Materials with low thermal conductivity are applied extensively in energy management,and breaking the amorphous limits of thermal conductivity to solids has attracted widespread attention from scientists.Doping is a c...Materials with low thermal conductivity are applied extensively in energy management,and breaking the amorphous limits of thermal conductivity to solids has attracted widespread attention from scientists.Doping is a common strategy for achieving low thermal conductivity that can offer abundant scattering centers in which heavier dopants always result in lower phonon group velocities and lower thermal conductivities.However,the amount of equivalent heavyatom single dopant available is limited.Unfortunately,nonequivalent heavy dopants have finite solubility because of charge imbalance.Here,we propose a charge balance strategy for SnS by substituting Sn2+with Ag^(+)and heavy Bi^(3+),improving the doping limit of Ag from 2%to 3%.Ag and Bi codoping increases the point defect concentration and introduces abundant boundaries simultaneously,scattering the phonons at both the atomic scale and nanoscale.The thermal conductivity of Ag0.03Bi0.03Sn0.94S decreased to 0.535 W·m^(−1)·K^(−1)at room temperature and 0.388 W·m^(−1)·K^(−1)at 275°C,which is below the amorphous limit of 0.450 W·m^(−1)·K^(−1)for SnS.This strategy offers a simple way to enhance the doping limit and achieve ultralow thermal conductivity in solids below the amorphous limit without precise structural modification.展开更多
Background Increasing evidence supports the role of microRNAs(miRNAs)in major depressive disorder(MDD),but the pathophysiological mechanism remains elusive.Aims To explore the mechanism of microRNA-451a(miR-451a)in th...Background Increasing evidence supports the role of microRNAs(miRNAs)in major depressive disorder(MDD),but the pathophysiological mechanism remains elusive.Aims To explore the mechanism of microRNA-451a(miR-451a)in the pathology and behaviours of depression.Methods Abnormal miRNAs such as miR-451a reported previously in the serum of patients with MDD were screened and then confirmed in a mouse model of depression induced by chronic restraint stress(CRS).Eight-week-old male C57BL/6 mice had miR-451a overexpression in the medial prefrontal cortex(mPFC)via adeno-associated virus serotype 9 vectors encoding a pri-mmu-miR-451a-GFP fusion protein followed by behavioural and pathological analyses.Finally,molecular biological experiments were conducted to investigate the potential mechanism of miR-451a against depression.Results The serum levels of miRNA-451awere significantly lower in patients with MDD,with a negative correlation with the Hamilton Depression Scale scores.Additionally,a negative association between serum miR-451a and behavioural despair or anhedonia was observed in CRS mice.Notably,miR-451a expression was significantly downregulated in the mPFC of CRS-susceptible mice.Overexpressing miR-451a in the mPFC reversed the loss of dendritic spines and the depression-like phenotype of CRS mice.Mechanistically,miR-451a could inhibit CRS-induced corticotropin-releasing factor receptor 1 expression via targeting transcription factor 2,subsequently protecting dendritic spine plasticity.Conclusions Together,these results highlighted miR-451a as a candidate biomarker and therapeutic target for MDD.展开更多
Objective:To evaluate the therapeutic efficacy of alanyl-glutamine(Ala-Gln)in the nutritional support of sepsis.Methods:120 cases of sepsis patients admitted to the hospital in the past three years were selected and g...Objective:To evaluate the therapeutic efficacy of alanyl-glutamine(Ala-Gln)in the nutritional support of sepsis.Methods:120 cases of sepsis patients admitted to the hospital in the past three years were selected and grouped by randomization method,Group A was treated with Ala-Gln,and Group B was treated with conventional nutritional support therapy,and the therapeutic effects were compared.Results:Before treatment,there was no difference in nutritional indexes,immune function indexes,and inflammatory factors between the two groups(P>0.05).After treatment,the nutritional indexes of Group A were higher than those of Group B,the immune function indexes were higher than those of Group B,and the inflammatory factors were lower than those of Group B(P<0.05).Except for mortality,the regression of group A was better than that of group B(P<0.05).Conclusion:Ala-Gln can improve the nutritional indexes of septicemia patients during the treatment period,enhance their immune function,reduce the inflammatory response of the body,and promote the regression of the disease.展开更多
In this study,HEA/AI composite interlayer was used to fabricate Ti/Mg bimetal composites by solidliquid compound casting process.The Al layer was prepared on the surface of TC4 alloy by hot dipping,and the FeCoNiCr HE...In this study,HEA/AI composite interlayer was used to fabricate Ti/Mg bimetal composites by solidliquid compound casting process.The Al layer was prepared on the surface of TC4 alloy by hot dipping,and the FeCoNiCr HEA layer was prepared by magnetron sputtering onto the Al layer.The influence of the HEA layer thickness and pouring temperature on interface evolution was investigated based on SEM observation and thermodynamic analysis.Results indicate that the sluggish diffusion effect of HEA can effectively inhibit the interfacial diffusion between Al and Mg,which is conducive to the formation of solid solution,especially when the thickness of HEA is 800 nm.With the increase of casting temperature from 720 ℃ to 730 ℃,740℃,and 750 ℃,α-Al(Mg),α-Al(Mg)+Al3Mg2,Al3Mg2+Al12Mg17,and Al12Mg17+δ-Mg are formed at the interface of Ti/Mg bimetal,respectively.When the thickness of the HEA layer is 800 nm and the pouring temperature is 720 ℃,the bonding strength of the Ti/Mg bimetal can reach the maximum of 93.6 MPa.展开更多
Glioblastoma(GBM)is the most common malignant brain tumor.Although current treatment strategies,including surgery,chemotherapy,and radiotherapy,have achieved clinical effects and prolonged the survival of patients,the...Glioblastoma(GBM)is the most common malignant brain tumor.Although current treatment strategies,including surgery,chemotherapy,and radiotherapy,have achieved clinical effects and prolonged the survival of patients,the gradual development of resistance against current therapies has led to a high recurrence rate and treatment failure.Mechanisms underlying the development of resistance involve multiple factors,including drug efflux,DNA damage repair,glioma stem cells,and a hypoxic tumor environment,which are usually correlative and promote each other.As many potential therapeutic targets have been discovered,combination therapy that regulates multiple resistance-related molecule pathways is considered an attractive strategy.In recent years,nanomedicine has revolutionized cancer therapies with optimized accumulation,penetration,internalization,and controlled release.Blood-brain barrier(BBB)penetration efficiency is also significantly improved through modifying ligands on nanomedicine and interacting with the receptors or transporters on the BBB.Moreover,different drugs for combination therapy usually process different pharmacokinetics and biodistribution,which can be further optimized with drug delivery systems to maximize the therapeutic efficiency of combination therapies.Herein the current achievements in nanomedicine-based combination therapy for GBM are discussed.This review aimed to provide a broader understanding of resistance mechanisms and nanomedicine-based combination therapies for future research on GBM treatment.展开更多
Interface engineering can improve the charge separation efficiency and inhibit photocorrosion is an emerging direction of developing more efficient and cost-effective photocatalytic systems.Herein,we report the sulfur...Interface engineering can improve the charge separation efficiency and inhibit photocorrosion is an emerging direction of developing more efficient and cost-effective photocatalytic systems.Herein,we report the sulfur-confined intimate Cd S intergrown Cd(Cd S/Cd)Ohmic junction(peanut-chocolate-ball like)for high-efficient H2production with superior anti-photocorrosion ability,which was fabricated from in-situ photoreduction of CdS intergrown Cd2SO4(OH)2(CdS/Cd2SO4(OH)2)prepared through a facile space-controlled-solvothermal method.The ratios of CdS/Cd can be effectively controlled by tunning that of CdS/Cd2SO4(OH)2which were prepared by adjusting the volume of reaction liquid and the remaining space of the reactor.Experiments investigations and density functional theory(DFT)calculations reveal that the Cd S intergrown Cd Ohmic junction interfaces(with appropriate content Cd intergrown on Cd S(19.54 wt%))are beneficial in facilitating the transfer of photogenerated electrons by constructing an interfacial electric field and forming sulfur-confined structures for preventing the positive holes(h+)oxidize the Cd S.This contributes to a high photocatalytic H2production activity of 95.40μmol h-1(about 32.3 times higher than bare Cd S)and possesses outstanding photocatalytic stability over 205 h,much longer than most Cd S-based photocatalysts previously reported.The interface engineering design inspired by the structure of peanut-chocolate-ball can greatly promote the future development of catalytic systems for wider application.展开更多
Objective Ubiquitin conjugate enzyme E2O(UBE2O)is a ubiquitin-conjugating enzyme that has been reported to be involved in tumorigenesis.This study investigated the role of UBE2O in hepatocellular carcinoma(HCC).Method...Objective Ubiquitin conjugate enzyme E2O(UBE2O)is a ubiquitin-conjugating enzyme that has been reported to be involved in tumorigenesis.This study investigated the role of UBE2O in hepatocellular carcinoma(HCC).Methods The expression of UBE2O was detected using qRT-PCR,Western blotting,and immunohistochemical staining.Cell proliferation and Transwell assays were used to detect proliferation,migration,and invasion of HCC cells,respectively.Bioinformatic analysis was performed to analyze the relationship between UBE2O and the clinical features,prognosis,and immune cell infiltration of HCC.Results UBE2O was significantly over-expressed in HCC tissues.High expression of UBE2O was associated with poor tumor grade and poor prognosis.Functional experiments showed that down-regulation of UBE2O inhibited HCC cell proliferation,migration,and invasion.Co-expression gene analysis and gene set enrichment analysis showed that UBE2O was associated with protein hydrolysis,cell cycle,and cancer-related pathways in HCC.The results of immune analysis revealed that the expression of UBE2O was positively correlated with the immune infiltration and expression of immune-related chemokines of HCC.Conclusions UBE2O is significantly correlated with the prognosis of HCC and may be a valuable prognostic biomarker for HCC.展开更多
If the 20th century was the age of mapping and controlling the external world,the 21st century is the biomedical age of mapping and controlling the biological internal world.The biomedical age is bringing new technolo...If the 20th century was the age of mapping and controlling the external world,the 21st century is the biomedical age of mapping and controlling the biological internal world.The biomedical age is bringing new technological breakthroughs for sensing and controlling human biomolecules,cells,tissues,and organs,which underpin new frontiers in the biomedical discovery,data,biomanufacturing,and translational sciences.This article reviews what we believe will be the next wave of biomedical engineering(BME)education in support of the biomedical age,what we have termed BME 2.0.BME 2.0 was announced on October 122017 at BMES 49(https://www.bme.jhu.edu/news-events/news/miller-opens-2017-bmes-annual-meeting-with-vision-for-new-bme-era/).We present several principles upon which we believe the BME 2.0 curriculum should be constructed,and from these principles,we describe what view as the foundations that form the next generations of curricula in support of the BME enterprise.The core principles of BME 2.0 education are(a)educate students bilingually,from day 1,in the languages of modern molecular biology and the analytical modeling of complex biological systems;(b)prepare every student to be a biomedical data scientist;(c)build a unique BME community for discovery and innovation via a vertically integrated and convergent learning environment spanning the university and hospital systems;(d)champion an educational culture of inclusive excellence;and(e)codify in the curriculum ongoing discoveries at the frontiers of the discipline,thus ensuring BME 2.0 as a launchpad for training the future leaders of the biotechnology marketplaces.We envision that the BME 2.0 education is the path for providing every student with the training to lead in this new era of engineering the future of medicine in the 21st century.展开更多
Mycoplasma synoviae(M.synoviae)infections have become an increasingly serious concern in China because they cause huge economic losses to the poultry industry.Antibiotic treatment is one of control strategies that can...Mycoplasma synoviae(M.synoviae)infections have become an increasingly serious concern in China because they cause huge economic losses to the poultry industry.Antibiotic treatment is one of control strategies that can be used to contain clinical outbreaks in M.synoviae-free flocks,especially because the bacteria can be transmitted through eggs.To understand M.synoviae infection status in farms of central China and the antibiotic susceptibility of the circulating strains in vivo and in vitro,485 samples were collected from five provinces from 2019 to 2021.Fifty-two strains were isolated and identified.Determination of the minimum inhibitory concentration(MIC)of eight antibiotics(tylvalosin,tiamulin,tilmicosin,lincomycin,enrofloxacin,chlortetracycline,doxycycline and tylosin)for isolates showed that tylvalosin,doxycycline and tiamulin were effective against 52 clinical isolates(MIC values≤0.0625-0.25μg/mL,≤0.0625-1μg/mL,and 0.25-2μg/mL,respectively).Tilmicosin,enrofloxacin and lincomycin had high MICo values(>32μg/mL).An artificial M.synoviae infection model was established in chickens for evaluation of the short-term therapeutic effect of these antibiotics.After 5 days of medication,doxycycline(200 mg/L)showed a superior ability to inhibit M.synoviae compared with other groups,as did tylvalosin(200 mg/L).Furthermore,the therapeutic efficacy of tylvalosin(0.4μg/mL)on intra-embryo-injected M.synoviae was higher than that of tiamulin at the same dose.A combination of MiC values determined in vitro and therapeutic effects observed in vivo revealed that tylvalosin and doxycycline had the best therapeutic effects.Tylvalosin also showed better inhibitory effects on the vertical transmis-sion of M.synoviae than tiamulin.展开更多
BACKGROUND Osteopetrosis is a rare genetic disorder characterized by increased bone density due to defective bone resorption of osteoclasts.Approximately,80%of autosomal dominant osteopetrosis type II(ADO-II)patients ...BACKGROUND Osteopetrosis is a rare genetic disorder characterized by increased bone density due to defective bone resorption of osteoclasts.Approximately,80%of autosomal dominant osteopetrosis type II(ADO-II)patients were usually affected by heterozygous dominant mutations in the chloride voltage-gated channel 7(ClCN7)gene and present early-onset osteoarthritis or recurrent fractures.In this study,we report a case of persistent joint pain without bone injury or underlying history.CASE SUMMARY We report a 53-year-old female with joint pain who was accidentally diagnosed with ADO-II.The clinical diagnosis was based on increased bone density and typical radiographic features.Two heterozygous mutations in the ClCN7 and Tcell immune regulator 1(TCIRG1)genes by whole exome sequencing were identified in the patient and her daughter.The missense mutation(c.857G>A)occurred in the CLCN7 gene p.R286Q,which is highly conserved across species.The TCIRG1 gene point mutation(c.714-20G>A)in intron 7(near the splicing site of exon 7)had no effect on subsequent transcription.CONCLUSION This ADO-II case had a pathogenic CLCN7 mutation and late onset without the usual clinical symptoms.For the diagnosis and assessment of the prognosis for osteopetrosis,genetic analysis is advised.展开更多
Drought seriously affects the growth and development of plants.MiR159 is a highly conserved and abundant microRNA family that plays a crucial role in plant growth and stress responses.However,studies of its function i...Drought seriously affects the growth and development of plants.MiR159 is a highly conserved and abundant microRNA family that plays a crucial role in plant growth and stress responses.However,studies of its function in woody plants are still lacking.Here,the expression of miR159a was significantly upregulated after drought treatment in poplar,and the overexpression of miR159a(OX159a)significantly reduced the open area of the stomata and improved water-use efficiency in poplar.After drought treatment,OX159a lines had better scavenging ability of reactive oxygen species and damage of the membrane system was less than that in wild-type lines.MYB was the target gene of miR159a,as verified by psRNATarget prediction,RT-qPCR,degradome sequencing,and 5′rapid amplification of cDNA ends(5′RACE).Additionally,miR159a-short tandem target mimic suppression(STTM)poplar lines showed increased sensitivity to drought stress.Transcriptomic analysis comparing OX159a lines with wild-type lines revealed upregulation of a series of genes related to response to water deprivation and metabolite synthesis.Moreover,drought-responsive miR172d and miR398 were significantly upregulated and downregulated respectively in OX159a lines.This investigation demonstrated that miR159a played a key role in the tolerance of poplar to drought by reducing stomata open area,increasing the number and total area of xylem vessels,and enhancing water-use efficiency,and provided new insights into the role of plant miR159a and crucial candidate genes for the molecular breeding of trees with tolerance to drought stress.展开更多
In the article“BME 2.0:Engineering the Future of Medicine”[1],the competing interests statement was inadvertently omitted by the publisher from the published version of the article.This has now been corrected in the...In the article“BME 2.0:Engineering the Future of Medicine”[1],the competing interests statement was inadvertently omitted by the publisher from the published version of the article.This has now been corrected in the PDF and HTML(full text).展开更多
Background: Community based cervical cancer screening models using self-collection can effectively place the identification of who is positive in the hands of the patient. The key areas we have identified as critical ...Background: Community based cervical cancer screening models using self-collection can effectively place the identification of who is positive in the hands of the patient. The key areas we have identified as critical are 1) education, 2) notification of screening opportunities, 3) registration, 4) submission of samples, 5) receiving results with an explanation, and 6) being advised where to receive evaluation and management from qualified healthcare personnel. Methods: Our primary objectives were to create, register, and pilot a website as a public platform for cervical cancer prevention for both city and rural, individual and organizational application. We selected two sites: Shenzhen City in China as the local city (individual participant) site, and Sangzhi County in Hunan Province as the remote (group management) site. The website was reviewable to all of China, but applications for screening and registration were open only to the women from the 2 pilot sites. In the local site, the women would first sign up (obtain a password) to view the website (www.mcareu.com), and then if they desired, they could register for screening using their true name and their state ID. After an offline confirmation of the address, the sampling kit would arrive. Results were available with additional education and guidance for care also on the website. Findings: 120,099 people nationwide visited the website in 27 months by the end of May, 2015, 1148 women from the sites registered at the website and 87.5% enrolled in the pilot trial. 72.3% of those testing positive returned for management. Virtually 100% of the registration/historical information was entered appropriately and 100% of the samples were handled properly. Interpretation: Web-based decision aids help patients through the uncertainties of healthcare. Applied to cervical cancer screening using self-collection, the effectiveness of the model specifically in respect to accessibility, education, registration, data input, and instructions for positive management was clearly demonstrated by this pilot as well as the potential for future diagnostics applicable to self-collection.展开更多
Metabolism of S-nitrosoglutathione （GSNO）, a major biologically active nitric oxide （NO） species, is catalyzed by the evolutionally conserved GSNO reductase （GSNOR）. Previous studies showed that the Arabidopsis ...Metabolism of S-nitrosoglutathione （GSNO）, a major biologically active nitric oxide （NO） species, is catalyzed by the evolutionally conserved GSNO reductase （GSNOR）. Previous studies showed that the Arabidopsis GSNOR1/ HOT5 gene regulates salicylic acid signaling and thermotolerance by modulating the intracellular S-nitrosothiol level. Here, we report the characterization of the Arabidopsisparaquat resistant2-1 （par2-1） mutant that shows an anti-cell death phenotype. The production of superoxide in par2-1 is comparable to that of wild-type plants when treated by paraquat （1,1＇-dimethyl-4,4＇-bipyridinium dichloride）, suggesting that PAR2 acts downstream of superoxide to regulate cell death. PAR2, identified by positional cloning, is shown to be identical to GSNOR1/HOT5. The par2-1 mutant carries a missense mutation in a highly conserved glycine, which renders the mutant protein unstable. Compared to wild type, par2-1 mutant has a higher NO level, as revealed by staining with 4,5-diaminofluorescein diacetate. Consistent with this result, wild-type plants treated with an NO donor display resistance to paraquat. Interestingly, the GSNOR1/HOT5/PAR2 protein level, other than its steady-state mRNA level, is induced by paraquat, but is reduced by NO donors. Taken together, these results suggest that GSNOR1/HOT5/PAR2 plays an important role in regulating cell death in plant cells through modulating intracellular NO level.展开更多
Mild therapeutic hypothermia has been shown to mitigate cerebral ischemia, reduce cerebral edema, and improve the prognosis of patients with cerebral ischemia. Adipose-derived stem cell-based therapy can decrease neur...Mild therapeutic hypothermia has been shown to mitigate cerebral ischemia, reduce cerebral edema, and improve the prognosis of patients with cerebral ischemia. Adipose-derived stem cell-based therapy can decrease neuronal death and infiltration of inflammatory cells, exerting a neuroprotective effect. We hypothesized that the combination of mild therapeutic hypothermia and adipose-derived stem cells would be neuroprotective for treatment of stroke. A rat model of transient middle cerebral artery occlusion was established using the nylon monofilament method. Mild therapeutic hypothermia（33°C） was induced after 2 hours of ischemia. Adipose-derived stem cells were administered through the femoral vein during reperfusion. The severity of neurological dysfunction was measured by a modified Neurological Severity Score Scaling System. The area of the infarct lesion was determined by 2,3,5-triphenyltetrazolium chloride staining. Apoptotic neurons were detected by terminal deoxynucleotidyl transferase-mediated d UTP-biotin nick end labeling（TUNEL） staining. The regeneration of microvessels and changes in the glial scar were detected by immunofluorescence staining. The inflammatory responses after ischemic brain injury were evaluated by in situ staining using markers of inflammatory cells. The expression of inflammatory cytokines was measured by reverse transcription-polymerase chain reaction. Compared with mild therapeutic hypothermia or adipose-derived stem cell treatment alone, their combination substantially improved neurological deficits and decreased infarct size. They synergistically reduced the number of TUNEL-positive cells and glial fibrillary acidic protein expression, increased vascular endothelial growth factor levels, effectively reduced inflammatory cell infiltration and down-regulated the m RNA expression of the proinflammatory cytokines interleukin-1β, tumor necrosis factor-α and interleukin-6. Our findings indicate that combined treatment is a better approach for treating stroke compared with mild therapeutic hypothermia or adipose-derived stem cells alone.展开更多
The aim of this present study is to examine the efficacy of attribution retraining group therapy （ARGT） and to compare the responses of outpatients with major depression disorder （MDD）, generalized anxiety disord...The aim of this present study is to examine the efficacy of attribution retraining group therapy （ARGT） and to compare the responses of outpatients with major depression disorder （MDD）, generalized anxiety disorder （GAD） and obsessive-compulsive disorder （OCD）. We carried out a prospective uncontrolled intervention study with a 8-weeks of ARGT on sixty three outpatients with MDD, GAD or OCD. Hamilton rating scale for depression, Hamilton rating scale for anxiety, Yale-Brown obsessive-compulsive scale, attribution style questionnaire, self-esteem scale, index of well-being, and social disability screening schedule were administered before and after treatment. Significant improvement in symptoms and psychological and social functions from pre- to posttreatment occurred for all participants. The changes favored MDD patients. Our study suggested that ARGT may improve the symptoms and psychological-social functions of MDD, GAD, and OCD patients. MDD patients showed the best response.展开更多
Objective:To detect the CHRNA7 gene mutation and polymorphism in Southern Han Chinese patients with nocturnal frontal lobe epilepsy(NFLE).Methods:Blood samples were collected from 215 Southern Han Chinese patients wit...Objective:To detect the CHRNA7 gene mutation and polymorphism in Southern Han Chinese patients with nocturnal frontal lobe epilepsy(NFLE).Methods:Blood samples were collected from 215 Southern Han Chinese patients with NFLE and 200 healthy Southern Han Chinese control subjects.Genomic DNA was extracted,and CHRNA7 whole genome exons were amplified by the polymerase chain reaction and subjected to Sanger sequencing.Results:No CHRNA7 gene mutation was detected in all of the NFLE patients.However,five single nucleotide polymorphisms(SNPs)in sporadic cases were found,located in exons 5,6.and 7 of the CHRNA7 gene.Among them,c.690G>A and c.698A>G are known SNPs,while c.370G>A,c.654C>T,and c.497-498delTG were newly discovered SNPs.These SNPs were also found in some of the healthy controls.Conclusions:No CHRNA7 gene mutation was identified in Southern Han Chinese patients with NFLE.The CHRNA7 gene is probably not responsible for NFLE in this population.展开更多
基金supported by the CAS Project for Young Scientists in Basic Research(YSBR-070)the National Natural Science Foundation of China(21925110,21890750,U2032161,12147105)+8 种基金the USTC Research Funds of the Double First-Class Initiative(YD2060002004)the National Key Research and Development Program of China(2022YFA1203600,2022YFA1203601,2022YFA1203602)the Natural Science Foundation of China-Anhui Joint Fund(U23A20121)the Outstanding Youth Foundation of Anhui Province(2208085J14)the Anhui Provincial Key Research and Development Project(202004a050200760)the Key R&D Program of Shandong Province(2021CXGC010302)the Users with Excellence Project of Hefei Science Center CAS(2021HSC-UE004)the Fellowship of the China Postdoctoral Science Foundation(2022M710141)the open foundation of the Key Laboratory of the Engineering Research Center of Building Energy Efficiency Control and Evaluation,Ministry of Education(AHJZNX-2023-04).
文摘Materials with low thermal conductivity are applied extensively in energy management,and breaking the amorphous limits of thermal conductivity to solids has attracted widespread attention from scientists.Doping is a common strategy for achieving low thermal conductivity that can offer abundant scattering centers in which heavier dopants always result in lower phonon group velocities and lower thermal conductivities.However,the amount of equivalent heavyatom single dopant available is limited.Unfortunately,nonequivalent heavy dopants have finite solubility because of charge imbalance.Here,we propose a charge balance strategy for SnS by substituting Sn2+with Ag^(+)and heavy Bi^(3+),improving the doping limit of Ag from 2%to 3%.Ag and Bi codoping increases the point defect concentration and introduces abundant boundaries simultaneously,scattering the phonons at both the atomic scale and nanoscale.The thermal conductivity of Ag0.03Bi0.03Sn0.94S decreased to 0.535 W·m^(−1)·K^(−1)at room temperature and 0.388 W·m^(−1)·K^(−1)at 275°C,which is below the amorphous limit of 0.450 W·m^(−1)·K^(−1)for SnS.This strategy offers a simple way to enhance the doping limit and achieve ultralow thermal conductivity in solids below the amorphous limit without precise structural modification.
基金grants from the National Natural Science Foundation of China(81801378 and 81871117).
文摘Background Increasing evidence supports the role of microRNAs(miRNAs)in major depressive disorder(MDD),but the pathophysiological mechanism remains elusive.Aims To explore the mechanism of microRNA-451a(miR-451a)in the pathology and behaviours of depression.Methods Abnormal miRNAs such as miR-451a reported previously in the serum of patients with MDD were screened and then confirmed in a mouse model of depression induced by chronic restraint stress(CRS).Eight-week-old male C57BL/6 mice had miR-451a overexpression in the medial prefrontal cortex(mPFC)via adeno-associated virus serotype 9 vectors encoding a pri-mmu-miR-451a-GFP fusion protein followed by behavioural and pathological analyses.Finally,molecular biological experiments were conducted to investigate the potential mechanism of miR-451a against depression.Results The serum levels of miRNA-451awere significantly lower in patients with MDD,with a negative correlation with the Hamilton Depression Scale scores.Additionally,a negative association between serum miR-451a and behavioural despair or anhedonia was observed in CRS mice.Notably,miR-451a expression was significantly downregulated in the mPFC of CRS-susceptible mice.Overexpressing miR-451a in the mPFC reversed the loss of dendritic spines and the depression-like phenotype of CRS mice.Mechanistically,miR-451a could inhibit CRS-induced corticotropin-releasing factor receptor 1 expression via targeting transcription factor 2,subsequently protecting dendritic spine plasticity.Conclusions Together,these results highlighted miR-451a as a candidate biomarker and therapeutic target for MDD.
文摘Objective:To evaluate the therapeutic efficacy of alanyl-glutamine(Ala-Gln)in the nutritional support of sepsis.Methods:120 cases of sepsis patients admitted to the hospital in the past three years were selected and grouped by randomization method,Group A was treated with Ala-Gln,and Group B was treated with conventional nutritional support therapy,and the therapeutic effects were compared.Results:Before treatment,there was no difference in nutritional indexes,immune function indexes,and inflammatory factors between the two groups(P>0.05).After treatment,the nutritional indexes of Group A were higher than those of Group B,the immune function indexes were higher than those of Group B,and the inflammatory factors were lower than those of Group B(P<0.05).Except for mortality,the regression of group A was better than that of group B(P<0.05).Conclusion:Ala-Gln can improve the nutritional indexes of septicemia patients during the treatment period,enhance their immune function,reduce the inflammatory response of the body,and promote the regression of the disease.
基金financial supports from the National Natural Science Foundation of China (No. 51875062)China Postdoctoral Science Foundation (No. 2021M700567)。
文摘In this study,HEA/AI composite interlayer was used to fabricate Ti/Mg bimetal composites by solidliquid compound casting process.The Al layer was prepared on the surface of TC4 alloy by hot dipping,and the FeCoNiCr HEA layer was prepared by magnetron sputtering onto the Al layer.The influence of the HEA layer thickness and pouring temperature on interface evolution was investigated based on SEM observation and thermodynamic analysis.Results indicate that the sluggish diffusion effect of HEA can effectively inhibit the interfacial diffusion between Al and Mg,which is conducive to the formation of solid solution,especially when the thickness of HEA is 800 nm.With the increase of casting temperature from 720 ℃ to 730 ℃,740℃,and 750 ℃,α-Al(Mg),α-Al(Mg)+Al3Mg2,Al3Mg2+Al12Mg17,and Al12Mg17+δ-Mg are formed at the interface of Ti/Mg bimetal,respectively.When the thickness of the HEA layer is 800 nm and the pouring temperature is 720 ℃,the bonding strength of the Ti/Mg bimetal can reach the maximum of 93.6 MPa.
基金supported by the National Key Research and Development Programs of China(Grant No.2018YFA0209700)National Natural Science Foundation of China(Grant No.22077073)+1 种基金Frontiers Science Center for New Organic Matter,Nankai University(Grant No.63181206)the Fundamental Research Funds for the Central Universities,Nankai University(Grant No.63206015)。
文摘Glioblastoma(GBM)is the most common malignant brain tumor.Although current treatment strategies,including surgery,chemotherapy,and radiotherapy,have achieved clinical effects and prolonged the survival of patients,the gradual development of resistance against current therapies has led to a high recurrence rate and treatment failure.Mechanisms underlying the development of resistance involve multiple factors,including drug efflux,DNA damage repair,glioma stem cells,and a hypoxic tumor environment,which are usually correlative and promote each other.As many potential therapeutic targets have been discovered,combination therapy that regulates multiple resistance-related molecule pathways is considered an attractive strategy.In recent years,nanomedicine has revolutionized cancer therapies with optimized accumulation,penetration,internalization,and controlled release.Blood-brain barrier(BBB)penetration efficiency is also significantly improved through modifying ligands on nanomedicine and interacting with the receptors or transporters on the BBB.Moreover,different drugs for combination therapy usually process different pharmacokinetics and biodistribution,which can be further optimized with drug delivery systems to maximize the therapeutic efficiency of combination therapies.Herein the current achievements in nanomedicine-based combination therapy for GBM are discussed.This review aimed to provide a broader understanding of resistance mechanisms and nanomedicine-based combination therapies for future research on GBM treatment.
基金supported by the National Natural Science Foundation of China(22162008,22162007)the Science and Technology Supporting Project of Guizhou Province([2022]208,[2021]480)the Basic Research Program of Science&Technology Department of Guizhou Province([2020]1Y055)。
文摘Interface engineering can improve the charge separation efficiency and inhibit photocorrosion is an emerging direction of developing more efficient and cost-effective photocatalytic systems.Herein,we report the sulfur-confined intimate Cd S intergrown Cd(Cd S/Cd)Ohmic junction(peanut-chocolate-ball like)for high-efficient H2production with superior anti-photocorrosion ability,which was fabricated from in-situ photoreduction of CdS intergrown Cd2SO4(OH)2(CdS/Cd2SO4(OH)2)prepared through a facile space-controlled-solvothermal method.The ratios of CdS/Cd can be effectively controlled by tunning that of CdS/Cd2SO4(OH)2which were prepared by adjusting the volume of reaction liquid and the remaining space of the reactor.Experiments investigations and density functional theory(DFT)calculations reveal that the Cd S intergrown Cd Ohmic junction interfaces(with appropriate content Cd intergrown on Cd S(19.54 wt%))are beneficial in facilitating the transfer of photogenerated electrons by constructing an interfacial electric field and forming sulfur-confined structures for preventing the positive holes(h+)oxidize the Cd S.This contributes to a high photocatalytic H2production activity of 95.40μmol h-1(about 32.3 times higher than bare Cd S)and possesses outstanding photocatalytic stability over 205 h,much longer than most Cd S-based photocatalysts previously reported.The interface engineering design inspired by the structure of peanut-chocolate-ball can greatly promote the future development of catalytic systems for wider application.
基金supported by grants from the National Natural Science Foundation of China(No.81670554 and No.8217113366)the Science and Technology Plan of Wuhan City(No.2020020601012208)+2 种基金the Natural Science Fund for Distinguished Young Scholars of Hubei Province(No.2017CFA068)the National Key R&D Program of China(No.2019YFC0121505)the Science and Technology Innovation Cultivation Fund of Zhongnan Hospital of Wuhan University(No.CXPY2020042).
文摘Objective Ubiquitin conjugate enzyme E2O(UBE2O)is a ubiquitin-conjugating enzyme that has been reported to be involved in tumorigenesis.This study investigated the role of UBE2O in hepatocellular carcinoma(HCC).Methods The expression of UBE2O was detected using qRT-PCR,Western blotting,and immunohistochemical staining.Cell proliferation and Transwell assays were used to detect proliferation,migration,and invasion of HCC cells,respectively.Bioinformatic analysis was performed to analyze the relationship between UBE2O and the clinical features,prognosis,and immune cell infiltration of HCC.Results UBE2O was significantly over-expressed in HCC tissues.High expression of UBE2O was associated with poor tumor grade and poor prognosis.Functional experiments showed that down-regulation of UBE2O inhibited HCC cell proliferation,migration,and invasion.Co-expression gene analysis and gene set enrichment analysis showed that UBE2O was associated with protein hydrolysis,cell cycle,and cancer-related pathways in HCC.The results of immune analysis revealed that the expression of UBE2O was positively correlated with the immune infiltration and expression of immune-related chemokines of HCC.Conclusions UBE2O is significantly correlated with the prognosis of HCC and may be a valuable prognostic biomarker for HCC.
基金This work was funded by NIH grants R01EB020062(M.I.M.),R01NS102670(M.I.M.)U19AG033655.
文摘If the 20th century was the age of mapping and controlling the external world,the 21st century is the biomedical age of mapping and controlling the biological internal world.The biomedical age is bringing new technological breakthroughs for sensing and controlling human biomolecules,cells,tissues,and organs,which underpin new frontiers in the biomedical discovery,data,biomanufacturing,and translational sciences.This article reviews what we believe will be the next wave of biomedical engineering(BME)education in support of the biomedical age,what we have termed BME 2.0.BME 2.0 was announced on October 122017 at BMES 49(https://www.bme.jhu.edu/news-events/news/miller-opens-2017-bmes-annual-meeting-with-vision-for-new-bme-era/).We present several principles upon which we believe the BME 2.0 curriculum should be constructed,and from these principles,we describe what view as the foundations that form the next generations of curricula in support of the BME enterprise.The core principles of BME 2.0 education are(a)educate students bilingually,from day 1,in the languages of modern molecular biology and the analytical modeling of complex biological systems;(b)prepare every student to be a biomedical data scientist;(c)build a unique BME community for discovery and innovation via a vertically integrated and convergent learning environment spanning the university and hospital systems;(d)champion an educational culture of inclusive excellence;and(e)codify in the curriculum ongoing discoveries at the frontiers of the discipline,thus ensuring BME 2.0 as a launchpad for training the future leaders of the biotechnology marketplaces.We envision that the BME 2.0 education is the path for providing every student with the training to lead in this new era of engineering the future of medicine in the 21st century.
基金This work was supported by the Key Research and Development Project of Hubei Province(Grant No.2021BBA252)the Earmarked Fund for China Agriculture Research System(CARS-41).
文摘Mycoplasma synoviae(M.synoviae)infections have become an increasingly serious concern in China because they cause huge economic losses to the poultry industry.Antibiotic treatment is one of control strategies that can be used to contain clinical outbreaks in M.synoviae-free flocks,especially because the bacteria can be transmitted through eggs.To understand M.synoviae infection status in farms of central China and the antibiotic susceptibility of the circulating strains in vivo and in vitro,485 samples were collected from five provinces from 2019 to 2021.Fifty-two strains were isolated and identified.Determination of the minimum inhibitory concentration(MIC)of eight antibiotics(tylvalosin,tiamulin,tilmicosin,lincomycin,enrofloxacin,chlortetracycline,doxycycline and tylosin)for isolates showed that tylvalosin,doxycycline and tiamulin were effective against 52 clinical isolates(MIC values≤0.0625-0.25μg/mL,≤0.0625-1μg/mL,and 0.25-2μg/mL,respectively).Tilmicosin,enrofloxacin and lincomycin had high MICo values(>32μg/mL).An artificial M.synoviae infection model was established in chickens for evaluation of the short-term therapeutic effect of these antibiotics.After 5 days of medication,doxycycline(200 mg/L)showed a superior ability to inhibit M.synoviae compared with other groups,as did tylvalosin(200 mg/L).Furthermore,the therapeutic efficacy of tylvalosin(0.4μg/mL)on intra-embryo-injected M.synoviae was higher than that of tiamulin at the same dose.A combination of MiC values determined in vitro and therapeutic effects observed in vivo revealed that tylvalosin and doxycycline had the best therapeutic effects.Tylvalosin also showed better inhibitory effects on the vertical transmis-sion of M.synoviae than tiamulin.
基金Supported by the Science and Technology Plan Program of Sichuan of China,No.2018JY0608。
文摘BACKGROUND Osteopetrosis is a rare genetic disorder characterized by increased bone density due to defective bone resorption of osteoclasts.Approximately,80%of autosomal dominant osteopetrosis type II(ADO-II)patients were usually affected by heterozygous dominant mutations in the chloride voltage-gated channel 7(ClCN7)gene and present early-onset osteoarthritis or recurrent fractures.In this study,we report a case of persistent joint pain without bone injury or underlying history.CASE SUMMARY We report a 53-year-old female with joint pain who was accidentally diagnosed with ADO-II.The clinical diagnosis was based on increased bone density and typical radiographic features.Two heterozygous mutations in the ClCN7 and Tcell immune regulator 1(TCIRG1)genes by whole exome sequencing were identified in the patient and her daughter.The missense mutation(c.857G>A)occurred in the CLCN7 gene p.R286Q,which is highly conserved across species.The TCIRG1 gene point mutation(c.714-20G>A)in intron 7(near the splicing site of exon 7)had no effect on subsequent transcription.CONCLUSION This ADO-II case had a pathogenic CLCN7 mutation and late onset without the usual clinical symptoms.For the diagnosis and assessment of the prognosis for osteopetrosis,genetic analysis is advised.
基金This work was supported by the National Natural Science Foundation of China(32371577)the Beijing Natural Science Foundation(6232030)the Major Project of Agricultural Biological Breeding(2022ZD0401503).
文摘Drought seriously affects the growth and development of plants.MiR159 is a highly conserved and abundant microRNA family that plays a crucial role in plant growth and stress responses.However,studies of its function in woody plants are still lacking.Here,the expression of miR159a was significantly upregulated after drought treatment in poplar,and the overexpression of miR159a(OX159a)significantly reduced the open area of the stomata and improved water-use efficiency in poplar.After drought treatment,OX159a lines had better scavenging ability of reactive oxygen species and damage of the membrane system was less than that in wild-type lines.MYB was the target gene of miR159a,as verified by psRNATarget prediction,RT-qPCR,degradome sequencing,and 5′rapid amplification of cDNA ends(5′RACE).Additionally,miR159a-short tandem target mimic suppression(STTM)poplar lines showed increased sensitivity to drought stress.Transcriptomic analysis comparing OX159a lines with wild-type lines revealed upregulation of a series of genes related to response to water deprivation and metabolite synthesis.Moreover,drought-responsive miR172d and miR398 were significantly upregulated and downregulated respectively in OX159a lines.This investigation demonstrated that miR159a played a key role in the tolerance of poplar to drought by reducing stomata open area,increasing the number and total area of xylem vessels,and enhancing water-use efficiency,and provided new insights into the role of plant miR159a and crucial candidate genes for the molecular breeding of trees with tolerance to drought stress.
文摘In the article“BME 2.0:Engineering the Future of Medicine”[1],the competing interests statement was inadvertently omitted by the publisher from the published version of the article.This has now been corrected in the PDF and HTML(full text).
文摘Background: Community based cervical cancer screening models using self-collection can effectively place the identification of who is positive in the hands of the patient. The key areas we have identified as critical are 1) education, 2) notification of screening opportunities, 3) registration, 4) submission of samples, 5) receiving results with an explanation, and 6) being advised where to receive evaluation and management from qualified healthcare personnel. Methods: Our primary objectives were to create, register, and pilot a website as a public platform for cervical cancer prevention for both city and rural, individual and organizational application. We selected two sites: Shenzhen City in China as the local city (individual participant) site, and Sangzhi County in Hunan Province as the remote (group management) site. The website was reviewable to all of China, but applications for screening and registration were open only to the women from the 2 pilot sites. In the local site, the women would first sign up (obtain a password) to view the website (www.mcareu.com), and then if they desired, they could register for screening using their true name and their state ID. After an offline confirmation of the address, the sampling kit would arrive. Results were available with additional education and guidance for care also on the website. Findings: 120,099 people nationwide visited the website in 27 months by the end of May, 2015, 1148 women from the sites registered at the website and 87.5% enrolled in the pilot trial. 72.3% of those testing positive returned for management. Virtually 100% of the registration/historical information was entered appropriately and 100% of the samples were handled properly. Interpretation: Web-based decision aids help patients through the uncertainties of healthcare. Applied to cervical cancer screening using self-collection, the effectiveness of the model specifically in respect to accessibility, education, registration, data input, and instructions for positive management was clearly demonstrated by this pilot as well as the potential for future diagnostics applicable to self-collection.
基金We thank Dr Gary Loake （University of Edinburgh, UK） for providing gsnor1-3 seeds. We are grateful to Drs Chuanyou Li, Shuhua Yang and Yiqin Wang for critically reading the manuscript. This study was supported by grants from the National Natural Science Foundation of China （30330360）, the Ministry of Science and Technology of China （2006AA 10A 112） and the Chinese Academy of Sciences （KSCX2-YW-N-015）.
文摘Metabolism of S-nitrosoglutathione （GSNO）, a major biologically active nitric oxide （NO） species, is catalyzed by the evolutionally conserved GSNO reductase （GSNOR）. Previous studies showed that the Arabidopsis GSNOR1/ HOT5 gene regulates salicylic acid signaling and thermotolerance by modulating the intracellular S-nitrosothiol level. Here, we report the characterization of the Arabidopsisparaquat resistant2-1 （par2-1） mutant that shows an anti-cell death phenotype. The production of superoxide in par2-1 is comparable to that of wild-type plants when treated by paraquat （1,1＇-dimethyl-4,4＇-bipyridinium dichloride）, suggesting that PAR2 acts downstream of superoxide to regulate cell death. PAR2, identified by positional cloning, is shown to be identical to GSNOR1/HOT5. The par2-1 mutant carries a missense mutation in a highly conserved glycine, which renders the mutant protein unstable. Compared to wild type, par2-1 mutant has a higher NO level, as revealed by staining with 4,5-diaminofluorescein diacetate. Consistent with this result, wild-type plants treated with an NO donor display resistance to paraquat. Interestingly, the GSNOR1/HOT5/PAR2 protein level, other than its steady-state mRNA level, is induced by paraquat, but is reduced by NO donors. Taken together, these results suggest that GSNOR1/HOT5/PAR2 plays an important role in regulating cell death in plant cells through modulating intracellular NO level.
基金supported by the National Natural Science Foundation of China,No.81371301
文摘Mild therapeutic hypothermia has been shown to mitigate cerebral ischemia, reduce cerebral edema, and improve the prognosis of patients with cerebral ischemia. Adipose-derived stem cell-based therapy can decrease neuronal death and infiltration of inflammatory cells, exerting a neuroprotective effect. We hypothesized that the combination of mild therapeutic hypothermia and adipose-derived stem cells would be neuroprotective for treatment of stroke. A rat model of transient middle cerebral artery occlusion was established using the nylon monofilament method. Mild therapeutic hypothermia（33°C） was induced after 2 hours of ischemia. Adipose-derived stem cells were administered through the femoral vein during reperfusion. The severity of neurological dysfunction was measured by a modified Neurological Severity Score Scaling System. The area of the infarct lesion was determined by 2,3,5-triphenyltetrazolium chloride staining. Apoptotic neurons were detected by terminal deoxynucleotidyl transferase-mediated d UTP-biotin nick end labeling（TUNEL） staining. The regeneration of microvessels and changes in the glial scar were detected by immunofluorescence staining. The inflammatory responses after ischemic brain injury were evaluated by in situ staining using markers of inflammatory cells. The expression of inflammatory cytokines was measured by reverse transcription-polymerase chain reaction. Compared with mild therapeutic hypothermia or adipose-derived stem cell treatment alone, their combination substantially improved neurological deficits and decreased infarct size. They synergistically reduced the number of TUNEL-positive cells and glial fibrillary acidic protein expression, increased vascular endothelial growth factor levels, effectively reduced inflammatory cell infiltration and down-regulated the m RNA expression of the proinflammatory cytokines interleukin-1β, tumor necrosis factor-α and interleukin-6. Our findings indicate that combined treatment is a better approach for treating stroke compared with mild therapeutic hypothermia or adipose-derived stem cells alone.
基金supported by national science and technology support projects (No.2009BA177B07)Natural Science Foundation of Jiangsu Province,China (No.PBBS1-102350)
文摘The aim of this present study is to examine the efficacy of attribution retraining group therapy （ARGT） and to compare the responses of outpatients with major depression disorder （MDD）, generalized anxiety disorder （GAD） and obsessive-compulsive disorder （OCD）. We carried out a prospective uncontrolled intervention study with a 8-weeks of ARGT on sixty three outpatients with MDD, GAD or OCD. Hamilton rating scale for depression, Hamilton rating scale for anxiety, Yale-Brown obsessive-compulsive scale, attribution style questionnaire, self-esteem scale, index of well-being, and social disability screening schedule were administered before and after treatment. Significant improvement in symptoms and psychological and social functions from pre- to posttreatment occurred for all participants. The changes favored MDD patients. Our study suggested that ARGT may improve the symptoms and psychological-social functions of MDD, GAD, and OCD patients. MDD patients showed the best response.
基金supported by 2010 National Nature Science Foundation of China General Program(Program NO.8107I046)2012 Guangdong Provincial Science and Technology Program of China(Program NO.2012B032000009)2013 Guangdong Provincial Science and Technology Program of China(Program NO.2013B022000004)
文摘Objective:To detect the CHRNA7 gene mutation and polymorphism in Southern Han Chinese patients with nocturnal frontal lobe epilepsy(NFLE).Methods:Blood samples were collected from 215 Southern Han Chinese patients with NFLE and 200 healthy Southern Han Chinese control subjects.Genomic DNA was extracted,and CHRNA7 whole genome exons were amplified by the polymerase chain reaction and subjected to Sanger sequencing.Results:No CHRNA7 gene mutation was detected in all of the NFLE patients.However,five single nucleotide polymorphisms(SNPs)in sporadic cases were found,located in exons 5,6.and 7 of the CHRNA7 gene.Among them,c.690G>A and c.698A>G are known SNPs,while c.370G>A,c.654C>T,and c.497-498delTG were newly discovered SNPs.These SNPs were also found in some of the healthy controls.Conclusions:No CHRNA7 gene mutation was identified in Southern Han Chinese patients with NFLE.The CHRNA7 gene is probably not responsible for NFLE in this population.
