Diabetic retinopathy is a prominent cause of blindness in adults,with early retinal ganglion cell loss contributing to visual dysfunction or blindness.In the brain,defects inγ-aminobutyric acid synaptic transmission ...Diabetic retinopathy is a prominent cause of blindness in adults,with early retinal ganglion cell loss contributing to visual dysfunction or blindness.In the brain,defects inγ-aminobutyric acid synaptic transmission are associated with pathophysiological and neurodegenerative disorders,whereas glucagon-like peptide-1 has demonstrated neuroprotective effects.However,it is not yet clear whether diabetes causes alterations in inhibitory input to retinal ganglion cells and whether and how glucagon-like peptide-1 protects against neurodegeneration in the diabetic retina through regulating inhibitory synaptic transmission to retinal ganglion cells.In the present study,we used the patch-clamp technique to recordγ-aminobutyric acid subtype A receptor-mediated miniature inhibitory postsynaptic currents in retinal ganglion cells from streptozotocin-induced diabetes model rats.We found that early diabetes(4 weeks of hyperglycemia)decreased the frequency of GABAergic miniature inhibitory postsynaptic currents in retinal ganglion cells without altering their amplitude,suggesting a reduction in the spontaneous release ofγ-aminobutyric acid to retinal ganglion cells.Topical administration of glucagon-like peptide-1 eyedrops over a period of 2 weeks effectively countered the hyperglycemia-induced downregulation of GABAergic mIPSC frequency,subsequently enhancing the survival of retinal ganglion cells.Concurrently,the protective effects of glucagon-like peptide-1 on retinal ganglion cells in diabetic rats were eliminated by topical administration of exendin-9-39,a specific glucagon-like peptide-1 receptor antagonist,or SR95531,a specific antagonist of theγ-aminobutyric acid subtype A receptor.Furthermore,extracellular perfusion of glucagon-like peptide-1 was found to elevate the frequencies of GABAergic miniature inhibitory postsynaptic currents in both ON-and OFF-type retinal ganglion cells.This elevation was shown to be mediated by activation of the phosphatidylinositol-phospholipase C/inositol 1,4,5-trisphosphate receptor/Ca2+/protein kinase C signaling pathway downstream of glucagon-like peptide-1 receptor activation.Moreover,multielectrode array recordings revealed that glucagon-like peptide-1 functionally augmented the photoresponses of ON-type retinal ganglion cells.Optomotor response tests demonstrated that diabetic rats exhibited reductions in visual acuity and contrast sensitivity that were significantly ameliorated by topical administration of glucagon-like peptide-1.These results suggest that glucagon-like peptide-1 facilitates the release ofγ-aminobutyric acid onto retinal ganglion cells through the activation of glucagon-like peptide-1 receptor,leading to the de-excitation of retinal ganglion cell circuits and the inhibition of excitotoxic processes associated with diabetic retinopathy.Collectively,our findings indicate that theγ-aminobutyric acid system has potential as a therapeutic target for mitigating early-stage diabetic retinopathy.Furthermore,the topical administration of glucagon-like peptide-1 eyedrops represents a non-invasive and effective treatment approach for managing early-stage diabetic retinopathy.展开更多
INTRODUCTIONSialyl Lewis-X antigen ,correlated with carcinoma, is a group of carbohydrate antigen containing oligosaccharide expressed of embryonic tisue and glycoproteins on cell surface of embryonic tissue[1].The SL...INTRODUCTIONSialyl Lewis-X antigen ,correlated with carcinoma, is a group of carbohydrate antigen containing oligosaccharide expressed of embryonic tisue and glycoproteins on cell surface of embryonic tissue[1].The SLeX antigen located on cell surface is synthesized principally by two enzymes ,al ,3fucosyltransfrease and a2, 3sialyctransferase.In adults ,SLeX antigen is expressed principally on the surfaces of granulocytic cells and some tumor cells .展开更多
As the only naturally occurring stable derivative of L-ascorbic acid(AA;vitamin C),2-O-β-D-glucopyranosyl-L-ascorbic acid(AA-2βG)is hydrolyzed in vivo to release active AA.AA-2βG exhibits strong antioxidant and ant...As the only naturally occurring stable derivative of L-ascorbic acid(AA;vitamin C),2-O-β-D-glucopyranosyl-L-ascorbic acid(AA-2βG)is hydrolyzed in vivo to release active AA.AA-2βG exhibits strong antioxidant and antiphotoaging effects comparable to those of AA,and it plays a key role in maintaining organismal health.Owing to its superior stability and bioavailability,AA-2βG is considered as a promising,longer-lasting natural alternative to conventional vitamin C.It was first identified and is particularly abundant in Lycii Fructus(Gouqizi in Chinese)but has been detected in several crop plants.This review offers a comprehensive overview of recent advances in AA-2βG research,covering key aspects including discovery,structure,natural sources,extraction and detection methods,chemical and in vitro enzymatic synthesis,biosynthetic pathways,as well as applications in health care,skin care,and functional foods.Additionally,we highlight strategies for leveraging plant resources and enhancing AA-2βG biosynthesis,which are expected to accelerate future research and support the sustainable development and utilization of AA-2βG and other high-value natural products.展开更多
AIM: To investigate the role of the mitochondrial pathway in JTE-522-induced apoptosis and to investigate the relationship between cytochrome C release, caspase activity and loss of mitochondrial membrane potential (D...AIM: To investigate the role of the mitochondrial pathway in JTE-522-induced apoptosis and to investigate the relationship between cytochrome C release, caspase activity and loss of mitochondrial membrane potential (Deltapsim). METHODS: Cell culture, cell counting, ELISA assay, TUNEL, flow cytometry, Western blot and fluorometric assay were employed to investigate the effect of JTE-522 on cell proliferation and apoptosis in AGS cells and related molecular mechanism. RESULTS: JTE-522 inhibited the growth of AGS cells and induced the apoptosis. Caspases 8 and 9 were activated during apoptosis as judged by the appearance of cleavage products from procaspase and the caspase activities to cleave specific fluorogenic substrates. To elucidate whether the activation of caspases 8 and 9 was required for the apoptosis induction, we examined the effect of caspase-specific inhibitors on apoptosis. The results showed that caspase inhibitors significantly inhibited the apoptosis induced by JTE-522. In addition, the membrane translocation of Bax and cytosolic release of cytochrome C accompanying with the decrease of the uptake of Rhodamin 123, were detected at an early stage of apoptosis. Furthermore, Bax translocation, cytochrome C release, and caspase 9 activation were blocked by Z-VAD.fmk and Z-IETD-CHO. CONCLUSION: The present data indicate a crucial association between activation of caspases 8, 9, cytochrome C release, membrane translocation of Bax, loss of Deltapsim and JTE-522-induced apoptosis in AGS cells.展开更多
Layered double hydroxides(LDHs)hold great promise as cathode materials for aqueous zinc-ion batteries(AZIBs).Nevertheless,they also face challenges of sluggish kinetics and rapid capacity loss.Herein,a conformational ...Layered double hydroxides(LDHs)hold great promise as cathode materials for aqueous zinc-ion batteries(AZIBs).Nevertheless,they also face challenges of sluggish kinetics and rapid capacity loss.Herein,a conformational entropy regulation strategy has been applied to surmount the shortcomings.A medium-entropy iron-based metal organic framework(MIL-88)derived NiCoFeInZnV-based layered double hydroxide with carbon loaded(ME-NiCoFeInZnV-LDH/C)has been first proposed and prepared with a designed method.The increased entropy optimizes electron conductivity and alleviates structure alteration and diffusion barrier during interactions with charge carriers,due to electron-induced effect and“cocktail”effect.Moreover,the nanosheet assembled hollow prismatic structures could homogenize flux distribution and electric field distribution.Therefore,the electrochemical kinetics,crystal structure stability,and activity could be dramatically improved.Leveraging the advantages of structure and composition regulation,Zn||ME-NiCoFeInZnV-LDH/C zinc battery delivers high specific capacities,rate performance,and cycling stability.This work proposes a novel and feasible medium-entropy strategy to prepare a high-performance cathode for advanced AZIBs,which is of prominent significance for the development of charge storage devices.展开更多
CO_(2)utilization powered by sustainable energy offers a promising route to mitigate carbon emissions while producing value-added chemicals[1].Among these pathways,CO_(2)hydrogenation is especially attractive because ...CO_(2)utilization powered by sustainable energy offers a promising route to mitigate carbon emissions while producing value-added chemicals[1].Among these pathways,CO_(2)hydrogenation is especially attractive because it integrates renewable H 2 with carbon resources,which have achieved notable success in producing methanol,CO,etc.[2,3].展开更多
Li_(3)V_(2)(PO_(4))_(3) is a promising high-voltage cathode for zincion batteries,but it suffers from a poor electronic conductivity and vanadium dissolution in aqueous electrolytes.The growth of carboncoated Li_(3)V_...Li_(3)V_(2)(PO_(4))_(3) is a promising high-voltage cathode for zincion batteries,but it suffers from a poor electronic conductivity and vanadium dissolution in aqueous electrolytes.The growth of carboncoated Li_(3)V_(2)(PO_(4))_(3)(LVP@C)nanoparticles on carbon nanofibers(CNFs)has been achieved by an electrospinning technique followed by calcination.The protective carbon coating prevents the aggregation of the LVP nanoparticles and suppresses V dissolution by preventing direct contact with aqueous electrolytes.The CNFs derived from the electrospun nanofibers provide a 3D network to increase the electronic conductivity of the LVP electrode,and the LVP@C-CNF hybrid film can be directly used as a freestanding cathode for zinc-ion batteries without adding conductive additives and binders.A mechanism for the formation of a uniform and continuous carbon coating has been proposed.This nanostructure,combined with the uniform and intact carbon coverage,significantly increases the electronic conductivity.This LVP@C-CNF freestanding electrode has an excellent rate capability(47.3%retention at 2 C)and cycling stability(61.2%retention after 100 cycles)within the voltage range 0.6 V to 1.95 V and is highly suitable for zinc-ion battery applications.展开更多
Objective:To evaluate the effectiveness of direct-acting antivirals(DAAs)in patients with chronic hepatitis C,assess changes in liver function and hepatic fibrosis following treatment,and identify independent predicto...Objective:To evaluate the effectiveness of direct-acting antivirals(DAAs)in patients with chronic hepatitis C,assess changes in liver function and hepatic fibrosis following treatment,and identify independent predictors of treatment failure.Methods:This retrospective cohort study included patients who received DAA therapy at Hospital Kuala Lumpur between January 2020 and December 2023.Sustained virologic response(SVR)was assessed at least 12 weeks post-treatment by reverse transcription-polymerase chain reaction for hepatitis C virus(HCV)RNA.Demographic,clinical,and laboratory data were collected and analyzed.Multiple logistic regression analysis was performed to identify independent predictors of treatment failure.Results:A total of 335 patients in the study.The overall SVR rate was 89%.After achieving SVR,significant improvements were observed in liver enzyme levels and non-invasive liver fibrosis scores,whereas the overall Model for End-Stage Liver Disease(MELD)scores remained unchanged.Significant independent predictors of treatment failure included non-compliance with DAA therapy[adjusted odds ratio(aOR)68.3;95%confidence interval(95%CI)16.3-285.0;P<0.001],treatment with sofosbuvir/velpatasvir(aOR 6.1;95%CI 1.4-26.5;P=0.015),MELD score of 10-15(aOR 4.6;95%CI 1.1-18.2;P=0.031),HCV genotype 3 infection(aOR 4.5;95%CI 1.1-17.6;P=0.031),and elevated serum total bilirubin level(aOR 1.1;95%CI 1.0-1.1;P=0.003).Conclusions:DAA therapy yielded a high SVR rate,and treatment failure was strongly associated with non-adherence to therapy and advanced liver disease.These findings underscore the necessity of adherence support,early diagnosis,and individualized clinical management to optimize treatment outcomes in patients with chronic hepatitis C.展开更多
Disruption of host physiological processes,leading to symptom expression,is a common hallmark during plant virus infections.The concept of“symptoms as strategy”is rapidly reshaping our understanding of plant virolog...Disruption of host physiological processes,leading to symptom expression,is a common hallmark during plant virus infections.The concept of“symptoms as strategy”is rapidly reshaping our understanding of plant virology.An emerging theme is that symptom expressions—such as stunting,curling,and yellowing,which devastate yield—may themselves be evolved viral adaptation strategies rather than collateral damage.展开更多
We report a theoretical investigation into superconductivity within the MAXH_(6) quaternary hydride system using first-principles calculations,where M and A denote alkali and alkaline earth elements,respectively,and X...We report a theoretical investigation into superconductivity within the MAXH_(6) quaternary hydride system using first-principles calculations,where M and A denote alkali and alkaline earth elements,respectively,and X represents transition metal elements.Systematic analysis of electronic band structures,phonon dispersions,and electron-phonon coupling reveals that substitution of MA binary metal combinations and X metal atoms can create favorable conditions for superconductivity.Mapping of superconducting critical temperatures,combined with dynamical stability analysis through phonon calculations,identifies ten superconducting candidates at ambient pressure.Among these,LiNaAgH_(6) exhibits nearly-free-electron behavior reminiscent of monovalent electron superconductors.It demonstrates exceptional superconducting properties with electron–phonon coupling λ=2.707,which yields a superconducting transition temperature T_(c) of 206.4 K using the Allen–Dynes formula.Its structural analogs MgNaPdH_(6),LiMgPdH_(6),LiMgAgH_(6),LiMgAuH_(6) all exhibit superconducting transition temperatures above 110 K.These findings advance our fundamental understanding of superconductivity in quaternary hydrides and provide guidance for rational design of new high-temperature superconducting materials.展开更多
Osteoclast differentiation depends on receptor activator of nuclear factor-κB(RANK) signaling,which can be divided into triggering,amplifying and targeting phases based on how active the master regulator nuclear fact...Osteoclast differentiation depends on receptor activator of nuclear factor-κB(RANK) signaling,which can be divided into triggering,amplifying and targeting phases based on how active the master regulator nuclear factor of activated T-cells cytoplasmic 1(NFATc1) is. The triggering phase is characterized by immediateearly RANK signaling induced by RANK ligand(RANKL) stimulation mediated by three adaptor proteins,tumor necrosis factor receptor-associated factor 6,Grb-2-associated binder-2 and phospholipase C(PLC)γ2,leading to activation of IκB kinase,mitogen-activated protein kinases and the transcription factors nuclear factor(NF)-κB and activator protein-1(AP-1). Mice lacking NF-κB p50/p52 or the AP-1 subunit c-Fos(encoded by Fos) exhibit severe osteopetrosis due to a differentiation block in the osteoclast lineage. The amplification phase occurs about 24 h later in a RANKLinduced osteoclastogenic culture when Ca2+ oscillation starts and the transcription factor NFATc1 is abundantly produced. In addition to Ca2+ oscillation-dependent nuclear translocation and transcriptional auto-induction of NFATc1,a Ca2+ oscillation-independent,osteoblastdependent mechanism stabilizes NFATc1 protein in dif-ferentiating osteoclasts. Osteoclast precursors lacking PLCγ2,inositol-1,4,5-trisphosphate receptors,regulator of G-protein signaling 10,or NFATc1 show an impaired transition from the triggering to amplifying phases. The final targeting phase is mediated by activation of numerous NFATc1 target genes responsible for cell-cell fusion and regulation of bone-resorptive function. This review focuses on molecular mechanisms for each of the three phases of RANK signaling during osteoclast differentiation.展开更多
INTRODUCTIONBoanmycin (Bleomycin A6, BAM ), a newantitumor antibiotic, was isolated from manycomponents of bleomycin (BLM) produced bystreptomyces pingyangensis which were obtainedfrom a soil sample collected in Pingy...INTRODUCTIONBoanmycin (Bleomycin A6, BAM ), a newantitumor antibiotic, was isolated from manycomponents of bleomycin (BLM) produced bystreptomyces pingyangensis which were obtainedfrom a soil sample collected in Pingyang County,Zhejiang Province, China. Boanmycin has a similarchemical structure to that of BLM, but the terminalamine moiety is different[ 1].展开更多
In this paper,we introduce the notion of G_(C)-X-injective modules,where X denotes a class of left S-modules and C represents a faithfully semidualizing bimodule.Under the condition that X satisfies certain hypotheses...In this paper,we introduce the notion of G_(C)-X-injective modules,where X denotes a class of left S-modules and C represents a faithfully semidualizing bimodule.Under the condition that X satisfies certain hypotheses,some properties and some equivalent characterizations of G_(C)-X-injective modules are investigated,and we also show that the triple(■,cores■,■)is a weak co-AB-context.As an application,two complete cotorsion pairs and a new model structure in Mod S are given.展开更多
Various kinds of organisms, including viruses, bacteria, trematodes and fungi are known carcinogens that cause cancer. Infectious identification related to cancer may lead to better treatment for both the prevention a...Various kinds of organisms, including viruses, bacteria, trematodes and fungi are known carcinogens that cause cancer. Infectious identification related to cancer may lead to better treatment for both the prevention and targeting of cancer therapy. Although nearly 20% of all cancers are caused by an infection of a microbe, the amount of evidence and information regarding the mechanisms associated with oncogenesis varies dramatically from one organism to the next. This review cannot be exhaustive because we are not aware of all infections worldwide in addition to their potential mechanisms for oncogenesis. More research is required for all of the species mentioned in this review.展开更多
Objective:To investigate the effect of Catalpa ovata fruit extract(COFE)on muscle growth and exercise performance in C2C12 myoblasts and mice.Me t h o d s:Cel l viabi l i ty was determined through a 3-(4,5-dimethylthi...Objective:To investigate the effect of Catalpa ovata fruit extract(COFE)on muscle growth and exercise performance in C2C12 myoblasts and mice.Me t h o d s:Cel l viabi l i ty was determined through a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay.Myogenic differentiation was observed using Giemsa staining.COFE was administered to mice orally at 50 and 200 mg/kg for 10 weeks.Muscular strength was evaluated using the whole-limb grip strength assay.The expression levels of myogenesis-and energy metabolism-related proteins in vitro and in vivo were determined using Western blotting.Results:COFE significantly improved myoblast-to-myotube differentiation in C2C12 myoblasts.It also increased the expression of myogenesis determination protein 1 and myogenin compared with the control group.Moreover,the expression levels of glucose transporter type 4(Glut4)and peroxisome proliferator-activated receptor-gamma coactivator 1-alpha(PGC-1α)were significantly elevated in the presence of COFE in C2C12 myoblasts.COFE also markedly increased phosphorylation of AMP-activated protein kinase,which regulates Glut4 and PGC-1αexpression levels in C2C12 myoblasts.Mice treated with COFE showed improved grip strength.Myogenesis-and energy metabolism-related protein levels in muscle tissue were significantly increased in COFE-administered mice.Conclusions:COFE treatment improves exercise performance by controlling myogenesis and energy metabolism in skeletal muscle.COFE has the potential to be used as an effective natural agent for enhancing muscular strength.展开更多
Regulation of apoptosis represents a key parameter in all living organisms.In this paper,an input-induced logic-gated modular nanocalculator is designed to regulate cancer cell apoptosis by programmatically combining ...Regulation of apoptosis represents a key parameter in all living organisms.In this paper,an input-induced logic-gated modular nanocalculator is designed to regulate cancer cell apoptosis by programmatically combining and connecting logic gate modules with different functions.Via rational design of the various logic gate modules of the nanocalculator,different apoptosis related operations including cancer cell targeting,apoptosis induction,and apoptosis monitoring could be performed.Importantly,each of these logic gate modules could independently perform apoptosis related YES logic operations when ran separately.After combining each YES logic gate module into a logic circuit and connecting it to the GO scaffold to construct a logic-gated nanocalculator,the input-induced logic-gated modular nanocalculator could selectively enter cancer cells and control the drug release to logically apoptosis(output),by performing AND logic gate operations when inputs(nucleolin and H^(+)) were included at the same time.Moreover,evidence suggests that these efficient logical calculations proceed in cancer cell apoptosis regulation without the general limiations of lithography in nanotechnology.As such,this work provides a new vision for the construction of a logic-gated modular nanocalculator with logical calculation proficiency potentially useful in cancer therapy and the regulation of life.展开更多
The development of Pt-free catalysts for the oxygen reduction reaction(ORR)is a great issue for meeting the cost challenges of proton exchange membrane fuel cells(PEMFCs)in commercial applications.In this work,a serie...The development of Pt-free catalysts for the oxygen reduction reaction(ORR)is a great issue for meeting the cost challenges of proton exchange membrane fuel cells(PEMFCs)in commercial applications.In this work,a series of RuCo/C catalysts were synthesized by NaBH4 reduction method under the premise that the total metal mass percentage was 20%.X-ray diffraction(XRD)patterns and scanning electron microscopy(SEM)confirmed the formation of single-phase nanoparticles with an average size of 33 nm.Cyclic voltammograms(CV)and linear sweep voltammograms(LSV)tests indicated that RuCo(2:1)/C catalyst had the optimal ORR properties.Additionally,the RuCo(2:1)/C catalyst remarkably sustained 98.1% of its activity even after 3000 cycles,surpassing the performance of Pt/C(84.8%).Analysis of the elemental state of the catalyst surface after cycling using X-ray photoelectron spectroscopy(XPS)revealed that the Ru^(0) percentage of RuCo(2:1)/C decreased by 2.2%(from 66.3% to 64.1%),while the Pt^(0) percentage of Pt/C decreased by 7.1%(from 53.3% to 46.2%).It is suggested that the synergy between Ru and Co holds the potential to pave the way for future low-cost and highly stable ORR catalysts,offering significant promise in the context of PEMFCs.展开更多
Background:Os Draconis is an important material in traditional Chinese medicine(TCM).However,its market is saturated with counterfeit products,and the limitations of current identification methods pose a serious threa...Background:Os Draconis is an important material in traditional Chinese medicine(TCM).However,its market is saturated with counterfeit products,and the limitations of current identification methods pose a serious threat to clinical effectiveness and drug safety.This study aims to establish a more accurate and comprehensive authentication system for Os Draconis.Methods:A comprehensive approach was employed to analyze authentic Os Draconis,fossilized Os Draconis,counterfeit products,and lab-prepared modern animal bones.The analytical techniques included ^(14)C dating,electron probe microanalysis(EPMA),polarized light microscopy,X-ray diffraction(XRD),inductively coupled plasma mass spectrometry(ICP-MS),and fourier-transform infrared spectroscopy(FTIR).The study focused on examining the microstructural features and micro-area elemental compositions to identify distinguishing characteristics.Results:Physical identification alone was insufficient to reliably distinguish authentic Os Draconis from its counterfeits.XRD analysis revealed that while hydroxyapatite is the main component in all samples,authentic Os Draconis also contains calcium carbonate and quartz,which were absent in counterfeit and lab-prepared samples.FTIR spectra identified the carbonate ion(CO_(3)^(2-))as a characteristic infrared marker for authentic Os Draconis.ICP-MS analysis showed that Ca and P are the major elements,with a notably high content of Lanthanum(La)among rare earth elements in authentic samples.The EPMA results demonstrated that the Ca/P ratio of authentic Os Draconis is distinct,falling between that of fossilized Os Draconis and counterfeit samples.Conclusion:This study successfully identified several precise markers,including the presence of calcium carbonate,the characteristic CO_(3)^(2-)infrared peak,a high La content,and a specific Ca/P ratio,for the accurate and rapid authentication of Os Draconis.Furthermore,the analysis of its natural porous structure,suitable pore size,and surface area suggests that Os Draconis has significant potential as a natural drug carrier.展开更多
基金supported by the National Natural Science Foundation of China,Nos.32070989(to YMZ),31872766(to YMZ),81790640(to XLY),and 82070993(to SJW)the grant from Sanming Project of Medicine in Shenzhen,No.SZSM202011015(to XLY)。
文摘Diabetic retinopathy is a prominent cause of blindness in adults,with early retinal ganglion cell loss contributing to visual dysfunction or blindness.In the brain,defects inγ-aminobutyric acid synaptic transmission are associated with pathophysiological and neurodegenerative disorders,whereas glucagon-like peptide-1 has demonstrated neuroprotective effects.However,it is not yet clear whether diabetes causes alterations in inhibitory input to retinal ganglion cells and whether and how glucagon-like peptide-1 protects against neurodegeneration in the diabetic retina through regulating inhibitory synaptic transmission to retinal ganglion cells.In the present study,we used the patch-clamp technique to recordγ-aminobutyric acid subtype A receptor-mediated miniature inhibitory postsynaptic currents in retinal ganglion cells from streptozotocin-induced diabetes model rats.We found that early diabetes(4 weeks of hyperglycemia)decreased the frequency of GABAergic miniature inhibitory postsynaptic currents in retinal ganglion cells without altering their amplitude,suggesting a reduction in the spontaneous release ofγ-aminobutyric acid to retinal ganglion cells.Topical administration of glucagon-like peptide-1 eyedrops over a period of 2 weeks effectively countered the hyperglycemia-induced downregulation of GABAergic mIPSC frequency,subsequently enhancing the survival of retinal ganglion cells.Concurrently,the protective effects of glucagon-like peptide-1 on retinal ganglion cells in diabetic rats were eliminated by topical administration of exendin-9-39,a specific glucagon-like peptide-1 receptor antagonist,or SR95531,a specific antagonist of theγ-aminobutyric acid subtype A receptor.Furthermore,extracellular perfusion of glucagon-like peptide-1 was found to elevate the frequencies of GABAergic miniature inhibitory postsynaptic currents in both ON-and OFF-type retinal ganglion cells.This elevation was shown to be mediated by activation of the phosphatidylinositol-phospholipase C/inositol 1,4,5-trisphosphate receptor/Ca2+/protein kinase C signaling pathway downstream of glucagon-like peptide-1 receptor activation.Moreover,multielectrode array recordings revealed that glucagon-like peptide-1 functionally augmented the photoresponses of ON-type retinal ganglion cells.Optomotor response tests demonstrated that diabetic rats exhibited reductions in visual acuity and contrast sensitivity that were significantly ameliorated by topical administration of glucagon-like peptide-1.These results suggest that glucagon-like peptide-1 facilitates the release ofγ-aminobutyric acid onto retinal ganglion cells through the activation of glucagon-like peptide-1 receptor,leading to the de-excitation of retinal ganglion cell circuits and the inhibition of excitotoxic processes associated with diabetic retinopathy.Collectively,our findings indicate that theγ-aminobutyric acid system has potential as a therapeutic target for mitigating early-stage diabetic retinopathy.Furthermore,the topical administration of glucagon-like peptide-1 eyedrops represents a non-invasive and effective treatment approach for managing early-stage diabetic retinopathy.
文摘INTRODUCTIONSialyl Lewis-X antigen ,correlated with carcinoma, is a group of carbohydrate antigen containing oligosaccharide expressed of embryonic tisue and glycoproteins on cell surface of embryonic tissue[1].The SLeX antigen located on cell surface is synthesized principally by two enzymes ,al ,3fucosyltransfrease and a2, 3sialyctransferase.In adults ,SLeX antigen is expressed principally on the surfaces of granulocytic cells and some tumor cells .
基金funded by the National Key Research and Development Program(Nos.2023YFC3504104 and 2024YFD2100700)the Fundamental Research Funds for the Central public welfare research institutes(No.ZZ13-YQ-101)Scientific and technological innovation project of China Academy of Chinese Medical Sciences(No.CI2023E002-Y-28).
文摘As the only naturally occurring stable derivative of L-ascorbic acid(AA;vitamin C),2-O-β-D-glucopyranosyl-L-ascorbic acid(AA-2βG)is hydrolyzed in vivo to release active AA.AA-2βG exhibits strong antioxidant and antiphotoaging effects comparable to those of AA,and it plays a key role in maintaining organismal health.Owing to its superior stability and bioavailability,AA-2βG is considered as a promising,longer-lasting natural alternative to conventional vitamin C.It was first identified and is particularly abundant in Lycii Fructus(Gouqizi in Chinese)but has been detected in several crop plants.This review offers a comprehensive overview of recent advances in AA-2βG research,covering key aspects including discovery,structure,natural sources,extraction and detection methods,chemical and in vitro enzymatic synthesis,biosynthetic pathways,as well as applications in health care,skin care,and functional foods.Additionally,we highlight strategies for leveraging plant resources and enhancing AA-2βG biosynthesis,which are expected to accelerate future research and support the sustainable development and utilization of AA-2βG and other high-value natural products.
基金National Natural Science Foundation of China,No.39770300,30070873the Overseas Chinese Affairs Office of the State Council Foundation,No.98-33
文摘AIM: To investigate the role of the mitochondrial pathway in JTE-522-induced apoptosis and to investigate the relationship between cytochrome C release, caspase activity and loss of mitochondrial membrane potential (Deltapsim). METHODS: Cell culture, cell counting, ELISA assay, TUNEL, flow cytometry, Western blot and fluorometric assay were employed to investigate the effect of JTE-522 on cell proliferation and apoptosis in AGS cells and related molecular mechanism. RESULTS: JTE-522 inhibited the growth of AGS cells and induced the apoptosis. Caspases 8 and 9 were activated during apoptosis as judged by the appearance of cleavage products from procaspase and the caspase activities to cleave specific fluorogenic substrates. To elucidate whether the activation of caspases 8 and 9 was required for the apoptosis induction, we examined the effect of caspase-specific inhibitors on apoptosis. The results showed that caspase inhibitors significantly inhibited the apoptosis induced by JTE-522. In addition, the membrane translocation of Bax and cytosolic release of cytochrome C accompanying with the decrease of the uptake of Rhodamin 123, were detected at an early stage of apoptosis. Furthermore, Bax translocation, cytochrome C release, and caspase 9 activation were blocked by Z-VAD.fmk and Z-IETD-CHO. CONCLUSION: The present data indicate a crucial association between activation of caspases 8, 9, cytochrome C release, membrane translocation of Bax, loss of Deltapsim and JTE-522-induced apoptosis in AGS cells.
基金the funding support from the National Natural Science Foundation of China(Grant No.52202217,52471222)the Natural Science Foundation of Jilin Province(Grant No.YDZJ202201ZYTS375).
文摘Layered double hydroxides(LDHs)hold great promise as cathode materials for aqueous zinc-ion batteries(AZIBs).Nevertheless,they also face challenges of sluggish kinetics and rapid capacity loss.Herein,a conformational entropy regulation strategy has been applied to surmount the shortcomings.A medium-entropy iron-based metal organic framework(MIL-88)derived NiCoFeInZnV-based layered double hydroxide with carbon loaded(ME-NiCoFeInZnV-LDH/C)has been first proposed and prepared with a designed method.The increased entropy optimizes electron conductivity and alleviates structure alteration and diffusion barrier during interactions with charge carriers,due to electron-induced effect and“cocktail”effect.Moreover,the nanosheet assembled hollow prismatic structures could homogenize flux distribution and electric field distribution.Therefore,the electrochemical kinetics,crystal structure stability,and activity could be dramatically improved.Leveraging the advantages of structure and composition regulation,Zn||ME-NiCoFeInZnV-LDH/C zinc battery delivers high specific capacities,rate performance,and cycling stability.This work proposes a novel and feasible medium-entropy strategy to prepare a high-performance cathode for advanced AZIBs,which is of prominent significance for the development of charge storage devices.
文摘CO_(2)utilization powered by sustainable energy offers a promising route to mitigate carbon emissions while producing value-added chemicals[1].Among these pathways,CO_(2)hydrogenation is especially attractive because it integrates renewable H 2 with carbon resources,which have achieved notable success in producing methanol,CO,etc.[2,3].
文摘Li_(3)V_(2)(PO_(4))_(3) is a promising high-voltage cathode for zincion batteries,but it suffers from a poor electronic conductivity and vanadium dissolution in aqueous electrolytes.The growth of carboncoated Li_(3)V_(2)(PO_(4))_(3)(LVP@C)nanoparticles on carbon nanofibers(CNFs)has been achieved by an electrospinning technique followed by calcination.The protective carbon coating prevents the aggregation of the LVP nanoparticles and suppresses V dissolution by preventing direct contact with aqueous electrolytes.The CNFs derived from the electrospun nanofibers provide a 3D network to increase the electronic conductivity of the LVP electrode,and the LVP@C-CNF hybrid film can be directly used as a freestanding cathode for zinc-ion batteries without adding conductive additives and binders.A mechanism for the formation of a uniform and continuous carbon coating has been proposed.This nanostructure,combined with the uniform and intact carbon coverage,significantly increases the electronic conductivity.This LVP@C-CNF freestanding electrode has an excellent rate capability(47.3%retention at 2 C)and cycling stability(61.2%retention after 100 cycles)within the voltage range 0.6 V to 1.95 V and is highly suitable for zinc-ion battery applications.
文摘Objective:To evaluate the effectiveness of direct-acting antivirals(DAAs)in patients with chronic hepatitis C,assess changes in liver function and hepatic fibrosis following treatment,and identify independent predictors of treatment failure.Methods:This retrospective cohort study included patients who received DAA therapy at Hospital Kuala Lumpur between January 2020 and December 2023.Sustained virologic response(SVR)was assessed at least 12 weeks post-treatment by reverse transcription-polymerase chain reaction for hepatitis C virus(HCV)RNA.Demographic,clinical,and laboratory data were collected and analyzed.Multiple logistic regression analysis was performed to identify independent predictors of treatment failure.Results:A total of 335 patients in the study.The overall SVR rate was 89%.After achieving SVR,significant improvements were observed in liver enzyme levels and non-invasive liver fibrosis scores,whereas the overall Model for End-Stage Liver Disease(MELD)scores remained unchanged.Significant independent predictors of treatment failure included non-compliance with DAA therapy[adjusted odds ratio(aOR)68.3;95%confidence interval(95%CI)16.3-285.0;P<0.001],treatment with sofosbuvir/velpatasvir(aOR 6.1;95%CI 1.4-26.5;P=0.015),MELD score of 10-15(aOR 4.6;95%CI 1.1-18.2;P=0.031),HCV genotype 3 infection(aOR 4.5;95%CI 1.1-17.6;P=0.031),and elevated serum total bilirubin level(aOR 1.1;95%CI 1.0-1.1;P=0.003).Conclusions:DAA therapy yielded a high SVR rate,and treatment failure was strongly associated with non-adherence to therapy and advanced liver disease.These findings underscore the necessity of adherence support,early diagnosis,and individualized clinical management to optimize treatment outcomes in patients with chronic hepatitis C.
基金supported by the National Natural Science Foundation of China(32272482)the Innovation Research 2035 Pilot Plan of Southwest University(SWU-XDZD22002).
文摘Disruption of host physiological processes,leading to symptom expression,is a common hallmark during plant virus infections.The concept of“symptoms as strategy”is rapidly reshaping our understanding of plant virology.An emerging theme is that symptom expressions—such as stunting,curling,and yellowing,which devastate yield—may themselves be evolved viral adaptation strategies rather than collateral damage.
基金supported by the National Key R&D Program of China (Grant No.2022YFA1403201)the National Natural Science Foundation of China (Grant Nos.12125404,T2495231,123B2049,and 12204138)+9 种基金the Advanced MaterialsNational Science and Technology Major Project (Grant No.2024ZD0607000)the Natural Science Foundation of Jiangsu Province (Grant Nos.BK20233001 and BK20253009)the Jiangsu Funding Program for Excellent Postdoctoral Talent (Grant No.2024ZB002)the China Postdoctoral Science Foundation (Grant No.2025M773331)the Fundamental and Interdisciplinary Disciplines Breakthrough Plan of the Ministry of Education of Chinathe AI&AI for Science program of Nanjing UniversityArtificial Intelligence and Quantum physics (AIQ) program of Nanjing Universitythe Fundamental Research Funds for the Central Universitiesthe Natural Science Foundation of Nanjing University of Posts and Telecommunications(Grant Nos.NY224165,NY220038,and NY219087)the Hua Li Talents Program of Nanjing University of Posts and Telecommunications。
文摘We report a theoretical investigation into superconductivity within the MAXH_(6) quaternary hydride system using first-principles calculations,where M and A denote alkali and alkaline earth elements,respectively,and X represents transition metal elements.Systematic analysis of electronic band structures,phonon dispersions,and electron-phonon coupling reveals that substitution of MA binary metal combinations and X metal atoms can create favorable conditions for superconductivity.Mapping of superconducting critical temperatures,combined with dynamical stability analysis through phonon calculations,identifies ten superconducting candidates at ambient pressure.Among these,LiNaAgH_(6) exhibits nearly-free-electron behavior reminiscent of monovalent electron superconductors.It demonstrates exceptional superconducting properties with electron–phonon coupling λ=2.707,which yields a superconducting transition temperature T_(c) of 206.4 K using the Allen–Dynes formula.Its structural analogs MgNaPdH_(6),LiMgPdH_(6),LiMgAgH_(6),LiMgAuH_(6) all exhibit superconducting transition temperatures above 110 K.These findings advance our fundamental understanding of superconductivity in quaternary hydrides and provide guidance for rational design of new high-temperature superconducting materials.
基金Supported by Grants from MEXT Japan,No.23790265(to Kuroda Y)and No.21390425(to Matsuo K)
文摘Osteoclast differentiation depends on receptor activator of nuclear factor-κB(RANK) signaling,which can be divided into triggering,amplifying and targeting phases based on how active the master regulator nuclear factor of activated T-cells cytoplasmic 1(NFATc1) is. The triggering phase is characterized by immediateearly RANK signaling induced by RANK ligand(RANKL) stimulation mediated by three adaptor proteins,tumor necrosis factor receptor-associated factor 6,Grb-2-associated binder-2 and phospholipase C(PLC)γ2,leading to activation of IκB kinase,mitogen-activated protein kinases and the transcription factors nuclear factor(NF)-κB and activator protein-1(AP-1). Mice lacking NF-κB p50/p52 or the AP-1 subunit c-Fos(encoded by Fos) exhibit severe osteopetrosis due to a differentiation block in the osteoclast lineage. The amplification phase occurs about 24 h later in a RANKLinduced osteoclastogenic culture when Ca2+ oscillation starts and the transcription factor NFATc1 is abundantly produced. In addition to Ca2+ oscillation-dependent nuclear translocation and transcriptional auto-induction of NFATc1,a Ca2+ oscillation-independent,osteoblastdependent mechanism stabilizes NFATc1 protein in dif-ferentiating osteoclasts. Osteoclast precursors lacking PLCγ2,inositol-1,4,5-trisphosphate receptors,regulator of G-protein signaling 10,or NFATc1 show an impaired transition from the triggering to amplifying phases. The final targeting phase is mediated by activation of numerous NFATc1 target genes responsible for cell-cell fusion and regulation of bone-resorptive function. This review focuses on molecular mechanisms for each of the three phases of RANK signaling during osteoclast differentiation.
基金Supported by the National Natural Science Foundation of China, No. 93090012-03
文摘INTRODUCTIONBoanmycin (Bleomycin A6, BAM ), a newantitumor antibiotic, was isolated from manycomponents of bleomycin (BLM) produced bystreptomyces pingyangensis which were obtainedfrom a soil sample collected in Pingyang County,Zhejiang Province, China. Boanmycin has a similarchemical structure to that of BLM, but the terminalamine moiety is different[ 1].
文摘In this paper,we introduce the notion of G_(C)-X-injective modules,where X denotes a class of left S-modules and C represents a faithfully semidualizing bimodule.Under the condition that X satisfies certain hypotheses,some properties and some equivalent characterizations of G_(C)-X-injective modules are investigated,and we also show that the triple(■,cores■,■)is a weak co-AB-context.As an application,two complete cotorsion pairs and a new model structure in Mod S are given.
文摘Various kinds of organisms, including viruses, bacteria, trematodes and fungi are known carcinogens that cause cancer. Infectious identification related to cancer may lead to better treatment for both the prevention and targeting of cancer therapy. Although nearly 20% of all cancers are caused by an infection of a microbe, the amount of evidence and information regarding the mechanisms associated with oncogenesis varies dramatically from one organism to the next. This review cannot be exhaustive because we are not aware of all infections worldwide in addition to their potential mechanisms for oncogenesis. More research is required for all of the species mentioned in this review.
基金supported by Project to Make Multi-Ministerial National Biological Research Resources More Advanced Program,Korea Environment Industry&Technology Institute,and funded by Korea Ministry of Environment(grant number RS-2023-00230403).
文摘Objective:To investigate the effect of Catalpa ovata fruit extract(COFE)on muscle growth and exercise performance in C2C12 myoblasts and mice.Me t h o d s:Cel l viabi l i ty was determined through a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay.Myogenic differentiation was observed using Giemsa staining.COFE was administered to mice orally at 50 and 200 mg/kg for 10 weeks.Muscular strength was evaluated using the whole-limb grip strength assay.The expression levels of myogenesis-and energy metabolism-related proteins in vitro and in vivo were determined using Western blotting.Results:COFE significantly improved myoblast-to-myotube differentiation in C2C12 myoblasts.It also increased the expression of myogenesis determination protein 1 and myogenin compared with the control group.Moreover,the expression levels of glucose transporter type 4(Glut4)and peroxisome proliferator-activated receptor-gamma coactivator 1-alpha(PGC-1α)were significantly elevated in the presence of COFE in C2C12 myoblasts.COFE also markedly increased phosphorylation of AMP-activated protein kinase,which regulates Glut4 and PGC-1αexpression levels in C2C12 myoblasts.Mice treated with COFE showed improved grip strength.Myogenesis-and energy metabolism-related protein levels in muscle tissue were significantly increased in COFE-administered mice.Conclusions:COFE treatment improves exercise performance by controlling myogenesis and energy metabolism in skeletal muscle.COFE has the potential to be used as an effective natural agent for enhancing muscular strength.
基金financially supported by the National Natural Science Foundation of China (NSFC,Nos.22134005 and 22074124)Chongqing Talents Program for Outstanding Scientists (No.cstc2021ycjh-bgzxm0178)+1 种基金Natural Science Foundation of Chongqing (No.CSTB2022NSCQ-MSX0521)the Chongqing Graduate Student Scientific Research Innovation Project (No.CYB21119)。
文摘Regulation of apoptosis represents a key parameter in all living organisms.In this paper,an input-induced logic-gated modular nanocalculator is designed to regulate cancer cell apoptosis by programmatically combining and connecting logic gate modules with different functions.Via rational design of the various logic gate modules of the nanocalculator,different apoptosis related operations including cancer cell targeting,apoptosis induction,and apoptosis monitoring could be performed.Importantly,each of these logic gate modules could independently perform apoptosis related YES logic operations when ran separately.After combining each YES logic gate module into a logic circuit and connecting it to the GO scaffold to construct a logic-gated nanocalculator,the input-induced logic-gated modular nanocalculator could selectively enter cancer cells and control the drug release to logically apoptosis(output),by performing AND logic gate operations when inputs(nucleolin and H^(+)) were included at the same time.Moreover,evidence suggests that these efficient logical calculations proceed in cancer cell apoptosis regulation without the general limiations of lithography in nanotechnology.As such,this work provides a new vision for the construction of a logic-gated modular nanocalculator with logical calculation proficiency potentially useful in cancer therapy and the regulation of life.
基金Funded by the 111 Project(No.B17034)Open Project of Hubei Key Laboratory of Power System Design and Test for Electrical Vehicle(No.ZDSYS202212)+1 种基金Innovative Research Team Development Program of Ministry of Education of China(No.IRT_17R83)the Science and Technology Project of China Southern Power Grid Co.,Ltd.(No.GDKJXM20222546)。
文摘The development of Pt-free catalysts for the oxygen reduction reaction(ORR)is a great issue for meeting the cost challenges of proton exchange membrane fuel cells(PEMFCs)in commercial applications.In this work,a series of RuCo/C catalysts were synthesized by NaBH4 reduction method under the premise that the total metal mass percentage was 20%.X-ray diffraction(XRD)patterns and scanning electron microscopy(SEM)confirmed the formation of single-phase nanoparticles with an average size of 33 nm.Cyclic voltammograms(CV)and linear sweep voltammograms(LSV)tests indicated that RuCo(2:1)/C catalyst had the optimal ORR properties.Additionally,the RuCo(2:1)/C catalyst remarkably sustained 98.1% of its activity even after 3000 cycles,surpassing the performance of Pt/C(84.8%).Analysis of the elemental state of the catalyst surface after cycling using X-ray photoelectron spectroscopy(XPS)revealed that the Ru^(0) percentage of RuCo(2:1)/C decreased by 2.2%(from 66.3% to 64.1%),while the Pt^(0) percentage of Pt/C decreased by 7.1%(from 53.3% to 46.2%).It is suggested that the synergy between Ru and Co holds the potential to pave the way for future low-cost and highly stable ORR catalysts,offering significant promise in the context of PEMFCs.
基金supported by the Scientific and Technological Innovation Project of the China Academy of Chinese Medical Sciences(CI2021A04013)the National Natural Science Foundation of China(82204610)+1 种基金the Qihang Talent Program(L2022046)the Fundamental Research Funds for the Central Public Welfare Research Institutes(ZZ15-YQ-041 and L2021029).
文摘Background:Os Draconis is an important material in traditional Chinese medicine(TCM).However,its market is saturated with counterfeit products,and the limitations of current identification methods pose a serious threat to clinical effectiveness and drug safety.This study aims to establish a more accurate and comprehensive authentication system for Os Draconis.Methods:A comprehensive approach was employed to analyze authentic Os Draconis,fossilized Os Draconis,counterfeit products,and lab-prepared modern animal bones.The analytical techniques included ^(14)C dating,electron probe microanalysis(EPMA),polarized light microscopy,X-ray diffraction(XRD),inductively coupled plasma mass spectrometry(ICP-MS),and fourier-transform infrared spectroscopy(FTIR).The study focused on examining the microstructural features and micro-area elemental compositions to identify distinguishing characteristics.Results:Physical identification alone was insufficient to reliably distinguish authentic Os Draconis from its counterfeits.XRD analysis revealed that while hydroxyapatite is the main component in all samples,authentic Os Draconis also contains calcium carbonate and quartz,which were absent in counterfeit and lab-prepared samples.FTIR spectra identified the carbonate ion(CO_(3)^(2-))as a characteristic infrared marker for authentic Os Draconis.ICP-MS analysis showed that Ca and P are the major elements,with a notably high content of Lanthanum(La)among rare earth elements in authentic samples.The EPMA results demonstrated that the Ca/P ratio of authentic Os Draconis is distinct,falling between that of fossilized Os Draconis and counterfeit samples.Conclusion:This study successfully identified several precise markers,including the presence of calcium carbonate,the characteristic CO_(3)^(2-)infrared peak,a high La content,and a specific Ca/P ratio,for the accurate and rapid authentication of Os Draconis.Furthermore,the analysis of its natural porous structure,suitable pore size,and surface area suggests that Os Draconis has significant potential as a natural drug carrier.
