CD36 is a highly glycosylated integral membrane protein that belongs to the scavenger receptor class B family and regulates the pathological progress of metabolic diseases.CD36 was recently found to be widely expresse...CD36 is a highly glycosylated integral membrane protein that belongs to the scavenger receptor class B family and regulates the pathological progress of metabolic diseases.CD36 was recently found to be widely expressed in various cell types in the nervous system,including endothelial cells,pericytes,astrocytes,and microglia.CD36 mediates a number of regulatory processes,such as endothelial dysfunction,oxidative stress,mitochondrial dysfunction,and inflammatory responses,which are involved in many central nervous system diseases,such as stroke,Alzheimer’s disease,Parkinson’s disease,and spinal cord injury.CD36 antagonists can suppress CD36 expression or prevent CD36 binding to its ligand,thereby achieving inhibition of CD36-mediated pathways or functions.Here,we reviewed the mechanisms of action of CD36 antagonists,such as Salvianolic acid B,tanshinone IIA,curcumin,sulfosuccinimidyl oleate,antioxidants,and small-molecule compounds.Moreover,we predicted the structures of binding sites between CD36 and antagonists.These sites can provide targets for more efficient and safer CD36 antagonists for the treatment of central nervous system diseases.展开更多
Corneal neuromas,also termed microneuromas,refer to microscopic,irregula rly-shaped enlargements of terminal subbasal nerve endings at sites of nerve damage or injury.The formation of corneal neuromas results from dam...Corneal neuromas,also termed microneuromas,refer to microscopic,irregula rly-shaped enlargements of terminal subbasal nerve endings at sites of nerve damage or injury.The formation of corneal neuromas results from damage to corneal nerves,such as following corneal pathology or corneal or intraocular surge ries.Initially,denervated areas of sensory nerve fibers become invaded by sprouts of intact sensory nerve fibers,and later injured axons regenerate and new sprouts called neuromas develop.In recent years,analysis of corneal nerve abnormalities including corneal neuromas which can be identified using in vivo confocal microscopy,a non-invasive imaging technique with microscopic resolution,has been used to evaluate corneal neuropathy and ocular surface dysfunction.Corneal neuromas have been shown to be associated with clinical symptoms of discomfort and dryness of eyes,and are a promising surrogate biomarker for ocular surface diseases,such as neuropathic corneal pain,dry eye disease,diabetic corneal neuropathy,neurotrophic keratopathy,Sjogren's syndrome,bullous keratopathy,post-refra ctive surgery,and others.In this review,we have summarized the current literature on the association between these ocular surface diseases and the presentation of corneal microneuromas,as well as elaborated on their pathogenesis,visualization via in vivo confocal microscopy,and utility in monitoring treatment efficacy.As current quantitative analysis on neuromas mainly relies on manual annotation and quantification,which is user-dependent and labor-intensive,future direction includes the development of artificial intelligence software to identify and quantify these potential imaging biomarkers in a more automated and sensitive manner,allowing it to be applied in clinical settings more efficiently.Combining imaging and molecular biomarkers may also help elucidate the associations between corneal neuromas and ocular surface diseases.展开更多
Exosomes exhibit complex biological functions and mediate a variety of biological processes,such as promoting axonal regeneration and functional recove ry after injury.Long non-coding RNAs(IncRNAs)have been reported t...Exosomes exhibit complex biological functions and mediate a variety of biological processes,such as promoting axonal regeneration and functional recove ry after injury.Long non-coding RNAs(IncRNAs)have been reported to play a crucial role in axonal regeneration.Howeve r,the role of the IncRNA-microRNAmessenger RNA(mRNA)-competitive endogenous RNA(ceRNA)network in exosome-mediated axonal regeneration remains unclear.In this study,we performed RNA transcriptome sequencing analysis to assess mRNA expression patterns in exosomes produced by cultured fibroblasts(FC-EXOs)and Schwann cells(SCEXOs).Diffe rential gene expression analysis,Gene Ontology analysis,Kyoto Encyclopedia of Genes and Genomes analysis,and protein-protein intera ction network analysis were used to explo re the functions and related pathways of RNAs isolated from FC-EXOs and SC-EXOs.We found that the ribosome-related central gene Rps5 was enriched in FC-EXOs and SC-EXOs,which suggests that it may promote axonal regeneration.In addition,using the miRWalk and Starbase prediction databases,we constructed a regulatory network of ceRNAs targeting Rps5,including 27 microRNAs and five IncRNAs.The ceRNA regulatory network,which included Ftx and Miat,revealed that exsosome-derived Rps5 inhibits scar formation and promotes axonal regeneration and functional recovery after nerve injury.Our findings suggest that exosomes derived from fibro blast and Schwann cells could be used to treat injuries of peripheral nervous system.展开更多
The shear behavior of backfill-rock composites is crucial for mine safety and the management of surface subsidence.For exposing the shear failure mechanism of backfill-rock composites,we conducted shear tests on backf...The shear behavior of backfill-rock composites is crucial for mine safety and the management of surface subsidence.For exposing the shear failure mechanism of backfill-rock composites,we conducted shear tests on backfill-rock composites under three constant normal loads,compared with the unfilled rock.To investigate the macro-and meso-failure characteristics of the samples in the shear tests,the cracking behavior of samples was recorded by a high-speed camera and acoustic emission monitoring.In parallel with the experimental test,the numerical models of backfill-rock composites and unfilled rock were established using the discrete element method to analyze the continuous-discontinuous shearing process.Based on the damage mechanics and statistics,a novel shear constitutive model was proposed to describe mechanical behavior.The results show that backfill-rock composites had a special bimodal phenomenon of shearing load-deformation curve,i.e.the first shearing peak corresponded to rock break and the second shearing peak induced by the broken of aeolian sand-cement/fly ash paste backfill.Moreover,the shearing characteristic curves of the backfill-rock composites could be roughly divided into four stages,i.e.the shear failure of the specimens experienced:stage I:stress concentration;stage II:crack propagation;stage III:crack coalescence;stage IV:shearing friction.The numerical simulation shows that the existence of aeolian sand-cement/fly ash paste backfill inevitably altered the coalescence type and failure mode of the specimens and had a strengthening effect on the shear strength of backfillrock composites.Based on damage mechanics and statistics,a shear constitutive model was proposed to describe the shear fracture characteristics of specimens,especially the bimodal phenomenon.Finally,the micro-and meso-mechanisms of shear failure were discussed by combining the micro-test and numerical results.The research can advance the better understanding of the shear behavior of backfill-rock composites and contribute to the safety of mining engineering.展开更多
Sedimentary process research is of great significance for understanding the distribution and characteristics of sediments.Through the detailed observation and measurement of the Sangyuan outcrop in Luanping Basin,this...Sedimentary process research is of great significance for understanding the distribution and characteristics of sediments.Through the detailed observation and measurement of the Sangyuan outcrop in Luanping Basin,this paper studies the depositional process of the hyperpycnal flow deposits,and divides their depositional process into three phases,namely,acceleration,erosion and deceleration.In the acceleration phase,hyperpycnal flow begins to enter the basin nearby,and then speeds up gradually.Deposits developed in the acceleration phase are reverse.In addition,the original deposits become unstable and are taken away by hyperpycnal flows under the eroding force.As a result,there are a lot of mixture of red mud pebbles outside the basin and gray mud pebbles within the basin.In the erosion phase,the reverse deposits are eroded and become thinner or even disappear.Therefore,no reverse grading characteristic is found in the proximal major channel that is closer to the source,but it is still preserved in the middle branch channel that is far from the source.After entering the deceleration phase,normally grading deposits appear and cover previous deposits.The final deposits in the basin are special.Some are reverse,and others are normal.They are superimposed with each other under the action of hyperpycnal flow.The analysis of the Sangyuan outcrop demonstrates the sedimentary process and distribution of hyperpycnites,and reasonably explain the sedimentary characteristics of hyperpycnites.It is helpful to the prediction of oil and gas exploration targets in gravity flow deposits.展开更多
Species closely related to wheat are important genetic resources for agricultural production,functional genomics studies and wheat improvement.In this study,a wheat gene related to regeneration,TaWOX5,was applied to e...Species closely related to wheat are important genetic resources for agricultural production,functional genomics studies and wheat improvement.In this study,a wheat gene related to regeneration,TaWOX5,was applied to establish the Agrobacterium-mediated transformation systems of Triticum monococcum,hexaploid triticale,and rye(Secale cereale L.)using their immature embryos.Transgenic plants were efficiently generated.During the transformation process,the Agrobacterium infection efficiency was assessed by histochemical staining forβ-glucuronidase(GUS).Finally,the transgenic nature of regenerated plants was verified by polymerase chain reaction(PCR)-based genotyping for the presence of the GUS and bialaphos resistance(bar)genes,histochemical staining for GUS protein,and the QuickStix strip assay for bar protein.The transformation efficiency of T.monococcum genotype PI428182 was 94.4%;the efficiencies of four hexaploid triticale genotypes Lin456,ZS3297,ZS1257,and ZS3224 were 52.1,41.2,19.4,and 16.0%,respectively;and the transformation efficiency of rye cultivar Lanzhou Heimai was 7.8%.Fluorescence in situ hybridization(FISH)and genomic in situ hybridization(GISH)analyses indicated that the GUS transgenes were integrated into the distal or near centromere(proximal)regions of the chromosomes in transgenic T.monococcum and hexaploid triticale plants.In the transgenic hexaploid triticale plants,the foreign DNA fragment was randomly integrated into the AABB and RR genomes.Furthermore,the transgene was almost stably inherited in the next generation by Mendel’s law.The findings in this study will promote the genetic improvement of the three plant species for grain or forage production and the improvement of cereal species including wheat for functional genomics studies.展开更多
X-ray fluorescence(XRF)sensor-based ore sorting enables efficient beneficiation of heterogeneous ores,while intraparticle heterogeneity can cause significant grade detection errors,leading to misclassifications and hi...X-ray fluorescence(XRF)sensor-based ore sorting enables efficient beneficiation of heterogeneous ores,while intraparticle heterogeneity can cause significant grade detection errors,leading to misclassifications and hindering widespread technology adoption.Accurate classification models are crucial to determine if actual grade exceeds the sorting threshold using localized XRF signals.Previous studies mainly used linear regression(LR)algorithms including simple linear regression(SLR),multivariable linear regression(MLR),and multivariable linear regression with interaction(MLRI)but often fell short attaining satisfactory results.This study employed the particle swarm optimization support vector machine(PSO-SVM)algorithm for sorting porphyritic copper ore pebble.Lab-scale results showed PSO-SVM out-performed LR and raw data(RD)models and the significant interaction effects among input features was observed.Despite poor input data quality,PSO-SVM demonstrated exceptional capabilities.Lab-scale sorting achieved 93.0%accuracy,0.24%grade increase,84.94%recovery rate,57.02%discard rate,and a remarkable 39.62 yuan/t net smelter return(NSR)increase compared to no sorting.These improvements were achieved by the PSO-SVM model with optimized input combinations and highest data quality(T=10,T is XRF testing times).The unsuitability of LR methods for XRF sensor-based sorting of investigated sample is illustrated.Input element selection and mineral association analysis elucidate element importance and influence mechanisms.展开更多
The organ-specific toxicity resulting from microplastic(MP)exposure has been extensively explored,particularly concerning the gut,liver,testis,and lung.However,under natural conditions,these effects are not restricted...The organ-specific toxicity resulting from microplastic(MP)exposure has been extensively explored,particularly concerning the gut,liver,testis,and lung.However,under natural conditions,these effects are not restricted to specific organs or tissues.Investigating whether MP exposure presents a systemic threat to an entire organism,impacting factors such as lifespan,sleep,and fecundity,is essential.In this study,we investigated the effects of dietary exposure to two different doses of MPs(1–5μm)using the terrestrial model organism Drosophila melanogaster.Results indicated that the particles caused gut damage and remained within the digestive system.Continuous MP exposure significantly shortened the lifespan of adult flies.Even short-term exposure disrupted sleep patterns,increasing the length of daytime sleep episodes.Additionally,one week of MP exposure reduced ovary size,with a trend towards decreased egg-laying in mated females.Although MPs did not penetrate the brain or ovaries,transcriptome analysis revealed altered gene expression in these tissues.In the ovary,Gene Ontology(GO)analysis indicated genotoxic effects impacting inflammation,circadian regulation,and metabolic processes,with significant impacts on extracellular structure-related pathways.In the brain,GO analysis identified changes in pathways associated with proteolysis and carbohydrate metabolism.Overall,this study provides compelling evidence of the systemic negative effects of MP exposure,highlighting the urgent need to address and mitigate environmental MP pollution.展开更多
Diabetic corneal neuropathy and diabetic retinopathy are ocular complications occurring in the context of diabetes mellitus.Diabetic corneal neuropathy refers to the progressive damage of corneal nerves.Diabetic retin...Diabetic corneal neuropathy and diabetic retinopathy are ocular complications occurring in the context of diabetes mellitus.Diabetic corneal neuropathy refers to the progressive damage of corneal nerves.Diabetic retinopathy has traditionally been considered as damage to the retinal microvasculature.However,growing evidence suggests that diabetic retinopathy is a complex neurovascular disorder resulting from dysfunction of the neurovascular unit,which includes both the retinal vascular structures and neural tissues.Diabetic retinopathy is one of the leading causes of blindness and is frequently screened for as part of diabetic ocular screening.However,diabetic corneal neuropathy is commonly overlooked and underdiagnosed,leading to severe ocular surface impairment.Several studies have found that these two conditions tend to occur together,and they share similarities in their pathogenesis pathways,being triggered by a status of chronic hyperglycemia.This review aims to discuss the interconnection between diabetic corneal neuropathy and diabetic retinopathy,whether diabetic corneal neuropathy precedes diabetic retinopathy,as well as the relation between the stage of diabetic retinopathy and the severity of corneal neuropathy.We also endeavor to explore the relevance of a corneal screening in diabetic eyes and the possibility of using corneal nerve measurements to monitor the progression of diabetic retinopathy.展开更多
Inspired by the function of crucial components in photosystemⅡ(PSⅡ),electrochemical and dyesensitized photoelectrochemical(DSPEC)water oxidation devices were constructed by the selfassembly of well-designed amphipat...Inspired by the function of crucial components in photosystemⅡ(PSⅡ),electrochemical and dyesensitized photoelectrochemical(DSPEC)water oxidation devices were constructed by the selfassembly of well-designed amphipathic Ru(bda)-based catalysts(bda=2,2'-bipyrdine-6,6'-dicarbonoxyl acid)and aliphatic chain decorated electrode surfaces,forming lipid bilayer membrane(LBM)-like structures.The Ru(bda)catalysts on electrode-supported LBM films demonstrated remarkable water oxidation performance with different O-O formation mechanisms.However,compared to the slow charge transfer process,the O-O formation pathways did not determine the PEC water oxidation efficiency of the dyesensitized photoanodes,and the different reaction rates for similar catalysts with different catalytic paths did not determine the PEC performance of the DSPECs.Instead,charge transfer plays a decisive role in the PEC water oxidation rate.When an indolo[3,2-b]carbazole derivative was introduced between the Ru(bda)catalysts and aliphatic chain-modified photosensitizer in LBM films,serving as a charge transfer mediator for the tyrosine-histidine pair in PSⅡ,the PEC water oxidation performance of the corresponding photoanodes was dramatically enhanced.展开更多
Background:Nonalcoholic fatty liver disease(NAFLD)is associated with disordered lipid and iron metabolism.Our previous study has substantiated the pivotal role of Caveolin-1(Cav-1)in protecting hepatocytes and mediati...Background:Nonalcoholic fatty liver disease(NAFLD)is associated with disordered lipid and iron metabolism.Our previous study has substantiated the pivotal role of Caveolin-1(Cav-1)in protecting hepatocytes and mediating iron metabolism in the liver.This study aimed to explore the specific mechanisms underlying the regulation of iron metabolism by Cav-1 in NAFLD.Methods:Hepatocyte-specific Cav-1 overexpression mice and knockout mice were used in this study.Cav-1-knockdown of RAW264.7 cells and mouse primary hepatocytes were performed to verify the changes in vitro.Moreover,a high-fat diet and palmitic acid plus oleic acid treatment were utilized to construct a NAFLD model in vivo and in vitro,respectively,while a high-iron diet was used to construct an in vivo iron overload model.Besides,iron concentration,the expression of Cav-1 and iron metabolism-related proteins in liver tissue or serum were detected using iron assay kit,Prussian blue staining,Western blotting,immunofluorescence staining,immunohistochemical staining and ELISA.The related indicators of lipid metabolism and oxidative stress were evaluated by the corresponding reagent kit and staining.Results:Significant disorder of lipid and iron metabolism occurred in NAFLD.The expression of Cav-1 was decreased in NAFLD hepatocytes(P<0.05),accompanied by iron metabolism disorder.Cav-1 enhanced the iron storage capacity of hepatocytes by activating the ferritin light chain/ferritin heavy chain pathway in NAFLD,subsequently alleviating the oxidative stress induced by excess ferrous ions in the liver.Further,CD68^(+) CD163^(+) macrophages expressing Cav-1 were found to accelerate iron accumulation in the liver,which was contrary to the effect of Cav-1 in hepatocytes.Positive correlations were also observed between the serum Cav-1 concentration and the serum iron-related protein levels in NAFLD patients and healthy volunteers(P<0.05).Conclusions:These findings confirm that Cav-1 is an essential target protein that regulates iron and lipid metabolic homeostasis.It is a pivotal molecule for predicting and protecting against the development of NAFLD.展开更多
BACKGROUND:There are currently no effective drugs to mitigate the ischemia/reperfusion injury caused by fluid resuscitation after hemorrhagic shock(HS).The aim of this study was to explore the potential of the histone...BACKGROUND:There are currently no effective drugs to mitigate the ischemia/reperfusion injury caused by fluid resuscitation after hemorrhagic shock(HS).The aim of this study was to explore the potential of the histone deacetylase 6(HDAC6)-specific inhibitor tubastatin A(TubA)to suppress nucleotide-binding oligomerization domain-like receptor protein 3(NLRP3)inflammasome activation in macrophages under hypoxia/reoxygenation(H/R)conditions.METHODS:The viability of RAW264.7 cells subjected to H/R after treatment with different concentrations of TubA was assessed using a cell-counting kit-8(CCK8)assay.Briefly,2.5μmol/L TubA was used with RAW264.7 cells under H/R condition.RAW264.7 cells were divided into three groups,namely the control,H/R,and TubA groups.The levels of reactive oxygen species(ROS)in the cells were detected using fluorescence microscopy.The protein expression of HDAC6,heat shock protein 90(Hsp90),inducible nitric oxide synthase(iNOS),NLRP3,gasdermin-D(GSDMD),Caspase-1,GSDMD-N,and Caspase-1 p20 was detected by western blotting.The levels of interleukin-1β(IL-1β)and IL-18 in the supernatants were detected using enzyme-linked immunosorbent assay(ELISA).RESULTS:HDAC6,Hsp90,and iNOS expression levels were significantly higher(P<0.01)in the H/R group than in the control group,but lower in the TubA group than in the H/R group(P<0.05).When comparing the H/R group to the control group,ROS levels were significantly higher(P<0.01),but significantly reduced in the TubA group(P<0.05).The H/R group had higher NLRP3,GSDMD,Caspase-1,GSDMD-N,and Caspase-1 p20 expression levels than the control group(P<0.05),however,the TubA group had significantly lower expression levels than the H/R group(P<0.05).IL-1βand IL-18 levels in the supernatants were significantly higher in the H/R group compared to the control group(P<0.01),but significantly lower in the TubA group compared to the H/R group(P<0.01).CONCLUSION:TubA inhibited the expression of HDAC6,Hsp90,and iNOS in macrophages subjected to H/R.This inhibition led to a decrease in the content of ROS in cells,which subsequently inhibited the activation of the NLRP3 inflammasome and the secretion of IL-1βand IL-18.展开更多
Negatively thermo-responsive 2D membranes,which mimic the stomatal opening/closing of plants,have drawn substantial interest for tunable molecular separation processes.However,these membranes are still restricted sign...Negatively thermo-responsive 2D membranes,which mimic the stomatal opening/closing of plants,have drawn substantial interest for tunable molecular separation processes.However,these membranes are still restricted significantly on account of low water permeability and poor dynamic tunability of 2D nanochannels under temperature stimulation.Here,we present a biomimetic negatively thermo-responsive MXene membrane by covalently grafting poly(N-isopropylacrylamide)(PNIPAm)onto MXene nanosheets.The uniformly grafted PNIPAm polymer chains can enlarge the interlayer spacings for increasing water permeability while also allowing more tunability of 2D nanochannels for enhancing the capability of gradually separating multiple molecules of different sizes.As expected,the constructed membrane exhibits ultrahigh water permeance of 95.6 L m^(-2) h^(-1) bar^(-1) at 25℃,which is eight-fold higher than the state-of-the-art negatively thermoresponsive 2D membranes.Moreover,the highly temperature-tunable 2D nanochannels enable the constructed membrane to perform excellent graded molecular sieving for dye-and antibiotic-based ternary mixtures.This strategy provides new perspectives in engineering smart 2D membrane and expands the scope of temperature-responsive membranes,showing promising applications in micro/nanofluidics and molecular separation.展开更多
Unfavorable environmental cues severely affect crop productivity resulting in significant economic losses to farmers. In plants, multiple regulatory genes, such as the WRKY transcription factor (TF) family, modulate t...Unfavorable environmental cues severely affect crop productivity resulting in significant economic losses to farmers. In plants, multiple regulatory genes, such as the WRKY transcription factor (TF) family, modulate the expression of defense genes. However, the role of the pineapple WRKY genes is poorly understood. Here, we studied the pineapple WRKY gene, AcWRKY28, by generating AcWRKY28 over-expressing transgenic pineapple plants. Overexpression of AcWRKY28 enhanced the salt stress resistance in transgenic pineapple lines. Comparative transcriptome analysis of transgenic and wild-type pineapple plants showed that “plant-pathogen interaction” pathway genes, including 9calcium-dependent protein kinases (CPKs), were up-regulated in AcWRKY28 over-expressing plants. Furthermore, chromatin immunoprecipitation and yeast one-hybrid assays revealed AcCPK12, AcCPK3, AcCPK8, AcCPK1, and AcCPK15 as direct targets of AcWRKY28. Consistently, the study of AcCPK12 over-expressing Arabidopsis lines showed that AcCPK12 enhances salt, drought, and disease resistance. This study shows that AcWRKY28 plays a crucial role in promoting salt stress resistance by activating the expression of AcCPK genes.展开更多
The efficient clinical treatment of oral squamous cell carcinoma(OSCC)is still a challenge that demands the development of effective new drugs.Phenformin has been shown to produce more potent anti-tumor activities tha...The efficient clinical treatment of oral squamous cell carcinoma(OSCC)is still a challenge that demands the development of effective new drugs.Phenformin has been shown to produce more potent anti-tumor activities than metformin on different tumors,however,not much is known about the influence of phenformin on OSCC cells.We found that phenformin suppresses OSCC cell proliferation,and promotes OSCC cell autophagy and apoptosis to significantly inhibit OSCC cell growth both in vivo and in vitro.RNA-seq analysis revealed that autophagy pathways were the main targets of phenformin and identified two new targets DDIT4(DNA damage inducible transcript 4)and NIBAN1(niban apoptosis regulator 1).We found that phenformin significantly induces the expression of both DDIT4 and NIBAN1 to promote OSCC autophagy.Further,the enhanced expression of DDIT4 and NIBAN1 elicited by phenformin was not blocked by the knockdown of AMPK but was suppressed by the knockdown of transcription factor ATF4(activation transcription factor 4),which was induced by phenformin treatment in OSCC cells.Mechanistically,these results revealed that phenformin triggers endoplasmic reticulum(ER)stress to activate PERK(protein kinase R-like ER kinase),which phosphorylates the transitional initial factor eIF2,and the increased phosphorylation of eIF2 leads to the increased translation of ATF4.In summary,we discovered that phenformin induces its new targets DDIT4 and especially NIBAN1 to promote autophagic and apoptotic cell death to suppress OSCC cell growth.Our study supports the potential clinical utility of phenformin for OSCC treatment in the future.展开更多
Many studies have revealed that gut microbes modulate host metabolism.In this study,we characterized the therapeutic effects of a novel gut commensal Luoshenia tenuis against host metabolic disorders.First,by in silic...Many studies have revealed that gut microbes modulate host metabolism.In this study,we characterized the therapeutic effects of a novel gut commensal Luoshenia tenuis against host metabolic disorders.First,by in silico analysis,we demonstrated that the L.tenuis was prevalent in the gut microbiomes of healthy humans but were depleted specifically in obesity cohorts.Further in vitro cultivation revealed that L.tenuis produced short chain fatty acids that were verified to modulate host metabolism and some other volatile metabolites to benefit hosts by anti-inflammation and anti-tumor.Second,gavage of the L.tenuis significantly decreased the body weight gain and food intake of high-fat diet-feeding C57BL/6J mice,which was in parallel with the changed expression level of genes related to satiety and feeding behavior.We then performed the gavage trial using diet induced obese mice,and it revealed that the administration of L.tenuis alleviated significantly the abnormal glucose and lipid metabolisms and reduced the inflammatory response.In summary,this study revealed a previously-unknown human gut commensal microbe that benefited host metabolism,and set the stage for the development of novel next-generation probiotic applicable for treatment of obesity and related metabolic disorders.展开更多
Dynamic monitoring of blood pressure (BP) is beneficial to obtain comprehensive cardiovascular information of patients throughout the day. However, the clinical BP measurement method relies on wearing a bulky cuff, wh...Dynamic monitoring of blood pressure (BP) is beneficial to obtain comprehensive cardiovascular information of patients throughout the day. However, the clinical BP measurement method relies on wearing a bulky cuff, which limits the long-term monitoring and control of BP. In this work, a microcavity assisted graphene pressure sensor (MAGPS) for single-vessel local BP monitoring is designed to replace the cuff. The microcavity structure increases the working range of the sensor by gas pressure buffering. Therefore, the MAGPS achieves a wide linear response of 0–1050 kPa and sensitivity of 15.4 kPa^(−1). The large working range and the microcavity structure enable the sensor to fully meet the requirements of BP detection at the radial artery. A database of 228 BP data (60-s data fragment detected by MAGPS) and 11,804 pulse waves from 9 healthy subjects and 5 hypertensive subjects is built. Finally, the BP was detected and analyzed automatically by combining MAGPS and a two-stage convolutional neural network algorithm. For the BP detection method at local radial artery, the first stage algorithm first determines whether the subject has hypertension by the pulse wave. Then, the second stage algorithm can diagnose systolic and diastolic BP with the accuracy of 93.5% and 97.8% within a 10 mmHg error, respectively. This work demonstrates a new BP detection method based on single vessel, which greatly promotes the efficiency of BP detection.展开更多
基金supported by the National Major Project of Research and Development,No.2022YFA1105500(to SZ)the National Natural Science Foundation of China,No.81870975(to SZ)Innovation Program for Graduate Students in Jiangsu Province of China,No.KYCX223335(to MZ)。
文摘CD36 is a highly glycosylated integral membrane protein that belongs to the scavenger receptor class B family and regulates the pathological progress of metabolic diseases.CD36 was recently found to be widely expressed in various cell types in the nervous system,including endothelial cells,pericytes,astrocytes,and microglia.CD36 mediates a number of regulatory processes,such as endothelial dysfunction,oxidative stress,mitochondrial dysfunction,and inflammatory responses,which are involved in many central nervous system diseases,such as stroke,Alzheimer’s disease,Parkinson’s disease,and spinal cord injury.CD36 antagonists can suppress CD36 expression or prevent CD36 binding to its ligand,thereby achieving inhibition of CD36-mediated pathways or functions.Here,we reviewed the mechanisms of action of CD36 antagonists,such as Salvianolic acid B,tanshinone IIA,curcumin,sulfosuccinimidyl oleate,antioxidants,and small-molecule compounds.Moreover,we predicted the structures of binding sites between CD36 and antagonists.These sites can provide targets for more efficient and safer CD36 antagonists for the treatment of central nervous system diseases.
文摘Corneal neuromas,also termed microneuromas,refer to microscopic,irregula rly-shaped enlargements of terminal subbasal nerve endings at sites of nerve damage or injury.The formation of corneal neuromas results from damage to corneal nerves,such as following corneal pathology or corneal or intraocular surge ries.Initially,denervated areas of sensory nerve fibers become invaded by sprouts of intact sensory nerve fibers,and later injured axons regenerate and new sprouts called neuromas develop.In recent years,analysis of corneal nerve abnormalities including corneal neuromas which can be identified using in vivo confocal microscopy,a non-invasive imaging technique with microscopic resolution,has been used to evaluate corneal neuropathy and ocular surface dysfunction.Corneal neuromas have been shown to be associated with clinical symptoms of discomfort and dryness of eyes,and are a promising surrogate biomarker for ocular surface diseases,such as neuropathic corneal pain,dry eye disease,diabetic corneal neuropathy,neurotrophic keratopathy,Sjogren's syndrome,bullous keratopathy,post-refra ctive surgery,and others.In this review,we have summarized the current literature on the association between these ocular surface diseases and the presentation of corneal microneuromas,as well as elaborated on their pathogenesis,visualization via in vivo confocal microscopy,and utility in monitoring treatment efficacy.As current quantitative analysis on neuromas mainly relies on manual annotation and quantification,which is user-dependent and labor-intensive,future direction includes the development of artificial intelligence software to identify and quantify these potential imaging biomarkers in a more automated and sensitive manner,allowing it to be applied in clinical settings more efficiently.Combining imaging and molecular biomarkers may also help elucidate the associations between corneal neuromas and ocular surface diseases.
基金supported by the National Natural Science Foundation of China,No.81870975(to SZ)。
文摘Exosomes exhibit complex biological functions and mediate a variety of biological processes,such as promoting axonal regeneration and functional recove ry after injury.Long non-coding RNAs(IncRNAs)have been reported to play a crucial role in axonal regeneration.Howeve r,the role of the IncRNA-microRNAmessenger RNA(mRNA)-competitive endogenous RNA(ceRNA)network in exosome-mediated axonal regeneration remains unclear.In this study,we performed RNA transcriptome sequencing analysis to assess mRNA expression patterns in exosomes produced by cultured fibroblasts(FC-EXOs)and Schwann cells(SCEXOs).Diffe rential gene expression analysis,Gene Ontology analysis,Kyoto Encyclopedia of Genes and Genomes analysis,and protein-protein intera ction network analysis were used to explo re the functions and related pathways of RNAs isolated from FC-EXOs and SC-EXOs.We found that the ribosome-related central gene Rps5 was enriched in FC-EXOs and SC-EXOs,which suggests that it may promote axonal regeneration.In addition,using the miRWalk and Starbase prediction databases,we constructed a regulatory network of ceRNAs targeting Rps5,including 27 microRNAs and five IncRNAs.The ceRNA regulatory network,which included Ftx and Miat,revealed that exsosome-derived Rps5 inhibits scar formation and promotes axonal regeneration and functional recovery after nerve injury.Our findings suggest that exosomes derived from fibro blast and Schwann cells could be used to treat injuries of peripheral nervous system.
文摘The shear behavior of backfill-rock composites is crucial for mine safety and the management of surface subsidence.For exposing the shear failure mechanism of backfill-rock composites,we conducted shear tests on backfill-rock composites under three constant normal loads,compared with the unfilled rock.To investigate the macro-and meso-failure characteristics of the samples in the shear tests,the cracking behavior of samples was recorded by a high-speed camera and acoustic emission monitoring.In parallel with the experimental test,the numerical models of backfill-rock composites and unfilled rock were established using the discrete element method to analyze the continuous-discontinuous shearing process.Based on the damage mechanics and statistics,a novel shear constitutive model was proposed to describe mechanical behavior.The results show that backfill-rock composites had a special bimodal phenomenon of shearing load-deformation curve,i.e.the first shearing peak corresponded to rock break and the second shearing peak induced by the broken of aeolian sand-cement/fly ash paste backfill.Moreover,the shearing characteristic curves of the backfill-rock composites could be roughly divided into four stages,i.e.the shear failure of the specimens experienced:stage I:stress concentration;stage II:crack propagation;stage III:crack coalescence;stage IV:shearing friction.The numerical simulation shows that the existence of aeolian sand-cement/fly ash paste backfill inevitably altered the coalescence type and failure mode of the specimens and had a strengthening effect on the shear strength of backfillrock composites.Based on damage mechanics and statistics,a shear constitutive model was proposed to describe the shear fracture characteristics of specimens,especially the bimodal phenomenon.Finally,the micro-and meso-mechanisms of shear failure were discussed by combining the micro-test and numerical results.The research can advance the better understanding of the shear behavior of backfill-rock composites and contribute to the safety of mining engineering.
基金the Scientific research and technology development project of Petro China(2021DJ5303)。
文摘Sedimentary process research is of great significance for understanding the distribution and characteristics of sediments.Through the detailed observation and measurement of the Sangyuan outcrop in Luanping Basin,this paper studies the depositional process of the hyperpycnal flow deposits,and divides their depositional process into three phases,namely,acceleration,erosion and deceleration.In the acceleration phase,hyperpycnal flow begins to enter the basin nearby,and then speeds up gradually.Deposits developed in the acceleration phase are reverse.In addition,the original deposits become unstable and are taken away by hyperpycnal flows under the eroding force.As a result,there are a lot of mixture of red mud pebbles outside the basin and gray mud pebbles within the basin.In the erosion phase,the reverse deposits are eroded and become thinner or even disappear.Therefore,no reverse grading characteristic is found in the proximal major channel that is closer to the source,but it is still preserved in the middle branch channel that is far from the source.After entering the deceleration phase,normally grading deposits appear and cover previous deposits.The final deposits in the basin are special.Some are reverse,and others are normal.They are superimposed with each other under the action of hyperpycnal flow.The analysis of the Sangyuan outcrop demonstrates the sedimentary process and distribution of hyperpycnites,and reasonably explain the sedimentary characteristics of hyperpycnites.It is helpful to the prediction of oil and gas exploration targets in gravity flow deposits.
基金supported by grants from the National Natural Science Foundation of China (31971946)the Technology Innovation Program of the Chinese Academy of Agricultural Sciences, China (2060302-2-23 and ASTIP-2060302-2-19).
文摘Species closely related to wheat are important genetic resources for agricultural production,functional genomics studies and wheat improvement.In this study,a wheat gene related to regeneration,TaWOX5,was applied to establish the Agrobacterium-mediated transformation systems of Triticum monococcum,hexaploid triticale,and rye(Secale cereale L.)using their immature embryos.Transgenic plants were efficiently generated.During the transformation process,the Agrobacterium infection efficiency was assessed by histochemical staining forβ-glucuronidase(GUS).Finally,the transgenic nature of regenerated plants was verified by polymerase chain reaction(PCR)-based genotyping for the presence of the GUS and bialaphos resistance(bar)genes,histochemical staining for GUS protein,and the QuickStix strip assay for bar protein.The transformation efficiency of T.monococcum genotype PI428182 was 94.4%;the efficiencies of four hexaploid triticale genotypes Lin456,ZS3297,ZS1257,and ZS3224 were 52.1,41.2,19.4,and 16.0%,respectively;and the transformation efficiency of rye cultivar Lanzhou Heimai was 7.8%.Fluorescence in situ hybridization(FISH)and genomic in situ hybridization(GISH)analyses indicated that the GUS transgenes were integrated into the distal or near centromere(proximal)regions of the chromosomes in transgenic T.monococcum and hexaploid triticale plants.In the transgenic hexaploid triticale plants,the foreign DNA fragment was randomly integrated into the AABB and RR genomes.Furthermore,the transgene was almost stably inherited in the next generation by Mendel’s law.The findings in this study will promote the genetic improvement of the three plant species for grain or forage production and the improvement of cereal species including wheat for functional genomics studies.
基金supported by State Key Laboratory of Mineral Processing (No.BGRIMM-KJSKL-2022-16)China Postdoctoral Science Foundation (No.2021M700387)+1 种基金National Natural Science Foundation of China (No.G2021105015L)Ministry of Science and Technology of the People’s Republic of China (No.2022YFC2904502)。
文摘X-ray fluorescence(XRF)sensor-based ore sorting enables efficient beneficiation of heterogeneous ores,while intraparticle heterogeneity can cause significant grade detection errors,leading to misclassifications and hindering widespread technology adoption.Accurate classification models are crucial to determine if actual grade exceeds the sorting threshold using localized XRF signals.Previous studies mainly used linear regression(LR)algorithms including simple linear regression(SLR),multivariable linear regression(MLR),and multivariable linear regression with interaction(MLRI)but often fell short attaining satisfactory results.This study employed the particle swarm optimization support vector machine(PSO-SVM)algorithm for sorting porphyritic copper ore pebble.Lab-scale results showed PSO-SVM out-performed LR and raw data(RD)models and the significant interaction effects among input features was observed.Despite poor input data quality,PSO-SVM demonstrated exceptional capabilities.Lab-scale sorting achieved 93.0%accuracy,0.24%grade increase,84.94%recovery rate,57.02%discard rate,and a remarkable 39.62 yuan/t net smelter return(NSR)increase compared to no sorting.These improvements were achieved by the PSO-SVM model with optimized input combinations and highest data quality(T=10,T is XRF testing times).The unsuitability of LR methods for XRF sensor-based sorting of investigated sample is illustrated.Input element selection and mineral association analysis elucidate element importance and influence mechanisms.
基金Key Collaborative Research Program of the Alliance of International Science Organizations(ANSO-CR-KP-2021-12 to L.L.)National Natural Science Foundation of China(32071009,32371063,82341248 to C.L.,31971072 and 32171154 to L.L.)+1 种基金Guangdong Basic and Applied Basic Research Foundation(2024A1515011500 to C.L.)Shenzhen Science Technology and Innovative Commission(SZSTI JCYJ20180508152336419 to L.L.and GJHZ20200731095406021 to S.J.)。
文摘The organ-specific toxicity resulting from microplastic(MP)exposure has been extensively explored,particularly concerning the gut,liver,testis,and lung.However,under natural conditions,these effects are not restricted to specific organs or tissues.Investigating whether MP exposure presents a systemic threat to an entire organism,impacting factors such as lifespan,sleep,and fecundity,is essential.In this study,we investigated the effects of dietary exposure to two different doses of MPs(1–5μm)using the terrestrial model organism Drosophila melanogaster.Results indicated that the particles caused gut damage and remained within the digestive system.Continuous MP exposure significantly shortened the lifespan of adult flies.Even short-term exposure disrupted sleep patterns,increasing the length of daytime sleep episodes.Additionally,one week of MP exposure reduced ovary size,with a trend towards decreased egg-laying in mated females.Although MPs did not penetrate the brain or ovaries,transcriptome analysis revealed altered gene expression in these tissues.In the ovary,Gene Ontology(GO)analysis indicated genotoxic effects impacting inflammation,circadian regulation,and metabolic processes,with significant impacts on extracellular structure-related pathways.In the brain,GO analysis identified changes in pathways associated with proteolysis and carbohydrate metabolism.Overall,this study provides compelling evidence of the systemic negative effects of MP exposure,highlighting the urgent need to address and mitigate environmental MP pollution.
文摘Diabetic corneal neuropathy and diabetic retinopathy are ocular complications occurring in the context of diabetes mellitus.Diabetic corneal neuropathy refers to the progressive damage of corneal nerves.Diabetic retinopathy has traditionally been considered as damage to the retinal microvasculature.However,growing evidence suggests that diabetic retinopathy is a complex neurovascular disorder resulting from dysfunction of the neurovascular unit,which includes both the retinal vascular structures and neural tissues.Diabetic retinopathy is one of the leading causes of blindness and is frequently screened for as part of diabetic ocular screening.However,diabetic corneal neuropathy is commonly overlooked and underdiagnosed,leading to severe ocular surface impairment.Several studies have found that these two conditions tend to occur together,and they share similarities in their pathogenesis pathways,being triggered by a status of chronic hyperglycemia.This review aims to discuss the interconnection between diabetic corneal neuropathy and diabetic retinopathy,whether diabetic corneal neuropathy precedes diabetic retinopathy,as well as the relation between the stage of diabetic retinopathy and the severity of corneal neuropathy.We also endeavor to explore the relevance of a corneal screening in diabetic eyes and the possibility of using corneal nerve measurements to monitor the progression of diabetic retinopathy.
基金conducted by the Fundamental Research Center of Artificial Photosynthesis(FReCAP)financially supported by the National Natural Science Foundation of China(22172011 and 22088102)+1 种基金the National Key R&D Program of China(2022YFA0911904)the Fundamental Research Funds for the Central Universities(DUT22LK06,DUT22QN213 and DUT23LAB611)。
文摘Inspired by the function of crucial components in photosystemⅡ(PSⅡ),electrochemical and dyesensitized photoelectrochemical(DSPEC)water oxidation devices were constructed by the selfassembly of well-designed amphipathic Ru(bda)-based catalysts(bda=2,2'-bipyrdine-6,6'-dicarbonoxyl acid)and aliphatic chain decorated electrode surfaces,forming lipid bilayer membrane(LBM)-like structures.The Ru(bda)catalysts on electrode-supported LBM films demonstrated remarkable water oxidation performance with different O-O formation mechanisms.However,compared to the slow charge transfer process,the O-O formation pathways did not determine the PEC water oxidation efficiency of the dyesensitized photoanodes,and the different reaction rates for similar catalysts with different catalytic paths did not determine the PEC performance of the DSPECs.Instead,charge transfer plays a decisive role in the PEC water oxidation rate.When an indolo[3,2-b]carbazole derivative was introduced between the Ru(bda)catalysts and aliphatic chain-modified photosensitizer in LBM films,serving as a charge transfer mediator for the tyrosine-histidine pair in PSⅡ,the PEC water oxidation performance of the corresponding photoanodes was dramatically enhanced.
基金financially supported by the National Natural Science Foundation of China(82074131,81774170,82260926)the Guangdong Basic and Applied Basic Research Foundation(2018B030306012,2022A1515220179,2021A1515011667)+2 种基金the Outstanding Youth Development Scheme project of Southern Medical University(G621299870)the Young Elite Scientists Sponsorship Program by CACM(2021-QNRC2-B28)the China Postdoctoral Science Foundation(2022M721532).
文摘Background:Nonalcoholic fatty liver disease(NAFLD)is associated with disordered lipid and iron metabolism.Our previous study has substantiated the pivotal role of Caveolin-1(Cav-1)in protecting hepatocytes and mediating iron metabolism in the liver.This study aimed to explore the specific mechanisms underlying the regulation of iron metabolism by Cav-1 in NAFLD.Methods:Hepatocyte-specific Cav-1 overexpression mice and knockout mice were used in this study.Cav-1-knockdown of RAW264.7 cells and mouse primary hepatocytes were performed to verify the changes in vitro.Moreover,a high-fat diet and palmitic acid plus oleic acid treatment were utilized to construct a NAFLD model in vivo and in vitro,respectively,while a high-iron diet was used to construct an in vivo iron overload model.Besides,iron concentration,the expression of Cav-1 and iron metabolism-related proteins in liver tissue or serum were detected using iron assay kit,Prussian blue staining,Western blotting,immunofluorescence staining,immunohistochemical staining and ELISA.The related indicators of lipid metabolism and oxidative stress were evaluated by the corresponding reagent kit and staining.Results:Significant disorder of lipid and iron metabolism occurred in NAFLD.The expression of Cav-1 was decreased in NAFLD hepatocytes(P<0.05),accompanied by iron metabolism disorder.Cav-1 enhanced the iron storage capacity of hepatocytes by activating the ferritin light chain/ferritin heavy chain pathway in NAFLD,subsequently alleviating the oxidative stress induced by excess ferrous ions in the liver.Further,CD68^(+) CD163^(+) macrophages expressing Cav-1 were found to accelerate iron accumulation in the liver,which was contrary to the effect of Cav-1 in hepatocytes.Positive correlations were also observed between the serum Cav-1 concentration and the serum iron-related protein levels in NAFLD patients and healthy volunteers(P<0.05).Conclusions:These findings confirm that Cav-1 is an essential target protein that regulates iron and lipid metabolic homeostasis.It is a pivotal molecule for predicting and protecting against the development of NAFLD.
基金supported by National Natural Science Foundation of China(82102315).
文摘BACKGROUND:There are currently no effective drugs to mitigate the ischemia/reperfusion injury caused by fluid resuscitation after hemorrhagic shock(HS).The aim of this study was to explore the potential of the histone deacetylase 6(HDAC6)-specific inhibitor tubastatin A(TubA)to suppress nucleotide-binding oligomerization domain-like receptor protein 3(NLRP3)inflammasome activation in macrophages under hypoxia/reoxygenation(H/R)conditions.METHODS:The viability of RAW264.7 cells subjected to H/R after treatment with different concentrations of TubA was assessed using a cell-counting kit-8(CCK8)assay.Briefly,2.5μmol/L TubA was used with RAW264.7 cells under H/R condition.RAW264.7 cells were divided into three groups,namely the control,H/R,and TubA groups.The levels of reactive oxygen species(ROS)in the cells were detected using fluorescence microscopy.The protein expression of HDAC6,heat shock protein 90(Hsp90),inducible nitric oxide synthase(iNOS),NLRP3,gasdermin-D(GSDMD),Caspase-1,GSDMD-N,and Caspase-1 p20 was detected by western blotting.The levels of interleukin-1β(IL-1β)and IL-18 in the supernatants were detected using enzyme-linked immunosorbent assay(ELISA).RESULTS:HDAC6,Hsp90,and iNOS expression levels were significantly higher(P<0.01)in the H/R group than in the control group,but lower in the TubA group than in the H/R group(P<0.05).When comparing the H/R group to the control group,ROS levels were significantly higher(P<0.01),but significantly reduced in the TubA group(P<0.05).The H/R group had higher NLRP3,GSDMD,Caspase-1,GSDMD-N,and Caspase-1 p20 expression levels than the control group(P<0.05),however,the TubA group had significantly lower expression levels than the H/R group(P<0.05).IL-1βand IL-18 levels in the supernatants were significantly higher in the H/R group compared to the control group(P<0.01),but significantly lower in the TubA group compared to the H/R group(P<0.01).CONCLUSION:TubA inhibited the expression of HDAC6,Hsp90,and iNOS in macrophages subjected to H/R.This inhibition led to a decrease in the content of ROS in cells,which subsequently inhibited the activation of the NLRP3 inflammasome and the secretion of IL-1βand IL-18.
基金supported by the National Nature Science Foundation of China(No.22278179,U23A20688)the National Key Research and Development Program of China(2021YFB3802600)+3 种基金the Fundamental Research Funds for the Central Universities(JUSRP622035)National First-Class Discipline Program of Light Industry Technology and Engineering(LIFE2018-19)MOE&SAFEA for the 111 Project(B13025)Natural Science Foundation of Xinjiang Uygur Autonomous Region(2022D01D030).
文摘Negatively thermo-responsive 2D membranes,which mimic the stomatal opening/closing of plants,have drawn substantial interest for tunable molecular separation processes.However,these membranes are still restricted significantly on account of low water permeability and poor dynamic tunability of 2D nanochannels under temperature stimulation.Here,we present a biomimetic negatively thermo-responsive MXene membrane by covalently grafting poly(N-isopropylacrylamide)(PNIPAm)onto MXene nanosheets.The uniformly grafted PNIPAm polymer chains can enlarge the interlayer spacings for increasing water permeability while also allowing more tunability of 2D nanochannels for enhancing the capability of gradually separating multiple molecules of different sizes.As expected,the constructed membrane exhibits ultrahigh water permeance of 95.6 L m^(-2) h^(-1) bar^(-1) at 25℃,which is eight-fold higher than the state-of-the-art negatively thermoresponsive 2D membranes.Moreover,the highly temperature-tunable 2D nanochannels enable the constructed membrane to perform excellent graded molecular sieving for dye-and antibiotic-based ternary mixtures.This strategy provides new perspectives in engineering smart 2D membrane and expands the scope of temperature-responsive membranes,showing promising applications in micro/nanofluidics and molecular separation.
基金supported by the Natural Science Foundation of Guangxi (Grant No.2022GXNSFBA035523)the China Postdoctoral Science Foundation (Grant No.2022MD713731)+1 种基金the Science and Technology Major Project of Guangxi Gui Ke (Grant No.AA22067096)the project of Guangxi featured fruit innovation team on pineapple breeding and cultivation post under national modern agricultural industry technology system (Grant No.nycytxgxcxtd-17-05)。
文摘Unfavorable environmental cues severely affect crop productivity resulting in significant economic losses to farmers. In plants, multiple regulatory genes, such as the WRKY transcription factor (TF) family, modulate the expression of defense genes. However, the role of the pineapple WRKY genes is poorly understood. Here, we studied the pineapple WRKY gene, AcWRKY28, by generating AcWRKY28 over-expressing transgenic pineapple plants. Overexpression of AcWRKY28 enhanced the salt stress resistance in transgenic pineapple lines. Comparative transcriptome analysis of transgenic and wild-type pineapple plants showed that “plant-pathogen interaction” pathway genes, including 9calcium-dependent protein kinases (CPKs), were up-regulated in AcWRKY28 over-expressing plants. Furthermore, chromatin immunoprecipitation and yeast one-hybrid assays revealed AcCPK12, AcCPK3, AcCPK8, AcCPK1, and AcCPK15 as direct targets of AcWRKY28. Consistently, the study of AcCPK12 over-expressing Arabidopsis lines showed that AcCPK12 enhances salt, drought, and disease resistance. This study shows that AcWRKY28 plays a crucial role in promoting salt stress resistance by activating the expression of AcCPK genes.
基金supported by the National Natural Science Foundations of China(82273554,82073470)the Shandong Provincial Key R&D Program(ZR2019ZD36).
文摘The efficient clinical treatment of oral squamous cell carcinoma(OSCC)is still a challenge that demands the development of effective new drugs.Phenformin has been shown to produce more potent anti-tumor activities than metformin on different tumors,however,not much is known about the influence of phenformin on OSCC cells.We found that phenformin suppresses OSCC cell proliferation,and promotes OSCC cell autophagy and apoptosis to significantly inhibit OSCC cell growth both in vivo and in vitro.RNA-seq analysis revealed that autophagy pathways were the main targets of phenformin and identified two new targets DDIT4(DNA damage inducible transcript 4)and NIBAN1(niban apoptosis regulator 1).We found that phenformin significantly induces the expression of both DDIT4 and NIBAN1 to promote OSCC autophagy.Further,the enhanced expression of DDIT4 and NIBAN1 elicited by phenformin was not blocked by the knockdown of AMPK but was suppressed by the knockdown of transcription factor ATF4(activation transcription factor 4),which was induced by phenformin treatment in OSCC cells.Mechanistically,these results revealed that phenformin triggers endoplasmic reticulum(ER)stress to activate PERK(protein kinase R-like ER kinase),which phosphorylates the transitional initial factor eIF2,and the increased phosphorylation of eIF2 leads to the increased translation of ATF4.In summary,we discovered that phenformin induces its new targets DDIT4 and especially NIBAN1 to promote autophagic and apoptotic cell death to suppress OSCC cell growth.Our study supports the potential clinical utility of phenformin for OSCC treatment in the future.
基金financially supported by the National Key Research and Development Program of China(2021YFA0717002)。
文摘Many studies have revealed that gut microbes modulate host metabolism.In this study,we characterized the therapeutic effects of a novel gut commensal Luoshenia tenuis against host metabolic disorders.First,by in silico analysis,we demonstrated that the L.tenuis was prevalent in the gut microbiomes of healthy humans but were depleted specifically in obesity cohorts.Further in vitro cultivation revealed that L.tenuis produced short chain fatty acids that were verified to modulate host metabolism and some other volatile metabolites to benefit hosts by anti-inflammation and anti-tumor.Second,gavage of the L.tenuis significantly decreased the body weight gain and food intake of high-fat diet-feeding C57BL/6J mice,which was in parallel with the changed expression level of genes related to satiety and feeding behavior.We then performed the gavage trial using diet induced obese mice,and it revealed that the administration of L.tenuis alleviated significantly the abnormal glucose and lipid metabolisms and reduced the inflammatory response.In summary,this study revealed a previously-unknown human gut commensal microbe that benefited host metabolism,and set the stage for the development of novel next-generation probiotic applicable for treatment of obesity and related metabolic disorders.
基金supported by the National Natural Science Foundation of China(Nos.62201624,32000939,21775168,22174167,51861145202 and U20A20168)the Guangdong Basic and Applied Basic Research Foundation(Nos.2024A1515012056 and 2019A1515111183)+4 种基金Shenzhen Science and Technology Program(No.RCBS20221008093310024)Shenzhen Research Funding Program(Nos.JCYJ20190807160401657 and JCYJ201908073000608)Open Research Fund Program of Beijing National Research Center for Information Science and Technology(No.BR2023KF02010)The authors are also thankful for the support from Key Laboratory of Sensing Technology and Biomedical Instruments of Guangdong Province(No.2020B1212060077)the Fundamental Research Funds for the Central Universities,Sun Yat-sen University(No.24xkjc034).
文摘Dynamic monitoring of blood pressure (BP) is beneficial to obtain comprehensive cardiovascular information of patients throughout the day. However, the clinical BP measurement method relies on wearing a bulky cuff, which limits the long-term monitoring and control of BP. In this work, a microcavity assisted graphene pressure sensor (MAGPS) for single-vessel local BP monitoring is designed to replace the cuff. The microcavity structure increases the working range of the sensor by gas pressure buffering. Therefore, the MAGPS achieves a wide linear response of 0–1050 kPa and sensitivity of 15.4 kPa^(−1). The large working range and the microcavity structure enable the sensor to fully meet the requirements of BP detection at the radial artery. A database of 228 BP data (60-s data fragment detected by MAGPS) and 11,804 pulse waves from 9 healthy subjects and 5 hypertensive subjects is built. Finally, the BP was detected and analyzed automatically by combining MAGPS and a two-stage convolutional neural network algorithm. For the BP detection method at local radial artery, the first stage algorithm first determines whether the subject has hypertension by the pulse wave. Then, the second stage algorithm can diagnose systolic and diastolic BP with the accuracy of 93.5% and 97.8% within a 10 mmHg error, respectively. This work demonstrates a new BP detection method based on single vessel, which greatly promotes the efficiency of BP detection.