Hybrid sterility is a major form of postzygotic reproductive isolation and frequently occurs in hybrids between divergent populations, such as the indica and japonica subspecies of Asian cultivated rice (Oryza sativa ...Hybrid sterility is a major form of postzygotic reproductive isolation and frequently occurs in hybrids between divergent populations, such as the indica and japonica subspecies of Asian cultivated rice (Oryza sativa L.). It has been a major barrier for utilization of the strong heterosis expressed in hybrids between indica and japonica. A large number of loci for rice inter-subspecific hybrid sterility have been identified by genetic analysis. Cytological studies revealed that male and female gamete abortions and reduced affinity between the uniting gametes all occurred in indica-japonica hybrids, suggesting the complexity of the causes for inter-subspecific hybrid sterility. Two genes conditioning embryo-sac and pollen sterility respectively in indica-japonica hybrids have been cloned recently, providing opportunities for molecular characterization of the indica-japonica hybrid sterility and wide-compatibility. Future studies should aim at cloning more genes for indica-japonica hybrid sterility, characterizing the underlying molecular mechanism, and utilization of the findings for the development of inter-subspecific hybrids to increase rice productivity.展开更多
Plants have developed various mechanisms for avoiding pathogen invasion,including resistance(R)genes.Most R genes encode nucleotide-binding domain and leucine-rich repeat containing proteins(NLRs).Here,we report the i...Plants have developed various mechanisms for avoiding pathogen invasion,including resistance(R)genes.Most R genes encode nucleotide-binding domain and leucine-rich repeat containing proteins(NLRs).Here,we report the isolation of three new bacterial blight R genes in rice,Xa1-2,Xa14,and Xa31(t),which were allelic to Xa1 and encoded atypical NLRs with unique central tandem repeats(CTRs).We also found that Xa31(t)was the same gene as Xa1-2.Although Xa1-2 and Xa14 conferred different resistance spectra,their performance could be attenuated by iTALEs,as has previously been reported for Xa1.XA1,XA1-2,XA14,and non-resistant RGAF differed mainly in the substructure of the leucine-rich repeat domain.They all contained unique CTRs and belonged to the CTR-NLRs,which existed only in Gramineae.We also found that interactions among these genes led to differing resistance performance.In conclusion,our results uncover a unique locus in rice consisting of at least three multiple alleles(Xa1,Xa1-2,and Xa14)that encode CTRNLRs and confer resistance to Xanthomonas oryzae pv.oryzae(Xoo).展开更多
Reproductive isolation is defined as processes that prevent individuals of different populations from mating, survival or producing fertile offspring. Reproductive isolation is critical for driving speciation and main...Reproductive isolation is defined as processes that prevent individuals of different populations from mating, survival or producing fertile offspring. Reproductive isolation is critical for driving speciation and maintaining species identity, which has been a fundamental concern in evolutionary biology. In plants,reproductive isolation can be divided into prezygotic and postzygotic reproductive barriers, according to its occurrence at different developmental stages. Postzygotic reproductive isolation caused by reduced fitness in hybrids is frequently observed in plants, which hinders gene flow between divergent populations and has substantial effects on genetic differentiation and speciation, and thus is a major obstacle for utilization of heterosis in hybrid crops. During the past decade, China has made tremendous progress in molecular and evolutionary basis of prezygotic and postzygotic reproductive barriers in plants. Present understandings in reproductive isolation especially with new data in the last several years well support three evolutionary genetic models, which represent a general mechanism underlying genomic differentiation and speciation. The updated understanding will offer new approaches for the development of wide-compatibility or neutral varieties, which facilitate breeding of hybrid rice as well as other hybrid crops.展开更多
The endoplasmic reticulum-associated degradation （ERAD） is a highly conserved mechanism to remove mis- folded membrane/secretory proteins from the endoplasmic reticulum （ER）. While many of the individual component...The endoplasmic reticulum-associated degradation （ERAD） is a highly conserved mechanism to remove mis- folded membrane/secretory proteins from the endoplasmic reticulum （ER）. While many of the individual components of the ERAD machinery are well characterized in yeast and mammals, our knowledge of a plant ERAD process is rather limited. Here, we report a functional study of an Arabidopsis homolog （AtOS9） of an ER luminal lectin Yos9 （OS-9 in mammals） that recognizes a unique asparagine-linked glycan on misfolded proteins. We discovered that AtOS9 is an ER-Iocalized glyco- protein that is co-expressed with many known/predicted ER chaperones. AT-DNA insertional atos9-t mutation blocks the degradation of a structurally imperfect yet biochemically competent brassinosteroid （BR） receptor bril-9, causing its increased accumulation in the ER and its consequent leakage to the cell surface responsible for restoring the BR sensitivity and suppressing the dwarfism of the bril-9 mutant. In addition, we identified a missense mutation in AtOS9 in a recently discovered ERAD mutant ems-rnutagenized bril suppressor 6 （ebs6-1）. Moreover, we showed that atos9-t also inhibits the ERAD of bril-5, another ER-retained BR receptor, and a misfolded EFR, a BRIl-like receptor for the bacterial translation elongation factor EF-Tu. Furthermore, we found that AtOS9 interacted biochemically and genetically with EBS5, an Arabidopsis homolog of the yeast Hrd3/mammalian SellL known to collaborate with Yos9/OS-9 to select ERAD clients. Taken together, our results demonstrated a functional role of AtOS9 in a plant ERAD process that degrades misfolded receptor-like kinases.展开更多
Dear Editor,Reproductive isolation is both the indicator and a primary force of speciation, and plays a key role in maintaining species identity. Understanding the origin and mechanisms of reproductive isola- tion is ...Dear Editor,Reproductive isolation is both the indicator and a primary force of speciation, and plays a key role in maintaining species identity. Understanding the origin and mechanisms of reproductive isola- tion is of fundamental importance in evolutionary biology. In recent years, a number of genes that induce reproductive barriers have been identified in several model organisms such as Drosophila, rodents, yeast, Arabidopsis.展开更多
Oral squamous cell carcinoma(OSCC)is the most common type of oral malignancy,and metastasis accounts for the poor prognosis of OSCC.Autophagy is considered to facilitate OSCC development by mitigating various cellular...Oral squamous cell carcinoma(OSCC)is the most common type of oral malignancy,and metastasis accounts for the poor prognosis of OSCC.Autophagy is considered to facilitate OSCC development by mitigating various cellular stresses;nevertheless,the mechanisms of autophagy in OSCC cell proliferation and metastasis remain unknown.In our study,high-sensitivity label-free quantitative proteomics analysis revealed nuclear protein 1(NUPR1)as the most significantly upregulated protein in formalin-fixed paraffin-embedded tumour samples derived from OSCC patients with or without lymphatic metastasis.展开更多
Reproductive transition of grasses is characterized by switching the pattern of lateral branches,featuring the suppression of outgrowth of the subtending leaves(bracts)and rapid formation of higher-order branches in t...Reproductive transition of grasses is characterized by switching the pattern of lateral branches,featuring the suppression of outgrowth of the subtending leaves(bracts)and rapid formation of higher-order branches in the inflorescence(panicle).However,the molecular mechanisms underlying such changes remain largely unknown.Here,we show that bract suppression is required for the reproductive branching in rice.We identified a pathway involving the intrinsic time ruler microRNAI56/529,their targets SQUAMOSA PROMOTER BINDING PROTEIN LIKE(SPL)genes,NECK LEAF1(NL1),and PLASTOCHRON1(PLA1),which regulates the bract outgrowth and thus affects the pattern switch between vegetative and reproductive branching.Suppression of the bract results in global reprogramming of transcriptome and chromatin accessibility following the reproductive transition,while these processes are largely dysregu-lated in the mutants of these genes.These discoveries contribute to our understanding of the dynamic plant architecture and provide novel insights for improving crop yields.展开更多
The wide adoption of hybrid rice has greatly increased rice yield in the last several decades.The utilization of heterosis facilitated by male sterility has been a common strategy for hybrid rice development.Here,we s...The wide adoption of hybrid rice has greatly increased rice yield in the last several decades.The utilization of heterosis facilitated by male sterility has been a common strategy for hybrid rice development.Here,we summarize our efforts in the genetic and molecular understanding of heterosis and male sterility together with the related progress from other research groups.Analyses of F1 diallel crosses show that strong heterosis widely exists in hybrids of diverse germplasms,and inter-subspecific hybrids often display higher heterosis.Using the elite hybrid Shanyou 63 as a model,an immortalized F2 population design is conducted for systematic characterization of the biological mechanism of heterosis,with identification of loci controlling heterosis of yield and yield component traits.Dominance,overdominance,and epistasis all play important roles in the genetic basis of heterosis;quantitative assessment of these components well addressed the three classical genetic hypotheses for heterosis.Environment-sensitive genic male sterility(EGMS)enables the development of two-line hybrids,and long noncoding RNAs often function as regulators of EGMS.Inter-subspecific hybrids show greatly reduced fertility;the identification and molecular characterization of hybrid sterility genes offer strategies for overcoming inter-subspecific hybrid sterility.These developments have significant implications for future hybrid rice improvement using genomic breeding.展开更多
Green energy storage devices play vital roles in reducing fossil fuel emissions and achieving carbon neutrality by 2050.Growing markets for portable electronics and electric vehicles create tremendous demand for advan...Green energy storage devices play vital roles in reducing fossil fuel emissions and achieving carbon neutrality by 2050.Growing markets for portable electronics and electric vehicles create tremendous demand for advanced lithium-ion batteries(LIBs)with high power and energy density,and novel electrode material with high capacity and energy density is one of the keys to next-generation LIBs.Silicon-based materials,with high specific capacity,abundant natural resources,high-level safety and environmental friendliness,are quite promising alternative anode materials.However,significant volume expansion and redundant side reactions with electrolytes lead to active lithium loss and decreased coulombic efficiency(CE)of silicon-based material,which hinders the commercial application of silicon-based anode.Prelithiation,preembedding extra lithium ions in the electrodes,is a promising approach to replenish the lithium loss during cycling.Recent progress on prelithiation strategies for silicon-based anode,including electrochemical method,chemical method,direct contact method,and active material method,and their practical potentials are reviewed and prospected here.The development of advanced Si-based material and prelithiation technologies is expected to provide promising approaches for the large-scale application of silicon-based materials.展开更多
Speciation has long been regarded as an irreversible process once the reproductive barriers had been established.However,unlike in natural populations,artificial selection might either accelerate or prevent speciation...Speciation has long been regarded as an irreversible process once the reproductive barriers had been established.However,unlike in natural populations,artificial selection might either accelerate or prevent speciation processes in domesticated species.Asian cultivated rice is a target crop for both domestication and artificial breeding;it contains two subspecies of indica and japonica,which usually produce sterile inter-subspecific hybrids due to reproductive barriers.In this study,we constructed the evolutionary trajectory of a reproductive isolation system S5,which regulates fertility in indica-japonica hybrids via three adjacent genes,based on the data of 606 accessions including two cultivated and 11 wild rice species.Although hybrid sterility haplotypes at S5 lead to establishment of a killer-protector reproductive barrier,origin of wide-compatibility haplotypes by complex hybridization and recombination provides an opposing force to reproductive isolation and thus prevents speciation during domestication.Analysis in a diallel set of 209 crosses involving 21 parents showed that the wide-compatibility genotypes largely rescued fertility of indica-japonica hybrids,indicating that the wide-compatibility gene would enable gene flow to maintain species coherence.This counteracting system indicates that combined effects of natural evolution and artificial selection may result in reversible processes of speciation in rice,which may also have implications for genetic improvement of rice.展开更多
Upgrading of atmospheric CO_(2) into high-value-added acetate using renewable electricity via electrocatalysis solely remains a great challenge.Here,inspired by microbial synthesis via biocatalysts,we present a couple...Upgrading of atmospheric CO_(2) into high-value-added acetate using renewable electricity via electrocatalysis solely remains a great challenge.Here,inspired by microbial synthesis via biocatalysts,we present a coupled system to produce acetate from CO_(2) by bridging inorganic electrocatalysis with microbial synthesis through formate intermediates.A 3D Bi_(2)O_(3)@CF integrated electrode with an ice-sugar gourd shape was fabricated via a straightforward hydrothermal synthesis strategy,wherein Bi_(2)O_(3) microspheres were decorated on carbon fibers.This ice-sugar gourd-shaped architecture endows electrodes with multiple structural advantages,including synergistic contribution,high mass transport capability,high structural stability,and large surface area.Consequently,the resultant Bi_(2)O_(3)@CF exhibited a maximum Faradic efficiency of 92.4%at−1.23 V versus Ag/AgCl for formate generation in 0.5 M KHCO_(3),exceeding that of Bi_(2)O_(3)/CF prepared using a conventional electrode preparation strategy.Benefiting from the high formate selectivity,unique architecture,and good biocompatibility,the Bi_(2)O_(3)@CF electrode attached with enriched CO_(2)-fixing electroautotrophs served as a biocathode.As a result,a considerable acetate yield rate of 0.269±0.009 g L^(−1) day^(−1)(a total acetate yield of 3.77±0.12 g L^(−1) during 14-day operation)was achieved in the electrochemical–microbial system equipped with Bi_(2)O_(3)@CF.展开更多
Hybrid rice has made considerable contributions to achieve the ambitious goal of food security for the world's population.Hybrid rice from indica/xian and japonica/geng subspecies shows much higher heter-osis and ...Hybrid rice has made considerable contributions to achieve the ambitious goal of food security for the world's population.Hybrid rice from indica/xian and japonica/geng subspecies shows much higher heter-osis and is thereby an important innovation in promoting rice production in the next decade.However,such inter-subspecific hybrid rice has long suffered from serious hybrid sterility,which is a major challenge that needs to be addressed.In this study,we performed a genome design strategy to produce fertile inter-subspecific hybrid by creation of wide compatibility varieties that are able to overcome hybrid sterility.Based on combined genetic analyses in two indica-japonica crosses,we determined that four hybrid ste-rility loci,S5,f5,pf12 and Sc,are the major QTLs controlling inter-subspecific hybrid sterility and thus the minimal targets that can be manipulated for breeding sub-specific hybrid rice.We then cloned the pf12 lo-cus,one of the most effective loci for hybrid male sterility,by map-based cloning,and showed that artificial disruption of pf12A gene at this locus could successfully rescue hybrid fertility.We further dissected the genetic basis of wide compatibility using three pairwise crosses from a wide-compatibility variety Dular and representative indica and japonica varieties.On this basis,we constructed and assembled different combinations of naturally compatible alleles of four loci,S5,Sc,pf12,and f5,and found that the improved lines could fully recover pollen and embryo sac fertility in test-crossed F,s,thereby completely fulfilling the demands of inter-subspecific hybrid spikelet fertility in agricultural production.This breeding scheme would facilitate redesign of future inter-subspecific hybrid rice with a higher yield potential.展开更多
G-protein signaling and ubiquitin-dependent degradation are both involved in grain development in rice,but how these pathways are coordinated in regulating this process is unknown.Here,we show that Chang Li Geng 1(CLG...G-protein signaling and ubiquitin-dependent degradation are both involved in grain development in rice,but how these pathways are coordinated in regulating this process is unknown.Here,we show that Chang Li Geng 1(CLG1),which encodes an E3 ligase,regulates grain size by targeting the Gγprotein GS3,a negative regulator of grain length,for degradation.Overexpression of CLG1 led to increased grain length,while overexpression of mutated CLG1 with changes in three conserved amino acids decreased grain length.We found that CLG1 physically interacts with and ubiquitinats GS3which is subsequently degraded through the endosome degradation pathway,leading to increased grain size.Furthermore,we identified a critical SNP in the exon 3 of CLG1 that is significantly associated with grain size variation in a core collection of cultivated rice.This SNP results in an amino acid substitution from Arg to Ser at position 163 of CLG1 that enhances the E3 ligase activity of CLG1 and thus increases rice grain size.Both the expression level of CLG1 and the SNP CLG1163S may be useful variations for manipulating grain size in rice.展开更多
N6-methyladenosine(m^(6)A)is the most prevalent modification in the eukaryotic transcriptome and has a wide range of functions in coding and noncoding RNAs.It affects the fate of the modified RNA,including its stabili...N6-methyladenosine(m^(6)A)is the most prevalent modification in the eukaryotic transcriptome and has a wide range of functions in coding and noncoding RNAs.It affects the fate of the modified RNA,including its stability,splicing,and translation,and plays an important role in post-transcriptional regulation.Bones play a key role in supporting and pro-tecting muscles and other organs,facilitating the movement of the organism,ensuring blood production,etc.Bone diseases such as osteoarthritis,osteoporosis,and bone tumors are serious public health problems.The processes of bone development and osteogenic differen-tiation require the precise regulation of gene expression through epigenetic mechanisms including histone,DNA,and RNA modifications.As a reversible dynamic epigenetic mark,m^(6)A modifications affect nearly every important biological process,cellular component,and molecular function,including skeletal development and homeostasis.In recent years,studies have shown that m^(6)A modification is involved in osteogenesis and bone-related diseases.In this review,we summarized the proteins involved in RNA m^(6)A modification and the latest progress in elucidating the regulatory role of m^(6)A modification in bone formation and stem cell direc-tional differentiation.We also discussed the pathological roles and potential molecular mech-anisms of m^(6)A modification in bone-related diseases like osteoporosis and osteosarcoma and suggested potential areas for new strategies that could be used to prevent or treat bone de-fects and bone diseases.展开更多
Background:A phase II trial on recombinant human tenecteplase tissue-type plasminogen activator(rhTNK-tPA)has previously shown its preliminary efficacy in ST elevation myocardial infarction(STEMI)patients.This study w...Background:A phase II trial on recombinant human tenecteplase tissue-type plasminogen activator(rhTNK-tPA)has previously shown its preliminary efficacy in ST elevation myocardial infarction(STEMI)patients.This study was designed as a pivotal postmarketing trial to compare its efficacy and safety with rrecombinant human tissue-type plasminogen activator alteplase(rt-PA)in Chinese patients with STEMI.Methods:In this multicenter,randomized,open-label,non-inferiority trial,patients with acute STEMI were randomly assigned(1:1)to receive an intravenous bolus of 16 mg rhTNK-tPA or an intravenous bolus of 8 mg rt-PA followed by an infusion of 42 mg in 90 min.The primary endpoint was recanalization defined by thrombolysis in myocardial infarction(TIMI)flow grade 2 or 3.The secondary endpoint was clinically justified recanalization.Other endpoints included 30-day major adverse cardiovascular and cerebrovascular events(MACCEs)and safety endpoints.Results:From July 2016 to September 2019,767 eligible patients were randomly assigned to receive rhTNK-tPA(n=384)or rt-PA(n=383).Among them,369 patients had coronary angiography data on TIMI flow,and 711 patients had data on clinically justified recanalization.Both used a–15%difference as the non-inferiority efficacy margin.In comparison to rt-PA,both the proportion of patients with TIMI grade 2 or 3 flow(78.3%[148/189]vs.81.7%[147/180];differences:–3.4%;95%confidence interval[CI]:–11.5%,4.8%)and clinically justified recanalization(85.4%[305/357]vs.85.9%[304/354];difference:–0.5%;95%CI:–5.6%,4.7%)in the rhTNK-tPA group were non-inferior.The occurrence of 30-day MACCEs(10.2%[39/384]vs.11.0%[42/383];hazard ratio:0.96;95%CI:0.61,1.50)did not differ significantly between groups.No safety outcomes significantly differed between groups.Conclusion:rhTNK-tPA was non-inferior to rt-PA in the effect of improving recanalization of the infarct-related artery,a validated surrogate of clinical outcomes,among Chinese patients with acute STEMI.Trial registration:www.ClinicalTrials.gov(No展开更多
Background:Existing treatments for cholangiocarcinoma have poor efficacy.However,chimeric antigen receptor-T(CAR-T)cells are emerging as a potential therapeutic strategy.Solid tumors possess multiple adverse factors i...Background:Existing treatments for cholangiocarcinoma have poor efficacy.However,chimeric antigen receptor-T(CAR-T)cells are emerging as a potential therapeutic strategy.Solid tumors possess multiple adverse factors in an immunosuppressive microenvironment that impair CAR-T cell infiltration and function.This study aimed to improve the function of CAR-T cells through knock down immune checkpoints and immunosuppressive molecular receptors.Methods:We evaluated the expression of epidermal growth factor receptor(EGFR)and B7 homolog 3 protein(B7H3)antigens in cholangiocarcinoma tissues using immunohistochemistry and screened specific immune checkpoints in the cholangiocarcinoma microenvironment via flow cytometry.Subsequently,we engineered CAR-T cells targeting EGFR and B7H3 antigens.We simultaneously knocked down immune checkpoints and immunosuppressive molecular receptors in CAR-T cells by constructing two clusters of small hairpin RNAs and evaluated the engineered CAR-T cells for antitumor activity both in vitro,using tumor cell lines and cholangiocarcinoma organoid models,and in vivo,using humanized mouse models.Results:We observed high expression of EGFR and B7H3 antigens in cholangiocarcinoma tissues.EGFR-CAR-T and B7H3-CAR-T cells demonstrated specific anti-tumor activity.We found an abundance of programmed cell death protein 1(PD-1),T cell immunoglobulin and mucin domain-containing protein 3(Tim-3),and T cell immunoglobulin and ITIM domain(Tigit)on infiltrated CD8^(+)T cells in the cholangiocarcinoma microenvironment.We then decreased the expression of these 3 proteins on the surface of CAR-T cells,named PTG-scFV-CAR-T cells.Furthermore,we knocked-down the expression of transforming growth factor beta receptor(TGFβR),interleukin-10 receptor(IL-10R),and interleukin-6 receptor(IL-6R)of PTG-scFV-CAR-T cells.Those cells,named PTG-T16R-scFVCAR-T cells,potently killed tumor cells in vitro and promoted apoptosis of tumor cells in a cholangiocarcinoma organoidmodel.Finally,the PTG-T16R-scFv-CART cells showed greater 展开更多
Artemisinin(ART)resistance has been an emerging clinical problem,severely compromising antimalarial efficacy and threatening the global malaria elimination campaign.Albeit intensive studies about the molecular mechani...Artemisinin(ART)resistance has been an emerging clinical problem,severely compromising antimalarial efficacy and threatening the global malaria elimination campaign.Albeit intensive studies about the molecular mechanism for ART resistance are under way,no effective therapeutic targets for reversing resistance have been applied.Here,we explore glutathione(GSH)as a therapeutic target to develop a thermo-responsive nanoplatform to specifically co-deliver ART and GSH synthesis inhibitor(L-buthionine sulfoximine,BSO)in a sustained manner,effectively reversing ART resistance in vivo.By combining with BSO,ART exerts increased antimalarial activity with reduced half-maximal inhibitory concentration(IC50)by 7.43-fold in ART-resistant strains.This work reveals that the GSH in ART-resistant parasites can be a promising therapeutic target for reversing ART resistance,paving the way for developing drug candidates and intelligent nanomedicines in malaria therapy.展开更多
Inbreeding depression refers to the reduced performance arising from increased homozygosity,a phenomenon that is the reverse of heterosis and exists among plants and animals.As a natural self-pollinated crop with stro...Inbreeding depression refers to the reduced performance arising from increased homozygosity,a phenomenon that is the reverse of heterosis and exists among plants and animals.As a natural self-pollinated crop with strong heterosis,the mechanism of inbreeding depression in rice is largely unknown.To understand the genetic basis of inbreeding depression,we constructed a successive inbreeding population from the F_(2)to F_(4)generation and observed inbreeding depression of all heterotic traits in the progeny along with the decay of heterozygosity in each generation.The expected depression effect was largely explained by 13 QTLs showing dominant effects for spikelets per panicle,11 for primary branches,and 12 for secondary branches,and these loci constitute the main correlation between heterosis and inbreeding depression.However,the genetic basis of inbreeding depression is also distinct from that of heterosis,such that a biased transmission ratio of alleles for QTLs with either dominant or additive effects in four segregation distortion regions would result in minor effects in expected depression.Noticeably,two-locus interactions may change the extent and direction of the depression effects of the target loci,and overall interactions would promote inbreeding depression among generations.Using an F_(2:3)variation population,the actual performance of the loci showing expected depression was evaluated considering the heterozygosity decay in the background after inbreeding.We found inconsistent or various degrees of background depression from the F_(2)to F_(3)generation assuming different genotypes of the target locus,which may affect the actual depression effect of the locus due to epistasis.The results suggest that the genetic architecture of inbreeding depression and heterosis is closely linked but also differs in their intrinsic mechanisms,which expand our understanding of the whole-genome architecture of inbreeding depression.展开更多
Central venous catheterization(CVC)is an invasive medical procedure used to measure central venous pressure and provides a stable route for continuous drug administration.CVC is widely used in the emergency department...Central venous catheterization(CVC)is an invasive medical procedure used to measure central venous pressure and provides a stable route for continuous drug administration.CVC is widely used in the emergency department and intensive care units.It is typically performed by inserting a catheter through the internal jugular vein(IJV)into the superior vena cava near the right atrium.[1,2]While catheterization is a fundamental skill proficiently performed by healthcare professionals,lethal complications may occasionally occur because of undesirable positioning,depth and diameter.展开更多
To improve drug utilization,reduce the drug administration frequency,increase the release time,and reduce the drug side effects in the human body,we prepared(KHA/CMC-Fe^(3+))@CS hydrogel spheres using green and natura...To improve drug utilization,reduce the drug administration frequency,increase the release time,and reduce the drug side effects in the human body,we prepared(KHA/CMC-Fe^(3+))@CS hydrogel spheres using green and natural potassium humate(KHA),carboxymethyl cellulose(CMC),and chitosan(CS)as raw materials and Fe3+as a crosslinking agent,and loaded them with riboflavin for drug sustainedrelease study using the drop ball method.The tests with FTIR,SEM,TG,and X-ray diffractometer showed that the coordination among KHA,CMC,and Fe^(3+)formed a three-dimensional network structure,where cs was encapsulated on the surface of the hydrogel spheres via noncovalent bonding,resulting in good thermal stability.The stability,drug loading,swelling,and in vitro release of the(KHA/CMC-Fe^(3+))@CS hydrogel spheres were investigated.The results showed that the hydrogel spheres were significantly pH-sensitive,with 11.16 g/g higher swelling in an alkaline environment(pH=7.4)than that in an acidic environment(pH=1.2).The swelling and drug release process of the hydrogel spheres were analyzed using mathematical models,concluding that the hydrogel swelling follows Schott second-order swelling kinetics,and the drug release mechanism was Fickian delivery mode.展开更多
基金Supported by grants partially from the National Special Key Project of China on Functional Genomics of Major Plants and Animals (Grant No. 2006AA10A103)National Natural Science Foundation of China (Grant No. 30621065)
文摘Hybrid sterility is a major form of postzygotic reproductive isolation and frequently occurs in hybrids between divergent populations, such as the indica and japonica subspecies of Asian cultivated rice (Oryza sativa L.). It has been a major barrier for utilization of the strong heterosis expressed in hybrids between indica and japonica. A large number of loci for rice inter-subspecific hybrid sterility have been identified by genetic analysis. Cytological studies revealed that male and female gamete abortions and reduced affinity between the uniting gametes all occurred in indica-japonica hybrids, suggesting the complexity of the causes for inter-subspecific hybrid sterility. Two genes conditioning embryo-sac and pollen sterility respectively in indica-japonica hybrids have been cloned recently, providing opportunities for molecular characterization of the indica-japonica hybrid sterility and wide-compatibility. Future studies should aim at cloning more genes for indica-japonica hybrid sterility, characterizing the underlying molecular mechanism, and utilization of the findings for the development of inter-subspecific hybrids to increase rice productivity.
基金supported by grants from the National Natural Science Foundation of China(grant nos.31821005,31772145,and 31200912)the China Scholarship Council(file no.201908420054).
文摘Plants have developed various mechanisms for avoiding pathogen invasion,including resistance(R)genes.Most R genes encode nucleotide-binding domain and leucine-rich repeat containing proteins(NLRs).Here,we report the isolation of three new bacterial blight R genes in rice,Xa1-2,Xa14,and Xa31(t),which were allelic to Xa1 and encoded atypical NLRs with unique central tandem repeats(CTRs).We also found that Xa31(t)was the same gene as Xa1-2.Although Xa1-2 and Xa14 conferred different resistance spectra,their performance could be attenuated by iTALEs,as has previously been reported for Xa1.XA1,XA1-2,XA14,and non-resistant RGAF differed mainly in the substructure of the leucine-rich repeat domain.They all contained unique CTRs and belonged to the CTR-NLRs,which existed only in Gramineae.We also found that interactions among these genes led to differing resistance performance.In conclusion,our results uncover a unique locus in rice consisting of at least three multiple alleles(Xa1,Xa1-2,and Xa14)that encode CTRNLRs and confer resistance to Xanthomonas oryzae pv.oryzae(Xoo).
基金supported by grants from the National Key Research and Development Program of China (2016YFD0100801)the National Natural Science Foundation of China (No.31771873)the National Program for Support of Top-notch Young Professionals
文摘Reproductive isolation is defined as processes that prevent individuals of different populations from mating, survival or producing fertile offspring. Reproductive isolation is critical for driving speciation and maintaining species identity, which has been a fundamental concern in evolutionary biology. In plants,reproductive isolation can be divided into prezygotic and postzygotic reproductive barriers, according to its occurrence at different developmental stages. Postzygotic reproductive isolation caused by reduced fitness in hybrids is frequently observed in plants, which hinders gene flow between divergent populations and has substantial effects on genetic differentiation and speciation, and thus is a major obstacle for utilization of heterosis in hybrid crops. During the past decade, China has made tremendous progress in molecular and evolutionary basis of prezygotic and postzygotic reproductive barriers in plants. Present understandings in reproductive isolation especially with new data in the last several years well support three evolutionary genetic models, which represent a general mechanism underlying genomic differentiation and speciation. The updated understanding will offer new approaches for the development of wide-compatibility or neutral varieties, which facilitate breeding of hybrid rice as well as other hybrid crops.
基金This work was partly supported by grants from National Institutes of Health （GM060519） and National Science Foundation （IOS 1121496） to J.L.
文摘The endoplasmic reticulum-associated degradation （ERAD） is a highly conserved mechanism to remove mis- folded membrane/secretory proteins from the endoplasmic reticulum （ER）. While many of the individual components of the ERAD machinery are well characterized in yeast and mammals, our knowledge of a plant ERAD process is rather limited. Here, we report a functional study of an Arabidopsis homolog （AtOS9） of an ER luminal lectin Yos9 （OS-9 in mammals） that recognizes a unique asparagine-linked glycan on misfolded proteins. We discovered that AtOS9 is an ER-Iocalized glyco- protein that is co-expressed with many known/predicted ER chaperones. AT-DNA insertional atos9-t mutation blocks the degradation of a structurally imperfect yet biochemically competent brassinosteroid （BR） receptor bril-9, causing its increased accumulation in the ER and its consequent leakage to the cell surface responsible for restoring the BR sensitivity and suppressing the dwarfism of the bril-9 mutant. In addition, we identified a missense mutation in AtOS9 in a recently discovered ERAD mutant ems-rnutagenized bril suppressor 6 （ebs6-1）. Moreover, we showed that atos9-t also inhibits the ERAD of bril-5, another ER-retained BR receptor, and a misfolded EFR, a BRIl-like receptor for the bacterial translation elongation factor EF-Tu. Furthermore, we found that AtOS9 interacted biochemically and genetically with EBS5, an Arabidopsis homolog of the yeast Hrd3/mammalian SellL known to collaborate with Yos9/OS-9 to select ERAD clients. Taken together, our results demonstrated a functional role of AtOS9 in a plant ERAD process that degrades misfolded receptor-like kinases.
文摘Dear Editor,Reproductive isolation is both the indicator and a primary force of speciation, and plays a key role in maintaining species identity. Understanding the origin and mechanisms of reproductive isola- tion is of fundamental importance in evolutionary biology. In recent years, a number of genes that induce reproductive barriers have been identified in several model organisms such as Drosophila, rodents, yeast, Arabidopsis.
基金This work was supported by the National Natural Science Foundation of China(81802716,32000552)the Natural Science Fund of Hunan Province of China(2020JJ5804)+3 种基金CAMS Innovation Fund for Medical Sciences(2019-I2M-5-037)Shanghai Clinical Research Center for Oral Diseases(19MC1910600)Shanghai Municipal Key Clinical Specialty(shslczdzk01601)Emerging Frontier Technology Joint Research Project(SHDC12018104),the project from Hainan Province Clinical Medical Center.
文摘Oral squamous cell carcinoma(OSCC)is the most common type of oral malignancy,and metastasis accounts for the poor prognosis of OSCC.Autophagy is considered to facilitate OSCC development by mitigating various cellular stresses;nevertheless,the mechanisms of autophagy in OSCC cell proliferation and metastasis remain unknown.In our study,high-sensitivity label-free quantitative proteomics analysis revealed nuclear protein 1(NUPR1)as the most significantly upregulated protein in formalin-fixed paraffin-embedded tumour samples derived from OSCC patients with or without lymphatic metastasis.
基金the National Key Research and Development Program of China(2016YFD0100903)the National Natural Science Foundation of China(31600983 and 31821005)+1 种基金the China Postdoctoral Science Foundation(2017T100564 and 2016M590699)the Earmarked Fund for the China Agricultural Research System(CARS-01-05).
文摘Reproductive transition of grasses is characterized by switching the pattern of lateral branches,featuring the suppression of outgrowth of the subtending leaves(bracts)and rapid formation of higher-order branches in the inflorescence(panicle).However,the molecular mechanisms underlying such changes remain largely unknown.Here,we show that bract suppression is required for the reproductive branching in rice.We identified a pathway involving the intrinsic time ruler microRNAI56/529,their targets SQUAMOSA PROMOTER BINDING PROTEIN LIKE(SPL)genes,NECK LEAF1(NL1),and PLASTOCHRON1(PLA1),which regulates the bract outgrowth and thus affects the pattern switch between vegetative and reproductive branching.Suppression of the bract results in global reprogramming of transcriptome and chromatin accessibility following the reproductive transition,while these processes are largely dysregu-lated in the mutants of these genes.These discoveries contribute to our understanding of the dynamic plant architecture and provide novel insights for improving crop yields.
基金supported by grants from the National Natural Science Foundation of China (31991223, 32170622 and 31821005)the Natural Science Foundation of Hubei Province (2019CFA061)the Fundamental Research Funds for the Central Universities (2662020SKPY005)
文摘The wide adoption of hybrid rice has greatly increased rice yield in the last several decades.The utilization of heterosis facilitated by male sterility has been a common strategy for hybrid rice development.Here,we summarize our efforts in the genetic and molecular understanding of heterosis and male sterility together with the related progress from other research groups.Analyses of F1 diallel crosses show that strong heterosis widely exists in hybrids of diverse germplasms,and inter-subspecific hybrids often display higher heterosis.Using the elite hybrid Shanyou 63 as a model,an immortalized F2 population design is conducted for systematic characterization of the biological mechanism of heterosis,with identification of loci controlling heterosis of yield and yield component traits.Dominance,overdominance,and epistasis all play important roles in the genetic basis of heterosis;quantitative assessment of these components well addressed the three classical genetic hypotheses for heterosis.Environment-sensitive genic male sterility(EGMS)enables the development of two-line hybrids,and long noncoding RNAs often function as regulators of EGMS.Inter-subspecific hybrids show greatly reduced fertility;the identification and molecular characterization of hybrid sterility genes offer strategies for overcoming inter-subspecific hybrid sterility.These developments have significant implications for future hybrid rice improvement using genomic breeding.
基金This work was supported by Guangdong Basic and Applied Basic Research Foundation(2019A1515110530,2022A1515010486)Shenzhen Science and Technology Program(JCYJ20210324140804013)Tsinghua Shenzhen International Graduate School(QD2021005N,JC2021007).
文摘Green energy storage devices play vital roles in reducing fossil fuel emissions and achieving carbon neutrality by 2050.Growing markets for portable electronics and electric vehicles create tremendous demand for advanced lithium-ion batteries(LIBs)with high power and energy density,and novel electrode material with high capacity and energy density is one of the keys to next-generation LIBs.Silicon-based materials,with high specific capacity,abundant natural resources,high-level safety and environmental friendliness,are quite promising alternative anode materials.However,significant volume expansion and redundant side reactions with electrolytes lead to active lithium loss and decreased coulombic efficiency(CE)of silicon-based material,which hinders the commercial application of silicon-based anode.Prelithiation,preembedding extra lithium ions in the electrodes,is a promising approach to replenish the lithium loss during cycling.Recent progress on prelithiation strategies for silicon-based anode,including electrochemical method,chemical method,direct contact method,and active material method,and their practical potentials are reviewed and prospected here.The development of advanced Si-based material and prelithiation technologies is expected to provide promising approaches for the large-scale application of silicon-based materials.
基金This research was supported by grants from the National Natural Science Foundation of China(31991223,30800678,and 31821005)the Hubei Provincial Natural Science Foundation of China(2019CFA061)the National Program for Support of Top-notch Young Professionals.
文摘Speciation has long been regarded as an irreversible process once the reproductive barriers had been established.However,unlike in natural populations,artificial selection might either accelerate or prevent speciation processes in domesticated species.Asian cultivated rice is a target crop for both domestication and artificial breeding;it contains two subspecies of indica and japonica,which usually produce sterile inter-subspecific hybrids due to reproductive barriers.In this study,we constructed the evolutionary trajectory of a reproductive isolation system S5,which regulates fertility in indica-japonica hybrids via three adjacent genes,based on the data of 606 accessions including two cultivated and 11 wild rice species.Although hybrid sterility haplotypes at S5 lead to establishment of a killer-protector reproductive barrier,origin of wide-compatibility haplotypes by complex hybridization and recombination provides an opposing force to reproductive isolation and thus prevents speciation during domestication.Analysis in a diallel set of 209 crosses involving 21 parents showed that the wide-compatibility genotypes largely rescued fertility of indica-japonica hybrids,indicating that the wide-compatibility gene would enable gene flow to maintain species coherence.This counteracting system indicates that combined effects of natural evolution and artificial selection may result in reversible processes of speciation in rice,which may also have implications for genetic improvement of rice.
基金National Key Research and Development Program of China,Grant/Award Number:2018YFA0901300National Natural Science Foundation of China,Grant/Award Numbers:21975124,52173173,21603209+1 种基金the Natural Science Foundation of Jiangsu Province,Grant/Award Numbers:BK20220051,BK20220002Jiangsu Province Carbon Peak and Neutrality Innovation Program,Grant/Award Numbers:BE2022002-3,BE2022031-4。
文摘Upgrading of atmospheric CO_(2) into high-value-added acetate using renewable electricity via electrocatalysis solely remains a great challenge.Here,inspired by microbial synthesis via biocatalysts,we present a coupled system to produce acetate from CO_(2) by bridging inorganic electrocatalysis with microbial synthesis through formate intermediates.A 3D Bi_(2)O_(3)@CF integrated electrode with an ice-sugar gourd shape was fabricated via a straightforward hydrothermal synthesis strategy,wherein Bi_(2)O_(3) microspheres were decorated on carbon fibers.This ice-sugar gourd-shaped architecture endows electrodes with multiple structural advantages,including synergistic contribution,high mass transport capability,high structural stability,and large surface area.Consequently,the resultant Bi_(2)O_(3)@CF exhibited a maximum Faradic efficiency of 92.4%at−1.23 V versus Ag/AgCl for formate generation in 0.5 M KHCO_(3),exceeding that of Bi_(2)O_(3)/CF prepared using a conventional electrode preparation strategy.Benefiting from the high formate selectivity,unique architecture,and good biocompatibility,the Bi_(2)O_(3)@CF electrode attached with enriched CO_(2)-fixing electroautotrophs served as a biocathode.As a result,a considerable acetate yield rate of 0.269±0.009 g L^(−1) day^(−1)(a total acetate yield of 3.77±0.12 g L^(−1) during 14-day operation)was achieved in the electrochemical–microbial system equipped with Bi_(2)O_(3)@CF.
基金supported by grants from the National Natural Science Foundation of China(31991223,31991222,32101688,32170622,and 31821005)the National Key Research and Development Program of China(2022YFF1002100)+1 种基金the Hubei Key R&D Program(2020BBA031 and 2020BBA034)Hubei Key R&D Program in Hongshan Lab(2021hszd005,2022hszd017).
文摘Hybrid rice has made considerable contributions to achieve the ambitious goal of food security for the world's population.Hybrid rice from indica/xian and japonica/geng subspecies shows much higher heter-osis and is thereby an important innovation in promoting rice production in the next decade.However,such inter-subspecific hybrid rice has long suffered from serious hybrid sterility,which is a major challenge that needs to be addressed.In this study,we performed a genome design strategy to produce fertile inter-subspecific hybrid by creation of wide compatibility varieties that are able to overcome hybrid sterility.Based on combined genetic analyses in two indica-japonica crosses,we determined that four hybrid ste-rility loci,S5,f5,pf12 and Sc,are the major QTLs controlling inter-subspecific hybrid sterility and thus the minimal targets that can be manipulated for breeding sub-specific hybrid rice.We then cloned the pf12 lo-cus,one of the most effective loci for hybrid male sterility,by map-based cloning,and showed that artificial disruption of pf12A gene at this locus could successfully rescue hybrid fertility.We further dissected the genetic basis of wide compatibility using three pairwise crosses from a wide-compatibility variety Dular and representative indica and japonica varieties.On this basis,we constructed and assembled different combinations of naturally compatible alleles of four loci,S5,Sc,pf12,and f5,and found that the improved lines could fully recover pollen and embryo sac fertility in test-crossed F,s,thereby completely fulfilling the demands of inter-subspecific hybrid spikelet fertility in agricultural production.This breeding scheme would facilitate redesign of future inter-subspecific hybrid rice with a higher yield potential.
基金This work was supported by grants from the National Key Research and Development Program(2016YFD0100901 and 2016YFD0100903)the Earmarked Fund for the China Agricultural Research System(CARS-01-05).
文摘G-protein signaling and ubiquitin-dependent degradation are both involved in grain development in rice,but how these pathways are coordinated in regulating this process is unknown.Here,we show that Chang Li Geng 1(CLG1),which encodes an E3 ligase,regulates grain size by targeting the Gγprotein GS3,a negative regulator of grain length,for degradation.Overexpression of CLG1 led to increased grain length,while overexpression of mutated CLG1 with changes in three conserved amino acids decreased grain length.We found that CLG1 physically interacts with and ubiquitinats GS3which is subsequently degraded through the endosome degradation pathway,leading to increased grain size.Furthermore,we identified a critical SNP in the exon 3 of CLG1 that is significantly associated with grain size variation in a core collection of cultivated rice.This SNP results in an amino acid substitution from Arg to Ser at position 163 of CLG1 that enhances the E3 ligase activity of CLG1 and thus increases rice grain size.Both the expression level of CLG1 and the SNP CLG1163S may be useful variations for manipulating grain size in rice.
基金supported by the National Natural Science Foundation of China(No.81870743,82170934)the Sichuan Science and Technology Program(China)(No.2022YFG0280)。
文摘N6-methyladenosine(m^(6)A)is the most prevalent modification in the eukaryotic transcriptome and has a wide range of functions in coding and noncoding RNAs.It affects the fate of the modified RNA,including its stability,splicing,and translation,and plays an important role in post-transcriptional regulation.Bones play a key role in supporting and pro-tecting muscles and other organs,facilitating the movement of the organism,ensuring blood production,etc.Bone diseases such as osteoarthritis,osteoporosis,and bone tumors are serious public health problems.The processes of bone development and osteogenic differen-tiation require the precise regulation of gene expression through epigenetic mechanisms including histone,DNA,and RNA modifications.As a reversible dynamic epigenetic mark,m^(6)A modifications affect nearly every important biological process,cellular component,and molecular function,including skeletal development and homeostasis.In recent years,studies have shown that m^(6)A modification is involved in osteogenesis and bone-related diseases.In this review,we summarized the proteins involved in RNA m^(6)A modification and the latest progress in elucidating the regulatory role of m^(6)A modification in bone formation and stem cell direc-tional differentiation.We also discussed the pathological roles and potential molecular mech-anisms of m^(6)A modification in bone-related diseases like osteoporosis and osteosarcoma and suggested potential areas for new strategies that could be used to prevent or treat bone de-fects and bone diseases.
基金supported by the Guangzhou Recomgen Biotech Co.,Ltd.The funder had no role in the design and conduct of the studycollection,management,analysis,and interpretation of the data
文摘Background:A phase II trial on recombinant human tenecteplase tissue-type plasminogen activator(rhTNK-tPA)has previously shown its preliminary efficacy in ST elevation myocardial infarction(STEMI)patients.This study was designed as a pivotal postmarketing trial to compare its efficacy and safety with rrecombinant human tissue-type plasminogen activator alteplase(rt-PA)in Chinese patients with STEMI.Methods:In this multicenter,randomized,open-label,non-inferiority trial,patients with acute STEMI were randomly assigned(1:1)to receive an intravenous bolus of 16 mg rhTNK-tPA or an intravenous bolus of 8 mg rt-PA followed by an infusion of 42 mg in 90 min.The primary endpoint was recanalization defined by thrombolysis in myocardial infarction(TIMI)flow grade 2 or 3.The secondary endpoint was clinically justified recanalization.Other endpoints included 30-day major adverse cardiovascular and cerebrovascular events(MACCEs)and safety endpoints.Results:From July 2016 to September 2019,767 eligible patients were randomly assigned to receive rhTNK-tPA(n=384)or rt-PA(n=383).Among them,369 patients had coronary angiography data on TIMI flow,and 711 patients had data on clinically justified recanalization.Both used a–15%difference as the non-inferiority efficacy margin.In comparison to rt-PA,both the proportion of patients with TIMI grade 2 or 3 flow(78.3%[148/189]vs.81.7%[147/180];differences:–3.4%;95%confidence interval[CI]:–11.5%,4.8%)and clinically justified recanalization(85.4%[305/357]vs.85.9%[304/354];difference:–0.5%;95%CI:–5.6%,4.7%)in the rhTNK-tPA group were non-inferior.The occurrence of 30-day MACCEs(10.2%[39/384]vs.11.0%[42/383];hazard ratio:0.96;95%CI:0.61,1.50)did not differ significantly between groups.No safety outcomes significantly differed between groups.Conclusion:rhTNK-tPA was non-inferior to rt-PA in the effect of improving recanalization of the infarct-related artery,a validated surrogate of clinical outcomes,among Chinese patients with acute STEMI.Trial registration:www.ClinicalTrials.gov(No
基金Guangzhou Science and Technology Innovation development Special fund,Grant/Award Number:202102020386Basic and Applied Basic Research Fund Committee of Guangdong Province,Grant/Award Numbers:2021A1515111209,2022A1515010547+1 种基金Science Foundation of Guangdong Provincial Bureau of traditional Chinese Medicine,Grant/Award Number:20211090National Natural Science Foundation of China,Grant/Award Numbers:82103331,82171825,82202036。
文摘Background:Existing treatments for cholangiocarcinoma have poor efficacy.However,chimeric antigen receptor-T(CAR-T)cells are emerging as a potential therapeutic strategy.Solid tumors possess multiple adverse factors in an immunosuppressive microenvironment that impair CAR-T cell infiltration and function.This study aimed to improve the function of CAR-T cells through knock down immune checkpoints and immunosuppressive molecular receptors.Methods:We evaluated the expression of epidermal growth factor receptor(EGFR)and B7 homolog 3 protein(B7H3)antigens in cholangiocarcinoma tissues using immunohistochemistry and screened specific immune checkpoints in the cholangiocarcinoma microenvironment via flow cytometry.Subsequently,we engineered CAR-T cells targeting EGFR and B7H3 antigens.We simultaneously knocked down immune checkpoints and immunosuppressive molecular receptors in CAR-T cells by constructing two clusters of small hairpin RNAs and evaluated the engineered CAR-T cells for antitumor activity both in vitro,using tumor cell lines and cholangiocarcinoma organoid models,and in vivo,using humanized mouse models.Results:We observed high expression of EGFR and B7H3 antigens in cholangiocarcinoma tissues.EGFR-CAR-T and B7H3-CAR-T cells demonstrated specific anti-tumor activity.We found an abundance of programmed cell death protein 1(PD-1),T cell immunoglobulin and mucin domain-containing protein 3(Tim-3),and T cell immunoglobulin and ITIM domain(Tigit)on infiltrated CD8^(+)T cells in the cholangiocarcinoma microenvironment.We then decreased the expression of these 3 proteins on the surface of CAR-T cells,named PTG-scFV-CAR-T cells.Furthermore,we knocked-down the expression of transforming growth factor beta receptor(TGFβR),interleukin-10 receptor(IL-10R),and interleukin-6 receptor(IL-6R)of PTG-scFV-CAR-T cells.Those cells,named PTG-T16R-scFVCAR-T cells,potently killed tumor cells in vitro and promoted apoptosis of tumor cells in a cholangiocarcinoma organoidmodel.Finally,the PTG-T16R-scFv-CART cells showed greater
基金supported by the National Natural Science Foundation of China(Nos.81803470 and 82173767)。
文摘Artemisinin(ART)resistance has been an emerging clinical problem,severely compromising antimalarial efficacy and threatening the global malaria elimination campaign.Albeit intensive studies about the molecular mechanism for ART resistance are under way,no effective therapeutic targets for reversing resistance have been applied.Here,we explore glutathione(GSH)as a therapeutic target to develop a thermo-responsive nanoplatform to specifically co-deliver ART and GSH synthesis inhibitor(L-buthionine sulfoximine,BSO)in a sustained manner,effectively reversing ART resistance in vivo.By combining with BSO,ART exerts increased antimalarial activity with reduced half-maximal inhibitory concentration(IC50)by 7.43-fold in ART-resistant strains.This work reveals that the GSH in ART-resistant parasites can be a promising therapeutic target for reversing ART resistance,paving the way for developing drug candidates and intelligent nanomedicines in malaria therapy.
基金supported by the National Key Research and Development Program of China(2022YFF1002100)the National Natural Science Foundation of China(31991223,32341031,32170622,31821005)+2 种基金the Hubei Key R&D Program(2020BBA034)the Hubei Key R&D Program in Hongshan Lab(2021hszd005,2022hszd017)the Fundamental Research Founds for the Central Universities(2662023PY002).
文摘Inbreeding depression refers to the reduced performance arising from increased homozygosity,a phenomenon that is the reverse of heterosis and exists among plants and animals.As a natural self-pollinated crop with strong heterosis,the mechanism of inbreeding depression in rice is largely unknown.To understand the genetic basis of inbreeding depression,we constructed a successive inbreeding population from the F_(2)to F_(4)generation and observed inbreeding depression of all heterotic traits in the progeny along with the decay of heterozygosity in each generation.The expected depression effect was largely explained by 13 QTLs showing dominant effects for spikelets per panicle,11 for primary branches,and 12 for secondary branches,and these loci constitute the main correlation between heterosis and inbreeding depression.However,the genetic basis of inbreeding depression is also distinct from that of heterosis,such that a biased transmission ratio of alleles for QTLs with either dominant or additive effects in four segregation distortion regions would result in minor effects in expected depression.Noticeably,two-locus interactions may change the extent and direction of the depression effects of the target loci,and overall interactions would promote inbreeding depression among generations.Using an F_(2:3)variation population,the actual performance of the loci showing expected depression was evaluated considering the heterozygosity decay in the background after inbreeding.We found inconsistent or various degrees of background depression from the F_(2)to F_(3)generation assuming different genotypes of the target locus,which may affect the actual depression effect of the locus due to epistasis.The results suggest that the genetic architecture of inbreeding depression and heterosis is closely linked but also differs in their intrinsic mechanisms,which expand our understanding of the whole-genome architecture of inbreeding depression.
文摘Central venous catheterization(CVC)is an invasive medical procedure used to measure central venous pressure and provides a stable route for continuous drug administration.CVC is widely used in the emergency department and intensive care units.It is typically performed by inserting a catheter through the internal jugular vein(IJV)into the superior vena cava near the right atrium.[1,2]While catheterization is a fundamental skill proficiently performed by healthcare professionals,lethal complications may occasionally occur because of undesirable positioning,depth and diameter.
基金supported by the National Natural Science Foundation of China(grant No.51803114)Shaanxi Province Key R&D Program(grant No.2022NY-195)+4 种基金Xi'an City Innovation Capability Strong Foundation Plan-Agricultural Technology R&D(grant No.21NYYF0025)Shaanxi Province Education Department Service Local Special Program Project(grant No.22jcO15)Shaanxi Province Key R&D Program(grant No.2020SF-411)Industry-University-Research Cooperation Project of Yulin Science and Technology Bureau(grant No.CXY-2020-086)National Key R&D Projects in 2021(grant No.2021YFC1808900).
文摘To improve drug utilization,reduce the drug administration frequency,increase the release time,and reduce the drug side effects in the human body,we prepared(KHA/CMC-Fe^(3+))@CS hydrogel spheres using green and natural potassium humate(KHA),carboxymethyl cellulose(CMC),and chitosan(CS)as raw materials and Fe3+as a crosslinking agent,and loaded them with riboflavin for drug sustainedrelease study using the drop ball method.The tests with FTIR,SEM,TG,and X-ray diffractometer showed that the coordination among KHA,CMC,and Fe^(3+)formed a three-dimensional network structure,where cs was encapsulated on the surface of the hydrogel spheres via noncovalent bonding,resulting in good thermal stability.The stability,drug loading,swelling,and in vitro release of the(KHA/CMC-Fe^(3+))@CS hydrogel spheres were investigated.The results showed that the hydrogel spheres were significantly pH-sensitive,with 11.16 g/g higher swelling in an alkaline environment(pH=7.4)than that in an acidic environment(pH=1.2).The swelling and drug release process of the hydrogel spheres were analyzed using mathematical models,concluding that the hydrogel swelling follows Schott second-order swelling kinetics,and the drug release mechanism was Fickian delivery mode.
