AIM:To explore the possibility and mechanism of inhibiting allogeneic T-cell responses by Kupffer cells (KC)pretreated with interferon-γ(IFN-γ)in vitro. METHODS:The expressions of indoleamine 2,3-dioxygenase(IDO)mRN...AIM:To explore the possibility and mechanism of inhibiting allogeneic T-cell responses by Kupffer cells (KC)pretreated with interferon-γ(IFN-γ)in vitro. METHODS:The expressions of indoleamine 2,3-dioxygenase(IDO)mRNA and FasL mRNA in KC pretreated with IFN-γwere studied with real-time polymerase chain reaction(PCR).The catabolism of tryptophan by IDO from KC was analyzed by high performance liquid chromatography.Allogeneic T-cell response was used to confirm the inhibition of KC in vitro.The proliferation of lymphocytes was detected using[ 3 H]thymidine incorporation.Cell cycle and lymphocyte apoptosis were evaluated by flow cytometric assay. RESULTS:Real-time PCR revealed IDO mRNA and FasL mRNA expressions in KC pretreated with IFN-γ,and IDO catabolic effect was confirmed by a decrease in tryptophan and increase in kynurenine concentration. KC expressing IDO and FasL in BABL/c mice acquired the ability to suppress the proliferation of T-cells from C57BL/6,which could be blocked by addition of 1-methyl-tryptophan and anti-FasL antibody.KC expressing IDO could induce allogeneic T-cell apoptosisCONCLUSION:In addition to Fas/FasL pathway,IDO may be another mechanism for KC to induce immune tolerance.展开更多
Inflammation is a multifaceted cellular and molecular response triggered by injury,infection,or various pathological conditions.Serving as a protective defense mechanism,the inflammatory response involves clinical sig...Inflammation is a multifaceted cellular and molecular response triggered by injury,infection,or various pathological conditions.Serving as a protective defense mechanism,the inflammatory response involves clinical signs like redness,swelling,pain,and increased body temperature.Immune cells,notably neutrophils and macrophages,play key roles in orchestrating this response.The delicate balance between proinflammatory and anti-inflammatory mediators,including cytokines and chemokines,regulates the inflammatory cascade.While acute inflammation is crucial for tissue repair,chronic inflammation may indicate an imbalance,contributing to conditions like autoimmune diseases.Understanding these mechanisms is vital for developing therapeutic strategies and managing chronic diseases.展开更多
Thermo-poro-mechanical responses along sliding zone/surface have been extensively studied.However,it has not been recognized that the potential contribution of other crucial engineering geological interfaces beyond th...Thermo-poro-mechanical responses along sliding zone/surface have been extensively studied.However,it has not been recognized that the potential contribution of other crucial engineering geological interfaces beyond the slip surface to progressive failure.Here,we aim to investigate the subsurface multiphysics of reservoir landslides under two extreme hydrologic conditions(i.e.wet and dry),particularly within sliding masses.Based on ultra-weak fiber Bragg grating(UWFBG)technology,we employ specialpurpose fiber optic sensing cables that can be implanted into boreholes as“nerves of the Earth”to collect data on soil temperature,water content,pore water pressure,and strain.The Xinpu landslide in the middle reach of the Three Gorges Reservoir Area in China was selected as a case study to establish a paradigm for in situ thermo-hydro-poro-mechanical monitoring.These UWFBG-based sensing cables were vertically buried in a 31 m-deep borehole at the foot of the landslide,with a resolution of 1 m except for the pressure sensor.We reported field measurements covering the period 2021 and 2022 and produced the spatiotemporal profiles throughout the borehole.Results show that wet years are more likely to motivate landslide motions than dry years.The annual thermally active layer of the landslide has a critical depth of roughly 9 m and might move downward in warmer years.The dynamic groundwater table is located at depths of 9e15 m,where the peaked strain undergoes a periodical response of leap and withdrawal to annual hydrometeorological cycles.These interface behaviors may support the interpretation of the contribution of reservoir regulation to slope stability,allowing us to correlate them to local damage events and potential global destabilization.This paper also offers a natural framework for interpreting thermo-hydro-poro-mechanical signatures from creeping reservoir bank slopes,which may form the basis for a landslide monitoring and early warning system.展开更多
With the rise of probiotics fermentation in food industry,fermented foods have attracted worldwide attention.In this study,protective effects of Rosa roxburghii&edible fungus fermentation broth(REFB)on immune func...With the rise of probiotics fermentation in food industry,fermented foods have attracted worldwide attention.In this study,protective effects of Rosa roxburghii&edible fungus fermentation broth(REFB)on immune function and gut health in Cyclophosphamide induced immunosuppressed mice were investigated.Results showed that REFB could improve the immune organ index,and promote the proliferation and differentiation of splenic T lymphocytes.In addition,it attenuated intestinal mucosal damage and improved intestinal cellular immunity.REFB administration also up-regulated the expression of IL-4,INF-γ,TNF-α,T-bet and GATA-3 mRNA in small intestine.Furthermore,administration of REFB modulated gut microbiota composition and increased the relative abundance of beneficial genus,such as Bacteroides.It also increased the production of fecal short-chain fatty acids.These indicate that REFB has the potential to improve immunity,alleviate intestinal injury and regulate gut microbiota in immunosuppressed mice.展开更多
Soil nonlinear behavior displays noticeable effects on the site seismic response.This study proposes a new functional expression of the skeleton curve to replace the hyperbolic skeleton curve.By integrating shear modu...Soil nonlinear behavior displays noticeable effects on the site seismic response.This study proposes a new functional expression of the skeleton curve to replace the hyperbolic skeleton curve.By integrating shear modulus and combining the dynamic skeleton curve and the damping degradation coefficient,the constitutive equation of the logarithmic dynamic skeleton can be obtained,which considers the damping effect in a soil dynamics problem.Based on the finite difference method and the multi-transmitting boundary condition,a 1D site seismic response analysis program called Soilresp1D has been developed herein and used to analyze the time-domain seismic response in three types of sites.At the same time,this study also provides numerical simulation results based on the hyperbolic constitutive model and the equivalent linear method.The results verify the rationality of the new soil dynamic constitutive model.It can analyze the mucky soil site nonlinear seismic response,reflecting the deformation characteristics and damping effect of the silty soil.The hysteresis loop area is more extensive,and the residual strain is evident.展开更多
Background:The mobilization and redistribution of severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)specific T-cells and neutralizing antibodies(nAbs)during exercise is purported to increase immune surveillan...Background:The mobilization and redistribution of severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)specific T-cells and neutralizing antibodies(nAbs)during exercise is purported to increase immune surveillance and protect against severe coronavirus disease 2019(COVID-19).We sought to determine if COVID-19 vaccination would elicit exercise-responsive SARS-CoV-2 T-cells and transiently alter nAb titers.Methods:Eighteen healthy participants completed a 20-min bout of graded cycling exercise before and/or after receiving a COVID-19 vaccine.All major leukocyte subtypes were enumerated before,during,and after exercise by flow cytometry,and immune responses to SARS-CoV-2 were determined using whole blood peptide stimulation assays,T-cell receptor(TCR)-βsequencing,and SARS-CoV-2 nAb serology.Results:COVID-19 vaccination had no effect on the mobilization or egress of major leukocyte subsets in response to intensity-controlled graded exercise.However,non-infected participants had a significantly reduced mobilization of CD4+and CD8+naive T-cells,as well as CD4+central memory T-cells,after vaccination(synthetic immunity group);this was not seen after vaccination in those with prior SARS-CoV-2 infection(hybrid immunity group).Acute exercise after vaccination robustly mobilized SARS-CoV-2 specific T-cells to blood in an intensity-dependent manner.Both groups mobilized T-cells that reacted to spike protein;however,only the hybrid immunity group mobilized T-cells that reacted to membrane and nucleocapsid antigens.nAbs increased significantly during exercise only in the hybrid immunity group.Conclusion:These data indicate that acute exercise mobilizes SARS-CoV-2 specific T-cells that recognize spike protein and increases the redistribution of nAbs in individuals with hybrid immunity.展开更多
Underground hydrogen storage(UHS)and compressed air energy storage(CAES)are two viable largescale energy storage technologies for mitigating the intermittency of wind and solar power.Therefore,it is meaningful to comp...Underground hydrogen storage(UHS)and compressed air energy storage(CAES)are two viable largescale energy storage technologies for mitigating the intermittency of wind and solar power.Therefore,it is meaningful to compare the properties of hydrogen and air with typical thermodynamic storage processes.This study employs a multi-physical coupling model to compare the operations of CAES and UHS,integrating gas thermodynamics within caverns,thermal conduction,and mechanical deformation around rock caverns.Gas thermodynamic responses are validated using additional simulations and the field test data.Temperature and pressure variations of air and hydrogen within rock caverns exhibit similarities under both adiabatic and diabatic simulation modes.Hydrogen reaches higher temperature and pressure following gas charging stage compared to air,and the ideal gas assumption may lead to overestimation of gas temperature and pressure.Unlike steel lining of CAES,the sealing layer(fibre-reinforced plastic FRP)in UHS is prone to deformation but can effectively mitigates stress in the sealing layer.In CAES,the first principal stress on the surface of the sealing layer and concrete lining is tensile stress,whereas UHS exhibits compressive stress in the same areas.Our present research can provide references for the selection of energy storage methods.展开更多
Long non-coding RNAs(lncRNAs)function as key modulators in mammalian immunity,particularly due to their involvement in lncRNA-mediated competitive endogenous RNA(ceRNA)crosstalk.Despite their recognized significance i...Long non-coding RNAs(lncRNAs)function as key modulators in mammalian immunity,particularly due to their involvement in lncRNA-mediated competitive endogenous RNA(ceRNA)crosstalk.Despite their recognized significance in mammals,research on lncRNAs in lower vertebrates remains limited.In the present study,we characterized the first immune-related lncRNA(pol-lnc78)in the teleost Japanese flounder(Paralichthys olivaceus).Results indicated that pol-lnc78 acted as a ceRNA for pol-miR-n199-3p to target the sterile alpha and armadillo motif-containing protein(SARM),the fifth discovered member of the Toll/interleukin 1(IL-1)receptor(TIR)adaptor family.This ceRNA network regulated the antibacterial responses of flounder via the Toll-like receptor(TLR)signaling pathway.Specifically,SARM acted as a negative regulator and exacerbated bacterial infection by inhibiting the expression of inflammatory cytokines IL-1βand tumor necrosis factor-α(TNF-α).Pol-miR-n199-3p reduced SARM expression by specifically interacting with the 3’untranslated region(UTR),thereby promoting SARM-dependent inflammatory cytokine expression and protecting the host against bacterial dissemination.Furthermore,pol-lnc78 sponged pol-miR-n199-3p to ameliorate the inhibition of SARM expression.During infection,the negative regulators pol-lnc78 and SARM were significantly down-regulated,while pol-miR-n199-3p was significantly up-regulated,thus favoring host antibacterial defense.These findings provide novel insights into the mechanisms underlying fish immunity and open new horizons to better understand ceRNA crosstalk in lower vertebrates.展开更多
Through combined applications of the transfer-matrix method and asymptotic expansion technique,we formulate a theory to predict the three-dimensional response of micropolar plates.No ad hoc assumptions regarding throu...Through combined applications of the transfer-matrix method and asymptotic expansion technique,we formulate a theory to predict the three-dimensional response of micropolar plates.No ad hoc assumptions regarding through-thickness assumptions of the field variables are made,and the governing equations are two-dimensional,with the displacements and microrotations of the mid-plane as the unknowns.Once the deformation of the mid-plane is solved,a three-dimensional micropolar elastic field within the plate is generated,which is exact up to the second order except in the boundary region close to the plate edge.As an illustrative example,the bending of a clamped infinitely long plate caused by a uniformly distributed transverse force is analyzed and discussed in detail.展开更多
Thermal transistor,the thermal analog of an electronic transistor,is one of the most important thermal devices for microscopic-scale heat manipulating.It is a three-terminal device,and the heat current flowing through...Thermal transistor,the thermal analog of an electronic transistor,is one of the most important thermal devices for microscopic-scale heat manipulating.It is a three-terminal device,and the heat current flowing through two terminals can be largely controlled by the temperature of the third one.Dynamic response plays an important role in the application of electric devices and also thermal devices,which represents the devices’ability to treat fast varying inputs.In this paper,we systematically study two typical dynamic responses of a thermal transistor,i.e.,the response to a step-function input(a switching process)and the response to a square-wave input.The role of the length L of the control segment is carefully studied.It is revealed that when L is increased,the performance of the thermal transistor worsens badly.Both the relaxation time for the former process and the cutoff frequency for the latter one follow the power-law dependence on L quite well,which agrees with our analytical expectation.However,the detailed power exponents deviate from the expected values noticeably.This implies the violation of the conventional assumptions that we adopt.展开更多
Avalanche photodetectors(APDs) featuring an avalanche multiplication region are vital for reaching high sensitivity and responsivity in optical transceivers. Waveguide-coupled Ge-on-Si separate absorption, charge, and...Avalanche photodetectors(APDs) featuring an avalanche multiplication region are vital for reaching high sensitivity and responsivity in optical transceivers. Waveguide-coupled Ge-on-Si separate absorption, charge, and multiplication(SACM)APDs are popular due to their straightforward fabrication process, low optical propagation loss, and high detection sensitivity in optical communications. This paper introduces a lateral SACM Ge-on-Si APD on a silicon-on-insulator(SOI) wafer, featuring a 10 μm-long, 0.5 μm-wide Ge layer at 1310 nm on a standard 8-inch silicon photonics platform. The dark current measures approximately 38.6 μA at-21 V, indicating a breakdown voltage greater than-21 V for the device. The APDs exhibit a unitgain responsivity of 0.5 A/W at-10 V. At-15 V, their responsivity reaches 2.98 and 2.91 A/W with input powers of-10 and-25 dBm, respectively. The device's 3-dB bandwidth is 15 GHz with an input power of-15 dBm and a gain is 11.68. Experimental results show a peak in impedance at high bias voltages, attributed to inductor and capacitor(LC) circuit resonance, enhancing frequency response. Furthermore, 20 Gbps eye diagrams at-21 V and-9 dBm input power reveal signal to noise ratio(SNRs) of 5.30. This lateral SACM APD, compatible with the stand complementary metal oxide semiconductor(CMOS) process,shows that utilizing the peaking effect at low optical power increases bandwidth.展开更多
The unfolded protein response(UPR)is a cellular stress response pathway activated when the endoplasmic reticulum,a crucial organelle for protein folding and modification,encounters an accumulation of unfolded or misfo...The unfolded protein response(UPR)is a cellular stress response pathway activated when the endoplasmic reticulum,a crucial organelle for protein folding and modification,encounters an accumulation of unfolded or misfolded proteins.The UPR aims to restore endoplasmic reticulum homeostasis by enhancing protein folding capacity,reducing protein biosynthesis,and promoting protein degradation.It also plays a pivotal role in coordinating signaling cascades to determine cell fate and function in response to endoplasmic reticulum stress.Recent research has highlighted the significance of the UPR not only in maintaining endoplasmic reticulum homeostasis but also in influencing various physiological processes in the nervous system.Here,we provide an overview of recent findings that underscore the UPR’s involvement in preserving the function and viability of neuronal and myelinating cells under physiological conditions,and highlight the critical role of the UPR in brain development,memory storage,retinal cone development,myelination,and maintenance of myelin thickness.展开更多
Background:According to clinical practice guidelines,transarterial chemoembolization(TACE)is the standard treatment modality for patients with intermediate-stage hepatocellular carcinoma(HCC).Early prediction of treat...Background:According to clinical practice guidelines,transarterial chemoembolization(TACE)is the standard treatment modality for patients with intermediate-stage hepatocellular carcinoma(HCC).Early prediction of treatment response can help patients choose a reasonable treatment plan.This study aimed to investigate the value of the radiomic-clinical model in predicting the efficacy of the first TACE treatment for HCC to prolong patient survival.Methods:A total of 164 patients with HCC who underwent the first TACE from January 2017 to September 2021 were analyzed.The tumor response was assessed by modified response evaluation criteria in solid tumors(mRECIST),and the response of the first TACE to each session and its correlation with overall survival were evaluated.The radiomic signatures associated with the treatment response were identified by the least absolute shrinkage and selection operator(LASSO),and four machine learning models were built with different types of regions of interest(ROIs)(tumor and corresponding tissues)and the model with the best performance was selected.The predictive performance was assessed with receiver operating characteristic(ROC)curves and calibration curves.Results:Of all the models,the random forest(RF)model with peritumor(+10 mm)radiomic signatures had the best performance[area under ROC curve(AUC)=0.964 in the training cohort,AUC=0.949 in the validation cohort].The RF model was used to calculate the radiomic score(Rad-score),and the optimal cutoff value(0.34)was calculated according to the Youden’s index.Patients were then divided into a high-risk group(Rad-score>0.34)and a low-risk group(Rad-score≤0.34),and a nomogram model was successfully established to predict treatment response.The predicted treatment response also allowed for significant discrimination of Kaplan-Meier curves.Multivariate Cox regression identified six independent prognostic factors for overall survival,including male[hazard ratio(HR)=0.500,95%confidence interval(CI):0.260–0.962,P=0.038],alpha-fetoprotein(HR=1.003,95%CI:1.002–1.004,P<0.001),alanine aminotransferase(HR=1.003,95%CI:1.001–1.005,P=0.025),performance status(HR=2.400,95%CI:1.200–4.800,P=0.013),the number of TACE sessions(HR=0.870,95%CI:0.780–0.970,P=0.012)and Rad-score(HR=3.480,95%CI:1.416–8.552,P=0.007).Conclusions:The radiomic signatures and clinical factors can be well-used to predict the response of HCC patients to the first TACE and may help identify the patients most likely to benefit from TACE.展开更多
White Hypsizygus marmoreus is a popular edible mushroom.Its mycelium is easy to be contaminated by Penicillium,which leads to a decrease in its quality and yield.Penicillium could compete for limited space and nutrien...White Hypsizygus marmoreus is a popular edible mushroom.Its mycelium is easy to be contaminated by Penicillium,which leads to a decrease in its quality and yield.Penicillium could compete for limited space and nutrients through rapid growth and produce a variety of harmful gases,such as benzene,aldehydes,phenols,etc.,to inhibit the growth of H.marmoreus mycelium.A series of changes occurred in H.marmoreus proteome after contamination when detected by the label-free tandem mass spectrometry(MS/MS)technique.Some proteins with up-regulated expression worked together to participate in some processes,such as the non-toxic transformation of harmful gases,glutathione metabolism,histone modification,nucleotide excision repair,clearing misfolded proteins,and synthesizing glutamine,which were mainly used in response to biological stress.The proteins with down-regulated expression are mainly related to the processes of ribosome function,protein processing,spliceosome,carbon metabolism,glycolysis,and gluconeogenesis.The reduction in the function of these proteins affected the production of the cell components,which might be an adjustment to adapt to growth retardation.This study further enhanced the understanding of the biological stress response and the growth restriction adaptation mechanisms in edible fungi.It also provided a theoretical basis for protein function exploration and edible mushroom food safety research.展开更多
To address the issues of limited demand response data,low generalization of demand response potential evaluation,and poor demand response effect,the article proposes a demand response potential feature extraction and ...To address the issues of limited demand response data,low generalization of demand response potential evaluation,and poor demand response effect,the article proposes a demand response potential feature extraction and prediction model based on data mining and a demand response potential assessment model for adjustable loads in demand response scenarios based on subjective and objective weight analysis.Firstly,based on the demand response process and demand response behavior,obtain demand response characteristics that characterize the process and behavior.Secondly,establish a feature extraction and prediction model based on data mining,including similar day clustering,time series decomposition,redundancy processing,and data prediction.The predicted values of each demand response feature on the response day are obtained.Thirdly,the predicted data of various characteristics on the response day are used as demand response potential evaluation indicators to represent different demand response scenarios and adjustable loads,and a demand response potential evaluation model based on subjective and objective weight allocation is established to calculate the demand response potential of different adjustable loads in different demand response scenarios.Finally,the effectiveness of the method proposed in the article is verified through examples,providing a reference for load aggregators to formulate demand response schemes.展开更多
Background:Choosing the appropriate antipsychotic drug(APD)treatment for patients with schizophrenia(SCZ)can be challenging,as the treatment response to APD is highly variable and difficult to predict due to the lack ...Background:Choosing the appropriate antipsychotic drug(APD)treatment for patients with schizophrenia(SCZ)can be challenging,as the treatment response to APD is highly variable and difficult to predict due to the lack of effective biomarkers.Previous studies have indicated the association between treatment response and genetic and epigenetic factors,but no effective biomarkers have been identified.Hence,further research is imperative to enhance precision medicine in SCZ treatment.Methods:Participants with SCZ were recruited from two randomized trials.The discovery cohort was recruited from the CAPOC trial(n=2307)involved 6 weeks of treatment and equally randomized the participants to the Olanzapine,Risperidone,Quetiapine,Aripiprazole,Ziprasidone,and Haloperidol/Perphenazine(subsequently equally assigned to one or the other)groups.The external validation cohort was recruited from the CAPEC trial(n=1379),which involved 8 weeks of treatment and equally randomized the participants to the Olanzapine,Risperidone,and Aripiprazole groups.Additionally,healthy controls(n=275)from the local community were utilized as a genetic/epigenetic reference.The genetic and epigenetic(DNA methylation)risks of SCZ were assessed using the polygenic risk score(PRS)and polymethylation score,respectively.The study also examined the genetic-epigenetic interactions with treatment response through differential methylation analysis,methylation quantitative trait loci,colocalization,and promoteranchored chromatin interaction.Machine learning was used to develop a prediction model for treatment response,which was evaluated for accuracy and clinical benefit using the area under curve(AUC)for classification,R^(2) for regression,and decision curve analysis.Results:Six risk genes for SCZ(LINC01795,DDHD2,SBNO1,KCNG2,SEMA7A,and RUFY1)involved in cortical morphology were identified as having a genetic-epigenetic interaction associated with treatment response.The developed and externally validated prediction model,which incorporated clinical information,PRS,genetic risk score(GRS),and proxy methylation level(proxyDNAm),demonstrated positive benefits for a wide range of patients receiving different APDs,regardless of sex[discovery cohort:AUC=0.874(95%CI 0.867-0.881),R^(2)=0.478;external validation cohort:AUC=0.851(95%CI 0.841-0.861),R^(2)=0.507].Conclusions:This study presents a promising precision medicine approach to evaluate treatment response,which has the potential to aid clinicians in making informed decisions about APD treatment for patients with SCZ.Trial registration Chinese Clinical Trial Registry(https://www.chictr.org.cn/),18 Aug 2009 retrospectively registered:CAPOC-ChiCTR-RNC-09000521(https://www.chictr.org.cn/showproj.aspx?proj=9014),CAPEC-ChiCTRRNC-09000522(https://www.chictr.org.cn/showproj.aspx?proj=9013).展开更多
Probiotics are live microorganisms exerting beneficial effects on the host’s health when administered in adequate amounts.Among the most popular and adequately studied probiotics are bacteria from the families Lactob...Probiotics are live microorganisms exerting beneficial effects on the host’s health when administered in adequate amounts.Among the most popular and adequately studied probiotics are bacteria from the families Lactobacillaceae,Bifidobacteriaceae and yeasts.Most of them have been shown,both in vitro and in vivo studies of intestinal inflammation models,to provide favorable results by means of improving the gut microbiota composition,promoting the wound healing process and shaping the immunological responses.Chronic intestinal conditions,such as inflammatory bowel diseases(IBD),are characterized by an imbalance in microbiota composition,with decreased diversity,and by relapsing and persisting inflammation,which may lead to mucosal damage.Although the results of the clinical studies investigating the effect of probiotics on patients with IBD are still controversial,it is without doubt that these microorganisms and their metabolites,now named postbiotics,have a positive influence on both the host’s microbiota and the immune system,and ultimately alter the topical tissue microenvironment.This influence is achieved through three axes:(1)By dis-placement of potential pathogens via competitive exclusion;(2)by offering protection to the host through the secretion of various defensive mediators;and(3)by supplying the host with essential nutrients.We will analyze and discuss almost all the in vitro and in vivo studies of the past 2 years dealing with the possible favorable effects of certain probiotic genus on gut immunological responses,highlighting which species are the most beneficial against intestinal inflammation.展开更多
Phaeocystis globosa is an important unicellular eukaryotic alga that can also form colonies.P.globosa can cause massive harmful algal blooms and plays an important role in the global carbon or sulfur cycling.Thus far,...Phaeocystis globosa is an important unicellular eukaryotic alga that can also form colonies.P.globosa can cause massive harmful algal blooms and plays an important role in the global carbon or sulfur cycling.Thus far,the ecophysiology of P.globosa has been investigated by numerous studies.However,the proteomic response of P.globosa to nitrogen depletion remains largely unknown.We compared four protein preparation methods of P.globosa for two-dimensional electrophoresis(2-DE)(Urea/Triton X-100 with trichloroacetic acid(TCA)/acetone precipitation;TCA/acetone precipitation;Radio Immuno Precipitation Assay(RIPA)with TCA/acetone precipitation;and Tris buffer).Results show that the combination of RIPA with TCA/acetone precipitation had a clear gel background and showed the best protein spot separation effect,based on which the proteomic response to nitrogen depletion was studied using 2-DE.In addition,we identified six differentially expressed proteins whose relative abundance increased or decreased more than 1.5-fold(P<0.05).Most proteins could not be identified,which might be attributed to the lack of genomic sequences of P.globosa.Under nitrogen limitation,replication protein-like,RNA ligase,and sn-glycerol-3-phosphate dehydrogenase were reduced,which may decrease the DNA replication level and ATP production in P.globosa cells.The increase of endonucleaseⅢand transcriptional regulator enzyme may affect the metabolic and antioxidant function of P.globosa cells and induce cell apoptosis.These findings provide a basis for further proteomic study of P.globosa and the optimization of protein preparation methods of marine microalgae.展开更多
The Tongbai Mountains is an ecologically sensi-tive region and the northern boundary of Pinus massoniana Lamb.To analyze the effect of different microenvironments on tree growth response to climate factors,we develope...The Tongbai Mountains is an ecologically sensi-tive region and the northern boundary of Pinus massoniana Lamb.To analyze the effect of different microenvironments on tree growth response to climate factors,we developed standard chronologies for earlywood width(EWW),late-wood width(LWW),and total ring width(TRW)of P.massoniana at two sampling sites on slopes with different orientations,then analyzed characteristics of the chronolo-gies and their correlations with climate variables from five stations in the region and with a regional normalized differ-ence vegetation index(NDVI).Statistical results showed that the TRW/EWW/LWW chronology consistency and charac-teristics(mean sensitivity,signal to noise ratio,expressed population signal)for trees growing on the southeastern slope were much higher than for trees on the northeastern slope.Correlations indicated that temperature in current March and August has a significant positive effect on TRW/EWW/LWW formation,and the effect on the northeastern slope was weaker than on the southeastern slope.Compared to temperature,precipitation has more complicated effects on tree growth,but the effect on the northeastern slope was also generally weaker than on the southeastern slope.Step-wise linear regression analyses showed that temperature in August was the main limiting factor at the two sampling sites.Similarly,the response of tree growth on the southeast-ern slope as determined by the NDVI is better than on the northeastern slope,and the TRW/EWW/LWW chronologies for the southeastern slope explained over 50%of the total NDVI variances in June.Overall,the results indicate that the difference in the climate response of P.massoniana at two sampling sites is clearly caused by differences in the microenvironment,and such differences should be properly considered in future studies of forest dynamics and climate reconstructions.展开更多
Fire warning is vital to human life,economy and ecology.However,the development of effective warning systems faces great challenges of fast response,adjustable threshold and remote detecting.Here,we propose an intelli...Fire warning is vital to human life,economy and ecology.However,the development of effective warning systems faces great challenges of fast response,adjustable threshold and remote detecting.Here,we propose an intelligent self-powered remote IoT fire warning system,by employing single-walled carbon nanotube/titanium carbide thermoelectric composite films.The flexible films,prepared by a convenient solution mixing,display p-type characteristic with excellent high-temperature stability,flame retardancy and TE(power factor of 239.7±15.8μW m^(-1) K^(-2))performances.The comprehensive morphology and structural analyses shed light on the underlying mechanisms.And the assembled TE devices(TEDs)exhibit fast fire warning with adjustable warning threshold voltages(1–10 mV).Excitingly,an ultrafast fire warning response time of~0.1 s at 1 mV threshold voltage is achieved,rivaling many state-of-the-art systems.Furthermore,TE fire warning systems reveal outstanding stability after 50 repeated cycles and desired durability even undergoing 180 days of air exposure.Finally,a TED-based wireless intelligent fire warning system has been developed by coupling an amplifier,analogto-digital converter and Bluetooth module.By combining TE characteristics,high-temperature stability and flame retardancy with wireless IoT signal transmission,TE-based hybrid system developed here is promising for next-generation self-powered remote IoT fire warning applications.展开更多
基金Supported by Natural Science Foundation of Fujian Province,No.2007J0073Young Talents Innovation Foundation of Fujian Province,No.2006F3033
文摘AIM:To explore the possibility and mechanism of inhibiting allogeneic T-cell responses by Kupffer cells (KC)pretreated with interferon-γ(IFN-γ)in vitro. METHODS:The expressions of indoleamine 2,3-dioxygenase(IDO)mRNA and FasL mRNA in KC pretreated with IFN-γwere studied with real-time polymerase chain reaction(PCR).The catabolism of tryptophan by IDO from KC was analyzed by high performance liquid chromatography.Allogeneic T-cell response was used to confirm the inhibition of KC in vitro.The proliferation of lymphocytes was detected using[ 3 H]thymidine incorporation.Cell cycle and lymphocyte apoptosis were evaluated by flow cytometric assay. RESULTS:Real-time PCR revealed IDO mRNA and FasL mRNA expressions in KC pretreated with IFN-γ,and IDO catabolic effect was confirmed by a decrease in tryptophan and increase in kynurenine concentration. KC expressing IDO and FasL in BABL/c mice acquired the ability to suppress the proliferation of T-cells from C57BL/6,which could be blocked by addition of 1-methyl-tryptophan and anti-FasL antibody.KC expressing IDO could induce allogeneic T-cell apoptosisCONCLUSION:In addition to Fas/FasL pathway,IDO may be another mechanism for KC to induce immune tolerance.
文摘Inflammation is a multifaceted cellular and molecular response triggered by injury,infection,or various pathological conditions.Serving as a protective defense mechanism,the inflammatory response involves clinical signs like redness,swelling,pain,and increased body temperature.Immune cells,notably neutrophils and macrophages,play key roles in orchestrating this response.The delicate balance between proinflammatory and anti-inflammatory mediators,including cytokines and chemokines,regulates the inflammatory cascade.While acute inflammation is crucial for tissue repair,chronic inflammation may indicate an imbalance,contributing to conditions like autoimmune diseases.Understanding these mechanisms is vital for developing therapeutic strategies and managing chronic diseases.
基金We acknowledge the funding support from the National Science Fund for Distinguished Young Scholars of National Natural Science Foundation of China(Grant No.42225702)the National Natural Science Foundation of China(Grant No.42077235).
文摘Thermo-poro-mechanical responses along sliding zone/surface have been extensively studied.However,it has not been recognized that the potential contribution of other crucial engineering geological interfaces beyond the slip surface to progressive failure.Here,we aim to investigate the subsurface multiphysics of reservoir landslides under two extreme hydrologic conditions(i.e.wet and dry),particularly within sliding masses.Based on ultra-weak fiber Bragg grating(UWFBG)technology,we employ specialpurpose fiber optic sensing cables that can be implanted into boreholes as“nerves of the Earth”to collect data on soil temperature,water content,pore water pressure,and strain.The Xinpu landslide in the middle reach of the Three Gorges Reservoir Area in China was selected as a case study to establish a paradigm for in situ thermo-hydro-poro-mechanical monitoring.These UWFBG-based sensing cables were vertically buried in a 31 m-deep borehole at the foot of the landslide,with a resolution of 1 m except for the pressure sensor.We reported field measurements covering the period 2021 and 2022 and produced the spatiotemporal profiles throughout the borehole.Results show that wet years are more likely to motivate landslide motions than dry years.The annual thermally active layer of the landslide has a critical depth of roughly 9 m and might move downward in warmer years.The dynamic groundwater table is located at depths of 9e15 m,where the peaked strain undergoes a periodical response of leap and withdrawal to annual hydrometeorological cycles.These interface behaviors may support the interpretation of the contribution of reservoir regulation to slope stability,allowing us to correlate them to local damage events and potential global destabilization.This paper also offers a natural framework for interpreting thermo-hydro-poro-mechanical signatures from creeping reservoir bank slopes,which may form the basis for a landslide monitoring and early warning system.
基金The financial supports from the Key Program of the National Natural Science Foundation of China(32130082)Jiangxi High Level Talent Cultivation Project(20204BCJ24006)+1 种基金Project of State Key Laboratory of Food Science and Technology(SKLF-ZZA-201911)Central Government Guide Local Special Fund Project for Scientific and Technological Development of Jiangxi Province(20212ZDD02008)。
文摘With the rise of probiotics fermentation in food industry,fermented foods have attracted worldwide attention.In this study,protective effects of Rosa roxburghii&edible fungus fermentation broth(REFB)on immune function and gut health in Cyclophosphamide induced immunosuppressed mice were investigated.Results showed that REFB could improve the immune organ index,and promote the proliferation and differentiation of splenic T lymphocytes.In addition,it attenuated intestinal mucosal damage and improved intestinal cellular immunity.REFB administration also up-regulated the expression of IL-4,INF-γ,TNF-α,T-bet and GATA-3 mRNA in small intestine.Furthermore,administration of REFB modulated gut microbiota composition and increased the relative abundance of beneficial genus,such as Bacteroides.It also increased the production of fecal short-chain fatty acids.These indicate that REFB has the potential to improve immunity,alleviate intestinal injury and regulate gut microbiota in immunosuppressed mice.
基金Major Program of the National Natural Science Foundation of China under Grant No.52192675 and the 111 Project of China under Grant No.D21001。
文摘Soil nonlinear behavior displays noticeable effects on the site seismic response.This study proposes a new functional expression of the skeleton curve to replace the hyperbolic skeleton curve.By integrating shear modulus and combining the dynamic skeleton curve and the damping degradation coefficient,the constitutive equation of the logarithmic dynamic skeleton can be obtained,which considers the damping effect in a soil dynamics problem.Based on the finite difference method and the multi-transmitting boundary condition,a 1D site seismic response analysis program called Soilresp1D has been developed herein and used to analyze the time-domain seismic response in three types of sites.At the same time,this study also provides numerical simulation results based on the hyperbolic constitutive model and the equivalent linear method.The results verify the rationality of the new soil dynamic constitutive model.It can analyze the mucky soil site nonlinear seismic response,reflecting the deformation characteristics and damping effect of the silty soil.The hysteresis loop area is more extensive,and the residual strain is evident.
文摘Background:The mobilization and redistribution of severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)specific T-cells and neutralizing antibodies(nAbs)during exercise is purported to increase immune surveillance and protect against severe coronavirus disease 2019(COVID-19).We sought to determine if COVID-19 vaccination would elicit exercise-responsive SARS-CoV-2 T-cells and transiently alter nAb titers.Methods:Eighteen healthy participants completed a 20-min bout of graded cycling exercise before and/or after receiving a COVID-19 vaccine.All major leukocyte subtypes were enumerated before,during,and after exercise by flow cytometry,and immune responses to SARS-CoV-2 were determined using whole blood peptide stimulation assays,T-cell receptor(TCR)-βsequencing,and SARS-CoV-2 nAb serology.Results:COVID-19 vaccination had no effect on the mobilization or egress of major leukocyte subsets in response to intensity-controlled graded exercise.However,non-infected participants had a significantly reduced mobilization of CD4+and CD8+naive T-cells,as well as CD4+central memory T-cells,after vaccination(synthetic immunity group);this was not seen after vaccination in those with prior SARS-CoV-2 infection(hybrid immunity group).Acute exercise after vaccination robustly mobilized SARS-CoV-2 specific T-cells to blood in an intensity-dependent manner.Both groups mobilized T-cells that reacted to spike protein;however,only the hybrid immunity group mobilized T-cells that reacted to membrane and nucleocapsid antigens.nAbs increased significantly during exercise only in the hybrid immunity group.Conclusion:These data indicate that acute exercise mobilizes SARS-CoV-2 specific T-cells that recognize spike protein and increases the redistribution of nAbs in individuals with hybrid immunity.
基金the financial support from the Natural Science Foundation of China (Nos.52179118,52209151 and 42307238)the Science and Technology Project of Jiangsu Provincial Department of Science and Technology-Carbon Emissions Peak and Carbon Neutrality Science and Technology Innovation Specia Fund Project (No.BK20220025)+3 种基金the Excellent Postdoctoral Program of Jiangsu Province (No.2023ZB602)the China Postdoctora Science Foundation (Nos.2023M733773 and 2023M733772)Xuzhou City Science and Technology Innovation Special Basic Research Plan (KC23045)State Key Laboratory of Intelligent Construction and Healthy Operation and Maintenance of Deep Underground Engineering,China University of Mining&Technology (No SKLGDUEK1916)。
文摘Underground hydrogen storage(UHS)and compressed air energy storage(CAES)are two viable largescale energy storage technologies for mitigating the intermittency of wind and solar power.Therefore,it is meaningful to compare the properties of hydrogen and air with typical thermodynamic storage processes.This study employs a multi-physical coupling model to compare the operations of CAES and UHS,integrating gas thermodynamics within caverns,thermal conduction,and mechanical deformation around rock caverns.Gas thermodynamic responses are validated using additional simulations and the field test data.Temperature and pressure variations of air and hydrogen within rock caverns exhibit similarities under both adiabatic and diabatic simulation modes.Hydrogen reaches higher temperature and pressure following gas charging stage compared to air,and the ideal gas assumption may lead to overestimation of gas temperature and pressure.Unlike steel lining of CAES,the sealing layer(fibre-reinforced plastic FRP)in UHS is prone to deformation but can effectively mitigates stress in the sealing layer.In CAES,the first principal stress on the surface of the sealing layer and concrete lining is tensile stress,whereas UHS exhibits compressive stress in the same areas.Our present research can provide references for the selection of energy storage methods.
基金supported by the National Natural Science Foundation of China(42006082)Natural Science Foundation of Jiangsu Province of China(BK20221323)+1 种基金“JBGS”Project of Seed Industry Revitalization in Jiangsu Province(JBGS[2021]034)State Key Laboratory of Developmental Biology of Freshwater Fish(2021KF009)。
文摘Long non-coding RNAs(lncRNAs)function as key modulators in mammalian immunity,particularly due to their involvement in lncRNA-mediated competitive endogenous RNA(ceRNA)crosstalk.Despite their recognized significance in mammals,research on lncRNAs in lower vertebrates remains limited.In the present study,we characterized the first immune-related lncRNA(pol-lnc78)in the teleost Japanese flounder(Paralichthys olivaceus).Results indicated that pol-lnc78 acted as a ceRNA for pol-miR-n199-3p to target the sterile alpha and armadillo motif-containing protein(SARM),the fifth discovered member of the Toll/interleukin 1(IL-1)receptor(TIR)adaptor family.This ceRNA network regulated the antibacterial responses of flounder via the Toll-like receptor(TLR)signaling pathway.Specifically,SARM acted as a negative regulator and exacerbated bacterial infection by inhibiting the expression of inflammatory cytokines IL-1βand tumor necrosis factor-α(TNF-α).Pol-miR-n199-3p reduced SARM expression by specifically interacting with the 3’untranslated region(UTR),thereby promoting SARM-dependent inflammatory cytokine expression and protecting the host against bacterial dissemination.Furthermore,pol-lnc78 sponged pol-miR-n199-3p to ameliorate the inhibition of SARM expression.During infection,the negative regulators pol-lnc78 and SARM were significantly down-regulated,while pol-miR-n199-3p was significantly up-regulated,thus favoring host antibacterial defense.These findings provide novel insights into the mechanisms underlying fish immunity and open new horizons to better understand ceRNA crosstalk in lower vertebrates.
基金Project supported by the National Natural Science Foundation of China (No. 12072337)。
文摘Through combined applications of the transfer-matrix method and asymptotic expansion technique,we formulate a theory to predict the three-dimensional response of micropolar plates.No ad hoc assumptions regarding through-thickness assumptions of the field variables are made,and the governing equations are two-dimensional,with the displacements and microrotations of the mid-plane as the unknowns.Once the deformation of the mid-plane is solved,a three-dimensional micropolar elastic field within the plate is generated,which is exact up to the second order except in the boundary region close to the plate edge.As an illustrative example,the bending of a clamped infinitely long plate caused by a uniformly distributed transverse force is analyzed and discussed in detail.
基金Project supported by the National Natural Science Foundation of China(Grant No.12075316)the Fundamental Research Funds for the Central Universitiesthe Research Funds of Renmin University of China(Grant No.21XNH091)(Q.R.)。
文摘Thermal transistor,the thermal analog of an electronic transistor,is one of the most important thermal devices for microscopic-scale heat manipulating.It is a three-terminal device,and the heat current flowing through two terminals can be largely controlled by the temperature of the third one.Dynamic response plays an important role in the application of electric devices and also thermal devices,which represents the devices’ability to treat fast varying inputs.In this paper,we systematically study two typical dynamic responses of a thermal transistor,i.e.,the response to a step-function input(a switching process)and the response to a square-wave input.The role of the length L of the control segment is carefully studied.It is revealed that when L is increased,the performance of the thermal transistor worsens badly.Both the relaxation time for the former process and the cutoff frequency for the latter one follow the power-law dependence on L quite well,which agrees with our analytical expectation.However,the detailed power exponents deviate from the expected values noticeably.This implies the violation of the conventional assumptions that we adopt.
文摘Avalanche photodetectors(APDs) featuring an avalanche multiplication region are vital for reaching high sensitivity and responsivity in optical transceivers. Waveguide-coupled Ge-on-Si separate absorption, charge, and multiplication(SACM)APDs are popular due to their straightforward fabrication process, low optical propagation loss, and high detection sensitivity in optical communications. This paper introduces a lateral SACM Ge-on-Si APD on a silicon-on-insulator(SOI) wafer, featuring a 10 μm-long, 0.5 μm-wide Ge layer at 1310 nm on a standard 8-inch silicon photonics platform. The dark current measures approximately 38.6 μA at-21 V, indicating a breakdown voltage greater than-21 V for the device. The APDs exhibit a unitgain responsivity of 0.5 A/W at-10 V. At-15 V, their responsivity reaches 2.98 and 2.91 A/W with input powers of-10 and-25 dBm, respectively. The device's 3-dB bandwidth is 15 GHz with an input power of-15 dBm and a gain is 11.68. Experimental results show a peak in impedance at high bias voltages, attributed to inductor and capacitor(LC) circuit resonance, enhancing frequency response. Furthermore, 20 Gbps eye diagrams at-21 V and-9 dBm input power reveal signal to noise ratio(SNRs) of 5.30. This lateral SACM APD, compatible with the stand complementary metal oxide semiconductor(CMOS) process,shows that utilizing the peaking effect at low optical power increases bandwidth.
基金supported by grants from the National Institutes of Health,No.NS105689(to WL)the Department of Defense through the Multiple Sclerosis Research Program,No.W81XWH-22-1-0757(to WL).
文摘The unfolded protein response(UPR)is a cellular stress response pathway activated when the endoplasmic reticulum,a crucial organelle for protein folding and modification,encounters an accumulation of unfolded or misfolded proteins.The UPR aims to restore endoplasmic reticulum homeostasis by enhancing protein folding capacity,reducing protein biosynthesis,and promoting protein degradation.It also plays a pivotal role in coordinating signaling cascades to determine cell fate and function in response to endoplasmic reticulum stress.Recent research has highlighted the significance of the UPR not only in maintaining endoplasmic reticulum homeostasis but also in influencing various physiological processes in the nervous system.Here,we provide an overview of recent findings that underscore the UPR’s involvement in preserving the function and viability of neuronal and myelinating cells under physiological conditions,and highlight the critical role of the UPR in brain development,memory storage,retinal cone development,myelination,and maintenance of myelin thickness.
文摘Background:According to clinical practice guidelines,transarterial chemoembolization(TACE)is the standard treatment modality for patients with intermediate-stage hepatocellular carcinoma(HCC).Early prediction of treatment response can help patients choose a reasonable treatment plan.This study aimed to investigate the value of the radiomic-clinical model in predicting the efficacy of the first TACE treatment for HCC to prolong patient survival.Methods:A total of 164 patients with HCC who underwent the first TACE from January 2017 to September 2021 were analyzed.The tumor response was assessed by modified response evaluation criteria in solid tumors(mRECIST),and the response of the first TACE to each session and its correlation with overall survival were evaluated.The radiomic signatures associated with the treatment response were identified by the least absolute shrinkage and selection operator(LASSO),and four machine learning models were built with different types of regions of interest(ROIs)(tumor and corresponding tissues)and the model with the best performance was selected.The predictive performance was assessed with receiver operating characteristic(ROC)curves and calibration curves.Results:Of all the models,the random forest(RF)model with peritumor(+10 mm)radiomic signatures had the best performance[area under ROC curve(AUC)=0.964 in the training cohort,AUC=0.949 in the validation cohort].The RF model was used to calculate the radiomic score(Rad-score),and the optimal cutoff value(0.34)was calculated according to the Youden’s index.Patients were then divided into a high-risk group(Rad-score>0.34)and a low-risk group(Rad-score≤0.34),and a nomogram model was successfully established to predict treatment response.The predicted treatment response also allowed for significant discrimination of Kaplan-Meier curves.Multivariate Cox regression identified six independent prognostic factors for overall survival,including male[hazard ratio(HR)=0.500,95%confidence interval(CI):0.260–0.962,P=0.038],alpha-fetoprotein(HR=1.003,95%CI:1.002–1.004,P<0.001),alanine aminotransferase(HR=1.003,95%CI:1.001–1.005,P=0.025),performance status(HR=2.400,95%CI:1.200–4.800,P=0.013),the number of TACE sessions(HR=0.870,95%CI:0.780–0.970,P=0.012)and Rad-score(HR=3.480,95%CI:1.416–8.552,P=0.007).Conclusions:The radiomic signatures and clinical factors can be well-used to predict the response of HCC patients to the first TACE and may help identify the patients most likely to benefit from TACE.
基金funded by the Shandong Provincial Natural Science Foundation,China (ZR2020QC005)the National Natural Science Foundation of China (32272789)+3 种基金the National Natural Science Foundation of China (32000041)the Shandong Edible Fungus Agricultural Technology System (SDAIT-07-02)the Shandong Provincial Key Research and Development Plan (2021ZDSYS28)the Qingdao Agricultural University Scientific Research Foundation (6631120076)。
文摘White Hypsizygus marmoreus is a popular edible mushroom.Its mycelium is easy to be contaminated by Penicillium,which leads to a decrease in its quality and yield.Penicillium could compete for limited space and nutrients through rapid growth and produce a variety of harmful gases,such as benzene,aldehydes,phenols,etc.,to inhibit the growth of H.marmoreus mycelium.A series of changes occurred in H.marmoreus proteome after contamination when detected by the label-free tandem mass spectrometry(MS/MS)technique.Some proteins with up-regulated expression worked together to participate in some processes,such as the non-toxic transformation of harmful gases,glutathione metabolism,histone modification,nucleotide excision repair,clearing misfolded proteins,and synthesizing glutamine,which were mainly used in response to biological stress.The proteins with down-regulated expression are mainly related to the processes of ribosome function,protein processing,spliceosome,carbon metabolism,glycolysis,and gluconeogenesis.The reduction in the function of these proteins affected the production of the cell components,which might be an adjustment to adapt to growth retardation.This study further enhanced the understanding of the biological stress response and the growth restriction adaptation mechanisms in edible fungi.It also provided a theoretical basis for protein function exploration and edible mushroom food safety research.
基金the National Natural Science Foundation of China Youth Fund,Research on Security Low Carbon Collaborative Situation Awareness of Comprehensive Energy System from the Perspective of Dynamic Security Domain(52307130).
文摘To address the issues of limited demand response data,low generalization of demand response potential evaluation,and poor demand response effect,the article proposes a demand response potential feature extraction and prediction model based on data mining and a demand response potential assessment model for adjustable loads in demand response scenarios based on subjective and objective weight analysis.Firstly,based on the demand response process and demand response behavior,obtain demand response characteristics that characterize the process and behavior.Secondly,establish a feature extraction and prediction model based on data mining,including similar day clustering,time series decomposition,redundancy processing,and data prediction.The predicted values of each demand response feature on the response day are obtained.Thirdly,the predicted data of various characteristics on the response day are used as demand response potential evaluation indicators to represent different demand response scenarios and adjustable loads,and a demand response potential evaluation model based on subjective and objective weight allocation is established to calculate the demand response potential of different adjustable loads in different demand response scenarios.Finally,the effectiveness of the method proposed in the article is verified through examples,providing a reference for load aggregators to formulate demand response schemes.
基金supported by the National Natural Science Foundation of China(81825009,82071505,81901358)the Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences(2021-I2MC&T-B-099,2019-I2M-5–006)+2 种基金the Program of Chinese Institute for Brain Research Beijing(2020-NKX-XM-12)the King’s College London-Peking University Health Science Center Joint Institute for Medical Research(BMU2020KCL001,BMU2019LCKXJ012)the National Key R&D Program of China(2021YFF1201103,2016YFC1307000).
文摘Background:Choosing the appropriate antipsychotic drug(APD)treatment for patients with schizophrenia(SCZ)can be challenging,as the treatment response to APD is highly variable and difficult to predict due to the lack of effective biomarkers.Previous studies have indicated the association between treatment response and genetic and epigenetic factors,but no effective biomarkers have been identified.Hence,further research is imperative to enhance precision medicine in SCZ treatment.Methods:Participants with SCZ were recruited from two randomized trials.The discovery cohort was recruited from the CAPOC trial(n=2307)involved 6 weeks of treatment and equally randomized the participants to the Olanzapine,Risperidone,Quetiapine,Aripiprazole,Ziprasidone,and Haloperidol/Perphenazine(subsequently equally assigned to one or the other)groups.The external validation cohort was recruited from the CAPEC trial(n=1379),which involved 8 weeks of treatment and equally randomized the participants to the Olanzapine,Risperidone,and Aripiprazole groups.Additionally,healthy controls(n=275)from the local community were utilized as a genetic/epigenetic reference.The genetic and epigenetic(DNA methylation)risks of SCZ were assessed using the polygenic risk score(PRS)and polymethylation score,respectively.The study also examined the genetic-epigenetic interactions with treatment response through differential methylation analysis,methylation quantitative trait loci,colocalization,and promoteranchored chromatin interaction.Machine learning was used to develop a prediction model for treatment response,which was evaluated for accuracy and clinical benefit using the area under curve(AUC)for classification,R^(2) for regression,and decision curve analysis.Results:Six risk genes for SCZ(LINC01795,DDHD2,SBNO1,KCNG2,SEMA7A,and RUFY1)involved in cortical morphology were identified as having a genetic-epigenetic interaction associated with treatment response.The developed and externally validated prediction model,which incorporated clinical information,PRS,genetic risk score(GRS),and proxy methylation level(proxyDNAm),demonstrated positive benefits for a wide range of patients receiving different APDs,regardless of sex[discovery cohort:AUC=0.874(95%CI 0.867-0.881),R^(2)=0.478;external validation cohort:AUC=0.851(95%CI 0.841-0.861),R^(2)=0.507].Conclusions:This study presents a promising precision medicine approach to evaluate treatment response,which has the potential to aid clinicians in making informed decisions about APD treatment for patients with SCZ.Trial registration Chinese Clinical Trial Registry(https://www.chictr.org.cn/),18 Aug 2009 retrospectively registered:CAPOC-ChiCTR-RNC-09000521(https://www.chictr.org.cn/showproj.aspx?proj=9014),CAPEC-ChiCTRRNC-09000522(https://www.chictr.org.cn/showproj.aspx?proj=9013).
文摘Probiotics are live microorganisms exerting beneficial effects on the host’s health when administered in adequate amounts.Among the most popular and adequately studied probiotics are bacteria from the families Lactobacillaceae,Bifidobacteriaceae and yeasts.Most of them have been shown,both in vitro and in vivo studies of intestinal inflammation models,to provide favorable results by means of improving the gut microbiota composition,promoting the wound healing process and shaping the immunological responses.Chronic intestinal conditions,such as inflammatory bowel diseases(IBD),are characterized by an imbalance in microbiota composition,with decreased diversity,and by relapsing and persisting inflammation,which may lead to mucosal damage.Although the results of the clinical studies investigating the effect of probiotics on patients with IBD are still controversial,it is without doubt that these microorganisms and their metabolites,now named postbiotics,have a positive influence on both the host’s microbiota and the immune system,and ultimately alter the topical tissue microenvironment.This influence is achieved through three axes:(1)By dis-placement of potential pathogens via competitive exclusion;(2)by offering protection to the host through the secretion of various defensive mediators;and(3)by supplying the host with essential nutrients.We will analyze and discuss almost all the in vitro and in vivo studies of the past 2 years dealing with the possible favorable effects of certain probiotic genus on gut immunological responses,highlighting which species are the most beneficial against intestinal inflammation.
基金the National Natural Science Foundation of China(Nos.42176142,41906111,41806127)the Marine Economic Development Project of Guangdong Province(No.2023B1111050011)+1 种基金the Basic and Applied Basic Research Project of Guangzhou(Nos.2023A04J1548,2023A04J1549)the Outstanding Innovative Talents Cultivation Funded Programs for Doctoral Students of Jinan University(No.2021CXB010)。
文摘Phaeocystis globosa is an important unicellular eukaryotic alga that can also form colonies.P.globosa can cause massive harmful algal blooms and plays an important role in the global carbon or sulfur cycling.Thus far,the ecophysiology of P.globosa has been investigated by numerous studies.However,the proteomic response of P.globosa to nitrogen depletion remains largely unknown.We compared four protein preparation methods of P.globosa for two-dimensional electrophoresis(2-DE)(Urea/Triton X-100 with trichloroacetic acid(TCA)/acetone precipitation;TCA/acetone precipitation;Radio Immuno Precipitation Assay(RIPA)with TCA/acetone precipitation;and Tris buffer).Results show that the combination of RIPA with TCA/acetone precipitation had a clear gel background and showed the best protein spot separation effect,based on which the proteomic response to nitrogen depletion was studied using 2-DE.In addition,we identified six differentially expressed proteins whose relative abundance increased or decreased more than 1.5-fold(P<0.05).Most proteins could not be identified,which might be attributed to the lack of genomic sequences of P.globosa.Under nitrogen limitation,replication protein-like,RNA ligase,and sn-glycerol-3-phosphate dehydrogenase were reduced,which may decrease the DNA replication level and ATP production in P.globosa cells.The increase of endonucleaseⅢand transcriptional regulator enzyme may affect the metabolic and antioxidant function of P.globosa cells and induce cell apoptosis.These findings provide a basis for further proteomic study of P.globosa and the optimization of protein preparation methods of marine microalgae.
基金This study was supported by National Key Research and Development Program of China(No.2018YFA0605601)National Natural Science Foundation of China(No.42077417 and41671042).
文摘The Tongbai Mountains is an ecologically sensi-tive region and the northern boundary of Pinus massoniana Lamb.To analyze the effect of different microenvironments on tree growth response to climate factors,we developed standard chronologies for earlywood width(EWW),late-wood width(LWW),and total ring width(TRW)of P.massoniana at two sampling sites on slopes with different orientations,then analyzed characteristics of the chronolo-gies and their correlations with climate variables from five stations in the region and with a regional normalized differ-ence vegetation index(NDVI).Statistical results showed that the TRW/EWW/LWW chronology consistency and charac-teristics(mean sensitivity,signal to noise ratio,expressed population signal)for trees growing on the southeastern slope were much higher than for trees on the northeastern slope.Correlations indicated that temperature in current March and August has a significant positive effect on TRW/EWW/LWW formation,and the effect on the northeastern slope was weaker than on the southeastern slope.Compared to temperature,precipitation has more complicated effects on tree growth,but the effect on the northeastern slope was also generally weaker than on the southeastern slope.Step-wise linear regression analyses showed that temperature in August was the main limiting factor at the two sampling sites.Similarly,the response of tree growth on the southeast-ern slope as determined by the NDVI is better than on the northeastern slope,and the TRW/EWW/LWW chronologies for the southeastern slope explained over 50%of the total NDVI variances in June.Overall,the results indicate that the difference in the climate response of P.massoniana at two sampling sites is clearly caused by differences in the microenvironment,and such differences should be properly considered in future studies of forest dynamics and climate reconstructions.
基金supported by the Guangdong Basic and Applied Basic Research Foundation(2022A1515110296,2022A1515110432)the Shenzhen Science and Technology Program(No.20231120171032001,20231122125728001).
文摘Fire warning is vital to human life,economy and ecology.However,the development of effective warning systems faces great challenges of fast response,adjustable threshold and remote detecting.Here,we propose an intelligent self-powered remote IoT fire warning system,by employing single-walled carbon nanotube/titanium carbide thermoelectric composite films.The flexible films,prepared by a convenient solution mixing,display p-type characteristic with excellent high-temperature stability,flame retardancy and TE(power factor of 239.7±15.8μW m^(-1) K^(-2))performances.The comprehensive morphology and structural analyses shed light on the underlying mechanisms.And the assembled TE devices(TEDs)exhibit fast fire warning with adjustable warning threshold voltages(1–10 mV).Excitingly,an ultrafast fire warning response time of~0.1 s at 1 mV threshold voltage is achieved,rivaling many state-of-the-art systems.Furthermore,TE fire warning systems reveal outstanding stability after 50 repeated cycles and desired durability even undergoing 180 days of air exposure.Finally,a TED-based wireless intelligent fire warning system has been developed by coupling an amplifier,analogto-digital converter and Bluetooth module.By combining TE characteristics,high-temperature stability and flame retardancy with wireless IoT signal transmission,TE-based hybrid system developed here is promising for next-generation self-powered remote IoT fire warning applications.