pH-responsive charge reversal loaded miRNA nanocomposite was prepared by electrostatic self-assembly.The morphology,particle size and zeta potential of the nanocomposites were analyzed by transmission electron microsc...pH-responsive charge reversal loaded miRNA nanocomposite was prepared by electrostatic self-assembly.The morphology,particle size and zeta potential of the nanocomposites were analyzed by transmission electron microscopy and dynamic light scattering.The synthesis of the polymer was analyzed by^(1)H-NMR.The zeta-potential changes and cellular uptake effects of the nanocomplexes under different pH environments were investigated.The experimental results show that the surface morphology of the nanocomposite is spherical,and the average particle size is about 135 nm.As the pH value of the solution gradually decreases,the surface charge of the nanocomposite reverses from negative charge to positive charge(from-9.4 to+17.1 mV).Cellular uptake mediated by pH-responsive nanocomposite is selective for tumor cells,and the cellular uptake effect in tumor cells at pH 6.5 was approximately 3 times higher than that at pH 7.4.This pH responsive charge reversal nanocomposite has promising application prospects for gene delivery in the weak acid environment of tumors.展开更多
Nanofiber membranes(NFMs) have become attractive candidates for next-generation flexible transparent materials due to their exceptional flexibility and breathability. However, improving the transmittance of NFMs is a ...Nanofiber membranes(NFMs) have become attractive candidates for next-generation flexible transparent materials due to their exceptional flexibility and breathability. However, improving the transmittance of NFMs is a great challenge due to the enormous reflection and incredibly poor transmission generated by the nanofiber-air interface. In this research, we report a general strategy for the preparation of flexible temperature-responsive transparent(TRT) membranes,which achieves a rapid transformation of NFMs from opaque to highly transparent under a narrow temperature window. In this process, the phase change material eicosane is coated on the surface of the polyurethane nanofibers by electrospray technology. When the temperature rises to 37 ℃, eicosane rapidly completes the phase transition and establishes the light transmission path between the nanofibers, preventing light loss from reflection at the nanofiber-air interface. The resulting TRT membrane exhibits high transmittance(> 90%), and fast response(5 s). This study achieves the first TRT transition of NFMs, offering a general strategy for building highly transparent nanofiber materials, shaping the future of next-generation intelligent temperature monitoring, anti-counterfeiting measures, and other high-performance devices.展开更多
Objective:To evaluate the effect of rosmarinic acid on tracheal smooth muscle responsiveness and lung pathological changes in ovalbumin-sensitized rats.Methods:Rats were randomly divided into six groups:the control gr...Objective:To evaluate the effect of rosmarinic acid on tracheal smooth muscle responsiveness and lung pathological changes in ovalbumin-sensitized rats.Methods:Rats were randomly divided into six groups:the control group,the asthmatic group,and the asthmatic groups treated with dexamethasone(1 mg/kg;oral gavage)or three doses of rosmarinic acid(0.5,1,and 2 mg/kg;oral gavage).For induction of asthma,rats received intraperitoneal injections and inhalation of ovalbumin.After 21 days,bronchoalveolar lavage fluid and lung samples were collected for histopathological analyses.Moreover,total and differential white blood cell counts were determined.Results:The rosmarinic acid-treated group had significantly lower tracheal smooth muscle responses to methacholine than the asthmatic group.In addition,rosmarinic acid reduced white blood cell count and the percentages of eosinophils,monocytes,and neutrophils while increasing the percentage of lymphocytes.Ovalbumin-induced lung pathological changes were significantly improved by treatment with rosmarinic acid.Conclusions:Rosmarinic acid improves tracheal smooth muscle responsiveness and lung pathological changes in ovalbumin-sensitized rats.展开更多
We developed a fluorescent double network hydrogel with ionic responsiveness and high mechanical properties for visual detection.The nanocomposite hydrogel of laponite and polyacrylamide serves as the first network,wh...We developed a fluorescent double network hydrogel with ionic responsiveness and high mechanical properties for visual detection.The nanocomposite hydrogel of laponite and polyacrylamide serves as the first network,while the ionic cross-linked hydrogel of terbium ions and sodium alginate serves as the second network.The double-network structure,the introduction of nanoparticles and the reversible ionic crosslinked interactions confer high mechanical properties to the hydrogel.Terbium ions are not only used as the ionic cross-linked points,but also used as green emitters to endow hydrogels with fluorescent properties.On the basis of the “antenna effect” of terbium ions and the ion exchange interaction,the fluorescence of the hydrogels can make selective responses to various ions(such as organic acid radical ions,transition metal ions) in aqueous solutions,which enables a convenient strategy for visual detection toward ions.Consequently,the fluorescent double network hydrogel fabricated in this study is promising for use in the field of visual sensor detection.展开更多
Hydrogen sulfide(H_(2)S)is a toxic,essential gas used in various biological and physical processes and has been the subject of many targeted studies on its role as a new gas transmitter.These studies have mainly focus...Hydrogen sulfide(H_(2)S)is a toxic,essential gas used in various biological and physical processes and has been the subject of many targeted studies on its role as a new gas transmitter.These studies have mainly focused on the production and pharmacological side effects caused by H_(2)S.Therefore,effective strategies to remove H_(2)S has become a key research topic.Furthermore,the development of novel nanoplatforms has provided new tools for the targeted removal of H_(2)S.This paper was performed to review the association between H_(2)S anddisease,relatedH_(2)S inhibitory drugs,aswell as H_(2)S responsive nanoplatforms(HRNs).This review first analyzed the role of H_(2)S in multiple tissues and conditions.Second,common drugs used to eliminate H_(2)S,as well as their potential for combination with anticancer agents,were summarized.Not only the existing studies on HRNs,but also the inhibition H_(2)S combined with different therapeutic methods were both sorted out in this review.Furthermore,this review provided in-depth analysis of the potential of HRNs about treatment or detection in detail.Finally,potential challenges of HRNs were proposed.This study demonstrates the excellent potential of HRNs for biomedical applications.展开更多
Inflammatory bowel disease (IBD) is a group of chronic, nonspecific intestinal inflammatory disorders characterized by localized and systemic inflammation. The use of biologic agents in the treatment of IBD patients i...Inflammatory bowel disease (IBD) is a group of chronic, nonspecific intestinal inflammatory disorders characterized by localized and systemic inflammation. The use of biologic agents in the treatment of IBD patients is widespread, and the occurrence of primary non-responsiveness during treatment is also significant. This review briefly summarizes the possible reasons for primary non-responsiveness in IBD patients, as well as predictive markers and current strategies to address it, providing a theoretical reference for early identification and management of IBD patients who do not respond to treatment.展开更多
Micro/nanorobots can propel and navigate in many hard-to-reach biological environments,and thus may bring revolutionary changes to biomedical research and applications.However,current MNRs lack the capability to colle...Micro/nanorobots can propel and navigate in many hard-to-reach biological environments,and thus may bring revolutionary changes to biomedical research and applications.However,current MNRs lack the capability to collectively perceive and report physicochemical changes in unknown microenvironments.Here we propose to develop swarming responsive photonic nanorobots that can map local physicochemical conditions on the fly and further guide localized photothermal treatment.The RPNRs consist of a photonic nanochain of periodically-assembled magnetic Fe_(3)O_(4)nanoparticles encapsulated in a responsive hydrogel shell,and show multiple integrated functions,including energetic magnetically-driven swarming motions,bright stimuli-responsive structural colors,and photothermal conversion.Thus,they can actively navigate in complex environments utilizing their controllable swarming motions,then visualize unknown targets(e.g.,tumor lesion)by collectively mapping out local abnormal physicochemical conditions(e.g.,pH,temperature,or glucose concentra-tion)via their responsive structural colors,and further guide external light irradiation to initiate localized photothermal treatment.This work facilitates the development of intelligent motile nanosensors and versatile multifunctional nanotheranostics for cancer and inflam-matory diseases.展开更多
Food allergy has become a significant public health problem affecting a large number of people worldwide.Maternal obesity causes inflammation and alters the immune system of offspring,which may exacerbate their food a...Food allergy has become a significant public health problem affecting a large number of people worldwide.Maternal obesity causes inflammation and alters the immune system of offspring,which may exacerbate their food allergy.The aim of this study was to determine whether offspring mice born to obese mothers would have more serve reactions to cow's milk protein-induced food allergy,and further investigate the underlying mechanisms.Female offspring BALB/c mice of mothers with normal and high-fat diets were sensitized withβ-lactoglobulin(BLG),respectively.Maternal obesity increased the serum immunoglobulin E and mouse mast cell protease levels,though did not have significant influence on anaphylactic symptom score,core temperature and diarrhea rate of offspring mice after BLG sensitization.Furthermore,maternal obesity led to a lower level of occludin mRNA expression in BLG-sensitized mice.The mice born to obese mothers exhibited increased mRNA expression levels of GATA-3,interleukin(IL)-4 and IL-10 in jejunum after BLG sensitization,indicating maternal obesity intensified Th2-type biased immune responses.In conclusion,maternal obesity exerted exacerbating effects on the responsiveness of their offspring to cow's milk protein sensitization.展开更多
The traditional multi-process to enhance tight oil recovery based on fracturing and huff-n-puff has obvious deficiencies,such as low recovery efficiency,rapid production decline,high cost,and complexity,etc.Therefore,...The traditional multi-process to enhance tight oil recovery based on fracturing and huff-n-puff has obvious deficiencies,such as low recovery efficiency,rapid production decline,high cost,and complexity,etc.Therefore,a new technology,the so-called fracturing-oil expulsion integration,which does not need flowback after fracturing while making full use of the fracturing energy and gel breaking fluids,are needed to enable efficient exploitation of tight oil.A novel triple-responsive smart fluid based on“pseudo-Gemini”zwitterionic viscoelastic surfactant(VES)consisting of N-erucylamidopropyl-N,N-dimethyl-3-ammonio-2-hydroxy-1-propane-sulfonate(EHSB),N,N,N′,N′-tetramethyl-1,3-propanediamine(TMEDA)and sodium p-toluenesulfonate(NaPts),is developed.Then,the rheology of smart fluid is systematically studied at varying conditions(CO_(2),temperature and pressure).Moreover,the mechanism of triple-response is discussed in detail.Finally,a series of fracturing and spontaneous imbibition performances are systematically investigated.The smart fluid shows excellent CO_(2)-,thermal-,and pressure-triple responsive behavior.It can meet the technical requirement of tight oil fracturing construction at 140°C in the presence of 3.5 MPa CO_(2).The gel breaking fluid shows excellent spontaneous imbibition oil expulsion(∼40%),salt resistance(1.2×104 mg/L Na+),temperature resistance(140°C)and aging stability(30 days).展开更多
During the chemotherapy of tumors,the cytotoxic effect of drugs is vital to kill tumor cells,and the delivery of a chemotherapeutic agent is of great importance for optimal therapeutic effects.The high in vivo clearan...During the chemotherapy of tumors,the cytotoxic effect of drugs is vital to kill tumor cells,and the delivery of a chemotherapeutic agent is of great importance for optimal therapeutic effects.The high in vivo clearance rate and low delivery efficiency of conventional chemotherapeutic agents affect the therapeutic effect.In recent years,the responsive drug delivery nanosystem has received increasing concern owing to its excellent biocompatibility,stable delivery performance,and controlled drug release strategies.To lucidly explain the cytocidal and immunotherapeutic effects of such responsive nanosystems in breast cancer,this review discusses the various stimuli and responses of drug-loaded liposomal nanosystems.The light/magnetic response of drug-loaded bionic membranes nanosystems and the heat/magnetic response of drug-loaded iron oxide nanosystems are also elaborated.Their cancer cell-killing efficacy and antitumor immunotherapeutic effects are also scrutinized.展开更多
Acyl-CoA-binding proteins(ACBPs)are important for the transport of acyl groups for macro molecular biosynthesis involved in plant growth,development,and diverse stress(e.g.,cold,drought,salinity,and heavy metals)respo...Acyl-CoA-binding proteins(ACBPs)are important for the transport of acyl groups for macro molecular biosynthesis involved in plant growth,development,and diverse stress(e.g.,cold,drought,salinity,and heavy metals)responses.Here,we report the phylogeny and characteristics of the ACBP family in the woody plant Populus trichocarpa.Eight genes encoding ACBP proteins were identified,and they are distributed on eight chromosomes in P.trichocarpa.These PtACBP genes were divided into four subgroups according to gene structure,conserved motifs and phylogenetic relationship.Promoter analysis revealed that cis-elements were related to stress response,phytohormone response,and physical and reproductive growth regulation.Expression levels of PtACBP genes varied among different organs,with the highest expression in leaves and the lowest in stems.Quantitative real-time PCR(qRT-PCR)analysis showed that under salinity-alkali stresses(i.e.,200 mM NaCl,75 mM Na2CO3,and 100 mM NaHCO3),four(PtACBP1,PtACBP3,PtACBP4 and PtACBP8)of eight PtACBP genes were significantly induced in roots and leaves.These data provide a comprehensive analysis of the ACBPs family in P.trichocarpa,which could be useful for gene function analyses.展开更多
Nitrogen(N)is one of the basic nutrients and signals for plant development and deficiency of it would always limit the productions of crops in the field.Quantitative research on expression of N-stress responsive prote...Nitrogen(N)is one of the basic nutrients and signals for plant development and deficiency of it would always limit the productions of crops in the field.Quantitative research on expression of N-stress responsive proteins on a proteome level remains elusive.In order to gain a deep insight into the proteins responding to nitrogen stress in rapeseed(Brassica napus L.),comparative proteomic analysis was performed to investigate changes of protein expression profiles from the root,stem and leaf under different N concentrations,respectively.More than 200 differential abundance proteins(DAPs)were detected and categorized into groups according to annotations,including“binding and catalytic activity”,“involved in primary metabolism and cellular processes”,“stress-response”and so on.Variation in chlorophyll(Chl)content and antioxidant activities further revealed that oxidative stress raised with the increase of N concentration.Bioinformatics analysis based on the expression level of total proteins suggested these DAPs might play important roles in adaptation to N-stress conditions.Generally,these results provides a new aspect into N-stress responding proteins in Brassica plants.展开更多
Dunaliella salina is a classic halophilic alga.However,its molecular mechanisms in response to high salinity at the post transcriptional level remain unknown.A unique halophilic alga strain,DS-CN1,was screened from fo...Dunaliella salina is a classic halophilic alga.However,its molecular mechanisms in response to high salinity at the post transcriptional level remain unknown.A unique halophilic alga strain,DS-CN1,was screened from four D.salina strains via cell biological,physiological,and biochemical methods.High-throughput sequencing of small RNAs(sRNAs)of DS-CN1 in culture medium containing 3.42-mol/L NaCl(SS group)or 0.05-mol/L NaCl(CO group)was performed on the BGISEQ-500 platform.The annotation and sequences of D.salina sRNAs were profiled.Altogether,44 novel salt stress-responsive microRNAs(miRNAs)with a relatively high C content,with the majority of them being 24 nt in length,were identified and characterized in DS-CN1.Twenty-one differentially expressed miRNAs(DEMs)in SS and CO were screened via bioinformatic analysis.A total of 319 putative salt stress-related genes targeted(104 overlapping genes)by novel miRNAs in this alga were screened based on our previous transcriptome sequencing research.Furthermore,these target genes were classified and enriched by GO and KEGG pathway analysis.Moreover,5 novel DEMs(dsa-mir3,dsa-mir16,dsa-mir17,and dsa-mir26 were significantly upregulated,and dsa-mir40 was significantly downregulated)and their corresponding 10 target genes involved in the 6 significantly enriched metabolic pathways were verified by quantitative real-time PCR.Next,their regulatory relationships were comprehensively analyzed.Lastly,a unique salt stress response metabolic network was constructed based on the novel DEM-target gene pairs.Taken together,our results suggest that 44 novel salt stress-responsive microRNAs were identified,and 4 of them might play important roles in D.salina upon salinity stress and contribute to clarify its distinctive halophilic feature.Our study will shed light on the regulatory mechanisms of salt stress responses.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
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
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
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
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
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
基金Funded by the National Key R&D Program of China(No.2023YFC2412300)the Natural Science Foundation of Hubei Province(No.2022CFB386)the National Natural Science Foundation of China(No.52073222)。
文摘pH-responsive charge reversal loaded miRNA nanocomposite was prepared by electrostatic self-assembly.The morphology,particle size and zeta potential of the nanocomposites were analyzed by transmission electron microscopy and dynamic light scattering.The synthesis of the polymer was analyzed by^(1)H-NMR.The zeta-potential changes and cellular uptake effects of the nanocomplexes under different pH environments were investigated.The experimental results show that the surface morphology of the nanocomposite is spherical,and the average particle size is about 135 nm.As the pH value of the solution gradually decreases,the surface charge of the nanocomposite reverses from negative charge to positive charge(from-9.4 to+17.1 mV).Cellular uptake mediated by pH-responsive nanocomposite is selective for tumor cells,and the cellular uptake effect in tumor cells at pH 6.5 was approximately 3 times higher than that at pH 7.4.This pH responsive charge reversal nanocomposite has promising application prospects for gene delivery in the weak acid environment of tumors.
基金financially supported by National Key Research and Development Program of China (2022YFB3804903, 2022YFB3804900)the National Natural Science Foundation of China (No. 52273052)+2 种基金the Fundamental Research Funds for the Central Universities (No. 2232023Y01)the Program of Shanghai Academic/Technology Research Leader (No. 21XD1420100)the International Cooperation Fund of Science and Technology Commission of Shanghai Municipality (No. 21130750100)。
文摘Nanofiber membranes(NFMs) have become attractive candidates for next-generation flexible transparent materials due to their exceptional flexibility and breathability. However, improving the transmittance of NFMs is a great challenge due to the enormous reflection and incredibly poor transmission generated by the nanofiber-air interface. In this research, we report a general strategy for the preparation of flexible temperature-responsive transparent(TRT) membranes,which achieves a rapid transformation of NFMs from opaque to highly transparent under a narrow temperature window. In this process, the phase change material eicosane is coated on the surface of the polyurethane nanofibers by electrospray technology. When the temperature rises to 37 ℃, eicosane rapidly completes the phase transition and establishes the light transmission path between the nanofibers, preventing light loss from reflection at the nanofiber-air interface. The resulting TRT membrane exhibits high transmittance(> 90%), and fast response(5 s). This study achieves the first TRT transition of NFMs, offering a general strategy for building highly transparent nanofiber materials, shaping the future of next-generation intelligent temperature monitoring, anti-counterfeiting measures, and other high-performance devices.
文摘Objective:To evaluate the effect of rosmarinic acid on tracheal smooth muscle responsiveness and lung pathological changes in ovalbumin-sensitized rats.Methods:Rats were randomly divided into six groups:the control group,the asthmatic group,and the asthmatic groups treated with dexamethasone(1 mg/kg;oral gavage)or three doses of rosmarinic acid(0.5,1,and 2 mg/kg;oral gavage).For induction of asthma,rats received intraperitoneal injections and inhalation of ovalbumin.After 21 days,bronchoalveolar lavage fluid and lung samples were collected for histopathological analyses.Moreover,total and differential white blood cell counts were determined.Results:The rosmarinic acid-treated group had significantly lower tracheal smooth muscle responses to methacholine than the asthmatic group.In addition,rosmarinic acid reduced white blood cell count and the percentages of eosinophils,monocytes,and neutrophils while increasing the percentage of lymphocytes.Ovalbumin-induced lung pathological changes were significantly improved by treatment with rosmarinic acid.Conclusions:Rosmarinic acid improves tracheal smooth muscle responsiveness and lung pathological changes in ovalbumin-sensitized rats.
基金Funded by the National Natural Science Foundation of China(No.51873167)the National Innovation and Entrepreneurship Training Program for College Students(No.226801001)。
文摘We developed a fluorescent double network hydrogel with ionic responsiveness and high mechanical properties for visual detection.The nanocomposite hydrogel of laponite and polyacrylamide serves as the first network,while the ionic cross-linked hydrogel of terbium ions and sodium alginate serves as the second network.The double-network structure,the introduction of nanoparticles and the reversible ionic crosslinked interactions confer high mechanical properties to the hydrogel.Terbium ions are not only used as the ionic cross-linked points,but also used as green emitters to endow hydrogels with fluorescent properties.On the basis of the “antenna effect” of terbium ions and the ion exchange interaction,the fluorescence of the hydrogels can make selective responses to various ions(such as organic acid radical ions,transition metal ions) in aqueous solutions,which enables a convenient strategy for visual detection toward ions.Consequently,the fluorescent double network hydrogel fabricated in this study is promising for use in the field of visual sensor detection.
基金supported by National Key Research and Development Program of China(contract No.2019YFA0904800)National Nature Science Foundation of China(32030065,31722033,92049304 to Y.Z.)+5 种基金Shanghai Sailing Program(contract No.21YF1410300)Science and Technology Commission of Shanghai Municipality(contract No.10DZ2220500)The Shanghai Committee of Science and Technology(grant No.11DZ2260600)Shanghai Frontiers Science Center of Optogenetic Techniques for CellMetabolism(Y.Z.)Research Unit of New Techniques for Live-cell Metabolic Imaging(Chinese Academy of Medical Sciences,2019-I2M-5-013 to Y.Z.)the State Key Laboratory of Bioreactor Engineering,the Fundamental Research Funds for the Central Universities.
文摘Hydrogen sulfide(H_(2)S)is a toxic,essential gas used in various biological and physical processes and has been the subject of many targeted studies on its role as a new gas transmitter.These studies have mainly focused on the production and pharmacological side effects caused by H_(2)S.Therefore,effective strategies to remove H_(2)S has become a key research topic.Furthermore,the development of novel nanoplatforms has provided new tools for the targeted removal of H_(2)S.This paper was performed to review the association between H_(2)S anddisease,relatedH_(2)S inhibitory drugs,aswell as H_(2)S responsive nanoplatforms(HRNs).This review first analyzed the role of H_(2)S in multiple tissues and conditions.Second,common drugs used to eliminate H_(2)S,as well as their potential for combination with anticancer agents,were summarized.Not only the existing studies on HRNs,but also the inhibition H_(2)S combined with different therapeutic methods were both sorted out in this review.Furthermore,this review provided in-depth analysis of the potential of HRNs about treatment or detection in detail.Finally,potential challenges of HRNs were proposed.This study demonstrates the excellent potential of HRNs for biomedical applications.
文摘Inflammatory bowel disease (IBD) is a group of chronic, nonspecific intestinal inflammatory disorders characterized by localized and systemic inflammation. The use of biologic agents in the treatment of IBD patients is widespread, and the occurrence of primary non-responsiveness during treatment is also significant. This review briefly summarizes the possible reasons for primary non-responsiveness in IBD patients, as well as predictive markers and current strategies to address it, providing a theoretical reference for early identification and management of IBD patients who do not respond to treatment.
基金supported by the National Key Research and Development Project(No.2021YFA1201400)National Natural Science Foundation of China(Nos.52073222,51573144 and 21474078)the Fundamental Research Funds for the Central Universities(WUT:2021IVA118 and 2022IVA201).
文摘Micro/nanorobots can propel and navigate in many hard-to-reach biological environments,and thus may bring revolutionary changes to biomedical research and applications.However,current MNRs lack the capability to collectively perceive and report physicochemical changes in unknown microenvironments.Here we propose to develop swarming responsive photonic nanorobots that can map local physicochemical conditions on the fly and further guide localized photothermal treatment.The RPNRs consist of a photonic nanochain of periodically-assembled magnetic Fe_(3)O_(4)nanoparticles encapsulated in a responsive hydrogel shell,and show multiple integrated functions,including energetic magnetically-driven swarming motions,bright stimuli-responsive structural colors,and photothermal conversion.Thus,they can actively navigate in complex environments utilizing their controllable swarming motions,then visualize unknown targets(e.g.,tumor lesion)by collectively mapping out local abnormal physicochemical conditions(e.g.,pH,temperature,or glucose concentra-tion)via their responsive structural colors,and further guide external light irradiation to initiate localized photothermal treatment.This work facilitates the development of intelligent motile nanosensors and versatile multifunctional nanotheranostics for cancer and inflam-matory diseases.
基金supported by the National Key Research and Development Program of China(2019YFC1605000)the Beijing Dairy Industry Innovation Team(BAIC06-2021)。
文摘Food allergy has become a significant public health problem affecting a large number of people worldwide.Maternal obesity causes inflammation and alters the immune system of offspring,which may exacerbate their food allergy.The aim of this study was to determine whether offspring mice born to obese mothers would have more serve reactions to cow's milk protein-induced food allergy,and further investigate the underlying mechanisms.Female offspring BALB/c mice of mothers with normal and high-fat diets were sensitized withβ-lactoglobulin(BLG),respectively.Maternal obesity increased the serum immunoglobulin E and mouse mast cell protease levels,though did not have significant influence on anaphylactic symptom score,core temperature and diarrhea rate of offspring mice after BLG sensitization.Furthermore,maternal obesity led to a lower level of occludin mRNA expression in BLG-sensitized mice.The mice born to obese mothers exhibited increased mRNA expression levels of GATA-3,interleukin(IL)-4 and IL-10 in jejunum after BLG sensitization,indicating maternal obesity intensified Th2-type biased immune responses.In conclusion,maternal obesity exerted exacerbating effects on the responsiveness of their offspring to cow's milk protein sensitization.
基金sincerely appreciate the financial support from the National Key Research and Development Project(2019YFA0708700)the National Natural Science Foundation of China(51834010,51874261,51874337)+1 种基金the Key Research and Development Program of Shaanxi(2021GY-112)a Discovery Grant from Natural Sciences and Engineering Research Council of Canada(NSERC RGPIN-2017-05080).
文摘The traditional multi-process to enhance tight oil recovery based on fracturing and huff-n-puff has obvious deficiencies,such as low recovery efficiency,rapid production decline,high cost,and complexity,etc.Therefore,a new technology,the so-called fracturing-oil expulsion integration,which does not need flowback after fracturing while making full use of the fracturing energy and gel breaking fluids,are needed to enable efficient exploitation of tight oil.A novel triple-responsive smart fluid based on“pseudo-Gemini”zwitterionic viscoelastic surfactant(VES)consisting of N-erucylamidopropyl-N,N-dimethyl-3-ammonio-2-hydroxy-1-propane-sulfonate(EHSB),N,N,N′,N′-tetramethyl-1,3-propanediamine(TMEDA)and sodium p-toluenesulfonate(NaPts),is developed.Then,the rheology of smart fluid is systematically studied at varying conditions(CO_(2),temperature and pressure).Moreover,the mechanism of triple-response is discussed in detail.Finally,a series of fracturing and spontaneous imbibition performances are systematically investigated.The smart fluid shows excellent CO_(2)-,thermal-,and pressure-triple responsive behavior.It can meet the technical requirement of tight oil fracturing construction at 140°C in the presence of 3.5 MPa CO_(2).The gel breaking fluid shows excellent spontaneous imbibition oil expulsion(∼40%),salt resistance(1.2×104 mg/L Na+),temperature resistance(140°C)and aging stability(30 days).
基金funded by the Basic Scientific Research Funds of Department of Education of Zhejiang Province(KYQN202103 and KYZD202103)A Project Supported by Scientific Research Fund of Zhejiang Provincial Education Department(Y202249203)+4 种基金General Program of the National Natural Science Foundation of China(61976075 to XX)the Key Research and Development Program of Zhejiang Province(2019C03002 to XX)National Innovation and Entrepreneurship Training Program for College Students(202213023011)Innovation and Entrepreneurship Training Program for College Students of Zhejiang Province(S202213023052)Zhejiang Provincial Natural Science Foundation of China under Grant No.LTGY23H180019.
文摘During the chemotherapy of tumors,the cytotoxic effect of drugs is vital to kill tumor cells,and the delivery of a chemotherapeutic agent is of great importance for optimal therapeutic effects.The high in vivo clearance rate and low delivery efficiency of conventional chemotherapeutic agents affect the therapeutic effect.In recent years,the responsive drug delivery nanosystem has received increasing concern owing to its excellent biocompatibility,stable delivery performance,and controlled drug release strategies.To lucidly explain the cytocidal and immunotherapeutic effects of such responsive nanosystems in breast cancer,this review discusses the various stimuli and responses of drug-loaded liposomal nanosystems.The light/magnetic response of drug-loaded bionic membranes nanosystems and the heat/magnetic response of drug-loaded iron oxide nanosystems are also elaborated.Their cancer cell-killing efficacy and antitumor immunotherapeutic effects are also scrutinized.
基金supported by grants from the Fundamental Research Funds for the Central Universities(Nos.2572018B03)the College Students Innovations Special Project funded by NEFU(No.202010225173)+1 种基金the Fundamental Research Funds for the Central Universities(Nos.2572019CT03)the Natural Science Foundation of Heilongjiang Province(No.ZD2019C003)。
文摘Acyl-CoA-binding proteins(ACBPs)are important for the transport of acyl groups for macro molecular biosynthesis involved in plant growth,development,and diverse stress(e.g.,cold,drought,salinity,and heavy metals)responses.Here,we report the phylogeny and characteristics of the ACBP family in the woody plant Populus trichocarpa.Eight genes encoding ACBP proteins were identified,and they are distributed on eight chromosomes in P.trichocarpa.These PtACBP genes were divided into four subgroups according to gene structure,conserved motifs and phylogenetic relationship.Promoter analysis revealed that cis-elements were related to stress response,phytohormone response,and physical and reproductive growth regulation.Expression levels of PtACBP genes varied among different organs,with the highest expression in leaves and the lowest in stems.Quantitative real-time PCR(qRT-PCR)analysis showed that under salinity-alkali stresses(i.e.,200 mM NaCl,75 mM Na2CO3,and 100 mM NaHCO3),four(PtACBP1,PtACBP3,PtACBP4 and PtACBP8)of eight PtACBP genes were significantly induced in roots and leaves.These data provide a comprehensive analysis of the ACBPs family in P.trichocarpa,which could be useful for gene function analyses.
基金funded by Modern Agro-Industry Technology Research System of China(CARS-12)Independent Innovation Project of SAAS(2022ZZCX004)+5 种基金1+9 Open Competition Project of SAAS(1+9KJGG002,1+9KJGG001)the Accurate Identification Project of Crop Germplasm from Sichuan Provincial Finance DepartmentSichuan Science and Technology Program(2022ZDZX0015)Sichuan Crop Breeding Community(2021YFYZ0018)Disciplinary Construction Project for Modern Agriculture in SAAS(2021XKJS003)Chengdu Science and Technology Project(2021-YF09-00062-SN).
文摘Nitrogen(N)is one of the basic nutrients and signals for plant development and deficiency of it would always limit the productions of crops in the field.Quantitative research on expression of N-stress responsive proteins on a proteome level remains elusive.In order to gain a deep insight into the proteins responding to nitrogen stress in rapeseed(Brassica napus L.),comparative proteomic analysis was performed to investigate changes of protein expression profiles from the root,stem and leaf under different N concentrations,respectively.More than 200 differential abundance proteins(DAPs)were detected and categorized into groups according to annotations,including“binding and catalytic activity”,“involved in primary metabolism and cellular processes”,“stress-response”and so on.Variation in chlorophyll(Chl)content and antioxidant activities further revealed that oxidative stress raised with the increase of N concentration.Bioinformatics analysis based on the expression level of total proteins suggested these DAPs might play important roles in adaptation to N-stress conditions.Generally,these results provides a new aspect into N-stress responding proteins in Brassica plants.
基金Supported by the National Natural Science Foundation of China(No.32170204)Science and Technology Strategy Research Special Project of Shanxi Province of China(No.202204031401051)+2 种基金the Basic Research Programs of Shanxi Province of China(No.202103021224009)the Teaching Reform and Innovation Project of Colleges and Universities in Shanxi of China(No.J20220046)the Shanxi“1331 Project”.
文摘Dunaliella salina is a classic halophilic alga.However,its molecular mechanisms in response to high salinity at the post transcriptional level remain unknown.A unique halophilic alga strain,DS-CN1,was screened from four D.salina strains via cell biological,physiological,and biochemical methods.High-throughput sequencing of small RNAs(sRNAs)of DS-CN1 in culture medium containing 3.42-mol/L NaCl(SS group)or 0.05-mol/L NaCl(CO group)was performed on the BGISEQ-500 platform.The annotation and sequences of D.salina sRNAs were profiled.Altogether,44 novel salt stress-responsive microRNAs(miRNAs)with a relatively high C content,with the majority of them being 24 nt in length,were identified and characterized in DS-CN1.Twenty-one differentially expressed miRNAs(DEMs)in SS and CO were screened via bioinformatic analysis.A total of 319 putative salt stress-related genes targeted(104 overlapping genes)by novel miRNAs in this alga were screened based on our previous transcriptome sequencing research.Furthermore,these target genes were classified and enriched by GO and KEGG pathway analysis.Moreover,5 novel DEMs(dsa-mir3,dsa-mir16,dsa-mir17,and dsa-mir26 were significantly upregulated,and dsa-mir40 was significantly downregulated)and their corresponding 10 target genes involved in the 6 significantly enriched metabolic pathways were verified by quantitative real-time PCR.Next,their regulatory relationships were comprehensively analyzed.Lastly,a unique salt stress response metabolic network was constructed based on the novel DEM-target gene pairs.Taken together,our results suggest that 44 novel salt stress-responsive microRNAs were identified,and 4 of them might play important roles in D.salina upon salinity stress and contribute to clarify its distinctive halophilic feature.Our study will shed light on the regulatory mechanisms of salt stress responses.
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(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.
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.
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).