Background:Shengmai decoction,which has been included in the diagnosis and treatment of coronavirus disease 2019(COVID-19),is effective in the early treatment of patients with severe COVID-19.Yiqi Fumai lyophilized in...Background:Shengmai decoction,which has been included in the diagnosis and treatment of coronavirus disease 2019(COVID-19),is effective in the early treatment of patients with severe COVID-19.Yiqi Fumai lyophilized injection(YQFM)is a modern Chinese medicine preparation of the Shengmai decoction.The mechanism of its intervention at the molecular level in the severe stage of COVID-19 remains unclear.Therefore,it is necessary to investigate the mechanism of YQFM in the treatment of patients with severe COVID-19.Methods:The corresponding target genes of the main active ingredients in YQFM and COVID-19 were obtained by using multiple databases and literature retrieval.A protein-protein interaction network was constructed,and enrichment analysis of the target was performed using Cytoscape 3.8.1.Lastly,the docking of all the identified compounds with angiotensin-converting enzyme II was confirmed by applying molecular docking technology.Results:YQFM has anti-inflammatory effects on RAW267.4 macrophages.The main active compounds of YQFM are all effective anti-inflammatory agents,and these active compounds also show beneficial physiological functions,such as anti-oxidation,anti-bacterial,and anticancer activities.Gene Ontology analysis showed enrichment in the following pathways:lipopolysaccharides,interleukins,NF-kappa B,interleukin-2 and others,revealing that YQFM may play a role in the treatment of patients with severe COVID-19 through these pathways.Conclusion:YQFM has multicomponent and multitarget characteristics,and it could reduce lung injury by inhibiting inflammatory reactions,promoting antiviral activities,and regulating immunity,among other functions,to treat patients with severe COVID-19.展开更多
Axonal remodeling is a critical aspect of ischemic brain repair processes and contributes to spontaneous functional recovery.Our previous in vitro study demonstrated that exosomes/small extracellular vesicles(sEVs)iso...Axonal remodeling is a critical aspect of ischemic brain repair processes and contributes to spontaneous functional recovery.Our previous in vitro study demonstrated that exosomes/small extracellular vesicles(sEVs)isolated from cerebral endothelial cells(CEC-sEVs)of ischemic brain promote axonal growth of embryonic cortical neurons and that microRNA 27a(miR-27a)is an elevated miRNA in ischemic CEC-sEVs.In the present study,we investigated whether normal CEC-sEVs engineered to enrich their levels of miR-27a(27a-sEVs)further enhance axonal growth and improve neurological outcomes after ischemic stroke when compared with treatment with non-engineered CEC-sEVs.27a-sEVs were isolated from the conditioned medium of healthy mouse CECs transfected with a lentiviral miR-27a expression vector.Small EVs isolated from CECs transfected with a scramble vector(Scra-sEVs)were used as a control.Adult male mice were subjected to permanent middle cerebral artery occlusion and then were randomly treated with 27a-sEVs or Scra-sEVs.An array of behavior assays was used to measure neurological function.Compared with treatment of ischemic stroke with Scra-sEVs,treatment with 27a-sEVs significantly augmented axons and spines in the peri-infarct zone and in the corticospinal tract of the spinal grey matter of the denervated side,and significantly improved neurological outcomes.In vitro studies demonstrated that CEC-sEVs carrying reduced miR-27a abolished 27a-sEV-augmented axonal growth.Ultrastructural analysis revealed that 27a-sEVs systemically administered preferentially localized to the pre-synaptic active zone,while quantitative reverse transcription-polymerase chain reaction and Western Blot analysis showed elevated miR-27a,and reduced axonal inhibitory proteins Semaphorin 6A and Ras Homolog Family Member A in the peri-infarct zone.Blockage of the Clathrin-dependent endocytosis pathway substantially reduced neuronal internalization of 27a-sEVs.Our data provide evidence that 27a-sEVs have a therapeutic effect on stroke recovery by promoting axonal remodeling and improving neurological outcomes.Our findings also suggest that suppression of axonal inhibitory proteins such as Semaphorin 6A may contribute to the beneficial effect of 27a-sEVs on axonal remodeling.展开更多
The recent increase in blast/bombing incidents all over the world has pushed the development of effective strengthening approaches to enhance the blast resistance of existing civil infrastructures.Engineered geopolyme...The recent increase in blast/bombing incidents all over the world has pushed the development of effective strengthening approaches to enhance the blast resistance of existing civil infrastructures.Engineered geopolymer composite(EGC)is a promising material featured by eco-friendly,fast-setting and strain-hardening characteristics for emergent strengthening and construction.However,the fiber optimization for preparing EGC and its protective effect on structural elements under blast scenarios are uncertain.In this study,laboratory tests were firstly conducted to evaluate the effects of fiber types on the properties of EGC in terms of workability,dry shrinkage,and mechanical properties in compression,tension and flexure.The experimental results showed that EGC containing PE fiber exhibited suitable workability,acceptable dry shrinkage and superior mechanical properties compared with other types of fibers.After that,a series of field tests were carried out to evaluate the effectiveness of EGC retrofitting layer on the enhancement of blast performance of typical elements.The tests include autoclaved aerated concrete(AAC)masonry walls subjected to vented gas explosion,reinforced AAC panels subjected to TNT explosion and plain concrete slabs subjected to contact explosion.It was found that EGC could effectively enhance the blast resistance of structural elements in different scenarios.For AAC masonry walls and panels,with the existence of EGC,the integrity of specimens could be maintained,and their deflections and damage were significantly reduced.For plain concrete slabs,the EGC overlay could reduce the diameter and depth of the crater and spallation of specimens.展开更多
BACKGROUND Sarcopenia may be associated with hepatocellular carcinoma(HCC)following hepatectomy.But traditional single clinical variables are still insufficient to predict recurrence.We still lack effective prediction...BACKGROUND Sarcopenia may be associated with hepatocellular carcinoma(HCC)following hepatectomy.But traditional single clinical variables are still insufficient to predict recurrence.We still lack effective prediction models for recent recurrence(time to recurrence<2 years)after hepatectomy for HCC.AIM To establish an interventable prediction model to estimate recurrence-free survival(RFS)after hepatectomy for HCC based on sarcopenia.METHODS We retrospectively analyzed 283 hepatitis B-related HCC patients who underwent curative hepatectomy for the first time,and the skeletal muscle index at the third lumbar spine was measured by preoperative computed tomography.94 of these patients were enrolled for external validation.Cox multivariate analysis was per-formed to identify the risk factors of postoperative recurrence in training cohort.A nomogram model was developed to predict the RFS of HCC patients,and its predictive performance was validated.The predictive efficacy of this model was evaluated using the receiver operating characteristic curve.RESULTS Multivariate analysis showed that sarcopenia[Hazard ratio(HR)=1.767,95%CI:1.166-2.678,P<0.05],alpha-fetoprotein≥40 ng/mL(HR=1.984,95%CI:1.307-3.011,P<0.05),the maximum diameter of tumor>5 cm(HR=2.222,95%CI:1.285-3.842,P<0.05),and hepatitis B virus DNA level≥2000 IU/mL(HR=2.1,95%CI:1.407-3.135,P<0.05)were independent risk factors associated with postoperative recurrence of HCC.Based on the sarcopenia to assess the RFS model of hepatectomy with hepatitis B-related liver cancer disease(SAMD)was established combined with other the above risk factors.The area under the curve of the SAMD model was 0.782(95%CI:0.705-0.858)in the training cohort(sensitivity 81%,specificity 63%)and 0.773(95%CI:0.707-0.838)in the validation cohort.Besides,a SAMD score≥110 was better to distinguish the high-risk group of postoperative recurrence of HCC.CONCLUSION Sarcopenia is associated with recent recurrence after hepatectomy for hepatitis B-related HCC.A nutritional status-based prediction model is first established for postoperative recurrence of hepatitis B-related HCC,which is superior to other models and contributes to prognosis prediction.展开更多
The northeastern Sichuan area in the northern Yangtze margin has unique Ediacaran geological records,especially the Doushantuo Formation(DST),and become a hot research area in recent years.However,the Cryogenian-Ediac...The northeastern Sichuan area in the northern Yangtze margin has unique Ediacaran geological records,especially the Doushantuo Formation(DST),and become a hot research area in recent years.However,the Cryogenian-Ediacaran(C-E)boundary has not been precisely identified,which restricts the in-depth study of geological information during this crucial transitional period and is unfavorable for a systematic and complete understanding of the Yangtze Block and even the global paleogeographic pattern.This study conducted stratigraphy,sedimentology,and chronostratigraphy to establish the stratigraphic framework and sedimentary evolution of the C-E transition strata in northeastern Sichuan.The results showed that the Ediacaran sediments,without the cap dolomite,unconformably overlaid the Cryogenian sediments in the studied area.The Member II of the DST,characterized by 50-160 m of red-green sandstone(approximately equivalent to the original Chengkou“Guanyinya Formation”),directly overlaid the Cryogenian sediments and displayed a 623±2.3 Ma maximum depositional age from the detrital zircon U-Pb dating.Regional stratigraphic correlations indicate that the C-E transition strata in northeastern Sichuan had a consistent lithological association and sedimentary sequence characteristics but differed from the Three Gorges.Typically,the upper Nantuo massive glacial diamictites transition to the icebergs rafted lonestone-bearing mudstones at the top,then change upward to DST barrier coast sandstones.The proposed DST of the northeastern Sichuan Basin was divided into three lithostratigraphic members without the regional Member I cap dolomite:(i)Member II purple-red,gray-green sandstone strata,(ii)MemberⅢblack mudstone strata,and(iii)Member IV P-Mn bearing strata.During the C-E transition,the study area experienced(i)the global deglaciation stage in the terminal Marinoan glaciation and(ii)the filling-leveling up stage with clastic rocks in the early Ediacaran.Overall,the early Ediacaran of northeastern Sichuan succeeded the paleogeographic features of the late Cryogenian.展开更多
The insufficient active sites and slow interfacial charge trans-fer of photocatalysts restrict the efficiency of CO_(2) photoreduction.The synchronized modulation of the above key issues is demanding and chal-lenging....The insufficient active sites and slow interfacial charge trans-fer of photocatalysts restrict the efficiency of CO_(2) photoreduction.The synchronized modulation of the above key issues is demanding and chal-lenging.Herein,strain-induced strategy is developed to construct the Bi–O-bonded interface in Cu porphyrin-based monoatomic layer(PML-Cu)and Bi_(12)O_(17)Br_(2)(BOB),which triggers the surface interface dual polarization of PML-Cu/BOB(PBOB).In this multi-step polarization,the built-in electric field formed between the interfaces induces the electron transfer from con-duction band(CB)of BOB to CB of PML-Cu and suppresses its reverse migration.Moreover,the surface polarization of PML-Cu further promotes the electron converge in Cu atoms.The introduction of PML-Cu endows a high density of dispersed Cu active sites on the surface of PBOB,significantly promoting the adsorption and activation of CO_(2) and CO desorption.The conversion rate of CO_(2) photoreduction to CO for PBOB can reach 584.3μmol g-1,which is 7.83 times higher than BOB and 20.01 times than PML-Cu.This work offers valuable insights into multi-step polarization regulation and active site design for catalysts.展开更多
For the reduction of bovine serum proteins from wastewater,a novel mixed matrix membrane was prepared by functionalizing the substrate material polyaryletherketone(PAEK),followed by carboxyl groups(C-SPAEKS),and then ...For the reduction of bovine serum proteins from wastewater,a novel mixed matrix membrane was prepared by functionalizing the substrate material polyaryletherketone(PAEK),followed by carboxyl groups(C-SPAEKS),and then adding amino-functionalized UiO-66-NH_(2)(Am-UiO-66-NH_(2)).Aminofunctionalization of UiO-66 was accomplished by melamine,followed by an amidation reaction to immobilize Am-UiO-66-NH_(2),which was immobilized on the surface of the membrane as well as in the pore channels,which enhanced the hydrophilicity of the membrane surface while increasing the negative potential of the membrane surface.This nanoparticle-loaded ultrafiltration membrane has good permeation performance,with a pure water flux of up to 482.3 L·m^(-2)·h^(-1) for C-SPAEKS/AmUiO-66-NH_(2) and a retention rate of up to 98.7%for bovine serum albumin(BSA)-contaminated solutions.Meanwhile,after several hydrophilic modifications,the flux recovery of BSA contaminants by this series of membranes increased from 56.2%to 80.55%of pure membranes.The results of ultra-filtration flux time tests performed at room temperature showed that the series of ultrafiltration membranes remained relatively stable over a test time of 300 min.Thus,the newly developed mixed matrix membrane showed potential for high efficiency and stability in wastewater treatment containing bovine serum proteins.展开更多
Understanding the hydrate adhesion is important to tackling hydrate accretion in petro-pipelines.Herein,the relationship between the Tetrahydrofuran(THF)hydrate adhesion strength(AS)and surface stiffness on elastic co...Understanding the hydrate adhesion is important to tackling hydrate accretion in petro-pipelines.Herein,the relationship between the Tetrahydrofuran(THF)hydrate adhesion strength(AS)and surface stiffness on elastic coatings is systemically examined by experimental shear force measurements and theoretical methods.The mechanical factor-elastic modulus of the coatings greatly dictates the hydrate AS,which is explained by the adhesion mechanics theory,beyond the usual factors such as wettability and structural roughness.Moreover,the hydrate AS increases with reducing the thickness of the elastic coatings,resulted from the decrease of the apparent surface elastic modulus.The effect of critical thickness for the elastic materials with variable elastic modulus on the hydrate AS is also revealed.This study provides deep perspectives on the regulation of the hydrate AS by the elastic modulus of elastic materials,which is of significance to design anti-hydrate surfaces for mitigation of hydrate accretion in petro-pipelines.展开更多
Chimeric antigen receptor-natural killer(CAR-NK) cells have emerged as another prominent player in the realm of tumor immunotherapy following CAR-T cells. The unique features of CAR-NK cells make it possible to compen...Chimeric antigen receptor-natural killer(CAR-NK) cells have emerged as another prominent player in the realm of tumor immunotherapy following CAR-T cells. The unique features of CAR-NK cells make it possible to compensate for deficiencies in CAR-T therapy, such as the complexity of the manufacturing process, clinical adverse events, and solid tumor challenges. To date, CAR-NK products from different allogeneic sources have exhibited remarkable anti-tumor effects on preclinical studies and have gradually been applied in clinical practice.However, each source has advantages and disadvantages. Selecting a suitable source may help maximize CAR-NK cell efficacy and increase the feasibility of clinical transformation. Therefore, this review discusses the development and challenges of CAR-NK cells from different sources to provide a reference for future exploration.展开更多
The High Altitude Detection of Astronomical Radiation(HADAR)experiment,which was constructed in Tibet,China,combines the wide-angle advantages of traditional EAS array detectors with the high-sensitivity advantages of...The High Altitude Detection of Astronomical Radiation(HADAR)experiment,which was constructed in Tibet,China,combines the wide-angle advantages of traditional EAS array detectors with the high-sensitivity advantages of focused Cherenkov detectors.Its objective is to observe transient sources such as gamma-ray bursts and the counterparts of gravitational waves.This study aims to utilize the latest AI technology to enhance the sensitivity of HADAR experiments.Training datasets and models with distinctive creativity were constructed by incorporating the relevant physical theories for various applications.These models can determine the type,energy,and direction of the incident particles after careful design.We obtained a background identification accuracy of 98.6%,a relative energy reconstruction error of 10.0%,and an angular resolution of 0.22°in a test dataset at 10 TeV.These findings demonstrate the significant potential for enhancing the precision and dependability of detector data analysis in astrophysical research.By using deep learning techniques,the HADAR experiment’s observational sensitivity to the Crab Nebula has surpassed that of MAGIC and H.E.S.S.at energies below 0.5 TeV and remains competitive with conventional narrow-field Cherenkov telescopes at higher energies.In addition,our experiment offers a new approach for dealing with strongly connected,scattered data.展开更多
Bacillus coagulans has been extensively studied so far,but there has been a lack of research on its usage in allergy.In this study,we designed to assess the effect of different concentrations of B.coagulans on food al...Bacillus coagulans has been extensively studied so far,but there has been a lack of research on its usage in allergy.In this study,we designed to assess the effect of different concentrations of B.coagulans on food allergy in a BALB/c mouse model of ovalbumin(OVA)-induced food allergy and its effect on gut microbes.The assessment of symptoms,specific immunoglobulin E(IgE),T-cell differentiation,and related gene expression levels in sensitized mice by assay indicated that high doses of oral B.coagulans could alleviate allergic symptoms.Treatment with B.coagulans,in the high-dose group,significantly reduced IgE and IgG1 levels and modulated the balance of T helper type 1 cell(Th1)and Th2 and the expression of relevant genes in the spleen.16S rRNA analysis showed that probiotics improved the structure of the microbiota,in particular by boosting the percentage of Clostridia,Bacteroides vulgatus and Enterococcus faecium,and by increasing the abundance of microbial species,thereby modulating the immune system.Therefore,this study can provide insights into the practical application of B.coagulans doses to alleviate OVA allergy.展开更多
An externally generated resonant magnetic perturbation can induce complex non-ideal MHD responses in their resonant surfaces.We have studied the plasma responses using Fitzpatrick's improved two-fluid model and pr...An externally generated resonant magnetic perturbation can induce complex non-ideal MHD responses in their resonant surfaces.We have studied the plasma responses using Fitzpatrick's improved two-fluid model and program LAYER.We calculated the error field penetration threshold for J-TEXT.In addition,we find that the island width increases slightly as the error field amplitude increases when the error field amplitude is below the critical penetration value.However,the island width suddenly jumps to a large value because the shielding effect of the plasma against the error field disappears after the penetration.By scanning the natural mode frequency,we find that the shielding effect of the plasma decreases as the natural mode frequency decreases.Finally,we obtain the m/n=2/1 penetration threshold scaling on density and temperature.展开更多
BACKGROUND Metabolic reprogramming plays a key role in cancer progression and clinical outcomes;however,the patterns and primary regulators of metabolic reprogramming in colorectal cancer(CRC)are not well understood.A...BACKGROUND Metabolic reprogramming plays a key role in cancer progression and clinical outcomes;however,the patterns and primary regulators of metabolic reprogramming in colorectal cancer(CRC)are not well understood.AIM To explore the role of nicotinamide adenine dinucleotide phosphate oxidase 4(NOX4)in promoting progression of CRC.METHODS We evaluated the expression and function of dysregulated and survival-related metabolic genes using Gene Ontology and Kyoto Encyclopedia of Genes and Genomes.Consensus clustering was used to cluster CRC based on dysregulated metabolic genes.A prediction model was constructed based on survival-related metabolic genes.Sphere formation,migration,invasion,proliferation,apoptosis and clone formation was used to evaluate the biological function of NOX4 in CRC.mRNA sequencing was utilized to explore the alterations of gene expression NOX4 over-expression tumor cells.In vivo subcutaneous and lung metastasis mouse tumor model was used to explore the effect of NOX4 on tumor growth.RESULTS We comprehensively analyzed 3341 metabolic genes in CRC and identified three clusters based on dysregulated metabolic genes.Among these genes,NOX4 was highly expressed in tumor tissues and correlated with worse survival.In vitro,NOX4 overexpression induced clone formation,migration,invasion,and stemness in CRC cells.Furthermore,RNA-sequencing analysis revealed that NOX4 overexpression activated the mitogen-activated protein kinase-MEK1/2-ERK1/2 signaling pathway.Trametinib,a MEK1/2 inhibitor,abolished the NOX4-mediated tumor progression.In vivo,NOX4 overexpression promoted subcutaneous tumor growth and lung metastasis,whereas trametinib treatment can reversed the metastasis.CONCLUSION Our study comprehensively analyzed metabolic gene expression and highlighted the importance of NOX4 in promoting CRC metastasis,suggesting that trametinib could be a potential therapeutic drugs of CRC clinical therapy targeting NOX4.展开更多
The morbidity and mortality of gastrointestinal(GI)malignancies are among the highest in the world,posing a serious threat to human health.Because of the insidious onset of the cancer,it is difficult for patients to b...The morbidity and mortality of gastrointestinal(GI)malignancies are among the highest in the world,posing a serious threat to human health.Because of the insidious onset of the cancer,it is difficult for patients to be diagnosed at an early stage,and it rapidly progresses to an advanced stage,resulting in poor treatment and prognosis.Fusobacterium nucleatum(F.nucleatum)is a gram-negative,sporefree anaerobic bacterium that primarily colonizes the oral cavity and is implicated in the development of colorectal,esophageal,gastric,and pancreatic cancers via various intricate mechanisms.Recent development in novel research suggests that F.nucleatum may function as a biomarker in GI malignancies.Detecting the abundance of F.nucleatum in stool,saliva,and serum samples of patients may aid in the diagnosis,risk assessment,and prognosis monitoring of GI malignancies.This editorial systematically describes the biological roles and mechanisms of F.nucleatum in GI malignancies focusing on the application of F.nucleatum as a biomarker in the diagnosis and prognosis of GI malignancies to promote the clinical translation of F.nucleatum and GI tumors-related research.展开更多
BACKGROUND The neuroendoscopic approach has the advantages of a clear operative field,convenient tumor removal,and less damage,and is the development direction of modern neurosurgery.At present,transnasal surgery for ...BACKGROUND The neuroendoscopic approach has the advantages of a clear operative field,convenient tumor removal,and less damage,and is the development direction of modern neurosurgery.At present,transnasal surgery for sphenoidal pituitary tumor is widely used.But it has been found in clinical practice that some patients with this type of surgery may experience post-operative nausea and vomiting and other discomforts.AIM To explore the effect of reserved gastric tube application in the neuroendoscopic endonasal resection of pituitary tumors.METHODS A total of 60 patients who underwent pituitary adenoma resection via the endoscopic endonasal approach were selected and randomly divided into the experimental and control groups,with 30 in each group.Experimental group:After anesthesia,a gastric tube was placed through the mouth under direct vision using a visual laryngoscope,and the fluid accumulated in the oropharynx was suctioned intermittently with low negative pressure throughout the whole process after nasal disinfection,during the operation,and when the patient recovered from anesthesia.Control group:Given the routine intraoperative care,no gastric tube was left.The number of cases of nausea/vomiting/aspiration within 24 h post-operation was counted and compared between the two groups;the scores of pharyngalgia after waking up,6 h post-operation,and 24 h postoperation.The frequency of postoperative cerebrospinal fluid leakage and intracranial infection were compared.The hospitalization days of the two groups were statistically compared.RESULTS The times of postoperative nausea and vomiting in the experimental group were lower than that in the control group,and the difference in the incidence of nausea was statistically significant(P<0.05).After the patient woke up,the scores of sore throat 6 h after the operation and 24 h after operation were lower than those in the control group,and the difference was statistically significant(P<0.05).The number of cases of postoperative cerebrospinal fluid leakage and intracranial infection was higher than that of the control group,but there was no statistically significant difference from the control group(P>0.05).The hospitalization days of the experimental group was lower than that of the control group,and the difference was statistically significant(P<0.05).CONCLUSION Reserving a gastric tube in the endoscopic endonasal resection of pituitary tumors,combined with intraoperative and postoperative gastrointestinal decompression,can effectively reduce the incidence of nausea,reduce the number of vomiting and aspiration in patients,and reduce the complications of sore throat The incidence rate shortened the hospitalization days of the patients.展开更多
基金National Natural Science Foundation of China(No.81673535)the Science and Technology Project of Tianjin(No.18ZXXYSY00080).
文摘Background:Shengmai decoction,which has been included in the diagnosis and treatment of coronavirus disease 2019(COVID-19),is effective in the early treatment of patients with severe COVID-19.Yiqi Fumai lyophilized injection(YQFM)is a modern Chinese medicine preparation of the Shengmai decoction.The mechanism of its intervention at the molecular level in the severe stage of COVID-19 remains unclear.Therefore,it is necessary to investigate the mechanism of YQFM in the treatment of patients with severe COVID-19.Methods:The corresponding target genes of the main active ingredients in YQFM and COVID-19 were obtained by using multiple databases and literature retrieval.A protein-protein interaction network was constructed,and enrichment analysis of the target was performed using Cytoscape 3.8.1.Lastly,the docking of all the identified compounds with angiotensin-converting enzyme II was confirmed by applying molecular docking technology.Results:YQFM has anti-inflammatory effects on RAW267.4 macrophages.The main active compounds of YQFM are all effective anti-inflammatory agents,and these active compounds also show beneficial physiological functions,such as anti-oxidation,anti-bacterial,and anticancer activities.Gene Ontology analysis showed enrichment in the following pathways:lipopolysaccharides,interleukins,NF-kappa B,interleukin-2 and others,revealing that YQFM may play a role in the treatment of patients with severe COVID-19 through these pathways.Conclusion:YQFM has multicomponent and multitarget characteristics,and it could reduce lung injury by inhibiting inflammatory reactions,promoting antiviral activities,and regulating immunity,among other functions,to treat patients with severe COVID-19.
基金supported by the NIH grants,R01 NS111801(to ZGZ)American Heart Association 16SDG29860003(to YZ)。
文摘Axonal remodeling is a critical aspect of ischemic brain repair processes and contributes to spontaneous functional recovery.Our previous in vitro study demonstrated that exosomes/small extracellular vesicles(sEVs)isolated from cerebral endothelial cells(CEC-sEVs)of ischemic brain promote axonal growth of embryonic cortical neurons and that microRNA 27a(miR-27a)is an elevated miRNA in ischemic CEC-sEVs.In the present study,we investigated whether normal CEC-sEVs engineered to enrich their levels of miR-27a(27a-sEVs)further enhance axonal growth and improve neurological outcomes after ischemic stroke when compared with treatment with non-engineered CEC-sEVs.27a-sEVs were isolated from the conditioned medium of healthy mouse CECs transfected with a lentiviral miR-27a expression vector.Small EVs isolated from CECs transfected with a scramble vector(Scra-sEVs)were used as a control.Adult male mice were subjected to permanent middle cerebral artery occlusion and then were randomly treated with 27a-sEVs or Scra-sEVs.An array of behavior assays was used to measure neurological function.Compared with treatment of ischemic stroke with Scra-sEVs,treatment with 27a-sEVs significantly augmented axons and spines in the peri-infarct zone and in the corticospinal tract of the spinal grey matter of the denervated side,and significantly improved neurological outcomes.In vitro studies demonstrated that CEC-sEVs carrying reduced miR-27a abolished 27a-sEV-augmented axonal growth.Ultrastructural analysis revealed that 27a-sEVs systemically administered preferentially localized to the pre-synaptic active zone,while quantitative reverse transcription-polymerase chain reaction and Western Blot analysis showed elevated miR-27a,and reduced axonal inhibitory proteins Semaphorin 6A and Ras Homolog Family Member A in the peri-infarct zone.Blockage of the Clathrin-dependent endocytosis pathway substantially reduced neuronal internalization of 27a-sEVs.Our data provide evidence that 27a-sEVs have a therapeutic effect on stroke recovery by promoting axonal remodeling and improving neurological outcomes.Our findings also suggest that suppression of axonal inhibitory proteins such as Semaphorin 6A may contribute to the beneficial effect of 27a-sEVs on axonal remodeling.
基金National Natural Science Foundation of China(Grant Nos.51908188 and 51938011).
文摘The recent increase in blast/bombing incidents all over the world has pushed the development of effective strengthening approaches to enhance the blast resistance of existing civil infrastructures.Engineered geopolymer composite(EGC)is a promising material featured by eco-friendly,fast-setting and strain-hardening characteristics for emergent strengthening and construction.However,the fiber optimization for preparing EGC and its protective effect on structural elements under blast scenarios are uncertain.In this study,laboratory tests were firstly conducted to evaluate the effects of fiber types on the properties of EGC in terms of workability,dry shrinkage,and mechanical properties in compression,tension and flexure.The experimental results showed that EGC containing PE fiber exhibited suitable workability,acceptable dry shrinkage and superior mechanical properties compared with other types of fibers.After that,a series of field tests were carried out to evaluate the effectiveness of EGC retrofitting layer on the enhancement of blast performance of typical elements.The tests include autoclaved aerated concrete(AAC)masonry walls subjected to vented gas explosion,reinforced AAC panels subjected to TNT explosion and plain concrete slabs subjected to contact explosion.It was found that EGC could effectively enhance the blast resistance of structural elements in different scenarios.For AAC masonry walls and panels,with the existence of EGC,the integrity of specimens could be maintained,and their deflections and damage were significantly reduced.For plain concrete slabs,the EGC overlay could reduce the diameter and depth of the crater and spallation of specimens.
基金Supported by Guizhou Provincial Science and Technology Projects,No.[2021]013 and No.[2021]053Doctor Foundation of Guizhou Provincial People's Hospital,No.GZSYBS[2021]07.
文摘BACKGROUND Sarcopenia may be associated with hepatocellular carcinoma(HCC)following hepatectomy.But traditional single clinical variables are still insufficient to predict recurrence.We still lack effective prediction models for recent recurrence(time to recurrence<2 years)after hepatectomy for HCC.AIM To establish an interventable prediction model to estimate recurrence-free survival(RFS)after hepatectomy for HCC based on sarcopenia.METHODS We retrospectively analyzed 283 hepatitis B-related HCC patients who underwent curative hepatectomy for the first time,and the skeletal muscle index at the third lumbar spine was measured by preoperative computed tomography.94 of these patients were enrolled for external validation.Cox multivariate analysis was per-formed to identify the risk factors of postoperative recurrence in training cohort.A nomogram model was developed to predict the RFS of HCC patients,and its predictive performance was validated.The predictive efficacy of this model was evaluated using the receiver operating characteristic curve.RESULTS Multivariate analysis showed that sarcopenia[Hazard ratio(HR)=1.767,95%CI:1.166-2.678,P<0.05],alpha-fetoprotein≥40 ng/mL(HR=1.984,95%CI:1.307-3.011,P<0.05),the maximum diameter of tumor>5 cm(HR=2.222,95%CI:1.285-3.842,P<0.05),and hepatitis B virus DNA level≥2000 IU/mL(HR=2.1,95%CI:1.407-3.135,P<0.05)were independent risk factors associated with postoperative recurrence of HCC.Based on the sarcopenia to assess the RFS model of hepatectomy with hepatitis B-related liver cancer disease(SAMD)was established combined with other the above risk factors.The area under the curve of the SAMD model was 0.782(95%CI:0.705-0.858)in the training cohort(sensitivity 81%,specificity 63%)and 0.773(95%CI:0.707-0.838)in the validation cohort.Besides,a SAMD score≥110 was better to distinguish the high-risk group of postoperative recurrence of HCC.CONCLUSION Sarcopenia is associated with recent recurrence after hepatectomy for hepatitis B-related HCC.A nutritional status-based prediction model is first established for postoperative recurrence of hepatitis B-related HCC,which is superior to other models and contributes to prognosis prediction.
基金supported by the China Geological Survey project(DD20221649)the National Natural Science Foundation of China(Nos.U19B6003,42072135,and 42172119)+1 种基金Chongqing Research Program of Basic Research and Frontier Technology(Grant No.cstc2021jcyj-msxm X0023)Open Fund(DGERA 20211105)of Key Laboratory of Deep-time Geography and Environment Reconstruction and Applications of Ministry of Natural Resources,Chengdu University of Technology。
文摘The northeastern Sichuan area in the northern Yangtze margin has unique Ediacaran geological records,especially the Doushantuo Formation(DST),and become a hot research area in recent years.However,the Cryogenian-Ediacaran(C-E)boundary has not been precisely identified,which restricts the in-depth study of geological information during this crucial transitional period and is unfavorable for a systematic and complete understanding of the Yangtze Block and even the global paleogeographic pattern.This study conducted stratigraphy,sedimentology,and chronostratigraphy to establish the stratigraphic framework and sedimentary evolution of the C-E transition strata in northeastern Sichuan.The results showed that the Ediacaran sediments,without the cap dolomite,unconformably overlaid the Cryogenian sediments in the studied area.The Member II of the DST,characterized by 50-160 m of red-green sandstone(approximately equivalent to the original Chengkou“Guanyinya Formation”),directly overlaid the Cryogenian sediments and displayed a 623±2.3 Ma maximum depositional age from the detrital zircon U-Pb dating.Regional stratigraphic correlations indicate that the C-E transition strata in northeastern Sichuan had a consistent lithological association and sedimentary sequence characteristics but differed from the Three Gorges.Typically,the upper Nantuo massive glacial diamictites transition to the icebergs rafted lonestone-bearing mudstones at the top,then change upward to DST barrier coast sandstones.The proposed DST of the northeastern Sichuan Basin was divided into three lithostratigraphic members without the regional Member I cap dolomite:(i)Member II purple-red,gray-green sandstone strata,(ii)MemberⅢblack mudstone strata,and(iii)Member IV P-Mn bearing strata.During the C-E transition,the study area experienced(i)the global deglaciation stage in the terminal Marinoan glaciation and(ii)the filling-leveling up stage with clastic rocks in the early Ediacaran.Overall,the early Ediacaran of northeastern Sichuan succeeded the paleogeographic features of the late Cryogenian.
基金This work was supported by the National Natural Science Foundation of China(Nos.22138011,22205108,22378206)Open Research Fund of Key Laboratory of the Ministry of Education for Advanced Catalysis Materials and Zhejiang Key Laboratory for Reactive Chemistry on Solid Surfaces(KLMEACM 202201),Zhejiang Normal University.
文摘The insufficient active sites and slow interfacial charge trans-fer of photocatalysts restrict the efficiency of CO_(2) photoreduction.The synchronized modulation of the above key issues is demanding and chal-lenging.Herein,strain-induced strategy is developed to construct the Bi–O-bonded interface in Cu porphyrin-based monoatomic layer(PML-Cu)and Bi_(12)O_(17)Br_(2)(BOB),which triggers the surface interface dual polarization of PML-Cu/BOB(PBOB).In this multi-step polarization,the built-in electric field formed between the interfaces induces the electron transfer from con-duction band(CB)of BOB to CB of PML-Cu and suppresses its reverse migration.Moreover,the surface polarization of PML-Cu further promotes the electron converge in Cu atoms.The introduction of PML-Cu endows a high density of dispersed Cu active sites on the surface of PBOB,significantly promoting the adsorption and activation of CO_(2) and CO desorption.The conversion rate of CO_(2) photoreduction to CO for PBOB can reach 584.3μmol g-1,which is 7.83 times higher than BOB and 20.01 times than PML-Cu.This work offers valuable insights into multi-step polarization regulation and active site design for catalysts.
基金financial support of this work by Natural Science Foundation of China(22075031,51673030,51603017 and 51803011)Jilin Provincial Science&Technology Department(20220201105GX)Chang Bai Mountain Scholars Program of Jilin Province.
文摘For the reduction of bovine serum proteins from wastewater,a novel mixed matrix membrane was prepared by functionalizing the substrate material polyaryletherketone(PAEK),followed by carboxyl groups(C-SPAEKS),and then adding amino-functionalized UiO-66-NH_(2)(Am-UiO-66-NH_(2)).Aminofunctionalization of UiO-66 was accomplished by melamine,followed by an amidation reaction to immobilize Am-UiO-66-NH_(2),which was immobilized on the surface of the membrane as well as in the pore channels,which enhanced the hydrophilicity of the membrane surface while increasing the negative potential of the membrane surface.This nanoparticle-loaded ultrafiltration membrane has good permeation performance,with a pure water flux of up to 482.3 L·m^(-2)·h^(-1) for C-SPAEKS/AmUiO-66-NH_(2) and a retention rate of up to 98.7%for bovine serum albumin(BSA)-contaminated solutions.Meanwhile,after several hydrophilic modifications,the flux recovery of BSA contaminants by this series of membranes increased from 56.2%to 80.55%of pure membranes.The results of ultra-filtration flux time tests performed at room temperature showed that the series of ultrafiltration membranes remained relatively stable over a test time of 300 min.Thus,the newly developed mixed matrix membrane showed potential for high efficiency and stability in wastewater treatment containing bovine serum proteins.
基金This work is financially supported by the Key Laboratory of Icing and Anti/De-icing of CARDC(Grant No.IADL20210402)the National Natural Science Foundation of China(Grant Nos.12002350,12172314,11772278 and 11904300)+1 种基金the Jiangxi Provincial Outstanding Young Talents Program(Grant No.20192BCBL23029)the Fundamental Research Funds for the Central Universities(Xiamen University:Grant No.20720210025).
文摘Understanding the hydrate adhesion is important to tackling hydrate accretion in petro-pipelines.Herein,the relationship between the Tetrahydrofuran(THF)hydrate adhesion strength(AS)and surface stiffness on elastic coatings is systemically examined by experimental shear force measurements and theoretical methods.The mechanical factor-elastic modulus of the coatings greatly dictates the hydrate AS,which is explained by the adhesion mechanics theory,beyond the usual factors such as wettability and structural roughness.Moreover,the hydrate AS increases with reducing the thickness of the elastic coatings,resulted from the decrease of the apparent surface elastic modulus.The effect of critical thickness for the elastic materials with variable elastic modulus on the hydrate AS is also revealed.This study provides deep perspectives on the regulation of the hydrate AS by the elastic modulus of elastic materials,which is of significance to design anti-hydrate surfaces for mitigation of hydrate accretion in petro-pipelines.
文摘Chimeric antigen receptor-natural killer(CAR-NK) cells have emerged as another prominent player in the realm of tumor immunotherapy following CAR-T cells. The unique features of CAR-NK cells make it possible to compensate for deficiencies in CAR-T therapy, such as the complexity of the manufacturing process, clinical adverse events, and solid tumor challenges. To date, CAR-NK products from different allogeneic sources have exhibited remarkable anti-tumor effects on preclinical studies and have gradually been applied in clinical practice.However, each source has advantages and disadvantages. Selecting a suitable source may help maximize CAR-NK cell efficacy and increase the feasibility of clinical transformation. Therefore, this review discusses the development and challenges of CAR-NK cells from different sources to provide a reference for future exploration.
文摘The High Altitude Detection of Astronomical Radiation(HADAR)experiment,which was constructed in Tibet,China,combines the wide-angle advantages of traditional EAS array detectors with the high-sensitivity advantages of focused Cherenkov detectors.Its objective is to observe transient sources such as gamma-ray bursts and the counterparts of gravitational waves.This study aims to utilize the latest AI technology to enhance the sensitivity of HADAR experiments.Training datasets and models with distinctive creativity were constructed by incorporating the relevant physical theories for various applications.These models can determine the type,energy,and direction of the incident particles after careful design.We obtained a background identification accuracy of 98.6%,a relative energy reconstruction error of 10.0%,and an angular resolution of 0.22°in a test dataset at 10 TeV.These findings demonstrate the significant potential for enhancing the precision and dependability of detector data analysis in astrophysical research.By using deep learning techniques,the HADAR experiment’s observational sensitivity to the Crab Nebula has surpassed that of MAGIC and H.E.S.S.at energies below 0.5 TeV and remains competitive with conventional narrow-field Cherenkov telescopes at higher energies.In addition,our experiment offers a new approach for dealing with strongly connected,scattered data.
基金financially supported by the National Key R&D Program of China (2019YFC1605003)the Zhejiang Provincial Natural Science Foundation of China (LGN21C200013)。
文摘Bacillus coagulans has been extensively studied so far,but there has been a lack of research on its usage in allergy.In this study,we designed to assess the effect of different concentrations of B.coagulans on food allergy in a BALB/c mouse model of ovalbumin(OVA)-induced food allergy and its effect on gut microbes.The assessment of symptoms,specific immunoglobulin E(IgE),T-cell differentiation,and related gene expression levels in sensitized mice by assay indicated that high doses of oral B.coagulans could alleviate allergic symptoms.Treatment with B.coagulans,in the high-dose group,significantly reduced IgE and IgG1 levels and modulated the balance of T helper type 1 cell(Th1)and Th2 and the expression of relevant genes in the spleen.16S rRNA analysis showed that probiotics improved the structure of the microbiota,in particular by boosting the percentage of Clostridia,Bacteroides vulgatus and Enterococcus faecium,and by increasing the abundance of microbial species,thereby modulating the immune system.Therefore,this study can provide insights into the practical application of B.coagulans doses to alleviate OVA allergy.
基金Project supported by the National Natural Science Foundation of China (Grant No.51821005)。
文摘An externally generated resonant magnetic perturbation can induce complex non-ideal MHD responses in their resonant surfaces.We have studied the plasma responses using Fitzpatrick's improved two-fluid model and program LAYER.We calculated the error field penetration threshold for J-TEXT.In addition,we find that the island width increases slightly as the error field amplitude increases when the error field amplitude is below the critical penetration value.However,the island width suddenly jumps to a large value because the shielding effect of the plasma against the error field disappears after the penetration.By scanning the natural mode frequency,we find that the shielding effect of the plasma decreases as the natural mode frequency decreases.Finally,we obtain the m/n=2/1 penetration threshold scaling on density and temperature.
基金Supported by Henan Province Medical Science and Technology Research Provincial and Ministry Co-constructed Projects,No.SBGJ202101010Major Public Welfare Projects in Henan Province,No.201300310400+1 种基金Joint Construction Project of Henan Medical Science and Technology Research Plan,No.LHGJ20220050Major Science and Technology Project of Henan Province,No.221100310100.
文摘BACKGROUND Metabolic reprogramming plays a key role in cancer progression and clinical outcomes;however,the patterns and primary regulators of metabolic reprogramming in colorectal cancer(CRC)are not well understood.AIM To explore the role of nicotinamide adenine dinucleotide phosphate oxidase 4(NOX4)in promoting progression of CRC.METHODS We evaluated the expression and function of dysregulated and survival-related metabolic genes using Gene Ontology and Kyoto Encyclopedia of Genes and Genomes.Consensus clustering was used to cluster CRC based on dysregulated metabolic genes.A prediction model was constructed based on survival-related metabolic genes.Sphere formation,migration,invasion,proliferation,apoptosis and clone formation was used to evaluate the biological function of NOX4 in CRC.mRNA sequencing was utilized to explore the alterations of gene expression NOX4 over-expression tumor cells.In vivo subcutaneous and lung metastasis mouse tumor model was used to explore the effect of NOX4 on tumor growth.RESULTS We comprehensively analyzed 3341 metabolic genes in CRC and identified three clusters based on dysregulated metabolic genes.Among these genes,NOX4 was highly expressed in tumor tissues and correlated with worse survival.In vitro,NOX4 overexpression induced clone formation,migration,invasion,and stemness in CRC cells.Furthermore,RNA-sequencing analysis revealed that NOX4 overexpression activated the mitogen-activated protein kinase-MEK1/2-ERK1/2 signaling pathway.Trametinib,a MEK1/2 inhibitor,abolished the NOX4-mediated tumor progression.In vivo,NOX4 overexpression promoted subcutaneous tumor growth and lung metastasis,whereas trametinib treatment can reversed the metastasis.CONCLUSION Our study comprehensively analyzed metabolic gene expression and highlighted the importance of NOX4 in promoting CRC metastasis,suggesting that trametinib could be a potential therapeutic drugs of CRC clinical therapy targeting NOX4.
基金Supported by the National Natural Science Foundation of China,No.81972005and Taishan Scholar Program of Shandong Province,No.tsqn202306346 and No.tstp20221156.
文摘The morbidity and mortality of gastrointestinal(GI)malignancies are among the highest in the world,posing a serious threat to human health.Because of the insidious onset of the cancer,it is difficult for patients to be diagnosed at an early stage,and it rapidly progresses to an advanced stage,resulting in poor treatment and prognosis.Fusobacterium nucleatum(F.nucleatum)is a gram-negative,sporefree anaerobic bacterium that primarily colonizes the oral cavity and is implicated in the development of colorectal,esophageal,gastric,and pancreatic cancers via various intricate mechanisms.Recent development in novel research suggests that F.nucleatum may function as a biomarker in GI malignancies.Detecting the abundance of F.nucleatum in stool,saliva,and serum samples of patients may aid in the diagnosis,risk assessment,and prognosis monitoring of GI malignancies.This editorial systematically describes the biological roles and mechanisms of F.nucleatum in GI malignancies focusing on the application of F.nucleatum as a biomarker in the diagnosis and prognosis of GI malignancies to promote the clinical translation of F.nucleatum and GI tumors-related research.
基金Traditional Chinese Medicine Science and Technology Project in Jiangsu Province,No.YB2015113the Science and Technology Program of Nantong Health Committee,No.MA2019003,No.MA2021017,No.MB2021026,and No.MB2021027+1 种基金Science and Technology Program of Nantong City,No.Key003,No.MS12015016 and No.JCZ2022040Kangda College of Nanjing Medical University,No.KD2021JYYJYB025,No.KD2022KYJJZD019,No.KD2022KYJJZD022,and No.2023ZC127.
文摘BACKGROUND The neuroendoscopic approach has the advantages of a clear operative field,convenient tumor removal,and less damage,and is the development direction of modern neurosurgery.At present,transnasal surgery for sphenoidal pituitary tumor is widely used.But it has been found in clinical practice that some patients with this type of surgery may experience post-operative nausea and vomiting and other discomforts.AIM To explore the effect of reserved gastric tube application in the neuroendoscopic endonasal resection of pituitary tumors.METHODS A total of 60 patients who underwent pituitary adenoma resection via the endoscopic endonasal approach were selected and randomly divided into the experimental and control groups,with 30 in each group.Experimental group:After anesthesia,a gastric tube was placed through the mouth under direct vision using a visual laryngoscope,and the fluid accumulated in the oropharynx was suctioned intermittently with low negative pressure throughout the whole process after nasal disinfection,during the operation,and when the patient recovered from anesthesia.Control group:Given the routine intraoperative care,no gastric tube was left.The number of cases of nausea/vomiting/aspiration within 24 h post-operation was counted and compared between the two groups;the scores of pharyngalgia after waking up,6 h post-operation,and 24 h postoperation.The frequency of postoperative cerebrospinal fluid leakage and intracranial infection were compared.The hospitalization days of the two groups were statistically compared.RESULTS The times of postoperative nausea and vomiting in the experimental group were lower than that in the control group,and the difference in the incidence of nausea was statistically significant(P<0.05).After the patient woke up,the scores of sore throat 6 h after the operation and 24 h after operation were lower than those in the control group,and the difference was statistically significant(P<0.05).The number of cases of postoperative cerebrospinal fluid leakage and intracranial infection was higher than that of the control group,but there was no statistically significant difference from the control group(P>0.05).The hospitalization days of the experimental group was lower than that of the control group,and the difference was statistically significant(P<0.05).CONCLUSION Reserving a gastric tube in the endoscopic endonasal resection of pituitary tumors,combined with intraoperative and postoperative gastrointestinal decompression,can effectively reduce the incidence of nausea,reduce the number of vomiting and aspiration in patients,and reduce the complications of sore throat The incidence rate shortened the hospitalization days of the patients.