4NLS^(r2) involved F4NLS-sCBE were also created using the same strategy. F4NLS-sCBE was proven to be much more efficient than sCBE in rice. These optimized base editors will serve as powerful genome-editing tools for basic research or molecular breeding in rice and will provide a reference for the development of superior editing tools for other plants or animals.展开更多
Two field experiments were conducted in the main seasons of 2021/22 at the farmers'farm in two districts of southwest Ethiopia to investigate the effects of lime and phosphorus on groundnut yield and yield compone...Two field experiments were conducted in the main seasons of 2021/22 at the farmers'farm in two districts of southwest Ethiopia to investigate the effects of lime and phosphorus on groundnut yield and yield components,employing four levels of lime(0,2,4,and 6 t CaCO_(3)ha^(-1))and phosphorus(0,46,69,and 92 kg P_(2)O_(5)ha^(-1))arranged in factorial RCBD design with three replications.Data on the yield and its components were collected and subjected to an ANOVA using SAS software.The result demonstrated that plant height,number of branches,canopy spread,and shelling percentage were affected significantly by liming while effective nodule number,total peg,matured pod,and pod yield of groundnut significantly influenced by the main factors and their interactions.The combined application of 4 t lime and 46 kg P_(2)O_(5)ha^(-1)resulted in the highest number of effective nodules(147.23 plant^(-1)),total pod(72.6 plant^(-1)),mature pod(62.4 plant^(-1)),pod yield(4.49 t ha^(-1)),oil content(50.6%)and protein content(33.1%)whereas the lowest values of these parameters were seen in plots where neither lime nor phosphorus was applied.Therefore,it is advised that groundnut growers in the study areas,and similar agroecologies,apply the combination of 4 t lime and 46 kg P_(2)O_(5)ha^(-1).展开更多
The genetic analysis of soybean isoflavone content and its components were carried out based on the NC Ⅱ matingdesign in eight soybean varieties. The results showed that the isoflavone contents and its components of ...The genetic analysis of soybean isoflavone content and its components were carried out based on the NC Ⅱ matingdesign in eight soybean varieties. The results showed that the isoflavone contents and its components of soybean seedare quite differences among the tested materials, the contents of isoflavone and daidzein are controlled not only byadditive effects and but also by non-additive effects, while the content of genistin is dominated by non-additive effects,and genistein, glycitin and daidzin are mainly controlled by additive effects. There are significant differences in thecontents of isoflavone and its components among the combinations derived from different parents. Results also indicatedthat the tested traits are negatively heterosis except for the contens of daidzein and daidzin are positively heterosis basedon the data of the GCA and SCA in average heterosis values. In this research we have a suggestion that soybean varietywith high isoflavone should be used as one of the parents in the breeding program, and it is the best choice that thecombinations crossed between two high isoflavone varieties or a high variety and a low one.展开更多
BACKGROUND Reactive oxygen species(ROS)are produced by multiple cellular processes and are maintained at optimal levels in normal cells by endogenous antioxidants.In recent years,the search for potential exogenous ant...BACKGROUND Reactive oxygen species(ROS)are produced by multiple cellular processes and are maintained at optimal levels in normal cells by endogenous antioxidants.In recent years,the search for potential exogenous antioxidants from dietary sources has gained considerable attention to eliminate excess ROS that is associated with oxidative stress related diseases including cancer.Propolis,a resinous honeybee product,has been shown to have protective effects against oxidative stress and anticancer effects against several types of neoplasms.AIM To investigate the antioxidant and anticancer potential of Lebanese propolis when applied alone or in combination with the promising anticancer compound Thymoquinone(TQ)the main constituent of Nigella sativa essential oil.METHODS Crude extracts of Lebanese propolis collected from two locations,Rashaya and Akkar-Danniyeh,were prepared in methanol and the total phenolic content was determined by Folin–Ciocalteu method.The antioxidant activity was assessed by the ability to scavenge 2,2-diphenyl-1-picrylhydrazyl(DPPH)free radical and to inhibit H2O2-induced oxidative hemolysis of human erythrocytes.The anticancer activity was evaluated by[3-(4,5-dimethylthiazol-2-yl)-2,5 diphenyl tetrazolium bromide]MTT assay against HCT-116 human colorectal cancer cells and MDAMB-231 human breast cancer cells.RESULTS The total phenolic content of propolis extract from Rashaya and Akkar-Danniyeh were 56.81μg and 83.503μg of gallic acid equivalent/mg of propolis,respectively.Both natural agents exhibited strong antioxidant activities as evidenced by their ability to scavenge DPPH free radical and to protect erythrocytes against H2O2-induced hemolysis.They also dose-dependently decreased the viability of both cancer cell lines.The IC50 value of each of propolis extract from Rashaya and Akkar-Danniyeh or TQ was 22.3,61.7,40.44μg/mL for breast cancer cells at 72 h and 33.3,50.9,33.5μg/mL for colorectal cancer cells at the same time point,respectively.Importantly,the inhibitory effects of propolis on DPPH radicals and cancer cell viability were achieved at half its concentration when combined with TQ.CONCLUSION Our results indicate that Lebanese propolis extract has antioxidant and anticancer potential and its combination with TQ could possibly prevent ROS-mediated diseases.展开更多
Traditional Chinese medicine(TCM)believes that the main pathogenesis of ulcerative colitis is spleen deficiency;damp heat in the large intestine as the symptom,the treatment must be warming,clearing,eliminating,tonify...Traditional Chinese medicine(TCM)believes that the main pathogenesis of ulcerative colitis is spleen deficiency;damp heat in the large intestine as the symptom,the treatment must be warming,clearing,eliminating,tonifying,astringing concurrently.From the concept of combining holism and the local treatment in TCM,idea of combining internal and external treatment is adopted.That is,the external treatment follows the therapeutic principle of using herbs with a bitter and cold nature to eliminate stagnation,and the seven carbon decoction,which can clear heat and dampness,cool the blood,and stop dysentery,is used as a rectal drip to retain the enema.Internal treatment follows the therapeutic principle of warmly tonifying and cultivating vital qi,with oral Chinese herbal medicine named Maodie Tang to strengthen the spleen and tonify the kidney,clearing heat and inducing dampness.展开更多
Objective: To explore the antibacterial activity of combined use of Shuanghuanglian and cefoperazone sulbactam sodium on resistant strains of Pseudomonas aeruginosa. Methods: The Pseudomonas aeruginosa strains which w...Objective: To explore the antibacterial activity of combined use of Shuanghuanglian and cefoperazone sulbactam sodium on resistant strains of Pseudomonas aeruginosa. Methods: The Pseudomonas aeruginosa strains which were sensitive and resistant to cefoperazone sulbactam sodium were selected to prepare different test bacterial solutions respectively;The experimental liquid of Shuanghuanglian and Cefoperazone Sulbactam Sodium were prepared separately and set as different test groups and control groups;The Drug Sensitivity Tests of Shuanghuanglian and cefoperazone sulbactam sodium at different concentration gradients which were used alone or used in combination were carried out for different strains with sensitivity and resistance, And use standard entry as a reference control. Result: The results of drug sensitivity test of Shuanghuanglian combined with Cefoperazone-Sulbactam sodium against the resistant strains of Pseudomonas aeruginosa were compared with the results of drug sensitivity test of the two separately used, and the difference was statistically significant (P 〈 0.05) [The drug sensitivity test results of Shuanghuanglian and cefoperazone sulbactam sodium to Pseudomonas aeruginosa resistant strains were statistically significant compared with the drug sensitivity test results of Shuanghuanglian and Cefoperazone Sulbactam Sodium used separately (P 〈 0.05)];There was a dependence between strains and concentration in the effect of the combination of the two drugs. Conclusion: The combination of Shuanghuanglian and cefoperazone sulbactam sodium has synergistic antibacterial or bactericidal effect on Pseudomonas aeruginosa resistant strains. .展开更多
The aim of the study was to evaluate the effect of different rates of organic farming aid (OFA) and inorganic fertilizer on the productivity of maize, chemical and microbial properties of soil for higher economic valu...The aim of the study was to evaluate the effect of different rates of organic farming aid (OFA) and inorganic fertilizer on the productivity of maize, chemical and microbial properties of soil for higher economic value. Field experiments were conducted during the 2020 and 2021 cropping seasons at the research fields of CSIR-Savanna Agricultural Research Institute located at Nyankpala in the Guinea savannah agroecology of Ghana. The study consisted of five treatment combinations: full rate of OFA, full rate of NPK, 1/2 OFA + 1/2 NPK, full OFA + 1/2 NPK and a control (no OFA and no NPK) which were arranged in a randomized complete block design with four replications. Analysis of variance indicated significant (P 0.05) treatment and year interaction effect for all the growth parameters except for plant height, leaf area and leaf area index. Apart from hundred seed weight, treatment and year interaction effect for all the yield and yield components was significant (P 0.05). Application of full rate of NPK (90:60:60) resulted in the highest grain yield of 4960 kg·ha<sup>-1</sup>, however it was statistically similar to those obtained by the combined application of full rate of OFA (250 ml·ha<sup>-1</sup>) + 1/2 NPK and 1/2 OFA + 1/2 NPK with grain yield of 4856 kg·ha<sup>-1</sup> and 4639 kg·ha<sup>-1</sup> respectively. There was also a yield advantage of 197. 5%, 191.3%, 178.3 and 79.1% over the control for full NPK rate, full OFA rate + 1/2 NPK rate, 1/2 OFA rate + 1/2 NPK and full OFA rate respectively. Application of full OFA rate + 1/2 NPK enhanced soil basal respiration (evolved CO<sub>2</sub>) and mineralizable C, implying that, combination of full OFA rate and NPK fertilizer would be necessary to boost soil microbial activity and soil labile nutrient pool (labile C pool). This suggests that combined use of full OFA rate + 1/2 NPK fertilizer can be a better strategic tool for improving soil quality. The highest benefit cost ratios (BCR) of 2.58 and 3.77 were obtained following the application of full OFA rate + 1/2 NPK and 1/2 OFA rate + 1/2 NPK respectively. Hence, it could be concluded that complementary use of OFA and NPK is more profitable than using single inputs (either OFA or NPK). Thus, in promoting technology packages to farmers, development practitioners must carefully consider the complementary of inputs that are cost-effective but economically rewarding.展开更多
基金Project supported by Youth Innovation Promotion Association of the Chinese Academy of Sciences (Grant No.2020029)。
文摘The ultrashort lasers working in pulse-burst mode reveal great machining performance in recent years. The number of pulses in bursts effects greatly on the removal rate and roughness. To generate a more equal amplitude of pulses in burst with linear polarization output and time gap adjustable, we propose a new method by the harmonic beam combining(HBC).The beam combining is commonly used in adding pulses into the output beam while maintaining the pulse waveform and beam quality. In the HBC, dichroic mirrors are used to combine laser pulses of fundamental wave(FW) into harmonic wave(HW), and nonlinear crystals are used to convert the FW into HW. Therefore, HBC can add arbitrarily more HW pulses to generate pulse-burst in linear polarization with simple structure. The amplitude of each pulse in bursts can be adjusted the same to increase the stability of the burst, the time gap of each pulse can be adjusted precisely by proper time delay. Because HBC adds pulses sequentially, the peak power density of the burst is the same as each pulse, pulses can be combined without concern of back-conversion which often occurs in high peak power density. In the demonstration, the extendibility of HBC was verified by combining two beams with a third beam. The combined efficiency rates were larger than 99%, and the beam quality of each beam was maintained at M^(2)≈1.4.
文摘Background As the most widely cultivated fiber crop,cotton production depends on hybridization to unlock the yield potential of current varieties.A deep understanding of genetic dissection is crucial for the cultivation of enhanced hybrid plants with desired traits,such as high yield and fine fiber quality.In this study,the general combining ability(GCA)and specific combining ability(SCA)of yield and fiber quality of nine cotton parents(six lines and three testers)and eighteen F1 crosses produced using a line×tester mating design were analyzed.Results The results revealed significant effects of genotypes,parents,crosses,and interactions between parents and crosses for most of the studied traits.Moreover,the effects of both additive and non-additive gene actions played a notably significant role in the inheritance of most of the yield and fiber quality attributes.The F1 hybrids of(Giza 90×Aust)×Giza 86,Uzbekistan 1×Giza 97,and Giza 96×Giza 97 demonstrated superior performance due to their favorable integration of high yield attributes and premium fiber quality characteristics.Path analysis revealed that lint yield has the highest positive direct effect on seed cotton yield,while lint percentage showed the highest negative direct effect on seed cotton yield.Principal component analysis identified specific parents and hybrids associated with higher cotton yield,fiber quality,and other agronomic traits.Conclusion This study provides insights into identifying potential single-and three-way cross hybrids with superior cotton yield and fiber quality characteristics,laying a foundation for future research on improving fiber quality in cotton.
基金Supported by NIH/National Cancer Institute Grant,No.R01CA138441 and No.R01CA269452UW Madison Centene Pancreas Cancer Collaborative Award,No.21-8568.
文摘BACKGROUND Pancreatic cancer is a leading cause of cancer-related deaths.Increased activity of the epidermal growth factor receptor(EGFR)is often observed in pancreatic cancer,and the small molecule EGFR inhibitor erlotinib has been approved for pancreatic cancer therapy by the food and drug administration.Nevertheless,erlotinib alone is ineffective and should be combined with other drugs to improve therapeutic outcomes.We previously showed that certain receptor tyrosine kinase inhibitors can increase mitochondrial membrane potential(Δψm),facilitate tumor cell uptake ofΔψm-sensitive agents,disrupt mitochondrial homeostasis,and subsequently trigger tumor cell death.Erlotinib has not been tested for this effect.AIM To determine whether erlotinib can elevateΔψm and increase tumor cell uptake ofΔψm-sensitive agents,subsequently triggering tumor cell death.METHODSΔψm-sensitive fluorescent dye was used to determine how erlotinib affectsΔψm in pancreatic adenocarcinoma(PDAC)cell lines.The viability of conventional and patient-derived primary PDAC cell lines in 2D-and 3D cultures was measured after treating cells sequentially with erlotinib and mitochondria-targeted ubiquinone(MitoQ),aΔψm-sensitive MitoQ.The synergy between erlotinib and MitoQ was then analyzed using SynergyFinder 2.0.The preclinical efficacy of the twodrug combination was determined using immune-compromised nude mice bearing PDAC cell line xenografts.RESULTS Erlotinib elevatedΔψm in PDAC cells,facilitating tumor cell uptake and mitochondrial enrichment ofΔψm-sensitive agents.MitoQ triggered caspase-dependent apoptosis in PDAC cells in culture if used at high doses,while erlotinib pretreatment potentiated low doses of MitoQ.SynergyFinder suggested that these drugs synergistically induced tumor cell lethality.Consistent with in vitro data,erlotinib and MitoQ combination suppressed human PDAC cell line xenografts in mice more effectively than single treatments of each agent.CONCLUSION Our findings suggest that a combination of erlotinib and MitoQ has the potential to suppress pancreatic tumor cell viability effectively.
基金Under the auspices of the National Key Research and Development Program of China (No.2017YFA0604902,2017YFA0604903,2017YFA0604901)。
文摘Mangroves play a pivotal role in tropical and subtropical coastal ecosystem,yet they are highly vulnerable to the effects of climate change,particularly the accelerated global sea level rise(SLR)and stronger tropical cyclones(TCs).However,there is a lack of research addressing future simultaneous combined impacts of the slow-onset of SLR and rapid-onset of TCs on China's mangroves.In order to develop a comprehensive risk assessment method considering the superimposed effects of these two factors and analyze risk for mangroves in Dongzhaigang,Hainan Island,China,we used observational and climate model data to assess the risks to mangroves under low,intermediate,and very high greenhouse gas(GHG)emission scenarios(such as SSP1-2.6,SSP2-4.5,and SSP5-8.5)in 2030,2050,and 2100,and compiled a risk assessment scheme for mangroves in Dongzhaigang,China.The results showed that the combined risks from SLR and TCs will continue to rise;however,SLRs will increase in intensity,and TCs will decrease.The comprehensive risk of the Dongzhaigang mangroves posed by climate change will remain low under SSP1-2.6 and SSP2-4.5 scenarios by 2030,but it will increase substantially by 2100.While under SSP5-8.5 scenario,the risks to mangroves in Dongzhaigang are projected to increase considerably by 2050,and approximately 68.8%of mangroves will be at very high risk by 2100.The risk to the Dongzhaigang mangroves is not only influenced by the hazards but also closely linked to their exposure and vulnerability.We therefore propose climate resilience developmental responses for mangroves to address the effects of climate change.This study for the combined impact of TCs and SLR on mangroves in Dongzhaigang,China can enrich the method system of mangrove risk assessment and provide references for scientific management.
文摘Objective:To analyze the importance of general practitioner residents using the combined teaching method(BOPPPS+mind maps).Methods:From September 2023 to August 2024,a study was conducted with 6 control group participants receiving traditional teaching and 6 observation group participants receiving the combined teaching method(BOPPPS+mind maps).The study analyzed various indicators between the two groups(including mind map scores and assessment results).Results:Compared with the control group,the assessment scores of the observation group were significantly higher(P<0.05).Conclusion:The application of the combined teaching method(BOPPPS+mind maps)by general practitioner residents can significantly improve their comprehensive abilities.
基金This study is funded by the National Nature Science Foundation of China(Grant Nos.:82074323,and 81673572)Key Research and Development Program of Shanxi Province(Program No.:202102130501010)+2 种基金The major science and technology project for“Significant New Drugs Creation”(Project No.:2017ZX09301047)Research Project Supported by Shanxi Scholarship Council of China(Project No.:2020019)The special fund for Science and Technology Innovation Teams of Shanxi Province(Grant No.:202204051002011).
文摘Radix Bupleuri(RB)is commonly used to treat depression,but it can also lead to hepatotoxicity after longterm use.In many anti-depression prescriptions,RB is often used in combination with Radix Paeoniae Alba(RPA)as an herb pair.However,whether RPA can alleviate RB-induced hepatotoxicity remain unclear.In this work,the results confirmed that RB had a dose-dependent antidepressant effect,but the optimal antidepressant dose caused hepatotoxicity.Notably,RPA effectively reversed RB-induced hepatotoxicity.Afterward,the mechanism of RB-induced hepatotoxicity was confirmed.The results showed that saikosaponin A and saikosaponin D could inhibit GSH synthase(GSS)activity in the liver,and further cause liver injury through oxidative stress and nuclear factor kappa B(NF-kB)/NOD-like receptor thermal protein domain associated protein 3(NLRP3)pathway.Furthermore,the mechanisms by which RPA attenuates RBinduced hepatotoxicity were investigated.The results demonstrated that RPA increased the abundance of intestinal bacteria with glycosidase activity,thereby promoting the conversion of saikosaponins to saikogenins in vivo.Different from saikosaponin A and saikosaponin D,which are directly combined with GSS as an inhibitor,their deglycosylation conversion products saikogenin F and saikogenin G exhibited no GSS binding activity.Based on this,RPA can alleviate the inhibitory effect of saikosaponins on GSS activity to reshape the liver redox balance and further reverse the RB-induced liver inflammatory response by the NFkB/NLRP3 pathway.In conclusion,the present study suggests that promoting the conversion of saikosaponins by modulating gut microbiota to attenuate the inhibition of GSS is the potential mechanism by which RPA prevents RB-induced hepatotoxicity.
基金Supported by the National Natural Science Foundation of China (No.81770972,No.81970843)。
文摘AIM:To evaluate the postoperative refractive prediction error(PE)and determine the factors that af fect the refractive outcomes of combined pars plana vitrectomy(PPV)or silicone oil removal(SOR)with cataract surgery.METHODS:The study is a retrospective,case-series study.Totally 301 eyes of 301 patients undergoing combined PPV/SOR with cataract surgery were enrolled.Eligible individuals were separated into four groups according to their preoperative diagnoses:silicone oil-filled eyes after PPV(group 1),epiretinal membrane(group 2),macular hole(group 3),and primary retinal detachment(RD;group 4).The variables af fecting postoperative refractive outcomes were analyzed,including age,gender,preoperative best-corrected visual acuity(BCVA),axial length(AL),keratometry average,anterior chamber depth(ACD),intraocular tamponade,and vitreoretinal pathology.The outcome measurements include the mean refractive PE and the proportions of eyes with a PE within±0.50 diopter(D)and±1.00 D.RESULTS:For all patients,the mean PE was-0.04±1.17 D,and 50.17%of patients(eyes)had a PE within±0.50 D.There was a significant difference in refractive outcomes among the four groups(P=0.028),with RD(group 4)showing the least favorable refractive outcome.In multivariate regression analysis,only AL,vitreoretinal pathology,and ACD were strongly associated with PE(all P<0.01).Univariate analysis revealed that longer eyes(AL>26 mm)and a deeper ACD were correlated with hyperopic PE,and shorter eyes(AL<26 mm)and a shallower ACD were correlated with myopic PE.CONCLUSION:RD patients have the least favorable refractive outcome.AL,vitreoretinal pathology,and ACD are strongly associated with PE in the combined surgery.These three factors affect refractive outcomes and thus can be used to predict a better postoperative refractive outcome in clinical practice.
基金Supported by the Cultivation Fund of National Natural Science Foundation,No.qiankehe2018-5764-11.
文摘BACKGROUND Gastric ulcer(GU)is a common digestive tract disease,and medical records of GU combined with depression are increasingly common.Currently,the risk factors and pathogenesis of GU complicated with depression remain unclear.Low immune function and gastrointestinal hormone levels may also be significant risk factors.Therefore,this study explored the immune function and gastrointestinal hormone levels in patients with GU combined with depression.AIM To explore the immune function,gastrointestinal hormone level,and clinical significance of patients with GU combined with depression.METHODS A retrospective analysis was conducted on 300 patients with GU combined with depression admitted to Guizhou Provincial People’s Hospital from January 2021 to June 2022 as the study subjects.According to the Hamilton Depression Scale(HAMD)score,patients were divided into mild-to-moderate(n=210)and heavy(n=90)groups.Basic data,immune function indices[immunoglobulin A(IgA),IgM,IgG,serum CD4+and CD8+percentage,and CD4+/CD8+ratio],and gastrointestinal hormone indices[serum gastrin(GAS),cholecystokinin(CCK),and motilin(MTL)levels]were collected.The basic data of the two groups were compared,and the immune function and gastrointestinal hormone indices were analyzed.Multivariate logistic regression was used to analyze the factors influencing the severity of GU complicated with depression.The receiver operating characteristic(ROC)curve and area under the ROC curve(AUC)were used to analyze the value of the immune function index,gastrointestinal hormone index,and combined index in predicting the severity of GU complicated with depression.RESULTS There were no marked differences in sex,age,body mass index,abdominal distension,abdominal pain,belching,nausea,vomiting,or sleep disorders between the heavy and mild-to-moderate groups(P>0.05).There was a marked difference in the family history of depression between the heavy and mild-to-moderate groups(P<0.05).There were significant differences in serum IgA and IgM levels and serum CD4+,CD8+,and CD4+/CD8+ratios between the heavy and mild-to-moderate groups(P<0.05).Multivariate analysis showed that IgA,IgM,GAS,and CCK serum levels influenced the severity of GU with depression(P<0.05).The AUC of the ROC curve for serum IgA level predicting GU with depression severity was 0.808[95%confidence interval(CI):0.760-0.857],the AUC of the serum IgM level was 0.757(95%CI:0.700-0.814),the AUC of the serum GAS level was 0.853(95%CI:0.810-0.897),the AUC of the serum CCK level was 0.762(95%CI:0.709-0.822),the AUC of immune function(IgA,IgM)and gastrointestinal hormone levels(GAS,CCK)for the prediction of GU with depression severity was 0.958(95%CI:0.933-0.976).CONCLUSION Important factors influencing GU complicated with depression are serum IgA,IgM,GAS,and CCK indicators.They can be used as indicators to predict the severity of GU complicated with depression.
基金Project supported by the National Natural Science Foundation of China (Grant Nos. 12074272 and 61905271)the National Defense Science and Technology Innovation Special Zone Project of China (Grant No. 20-163-02-ZT-008-009-01)Guangdong Basic and Applied Basic Research Foundation (Grant No. 2020A1515011083)。
文摘The generation of terahertz(THz) waves by focusing a femtosecond pulsed laser beam at a distance is able to overcome the strong absorption properties of air and has rapidly attracted the attention of industry. However, the poor directionality of the THz wave radiation generated by this method is not conducive to THz wave applications. By controlling the morphology of the ultrafast laser-excited plasma filament and its electron density distribution through coherent beam combining technology, we achieve direct THz beam shaping and are able to obtain THz wave radiation of Gaussian or arbitrary transverse distribution. The novel experimental approach proposed in this paper opens up the research field of direct THz wave shaping using plasma. Moreover, it innovates multi-parameter convergence algorithms and, by doing so, has the potential to find beam patterns with higher energy conversion efficiency and break the energy limit of THz waves emitted by lasers at high power.
文摘Background For the purpose of utilising hybrid vigour to produce possible hybrids with a suitable level of stability,the knowledge of gene activity and combining ability is a crucial prerequisite before choosing desirable parents.The present study was carried out with six parents crossed in full diallel fashion and generated 30 F1 hybrids.These hybrids were evaluated in two replications in Randomized Block Design at Department of Cotton,TNAU for combining ability and gene action.Diallel analysis was carried out according to Griffing’s method-I(parents + F_(1) + reciprocals) and model-I and Hayman’s graphical approach by using INDOSTAT software.Results Analysis of variance for combining ability indicated that mean square values of GCA,SCA and reciprocals were highly significant for all the traits except for the uniformity index.RG763 and K12 showed highly positively significant GCA effects for most of the yield traits while PA838 and K12 for fibre quality traits,so they were found as best general combiners.PAIG379 × K12 and PDB29 × K12 for yield traits,and PDB29 × PA838,RG763 × PA838,and CNA1007 × RG763 cross combinations for fibre quality traits could be recommended for future breeding programms.Conclusion The results of both Griffing’s and Hayman’s approaches showed that non-additive gene action predominates as SCA variance was bigger than GCA variance,so heterosis breeding is thought to be a more fruitful option for enhancing GCA of many traits.
基金funded by the Karamay Innovative Environment Construction Plan(Innovative Talents)Project(No.20212022hjcxrc0015)the Research Foundation of China University of Petroleum-Beijing at Karamay(No.XQZX20200010)+3 种基金the University Scientific Research Project of Xinjiang Uygur Autonomous Region(No.XJEDU2019Y067)the Natural Science Foundation of Xinjiang Uygur Autonomous Region(No.2019D01B57)the CNPC Strategic Cooperation Science and Technology Project(No.ZLZX2020-01-04-04)the Sichuan Province Regional Innovation Cooperation Project(No.2020YFQ0036).
文摘Nanomaterials and low-salinity water(LSW)are two popular enhanced oil recovery(EOR)methods that have been widely studied in recent years.The former is used for in-depth conformance improvement and the latter for microscopic oil displacement(by altering the potential and contact angle).However,there are few literature on combining them to achieve synergistic effects,especially for tight sandstone res-ervoirs.Based on the reservoir conditions of the Jimusar Oilfield,this study investigated the oil recovery mechanism of the combined imbibition system,which was composed of black nanosheet(BN)and LSW.Its performances including decreasing interfacial tension,emulsification,and wettability alterations were evaluated.The imbibition differences between the single system of BN and LSW and the combined BN-LsW imbibition system were then compared.Results showed that the combined imbibition system had a better emulsification effect on the crude oil and could also alter the wettability of the core surface.Moreover,the combined system could increase both the imbibition rate and the ultimate oil recovery.The nuclear magnetic T2 spectrum also indicated that the addition of black nanosheets could divert more fluid into small pores and thus improve the microscopic sweep efficiency.
文摘The treatment of patients with inflammatory bowel disease(IBD),especially those with severe or refractory disease,represents an important challenge for the clinical gastroenterologist.It seems to be no exaggeration to say that in these patients,not only the scientific background of the gastroenterologist is tested,but also the abundance of“gifts”that he should possess(insight,intuition,determ-ination,ability to take initiative,etc.)for the successful outcome of the treatment.In daily clinical practice,depending on the severity of the attack,IBD is treated with one or a combination of two or more pharmaceutical agents.These combin-ations include not only the first-line drugs(e.g.,mesalazine,corticosteroids,antibiotics,etc)but also second-and third-line drugs(immunosuppressants and biologic agents).It is a fact that despite the significant therapeutic advances there is still a significant percentage of patients who do not satisfactorily respond to the treatment applied.Therefore,a part of these patients are going to surgery.In recent years,several small-size clinical studies,reviews,and case reports have been published combining not only biological agents with other drugs(e.g.,immunosuppressants or corticosteroids)but also the combination of two biologi-cal agents simultaneously,especially in severe cases.In our opinion,it is at least a strange(and largely unexplained)fact that we often use combinations of drugs in a given patient although studies comparing the simultaneous administration of two or more drugs with monotherapy are very few.As mentioned above,there is a timid tendency in the literature to combine two biological agents in severe cases unresponsive to the applied treatment or patients with severe extraintestinal manifestations.The appropriate dosage,the duration of the administration,the suitable timing for checking the clinical and laboratory outcome,as well as the treatment side-effects,should be the subject of intense clinical research shortly.In this editorial,we attempt to summarize the existing data regarding the already applied combination therapies and to humbly formulate thoughts and suggestions for the future application of the combination treatment of biological agents in a well-defined category of patients.We suggest that the application of biomarkers and artificial intelligence could help in establishing new forms of treatment using the available modern drugs in patients with IBD resistant to treatment.
基金the Science and Technology Commission of Shanghai,China(Grant Nos.:20DZ2270800 and 19JC1410200)Innovative Research Team of High-Level Local Universities in Shanghai,China(Grant No.:SHSMU-ZDCX20210900)the National Natural Science Foundation of China(Grant No.:82073889).
文摘The reversible and precise temporal and spatial regulation of histone lysine methyltransferases(KMTs)is essential for epigenome homeostasis.The dysregulation of KMTs is associated with tumor initiation,metastasis,chemoresistance,invasiveness,and the immune microenvironment.Therapeutically,their promising effects are being evaluated in diversified preclinical and clinical trials,demonstrating encouraging outcomes in multiple malignancies.In this review,we have updated recent understandings of KMTs'functions and the development of their targeted inhibitors.First,we provide an updated overview of the regulatory roles of several KMT activities in oncogenesis,tumor suppression,and immune regulation.In addition,we summarize the current targeting strategies in different cancer types and multiple ongoing clinical trials of combination therapies with KMT inhibitors.In summary,we endeavor to depict the regulation of KMT-mediated epigenetic landscape and provide potential epigenetic targets in the treatment of cancers.
基金supported by the Beijing Scholars Program[BSP041]。
文摘The clustered regularly interspaced short palindromic repeats(CRISPR)–CRISPR-associated protein(Cas) system has been widely used for genome editing. In this system, the cytosine base editor(CBE) and adenine base editor(ABE) allow generating precise and irreversible base mutations in a programmable manner and have been used in many different types of cells and organisms. However, their applications are limited by low editing efficiency at certain genomic target sites or at specific target cytosine(C) or adenine(A) residues. Using a strategy of combining optimized synergistic core components, we developed a new multiplex super-assembled ABE(sABE) in rice that showed higher base-editing efficiency than previously developed ABEs. We also designed a new type of nuclear localization signal(NLS) comprising a FLAG epitope tag with four copies of a codon-optimized NLS(F4NLS^(r2)) to generate another ABE named F4NLS-sABE. This new NLS increased editing efficiency or edited additional A at several target sites. A new multiplex super-assembled CBE(sCBE) and F4NLS^(r2) involved F4NLS-sCBE were also created using the same strategy. F4NLS-sCBE was proven to be much more efficient than sCBE in rice. These optimized base editors will serve as powerful genome-editing tools for basic research or molecular breeding in rice and will provide a reference for the development of superior editing tools for other plants or animals.
基金Mattu University Research Affairs directorate and Mattu University Bedele Campus research coordination office for their administrative and financial support.
文摘Two field experiments were conducted in the main seasons of 2021/22 at the farmers'farm in two districts of southwest Ethiopia to investigate the effects of lime and phosphorus on groundnut yield and yield components,employing four levels of lime(0,2,4,and 6 t CaCO_(3)ha^(-1))and phosphorus(0,46,69,and 92 kg P_(2)O_(5)ha^(-1))arranged in factorial RCBD design with three replications.Data on the yield and its components were collected and subjected to an ANOVA using SAS software.The result demonstrated that plant height,number of branches,canopy spread,and shelling percentage were affected significantly by liming while effective nodule number,total peg,matured pod,and pod yield of groundnut significantly influenced by the main factors and their interactions.The combined application of 4 t lime and 46 kg P_(2)O_(5)ha^(-1)resulted in the highest number of effective nodules(147.23 plant^(-1)),total pod(72.6 plant^(-1)),mature pod(62.4 plant^(-1)),pod yield(4.49 t ha^(-1)),oil content(50.6%)and protein content(33.1%)whereas the lowest values of these parameters were seen in plots where neither lime nor phosphorus was applied.Therefore,it is advised that groundnut growers in the study areas,and similar agroecologies,apply the combination of 4 t lime and 46 kg P_(2)O_(5)ha^(-1).
基金This work was jointly spored by the grants from the Natural Science Foundation of Henan Province(0511030500)the National 863 Program of China(2004AA2111112)the N ational Natural Science Foundation of China(30490250).
文摘The genetic analysis of soybean isoflavone content and its components were carried out based on the NC Ⅱ matingdesign in eight soybean varieties. The results showed that the isoflavone contents and its components of soybean seedare quite differences among the tested materials, the contents of isoflavone and daidzein are controlled not only byadditive effects and but also by non-additive effects, while the content of genistin is dominated by non-additive effects,and genistein, glycitin and daidzin are mainly controlled by additive effects. There are significant differences in thecontents of isoflavone and its components among the combinations derived from different parents. Results also indicatedthat the tested traits are negatively heterosis except for the contens of daidzein and daidzin are positively heterosis basedon the data of the GCA and SCA in average heterosis values. In this research we have a suggestion that soybean varietywith high isoflavone should be used as one of the parents in the breeding program, and it is the best choice that thecombinations crossed between two high isoflavone varieties or a high variety and a low one.
基金Supported by the Lebanese University and the Undergraduate Research Experience funds at the American University of Beirut.
文摘BACKGROUND Reactive oxygen species(ROS)are produced by multiple cellular processes and are maintained at optimal levels in normal cells by endogenous antioxidants.In recent years,the search for potential exogenous antioxidants from dietary sources has gained considerable attention to eliminate excess ROS that is associated with oxidative stress related diseases including cancer.Propolis,a resinous honeybee product,has been shown to have protective effects against oxidative stress and anticancer effects against several types of neoplasms.AIM To investigate the antioxidant and anticancer potential of Lebanese propolis when applied alone or in combination with the promising anticancer compound Thymoquinone(TQ)the main constituent of Nigella sativa essential oil.METHODS Crude extracts of Lebanese propolis collected from two locations,Rashaya and Akkar-Danniyeh,were prepared in methanol and the total phenolic content was determined by Folin–Ciocalteu method.The antioxidant activity was assessed by the ability to scavenge 2,2-diphenyl-1-picrylhydrazyl(DPPH)free radical and to inhibit H2O2-induced oxidative hemolysis of human erythrocytes.The anticancer activity was evaluated by[3-(4,5-dimethylthiazol-2-yl)-2,5 diphenyl tetrazolium bromide]MTT assay against HCT-116 human colorectal cancer cells and MDAMB-231 human breast cancer cells.RESULTS The total phenolic content of propolis extract from Rashaya and Akkar-Danniyeh were 56.81μg and 83.503μg of gallic acid equivalent/mg of propolis,respectively.Both natural agents exhibited strong antioxidant activities as evidenced by their ability to scavenge DPPH free radical and to protect erythrocytes against H2O2-induced hemolysis.They also dose-dependently decreased the viability of both cancer cell lines.The IC50 value of each of propolis extract from Rashaya and Akkar-Danniyeh or TQ was 22.3,61.7,40.44μg/mL for breast cancer cells at 72 h and 33.3,50.9,33.5μg/mL for colorectal cancer cells at the same time point,respectively.Importantly,the inhibitory effects of propolis on DPPH radicals and cancer cell viability were achieved at half its concentration when combined with TQ.CONCLUSION Our results indicate that Lebanese propolis extract has antioxidant and anticancer potential and its combination with TQ could possibly prevent ROS-mediated diseases.
基金supported by the Clinical Effect Evaluation of Chinese Medicine on Moderately Active Ulcerative Colitis(2018YFC1705403).
文摘Traditional Chinese medicine(TCM)believes that the main pathogenesis of ulcerative colitis is spleen deficiency;damp heat in the large intestine as the symptom,the treatment must be warming,clearing,eliminating,tonifying,astringing concurrently.From the concept of combining holism and the local treatment in TCM,idea of combining internal and external treatment is adopted.That is,the external treatment follows the therapeutic principle of using herbs with a bitter and cold nature to eliminate stagnation,and the seven carbon decoction,which can clear heat and dampness,cool the blood,and stop dysentery,is used as a rectal drip to retain the enema.Internal treatment follows the therapeutic principle of warmly tonifying and cultivating vital qi,with oral Chinese herbal medicine named Maodie Tang to strengthen the spleen and tonify the kidney,clearing heat and inducing dampness.
文摘Objective: To explore the antibacterial activity of combined use of Shuanghuanglian and cefoperazone sulbactam sodium on resistant strains of Pseudomonas aeruginosa. Methods: The Pseudomonas aeruginosa strains which were sensitive and resistant to cefoperazone sulbactam sodium were selected to prepare different test bacterial solutions respectively;The experimental liquid of Shuanghuanglian and Cefoperazone Sulbactam Sodium were prepared separately and set as different test groups and control groups;The Drug Sensitivity Tests of Shuanghuanglian and cefoperazone sulbactam sodium at different concentration gradients which were used alone or used in combination were carried out for different strains with sensitivity and resistance, And use standard entry as a reference control. Result: The results of drug sensitivity test of Shuanghuanglian combined with Cefoperazone-Sulbactam sodium against the resistant strains of Pseudomonas aeruginosa were compared with the results of drug sensitivity test of the two separately used, and the difference was statistically significant (P 〈 0.05) [The drug sensitivity test results of Shuanghuanglian and cefoperazone sulbactam sodium to Pseudomonas aeruginosa resistant strains were statistically significant compared with the drug sensitivity test results of Shuanghuanglian and Cefoperazone Sulbactam Sodium used separately (P 〈 0.05)];There was a dependence between strains and concentration in the effect of the combination of the two drugs. Conclusion: The combination of Shuanghuanglian and cefoperazone sulbactam sodium has synergistic antibacterial or bactericidal effect on Pseudomonas aeruginosa resistant strains. .
文摘The aim of the study was to evaluate the effect of different rates of organic farming aid (OFA) and inorganic fertilizer on the productivity of maize, chemical and microbial properties of soil for higher economic value. Field experiments were conducted during the 2020 and 2021 cropping seasons at the research fields of CSIR-Savanna Agricultural Research Institute located at Nyankpala in the Guinea savannah agroecology of Ghana. The study consisted of five treatment combinations: full rate of OFA, full rate of NPK, 1/2 OFA + 1/2 NPK, full OFA + 1/2 NPK and a control (no OFA and no NPK) which were arranged in a randomized complete block design with four replications. Analysis of variance indicated significant (P 0.05) treatment and year interaction effect for all the growth parameters except for plant height, leaf area and leaf area index. Apart from hundred seed weight, treatment and year interaction effect for all the yield and yield components was significant (P 0.05). Application of full rate of NPK (90:60:60) resulted in the highest grain yield of 4960 kg·ha<sup>-1</sup>, however it was statistically similar to those obtained by the combined application of full rate of OFA (250 ml·ha<sup>-1</sup>) + 1/2 NPK and 1/2 OFA + 1/2 NPK with grain yield of 4856 kg·ha<sup>-1</sup> and 4639 kg·ha<sup>-1</sup> respectively. There was also a yield advantage of 197. 5%, 191.3%, 178.3 and 79.1% over the control for full NPK rate, full OFA rate + 1/2 NPK rate, 1/2 OFA rate + 1/2 NPK and full OFA rate respectively. Application of full OFA rate + 1/2 NPK enhanced soil basal respiration (evolved CO<sub>2</sub>) and mineralizable C, implying that, combination of full OFA rate and NPK fertilizer would be necessary to boost soil microbial activity and soil labile nutrient pool (labile C pool). This suggests that combined use of full OFA rate + 1/2 NPK fertilizer can be a better strategic tool for improving soil quality. The highest benefit cost ratios (BCR) of 2.58 and 3.77 were obtained following the application of full OFA rate + 1/2 NPK and 1/2 OFA rate + 1/2 NPK respectively. Hence, it could be concluded that complementary use of OFA and NPK is more profitable than using single inputs (either OFA or NPK). Thus, in promoting technology packages to farmers, development practitioners must carefully consider the complementary of inputs that are cost-effective but economically rewarding.