Genome engineering of Rhodococcus opacus PD630,an important microorganism used for the bioconversion of lignin,is currently dependent on inefficient homologous recombination.Although a CRISPR interference procedure fo...Genome engineering of Rhodococcus opacus PD630,an important microorganism used for the bioconversion of lignin,is currently dependent on inefficient homologous recombination.Although a CRISPR interference procedure for gene repression has previously been developed for R.opacus PD630,a CRISPR/Cas9 system for gene knockout has yet to be reported for the strain.In this study,we found that the cytotoxicity of Cas9 and the deficiency in pathways for repairing DNA double-strand breaks(DSBs)were the major causes of the failure of conventional CRISPR/Cas9 technologies in R.opacus,even when augmented with the recombinases Che9c60 and Che9c61.We successfully developed an efficient single-stranded DNA(ssDNA)recombineering system coupled with CRISPR/Cas9 counter-selection,which facilitated rapid and scarless editing of the R.opacus genome.A two-plasmid system,comprising Cas9 driven by a weak Rhodococcus promoter Pniami,designed to prevent cytotoxicity,and a single-guide RNA(sgRNA)under the control of a strong constitutive promoter,was proven to be appropriate with respect to cleavage function.A novel recombinase,RrRecT derived from a Rhodococcus ruber prophage,was identified for the first time,which facilitated recombination of short ssDNA donors(40-80 nt)targeted to the lagging strand and enabled us to obtain a recombination efficiency up to 103-fold higher than that of endogenous pathways.Finally,by incorporating RrRecT and Cas9 into a single plasmid and then co-transforming cells with sgRNA plasmids and short ssDNA donors,we efficiently achieved gene disruption and base mutation in R.opacus,with editing efficiencies ranging from 22%to 100%.Simultaneous disruption of double genes was also confirmed,although at a lower efficiency.This effective genome editing tool will accelerate the engineering of R.opacus metabolism.展开更多
Iron is essential for bacterial survival,and most bacteria capture iron by producing siderophores.Burkholde-riales bacteria produce various types of bioactive secondary metabolites,such as ornibactin and malleobactin ...Iron is essential for bacterial survival,and most bacteria capture iron by producing siderophores.Burkholde-riales bacteria produce various types of bioactive secondary metabolites,such as ornibactin and malleobactin siderophores.In this study,the genome analysis of Burkholderiales genomes showed a putative novel siderophore gene cluster crb,which is highly similar to the ornibactin and malleobactin gene clusters but does not have pvdF,a gene encoding a formyltransferase for N-δ-hydroxy-ornithine formylation.Establishing the bacteriophage recom-binase Redγ-Redδβ7029 mediated genome editing system in a non-model Burkholderiales strain Paraburkholderia caribensis CICC 10960 allowed the rapid identification of the products of crb gene cluster,caribactins A-F(1-6).Caribactins contain a special amino acid residue N-δ-hydroxy-N-δ-acetylornithine(haOrn),which differs from the counterpart N-δ-hydroxy-N-δ-formylornithine(hOrn)in ornibactin and malleobactin,owing to the absence of pvdF.Gene inactivation showed that the acetylation of hOrn is catalyzed by CrbK,whose homologs proba-bly not be involved in the biosynthesis of ornibactin and malleobactin,showing possible evolutionary clues of these siderophore biosynthetic pathways from different genera.Caribactins promote biofilm production and en-hance swarming and swimming abilities,suggesting that they may play crucial roles in biofilm formation.This study also revealed that recombineering has the capability to mine novel secondary metabolites from non-model Burkholderiales species.展开更多
Recombineering is an essential tool for molecular biologists,allowing for the facile and efficient manipulation of bacterial genomes directly in cells without the need for costly and laborious in vitro manipulations i...Recombineering is an essential tool for molecular biologists,allowing for the facile and efficient manipulation of bacterial genomes directly in cells without the need for costly and laborious in vitro manipulations involving restriction enzymes.The main workhorses behind recombineering are bacteriophage proteins that promote the single-strand annealing(SSA)homologous recombination pathway to repair double-stranded DNA breaks.While there have been several reviews examining recombineering methods and applications,comparatively few have focused on the mechanisms of the proteins that are the key players in the SSA pathway:a 5′→3′exonuclease and a single-strand annealing protein(SSAP or“annealase”).This review dives into the structures and functions of the two SSA recombination systems that were the first to be developed for recombineering in E.coli:the RecET system from E.coli Rac prophage and the𝜆Red system from bacteriophageλ.By comparing the structures of the RecT and Red𝛽annealases,and the RecE and𝜆Exo exonucleases,we provide new insights into how the structures of these proteins dictate their function.Examining the sequence conservation of the𝜆λExo and RecE exonucleases gives more profound insights into their critical functional features.Ultimately,as recombineering accelerates and evolves in the laboratory,a better understanding of the mechanisms of the proteins behind this powerful technique will drive the development of improved and expanded capabilities in the future.展开更多
Recombineering is a valuable technique for generating recombinant DNA in vivo,primarily in bacterial cells,and is based on homologous recombination using phage-encoded homologous recombinases,such as Red βγ from the...Recombineering is a valuable technique for generating recombinant DNA in vivo,primarily in bacterial cells,and is based on homologous recombination using phage-encoded homologous recombinases,such as Red βγ from the lambda phage and RecET from the Rac prophage.The recombineering technique can efficiently mediate homol-ogous recombination using short homologous arms(∼50 bp)and is unlimited by the size of the DNA molecules or positions of restriction sites.In this review,we summarize characteristics of recombinases,mechanism of recombineering,and advances in recombineering for DNA manipulation in Escherichia coli and other bacteria.Furthermore,the broad applications of recombineering for mining new bioactive microbial natural products,and for viral mutagenesis,phage genome engineering,and understanding bacterial metabolism are also reviewed.展开更多
This article uses a real-life example to illustrate the concept and methodology of recombineering, arevolutionary genetic engineering technique based on phage-mediated homologous recombination. A step-by-step approach...This article uses a real-life example to illustrate the concept and methodology of recombineering, arevolutionary genetic engineering technique based on phage-mediated homologous recombination. A step-by-step approach is presented along with a flow diagram, from obtaining gene-harboring BACs to the in vitro generation of a conditional null allele. This method can be used to target any gene at any position, without the knowledge or use of any restriction site. The extensive applicability of recombineering to gene manipulation is discussed.展开更多
Electron–hole(e–h)recombination is a fundamental process that governs energy dissipation and device efficiency in semiconductors.In two-dimensional(2D)materials,the formation of tightly bound excitons makes exciton-...Electron–hole(e–h)recombination is a fundamental process that governs energy dissipation and device efficiency in semiconductors.In two-dimensional(2D)materials,the formation of tightly bound excitons makes exciton-mediated e–h recombination the dominant decay pathway.In this work,nonradiative e–h recombination within excitons in monolayer MoS2 is investigated using first-principles simulations that combine nonadiabatic molecular dynamics with𝐺𝑊and real-time Bethe–Salpeter equation(BSE)propagation.A two-step process is identified:rapid intervalley redistribution induced by exchange interaction,followed by slower phonon-assisted recombination facilitated by exciton binding.By selectively removing the screened Coulomb and exchange terms from the BSE Hamiltonian,their respective contributions are disentangled—exchange interaction is found to increase the number of accessible recombination pathways,while binding reduces the excitation energy and enhances nonradiative decay.A reduction in recombination lifetime by over an order of magnitude is observed due to the excitonic many-body effects.These findings provide microscopic insights for understanding and tuning exciton lifetimes in 2D transition-metal dichalcogenides.展开更多
The published article titled“Truncated Bid Overexpression Induced by Recombinant Adenovirus Cre/LoxP System Suppresses the Tumorigenic Potential of CD133+Ovarian Cancer Stem Cells”has been retracted from Oncology Re...The published article titled“Truncated Bid Overexpression Induced by Recombinant Adenovirus Cre/LoxP System Suppresses the Tumorigenic Potential of CD133+Ovarian Cancer Stem Cells”has been retracted from Oncology Research,Vol.25,No.4,2017,pp.595–603.展开更多
Bacillus subtilis plays an important role in fundamental and applied research,and it has been widely used as a cell factory for the production of enzymes,antimicrobial materials,and chemicals for agriculture,medicine,...Bacillus subtilis plays an important role in fundamental and applied research,and it has been widely used as a cell factory for the production of enzymes,antimicrobial materials,and chemicals for agriculture,medicine,and industry.However,genetic manipulation tools for B.subtilis have low efficiency.In this work,our goal was to develop a simple recombineering system for B.subtilis.We showed that genome editing can be achieved in B.subtiliis 1A751 through co-expression of YqaJ/YqaK,a native phage recombinase pair found in B.sub-tilis 168,and the competence master regulator ComK using a double-stranded DNA substrate with short ho-mology arms(100 bp)and a phosphorothioate modification at the 5′-end.Efficient gene knockouts and large DNA insertions were achieved using this new recombineering system in B.subtilis 1A751.As far as we know,this is the first recombineering system using the native phage recombinase pair YqaJ/YqaK in B.subtilis.In conclusion,this new recombineering system provides a simple and fast tool for genetic manipulation of B.sub-tilis,and it will promote studies of genome function,construction of production strains,and genome mining in B.subtilis.展开更多
Recombinant tissue plasminogen activator is commonly used for hematoma evacuation in minimally invasive surgery following intracerebral hemorrhage.However,during minimally invasive surgery,recombinant tissue plasminog...Recombinant tissue plasminogen activator is commonly used for hematoma evacuation in minimally invasive surgery following intracerebral hemorrhage.However,during minimally invasive surgery,recombinant tissue plasminogen activator may come into contact with brain tissue.Therefore,a thorough assessment of its safety is required.In this study,we established a mouse model of intracerebral hemorrhage induced by type VII collagenase.We observed that the administration of recombinant tissue plasminogen activator without hematoma aspiration significantly improved the neurological function of mice with intracerebral hemorrhage,reduced pathological damage,and lowered the levels of apoptosis and autophagy in the tissue surrounding the hematoma.In an in vitro model of intracerebral hemorrhage using primary cortical neurons induced by hemin,the administration of recombinant tissue plasminogen activator suppressed neuronal apoptosis,autophagy,and endoplasmic reticulum stress.Transcriptome sequencing analysis revealed that recombinant tissue plasminogen activator upregulated the phosphoinositide 3-kinase/RAC-alpha serine/threonine-protein kinase/mammalian target of rapamycin pathway in neurons.Moreover,the phosphoinositide 3-kinase inhibitor LY294002 abrogated the neuroprotective effects of recombinant tissue plasminogen activator in inhibiting excessive apoptosis,autophagy,and endoplasmic reticulum stress.Furthermore,to specify the domain of recombinant tissue plasminogen activator responsible for its neuroprotective effects,various inhibitors were used to target distinct domains.It has been revealed that the epidermal growth factor receptor inhibitor AG-1478 reversed the effect of recombinant tissue plasminogen activator on the phosphoinositide 3-kinase/RAC-alpha serine/threonineprotein kinase/mammalian target of rapamycin pathway.These findings suggest that recombinant tissue plasminogen activator exerts a direct neuroprotective effect on neurons following intracerebral hemorrhage,possibly through activation of the phosphoinositide 3-kinase/RAC-alpha serine/threonine-protein kinase/mammalian target of rapamycin pathway.展开更多
Adenoviruses typically cause mild illnesses,but severe diseases may occur primarily in immunodeficient individuals,particularly children.Recently,adenoviruses have garnered significant interest as a versatile tool in ...Adenoviruses typically cause mild illnesses,but severe diseases may occur primarily in immunodeficient individuals,particularly children.Recently,adenoviruses have garnered significant interest as a versatile tool in gene therapy,tumor treatment,and vaccine vector development.Over the past two decades,the advent of recombineering,a method based on homologous recombination,has notably enhanced the utility of adenoviral vectors in therapeutic applications.This review summarizes recent advancements in the use of human adenoviral vectors in medicine and discusses the pivotal role of recombineering in the development of these vectors.Additionally,it highlights the current achievements and potential future impact of therapeutic adenoviral vectors.展开更多
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
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
Objective:Patients with homologous recombination deficiency(HRD)demonstrate distinct clinicopathological and prognostic features.However,standardised and clinically validated HRD detection methodologies specifically t...Objective:Patients with homologous recombination deficiency(HRD)demonstrate distinct clinicopathological and prognostic features.However,standardised and clinically validated HRD detection methodologies specifically tailored for non-small cell lung cancer(NSCLC)have yet to be established.Further research is needed to clarify the precise role and clinical implications of HRD in NSCLC.Methods:A cohort of 580 treatment-naive NSCLC patients was retrospectively enrolled.Comprehensive genomic profiling(CGP)was performed for all patients,and HRD status was evaluated using two genomic scar score(GSS)-based algorithms:a machine learning-based GSS(ML-GSS)and a continuous linear regression-based GSS(CLR-GSS).To assess the diagnostic performance(sensitivity and specificity)of the ML-GSS and CLR-GSS algorithms for HRD detection,immunohistochemical(IHC)staining was conducted for two HRD-related biomarkers:Schlafen 11(SLFN11)and RAD51.Survival analysis,including progression-free survival(PFS),along with multivariable Cox proportional hazards models,was performed to compare the prognostic value of the two HRD algorithms.Results:Among all patients,146(25.2%)and 46(7.9%)were classified as HRD-positive(HRD+)by ML-GSS and CLR-GSS,respectively.Using SLFN11 IHC expression as the reference standard,comparative analysis demonstrated that ML-GSS exhibited significantly higher sensitivity but lower specificity than CLR-GSS.This trend was consistently observed in RAD51 staining analysis.Compared to HRD-negative(HRD-)patients,MLGSS-defined HRD+cases displayed distinct clinicopathological and genomic features,including a higher prevalence of homologous recombination(HR)-related genes mutations,BRCA1/2 mutations,TP53 mutations,elevated tumor mutation burden(TMB),and increased copy number variations(CNVs).In contrast,CLR-GSSdefined HRD+patients were only enriched for BRCA1/2 mutations,TP53 mutations,and elevated TMB.Furthermore,ML-GSS-defined HRD+status was associated with significantly worse prognosis following first-line therapy compared to HRD-patients.Univariate and multivariable Cox analyses identified ML-GSS-defined HRD+and TP53 mutations as significant predictors and independent risk factors,respectively.No such associations were observed in the CLR-GSS-defined HRD+cohort.Conclusions:ML-GSS demonstrated superior performance to CLR-GSS in assessing chromosomal instability(CIN)and showed greater clinical utility.We recommend the ML-GSS algorithm as a robust and clinically validated tool for HRD/CIN evaluation in NSCLC.Furthermore,ML-GSS-defined HRD+status was identified as both a significant predictor and an independent risk factor.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
Cu_(2)ZnSn(S,Se)_(4)(CZTSSe)is considered to be the most potential light-absorbing material to replace CuInGaSe_(2)(CIGS),but the actual photoelectric conversion efficiency of such cells is much lower than that of CIG...Cu_(2)ZnSn(S,Se)_(4)(CZTSSe)is considered to be the most potential light-absorbing material to replace CuInGaSe_(2)(CIGS),but the actual photoelectric conversion efficiency of such cells is much lower than that of CIGS.One of the reasons is the high recombination rate of carriers at the interface.In this paper,in order to reduce the carrier recombination,a new solar cell structure with double absorber layers of Al-doped ZnO(AZO)/intrinsic(i)-ZnO/CdS/CZTS_(x1)Se_(1−x1)(CZTSSe_(1))/CZTS_(x2)Se_(1−x2)(CZTSSe_(2))/Mo was proposed,and the optimal conduction band offsets(CBOs)of CdS/CZTSSe_(1) interface and CZTSSe_(1)/CZTSSe_(2) interface were determined by changing the S ratio in CZTSSe_(1) and CZTSSe_(2),and the effect of thickness of CZTSSe_(1) on the performance of the cell was studied.The efficiencies of the optimized single and double absorber layers reached 17.97%and 23.4%,respectively.Compared with the single absorber layer structure,the proposed structure with double absorber layers has better cell performance.展开更多
BACKGROUND Valvular heart disease affects more than 100 million people worldwide and is associated with significant morbidity and mortality.The prevalence of at least moderate valvular heart disease is 2.5%across all ...BACKGROUND Valvular heart disease affects more than 100 million people worldwide and is associated with significant morbidity and mortality.The prevalence of at least moderate valvular heart disease is 2.5%across all age groups,but its prevalence increases with age.Mitral regurgitation and aortic stenosis are the most frequent types of valvular heart disease in the community and hospital context,res-pectively.Surgical valve replacement(or mitral valve repair)is the standard of care for treating heart valve disease.However,the replacement of a prosthetic heart valve can lead to complications,either in the peri-procedural phase or in the long-term follow-up period.CASE SUMMARY We present a case of a 71-year-old female patient with a history of mitral valve replacement and warfarin anti-coagulation therapy.She was admitted to the intensive care unit due to spontaneously reperfused ischemic stroke of probable cardioembolic etiology.A dysfunctional mitral prosthesis was identified due to malfunction of one of the fixed discs.Furthermore,a possible microthrombotic lesion was suspected.Therefore,systemic thrombolysis was performed with subsequent normalization of mitral disc opening and closing.CONCLUSION This case underscores the critical importance of a multidisciplinary approach for timely decision-making in critically ill patients with prosthetic valve complications.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
基金supported by the National Key R&D Program of China(2018YFA0902200)Natural Science Foundation of China(No.21776157,No.22078173)。
文摘Genome engineering of Rhodococcus opacus PD630,an important microorganism used for the bioconversion of lignin,is currently dependent on inefficient homologous recombination.Although a CRISPR interference procedure for gene repression has previously been developed for R.opacus PD630,a CRISPR/Cas9 system for gene knockout has yet to be reported for the strain.In this study,we found that the cytotoxicity of Cas9 and the deficiency in pathways for repairing DNA double-strand breaks(DSBs)were the major causes of the failure of conventional CRISPR/Cas9 technologies in R.opacus,even when augmented with the recombinases Che9c60 and Che9c61.We successfully developed an efficient single-stranded DNA(ssDNA)recombineering system coupled with CRISPR/Cas9 counter-selection,which facilitated rapid and scarless editing of the R.opacus genome.A two-plasmid system,comprising Cas9 driven by a weak Rhodococcus promoter Pniami,designed to prevent cytotoxicity,and a single-guide RNA(sgRNA)under the control of a strong constitutive promoter,was proven to be appropriate with respect to cleavage function.A novel recombinase,RrRecT derived from a Rhodococcus ruber prophage,was identified for the first time,which facilitated recombination of short ssDNA donors(40-80 nt)targeted to the lagging strand and enabled us to obtain a recombination efficiency up to 103-fold higher than that of endogenous pathways.Finally,by incorporating RrRecT and Cas9 into a single plasmid and then co-transforming cells with sgRNA plasmids and short ssDNA donors,we efficiently achieved gene disruption and base mutation in R.opacus,with editing efficiencies ranging from 22%to 100%.Simultaneous disruption of double genes was also confirmed,although at a lower efficiency.This effective genome editing tool will accelerate the engineering of R.opacus metabolism.
基金supported by the National Key R&D Program of China(2019YFA0905700)National Natural Science Foundation of China(32070060).
文摘Iron is essential for bacterial survival,and most bacteria capture iron by producing siderophores.Burkholde-riales bacteria produce various types of bioactive secondary metabolites,such as ornibactin and malleobactin siderophores.In this study,the genome analysis of Burkholderiales genomes showed a putative novel siderophore gene cluster crb,which is highly similar to the ornibactin and malleobactin gene clusters but does not have pvdF,a gene encoding a formyltransferase for N-δ-hydroxy-ornithine formylation.Establishing the bacteriophage recom-binase Redγ-Redδβ7029 mediated genome editing system in a non-model Burkholderiales strain Paraburkholderia caribensis CICC 10960 allowed the rapid identification of the products of crb gene cluster,caribactins A-F(1-6).Caribactins contain a special amino acid residue N-δ-hydroxy-N-δ-acetylornithine(haOrn),which differs from the counterpart N-δ-hydroxy-N-δ-formylornithine(hOrn)in ornibactin and malleobactin,owing to the absence of pvdF.Gene inactivation showed that the acetylation of hOrn is catalyzed by CrbK,whose homologs proba-bly not be involved in the biosynthesis of ornibactin and malleobactin,showing possible evolutionary clues of these siderophore biosynthetic pathways from different genera.Caribactins promote biofilm production and en-hance swarming and swimming abilities,suggesting that they may play crucial roles in biofilm formation.This study also revealed that recombineering has the capability to mine novel secondary metabolites from non-model Burkholderiales species.
基金the National Science Foundation Grant MCB-2212951(to CEB)and NHMRC Ideas grant APP1184012/GNT1184012(to GT).
文摘Recombineering is an essential tool for molecular biologists,allowing for the facile and efficient manipulation of bacterial genomes directly in cells without the need for costly and laborious in vitro manipulations involving restriction enzymes.The main workhorses behind recombineering are bacteriophage proteins that promote the single-strand annealing(SSA)homologous recombination pathway to repair double-stranded DNA breaks.While there have been several reviews examining recombineering methods and applications,comparatively few have focused on the mechanisms of the proteins that are the key players in the SSA pathway:a 5′→3′exonuclease and a single-strand annealing protein(SSAP or“annealase”).This review dives into the structures and functions of the two SSA recombination systems that were the first to be developed for recombineering in E.coli:the RecET system from E.coli Rac prophage and the𝜆Red system from bacteriophageλ.By comparing the structures of the RecT and Red𝛽annealases,and the RecE and𝜆Exo exonucleases,we provide new insights into how the structures of these proteins dictate their function.Examining the sequence conservation of the𝜆λExo and RecE exonucleases gives more profound insights into their critical functional features.Ultimately,as recombineering accelerates and evolves in the laboratory,a better understanding of the mechanisms of the proteins behind this powerful technique will drive the development of improved and expanded capabilities in the future.
基金supported by the National Key R&D Program of China(2019YFA0904000)the National Natural Science Foundation of China(31570094,81502962,32170038,32270088)+1 种基金the Taishan Scholar Pro-gram of Shandong Province,the Shandong Provincial Natural Science Foundation of China(ZR2020MC015,ZR2022MC142)the Funda-mental Research Funds of Shandong University(2018GN021).
文摘Recombineering is a valuable technique for generating recombinant DNA in vivo,primarily in bacterial cells,and is based on homologous recombination using phage-encoded homologous recombinases,such as Red βγ from the lambda phage and RecET from the Rac prophage.The recombineering technique can efficiently mediate homol-ogous recombination using short homologous arms(∼50 bp)and is unlimited by the size of the DNA molecules or positions of restriction sites.In this review,we summarize characteristics of recombinases,mechanism of recombineering,and advances in recombineering for DNA manipulation in Escherichia coli and other bacteria.Furthermore,the broad applications of recombineering for mining new bioactive microbial natural products,and for viral mutagenesis,phage genome engineering,and understanding bacterial metabolism are also reviewed.
文摘This article uses a real-life example to illustrate the concept and methodology of recombineering, arevolutionary genetic engineering technique based on phage-mediated homologous recombination. A step-by-step approach is presented along with a flow diagram, from obtaining gene-harboring BACs to the in vitro generation of a conditional null allele. This method can be used to target any gene at any position, without the knowledge or use of any restriction site. The extensive applicability of recombineering to gene manipulation is discussed.
基金supported by the National Key Research and Development Program of China (Grant Nos.2024YFA1409800 for J.Z.and2024YFA1408603 for Q.Z.)the National Natural Science Foundation of China (Grant Nos.12125408,12334004for J.Z.,and 12174363 for Q.Z.)+1 种基金the Innovation Program for Quantum Science and Technology (Grant No.2021ZD0303306 for J.Z.)the Strategic Priority Research Program of the Chinese Academy of Sciences(Grant No.XDB0450101 for J.Z.)。
文摘Electron–hole(e–h)recombination is a fundamental process that governs energy dissipation and device efficiency in semiconductors.In two-dimensional(2D)materials,the formation of tightly bound excitons makes exciton-mediated e–h recombination the dominant decay pathway.In this work,nonradiative e–h recombination within excitons in monolayer MoS2 is investigated using first-principles simulations that combine nonadiabatic molecular dynamics with𝐺𝑊and real-time Bethe–Salpeter equation(BSE)propagation.A two-step process is identified:rapid intervalley redistribution induced by exchange interaction,followed by slower phonon-assisted recombination facilitated by exciton binding.By selectively removing the screened Coulomb and exchange terms from the BSE Hamiltonian,their respective contributions are disentangled—exchange interaction is found to increase the number of accessible recombination pathways,while binding reduces the excitation energy and enhances nonradiative decay.A reduction in recombination lifetime by over an order of magnitude is observed due to the excitonic many-body effects.These findings provide microscopic insights for understanding and tuning exciton lifetimes in 2D transition-metal dichalcogenides.
文摘The published article titled“Truncated Bid Overexpression Induced by Recombinant Adenovirus Cre/LoxP System Suppresses the Tumorigenic Potential of CD133+Ovarian Cancer Stem Cells”has been retracted from Oncology Research,Vol.25,No.4,2017,pp.595–603.
基金supported by the National Key R&D Program of China(2019YFA0904000)the National Natural Science Foundation of China(31570094,81502962,32270088)+6 种基金the 111 Project(B16030)the Shan-dong Provincial Natural Science Foundation of China(ZR2020MC015,ZR2018ZC2261)the Taishan Scholar Program of Shandong Provincethe Fundamental Research Funds of Shandong University(2018GN021)the Open Project Program of the State Key Laboratory of Bio-based Material and Green Papermaking(KF201825)the Science and Technology Project of Hunan Province(2021NK1040)Natural Science Foundation of Changsha(KQ2208130).
文摘Bacillus subtilis plays an important role in fundamental and applied research,and it has been widely used as a cell factory for the production of enzymes,antimicrobial materials,and chemicals for agriculture,medicine,and industry.However,genetic manipulation tools for B.subtilis have low efficiency.In this work,our goal was to develop a simple recombineering system for B.subtilis.We showed that genome editing can be achieved in B.subtiliis 1A751 through co-expression of YqaJ/YqaK,a native phage recombinase pair found in B.sub-tilis 168,and the competence master regulator ComK using a double-stranded DNA substrate with short ho-mology arms(100 bp)and a phosphorothioate modification at the 5′-end.Efficient gene knockouts and large DNA insertions were achieved using this new recombineering system in B.subtilis 1A751.As far as we know,this is the first recombineering system using the native phage recombinase pair YqaJ/YqaK in B.subtilis.In conclusion,this new recombineering system provides a simple and fast tool for genetic manipulation of B.sub-tilis,and it will promote studies of genome function,construction of production strains,and genome mining in B.subtilis.
基金supported by the National Natural Science Foundation of China,Nos.92148206,82071330(both to ZT)a grant from the Major Program of Hubei Province,No.2023BAA005(to ZT)+1 种基金a grant from the Key Research and Discovery Program of Hubei Province,No.2021BCA109(to ZT)the Research Foundation of Tongji Hospital,No.2022B37(to PZ)。
文摘Recombinant tissue plasminogen activator is commonly used for hematoma evacuation in minimally invasive surgery following intracerebral hemorrhage.However,during minimally invasive surgery,recombinant tissue plasminogen activator may come into contact with brain tissue.Therefore,a thorough assessment of its safety is required.In this study,we established a mouse model of intracerebral hemorrhage induced by type VII collagenase.We observed that the administration of recombinant tissue plasminogen activator without hematoma aspiration significantly improved the neurological function of mice with intracerebral hemorrhage,reduced pathological damage,and lowered the levels of apoptosis and autophagy in the tissue surrounding the hematoma.In an in vitro model of intracerebral hemorrhage using primary cortical neurons induced by hemin,the administration of recombinant tissue plasminogen activator suppressed neuronal apoptosis,autophagy,and endoplasmic reticulum stress.Transcriptome sequencing analysis revealed that recombinant tissue plasminogen activator upregulated the phosphoinositide 3-kinase/RAC-alpha serine/threonine-protein kinase/mammalian target of rapamycin pathway in neurons.Moreover,the phosphoinositide 3-kinase inhibitor LY294002 abrogated the neuroprotective effects of recombinant tissue plasminogen activator in inhibiting excessive apoptosis,autophagy,and endoplasmic reticulum stress.Furthermore,to specify the domain of recombinant tissue plasminogen activator responsible for its neuroprotective effects,various inhibitors were used to target distinct domains.It has been revealed that the epidermal growth factor receptor inhibitor AG-1478 reversed the effect of recombinant tissue plasminogen activator on the phosphoinositide 3-kinase/RAC-alpha serine/threonineprotein kinase/mammalian target of rapamycin pathway.These findings suggest that recombinant tissue plasminogen activator exerts a direct neuroprotective effect on neurons following intracerebral hemorrhage,possibly through activation of the phosphoinositide 3-kinase/RAC-alpha serine/threonine-protein kinase/mammalian target of rapamycin pathway.
基金the DFG grant EH 192/5-3(to AE),the internal grant program(project IFF 2024-91)f the Faculty of Health at Witten/Herdecke University(WZ and KS)and the PhD program at Witten/Herdecke University(LK).
文摘Adenoviruses typically cause mild illnesses,but severe diseases may occur primarily in immunodeficient individuals,particularly children.Recently,adenoviruses have garnered significant interest as a versatile tool in gene therapy,tumor treatment,and vaccine vector development.Over the past two decades,the advent of recombineering,a method based on homologous recombination,has notably enhanced the utility of adenoviral vectors in therapeutic applications.This review summarizes recent advancements in the use of human adenoviral vectors in medicine and discusses the pivotal role of recombineering in the development of these vectors.Additionally,it highlights the current achievements and potential future impact of therapeutic adenoviral vectors.
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 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.
基金supported by the National High Level Hospital Clinical Research Funding(No.BJ-2019-195)the National High Level Hospital Clinical Research Funding(No.BJ-2023-090)。
文摘Objective:Patients with homologous recombination deficiency(HRD)demonstrate distinct clinicopathological and prognostic features.However,standardised and clinically validated HRD detection methodologies specifically tailored for non-small cell lung cancer(NSCLC)have yet to be established.Further research is needed to clarify the precise role and clinical implications of HRD in NSCLC.Methods:A cohort of 580 treatment-naive NSCLC patients was retrospectively enrolled.Comprehensive genomic profiling(CGP)was performed for all patients,and HRD status was evaluated using two genomic scar score(GSS)-based algorithms:a machine learning-based GSS(ML-GSS)and a continuous linear regression-based GSS(CLR-GSS).To assess the diagnostic performance(sensitivity and specificity)of the ML-GSS and CLR-GSS algorithms for HRD detection,immunohistochemical(IHC)staining was conducted for two HRD-related biomarkers:Schlafen 11(SLFN11)and RAD51.Survival analysis,including progression-free survival(PFS),along with multivariable Cox proportional hazards models,was performed to compare the prognostic value of the two HRD algorithms.Results:Among all patients,146(25.2%)and 46(7.9%)were classified as HRD-positive(HRD+)by ML-GSS and CLR-GSS,respectively.Using SLFN11 IHC expression as the reference standard,comparative analysis demonstrated that ML-GSS exhibited significantly higher sensitivity but lower specificity than CLR-GSS.This trend was consistently observed in RAD51 staining analysis.Compared to HRD-negative(HRD-)patients,MLGSS-defined HRD+cases displayed distinct clinicopathological and genomic features,including a higher prevalence of homologous recombination(HR)-related genes mutations,BRCA1/2 mutations,TP53 mutations,elevated tumor mutation burden(TMB),and increased copy number variations(CNVs).In contrast,CLR-GSSdefined HRD+patients were only enriched for BRCA1/2 mutations,TP53 mutations,and elevated TMB.Furthermore,ML-GSS-defined HRD+status was associated with significantly worse prognosis following first-line therapy compared to HRD-patients.Univariate and multivariable Cox analyses identified ML-GSS-defined HRD+and TP53 mutations as significant predictors and independent risk factors,respectively.No such associations were observed in the CLR-GSS-defined HRD+cohort.Conclusions:ML-GSS demonstrated superior performance to CLR-GSS in assessing chromosomal instability(CIN)and showed greater clinical utility.We recommend the ML-GSS algorithm as a robust and clinically validated tool for HRD/CIN evaluation in NSCLC.Furthermore,ML-GSS-defined HRD+status was identified as both a significant predictor and an independent risk factor.
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supported by the Science and Technology Innovation Development Program(No.70304901).
文摘Cu_(2)ZnSn(S,Se)_(4)(CZTSSe)is considered to be the most potential light-absorbing material to replace CuInGaSe_(2)(CIGS),but the actual photoelectric conversion efficiency of such cells is much lower than that of CIGS.One of the reasons is the high recombination rate of carriers at the interface.In this paper,in order to reduce the carrier recombination,a new solar cell structure with double absorber layers of Al-doped ZnO(AZO)/intrinsic(i)-ZnO/CdS/CZTS_(x1)Se_(1−x1)(CZTSSe_(1))/CZTS_(x2)Se_(1−x2)(CZTSSe_(2))/Mo was proposed,and the optimal conduction band offsets(CBOs)of CdS/CZTSSe_(1) interface and CZTSSe_(1)/CZTSSe_(2) interface were determined by changing the S ratio in CZTSSe_(1) and CZTSSe_(2),and the effect of thickness of CZTSSe_(1) on the performance of the cell was studied.The efficiencies of the optimized single and double absorber layers reached 17.97%and 23.4%,respectively.Compared with the single absorber layer structure,the proposed structure with double absorber layers has better cell performance.
文摘BACKGROUND Valvular heart disease affects more than 100 million people worldwide and is associated with significant morbidity and mortality.The prevalence of at least moderate valvular heart disease is 2.5%across all age groups,but its prevalence increases with age.Mitral regurgitation and aortic stenosis are the most frequent types of valvular heart disease in the community and hospital context,res-pectively.Surgical valve replacement(or mitral valve repair)is the standard of care for treating heart valve disease.However,the replacement of a prosthetic heart valve can lead to complications,either in the peri-procedural phase or in the long-term follow-up period.CASE SUMMARY We present a case of a 71-year-old female patient with a history of mitral valve replacement and warfarin anti-coagulation therapy.She was admitted to the intensive care unit due to spontaneously reperfused ischemic stroke of probable cardioembolic etiology.A dysfunctional mitral prosthesis was identified due to malfunction of one of the fixed discs.Furthermore,a possible microthrombotic lesion was suspected.Therefore,systemic thrombolysis was performed with subsequent normalization of mitral disc opening and closing.CONCLUSION This case underscores the critical importance of a multidisciplinary approach for timely decision-making in critically ill patients with prosthetic valve complications.
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.
