Objective Poxviruses are zoonotic pathogens that infect humans,mammals,vertebrates,and arthropods.However,the specific role of ticks in transmission and evolution of these viruses remains unclear.Methods Transcriptomi...Objective Poxviruses are zoonotic pathogens that infect humans,mammals,vertebrates,and arthropods.However,the specific role of ticks in transmission and evolution of these viruses remains unclear.Methods Transcriptomic and metatranscriptomic raw data from 329 sampling pools of seven tick species across five continents were mined to assess the diversity and abundance of poxviruses.Chordopoxviral sequences were assembled and subjected to phylogenetic analysis to trace the origins of the unblasted fragments within these sequences.Results Fifty-eight poxvirus species,representing two subfamilies and 20 genera,were identified,with 212 poxviral sequences assembled.A substantial proportion of AT-rich fragments were detected in the assembled poxviral genomes.These genomic sequences contained fragments originating from rodents,archaea,and arthropods.Conclusion Our findings indicate that ticks play a significant role in the transmission and evolution of poxviruses.These viruses demonstrate the capacity to modulate virulence and adaptability through horizontal gene transfer,gene recombination,and gene mutations,thereby promoting co-existence and co-evolution with their hosts.This study advances understanding of the ecological dynamics of poxvirus transmission and evolution and highlights the potential role of ticks as vectors and vessels in these processes.展开更多
Objective:Triple-negative breast cancer(TNBC)is a highly aggressive subtype that lacks targeted therapies,leading to a poorer prognosis.However,some patients achieve long-term recurrence-free survival(RFS),offering va...Objective:Triple-negative breast cancer(TNBC)is a highly aggressive subtype that lacks targeted therapies,leading to a poorer prognosis.However,some patients achieve long-term recurrence-free survival(RFS),offering valuable insights into tumor biology and potential treatment strategies.Methods:We conducted a comprehensive multi-omics analysis of 132 patients with American Joint Committee on Cancer(AJCC)stage III TNBC,comprising 36 long-term survivors(RFS≥8 years),62 moderate-term survivors(RFS:3-8 years),and 34 short-term survivors(RFS<3 years).Analyses investigated clinicopathological factors,whole-exome sequencing,germline mutations,copy number alterations(CNAs),RNA sequences,and metabolomic profiles.Results:Long-term survivors exhibited fewer metastatic regional lymph nodes,along with tumors showing reduced stromal fibrosis and lower Ki67 index.Molecularly,these tumors exhibited multiple alterations in genes related to homologous recombination repair,with higher frequencies of germline mutations and somatic CNAs.Additionally,tumors from long-term survivors demonstrated significant downregulation of the RTK-RAS signaling pathway.Metabolomic profiling revealed decreased levels of lipids and carbohydrate,particularly those involved in glycerophospholipid,fructose,and mannose metabolism,in long-term survival group.Multivariate Cox analysis identified fibrosis[hazard ratio(HR):12.70,95%confidence interval(95%CI):2.19-73.54,P=0.005]and RAC1copy number loss/deletion(HR:0.22,95%CI:0.06-0.83,P=0.026)as independent predictors of RFS.Higher fructose/mannose metabolism was associated with worse overall survival(HR:1.30,95%CI:1.01-1.68,P=0.045).Our findings emphasize the association between biological determinants and prolonged survival in patients with TNBC.Conclusions:Our study systematically identified the key molecular and metabolic features associated with prolonged survival in AJCC stage III TNBC,suggesting potential therapeutic targets to improve patient outcomes.展开更多
Trap-assisted charge recombination is one of the primary limitationsof restricting the performance of organic solar cells. However, effectivelyreducing the presence of traps in the photoactive layer remains challengin...Trap-assisted charge recombination is one of the primary limitationsof restricting the performance of organic solar cells. However, effectivelyreducing the presence of traps in the photoactive layer remains challenging.Herein, wide bandgap polymer donor PTzBI-dF is demonstrated as an effectivemodulator for enhancing the crystallinity of the bulk heterojunction active layerscomposed of D18 derivatives blended with Y6, leading to dense and orderedmolecular packings, and thus, improves photoluminescence quenching properties.As a result, the photovoltaic devices exhibit reduced trap-assisted charge recombinationlosses, achieving an optimized power conversion efficiency of over 19%.Besides the efficiency enhancement, the devices comprised of PTzBI-dF as athird component simultaneously attain decreased current leakage, improved chargecarrier mobilities, and suppressed bimolecular charge recombination, leading toreduced energy losses. The advanced crystalline structures induced by PTzBI-dFand its characteristics, such as well-aligned energy level, and complementaryabsorption spectra, are ascribed to the promising performance improvements.Our findings suggest that donor phase engineering is a feasible approach to tuning the molecular packings in the active layer, providingguidelines for designing effective morphology modulators for high-performance organic solar cells.展开更多
Two-terminal(2-T)perovskite(PVK)/CuIn(Ga)Se_(2)(CIGS)tandem solar cells(TSCs)have been considered as an ideal tandem cell because of their best bandgap matching regarding to Shockley–Queisser(S–Q)limits.However,the ...Two-terminal(2-T)perovskite(PVK)/CuIn(Ga)Se_(2)(CIGS)tandem solar cells(TSCs)have been considered as an ideal tandem cell because of their best bandgap matching regarding to Shockley–Queisser(S–Q)limits.However,the nature of the irregular rough morphology of commercial CIGS prevents people from improving tandem device performances.In this paper,D-homoserine lactone hydrochloride is proven to improve coverage of PVK materials on irregular rough CIGS surfaces and also passivate bulk defects by modulating the growth of PVK crystals.In addition,the minority carriers near the PVK/C60 interface and the incompletely passivated trap states caused interface recombination.A surface reconstruction with 2-thiopheneethylammonium iodide and N,N-dimethylformamide assisted passivates the defect sites located at the surface and grain boundaries.Meanwhile,LiF is used to create this field effect,repelling hole carriers away from the PVK and C60 interface and thus reducing recombination.As a result,a 2-T PVK/CIGS tandem yielded a power conversion efficiency of 24.6%(0.16 cm^(2)),one of the highest results for 2-T PVK/CIGS TSCs to our knowledge.This validation underscores the potential of our methodology in achieving superior performance in PVK/CIGS tandem solar cells.展开更多
Postoperative cognitive dysfunction is a seve re complication of the central nervous system that occurs after anesthesia and surgery,and has received attention for its high incidence and effect on the quality of life ...Postoperative cognitive dysfunction is a seve re complication of the central nervous system that occurs after anesthesia and surgery,and has received attention for its high incidence and effect on the quality of life of patients.To date,there are no viable treatment options for postoperative cognitive dysfunction.The identification of postoperative cognitive dysfunction hub genes could provide new research directions and therapeutic targets for future research.To identify the signaling mechanisms contributing to postoperative cognitive dysfunction,we first conducted Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses of the Gene Expression Omnibus GSE95426 dataset,which consists of mRNAs and long non-coding RNAs differentially expressed in mouse hippocampus3 days after tibial fracture.The dataset was enriched in genes associated with the biological process"regulation of immune cells,"of which Chill was identified as a hub gene.Therefore,we investigated the contribution of chitinase-3-like protein 1 protein expression changes to postoperative cognitive dysfunction in the mouse model of tibial fractu re surgery.Mice were intraperitoneally injected with vehicle or recombinant chitinase-3-like protein 124 hours post-surgery,and the injection groups were compared with untreated control mice for learning and memory capacities using the Y-maze and fear conditioning tests.In addition,protein expression levels of proinflammatory factors(interleukin-1βand inducible nitric oxide synthase),M2-type macrophage markers(CD206 and arginase-1),and cognition-related proteins(brain-derived neurotropic factor and phosphorylated NMDA receptor subunit NR2B)were measured in hippocampus by western blotting.Treatment with recombinant chitinase-3-like protein 1 prevented surgery-induced cognitive impairment,downregulated interleukin-1βand nducible nitric oxide synthase expression,and upregulated CD206,arginase-1,pNR2B,and brain-derived neurotropic factor expression compared with vehicle treatment.Intraperitoneal administration of the specific ERK inhibitor PD98059 diminished the effects of recombinant chitinase-3-like protein 1.Collectively,our findings suggest that recombinant chitinase-3-like protein 1 ameliorates surgery-induced cognitive decline by attenuating neuroinflammation via M2 microglial polarization in the hippocampus.Therefore,recombinant chitinase-3-like protein1 may have therapeutic potential fo r postoperative cognitive dysfunction.展开更多
A new type of 785 nm semiconductor laser device has been proposed.The thin cladding and mode expansion layer structure incorporated into the epitaxy on the p-side significantly impacts the regulation of grating etchin...A new type of 785 nm semiconductor laser device has been proposed.The thin cladding and mode expansion layer structure incorporated into the epitaxy on the p-side significantly impacts the regulation of grating etching depth.Thinning of the p-side waveguide layer makes the light field bias to the n-side cladding layer.By coordinating the confinement effect of the cladding layer,the light confinement factor on the p-side is regulated.On the other hand,the introduction of a mode expansion layer facilitates the expansion of the mode profile on the p side cladding layer.Both these factors contribute positively to reducing the grating etching depth.Compared to the reported epitaxial structures of symmetric waveguides,the new structure significantly reduces the etching depth of the grating while ensuring adequate reflection intensity and maintaining resonance.Moreover,to improve the output performance of the device,the new epitaxial structure has been optimized.Based on the traditional epitaxial structure,an energy release layer and an electron blocking layer are added to improve the electronic recombination efficiency.This improved structure has an output performance comparable to that of a symmetric waveguide,despite being able to have a smaller gain area.展开更多
[Objective]To design and express a recombinant protein rMKIBV incorporating confirmed antigenic epitopes of infectious bronchitis virus(IBV)as a vaccine to provide comprehensive protection.Additionally,it explores the...[Objective]To design and express a recombinant protein rMKIBV incorporating confirmed antigenic epitopes of infectious bronchitis virus(IBV)as a vaccine to provide comprehensive protection.Additionally,it explores the potential of polyclonal yolk antibodies(IgY)harvested from laying hens immunized with the rMKIBV vaccine in the prevention and control of IBV.[Methods]The antigenic epitope sequences of IBV,obtained from online databases,were compared with sequences of representative IBV strains from GenBank.Flexible peptides were designed to link all antigenic peptides.The constructed amino acid sequence was analyzed,reverse-translated,codon-optimized,and then inserted into the pET-28a(+)cloning vector.The recombinant vector was introduced into Escherichia coli for expression.The purified,desalted,and endotoxin-removed rMKIBV protein was used as a vaccine to immunize animals for investigation of its immunogenicity and ability to stimulate specific IgY production in laying hens.[Results]The retrieved IBV antigenic epitope sequences showed high similarity with the published N and S protein sequences of 22 representative IBV strains.The predicted isoelectric point and molecular weight of rMKIBV were 10.25 and 63.39 kDa,respectively.The secondary structure of rMKIBV included a high proportion of random coils,which suggested strong antigenicity.High-purity rMKIBV was obtained from E.coli transformed with the recombinant plasmid pET-28a-mkibv.This protein specifically bound to anti-His-tag antibodies,N protein antibodies,and S protein antibodies.The mice immunized with this protein showed increases in the spleen index(P<0.05),elevations in the levels of serum-specific IgG antibodies(P<0.01)and IFN-γ(P<0.05),and no significant change in the IL-2 level.Immunized laying hens successfully produced IgY in egg yolks,with specific IgY antibody levels significantly increasing.Moreover,the IgY antibody titer gradually rose after immunization,reaching the peak after about 50 days and then gradually declining to reach a stable level.[Conclusion]We successfully constructed and expressed the recombinant protein rMKIBV.The protein demonstrated good immunogenicity,stimulating specific antibody production in both mice and laying hens.Notably,the IgY extracted from the yolks of immunized laying hens offers a novel approach to IBV prevention and control.These findings hold significant scientific and practical value for the development of vaccines against IBV.展开更多
Exciton is an electron-hole pair with Coulomb interaction,which represents the binding energy of the two particles.The electron and hole in exciton may have either the opposite or the parallel spin directions,correspo...Exciton is an electron-hole pair with Coulomb interaction,which represents the binding energy of the two particles.The electron and hole in exciton may have either the opposite or the parallel spin directions,corresponding to bright(emissive)singlet exciton or dark(non-emissive)triplet exciton,respectively.Triplet states lie below but are three times abundant than singlet states.展开更多
Single-stranded DNA-binding proteins(SSBs)play essential roles in the replication,recombination and repair processes of organellar DNA molecules.In Arabidopsis thaliana,SSBs are encoded by a small family of two genes(...Single-stranded DNA-binding proteins(SSBs)play essential roles in the replication,recombination and repair processes of organellar DNA molecules.In Arabidopsis thaliana,SSBs are encoded by a small family of two genes(SSB1 and SSB2).However,the functional divergence of these two SSB copies in plants remains largely unknown,and detailed studies regarding their roles in the replication and recombination of organellar genomes are still incomplete.In this study,phylogenetic,gene structure and protein motif analyses all suggested that SSB1 and SSB2 probably diverged during the early evolution of seed plants.Based on accurate long-read sequencing results,ssb1 and ssb2 mutants had decreased copy numbers for both mitochondrial DNA(mtDNA)and plastid DNA(ptDNA),accompanied by a slight increase in structural rearrangements mediated by intermediate-sized repeats in mt genome and small-scale variants in both genomes.Our findings provide an important foundation for further investigating the effects of DNA dosage in the regulation of mutation frequencies in plant organellar genomes.展开更多
Since its discovery in the 1980s,the insect cell-baculovirus expression vector system(IC-BEVS)has been widely used in biomedical applications,such as recombinant protein expression,drug screening,vaccine development,g...Since its discovery in the 1980s,the insect cell-baculovirus expression vector system(IC-BEVS)has been widely used in biomedical applications,such as recombinant protein expression,drug screening,vaccine development,gene therapy and so on[1].As a eukaryotic system,IC-BEVS has great development prospects due to its advantages such as high safety,simple operation,simultaneous expression of multi-subunit proteins,and suitability for large-scale cultivation[2].展开更多
Biotechnology has revolutionized agriculture through innovations such as genetically modified(GM)technology and CRISPR/Cas9 genome editing.In this review,a comparative analysis of these methods that addresses the conc...Biotechnology has revolutionized agriculture through innovations such as genetically modified(GM)technology and CRISPR/Cas9 genome editing.In this review,a comparative analysis of these methods that addresses the concerns regarding the oversimplification of the notion that the CRISPR-based editing approach is equivalent to traditional GM approaches is offered.Since the 1990s,despite the potential benefits for crop improvement and food security,controversies have arisen around recombinant technology and the introduction of GM products due to perceived environmental and health concerns.In contrast,the recent emergence of the CRISPR/Cas systemas a precise genome editing tool has garnered relatively less public resistance.In this review,the reasons for these contrasting findings are explored to shed light on the distinct characteristics inherent to each approach.Additionally,we conduct a bibliographic analysis to examine the shift in research priorities between the two technological eras,followed by a comprehensive comparison of the two approaches,to enable a better understanding of the potential synergies that can be achieved between agricultural biotechnology and conventional techniques for enhancing modern agriculture.A nuanced understanding of these technologies is crucial for informed decision-making,responsible implementation,and addressing the concerns surrounding agricultural biotechnology.展开更多
The lead-free inorganic perovskite CsSnI_(3) is considered as one of the best candidates for emerging photovoltaics.Nevertheless,CsSnI_(3)-based perovskite solar cells experience a significant drop in performance due ...The lead-free inorganic perovskite CsSnI_(3) is considered as one of the best candidates for emerging photovoltaics.Nevertheless,CsSnI_(3)-based perovskite solar cells experience a significant drop in performance due to the nonradiative recombination facilitated by trapping.Here,we show an electron donor passivation method to regulate deep-level defects for CsSnI_(3) perovskite with electron donor pyrrole.Experimental observations combined with theoretical simulations verify that the saturation of Tin dangling bonds with pyrrole on the CsSnI_(3) surface via a Lewis acid-base addition reaction can significantly reduce the density of deep-level defects.Consequently,the printable mesoporous perovskite solar cells with an FTO/compact-TiO_(2)/mesoporous-TiO_(2)/Al_(2)O_(3)/NiO/carbon framework device structure penetrated with CsSnI_(3) achieve a power conversion efficiency of up to 10.11%.To our knowledge,this represents the highest efficiency reported to date for lead-free pero vs kite-based printable mesoporous solar cells.Furthermore,the unencapsulated devices demonstrated remarkable long-term stability,retaining 92%of their initial efficiency even after 2400 h of aging in a nitrogen atmosphere.展开更多
BACKGROUND Patients with colorectal cancer(CRC)exhibiting microsatellite instability(MSI)-high generally demonstrate a favorable response to immunotherapy.In contrast,the efficacy of immunotherapy in microsatellite-st...BACKGROUND Patients with colorectal cancer(CRC)exhibiting microsatellite instability(MSI)-high generally demonstrate a favorable response to immunotherapy.In contrast,the efficacy of immunotherapy in microsatellite-stable(MSS)CRC patients is considerably restricted.This study sought to evaluate the effectiveness of immu-notherapy in MSS patients characterized by homologous recombination defi-ciency(HRD)as opposed to those with homologous recombination proficiency(HRP).AIM To investigate and compare the clinicopathological characteristics,treatment modalities,and outcomes between the HRD and HRP groups in CRC.METHODS Next-generation sequencing was performed on 268 CRC patients to identify tumor-associated genetic alterations and assess their HRD scores and MSI status.Patients with HRD-related gene alterations or an HRD score≥30 were classified into the HRD group,while the remaining patients were assigned to the HRP group.Clinical data,including staging and treatment regimens,were collected for analysis.Cox regression and Kaplan-Meier survival curves were employed to evaluate whether the HRD group demonstrated improved survival outcomes following immunotherapy treatment.RESULTS Among the 268 patients,64 were classified into the HRD group,which had a higher proportion of early-stage CRC diagnoses compared to the HRP group.Kaplan-Meier survival curves indicated significantly better survival rates in the HRD group compared to the HRP group across all cohorts,as well as among MSS patients treated with immunotherapy(P<0.05).CONCLUSION This study demonstrates that CRC patients with HRD have a more favorable prognosis and suggests that HRD status could serve as a predictive marker for immunotherapy response in MSS patients.展开更多
The deployment of non-precious metal catalysts for the production of COx-free hydrogen via the ammonia decomposition reaction(ADR)presents a promising yet great challenge.In the present study,two crystal structures of...The deployment of non-precious metal catalysts for the production of COx-free hydrogen via the ammonia decomposition reaction(ADR)presents a promising yet great challenge.In the present study,two crystal structures of α-MoC and β-Mo_(2)C catalysts with different Mo/C ratios were synthesized,and their ammonia decomposition performance as well as structural evolution in ADR was investigated.The β-Mo_(2)C catalyst,characterized by a higher Mo/C ratio,demonstrated a remarkable turnover frequency of 1.3 s^(-1),which is over tenfold higher than that ofα-MoC(0.1 s^(-1)).An increase in the Mo/C ratio of molybdenum carbide revealed a direct correlation between the surface Mo/C ratio and the hydrogen yield.The transient response surface reaction indicated that the combination of N*and N*derived from NH_(3) dissociation represents the rate-determining step in the ADR,andβ-Mo2C exhibited exceptional proficiency in facilitating this pivotal step.Concurrently,the accumulation of N*species on the carbide surface could induce the phase transition of molybdenum carbide to nitride,which follows a topological transformation.It is discovered that such phase evolution was affected by the Mo-C surface and reaction temperature simultaneously.When the kinetics of combination of N*was accelerated by rising temperatures and its accumulation on the carbide surface was mitigated,β-Mo_(2)C maintained its carbide phase,preventing nitridation during the ADR at 810℃.Our results contribute to an in-depth understanding of the molybdenum carbides’catalytic properties in ADR and highlight the nature of the carbide-nitride phase transition in the reaction.展开更多
BACKGROUND Studies on the application of recombinant human endostatin(RH-endostatin)intraperitoneal perfusion in gastric cancer(GC)with malignant ascites are limited.AIM To explore the effectiveness,prognosis,and safe...BACKGROUND Studies on the application of recombinant human endostatin(RH-endostatin)intraperitoneal perfusion in gastric cancer(GC)with malignant ascites are limited.AIM To explore the effectiveness,prognosis,and safety of intraperitoneal RH-endostatin perfusion in treating patients with GC and malignant ascites.METHODS Patients with GC and malignant ascites were divided into the cisplatin intraperi-toneal perfusion(control group)group and the cisplatin combined with RH-endostatin intraperitoneal perfusion group(RH-endostatin group).Efficient ascites control,overall survival(OS),quality of life,and adverse events were observed,and possible influencing factors on prognosis outcomes analyzed.RESULTS We identified no significant differences in baseline characteristics between the control and RH-endostatin groups.The latter group had higher ascites control rates than the control group.Treatment methods were identified as an independent OS factor.Clinically,RH-endostatin-treated patients had significantly improved OS rates when compared with control patients,particularly in those with small and moderate ascites volumes.Quality of life improvements in control patients were significantly lower when compared with RH-endostatin patients.Adverse events were balanced between the groups.CONCLUSION Overall,intraperitoneal RH-endostatin improved treatment efficacy and prolonged prognosis in patients with GC and malignant ascites.This approach may benefit further clinical applications for treating GC.展开更多
Pentaploid hybrids produced from crosses between hexaploid and tetraploid wheats combine the genetic variation of both parents.Crossing a synthetic hexaploid wheat LM/AT23 with its AB-genome donor,the durum wheat LM,a...Pentaploid hybrids produced from crosses between hexaploid and tetraploid wheats combine the genetic variation of both parents.Crossing a synthetic hexaploid wheat LM/AT23 with its AB-genome donor,the durum wheat LM,and selfing the pentaploid hybrids to the F7 generation yielded mostly euploid tetraploids and a few hexaploids.Two special derivatives of tetraploid were isolated,including a 4D(4B)substitution line with large panicles and high resistance to stripe rust and a 2DS.2AL translocation line with non-waxy epidermis.The discovery of small D-genome introgressions in the A and B genomes suggested that pentaploidization can be used to induce homoeologous recombination.The introgression of D genome from Aegilops tauschii to the AB genomes might promote the development of super tetraploid wheat with hexaploid biological characteristics(especially stress resistance)and quality functions and the functional study of the introduced chromosomes or fragments.展开更多
Chromosomal DNA double-strand breaks(DSBs)are often generated in the genome of all living organisms.To combat DNA damage,organisms have evolved several DSB repair mechanisms,with nonhomologous end-joining(NHEJ)and hom...Chromosomal DNA double-strand breaks(DSBs)are often generated in the genome of all living organisms.To combat DNA damage,organisms have evolved several DSB repair mechanisms,with nonhomologous end-joining(NHEJ)and homologous recombination(HR)being the two most prominent.Although two major pathways have been extensively studied in Arabidopsis,rice and other mammals,the exact functions and differences between the two DSB repair pathways in maize still remain less well understood.Here,we characterized mre11a and rad50,mutants of HR pathway patterns,which showed drastic degradation of the typically persistent embryo and endosperm during kernel development.Loss of MRE11 or RAD50 function led to chromosomal fragments and chromosomal bridges in anaphase.While we also reported that the NHEJ pathway patterns,KU70 and KU80 are associated with developmental growth and genome stability.ku70 and ku80 both displayed an obvious dwarf phenotype.Cytological analysis of the mutants revealed extensive chromosome fragmentation in metaphase and subsequent stages.Loss of KU70/80 function upregulated the expression of genes involved in cell cycle progression and nuclear division.These results provide insights into how NHEJ and HR are mechanistically executed during different plant developmental periods and highlight a competitive and complementary relationship between the NHEJ and HR pathways for DNA double-strand break repair in maize.展开更多
Objective Recombination events are common and serve as the primary driving force of diverse human adenovirus(HAdV),particularly in children with acute respiratory tract infections(ARIs).Therefore,continual monitoring ...Objective Recombination events are common and serve as the primary driving force of diverse human adenovirus(HAdV),particularly in children with acute respiratory tract infections(ARIs).Therefore,continual monitoring of these events is essential for effective viral surveillance and control.Methods Respiratory specimens were collected from children with ARIs between January 2022 and December 2023.The penton base,hexon,and fiber genes were amplified from HAdV-positive specimens and sequenced to determine the virus type.In cases with inconsistent typing results,genes were cloned into the pGEM-T vector to detect recombination events.Metagenomic next-generation sequencing(mNGS)was performed to characterize the recombinant HAdV genomes.Results Among 6,771 specimens,277(4.09%,277/6,771)were positvie for HAdV,of which 157(56.68%,157/277)were successfully typed,with HAdV-B3 being the dominant type(91.08%,143/157),and 14(5.05%,14/277)exhibited inconsistent typing results,six of which belonged to species B.The penton base genes of these six specimens were classified as HAdV-B7,whereas their hexon and fiber genes were classified as HAdV-B3,resulting in a recombinant genotype designated P7H3F3,which closely resembled HAdV-B114.Additionally,a partial gene encoding L152/55 kD was identified,which originated from HAdV-B16.Conclusion A novel recombinant,P7H3F3,was identified,containing sequences derived from HAdV-B3 and HAdV-B7,which is similar to HAdV-B114,along with additional sequences from HAdV-B16.展开更多
BACKGROUND Patients with acute-on-chronic liver failure(ACLF)have a high mortality rate,poor prognosis,and often experience concurrent thrombocytopenia and bleeding events.AIM To evaluate the efficacy and safety of re...BACKGROUND Patients with acute-on-chronic liver failure(ACLF)have a high mortality rate,poor prognosis,and often experience concurrent thrombocytopenia and bleeding events.AIM To evaluate the efficacy and safety of recombinant human thrombopoietin(rhTPO)in patients with ACLF with concomitant severe thrombocytopenia.METHODS This was a prospective,open-label study.We assigned 70 ACLF patients with severe thrombocytopenia into the rhTPO group and control group,with 35 patients in each group.Patients in the rhTPO group received subcutaneous injections of rhTPO at a dose of 15000 IU/day for 7 consecutive days,while patients in the control group did not receive rhTPO treatment.The primary endpoint was the proportion of patients with platelet count>50×10^(9)/L on day 14.RESULTS The proportion of patients with platelet count>50×10^(9)/L on day 14 was 60.7%in the rhTPO group,which was significantly higher than that(12.0%)in the control group(P<0.001).The platelet count in the rhTPO group on day 14 was 64×10^(9)/L,exceeding the baseline of 28×10^(9)/L.Compared to the control group,the rhTPO group exhibited a significant increase in platelet count from baseline(P<0.05).Model for end-stage liver disease score,albumin level and international normalized ratio improved significantly from baseline on day 14 after rhTPO injection.The concentrations of serum thrombopoietin and hepatocyte growth factor in the rhTPO group after 7 days were 143.7 and 195.4 pg/mL,respectively,showing a significant increase from baseline(P<0.05).Eight(22.9%)patients had bleeding events in the control group compared with four(11.4%)in the rhTPO group.The incidence of 90-day mortality was also higher in the control group(6,17.1%)than that in the rhTPO group(3,8.6%).CONCLUSION rhTPO significantly increased the platelet count in ACLF patients with thrombocytopenia and reduce the occurrence of bleeding events,with a good safety profile.展开更多
基金financially supported by the Shanghai New Three-Year Action Plan for Public Health(Grant No.GWVI-11.1-03)National Natural Science Foundation of China(Grant No.81872673).
文摘Objective Poxviruses are zoonotic pathogens that infect humans,mammals,vertebrates,and arthropods.However,the specific role of ticks in transmission and evolution of these viruses remains unclear.Methods Transcriptomic and metatranscriptomic raw data from 329 sampling pools of seven tick species across five continents were mined to assess the diversity and abundance of poxviruses.Chordopoxviral sequences were assembled and subjected to phylogenetic analysis to trace the origins of the unblasted fragments within these sequences.Results Fifty-eight poxvirus species,representing two subfamilies and 20 genera,were identified,with 212 poxviral sequences assembled.A substantial proportion of AT-rich fragments were detected in the assembled poxviral genomes.These genomic sequences contained fragments originating from rodents,archaea,and arthropods.Conclusion Our findings indicate that ticks play a significant role in the transmission and evolution of poxviruses.These viruses demonstrate the capacity to modulate virulence and adaptability through horizontal gene transfer,gene recombination,and gene mutations,thereby promoting co-existence and co-evolution with their hosts.This study advances understanding of the ecological dynamics of poxvirus transmission and evolution and highlights the potential role of ticks as vectors and vessels in these processes.
基金supported by grants from the Medical Engineering Jiont Fund of the Fudan University(No.IDH2310117)。
文摘Objective:Triple-negative breast cancer(TNBC)is a highly aggressive subtype that lacks targeted therapies,leading to a poorer prognosis.However,some patients achieve long-term recurrence-free survival(RFS),offering valuable insights into tumor biology and potential treatment strategies.Methods:We conducted a comprehensive multi-omics analysis of 132 patients with American Joint Committee on Cancer(AJCC)stage III TNBC,comprising 36 long-term survivors(RFS≥8 years),62 moderate-term survivors(RFS:3-8 years),and 34 short-term survivors(RFS<3 years).Analyses investigated clinicopathological factors,whole-exome sequencing,germline mutations,copy number alterations(CNAs),RNA sequences,and metabolomic profiles.Results:Long-term survivors exhibited fewer metastatic regional lymph nodes,along with tumors showing reduced stromal fibrosis and lower Ki67 index.Molecularly,these tumors exhibited multiple alterations in genes related to homologous recombination repair,with higher frequencies of germline mutations and somatic CNAs.Additionally,tumors from long-term survivors demonstrated significant downregulation of the RTK-RAS signaling pathway.Metabolomic profiling revealed decreased levels of lipids and carbohydrate,particularly those involved in glycerophospholipid,fructose,and mannose metabolism,in long-term survival group.Multivariate Cox analysis identified fibrosis[hazard ratio(HR):12.70,95%confidence interval(95%CI):2.19-73.54,P=0.005]and RAC1copy number loss/deletion(HR:0.22,95%CI:0.06-0.83,P=0.026)as independent predictors of RFS.Higher fructose/mannose metabolism was associated with worse overall survival(HR:1.30,95%CI:1.01-1.68,P=0.045).Our findings emphasize the association between biological determinants and prolonged survival in patients with TNBC.Conclusions:Our study systematically identified the key molecular and metabolic features associated with prolonged survival in AJCC stage III TNBC,suggesting potential therapeutic targets to improve patient outcomes.
基金support from the National Natural Science Foundation of China(62275057)the Guangxi Natural Science Foundation(2023GXNSFFA026004 and 2022GXNSFDA035066)+2 种基金the Innovation Project of Guangxi Graduate Education(YCBZ2024034)Natural Science Foundation of Ningbo under grant(2022J149)Natural Science Foundation of Ningbo under grant(2022A-230-G)
文摘Trap-assisted charge recombination is one of the primary limitationsof restricting the performance of organic solar cells. However, effectivelyreducing the presence of traps in the photoactive layer remains challenging.Herein, wide bandgap polymer donor PTzBI-dF is demonstrated as an effectivemodulator for enhancing the crystallinity of the bulk heterojunction active layerscomposed of D18 derivatives blended with Y6, leading to dense and orderedmolecular packings, and thus, improves photoluminescence quenching properties.As a result, the photovoltaic devices exhibit reduced trap-assisted charge recombinationlosses, achieving an optimized power conversion efficiency of over 19%.Besides the efficiency enhancement, the devices comprised of PTzBI-dF as athird component simultaneously attain decreased current leakage, improved chargecarrier mobilities, and suppressed bimolecular charge recombination, leading toreduced energy losses. The advanced crystalline structures induced by PTzBI-dFand its characteristics, such as well-aligned energy level, and complementaryabsorption spectra, are ascribed to the promising performance improvements.Our findings suggest that donor phase engineering is a feasible approach to tuning the molecular packings in the active layer, providingguidelines for designing effective morphology modulators for high-performance organic solar cells.
基金supported by“National Natural Science Foundation of China(U21A20171,U20A20245)”“Hubei Provincial Natural Science Foundation of China(2023AFA010)”+1 种基金“Independent Innovation Projects of the Hubei Longzhong Laboratory(2022ZZ-09)”“Social Public Welfare and Basic Research Special Project of Zhongshan(2020B2015).”。
文摘Two-terminal(2-T)perovskite(PVK)/CuIn(Ga)Se_(2)(CIGS)tandem solar cells(TSCs)have been considered as an ideal tandem cell because of their best bandgap matching regarding to Shockley–Queisser(S–Q)limits.However,the nature of the irregular rough morphology of commercial CIGS prevents people from improving tandem device performances.In this paper,D-homoserine lactone hydrochloride is proven to improve coverage of PVK materials on irregular rough CIGS surfaces and also passivate bulk defects by modulating the growth of PVK crystals.In addition,the minority carriers near the PVK/C60 interface and the incompletely passivated trap states caused interface recombination.A surface reconstruction with 2-thiopheneethylammonium iodide and N,N-dimethylformamide assisted passivates the defect sites located at the surface and grain boundaries.Meanwhile,LiF is used to create this field effect,repelling hole carriers away from the PVK and C60 interface and thus reducing recombination.As a result,a 2-T PVK/CIGS tandem yielded a power conversion efficiency of 24.6%(0.16 cm^(2)),one of the highest results for 2-T PVK/CIGS TSCs to our knowledge.This validation underscores the potential of our methodology in achieving superior performance in PVK/CIGS tandem solar cells.
基金supported by the National Natural Science Foundation of China,Nos.81730033,82171193(to XG)the Key Talent Project for Strengthening Health during the 13^(th)Five-Year Plan Period,No.ZDRCA2016069(to XG)+1 种基金the National Key R&D Program of China,No.2018YFC2001901(to XG)Jiangsu Provincial Medical Key Discipline,No.ZDXK202232(to XG)。
文摘Postoperative cognitive dysfunction is a seve re complication of the central nervous system that occurs after anesthesia and surgery,and has received attention for its high incidence and effect on the quality of life of patients.To date,there are no viable treatment options for postoperative cognitive dysfunction.The identification of postoperative cognitive dysfunction hub genes could provide new research directions and therapeutic targets for future research.To identify the signaling mechanisms contributing to postoperative cognitive dysfunction,we first conducted Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses of the Gene Expression Omnibus GSE95426 dataset,which consists of mRNAs and long non-coding RNAs differentially expressed in mouse hippocampus3 days after tibial fracture.The dataset was enriched in genes associated with the biological process"regulation of immune cells,"of which Chill was identified as a hub gene.Therefore,we investigated the contribution of chitinase-3-like protein 1 protein expression changes to postoperative cognitive dysfunction in the mouse model of tibial fractu re surgery.Mice were intraperitoneally injected with vehicle or recombinant chitinase-3-like protein 124 hours post-surgery,and the injection groups were compared with untreated control mice for learning and memory capacities using the Y-maze and fear conditioning tests.In addition,protein expression levels of proinflammatory factors(interleukin-1βand inducible nitric oxide synthase),M2-type macrophage markers(CD206 and arginase-1),and cognition-related proteins(brain-derived neurotropic factor and phosphorylated NMDA receptor subunit NR2B)were measured in hippocampus by western blotting.Treatment with recombinant chitinase-3-like protein 1 prevented surgery-induced cognitive impairment,downregulated interleukin-1βand nducible nitric oxide synthase expression,and upregulated CD206,arginase-1,pNR2B,and brain-derived neurotropic factor expression compared with vehicle treatment.Intraperitoneal administration of the specific ERK inhibitor PD98059 diminished the effects of recombinant chitinase-3-like protein 1.Collectively,our findings suggest that recombinant chitinase-3-like protein 1 ameliorates surgery-induced cognitive decline by attenuating neuroinflammation via M2 microglial polarization in the hippocampus.Therefore,recombinant chitinase-3-like protein1 may have therapeutic potential fo r postoperative cognitive dysfunction.
文摘A new type of 785 nm semiconductor laser device has been proposed.The thin cladding and mode expansion layer structure incorporated into the epitaxy on the p-side significantly impacts the regulation of grating etching depth.Thinning of the p-side waveguide layer makes the light field bias to the n-side cladding layer.By coordinating the confinement effect of the cladding layer,the light confinement factor on the p-side is regulated.On the other hand,the introduction of a mode expansion layer facilitates the expansion of the mode profile on the p side cladding layer.Both these factors contribute positively to reducing the grating etching depth.Compared to the reported epitaxial structures of symmetric waveguides,the new structure significantly reduces the etching depth of the grating while ensuring adequate reflection intensity and maintaining resonance.Moreover,to improve the output performance of the device,the new epitaxial structure has been optimized.Based on the traditional epitaxial structure,an energy release layer and an electron blocking layer are added to improve the electronic recombination efficiency.This improved structure has an output performance comparable to that of a symmetric waveguide,despite being able to have a smaller gain area.
文摘[Objective]To design and express a recombinant protein rMKIBV incorporating confirmed antigenic epitopes of infectious bronchitis virus(IBV)as a vaccine to provide comprehensive protection.Additionally,it explores the potential of polyclonal yolk antibodies(IgY)harvested from laying hens immunized with the rMKIBV vaccine in the prevention and control of IBV.[Methods]The antigenic epitope sequences of IBV,obtained from online databases,were compared with sequences of representative IBV strains from GenBank.Flexible peptides were designed to link all antigenic peptides.The constructed amino acid sequence was analyzed,reverse-translated,codon-optimized,and then inserted into the pET-28a(+)cloning vector.The recombinant vector was introduced into Escherichia coli for expression.The purified,desalted,and endotoxin-removed rMKIBV protein was used as a vaccine to immunize animals for investigation of its immunogenicity and ability to stimulate specific IgY production in laying hens.[Results]The retrieved IBV antigenic epitope sequences showed high similarity with the published N and S protein sequences of 22 representative IBV strains.The predicted isoelectric point and molecular weight of rMKIBV were 10.25 and 63.39 kDa,respectively.The secondary structure of rMKIBV included a high proportion of random coils,which suggested strong antigenicity.High-purity rMKIBV was obtained from E.coli transformed with the recombinant plasmid pET-28a-mkibv.This protein specifically bound to anti-His-tag antibodies,N protein antibodies,and S protein antibodies.The mice immunized with this protein showed increases in the spleen index(P<0.05),elevations in the levels of serum-specific IgG antibodies(P<0.01)and IFN-γ(P<0.05),and no significant change in the IL-2 level.Immunized laying hens successfully produced IgY in egg yolks,with specific IgY antibody levels significantly increasing.Moreover,the IgY antibody titer gradually rose after immunization,reaching the peak after about 50 days and then gradually declining to reach a stable level.[Conclusion]We successfully constructed and expressed the recombinant protein rMKIBV.The protein demonstrated good immunogenicity,stimulating specific antibody production in both mice and laying hens.Notably,the IgY extracted from the yolks of immunized laying hens offers a novel approach to IBV prevention and control.These findings hold significant scientific and practical value for the development of vaccines against IBV.
文摘Exciton is an electron-hole pair with Coulomb interaction,which represents the binding energy of the two particles.The electron and hole in exciton may have either the opposite or the parallel spin directions,corresponding to bright(emissive)singlet exciton or dark(non-emissive)triplet exciton,respectively.Triplet states lie below but are three times abundant than singlet states.
基金supported by grants from the National Natural Science Foundation of China(32170238,32400191)Guangdong Basic and Applied Basic Research Foundation(2023A1515111029)+2 种基金the Science,Technology and Innovation Commission of Shenzhen Municipality(RCYX20200714114538196)the Chinese Academy of Agricultural Sciences Elite Youth Program(grant 110243160001007)the Guangdong Pearl River Talent Program(2021QN02N792)。
文摘Single-stranded DNA-binding proteins(SSBs)play essential roles in the replication,recombination and repair processes of organellar DNA molecules.In Arabidopsis thaliana,SSBs are encoded by a small family of two genes(SSB1 and SSB2).However,the functional divergence of these two SSB copies in plants remains largely unknown,and detailed studies regarding their roles in the replication and recombination of organellar genomes are still incomplete.In this study,phylogenetic,gene structure and protein motif analyses all suggested that SSB1 and SSB2 probably diverged during the early evolution of seed plants.Based on accurate long-read sequencing results,ssb1 and ssb2 mutants had decreased copy numbers for both mitochondrial DNA(mtDNA)and plastid DNA(ptDNA),accompanied by a slight increase in structural rearrangements mediated by intermediate-sized repeats in mt genome and small-scale variants in both genomes.Our findings provide an important foundation for further investigating the effects of DNA dosage in the regulation of mutation frequencies in plant organellar genomes.
文摘Since its discovery in the 1980s,the insect cell-baculovirus expression vector system(IC-BEVS)has been widely used in biomedical applications,such as recombinant protein expression,drug screening,vaccine development,gene therapy and so on[1].As a eukaryotic system,IC-BEVS has great development prospects due to its advantages such as high safety,simple operation,simultaneous expression of multi-subunit proteins,and suitability for large-scale cultivation[2].
基金supported by the by the Fundamental Research Grant Scheme(Grant No.FRGS/1/2023/STG03/UM/02/2)Universiti Malaya RU Fund(Grant No.ST087-2022).
文摘Biotechnology has revolutionized agriculture through innovations such as genetically modified(GM)technology and CRISPR/Cas9 genome editing.In this review,a comparative analysis of these methods that addresses the concerns regarding the oversimplification of the notion that the CRISPR-based editing approach is equivalent to traditional GM approaches is offered.Since the 1990s,despite the potential benefits for crop improvement and food security,controversies have arisen around recombinant technology and the introduction of GM products due to perceived environmental and health concerns.In contrast,the recent emergence of the CRISPR/Cas systemas a precise genome editing tool has garnered relatively less public resistance.In this review,the reasons for these contrasting findings are explored to shed light on the distinct characteristics inherent to each approach.Additionally,we conduct a bibliographic analysis to examine the shift in research priorities between the two technological eras,followed by a comprehensive comparison of the two approaches,to enable a better understanding of the potential synergies that can be achieved between agricultural biotechnology and conventional techniques for enhancing modern agriculture.A nuanced understanding of these technologies is crucial for informed decision-making,responsible implementation,and addressing the concerns surrounding agricultural biotechnology.
基金supported by the National Key Research and Development Program of China(2022YFB4200305)the National Natural Science Foundation of China(22379049)Hubei Provincial Key Research and Development Program(2023BAB113)。
文摘The lead-free inorganic perovskite CsSnI_(3) is considered as one of the best candidates for emerging photovoltaics.Nevertheless,CsSnI_(3)-based perovskite solar cells experience a significant drop in performance due to the nonradiative recombination facilitated by trapping.Here,we show an electron donor passivation method to regulate deep-level defects for CsSnI_(3) perovskite with electron donor pyrrole.Experimental observations combined with theoretical simulations verify that the saturation of Tin dangling bonds with pyrrole on the CsSnI_(3) surface via a Lewis acid-base addition reaction can significantly reduce the density of deep-level defects.Consequently,the printable mesoporous perovskite solar cells with an FTO/compact-TiO_(2)/mesoporous-TiO_(2)/Al_(2)O_(3)/NiO/carbon framework device structure penetrated with CsSnI_(3) achieve a power conversion efficiency of up to 10.11%.To our knowledge,this represents the highest efficiency reported to date for lead-free pero vs kite-based printable mesoporous solar cells.Furthermore,the unencapsulated devices demonstrated remarkable long-term stability,retaining 92%of their initial efficiency even after 2400 h of aging in a nitrogen atmosphere.
基金Supported by Natural Science Foundation of Guangdong Province,No.2021A1515011146 and No.2023A1515010785Key Areas Research and Development Programs of Guangdong Province,No.2023B1111050009.
文摘BACKGROUND Patients with colorectal cancer(CRC)exhibiting microsatellite instability(MSI)-high generally demonstrate a favorable response to immunotherapy.In contrast,the efficacy of immunotherapy in microsatellite-stable(MSS)CRC patients is considerably restricted.This study sought to evaluate the effectiveness of immu-notherapy in MSS patients characterized by homologous recombination defi-ciency(HRD)as opposed to those with homologous recombination proficiency(HRP).AIM To investigate and compare the clinicopathological characteristics,treatment modalities,and outcomes between the HRD and HRP groups in CRC.METHODS Next-generation sequencing was performed on 268 CRC patients to identify tumor-associated genetic alterations and assess their HRD scores and MSI status.Patients with HRD-related gene alterations or an HRD score≥30 were classified into the HRD group,while the remaining patients were assigned to the HRP group.Clinical data,including staging and treatment regimens,were collected for analysis.Cox regression and Kaplan-Meier survival curves were employed to evaluate whether the HRD group demonstrated improved survival outcomes following immunotherapy treatment.RESULTS Among the 268 patients,64 were classified into the HRD group,which had a higher proportion of early-stage CRC diagnoses compared to the HRP group.Kaplan-Meier survival curves indicated significantly better survival rates in the HRD group compared to the HRP group across all cohorts,as well as among MSS patients treated with immunotherapy(P<0.05).CONCLUSION This study demonstrates that CRC patients with HRD have a more favorable prognosis and suggests that HRD status could serve as a predictive marker for immunotherapy response in MSS patients.
文摘The deployment of non-precious metal catalysts for the production of COx-free hydrogen via the ammonia decomposition reaction(ADR)presents a promising yet great challenge.In the present study,two crystal structures of α-MoC and β-Mo_(2)C catalysts with different Mo/C ratios were synthesized,and their ammonia decomposition performance as well as structural evolution in ADR was investigated.The β-Mo_(2)C catalyst,characterized by a higher Mo/C ratio,demonstrated a remarkable turnover frequency of 1.3 s^(-1),which is over tenfold higher than that ofα-MoC(0.1 s^(-1)).An increase in the Mo/C ratio of molybdenum carbide revealed a direct correlation between the surface Mo/C ratio and the hydrogen yield.The transient response surface reaction indicated that the combination of N*and N*derived from NH_(3) dissociation represents the rate-determining step in the ADR,andβ-Mo2C exhibited exceptional proficiency in facilitating this pivotal step.Concurrently,the accumulation of N*species on the carbide surface could induce the phase transition of molybdenum carbide to nitride,which follows a topological transformation.It is discovered that such phase evolution was affected by the Mo-C surface and reaction temperature simultaneously.When the kinetics of combination of N*was accelerated by rising temperatures and its accumulation on the carbide surface was mitigated,β-Mo_(2)C maintained its carbide phase,preventing nitridation during the ADR at 810℃.Our results contribute to an in-depth understanding of the molybdenum carbides’catalytic properties in ADR and highlight the nature of the carbide-nitride phase transition in the reaction.
基金Supported by Scientific Research Project of Tianjin Municipal Education Commission,No.2018KJ015.
文摘BACKGROUND Studies on the application of recombinant human endostatin(RH-endostatin)intraperitoneal perfusion in gastric cancer(GC)with malignant ascites are limited.AIM To explore the effectiveness,prognosis,and safety of intraperitoneal RH-endostatin perfusion in treating patients with GC and malignant ascites.METHODS Patients with GC and malignant ascites were divided into the cisplatin intraperi-toneal perfusion(control group)group and the cisplatin combined with RH-endostatin intraperitoneal perfusion group(RH-endostatin group).Efficient ascites control,overall survival(OS),quality of life,and adverse events were observed,and possible influencing factors on prognosis outcomes analyzed.RESULTS We identified no significant differences in baseline characteristics between the control and RH-endostatin groups.The latter group had higher ascites control rates than the control group.Treatment methods were identified as an independent OS factor.Clinically,RH-endostatin-treated patients had significantly improved OS rates when compared with control patients,particularly in those with small and moderate ascites volumes.Quality of life improvements in control patients were significantly lower when compared with RH-endostatin patients.Adverse events were balanced between the groups.CONCLUSION Overall,intraperitoneal RH-endostatin improved treatment efficacy and prolonged prognosis in patients with GC and malignant ascites.This approach may benefit further clinical applications for treating GC.
基金funded by the Natural Science Foundation of Sichuan Province for Young Scholars(2024NSFSC1218)the HighLevel Talent Introduction Project of Sichuan Academy of Agricultural Sciences(NKYRCZX2024022)+1 种基金the Accurate Identification Project of Crop Germplasm from Sichuan Provincial Finance Department(1+3 ZYGG001)the Strategic Scientist Studio of Sichuan Academy of Agricultural Sciences.
文摘Pentaploid hybrids produced from crosses between hexaploid and tetraploid wheats combine the genetic variation of both parents.Crossing a synthetic hexaploid wheat LM/AT23 with its AB-genome donor,the durum wheat LM,and selfing the pentaploid hybrids to the F7 generation yielded mostly euploid tetraploids and a few hexaploids.Two special derivatives of tetraploid were isolated,including a 4D(4B)substitution line with large panicles and high resistance to stripe rust and a 2DS.2AL translocation line with non-waxy epidermis.The discovery of small D-genome introgressions in the A and B genomes suggested that pentaploidization can be used to induce homoeologous recombination.The introgression of D genome from Aegilops tauschii to the AB genomes might promote the development of super tetraploid wheat with hexaploid biological characteristics(especially stress resistance)and quality functions and the functional study of the introduced chromosomes or fragments.
基金supported by the National Natural Science Foundation of China(32372116)to Yan He.
文摘Chromosomal DNA double-strand breaks(DSBs)are often generated in the genome of all living organisms.To combat DNA damage,organisms have evolved several DSB repair mechanisms,with nonhomologous end-joining(NHEJ)and homologous recombination(HR)being the two most prominent.Although two major pathways have been extensively studied in Arabidopsis,rice and other mammals,the exact functions and differences between the two DSB repair pathways in maize still remain less well understood.Here,we characterized mre11a and rad50,mutants of HR pathway patterns,which showed drastic degradation of the typically persistent embryo and endosperm during kernel development.Loss of MRE11 or RAD50 function led to chromosomal fragments and chromosomal bridges in anaphase.While we also reported that the NHEJ pathway patterns,KU70 and KU80 are associated with developmental growth and genome stability.ku70 and ku80 both displayed an obvious dwarf phenotype.Cytological analysis of the mutants revealed extensive chromosome fragmentation in metaphase and subsequent stages.Loss of KU70/80 function upregulated the expression of genes involved in cell cycle progression and nuclear division.These results provide insights into how NHEJ and HR are mechanistically executed during different plant developmental periods and highlight a competitive and complementary relationship between the NHEJ and HR pathways for DNA double-strand break repair in maize.
基金supported by the Capital’s Funds for Health Improvement and Research(CFH,shoufa-2022-1G-1131 and shoufa 2022-4G-1133)the High Level Technical Talent Construction Project of Beijing Municipal Health Commission(Discipline Leader-02-20)+1 种基金Beijing Municipal Public Welfare Development and Reform Pilot Project for Medical Research Institutes(JYY2023-10)the Pathogen Spectrum and Host Marker Analysis in Children with Respiratory Tract Infections of Children(Grant 2024-0040).
文摘Objective Recombination events are common and serve as the primary driving force of diverse human adenovirus(HAdV),particularly in children with acute respiratory tract infections(ARIs).Therefore,continual monitoring of these events is essential for effective viral surveillance and control.Methods Respiratory specimens were collected from children with ARIs between January 2022 and December 2023.The penton base,hexon,and fiber genes were amplified from HAdV-positive specimens and sequenced to determine the virus type.In cases with inconsistent typing results,genes were cloned into the pGEM-T vector to detect recombination events.Metagenomic next-generation sequencing(mNGS)was performed to characterize the recombinant HAdV genomes.Results Among 6,771 specimens,277(4.09%,277/6,771)were positvie for HAdV,of which 157(56.68%,157/277)were successfully typed,with HAdV-B3 being the dominant type(91.08%,143/157),and 14(5.05%,14/277)exhibited inconsistent typing results,six of which belonged to species B.The penton base genes of these six specimens were classified as HAdV-B7,whereas their hexon and fiber genes were classified as HAdV-B3,resulting in a recombinant genotype designated P7H3F3,which closely resembled HAdV-B114.Additionally,a partial gene encoding L152/55 kD was identified,which originated from HAdV-B16.Conclusion A novel recombinant,P7H3F3,was identified,containing sequences derived from HAdV-B3 and HAdV-B7,which is similar to HAdV-B114,along with additional sequences from HAdV-B16.
基金Supported by Tianjin Key Medical Discipline(Specialty)Construction Project,No.TJYXZDXK-034A.
文摘BACKGROUND Patients with acute-on-chronic liver failure(ACLF)have a high mortality rate,poor prognosis,and often experience concurrent thrombocytopenia and bleeding events.AIM To evaluate the efficacy and safety of recombinant human thrombopoietin(rhTPO)in patients with ACLF with concomitant severe thrombocytopenia.METHODS This was a prospective,open-label study.We assigned 70 ACLF patients with severe thrombocytopenia into the rhTPO group and control group,with 35 patients in each group.Patients in the rhTPO group received subcutaneous injections of rhTPO at a dose of 15000 IU/day for 7 consecutive days,while patients in the control group did not receive rhTPO treatment.The primary endpoint was the proportion of patients with platelet count>50×10^(9)/L on day 14.RESULTS The proportion of patients with platelet count>50×10^(9)/L on day 14 was 60.7%in the rhTPO group,which was significantly higher than that(12.0%)in the control group(P<0.001).The platelet count in the rhTPO group on day 14 was 64×10^(9)/L,exceeding the baseline of 28×10^(9)/L.Compared to the control group,the rhTPO group exhibited a significant increase in platelet count from baseline(P<0.05).Model for end-stage liver disease score,albumin level and international normalized ratio improved significantly from baseline on day 14 after rhTPO injection.The concentrations of serum thrombopoietin and hepatocyte growth factor in the rhTPO group after 7 days were 143.7 and 195.4 pg/mL,respectively,showing a significant increase from baseline(P<0.05).Eight(22.9%)patients had bleeding events in the control group compared with four(11.4%)in the rhTPO group.The incidence of 90-day mortality was also higher in the control group(6,17.1%)than that in the rhTPO group(3,8.6%).CONCLUSION rhTPO significantly increased the platelet count in ACLF patients with thrombocytopenia and reduce the occurrence of bleeding events,with a good safety profile.
