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
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
Genome rearrangement is an important process that leads to genetic diversity,including mutation-related insertions,deletions,or inversions in the genome[1,2].
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
Metal halide perovskites have rapidly emerged as outstanding semiconductors for laser applications.Surface plasmon resonances of metals offer a platform for improving the perovskite lasing properties of metal halide p...Metal halide perovskites have rapidly emerged as outstanding semiconductors for laser applications.Surface plasmon resonances of metals offer a platform for improving the perovskite lasing properties of metal halide perovskites by accelerating radiative recombination.However,the constraint on degrees of freedom of perovskite-metal interactions in two dimensions keeps us from getting a full picture of plasmon-involved carrier dynamics and reaching the optimum perovskite lasing performance.Here we report a strategy of synthesizing quantitative coassemblies of perovskite and metal nanocrystals for studying the effect of surface plasmons on carrier dynamics in depth and exploring plasmon-enhanced perovskite lasing performance.Within the coassembly,each metal nanocrystal supports localized surface plasmon resonances capable of accelerating radiative recombination of all adjacent perovskite nanocrystals in three dimensions.The quantitative coassemblies disclose the evolution of radiative and nonradiative recombination processes in perovskite nanocrystals with the plasmon modes,identifying an optimal metal nanocrystal content for fulfilling the highest radiative efficiency in perovskite nanocrystals.By virtue of accelerated radiative recombination,the coassemblies of perovskite and metal nanocrystals allowed for the construction of microlaser arrays with enhanced performance including low thresholds and ultrafast outputs.This work fundamentally advances the perovskite-metal systems for plasmonically enhancing perovskite optoelectronic performance.展开更多
In this study, RT-PCR was performed on lung tissue samples from sick pigs in a suspected outbreak of porcine reproductive and respiratory syndrome (PRRS) at a pig farm in Mianyang City, Sichuan Province, China. Positi...In this study, RT-PCR was performed on lung tissue samples from sick pigs in a suspected outbreak of porcine reproductive and respiratory syndrome (PRRS) at a pig farm in Mianyang City, Sichuan Province, China. Positive samples were inoculated into Marc-145 cells to observe lesions. The Marc-145 cells with cytopathic lesions were identified by indirect immunofluorescence. The whole genome sequences of the isolated and purified strains were amplified by RT-PCR and analyzed for homology and genetic evolution. A strain of porcine reproductive and respiratory syndrome virus (PRRSV), named SCMY2023 (GenBank No. PQ179742), was successfully isolated. SCMY2023 has a genome length of 15,321 base pairs (without a poly A tail). Nucleotide and amino acid homology analyses suggest that this strain belongs to Lineage 8, a variant of the highly pathogenic porcine reproductive and respiratory syndrome virus (HP-PRRSV) prevalent in China. Recombination and genetic evolution analyses indicate that this isolate is a PRRSV variant that recombined with HuN-ZZ (Lineage 8, 98.79% homology) on the backbone of the SCSN2020 strain (Lineage 8, 99.35% homology) in the recombination region from 4407 to 13,107 nucleotides (ORF1a to ORF3). In-depth study of the genetic recombination of this isolate can provide a reference for the prevention and control of PRRS.展开更多
A new tunnel recombination junction is fabricated for n-i-p type micromorph tandem solar cells. We insert a thin heavily doped hydrogenated amorphous silicon （a-Si：H） p^＋ recombination layer between the n a-Si：H ...A new tunnel recombination junction is fabricated for n-i-p type micromorph tandem solar cells. We insert a thin heavily doped hydrogenated amorphous silicon （a-Si：H） p^＋ recombination layer between the n a-Si：H and the p hydrogenated nanocrystalline silicon （nc-Si：H） layers to improve the performance of the n-i-p tandem solar cells. The effects of the boron doping gas ratio and the deposition time of the p-a-Si：H recombination layer on the tunnel recombination junctions have been investigated. The current-voltage characteristic of the tunnel recombination junction shows a nearly ohmic characteristic, and the resistance of the tunnel recombination junction can be as low as 1.5 Ω-cm^2 by using the optimized p-a-Si：H recombination layer. We obtain tandem solar cells with open circuit voltage Voc = 1.4 V, which is nearly the sum of the Vocs of the two corresponding single cells, indicating no Voc losses at the tunnel recombination junction.展开更多
We use the method of device simulation to study the losses and influences of geminate and bimolecular recombinations on the performances and properties of the bulk heterojunction organic solar cells. We find that a fr...We use the method of device simulation to study the losses and influences of geminate and bimolecular recombinations on the performances and properties of the bulk heterojunction organic solar cells. We find that a fraction of electrons（holes）in the device are collected by anode（cathode）. The direction of the corresponding current is opposite to the direction of photocurrent. And the current density increases with the bias increasing but decreases as bimolecular recombination（BR）or geminate recombination（GR） intensity increases. The maximum power, short circuit current, and fill factor display a stronger dependence on GR than on BR. While the influences of GR and BR on open circuit voltage are about the same.Our studies shed a new light on the loss mechanism and may provide a new way of improving the efficiency of bulk heterojunction organic solar cells.展开更多
Many eukaryotic genes are members of multi-gene families due to gene duplications, which generate new copies that allow functional divergence. However, the relationship between
The dynamics of produced excited carriers under the irradiation of Ge crystal is investigated theoretically by using femtosecond laser pulse.A two-temperature model combined with the Drude model is also used to study ...The dynamics of produced excited carriers under the irradiation of Ge crystal is investigated theoretically by using femtosecond laser pulse.A two-temperature model combined with the Drude model is also used to study the nonequilibrium carrier density,carrier and lattice temperatures,and optical properties of the crystal.The properties of the surface plasmon wave when excited are also studied.The influences of non-radiation and radiative recombination process on the photoexcitation of the semiconductor during pulse and the relaxation after the pulse are described in detail.The results show that the effects of Auger recombination on the nonequilibrium carrier density and optical properties of the crystal and the properties of the surface plasmon polariton are great,whereas the effect of radiative recombination is extremely small.展开更多
The electron–ion recombination for phosphorus-like^（112） Sn^（35＋）has been measured at the main cooler storage ring of the Heavy Ion Research Facility in Lanzhou, China, employing an electron–ion merged-beams te...The electron–ion recombination for phosphorus-like^（112） Sn^（35＋）has been measured at the main cooler storage ring of the Heavy Ion Research Facility in Lanzhou, China, employing an electron–ion merged-beams technique. The absolute total recombination rate coefficients for electron–ion collision energies from 0 e V–14 e V are presented. Theoretical calculations of recombination rate coefficients were performed using the Flexible Atomic Code to compare with the experimental results. The contributions of dielectronic recombination and trielectronic recombination on the experimental rate coefficients have been identified with the help of the theoretical calculation. The present results show that the trielectronic recombination has a substantial contribution to the measured electron–ion recombination spectrum of^（112）Sn^（35＋）. Although a reasonable agreement is found between the experimental and theoretical results the precise calculation of the electron–ion recombination rate coefficients for M-shell ions is still challengeable for the current theory.展开更多
Recently, the efficiency of CdTe thin film solar cell has been improved by using new type of window layer Mg_(x)Zn_(1-x)O(MZO). However, it is hard to achieve such a high efficiency as expected. In this report a compa...Recently, the efficiency of CdTe thin film solar cell has been improved by using new type of window layer Mg_(x)Zn_(1-x)O(MZO). However, it is hard to achieve such a high efficiency as expected. In this report a comparative study is carried out between the MZO/CdTe and CdS/CdTe solar cells to investigate the factors affecting the device performance of MZO/CdTe solar cells. The efficiency loss quantified by voltage-dependent photocurrent collection efficiency(ηC(V′)) is 3.89% for MZO/CdTe and 1.53% for CdS/CdTe solar cells. The higher efficiency loss for the MZO/CdTe solar cell is induced by more severe carrier recombination at the MZO/CdTe p-n junction interface and in CdTe bulk region than that for the CdS/CdTe solar cell. Activation energy(Ea) of the reverse saturation current of the MZO/CdTe and CdS/CdTe solar cells are found to be 1.08 e V and 1.36 e V, respectively. These values indicate that for the CdS/CdTe solar cell the carrier recombination is dominated by bulk Shockley-Read-Hall(SRH) recombination and for the MZO/CdTe solar cell the carrier recombination is dominated by the p-n junction interface recombination. It is found that the tunneling-enhanced interface recombination is also involved in carrier recombination in the MZO/CdTe solar cell. This work demonstrates the poor device performance of the MZO/CdTe solar cell is induced by more severe interface and bulk recombination than that of the CdS/CdTe solar cell.展开更多
A bilayer model with ohmic anode contact and injection limited cathode contact has been proposed to calculate the recombination efficiency and recombination zone width of the device. The effects of the thickness of ho...A bilayer model with ohmic anode contact and injection limited cathode contact has been proposed to calculate the recombination efficiency and recombination zone width of the device. The effects of the thickness of hole transport layer and the barriers of organic/organic interface on the combination efficiency and recombination width have been discussed. It is found that： （1） When the electrons are blocked fully and the holes are not blocked significantly at the organic/organic interface, for a given Lh/L, the recombination efficiency increases with increasing the applied voltage, but at a higher applied voltage, the recombination efficiency decreases with increasing Lh/L; （2） The recombination efficiency increases with increasing applied voltage and Hh＇, and when applied voltage and Hh＇ exceed some value, the recombination efficiency appears as a plateau; （3） The recombination width decreases with increasing the applied voltage and Lh/L. This model might explain the relative experiment phenomena.展开更多
BACKGROUND Poly(ADP-ribose)polymerase inhibitors(PARPis)are approved as first-line therapies for breast cancer gene(BRCA)-positive,human epidermal growth factor receptor 2-negative locally advanced or metastatic breas...BACKGROUND Poly(ADP-ribose)polymerase inhibitors(PARPis)are approved as first-line therapies for breast cancer gene(BRCA)-positive,human epidermal growth factor receptor 2-negative locally advanced or metastatic breast cancer.They are also effective for new and recurrent ovarian cancers that are BRCA-or homologous recombination deficiency(HRD)-positive.However,data on these mutations and PARPi use in the Middle East are limited.AIM To assess BRCA/HRD prevalence and PARPi use in patients in the Middle East with breast/ovarian cancer.METHODS This was a single-center retrospective study of 57 of 472 breast cancer patients tested for BRCA mutations,and 25 of 65 ovarian cancer patients tested for HRD.These adult patients participated in at least four visits to the oncology service at our center between August 2021 and May 2023.Data were summarized using descriptive statistics and compared using counts and percentages.Response to treatment was assessed using Response Evaluation Criteria in Solid Tumors criteria.RESULTS Among the 472 breast cancer patients,12.1%underwent BRCA testing,and 38.5%of 65 ovarian cancer patients received HRD testing.Pathogenic mutations were found in 25.6%of the tested patients:26.3%breast cancers had germline BRCA(gBRCA)mutations and 24.0%ovarian cancers showed HRD.Notably,40.0%of gBRCA-positive breast cancers and 66.0%of HRD-positive ovarian cancers were Middle Eastern and Asian patients,respectively.PARPi treatment was used in 5(33.3%)gBRCA-positive breast cancer patients as first-line therapy(n=1;7-months progression-free),for maintenance(n=2;>15-months progression-free),or at later stages due to compliance issues(n=2).Four patients(66.6%)with HRD-positive ovarian cancer received PARPi and all remained progression-free.CONCLUSION Lower testing rates but higher BRCA mutations in breast cancer were found.Ethnicity reflected United Arab Emirates demographics,with breast cancer in Middle Eastern and ovarian cancer in Asian patients.展开更多
Background:The homologous recombination deficiency(HRD)score serves as a promising biomarker to iden-tify patients who are eligible for treatment with PARP inhibitors(PARPi).Previous studies have suggested a 3-biomark...Background:The homologous recombination deficiency(HRD)score serves as a promising biomarker to iden-tify patients who are eligible for treatment with PARP inhibitors(PARPi).Previous studies have suggested a 3-biomarker Genomic Instability Score(GIS)threshold of≥42 as a valid biomarker to predict response to PARPi in patients with ovarian cancer and breast cancer.However,the GIS threshold for prostate cancer(PCa)is still lacking.Here,we conducted an exploratory analysis to investigate an appropriate HRD score threshold and to evaluate its ability to predict response to PARPi in PCa patients.Methods:A total of 181 patients with metastatic castration-resistant PCa were included in this study.Tumor tissue specimens were collected for targeted next-generation sequencing for homologous recombination repair(HRR)genes and copy number variation(CNV)analysis.The HRD score was calculated based on over 50,000 single-nucleotide polymorphisms(SNP)distributed across the human genome,incorporating three SNP-based as-says:loss of heterozygosity,telomeric allelic imbalance,and large-scale state transition.The HRD score threshold was set at the last 5th percentile of the HRD scores in our cohort of known HRR-deficient tumors.The relation-ship between the HRD score and the efficacy in 16 patients of our cohort who received PARPi treatment were retrospectively analyzed.Results:Genomic testing was succeeded in 162 patients.In our cohort,61 patients(37.7%)had HRR mutations(HRRm).BRCA mutations occurred in 15 patients(9.3%).The median HRD score was 4(ranged from 0 to 57)in the total cohort,which is much lower than that in breast and ovarian cancers.Patients who harbored HRRm and BRCA or TP53 mutations had higher HRD scores.CNV occured more frequently in patients with HRRm.The last 5th percentile of HRD scores was 43 in the HRR-mutant cohort and consequently HRD high was defined as HRD scores≥43.In the 16 patients who received PARPi in our cohort,4 patients with a high HRD score achieved an objective response rate(ORR)of 100%while 12 patients with a low HRD score achieved an ORR of 8.3%.Progression-free survival(PFS)in HRD high patients was longer compared to HRD low patients,regardless of HRRm.Conclusions:A HRD score threshold of 43 was established and preliminarily validated to predict the efficacy of PARPi in this study.Future studies are needed to further verify this threshold.展开更多
Influence of recombination centers’ changes on the form of phase portraits has been studied. It has been shown that the shape of the phase portraits depends on the concentration of semiconductor materials’ recombina...Influence of recombination centers’ changes on the form of phase portraits has been studied. It has been shown that the shape of the phase portraits depends on the concentration of semiconductor materials’ recombination centers.展开更多
Homologous recombination （HR） comprises a series of interrelated pathways that function in the repair of DNA double-stranded breaks （DSBs） and interstrand crosslinks （ICLs）. In addition, recombination provides c...Homologous recombination （HR） comprises a series of interrelated pathways that function in the repair of DNA double-stranded breaks （DSBs） and interstrand crosslinks （ICLs）. In addition, recombination provides critical support for DNA replication in the recovery of stalled or broken replication forks, contributing to tolerance of DNA damage. A central core of proteins, most critically the RecA homolog Rad51, catalyzes the key reactions that typify HR： homology search and DNA strand invasion. The diverse functions of recombination are reflected in the need for context-specific factors that perform supplemental functions in conjunction with the core proteins. The inability to properly repair complex DNA damage and resolve DNA replication stress leads to genomic instability and contributes to cancer etiology. Mutations in the BRCA2 recombination gene cause predisposition to breast and ovarian cancer as well as Fanconi anemia, a cancer predisposition syndrome characterized by a defect in the repair of DNA interstrand crosslinks. The cellular functions of recombination are also germane to DNA-based treatment modalities of cancer, which target replicating cells by the direct or indirect induction of DNA lesions that are substrates for recombination pathways. This review focuses on mechanistic aspects of HR relating to DSB and ICL repair as well as replication fork support.展开更多
A novel method for predicting hotspots and coldspots using support vector machine （SVM） based on statistical learning theory is developed. This method is applied to published 303 hot and 48 cold open reading frames ...A novel method for predicting hotspots and coldspots using support vector machine （SVM） based on statistical learning theory is developed. This method is applied to published 303 hot and 48 cold open reading frames （ORFs） in Saccharomyces cerevisiae. The sequence features of general dinucleotide abundance and dinucleotide abundance based on codon usage are extracted, and then the data sets are classified with different parameters and kernel functions combined with the method of two-fold cross validation. The result indicates that 87.47% accuracy can be reached when classifying hot and cold ORF sequences with the kernel of radial basis function combined with dinucleotide abundance based on codon usage.展开更多
The multi-factor recombination and processes superimposition model for hydrocarbon accumulation is put forward in view of the hydrocarbon geological characteristics of multiple episodes of structural evolution, multip...The multi-factor recombination and processes superimposition model for hydrocarbon accumulation is put forward in view of the hydrocarbon geological characteristics of multiple episodes of structural evolution, multiple sets of source-reservoir-seal assemblage, multiple cycles of hydrocarbon accumulation and multiple episodes of readjustment and reconstruction in the complex superimposed basins in China. It is a system including theories and methods that can help to predict favorable exploration regions. According to this model, the basic discipline for hydrocarbon generation, evolution and distribution in the superimposed basins can be summarized in multi-factor recombination, processes superimposition, multiple stages of oil filling and latest stage preservation. With the Silurian of the Tarim basin as an example, based on the reconstruction of the evolution history of the four factors （paleo-anticline, source rock, regional cap rock and kinematic equilibrium belt） controlling hydrocarbon accumulation, this model was adopted to predict favorable hydrocarbon accumulation areas and favorable exploration regions following structural destruction in three stages of oil filling, to provide guidance for further exploration ofoil and gas in the Silurian of the Tarim basin.展开更多
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.
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.
基金supported by grants(92168103,32171417,2019CXJQ01)from the National Nature Science Foundation of China,Shanghai Municipal GovernmentPeak Disciplines(Type IV)of Institutions of Higher Learning in Shanghai.
文摘Genome rearrangement is an important process that leads to genetic diversity,including mutation-related insertions,deletions,or inversions in the genome[1,2].
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 the National Natural Science Foundation of China(Nos.52272186,22090023 and 22375207)Beijing Institute of Technology Research Fund Program for Young Scholars(No.XSQD-6120220081)
文摘Metal halide perovskites have rapidly emerged as outstanding semiconductors for laser applications.Surface plasmon resonances of metals offer a platform for improving the perovskite lasing properties of metal halide perovskites by accelerating radiative recombination.However,the constraint on degrees of freedom of perovskite-metal interactions in two dimensions keeps us from getting a full picture of plasmon-involved carrier dynamics and reaching the optimum perovskite lasing performance.Here we report a strategy of synthesizing quantitative coassemblies of perovskite and metal nanocrystals for studying the effect of surface plasmons on carrier dynamics in depth and exploring plasmon-enhanced perovskite lasing performance.Within the coassembly,each metal nanocrystal supports localized surface plasmon resonances capable of accelerating radiative recombination of all adjacent perovskite nanocrystals in three dimensions.The quantitative coassemblies disclose the evolution of radiative and nonradiative recombination processes in perovskite nanocrystals with the plasmon modes,identifying an optimal metal nanocrystal content for fulfilling the highest radiative efficiency in perovskite nanocrystals.By virtue of accelerated radiative recombination,the coassemblies of perovskite and metal nanocrystals allowed for the construction of microlaser arrays with enhanced performance including low thresholds and ultrafast outputs.This work fundamentally advances the perovskite-metal systems for plasmonically enhancing perovskite optoelectronic performance.
文摘In this study, RT-PCR was performed on lung tissue samples from sick pigs in a suspected outbreak of porcine reproductive and respiratory syndrome (PRRS) at a pig farm in Mianyang City, Sichuan Province, China. Positive samples were inoculated into Marc-145 cells to observe lesions. The Marc-145 cells with cytopathic lesions were identified by indirect immunofluorescence. The whole genome sequences of the isolated and purified strains were amplified by RT-PCR and analyzed for homology and genetic evolution. A strain of porcine reproductive and respiratory syndrome virus (PRRSV), named SCMY2023 (GenBank No. PQ179742), was successfully isolated. SCMY2023 has a genome length of 15,321 base pairs (without a poly A tail). Nucleotide and amino acid homology analyses suggest that this strain belongs to Lineage 8, a variant of the highly pathogenic porcine reproductive and respiratory syndrome virus (HP-PRRSV) prevalent in China. Recombination and genetic evolution analyses indicate that this isolate is a PRRSV variant that recombined with HuN-ZZ (Lineage 8, 98.79% homology) on the backbone of the SCSN2020 strain (Lineage 8, 99.35% homology) in the recombination region from 4407 to 13,107 nucleotides (ORF1a to ORF3). In-depth study of the genetic recombination of this isolate can provide a reference for the prevention and control of PRRS.
基金Project supported by the National Basic Research Program of China (Grant No. 2006CB202604)the Knowledge Innovation Program of Chinese Academy of Sciences (Grant No. 1KGCX2-YW-383-1)the National High Technology Research and Development Program of China (Grant No. SQ2010AA0521758001)
文摘A new tunnel recombination junction is fabricated for n-i-p type micromorph tandem solar cells. We insert a thin heavily doped hydrogenated amorphous silicon （a-Si：H） p^＋ recombination layer between the n a-Si：H and the p hydrogenated nanocrystalline silicon （nc-Si：H） layers to improve the performance of the n-i-p tandem solar cells. The effects of the boron doping gas ratio and the deposition time of the p-a-Si：H recombination layer on the tunnel recombination junctions have been investigated. The current-voltage characteristic of the tunnel recombination junction shows a nearly ohmic characteristic, and the resistance of the tunnel recombination junction can be as low as 1.5 Ω-cm^2 by using the optimized p-a-Si：H recombination layer. We obtain tandem solar cells with open circuit voltage Voc = 1.4 V, which is nearly the sum of the Vocs of the two corresponding single cells, indicating no Voc losses at the tunnel recombination junction.
基金Project supported by the Natural Science Foundation of Hebei Province,China(Grant No.A2012203016)the Science Fund from the Education Department of Hebei Province,China(Grant Nos.QN20131103 and Z2009114)+1 种基金the Doctor Foundation of Yanshan University,China(Grant No.B580)the Young Teachers’Research Project of Yanshan University,China(Grant No.13LGB028)
文摘We use the method of device simulation to study the losses and influences of geminate and bimolecular recombinations on the performances and properties of the bulk heterojunction organic solar cells. We find that a fraction of electrons（holes）in the device are collected by anode（cathode）. The direction of the corresponding current is opposite to the direction of photocurrent. And the current density increases with the bias increasing but decreases as bimolecular recombination（BR）or geminate recombination（GR） intensity increases. The maximum power, short circuit current, and fill factor display a stronger dependence on GR than on BR. While the influences of GR and BR on open circuit voltage are about the same.Our studies shed a new light on the loss mechanism and may provide a new way of improving the efficiency of bulk heterojunction organic solar cells.
文摘Many eukaryotic genes are members of multi-gene families due to gene duplications, which generate new copies that allow functional divergence. However, the relationship between
基金Project supported by the Young Scientists Fund of the National Natural Science Foundation of China(Grant No.11804227).
文摘The dynamics of produced excited carriers under the irradiation of Ge crystal is investigated theoretically by using femtosecond laser pulse.A two-temperature model combined with the Drude model is also used to study the nonequilibrium carrier density,carrier and lattice temperatures,and optical properties of the crystal.The properties of the surface plasmon wave when excited are also studied.The influences of non-radiation and radiative recombination process on the photoexcitation of the semiconductor during pulse and the relaxation after the pulse are described in detail.The results show that the effects of Auger recombination on the nonequilibrium carrier density and optical properties of the crystal and the properties of the surface plasmon polariton are great,whereas the effect of radiative recombination is extremely small.
基金supported by the National Key Research and Development Program of China(Grant No.2017YFA0402300)the Chinese Academy of Sciencesthe National Natural Science Foundation of China(Grant Nos.U1732133,11320101003,11611530684,and 11604003)
文摘The electron–ion recombination for phosphorus-like^（112） Sn^（35＋）has been measured at the main cooler storage ring of the Heavy Ion Research Facility in Lanzhou, China, employing an electron–ion merged-beams technique. The absolute total recombination rate coefficients for electron–ion collision energies from 0 e V–14 e V are presented. Theoretical calculations of recombination rate coefficients were performed using the Flexible Atomic Code to compare with the experimental results. The contributions of dielectronic recombination and trielectronic recombination on the experimental rate coefficients have been identified with the help of the theoretical calculation. The present results show that the trielectronic recombination has a substantial contribution to the measured electron–ion recombination spectrum of^（112）Sn^（35＋）. Although a reasonable agreement is found between the experimental and theoretical results the precise calculation of the electron–ion recombination rate coefficients for M-shell ions is still challengeable for the current theory.
基金Project supported by the National Natural Science Foundation of China (Grant Nos. 61774140 and 61474103)。
文摘Recently, the efficiency of CdTe thin film solar cell has been improved by using new type of window layer Mg_(x)Zn_(1-x)O(MZO). However, it is hard to achieve such a high efficiency as expected. In this report a comparative study is carried out between the MZO/CdTe and CdS/CdTe solar cells to investigate the factors affecting the device performance of MZO/CdTe solar cells. The efficiency loss quantified by voltage-dependent photocurrent collection efficiency(ηC(V′)) is 3.89% for MZO/CdTe and 1.53% for CdS/CdTe solar cells. The higher efficiency loss for the MZO/CdTe solar cell is induced by more severe carrier recombination at the MZO/CdTe p-n junction interface and in CdTe bulk region than that for the CdS/CdTe solar cell. Activation energy(Ea) of the reverse saturation current of the MZO/CdTe and CdS/CdTe solar cells are found to be 1.08 e V and 1.36 e V, respectively. These values indicate that for the CdS/CdTe solar cell the carrier recombination is dominated by bulk Shockley-Read-Hall(SRH) recombination and for the MZO/CdTe solar cell the carrier recombination is dominated by the p-n junction interface recombination. It is found that the tunneling-enhanced interface recombination is also involved in carrier recombination in the MZO/CdTe solar cell. This work demonstrates the poor device performance of the MZO/CdTe solar cell is induced by more severe interface and bulk recombination than that of the CdS/CdTe solar cell.
基金Excellent Youth Foundation of Hunan Province(03JJY1008) Science Foundation for Post-doctorate of China(2004035083)
文摘A bilayer model with ohmic anode contact and injection limited cathode contact has been proposed to calculate the recombination efficiency and recombination zone width of the device. The effects of the thickness of hole transport layer and the barriers of organic/organic interface on the combination efficiency and recombination width have been discussed. It is found that： （1） When the electrons are blocked fully and the holes are not blocked significantly at the organic/organic interface, for a given Lh/L, the recombination efficiency increases with increasing the applied voltage, but at a higher applied voltage, the recombination efficiency decreases with increasing Lh/L; （2） The recombination efficiency increases with increasing applied voltage and Hh＇, and when applied voltage and Hh＇ exceed some value, the recombination efficiency appears as a plateau; （3） The recombination width decreases with increasing the applied voltage and Lh/L. This model might explain the relative experiment phenomena.
文摘BACKGROUND Poly(ADP-ribose)polymerase inhibitors(PARPis)are approved as first-line therapies for breast cancer gene(BRCA)-positive,human epidermal growth factor receptor 2-negative locally advanced or metastatic breast cancer.They are also effective for new and recurrent ovarian cancers that are BRCA-or homologous recombination deficiency(HRD)-positive.However,data on these mutations and PARPi use in the Middle East are limited.AIM To assess BRCA/HRD prevalence and PARPi use in patients in the Middle East with breast/ovarian cancer.METHODS This was a single-center retrospective study of 57 of 472 breast cancer patients tested for BRCA mutations,and 25 of 65 ovarian cancer patients tested for HRD.These adult patients participated in at least four visits to the oncology service at our center between August 2021 and May 2023.Data were summarized using descriptive statistics and compared using counts and percentages.Response to treatment was assessed using Response Evaluation Criteria in Solid Tumors criteria.RESULTS Among the 472 breast cancer patients,12.1%underwent BRCA testing,and 38.5%of 65 ovarian cancer patients received HRD testing.Pathogenic mutations were found in 25.6%of the tested patients:26.3%breast cancers had germline BRCA(gBRCA)mutations and 24.0%ovarian cancers showed HRD.Notably,40.0%of gBRCA-positive breast cancers and 66.0%of HRD-positive ovarian cancers were Middle Eastern and Asian patients,respectively.PARPi treatment was used in 5(33.3%)gBRCA-positive breast cancer patients as first-line therapy(n=1;7-months progression-free),for maintenance(n=2;>15-months progression-free),or at later stages due to compliance issues(n=2).Four patients(66.6%)with HRD-positive ovarian cancer received PARPi and all remained progression-free.CONCLUSION Lower testing rates but higher BRCA mutations in breast cancer were found.Ethnicity reflected United Arab Emirates demographics,with breast cancer in Middle Eastern and ovarian cancer in Asian patients.
基金supported by the National Natural Science Foundation of China(grant number:82303223)the Basic and Applied Basic Research Foundation of Guangdong Province(grant numbers:2021A1515220064,2022A1515110299)the Medical Scientific Re-search Foundation of Guangdong Province(grant number:A2022492).
文摘Background:The homologous recombination deficiency(HRD)score serves as a promising biomarker to iden-tify patients who are eligible for treatment with PARP inhibitors(PARPi).Previous studies have suggested a 3-biomarker Genomic Instability Score(GIS)threshold of≥42 as a valid biomarker to predict response to PARPi in patients with ovarian cancer and breast cancer.However,the GIS threshold for prostate cancer(PCa)is still lacking.Here,we conducted an exploratory analysis to investigate an appropriate HRD score threshold and to evaluate its ability to predict response to PARPi in PCa patients.Methods:A total of 181 patients with metastatic castration-resistant PCa were included in this study.Tumor tissue specimens were collected for targeted next-generation sequencing for homologous recombination repair(HRR)genes and copy number variation(CNV)analysis.The HRD score was calculated based on over 50,000 single-nucleotide polymorphisms(SNP)distributed across the human genome,incorporating three SNP-based as-says:loss of heterozygosity,telomeric allelic imbalance,and large-scale state transition.The HRD score threshold was set at the last 5th percentile of the HRD scores in our cohort of known HRR-deficient tumors.The relation-ship between the HRD score and the efficacy in 16 patients of our cohort who received PARPi treatment were retrospectively analyzed.Results:Genomic testing was succeeded in 162 patients.In our cohort,61 patients(37.7%)had HRR mutations(HRRm).BRCA mutations occurred in 15 patients(9.3%).The median HRD score was 4(ranged from 0 to 57)in the total cohort,which is much lower than that in breast and ovarian cancers.Patients who harbored HRRm and BRCA or TP53 mutations had higher HRD scores.CNV occured more frequently in patients with HRRm.The last 5th percentile of HRD scores was 43 in the HRR-mutant cohort and consequently HRD high was defined as HRD scores≥43.In the 16 patients who received PARPi in our cohort,4 patients with a high HRD score achieved an objective response rate(ORR)of 100%while 12 patients with a low HRD score achieved an ORR of 8.3%.Progression-free survival(PFS)in HRD high patients was longer compared to HRD low patients,regardless of HRRm.Conclusions:A HRD score threshold of 43 was established and preliminarily validated to predict the efficacy of PARPi in this study.Future studies are needed to further verify this threshold.
文摘Influence of recombination centers’ changes on the form of phase portraits has been studied. It has been shown that the shape of the phase portraits depends on the concentration of semiconductor materials’ recombination centers.
文摘Homologous recombination （HR） comprises a series of interrelated pathways that function in the repair of DNA double-stranded breaks （DSBs） and interstrand crosslinks （ICLs）. In addition, recombination provides critical support for DNA replication in the recovery of stalled or broken replication forks, contributing to tolerance of DNA damage. A central core of proteins, most critically the RecA homolog Rad51, catalyzes the key reactions that typify HR： homology search and DNA strand invasion. The diverse functions of recombination are reflected in the need for context-specific factors that perform supplemental functions in conjunction with the core proteins. The inability to properly repair complex DNA damage and resolve DNA replication stress leads to genomic instability and contributes to cancer etiology. Mutations in the BRCA2 recombination gene cause predisposition to breast and ovarian cancer as well as Fanconi anemia, a cancer predisposition syndrome characterized by a defect in the repair of DNA interstrand crosslinks. The cellular functions of recombination are also germane to DNA-based treatment modalities of cancer, which target replicating cells by the direct or indirect induction of DNA lesions that are substrates for recombination pathways. This review focuses on mechanistic aspects of HR relating to DSB and ICL repair as well as replication fork support.
文摘A novel method for predicting hotspots and coldspots using support vector machine （SVM） based on statistical learning theory is developed. This method is applied to published 303 hot and 48 cold open reading frames （ORFs） in Saccharomyces cerevisiae. The sequence features of general dinucleotide abundance and dinucleotide abundance based on codon usage are extracted, and then the data sets are classified with different parameters and kernel functions combined with the method of two-fold cross validation. The result indicates that 87.47% accuracy can be reached when classifying hot and cold ORF sequences with the kernel of radial basis function combined with dinucleotide abundance based on codon usage.
文摘The multi-factor recombination and processes superimposition model for hydrocarbon accumulation is put forward in view of the hydrocarbon geological characteristics of multiple episodes of structural evolution, multiple sets of source-reservoir-seal assemblage, multiple cycles of hydrocarbon accumulation and multiple episodes of readjustment and reconstruction in the complex superimposed basins in China. It is a system including theories and methods that can help to predict favorable exploration regions. According to this model, the basic discipline for hydrocarbon generation, evolution and distribution in the superimposed basins can be summarized in multi-factor recombination, processes superimposition, multiple stages of oil filling and latest stage preservation. With the Silurian of the Tarim basin as an example, based on the reconstruction of the evolution history of the four factors （paleo-anticline, source rock, regional cap rock and kinematic equilibrium belt） controlling hydrocarbon accumulation, this model was adopted to predict favorable hydrocarbon accumulation areas and favorable exploration regions following structural destruction in three stages of oil filling, to provide guidance for further exploration ofoil and gas in the Silurian of the Tarim basin.
