The central nervous system, information integration center of the body, is mainly composed of neurons and glial cells. The neuron is one of the most basic and important structural and functional units of the central n...The central nervous system, information integration center of the body, is mainly composed of neurons and glial cells. The neuron is one of the most basic and important structural and functional units of the central nervous system, with sensory stimulation and excitation conduction functions. Astrocytes and microglia belong to the glial cell family, which is the main source of cytokines and represents the main defense system of the central nervous system. Nerve cells undergo neurotransmission or gliotransmission, which regulates neuronal activity via the ion channels, receptors, or transporters expressed on nerve cell membranes. Ion channels, composed of large transmembrane proteins, play crucial roles in maintaining nerve cell homeostasis. These channels are also important for control of the membrane potential and in the secretion of neurotransmitters. A variety of cellular functions and life activities, including functional regulation of the central nervous system, the generation and conduction of nerve excitation, the occurrence of receptor potential, heart pulsation, smooth muscle peristalsis, skeletal muscle contraction, and hormone secretion, are closely related to ion channels associated with passive transmembrane transport. Two types of ion channels in the central nervous system, potassium channels and calcium channels, are closely related to various neurological disorders, including Alzheimer's disease, Parkinson's disease, and epilepsy. Accordingly, various drugs that can affect these ion channels have been explored deeply to provide new directions for the treatment of these neurological disorders. In this review, we focus on the functions of potassium and calcium ion channels in different nerve cells and their involvement in neurological disorders such as Parkinson's disease, Alzheimer's disease, depression, epilepsy, autism, and rare disorders. We also describe several clinical drugs that target potassium or calcium channels in nerve cells and could be used to treat these disorders. We concluded that there are few clinical drugs that can improve the pathology these diseases by acting on potassium or calcium ions. Although a few novel ion-channelspecific modulators have been discovered, meaningful therapies have largely not yet been realized. The lack of target-specific drugs, their requirement to cross the blood–brain barrier, and their exact underlying mechanisms all need further attention. This review aims to explain the urgent problems that need research progress and provide comprehensive information aiming to arouse the research community's interest in the development of ion channel-targeting drugs and the identification of new therapeutic targets for that can increase the cure rate of nervous system diseases and reduce the occurrence of adverse reactions in other systems.展开更多
The aim of this study was to investigate the role of Dendrobium officinale crude polysaccharides(DOPS)and D.officinale purified polysaccharides(DOPS100)in attenuating immune dysfunction in subfertile mice.The results ...The aim of this study was to investigate the role of Dendrobium officinale crude polysaccharides(DOPS)and D.officinale purified polysaccharides(DOPS100)in attenuating immune dysfunction in subfertile mice.The results of the study revealed several noteworthy findings.First,DOPS and DOPS100 treatments led to significant improvement in weight gain and reversal of fatigue-related behaviors compared to the normal group.Second,both DOPS and DOPS100 showed effectiveness in reducing immune organ swelling,modulating immunoglobulin A(IgA)and immunoglobulin M(IgM)levels,and restoring complement(C3c and C4)levels.In addition,they demonstrated a significant ability to enhance the integrity of the intestinal mechanical barrier by differentially upregulating the tight junction proteins Occludin and Zonula occludens 1(ZO-1).In addition,it was found that DOPS100 specifically enhanced the CD4^(+)-T helper 17 cell(Th17)/regulatory T cell(Treg)immune axis in the gut,as evidenced by increased expression of forkhead box protein 3(Foxp3)as well as decreased expression of retinoic acid receptor-related orphan receptor γt(RORγt),and further modulation of interleukin 10(IL-10),interleukin 22(IL-22),and interleukin 17A(IL-17A)expression levels of inflammatory factors.These findings collectively suggest that DOPS100 holds significant potential in improving sub-healthy status by repairing the intestinal barrier,restoring local immune homeostasis,and activating the intestinal immune regulatory network.The study’s outcomes provide valuable insights into the therapeutic implications of DOPS and DOPS100 in addressing immune dysfunction in sub-healthy conditions.展开更多
Sharp eyespot(Rhizoctonia cerealis)is a widespread soil-borne fungal disease that poses a severe threat to wheat health,and it is one of the main obstacles to achieving stable and high-quality wheat yields in China.Ou...Sharp eyespot(Rhizoctonia cerealis)is a widespread soil-borne fungal disease that poses a severe threat to wheat health,and it is one of the main obstacles to achieving stable and high-quality wheat yields in China.Our collaborative team has developed a novel,efficient,and low-toxicity fungicide named Y17991(N-(2-(2,4-bis-(trifluoromethyl)phenoxy)phenyl)-3-(difluoromethyl)-1-methyl-1H-pyrazole-4-carboxamide).Preliminary laboratory tests confirmed the significant inhibitory effect of this agent on R.cerealis.Large-area field trials also demonstrated its efficacy,with a disease prevention index of 83.52%,which is 1.97%greater than that of the widely used thifluzamide,and it significantly increased the wheat yield.Moreover,this study explored the impacts of Y17991 on the structure and function of the microbial community in wheat rhizosphere soil.Bacterial communities were more strongly affected than fungal communities.Y17991 significantly modulated key amino acid metabolic pathways and certain biosynthetic processes in diseased wheat rhizospheres,and it also enhanced certain biosynthetic pathways and metabolic activities in healthy wheat rhizospheres.Additionally,the application of Y17991 regulated rhizosphere metabolites,thus exerting significant control over the microbial community.We identified 15 microbial strains potentially involved in the prevention and treatment of R.cerealis,and Y17991 treatment promoted the growth of Pedobacter and Bacillus strains.These strains not only aid in plant growth but they also have the potential for disease prevention.In summary,Y17991 application at a reasonable dose does not cause significant disruption to nontarget rhizosphere microbial communities.In future studies,we will continue to investigate the impacts of Y17991 on nonmicrobial components in soil ecosystems,such as protozoa and nematodes.Our research provides a theoretical basis for the scientific application and promotion of new fungicides and offers a significant reference for establishing a comprehensive system for assessing the ecological impact of pesticides on the environment.展开更多
Vibration energy harvesting presents a significant opportunity for powering wireless sensor networks and internet of things(IoT)devices,offering a sustainable alternative to traditional battery-based power sources.How...Vibration energy harvesting presents a significant opportunity for powering wireless sensor networks and internet of things(IoT)devices,offering a sustainable alternative to traditional battery-based power sources.However,environmental vibrations are predominantly low-frequency,which presents a significant challenge to the efficient conversion of such energy.To address this challenge,this paper proposes a novel twodegree-of-freedom(2-DOF)energy harvester.The first layer of the harvester incorporates a piezoelectric composite beam(PCB)paired with permanent magnets to form a negative stiffness mechanism(NSM),which counteracts the stiffness of linear springs,thereby achieving quasi-zero stiffness(QZS)or bistable characteristics.The second layer integrates piezoelectric transduction units with triboelectric nanogenerator(TENG)units to further enhance the efficiency of low-frequency vibration energy conversion.By considering the modal characteristics of the PCB,this paper establishes the electromechanical coupling equations of the harvester from an energy perspective.The mechanical responses of the masses in both layers,as well as the electrical outputs of the PCB,are analytically solved.Furthermore,the effects of the system parameters on the efficiency of low-frequency vibration energy harvesting are thoroughly analyzed.This work provides a theoretical foundation for the development of self-powered IoT sensor nodes,enabling efficient energy harvesting from ambient low-frequency vibrations.展开更多
Ultra-performance liquid chromatography-mass spectrometry(UPLC-MS)technology was employed to analyze the chemical composition of three Clematidis Radix et Rhizoma sourced from different origins.Common characteristic c...Ultra-performance liquid chromatography-mass spectrometry(UPLC-MS)technology was employed to analyze the chemical composition of three Clematidis Radix et Rhizoma sourced from different origins.Common characteristic components were identified through comprehensive literature review and the integration of fragment ion data.A rheumatoid arthritis(AA)model was induced in Sprague-Dawley(SD)rats using Freund’s complete adjuvant,and simultaneous administration of extracts from the three original plants of Clematidis Radix et Rhizoma,along with different doses of magnoflorine,was conducted to evaluate differences in therapeutic efficacy.A common characteristic component was identified,magnoflorine,present in Clematis chinensis Osbeck.Clematis hexapetala Pall.,and Clematis manshurica Rupr.Extracts from all three original plants,as well as each dose group of the Rhizomas of Clematis chinensis Osbeck.Clematis hexapetala Pall.,Clematis manshurica Rupr.,and magnoflorine,demonstrated efficacy in alleviating rheumatoid arthritis symptoms by enhancing cellular infiltration,reducing vascular opacification,and lowering serum levels of inflammatory factors.Magnoflorine has the potential to be used as a quality marker for the three original plants of Clematidis Radix et Rhizoma.Additionally,both the three original plants and magnoflorine exhibit therapeutic potential for rheumatoid arthritis,which provides a solid theoretical and experimental basis for the establishment of more scientifically grounded quality standards of Clematidis Radix et Rhizoma and promotes the rational utilization of medicinal resources.展开更多
The effects of direct aging(DA)on the microstructure and mechanical properties of TiB_(2)/AlSi7Mg alloys fabricated via laser powder bed fusion(LPBF)were systematically investigated.DA significantly improves strength ...The effects of direct aging(DA)on the microstructure and mechanical properties of TiB_(2)/AlSi7Mg alloys fabricated via laser powder bed fusion(LPBF)were systematically investigated.DA significantly improves strength while maintaining satisfactory ductility.Optimal performance is obtained through under-aging(UA)at 150℃ for 4 h,resulting in a yield strength of 361 MPa,tensile strength of 503 MPa,and elongation of 9.1%in the horizontal direction.DA does not substantially alter the grain size or cellular structure but pro-motes the formation of nanoprecipitates within theα-Al matrix.Specifically,UA induces dot-like and needle-like Si precipitates,whereas over-aging(OA)additionally generates short rod-likeβ'-Mg_(1.8)Si phases.The strengthening mechanism is attributed to the Hall-Petch ef-fect associated with grain and cell boundaries,and the Orowan mechanism induced by nanoprecipitates.Work-hardening behavior is gov-erned by interactions between dislocations and nanoprecipitates.The OA sample exhibits rapid saturation of work hardening due to a high initial hardening rate and dynamic recovery of dislocations,resulting in limited uniform elongation.In contrast,the UA sample demon-strates a more balanced work hardening response.These findings provide theoretical and experimental validation of DA as an effective post-processing approach aimed at enhancing the performance of LPBF Al-Si-Mg alloys in engineering applications.展开更多
Enterovirus D68(EV-D68)and enterovirus A71(EV-A71)are two major types of enteroviruses that pose emerging challenges to public health and have the potential to cause outbreaks,yet their pathogenic mechanisms remain la...Enterovirus D68(EV-D68)and enterovirus A71(EV-A71)are two major types of enteroviruses that pose emerging challenges to public health and have the potential to cause outbreaks,yet their pathogenic mechanisms remain largely unexplored.Arrestin domain containing 3(ARRDC3)is a vital regulator of glucose metabolism,cancer development,and inflammation.Whether ARRDC3 contributes to innate antiviral immunity is undefined.Here,we found that enterovirus infection induces ARRDC3 expression at both the mRNA and protein levels,thereby inhibiting enterovirus replication.Moreover,we demonstrate that the expression of Yes-associated protein(YAP),a key effector of the Hippo pathway,is severely downregulated by ARRDC3 via lysosomal pathway.YAP facilitates enterovirus replication by suppressing the interferon pathway during the later stage of enterovirus infection,independent of its transcriptional activity.Finally,the ARRDC3-YAP pathway exhibits a broad-spectrum antiviral effect in various viral infections,including those caused by human parainfluenza virus type 3(HPIV3)and vesicular stomatitis virus(VSV).Collectively,our results identify the critical role of ARRDC3 and its negative regulatory effect on YAP in the innate antiviral response,suggesting a novel therapeutic strategy against virus infection.展开更多
For non-stationary complex dynamic systems,a standardized algorithm is developed to compute time correlation functions,addressing the limitations of traditional methods reliant on the stationary assumption.The propose...For non-stationary complex dynamic systems,a standardized algorithm is developed to compute time correlation functions,addressing the limitations of traditional methods reliant on the stationary assumption.The proposed algorithm integrates two-point and multi-point time correlation functions into a unified framework.Further,it is verified by a practical application in complex financial systems,demonstrating its potential in various complex dynamic systems.展开更多
It is common for datasets to contain both categorical and continuous variables. However, many feature screening methods designed for high-dimensional classification assume that the variables are continuous. This limit...It is common for datasets to contain both categorical and continuous variables. However, many feature screening methods designed for high-dimensional classification assume that the variables are continuous. This limits the applicability of existing methods in handling this complex scenario. To address this issue, we propose a model-free feature screening approach for ultra-high-dimensional multi-classification that can handle both categorical and continuous variables. Our proposed feature screening method utilizes the Maximal Information Coefficient to assess the predictive power of the variables. By satisfying certain regularity conditions, we have proven that our screening procedure possesses the sure screening property and ranking consistency properties. To validate the effectiveness of our approach, we conduct simulation studies and provide real data analysis examples to demonstrate its performance in finite samples. In summary, our proposed method offers a solution for effectively screening features in ultra-high-dimensional datasets with a mixture of categorical and continuous covariates.展开更多
Compared to drought-susceptible rice cultivars(DSRs),drought-resistance rice cultivars(DRRs)could drastically reduce the amount of irrigation water input and simultaneously result in higher grain yield under water-sav...Compared to drought-susceptible rice cultivars(DSRs),drought-resistance rice cultivars(DRRs)could drastically reduce the amount of irrigation water input and simultaneously result in higher grain yield under water-saving irrigation conditions.However,the mechanisms underlying these properties are unclear.We investigated how improved agronomic traits contribute to higher yield and higher water use efficiency(WUE)in DRRs than in DSRs under alternate wetting and drying(AWD).Two DRRs and two DSRs were field-grown in 2015 and 2016 using two different irrigation regimes:continuous flooding(CF)and AWD.Under CF,no statistical differences in grain yield and WUE were observed between DRRs and DSRs.Irrigation water under the AWD regime was 275–349 mm,an amount 49.8%–56.2% of that(552–620 mm)applied under the CF regime.Compared to CF,AWD significantly decreased grain yield in both DRRs and DSRs,with a more significant reduction in DSRs,and WUE was increased in DRRs,but not in DSRs,by 9.9%–23.0% under AWD.Under AWD,DRRs showed a 20.2%–26.2% increase in grain yield and an 18.6%–24.5% increase in WUE compared to DSRs.Compared to DSRs,DRRs showed less redundant vegetative growth,greater sink capacity,higher grain filling efficiency,larger root biomass,and deeper root distribution under AWD.We conclude that these improved agronomic traits exert positive influences on WUE in DRRs under AWD.展开更多
Paeoniflorin(PA) is an anti-Parkinson Chinese medicine with inferior bioavailability and difficulty in delivery to the brain. This research is to develop an efficacious PA nanocrystal formulation(PA-NCs) that is suita...Paeoniflorin(PA) is an anti-Parkinson Chinese medicine with inferior bioavailability and difficulty in delivery to the brain. This research is to develop an efficacious PA nanocrystal formulation(PA-NCs) that is suitable for intranasal administration to treat Parkinson’s disease(PD). PA-NCs were fabricated through an antisolvent precipitation method using TPGS as the stabilizer. The rod-shaped PA-NCs had particle size of 139.6 ± 1.3 nm and zeta potential of-23.2 ± 0.529 mV. A molecular dynamics simulation indicated that van der Waals forces are the primary drivers of interactions between PA and TPGS. In the ex vivo nasal mucosa permeation assay, the cumulative drug release at 24 h was 87.14% ± 5.34%,which was significantly higher than that of free PA. PA-NCs exhibited substantially improved cellular uptake as well as permeability on Calu-3 cells as compared to PA alone. FRET imaging analysis demonstrated that intact NCs could be internalized into Calu-3 cells.Moreover, PA-NCs conferred desirable protective effect against MPP+-induced SH-SY5Y cellular damage. Pharmacokinetic studies revealed a higher PA concentration in the brain following intranasal delivery of PA-NCs. In summary, the intranasal administration of PANCs is a promising treatment strategy for PD.展开更多
Bulk graphene nanofilms feature fast electronic and phonon transport in combination with strong light-matter interaction and thus have great potential for versatile applications,spanning from photonic,electronic,and o...Bulk graphene nanofilms feature fast electronic and phonon transport in combination with strong light-matter interaction and thus have great potential for versatile applications,spanning from photonic,electronic,and optoelectronic devices to charge-stripping and electromagnetic shielding,etc.However,large-area flexible close-stacked graphene nanofilms with a wide thickness range have yet to be reported.Here,we report a polyacrylonitrile-assisted’substrate replacement’strategy to fabricate large-area free-standing graphene oxide/polyacrylonitrile nanofilms(lateral size~20 cm).Linear polyacrylonitrile chains-derived nanochannels promote the escape of gases and enable macro-assembled graphene nanofilms(nMAGs)of 50-600 nm thickness following heat treatment at 3,000℃.The uniform nMAGs exhibit 802-1,540 cm^(2)V-1s-1carrier mobility,4.3-4.7 ps carrier lifetime,and>1,581 W m^(-1)K^(-1)thermal conductivity(n MAG-assembled 10μm-thick films,mMAGs).nMAGs are highly flexible and show no structure damage even after 1.0×10^(5)cycles of folding-unfolding.Furthermore,n MAGs broaden the detection region of graphene/silicon heterojunction from near-infrared to mid-infrared and demonstrate higher absolute electromagnetic interference(EMI)shielding effectiveness than state-of-the-art EMI materials of the same thickness.These results are expected to lead to the broad applications of such bulk nanofilms,especially as micro/nanoelectronic and optoelectronic platforms.展开更多
One-time application of mixed fertilizer formed by the compounding of two controlled-release nitrogen fertilizers(CRUs)with targeted N supply during the periods from transplantation(TS)to panicle initiation(PI)and fro...One-time application of mixed fertilizer formed by the compounding of two controlled-release nitrogen fertilizers(CRUs)with targeted N supply during the periods from transplantation(TS)to panicle initiation(PI)and from PI to heading(HS)is expected to synchronize the double-peak N demand of rice.However,its effects on the yield and N use efficiency(NUE)of labor-intensive double-cropping rice were unknown.Two targeted CRU(CRU_(A)and CRU_(B))were compounded in five ratios(CRU_(A):CRU_(B)=10:0,7:3,5:5,3:7,and 0:10)to form five mixed fertilizers(BBFs):BBF1-5.A field experiment was performed to investigate the characteristics of N supply in early and late seasons under different BBFs and their effects on N uptake,yield,and ammonia volatilization(AV)loss from paddy fields of double-cropping rice.Conventional high-yield fertilization(CK,three split applications of urea)and zero-N treatments were established as controls.The N supply dropped significantly with the increased compound ratio of CRU_(B)during the period from TS to PI,but increased during the period from PI to HS.With the exception of the period from TS to PI in the late rice season,the N uptake of early and late rice maintained close synchronicity with the N supply of BBFs during the double-peak periods.Excessive N supply(BBF1 and BBF2)in the late rice season during the period from TS to PI increased N loss by AV.The effect of BBF on grain yield increase varied widely between seasons,irrespective of year.Among the BBFs,the BBF2 treatment of early rice not only stabilized the spikelets per panicle but also ensured a high number of effective panicles by promoting N uptake during the period from TS to PI and a high grain-filling percentage by appropriately reducing the N supply at the later PI stage,resulting in the highest rice yield.While stabilizing the effective panicle number,the BBF4 treatment of late rice increased the number of spikelets per panicle by promoting N uptake during the period from PI to HS,resulting in the highest rice yield.The two-year average yield and apparent N recovery efficiency of the BBF2 treatment during the early rice season were 9.6 t ha 1 and 45.3%,while those of late rice in BBF4 were 9.6 t ha 1 and 43.0%,respectively.The yield and NUE indexes of BBF2 in early rice and BBF4 in late rice showed no significant difference from those of CK.The AVs of BBF2 during the early rice season and of BBF4 during the late rice season were 50.0%and 76.8%lower,respectively,than those of CK.BBF2 and BBF4 could effectively replace conventional urea split fertilization in early and late rice seasons,ensuring rice yield and NUE and reducing AV loss in paddy fields.展开更多
Objective:Natural extracts,including nobiletin,have been reported to enhance the efficacy and sensitivity of chemotherapeutic drugs.However,whether and how nobiletin affects tumor growth and progression in renal cell ...Objective:Natural extracts,including nobiletin,have been reported to enhance the efficacy and sensitivity of chemotherapeutic drugs.However,whether and how nobiletin affects tumor growth and progression in renal cell carcinoma(RCC)are still unclear.Methods:Cell proliferation,cell cycle and apoptosis analyses,colony-formation assays,immunoblotting analysis,and q RT-PCR analysis were performed to investigate how nobiletin affected RCC cell proliferation in vitro.The nude mouse model was used to test the efficacy of nobiletin alone or in combination with palbociclib.Results:Nobiletin inhibited cell proliferation by inducing G1 cell cycle arrest and cell apoptosis in RCC cells.Mechanistically,nobiletin decreased SKP2 protein expression by reducing its transcriptional level.The downregulated SKP2 caused accumulation of its substrates,p27 and p21,which further inhibited the activity of the G1 phase-related protein,CDK2,leading to inhibition of cell proliferation and tumor formation.A higher SKP2 protein level indicated less sensitivity to the CDK4/6 inhibitor,palbociclib.A combination of nobiletin and palbociclib showed a synergistic tumor inhibition in vitro and in an in vivo model.Conclusions:Nobiletin downregulated the SKP2-p21/p27-CDK2 axis to inhibit tumor progression and showed synergistic tumor inhibition effects with the CDK4/6 inhibitor,palbociclib,on RCC,which indicates a potential new therapeutic strategy.展开更多
基金supported by the National Natural Science Foundation of China,Nos.81901098(to TC),82201668(to HL)Fujian Provincial Health Technology Project,No.2021QNA072(to HL)。
文摘The central nervous system, information integration center of the body, is mainly composed of neurons and glial cells. The neuron is one of the most basic and important structural and functional units of the central nervous system, with sensory stimulation and excitation conduction functions. Astrocytes and microglia belong to the glial cell family, which is the main source of cytokines and represents the main defense system of the central nervous system. Nerve cells undergo neurotransmission or gliotransmission, which regulates neuronal activity via the ion channels, receptors, or transporters expressed on nerve cell membranes. Ion channels, composed of large transmembrane proteins, play crucial roles in maintaining nerve cell homeostasis. These channels are also important for control of the membrane potential and in the secretion of neurotransmitters. A variety of cellular functions and life activities, including functional regulation of the central nervous system, the generation and conduction of nerve excitation, the occurrence of receptor potential, heart pulsation, smooth muscle peristalsis, skeletal muscle contraction, and hormone secretion, are closely related to ion channels associated with passive transmembrane transport. Two types of ion channels in the central nervous system, potassium channels and calcium channels, are closely related to various neurological disorders, including Alzheimer's disease, Parkinson's disease, and epilepsy. Accordingly, various drugs that can affect these ion channels have been explored deeply to provide new directions for the treatment of these neurological disorders. In this review, we focus on the functions of potassium and calcium ion channels in different nerve cells and their involvement in neurological disorders such as Parkinson's disease, Alzheimer's disease, depression, epilepsy, autism, and rare disorders. We also describe several clinical drugs that target potassium or calcium channels in nerve cells and could be used to treat these disorders. We concluded that there are few clinical drugs that can improve the pathology these diseases by acting on potassium or calcium ions. Although a few novel ion-channelspecific modulators have been discovered, meaningful therapies have largely not yet been realized. The lack of target-specific drugs, their requirement to cross the blood–brain barrier, and their exact underlying mechanisms all need further attention. This review aims to explain the urgent problems that need research progress and provide comprehensive information aiming to arouse the research community's interest in the development of ion channel-targeting drugs and the identification of new therapeutic targets for that can increase the cure rate of nervous system diseases and reduce the occurrence of adverse reactions in other systems.
基金supported by the National Natural Science Foundation of China(82274134)the National Key R&D Plan(2017YFC1702200,2017YFC1702202)+1 种基金Key R&D Program Projects in Zhejiang Province(2020C04020)the Key Research and Development Program of Zhejiang Province(2025C02183).
文摘The aim of this study was to investigate the role of Dendrobium officinale crude polysaccharides(DOPS)and D.officinale purified polysaccharides(DOPS100)in attenuating immune dysfunction in subfertile mice.The results of the study revealed several noteworthy findings.First,DOPS and DOPS100 treatments led to significant improvement in weight gain and reversal of fatigue-related behaviors compared to the normal group.Second,both DOPS and DOPS100 showed effectiveness in reducing immune organ swelling,modulating immunoglobulin A(IgA)and immunoglobulin M(IgM)levels,and restoring complement(C3c and C4)levels.In addition,they demonstrated a significant ability to enhance the integrity of the intestinal mechanical barrier by differentially upregulating the tight junction proteins Occludin and Zonula occludens 1(ZO-1).In addition,it was found that DOPS100 specifically enhanced the CD4^(+)-T helper 17 cell(Th17)/regulatory T cell(Treg)immune axis in the gut,as evidenced by increased expression of forkhead box protein 3(Foxp3)as well as decreased expression of retinoic acid receptor-related orphan receptor γt(RORγt),and further modulation of interleukin 10(IL-10),interleukin 22(IL-22),and interleukin 17A(IL-17A)expression levels of inflammatory factors.These findings collectively suggest that DOPS100 holds significant potential in improving sub-healthy status by repairing the intestinal barrier,restoring local immune homeostasis,and activating the intestinal immune regulatory network.The study’s outcomes provide valuable insights into the therapeutic implications of DOPS and DOPS100 in addressing immune dysfunction in sub-healthy conditions.
基金supported by the National Natural Science Foundation of China(32270296)the Shenzhen Postdoctoral Scientific Research,China(77000-42100004)+1 种基金the Key Basic Research and Development Program of Hubei Province,China(2020BBA052)the Natural Science Foundation of Guangdong Province,China(2024A1515010498)and the Fundamental Research Funds for the Central Universities,Sun Yat-sen University,China.
文摘Sharp eyespot(Rhizoctonia cerealis)is a widespread soil-borne fungal disease that poses a severe threat to wheat health,and it is one of the main obstacles to achieving stable and high-quality wheat yields in China.Our collaborative team has developed a novel,efficient,and low-toxicity fungicide named Y17991(N-(2-(2,4-bis-(trifluoromethyl)phenoxy)phenyl)-3-(difluoromethyl)-1-methyl-1H-pyrazole-4-carboxamide).Preliminary laboratory tests confirmed the significant inhibitory effect of this agent on R.cerealis.Large-area field trials also demonstrated its efficacy,with a disease prevention index of 83.52%,which is 1.97%greater than that of the widely used thifluzamide,and it significantly increased the wheat yield.Moreover,this study explored the impacts of Y17991 on the structure and function of the microbial community in wheat rhizosphere soil.Bacterial communities were more strongly affected than fungal communities.Y17991 significantly modulated key amino acid metabolic pathways and certain biosynthetic processes in diseased wheat rhizospheres,and it also enhanced certain biosynthetic pathways and metabolic activities in healthy wheat rhizospheres.Additionally,the application of Y17991 regulated rhizosphere metabolites,thus exerting significant control over the microbial community.We identified 15 microbial strains potentially involved in the prevention and treatment of R.cerealis,and Y17991 treatment promoted the growth of Pedobacter and Bacillus strains.These strains not only aid in plant growth but they also have the potential for disease prevention.In summary,Y17991 application at a reasonable dose does not cause significant disruption to nontarget rhizosphere microbial communities.In future studies,we will continue to investigate the impacts of Y17991 on nonmicrobial components in soil ecosystems,such as protozoa and nematodes.Our research provides a theoretical basis for the scientific application and promotion of new fungicides and offers a significant reference for establishing a comprehensive system for assessing the ecological impact of pesticides on the environment.
基金supported by the National Key R&D Program of China(No.2024YFB3408700)the National Natural Science Foundation of China(Nos.12272129 and 12122206)+1 种基金the Natural Science Foundation of Hunan Province(Nos.2024JJ4004 and 2024JJ3003)the Postgraduate Scientific Research Innovation of Hunan Province(No.CX20240444)。
文摘Vibration energy harvesting presents a significant opportunity for powering wireless sensor networks and internet of things(IoT)devices,offering a sustainable alternative to traditional battery-based power sources.However,environmental vibrations are predominantly low-frequency,which presents a significant challenge to the efficient conversion of such energy.To address this challenge,this paper proposes a novel twodegree-of-freedom(2-DOF)energy harvester.The first layer of the harvester incorporates a piezoelectric composite beam(PCB)paired with permanent magnets to form a negative stiffness mechanism(NSM),which counteracts the stiffness of linear springs,thereby achieving quasi-zero stiffness(QZS)or bistable characteristics.The second layer integrates piezoelectric transduction units with triboelectric nanogenerator(TENG)units to further enhance the efficiency of low-frequency vibration energy conversion.By considering the modal characteristics of the PCB,this paper establishes the electromechanical coupling equations of the harvester from an energy perspective.The mechanical responses of the masses in both layers,as well as the electrical outputs of the PCB,are analytically solved.Furthermore,the effects of the system parameters on the efficiency of low-frequency vibration energy harvesting are thoroughly analyzed.This work provides a theoretical foundation for the development of self-powered IoT sensor nodes,enabling efficient energy harvesting from ambient low-frequency vibrations.
基金support from various sources including 2023 Basic Research Project of Colleges and Universities of Liaoning Provincial Department of Education(JYTZD2023137)Career Development Support Plan for Young and Middle-aged Teachers in Shenyang Pharmaceutical University(ZQN2021014)+2 种基金2024 Basic Scientific Research Funding Project of Liaoning Provincial Department of Education(LJ212410163051)Liaoning Province Science and Technology Plan Joint Plan(2024-MSLH-448)Liaoning Provincial Innovation Capacity Promotion Joint Fund(2022-NLTS-12-01).
文摘Ultra-performance liquid chromatography-mass spectrometry(UPLC-MS)technology was employed to analyze the chemical composition of three Clematidis Radix et Rhizoma sourced from different origins.Common characteristic components were identified through comprehensive literature review and the integration of fragment ion data.A rheumatoid arthritis(AA)model was induced in Sprague-Dawley(SD)rats using Freund’s complete adjuvant,and simultaneous administration of extracts from the three original plants of Clematidis Radix et Rhizoma,along with different doses of magnoflorine,was conducted to evaluate differences in therapeutic efficacy.A common characteristic component was identified,magnoflorine,present in Clematis chinensis Osbeck.Clematis hexapetala Pall.,and Clematis manshurica Rupr.Extracts from all three original plants,as well as each dose group of the Rhizomas of Clematis chinensis Osbeck.Clematis hexapetala Pall.,Clematis manshurica Rupr.,and magnoflorine,demonstrated efficacy in alleviating rheumatoid arthritis symptoms by enhancing cellular infiltration,reducing vascular opacification,and lowering serum levels of inflammatory factors.Magnoflorine has the potential to be used as a quality marker for the three original plants of Clematidis Radix et Rhizoma.Additionally,both the three original plants and magnoflorine exhibit therapeutic potential for rheumatoid arthritis,which provides a solid theoretical and experimental basis for the establishment of more scientifically grounded quality standards of Clematidis Radix et Rhizoma and promotes the rational utilization of medicinal resources.
基金supported by the National Natural Science Foundation of China(No.52204393)the Ningbo International Science and Technology Cooperation Program,China(No.2023H004).
文摘The effects of direct aging(DA)on the microstructure and mechanical properties of TiB_(2)/AlSi7Mg alloys fabricated via laser powder bed fusion(LPBF)were systematically investigated.DA significantly improves strength while maintaining satisfactory ductility.Optimal performance is obtained through under-aging(UA)at 150℃ for 4 h,resulting in a yield strength of 361 MPa,tensile strength of 503 MPa,and elongation of 9.1%in the horizontal direction.DA does not substantially alter the grain size or cellular structure but pro-motes the formation of nanoprecipitates within theα-Al matrix.Specifically,UA induces dot-like and needle-like Si precipitates,whereas over-aging(OA)additionally generates short rod-likeβ'-Mg_(1.8)Si phases.The strengthening mechanism is attributed to the Hall-Petch ef-fect associated with grain and cell boundaries,and the Orowan mechanism induced by nanoprecipitates.Work-hardening behavior is gov-erned by interactions between dislocations and nanoprecipitates.The OA sample exhibits rapid saturation of work hardening due to a high initial hardening rate and dynamic recovery of dislocations,resulting in limited uniform elongation.In contrast,the UA sample demon-strates a more balanced work hardening response.These findings provide theoretical and experimental validation of DA as an effective post-processing approach aimed at enhancing the performance of LPBF Al-Si-Mg alloys in engineering applications.
基金supported by the National Natural Science Foundation of China(31600139)the Chongqing Science and Technology Bureau(cstc2016jcyjA0020+3 种基金CSTB2024NSCQ-KJFZMSX0067)the Yuzhong District Science and Technology Commission(20190123)the Chongqing Municipal Education Commission(KJQN202300415)the Project of Undergraduates Innovating Experiment,and the Project of Tutorial System of Excellent Medical Undergraduates in the Lab Teaching and Management Center of Chongqing Medical University(S202410631068,LTMCMTS202458,LTMCMTS202459,LTMCMTS202460 and LTMCMTS202461).
文摘Enterovirus D68(EV-D68)and enterovirus A71(EV-A71)are two major types of enteroviruses that pose emerging challenges to public health and have the potential to cause outbreaks,yet their pathogenic mechanisms remain largely unexplored.Arrestin domain containing 3(ARRDC3)is a vital regulator of glucose metabolism,cancer development,and inflammation.Whether ARRDC3 contributes to innate antiviral immunity is undefined.Here,we found that enterovirus infection induces ARRDC3 expression at both the mRNA and protein levels,thereby inhibiting enterovirus replication.Moreover,we demonstrate that the expression of Yes-associated protein(YAP),a key effector of the Hippo pathway,is severely downregulated by ARRDC3 via lysosomal pathway.YAP facilitates enterovirus replication by suppressing the interferon pathway during the later stage of enterovirus infection,independent of its transcriptional activity.Finally,the ARRDC3-YAP pathway exhibits a broad-spectrum antiviral effect in various viral infections,including those caused by human parainfluenza virus type 3(HPIV3)and vesicular stomatitis virus(VSV).Collectively,our results identify the critical role of ARRDC3 and its negative regulatory effect on YAP in the innate antiviral response,suggesting a novel therapeutic strategy against virus infection.
基金Project supported by the Postdoctoral Fellowship Program of China Postdoctoral Science Foundation(Grant No.GZC20231050)the National Natural Science Foundation of China(Grant Nos.12175193 and 11905183)the 13th Five-year plan for Education Science Funding of Guangdong Province(Grant No.2021GXJK349)。
文摘For non-stationary complex dynamic systems,a standardized algorithm is developed to compute time correlation functions,addressing the limitations of traditional methods reliant on the stationary assumption.The proposed algorithm integrates two-point and multi-point time correlation functions into a unified framework.Further,it is verified by a practical application in complex financial systems,demonstrating its potential in various complex dynamic systems.
文摘It is common for datasets to contain both categorical and continuous variables. However, many feature screening methods designed for high-dimensional classification assume that the variables are continuous. This limits the applicability of existing methods in handling this complex scenario. To address this issue, we propose a model-free feature screening approach for ultra-high-dimensional multi-classification that can handle both categorical and continuous variables. Our proposed feature screening method utilizes the Maximal Information Coefficient to assess the predictive power of the variables. By satisfying certain regularity conditions, we have proven that our screening procedure possesses the sure screening property and ranking consistency properties. To validate the effectiveness of our approach, we conduct simulation studies and provide real data analysis examples to demonstrate its performance in finite samples. In summary, our proposed method offers a solution for effectively screening features in ultra-high-dimensional datasets with a mixture of categorical and continuous covariates.
基金Supported by the National Natural Science Foundation of China(NSFC)(21002092,21272215)by the Open Project of State Key Laboratoryof Pharmaceutical Biotechnology in Nanjing University(KF-GN-201411)
基金the National Key Research and Development Program of China (2016YFD0300507,2016YFD0300108)the National Natural Science Foundation of China (31671630,31671638,31501264)the China Agriculture Research System (CARS-01)
文摘Compared to drought-susceptible rice cultivars(DSRs),drought-resistance rice cultivars(DRRs)could drastically reduce the amount of irrigation water input and simultaneously result in higher grain yield under water-saving irrigation conditions.However,the mechanisms underlying these properties are unclear.We investigated how improved agronomic traits contribute to higher yield and higher water use efficiency(WUE)in DRRs than in DSRs under alternate wetting and drying(AWD).Two DRRs and two DSRs were field-grown in 2015 and 2016 using two different irrigation regimes:continuous flooding(CF)and AWD.Under CF,no statistical differences in grain yield and WUE were observed between DRRs and DSRs.Irrigation water under the AWD regime was 275–349 mm,an amount 49.8%–56.2% of that(552–620 mm)applied under the CF regime.Compared to CF,AWD significantly decreased grain yield in both DRRs and DSRs,with a more significant reduction in DSRs,and WUE was increased in DRRs,but not in DSRs,by 9.9%–23.0% under AWD.Under AWD,DRRs showed a 20.2%–26.2% increase in grain yield and an 18.6%–24.5% increase in WUE compared to DSRs.Compared to DSRs,DRRs showed less redundant vegetative growth,greater sink capacity,higher grain filling efficiency,larger root biomass,and deeper root distribution under AWD.We conclude that these improved agronomic traits exert positive influences on WUE in DRRs under AWD.
基金the Guangdong Provincial Natural Science Foundation of China(2018A030310623)the Guangdong Provincial Medical Scientific Research Foundation of China(A2019027)the Guangzhou Science Technology and Innovation Commission Technology Research Projects(201805010005)。
文摘Paeoniflorin(PA) is an anti-Parkinson Chinese medicine with inferior bioavailability and difficulty in delivery to the brain. This research is to develop an efficacious PA nanocrystal formulation(PA-NCs) that is suitable for intranasal administration to treat Parkinson’s disease(PD). PA-NCs were fabricated through an antisolvent precipitation method using TPGS as the stabilizer. The rod-shaped PA-NCs had particle size of 139.6 ± 1.3 nm and zeta potential of-23.2 ± 0.529 mV. A molecular dynamics simulation indicated that van der Waals forces are the primary drivers of interactions between PA and TPGS. In the ex vivo nasal mucosa permeation assay, the cumulative drug release at 24 h was 87.14% ± 5.34%,which was significantly higher than that of free PA. PA-NCs exhibited substantially improved cellular uptake as well as permeability on Calu-3 cells as compared to PA alone. FRET imaging analysis demonstrated that intact NCs could be internalized into Calu-3 cells.Moreover, PA-NCs conferred desirable protective effect against MPP+-induced SH-SY5Y cellular damage. Pharmacokinetic studies revealed a higher PA concentration in the brain following intranasal delivery of PA-NCs. In summary, the intranasal administration of PANCs is a promising treatment strategy for PD.
基金supported by the National Natural Science Foundation of China(No.52090030)the China Postdoctoral Science Foundation(2022T150558,2020M681819)+1 种基金the Fundamental Research Funds for the Central Universities(No.2021FZZX001-17)the Postdoctoral Research Program of Zhejiang Province(ZJ2021145).
文摘Bulk graphene nanofilms feature fast electronic and phonon transport in combination with strong light-matter interaction and thus have great potential for versatile applications,spanning from photonic,electronic,and optoelectronic devices to charge-stripping and electromagnetic shielding,etc.However,large-area flexible close-stacked graphene nanofilms with a wide thickness range have yet to be reported.Here,we report a polyacrylonitrile-assisted’substrate replacement’strategy to fabricate large-area free-standing graphene oxide/polyacrylonitrile nanofilms(lateral size~20 cm).Linear polyacrylonitrile chains-derived nanochannels promote the escape of gases and enable macro-assembled graphene nanofilms(nMAGs)of 50-600 nm thickness following heat treatment at 3,000℃.The uniform nMAGs exhibit 802-1,540 cm^(2)V-1s-1carrier mobility,4.3-4.7 ps carrier lifetime,and>1,581 W m^(-1)K^(-1)thermal conductivity(n MAG-assembled 10μm-thick films,mMAGs).nMAGs are highly flexible and show no structure damage even after 1.0×10^(5)cycles of folding-unfolding.Furthermore,n MAGs broaden the detection region of graphene/silicon heterojunction from near-infrared to mid-infrared and demonstrate higher absolute electromagnetic interference(EMI)shielding effectiveness than state-of-the-art EMI materials of the same thickness.These results are expected to lead to the broad applications of such bulk nanofilms,especially as micro/nanoelectronic and optoelectronic platforms.
基金provided by the National Key Research and Development Program of China(2018YFD0300904)Anhui Natural Science Foundation(2008085QC119)Key Fund Project of Anhui Department of Education(KJ2019A0176).
文摘One-time application of mixed fertilizer formed by the compounding of two controlled-release nitrogen fertilizers(CRUs)with targeted N supply during the periods from transplantation(TS)to panicle initiation(PI)and from PI to heading(HS)is expected to synchronize the double-peak N demand of rice.However,its effects on the yield and N use efficiency(NUE)of labor-intensive double-cropping rice were unknown.Two targeted CRU(CRU_(A)and CRU_(B))were compounded in five ratios(CRU_(A):CRU_(B)=10:0,7:3,5:5,3:7,and 0:10)to form five mixed fertilizers(BBFs):BBF1-5.A field experiment was performed to investigate the characteristics of N supply in early and late seasons under different BBFs and their effects on N uptake,yield,and ammonia volatilization(AV)loss from paddy fields of double-cropping rice.Conventional high-yield fertilization(CK,three split applications of urea)and zero-N treatments were established as controls.The N supply dropped significantly with the increased compound ratio of CRU_(B)during the period from TS to PI,but increased during the period from PI to HS.With the exception of the period from TS to PI in the late rice season,the N uptake of early and late rice maintained close synchronicity with the N supply of BBFs during the double-peak periods.Excessive N supply(BBF1 and BBF2)in the late rice season during the period from TS to PI increased N loss by AV.The effect of BBF on grain yield increase varied widely between seasons,irrespective of year.Among the BBFs,the BBF2 treatment of early rice not only stabilized the spikelets per panicle but also ensured a high number of effective panicles by promoting N uptake during the period from TS to PI and a high grain-filling percentage by appropriately reducing the N supply at the later PI stage,resulting in the highest rice yield.While stabilizing the effective panicle number,the BBF4 treatment of late rice increased the number of spikelets per panicle by promoting N uptake during the period from PI to HS,resulting in the highest rice yield.The two-year average yield and apparent N recovery efficiency of the BBF2 treatment during the early rice season were 9.6 t ha 1 and 45.3%,while those of late rice in BBF4 were 9.6 t ha 1 and 43.0%,respectively.The yield and NUE indexes of BBF2 in early rice and BBF4 in late rice showed no significant difference from those of CK.The AVs of BBF2 during the early rice season and of BBF4 during the late rice season were 50.0%and 76.8%lower,respectively,than those of CK.BBF2 and BBF4 could effectively replace conventional urea split fertilization in early and late rice seasons,ensuring rice yield and NUE and reducing AV loss in paddy fields.
基金supported by the National Natural Science Foundation of China(Grant Nos.81772702 and 81502214)。
文摘Objective:Natural extracts,including nobiletin,have been reported to enhance the efficacy and sensitivity of chemotherapeutic drugs.However,whether and how nobiletin affects tumor growth and progression in renal cell carcinoma(RCC)are still unclear.Methods:Cell proliferation,cell cycle and apoptosis analyses,colony-formation assays,immunoblotting analysis,and q RT-PCR analysis were performed to investigate how nobiletin affected RCC cell proliferation in vitro.The nude mouse model was used to test the efficacy of nobiletin alone or in combination with palbociclib.Results:Nobiletin inhibited cell proliferation by inducing G1 cell cycle arrest and cell apoptosis in RCC cells.Mechanistically,nobiletin decreased SKP2 protein expression by reducing its transcriptional level.The downregulated SKP2 caused accumulation of its substrates,p27 and p21,which further inhibited the activity of the G1 phase-related protein,CDK2,leading to inhibition of cell proliferation and tumor formation.A higher SKP2 protein level indicated less sensitivity to the CDK4/6 inhibitor,palbociclib.A combination of nobiletin and palbociclib showed a synergistic tumor inhibition in vitro and in an in vivo model.Conclusions:Nobiletin downregulated the SKP2-p21/p27-CDK2 axis to inhibit tumor progression and showed synergistic tumor inhibition effects with the CDK4/6 inhibitor,palbociclib,on RCC,which indicates a potential new therapeutic strategy.
