Methane(CH_(4))as a substitute for other mineral fuels plays a crucial role in reducing energy consumption and preventing environmental pollution.The present study employs a solvothermal method to fabricate a porous f...Methane(CH_(4))as a substitute for other mineral fuels plays a crucial role in reducing energy consumption and preventing environmental pollution.The present study employs a solvothermal method to fabricate a porous framework Co-metal-organic framework(Co-MOF)containing two distinct secondary building units(SBUs):an anionic[Co_(2)(μ_(2)-OH)(COO)_(4)(H_(2)O)]and a neutral[CoN_(2)(COO)_(2)].Notably,within the anionic SBUs,the coordinated water molecules induce the generation of divergent unsaturated Co(Ⅱ)centers in the unidirectional porous channels,thereby creating open metal sites.The adsorption performance of Co-MOF towards pure component gases was systematically investigated.The results demonstrated that Co-MOF exhibits superior adsorption capacity for C_(2)-C_(3) hydrocarbons compared to CH_(4),which offers the potential for efficient adsorption and separation of CH_(4) from C_(2)-C_(3) hydrocarbons.The gas selectivity separation ratios of Co-MOF for C_(2)H_(6)/CH_(4) and C_(3)H_8/CH_(4) were calculated using the ideal adsorbed solution theory method at 273/298 K and 0.1 MPa.The results revealed that Co-MOF achieved remarkable equilibrium separation selectivity for CH_(4) and C_(2)-C_(3) hydrocarbon gases among non-modified MOFs,signifying the potential of the synthesized Co-MOF for efficient recovery and purification of CH_(4) from C_(2)-C_(3) hydrocarbons.Breakthrough experiments further demonstrate the ability of Co-MOF to purify methane from C_(2)-C_(3) hydrocarbons in practical gas separation scenarios.Additionally,molecular simulation calculations further substantiate the propensity of anionic SBUs to interact with C_(2)-C_(3) hydrocarbon compounds.This study provides a novel paradigm for the development of porous MOF materials in the application of gas mixture separation.展开更多
Objective In kinesin-3,the neck coil correlates with the following segments to form an extended neck that contains a characteristic hinge diverse from a proline in KIF13B to a long flexible linker in KIF1A.The functio...Objective In kinesin-3,the neck coil correlates with the following segments to form an extended neck that contains a characteristic hinge diverse from a proline in KIF13B to a long flexible linker in KIF1A.The function of this neck hinge for controlling processive movement,however,remains unclear.Methods We made a series of modifications to the neck hinges of KIF13B and KIF1A and tested their movement using a single-molecule motility assay.Results In KIF13B,the insertion of flexible residues before or after the proline differentially impacts the processivity or velocity,while the removal of this proline increases the both.In KIF1A,the deletion of entire flexible neck hinge merely enhances the processivity.The engineering of these hinge-truncated necks of kinesin-3 into kinesin-1 similarly boosts the processive movement of kinesin-1.Conclusion The neck hinge in kinesin-3 controls its processive movement and proper modifications tune the motor motility,which provides a novel strategy to reshape the processive movement of kinesin motors.展开更多
FL-Online(http://fanlab.ac.cn) is an out-of-box modern web service featuring a user-friendly interface and simplified parameters, providing academic users with access to a series of online programs for biomolecular cr...FL-Online(http://fanlab.ac.cn) is an out-of-box modern web service featuring a user-friendly interface and simplified parameters, providing academic users with access to a series of online programs for biomolecular crystallography, including SAPI-online, OASIS-online, C-IPCAS-online and a series of upcoming software releases. Meanwhile, it is a highly scalable and maintainable web application framework that provides a powerful and flexible solution for academic web development needs. All the codes are open-source under MIT licenses in GitHub.展开更多
Positional information encoded in spatial concentration patterns is crucial for the development of multicellular organisms.However,it is still unclear how such information is affected by the physically dissipative dif...Positional information encoded in spatial concentration patterns is crucial for the development of multicellular organisms.However,it is still unclear how such information is affected by the physically dissipative diffusion process.Here we study one-dimensional patterning systems with analytical derivation and numerical simulations.We find that the diffusion constant of the patterning molecules exhibits a nonmonotonic effect on the readout of the positional information from the concentration patterns.Specifically,there exists an optimal diffusion constant that maximizes the positional information.Moreover,we find that the energy dissipation due to the physical diffusion imposes a fundamental upper limit on the positional information.展开更多
Cancer treatment is a multifaceted challenge,and therapeutic vaccines have emerged as a promising approach.The micellar preparation efficiently encapsulates antigen polypeptides and enhances antigen presentation throu...Cancer treatment is a multifaceted challenge,and therapeutic vaccines have emerged as a promising approach.The micellar preparation efficiently encapsulates antigen polypeptides and enhances antigen presentation through the major histocompatibility class I pathway,promoting cytotoxic T lymphocyte immune responses.Moreover,it enables codelivery of both antigen and adjuvant to the same target antigen-presenting cells.Combining themicellar vaccine with traditional cancer treatments(such as chemotherapy,radiotherapy,and surgery)has demonstrated improved efficacy in murine tumor models.Overall,the polyethylene glycol-phosphatidylethanolamine micelle-based vaccine presents a promising platformfor cancer therapeutic vaccines.By leveraging the strengths of various treatmentmodalities,this innovative vaccine approach holds the potential to revolutionize cancer therapy and bring new possibilities for cancer patients.展开更多
Cladocera are filter feeders abundant in freshwaters,which consume phytoplankton particles in wide size and taxonomic ranges.The ability of cladocerans to control phytoplankton abundance by grazing is determined by va...Cladocera are filter feeders abundant in freshwaters,which consume phytoplankton particles in wide size and taxonomic ranges.The ability of cladocerans to control phytoplankton abundance by grazing is determined by various factors including the characteristics of phytoplankton.Freshwater salinization may reduce the strength of top-down grazing control of phytoplankton because of the detrimental effects of salinity on the grazing intensity of zooplankters.We performed grazing experiments with two species of Cladocera of different body lengths to test their ability to graze on phytoplankton in natural waters differing in salinity and size and taxonomic composition of food particles.Grazing experiments demonstrated that the grazing rate was mostly controlled by the abundance of phytoplankton in the medium.The grazing rate was reduced at salinity ca.above 3 g/L of NaCl in the medium.The lower grazing rate was observed in the medium with larger phytoplankton particles.Both species predominantly consumed phytoplankton particles with a diameter of 6-12μm,which may shift the size distribution of phytoplankton towards a larger average diameter of particles.The taxon-specific feeding was also observed,as both species predominantly consumed diatom algae.Thus,we found that because of grazing,the size and taxonomic characteristics of phytoplankton are shifted towards a less edible community.The detrimental effect of elevated salinity on grazing rate supports growing concern about freshwater salinization negatively affecting water quality,particularly reducing top-down grazing control of phytoplankton.展开更多
The long-term data(1996-2021)on the summer abundances of the dominant zooplankton species(copepod Arctodiaptomus salinus(Daday,1885),rotifers Brachionus plicatilis(Müller,1786)and Hexarthra sp.)in saline Lake Shi...The long-term data(1996-2021)on the summer abundances of the dominant zooplankton species(copepod Arctodiaptomus salinus(Daday,1885),rotifers Brachionus plicatilis(Müller,1786)and Hexarthra sp.)in saline Lake Shira were used to analyze the response of zooplankton to air temperature and a change in the circulation regime of the lake:breakdown and reestablishment of meromixis.All groups of zooplankton responded to prolonged summer elevated temperatures by increasing their abundance.During the breakdown of the stable stratification of Lake Shira(2015-2016),zooplankton abundance increased on average by a factor of two and amounted to 9×10^(5)inds./m^(2)in the water column for copepods.That increase coincided with similar responses of other components of the lake’s mixolimnion ecosystem,whose biomasses increased approximately two-fold during that period.After the reestablishment of the meromixis,the abundance of zooplankton decreased to previous values.Thus,the abundance of zooplankton is largely determined by weather(the effect of temperature)and ecological factors(mixing regime).展开更多
Microtubule catalyzes the mechanochemical cycle of kinesin,a kind of molecular motor,through its crucial roles in kinesin's gating,ATPase and force-generation process.These functions of microtubule are realized th...Microtubule catalyzes the mechanochemical cycle of kinesin,a kind of molecular motor,through its crucial roles in kinesin's gating,ATPase and force-generation process.These functions of microtubule are realized through the kinesin-microtubule interaction.The binding site of kinesin on the microtubule surface is fixed.For most of the kinesin-family members,the binding site on microtubule is in the groove betweenα-tubulin andβ-tubulin in a protofilament.The mechanism of kinesin searching for the appropriate binding site on microtubule is still unclear.Using the molecular dynamics simulation method,we investigate the interactions between kinesin-1 and the different binding positions on microtubule.The key non-bonded interactions between the motor domain and tubulins in kinesin's different nucleotide-binding states are listed.The differences of the amino-acid sequences betweenα-andβ-tubulins make kinesin-1 binding to theα–βgroove much more favorable than to theβ–αgroove.From these results,a two-step mechanism of kinesin-1 to discriminate the correct binding site on microtubule is proposed.Most of the kinesin-family members have the conserved motor domain and bind to the same site on microtubule,the mechanism may also be shared by other family members of kinesin.展开更多
Breast cancer is a malignant disease that seriously threatens women's health.Studying the mechanism of cancer occurrence and development is an urgent problem to be solved.In this paper,the eigen-microstate method ...Breast cancer is a malignant disease that seriously threatens women's health.Studying the mechanism of cancer occurrence and development is an urgent problem to be solved.In this paper,the eigen-microstate method was used to study conversion of normal breast cells into breast cancer cells and the reason.The main conclusions are as follows:the microstates of normal breast cell and breast cancer cell are different.There is a state conversion when a normal breast cell transforms into a breast cancer cell.The main reason for this state conversion is the combined effect of tumor suppressor genes and oncogenes.By analyzing the function of key genes,it was found that these genes do play an important role in the development of breast cancer.The findings contribute to understanding the mechanism by which breast cancer occurs and progresses,and key genes can serve as potential biomarkers or target genes for breast cancer treatment.展开更多
The human serotonin transporter(SERT)terminates neurotransmission by removing serotonin from the synaptic cleft,which is an essential process that plays an important role in depression.In addition to natural substrate...The human serotonin transporter(SERT)terminates neurotransmission by removing serotonin from the synaptic cleft,which is an essential process that plays an important role in depression.In addition to natural substrate serotonin,SERT is also the target of the abused drug cocaine and,clinically used antidepressants,escitalopram,and paroxetine.To date,few studies have attempted to investigate the unbinding mechanism underlying the orthosteric and allosteric modulation of SERT.In this article,the conserved property of the orthosteric and allosteric sites(S1 and S2)of SERT was revealed by combining the high resolutions of x-ray crystal structures and molecular dynamics(MD)simulations.The residues Tyr95 and Ser438 located within the S1 site,and Arg104 located within the S2 site in SERT illustrate conserved interactions(hydrogen bonds and hydrophobic interactions),as responses to selective serotonin reuptake inhibitors.Van der Waals interactions were keys to designing effective drugs inhibiting SERT and further,electrostatic interactions highlighted escitalopram as a potent antidepressant.We found that cocaine,escitalopram,and paroxetine,whether the S1 site or the S2 site,were more competitive.According to this potential of mean force(PMF)simulations,the new insights reveal the principles of competitive inhibitors that lengths of trails from central SERT to an opening were~18A for serotonin and~22 A for the above-mentioned three drugs.Furthermore,the distance between the natural substrate serotonin and cocaine(or escitalopram)at the allosteric site was~3A.Thus,it can be inferred that the potent antidepressants tended to bind at deeper positions of the S1 or the S2 site of SERT in comparison to the substrate.Continuing exploring the processes of unbinding four ligands against the two target pockets of SERT,this study observed a broad pathway in which serotonin,cocaine,escitalopram(at the S1 site),and paroxetine all were pulled out to an opening between MT1b and MT6a,which may be helpful to understand the dissociation mechanism of antidepressants.展开更多
The degradation of titin could make the myofibrillar fragmentation to improve meat tenderization during postmortem.This study aimed to investigate effect of phosphorylation on titin degradation.Protein kinase A(PKA)an...The degradation of titin could make the myofibrillar fragmentation to improve meat tenderization during postmortem.This study aimed to investigate effect of phosphorylation on titin degradation.Protein kinase A(PKA)and alkaline phosphatase(AP)were added to crude titin extracted from ovine longissimus lumborum(LL)muscles.Phosphorylated/dephosphorylated titin were incubated withμ-calpain at 4℃ for 2 days.Results showed titin in AP group started degradation earlier than that in PKA and control groups.There were 20,16 and 12 phosphorylated sites identified by iTRAQ in the PKA,control and AP group,respectively.3D structure of dephosphorylated titin fragment was simulated and its molecular dynamics trajectory analysis was performed using Discovery StudioTM.The dihedral angle in AP group was less and the dephosphorylated fragment had a higher kinetic energy and total energy.We suggested that changes caused by AP treatment might make titin unstable,which easily degraded byμ-calpain.展开更多
Saline lakes are widespread on all continents.Since 1979,an informal international association of salt lake researchers from a variety of disciplines has sponsored a series of triennial conferences to foster scientifi...Saline lakes are widespread on all continents.Since 1979,an informal international association of salt lake researchers from a variety of disciplines has sponsored a series of triennial conferences to foster scientific exchange and our understanding of saline lakes.International Society for Salt Lake Research(ISSLR,www.isslr.org)was founded in 1994 to establish effective liaison between persons interested in any aspect of inland saline waters,to encourage these interests,and to educate the public in the scientific use,management,and conservation of salt lakes.ISSLR conferences are held triennially.The conferences are usually hosted by a local University or research institution and provide an excellent opportunity for networking among globally dispe rsed researchers.展开更多
In higher eukaryotes,DNA replication ensures precise transmission of genetic information from parental DNA to progeny,and the correct selection of replication origins is a critical step in this process.A very recent s...In higher eukaryotes,DNA replication ensures precise transmission of genetic information from parental DNA to progeny,and the correct selection of replication origins is a critical step in this process.A very recent study has shown that nucleosomes containing histone variant H2A.Z recruit SUV420H1,a histone H4 lysine 20 specific methyltransferase.Moreover,SUV420H1 promotes the H4K20 dimethylation,which can recruit the origin recognition complex to fulfill the selection and licensing of the replication origins.展开更多
Pathogens have developed an extensive array of proteins during the co-evolutionary arms race with their hosts.This is particularly true for Phytophthora,a genus that causes significant damage to agriculture and forest...Pathogens have developed an extensive array of proteins during the co-evolutionary arms race with their hosts.This is particularly true for Phytophthora,a genus that causes significant damage to agriculture and forestry.One well-known species,Phytophthora infestans,caused the devastating late blight pandemic during the Irish potato famine.Each Phytophthora species encodes hundreds of effector proteins that play essential roles in manipulating host cellular processes and promoting disease development.展开更多
Developing high-performance aqueous Zn-ion batteries from sustainable biomass becomes increasingly vital for large-scale energy storage in the foreseeable future.Therefore,γ-MnO_(2) uniformly loaded on N-doped carbon...Developing high-performance aqueous Zn-ion batteries from sustainable biomass becomes increasingly vital for large-scale energy storage in the foreseeable future.Therefore,γ-MnO_(2) uniformly loaded on N-doped carbon derived from grapefruit peel is successfully fabricated in this work,and particularly the composite cathode with carbon carrier quality percentage of 20 wt%delivers the specific capacity of 391.2 mAh g^(−1)at 0.1 A g^(−1),outstanding cyclic stability of 92.17%after 3000 cycles at 5 A g^(−1),and remarkable energy density of 553.12 Wh kg^(−1) together with superior coulombic efficiency of~100%.Additionally,the cathodic biosafety is further explored specifically through in vitro cell toxicity experiments,which verifies its tremendous potential in the application of clinical medicine.Besides,Zinc ion energy storage mechanism of the cathode is mainly discussed from the aspects of Jahn–Teller effect and Mn domains distribution combined with theoretical analysis and experimental data.Thus,a novel perspective of the conversion from biomass waste to biocompatible Mn-based cathode is successfully developed.展开更多
Optical-neural stimulation,which encompasses cutting-edge techniques such as optogenetics and infrared neurostimulation,employs distinct mechanisms to modulate brain function and behavior.These advanced neuromodulatio...Optical-neural stimulation,which encompasses cutting-edge techniques such as optogenetics and infrared neurostimulation,employs distinct mechanisms to modulate brain function and behavior.These advanced neuromodulation techniques offer accurate manipulation of targeted areas,even selectively modulating specific neurons,in the brain.This makes it possible to investigate the cause-and-effect connections between neural activity and behavior,allowing for a better comprehension of the intricate brain dynamics towards complex environments.Non-human primates serve as an essential animal model for investigating these complex functions in brain research,bridging the gap between the basic research and clinical applications.One of the earliest optical studies utilizing optogenetic neuromodulation in monkeys was conducted in 2009.Since then,the optical-neural stimulations have been effectively applied in non-human primates.This review summarises recent research that employed optogenetics or infrared neurostimulation techniques to regulate brain function and behavior in non-human primates.The current state of optical-neural stimulations discussed here demonstrates their efficacy in advancing the understanding of brain systems.Nevertheless,there are still challenges that need to be addressed before they can fully achieve their potential.展开更多
Cardiovascular diseases are a group of disorders of the heart and blood vessels,primarily including coronary heart disease,stroke,and other diseases.It is the world’s leading cause of death,and its incidence is incre...Cardiovascular diseases are a group of disorders of the heart and blood vessels,primarily including coronary heart disease,stroke,and other diseases.It is the world’s leading cause of death,and its incidence is increasing yearly.Hypertension is a major risk factor for cardiovascular disease.Wnt signaling comprises a series of highly conservative cascading events controlling fundamental biological processes.Wnt signaling pathways include the canonical Wnt pathway(or Wnt/β-catenin pathway),the non canonical planar cell-polarity pathway,and the non-canonical calcium-dependent pathways.Abnormal Wnt signaling promotes cell proliferation and differentiation,cardiac malformations,various malignancies,so drugs targeting Wnt signaling play a great therapeutic potential.Wnt/β-catenin pathway is involved in the occurrence and development of cardiovascular diseases such as atherosclerosis and stroke by regulating cell proliferation,migration,apoptosis,blood-brain barrier permeability,inflammation,oxidative stress,and immune response.Based on the latest research progress,this review summarizes the role of Wnt/β-catenin signaling in cardiovascular diseases,in order to provide new ideas for the prevention and treatment of cardiovascular diseases.展开更多
Head and neck squamous cell carcinoma (HNSCC) is a prevalent and lethal solid tumor with a high mortality rate. Conventional cancertreatments, including surgery, radiotherapy, and chemotherapy, primarily target cancer...Head and neck squamous cell carcinoma (HNSCC) is a prevalent and lethal solid tumor with a high mortality rate. Conventional cancertreatments, including surgery, radiotherapy, and chemotherapy, primarily target cancer cell eradication. However, uncontrolled proliferation and metabolic activities of these cells result in abnormalities in nutrient levels, hypoxia, and immunosuppression within the tumor microenvironment (TME). These factors constrain the efficacy of traditional treatments by promoting drug resistance, recurrence, and metastasis. Nanomaterials (NMs), such as nanozymes, can exhibit enzymatic activity similar to that of natural enzymes and offer a promising avenuefor the direct modification of the TME through catalytic oxidation-reduction processes. Moreover, they can serve as sensitizers or drug deliverycarriers, enhancing the efficacy of traditional treatment methods. Recently, NMs have garnered significant attention from oncologists. Thisreview begins with an overview of the composition and unique characteristics of the TME. Subsequently, we comprehensively exploredthe application of NMs in the treatment of HNSCC. Finally, we discuss the potential prospects and challenges associated with usingNMs in biomedical research.展开更多
The team of Dr.LI Dong from the Institute of Biophysics(IBP)of the Chinese Academy of Sciences,in collaboration with the team of Dr.DAI Qionghai from the Department of Automation at Tsinghua University,published a res...The team of Dr.LI Dong from the Institute of Biophysics(IBP)of the Chinese Academy of Sciences,in collaboration with the team of Dr.DAI Qionghai from the Department of Automation at Tsinghua University,published a research paper in Nature Communications on May 16.Based on the noise model of microscopic images and zero-sample learning theory,they proposed the zero-shot deconvolution networks(ZS-DeconvNet)and developed the corresponding one-click microscopic image processing software.展开更多
Our previous study has demonstrated that CD 146 molecule is a biomarker on vascular endothelium, which is involved in angiogenesis and tumor growth. However the mechanism behind is not clear. Here we have for the firs...Our previous study has demonstrated that CD 146 molecule is a biomarker on vascular endothelium, which is involved in angiogenesis and tumor growth. However the mechanism behind is not clear. Here we have for the first time developed a novel CD146 blockade system using CD146 siRNA to study its function on endothelial cells. Our data showed that CD146 siRNA specifically blocked the expression of CD146 on both mRNA and protein levels, leading to the significant suppression of HUVEC proliferation, adhesion and migration. These results demonstrate that CD146 plays a key role in vascular endothelial cell activity and angiogenesis, and CD146 siRNA can be used as a new inhibitor for anti-angiogenesis therapy.展开更多
基金supported by the National Natural Science Foundation of China(21401099)the Natural Science Foundation of Shanxi Province(202203021212331)+3 种基金Science and Technology Innovation Project of Colleges and Universities of Shanxi Province(2022L532)the National Natural Science Foundation of Anhui Province(2008085MB32 and KJ2021ZD0073)Natural Science Foundation of Shandong Province(ZR2021QB159)supported by the Talent Program Foundation of Dezhou University(2021xjrc102)。
文摘Methane(CH_(4))as a substitute for other mineral fuels plays a crucial role in reducing energy consumption and preventing environmental pollution.The present study employs a solvothermal method to fabricate a porous framework Co-metal-organic framework(Co-MOF)containing two distinct secondary building units(SBUs):an anionic[Co_(2)(μ_(2)-OH)(COO)_(4)(H_(2)O)]and a neutral[CoN_(2)(COO)_(2)].Notably,within the anionic SBUs,the coordinated water molecules induce the generation of divergent unsaturated Co(Ⅱ)centers in the unidirectional porous channels,thereby creating open metal sites.The adsorption performance of Co-MOF towards pure component gases was systematically investigated.The results demonstrated that Co-MOF exhibits superior adsorption capacity for C_(2)-C_(3) hydrocarbons compared to CH_(4),which offers the potential for efficient adsorption and separation of CH_(4) from C_(2)-C_(3) hydrocarbons.The gas selectivity separation ratios of Co-MOF for C_(2)H_(6)/CH_(4) and C_(3)H_8/CH_(4) were calculated using the ideal adsorbed solution theory method at 273/298 K and 0.1 MPa.The results revealed that Co-MOF achieved remarkable equilibrium separation selectivity for CH_(4) and C_(2)-C_(3) hydrocarbon gases among non-modified MOFs,signifying the potential of the synthesized Co-MOF for efficient recovery and purification of CH_(4) from C_(2)-C_(3) hydrocarbons.Breakthrough experiments further demonstrate the ability of Co-MOF to purify methane from C_(2)-C_(3) hydrocarbons in practical gas separation scenarios.Additionally,molecular simulation calculations further substantiate the propensity of anionic SBUs to interact with C_(2)-C_(3) hydrocarbon compounds.This study provides a novel paradigm for the development of porous MOF materials in the application of gas mixture separation.
文摘Objective In kinesin-3,the neck coil correlates with the following segments to form an extended neck that contains a characteristic hinge diverse from a proline in KIF13B to a long flexible linker in KIF1A.The function of this neck hinge for controlling processive movement,however,remains unclear.Methods We made a series of modifications to the neck hinges of KIF13B and KIF1A and tested their movement using a single-molecule motility assay.Results In KIF13B,the insertion of flexible residues before or after the proline differentially impacts the processivity or velocity,while the removal of this proline increases the both.In KIF1A,the deletion of entire flexible neck hinge merely enhances the processivity.The engineering of these hinge-truncated necks of kinesin-3 into kinesin-1 similarly boosts the processive movement of kinesin-1.Conclusion The neck hinge in kinesin-3 controls its processive movement and proper modifications tune the motor motility,which provides a novel strategy to reshape the processive movement of kinesin motors.
基金Project supported by the National Natural Science Foundation of China(Grant Nos.32371280 and T2350011)。
文摘FL-Online(http://fanlab.ac.cn) is an out-of-box modern web service featuring a user-friendly interface and simplified parameters, providing academic users with access to a series of online programs for biomolecular crystallography, including SAPI-online, OASIS-online, C-IPCAS-online and a series of upcoming software releases. Meanwhile, it is a highly scalable and maintainable web application framework that provides a powerful and flexible solution for academic web development needs. All the codes are open-source under MIT licenses in GitHub.
基金Project supported by the National Natural Science Foundation of China (Grant Nos.32271293 and 11875076)。
文摘Positional information encoded in spatial concentration patterns is crucial for the development of multicellular organisms.However,it is still unclear how such information is affected by the physically dissipative diffusion process.Here we study one-dimensional patterning systems with analytical derivation and numerical simulations.We find that the diffusion constant of the patterning molecules exhibits a nonmonotonic effect on the readout of the positional information from the concentration patterns.Specifically,there exists an optimal diffusion constant that maximizes the positional information.Moreover,we find that the energy dissipation due to the physical diffusion imposes a fundamental upper limit on the positional information.
基金supported by a grant from the Strategic Priority Research Program of the Chinese Academy of Sciences(no.XDA09030303).
文摘Cancer treatment is a multifaceted challenge,and therapeutic vaccines have emerged as a promising approach.The micellar preparation efficiently encapsulates antigen polypeptides and enhances antigen presentation through the major histocompatibility class I pathway,promoting cytotoxic T lymphocyte immune responses.Moreover,it enables codelivery of both antigen and adjuvant to the same target antigen-presenting cells.Combining themicellar vaccine with traditional cancer treatments(such as chemotherapy,radiotherapy,and surgery)has demonstrated improved efficacy in murine tumor models.Overall,the polyethylene glycol-phosphatidylethanolamine micelle-based vaccine presents a promising platformfor cancer therapeutic vaccines.By leveraging the strengths of various treatmentmodalities,this innovative vaccine approach holds the potential to revolutionize cancer therapy and bring new possibilities for cancer patients.
基金supported by the State Assignment of the Ministry of Science and Higher Education of the RF(No.0287-2021-0019).
文摘Cladocera are filter feeders abundant in freshwaters,which consume phytoplankton particles in wide size and taxonomic ranges.The ability of cladocerans to control phytoplankton abundance by grazing is determined by various factors including the characteristics of phytoplankton.Freshwater salinization may reduce the strength of top-down grazing control of phytoplankton because of the detrimental effects of salinity on the grazing intensity of zooplankters.We performed grazing experiments with two species of Cladocera of different body lengths to test their ability to graze on phytoplankton in natural waters differing in salinity and size and taxonomic composition of food particles.Grazing experiments demonstrated that the grazing rate was mostly controlled by the abundance of phytoplankton in the medium.The grazing rate was reduced at salinity ca.above 3 g/L of NaCl in the medium.The lower grazing rate was observed in the medium with larger phytoplankton particles.Both species predominantly consumed phytoplankton particles with a diameter of 6-12μm,which may shift the size distribution of phytoplankton towards a larger average diameter of particles.The taxon-specific feeding was also observed,as both species predominantly consumed diatom algae.Thus,we found that because of grazing,the size and taxonomic characteristics of phytoplankton are shifted towards a less edible community.The detrimental effect of elevated salinity on grazing rate supports growing concern about freshwater salinization negatively affecting water quality,particularly reducing top-down grazing control of phytoplankton.
基金Supported by the RFBR and Krasnoyarsk Krai Government and the Krasnoyarsk Regional Fund of Science(No.19-44-240002)supported by the State Assignment of the Ministry of Science and Higher Education of the RF(No.0287-2021-0019).
文摘The long-term data(1996-2021)on the summer abundances of the dominant zooplankton species(copepod Arctodiaptomus salinus(Daday,1885),rotifers Brachionus plicatilis(Müller,1786)and Hexarthra sp.)in saline Lake Shira were used to analyze the response of zooplankton to air temperature and a change in the circulation regime of the lake:breakdown and reestablishment of meromixis.All groups of zooplankton responded to prolonged summer elevated temperatures by increasing their abundance.During the breakdown of the stable stratification of Lake Shira(2015-2016),zooplankton abundance increased on average by a factor of two and amounted to 9×10^(5)inds./m^(2)in the water column for copepods.That increase coincided with similar responses of other components of the lake’s mixolimnion ecosystem,whose biomasses increased approximately two-fold during that period.After the reestablishment of the meromixis,the abundance of zooplankton decreased to previous values.Thus,the abundance of zooplankton is largely determined by weather(the effect of temperature)and ecological factors(mixing regime).
基金supported by the Natural Science Foundation of Hebei Province of China(Grant No.A2020202007)the National Natural Science Foundation of China(Grant No.11605038)。
文摘Microtubule catalyzes the mechanochemical cycle of kinesin,a kind of molecular motor,through its crucial roles in kinesin's gating,ATPase and force-generation process.These functions of microtubule are realized through the kinesin-microtubule interaction.The binding site of kinesin on the microtubule surface is fixed.For most of the kinesin-family members,the binding site on microtubule is in the groove betweenα-tubulin andβ-tubulin in a protofilament.The mechanism of kinesin searching for the appropriate binding site on microtubule is still unclear.Using the molecular dynamics simulation method,we investigate the interactions between kinesin-1 and the different binding positions on microtubule.The key non-bonded interactions between the motor domain and tubulins in kinesin's different nucleotide-binding states are listed.The differences of the amino-acid sequences betweenα-andβ-tubulins make kinesin-1 binding to theα–βgroove much more favorable than to theβ–αgroove.From these results,a two-step mechanism of kinesin-1 to discriminate the correct binding site on microtubule is proposed.Most of the kinesin-family members have the conserved motor domain and bind to the same site on microtubule,the mechanism may also be shared by other family members of kinesin.
基金the National Natural Science Foundation of China(Grant No.11735006)。
文摘Breast cancer is a malignant disease that seriously threatens women's health.Studying the mechanism of cancer occurrence and development is an urgent problem to be solved.In this paper,the eigen-microstate method was used to study conversion of normal breast cells into breast cancer cells and the reason.The main conclusions are as follows:the microstates of normal breast cell and breast cancer cell are different.There is a state conversion when a normal breast cell transforms into a breast cancer cell.The main reason for this state conversion is the combined effect of tumor suppressor genes and oncogenes.By analyzing the function of key genes,it was found that these genes do play an important role in the development of breast cancer.The findings contribute to understanding the mechanism by which breast cancer occurs and progresses,and key genes can serve as potential biomarkers or target genes for breast cancer treatment.
基金Project supported by the National Natural Science Foundation of China(Grant Nos.11904036 and 12175081)Fundamental Research Funds for the Central Universities(Grant No.CCNU22QNOO4)。
文摘The human serotonin transporter(SERT)terminates neurotransmission by removing serotonin from the synaptic cleft,which is an essential process that plays an important role in depression.In addition to natural substrate serotonin,SERT is also the target of the abused drug cocaine and,clinically used antidepressants,escitalopram,and paroxetine.To date,few studies have attempted to investigate the unbinding mechanism underlying the orthosteric and allosteric modulation of SERT.In this article,the conserved property of the orthosteric and allosteric sites(S1 and S2)of SERT was revealed by combining the high resolutions of x-ray crystal structures and molecular dynamics(MD)simulations.The residues Tyr95 and Ser438 located within the S1 site,and Arg104 located within the S2 site in SERT illustrate conserved interactions(hydrogen bonds and hydrophobic interactions),as responses to selective serotonin reuptake inhibitors.Van der Waals interactions were keys to designing effective drugs inhibiting SERT and further,electrostatic interactions highlighted escitalopram as a potent antidepressant.We found that cocaine,escitalopram,and paroxetine,whether the S1 site or the S2 site,were more competitive.According to this potential of mean force(PMF)simulations,the new insights reveal the principles of competitive inhibitors that lengths of trails from central SERT to an opening were~18A for serotonin and~22 A for the above-mentioned three drugs.Furthermore,the distance between the natural substrate serotonin and cocaine(or escitalopram)at the allosteric site was~3A.Thus,it can be inferred that the potent antidepressants tended to bind at deeper positions of the S1 or the S2 site of SERT in comparison to the substrate.Continuing exploring the processes of unbinding four ligands against the two target pockets of SERT,this study observed a broad pathway in which serotonin,cocaine,escitalopram(at the S1 site),and paroxetine all were pulled out to an opening between MT1b and MT6a,which may be helpful to understand the dissociation mechanism of antidepressants.
基金financially supported by National Natural Science Foundation(32102035)the Agricultural Science and Technology Innovation Program(CAAS-ASTIP-2020-IFST-03)Central Public-interest Scientific Institution Basal Research(S2019RCJC01,S2020JBKY-16).
文摘The degradation of titin could make the myofibrillar fragmentation to improve meat tenderization during postmortem.This study aimed to investigate effect of phosphorylation on titin degradation.Protein kinase A(PKA)and alkaline phosphatase(AP)were added to crude titin extracted from ovine longissimus lumborum(LL)muscles.Phosphorylated/dephosphorylated titin were incubated withμ-calpain at 4℃ for 2 days.Results showed titin in AP group started degradation earlier than that in PKA and control groups.There were 20,16 and 12 phosphorylated sites identified by iTRAQ in the PKA,control and AP group,respectively.3D structure of dephosphorylated titin fragment was simulated and its molecular dynamics trajectory analysis was performed using Discovery StudioTM.The dihedral angle in AP group was less and the dephosphorylated fragment had a higher kinetic energy and total energy.We suggested that changes caused by AP treatment might make titin unstable,which easily degraded byμ-calpain.
基金supported by the State Assignment of the Ministry of Science and Higher Education of the Russian Federation(No.0287-2021-0019)。
文摘Saline lakes are widespread on all continents.Since 1979,an informal international association of salt lake researchers from a variety of disciplines has sponsored a series of triennial conferences to foster scientific exchange and our understanding of saline lakes.International Society for Salt Lake Research(ISSLR,www.isslr.org)was founded in 1994 to establish effective liaison between persons interested in any aspect of inland saline waters,to encourage these interests,and to educate the public in the scientific use,management,and conservation of salt lakes.ISSLR conferences are held triennially.The conferences are usually hosted by a local University or research institution and provide an excellent opportunity for networking among globally dispe rsed researchers.
文摘In higher eukaryotes,DNA replication ensures precise transmission of genetic information from parental DNA to progeny,and the correct selection of replication origins is a critical step in this process.A very recent study has shown that nucleosomes containing histone variant H2A.Z recruit SUV420H1,a histone H4 lysine 20 specific methyltransferase.Moreover,SUV420H1 promotes the H4K20 dimethylation,which can recruit the origin recognition complex to fulfill the selection and licensing of the replication origins.
文摘Pathogens have developed an extensive array of proteins during the co-evolutionary arms race with their hosts.This is particularly true for Phytophthora,a genus that causes significant damage to agriculture and forestry.One well-known species,Phytophthora infestans,caused the devastating late blight pandemic during the Irish potato famine.Each Phytophthora species encodes hundreds of effector proteins that play essential roles in manipulating host cellular processes and promoting disease development.
基金supported by the National Natural Science Foundation of China[Grant no.51821004].
文摘Developing high-performance aqueous Zn-ion batteries from sustainable biomass becomes increasingly vital for large-scale energy storage in the foreseeable future.Therefore,γ-MnO_(2) uniformly loaded on N-doped carbon derived from grapefruit peel is successfully fabricated in this work,and particularly the composite cathode with carbon carrier quality percentage of 20 wt%delivers the specific capacity of 391.2 mAh g^(−1)at 0.1 A g^(−1),outstanding cyclic stability of 92.17%after 3000 cycles at 5 A g^(−1),and remarkable energy density of 553.12 Wh kg^(−1) together with superior coulombic efficiency of~100%.Additionally,the cathodic biosafety is further explored specifically through in vitro cell toxicity experiments,which verifies its tremendous potential in the application of clinical medicine.Besides,Zinc ion energy storage mechanism of the cathode is mainly discussed from the aspects of Jahn–Teller effect and Mn domains distribution combined with theoretical analysis and experimental data.Thus,a novel perspective of the conversion from biomass waste to biocompatible Mn-based cathode is successfully developed.
文摘Optical-neural stimulation,which encompasses cutting-edge techniques such as optogenetics and infrared neurostimulation,employs distinct mechanisms to modulate brain function and behavior.These advanced neuromodulation techniques offer accurate manipulation of targeted areas,even selectively modulating specific neurons,in the brain.This makes it possible to investigate the cause-and-effect connections between neural activity and behavior,allowing for a better comprehension of the intricate brain dynamics towards complex environments.Non-human primates serve as an essential animal model for investigating these complex functions in brain research,bridging the gap between the basic research and clinical applications.One of the earliest optical studies utilizing optogenetic neuromodulation in monkeys was conducted in 2009.Since then,the optical-neural stimulations have been effectively applied in non-human primates.This review summarises recent research that employed optogenetics or infrared neurostimulation techniques to regulate brain function and behavior in non-human primates.The current state of optical-neural stimulations discussed here demonstrates their efficacy in advancing the understanding of brain systems.Nevertheless,there are still challenges that need to be addressed before they can fully achieve their potential.
文摘Cardiovascular diseases are a group of disorders of the heart and blood vessels,primarily including coronary heart disease,stroke,and other diseases.It is the world’s leading cause of death,and its incidence is increasing yearly.Hypertension is a major risk factor for cardiovascular disease.Wnt signaling comprises a series of highly conservative cascading events controlling fundamental biological processes.Wnt signaling pathways include the canonical Wnt pathway(or Wnt/β-catenin pathway),the non canonical planar cell-polarity pathway,and the non-canonical calcium-dependent pathways.Abnormal Wnt signaling promotes cell proliferation and differentiation,cardiac malformations,various malignancies,so drugs targeting Wnt signaling play a great therapeutic potential.Wnt/β-catenin pathway is involved in the occurrence and development of cardiovascular diseases such as atherosclerosis and stroke by regulating cell proliferation,migration,apoptosis,blood-brain barrier permeability,inflammation,oxidative stress,and immune response.Based on the latest research progress,this review summarizes the role of Wnt/β-catenin signaling in cardiovascular diseases,in order to provide new ideas for the prevention and treatment of cardiovascular diseases.
基金supported by medical science research joint construction project of Henan(71188)Henan Provincial Department of Education under grant no.21B320008.
文摘Head and neck squamous cell carcinoma (HNSCC) is a prevalent and lethal solid tumor with a high mortality rate. Conventional cancertreatments, including surgery, radiotherapy, and chemotherapy, primarily target cancer cell eradication. However, uncontrolled proliferation and metabolic activities of these cells result in abnormalities in nutrient levels, hypoxia, and immunosuppression within the tumor microenvironment (TME). These factors constrain the efficacy of traditional treatments by promoting drug resistance, recurrence, and metastasis. Nanomaterials (NMs), such as nanozymes, can exhibit enzymatic activity similar to that of natural enzymes and offer a promising avenuefor the direct modification of the TME through catalytic oxidation-reduction processes. Moreover, they can serve as sensitizers or drug deliverycarriers, enhancing the efficacy of traditional treatment methods. Recently, NMs have garnered significant attention from oncologists. Thisreview begins with an overview of the composition and unique characteristics of the TME. Subsequently, we comprehensively exploredthe application of NMs in the treatment of HNSCC. Finally, we discuss the potential prospects and challenges associated with usingNMs in biomedical research.
文摘The team of Dr.LI Dong from the Institute of Biophysics(IBP)of the Chinese Academy of Sciences,in collaboration with the team of Dr.DAI Qionghai from the Department of Automation at Tsinghua University,published a research paper in Nature Communications on May 16.Based on the noise model of microscopic images and zero-sample learning theory,they proposed the zero-shot deconvolution networks(ZS-DeconvNet)and developed the corresponding one-click microscopic image processing software.
文摘Our previous study has demonstrated that CD 146 molecule is a biomarker on vascular endothelium, which is involved in angiogenesis and tumor growth. However the mechanism behind is not clear. Here we have for the first time developed a novel CD146 blockade system using CD146 siRNA to study its function on endothelial cells. Our data showed that CD146 siRNA specifically blocked the expression of CD146 on both mRNA and protein levels, leading to the significant suppression of HUVEC proliferation, adhesion and migration. These results demonstrate that CD146 plays a key role in vascular endothelial cell activity and angiogenesis, and CD146 siRNA can be used as a new inhibitor for anti-angiogenesis therapy.