Clinical and molecular significance of homologous recombination deficiency positive non-small cell lung cancer in Chinese population:An integrated genomic and transcriptional analysis

Objective:The clinical significance of homologous recombination deficiency(HRD)in breast cancer,ovarian cancer,and prostate cancer has been established,but the value of HRD in non-small cell lung cancer(NSCLC)has not been fully investigated.This study aimed to systematically analyze the HRD status of untreated NSCLC and its relationship with patient prognosis to further guide clinical care.Methods:A total of 355 treatment-naïve NSCLC patients were retrospectively enrolled.HRD status was assessed using the AmoyDx Genomic Scar Score(GSS),with a score of≥50 considered HRD-positive.Genomic,transcriptomic,tumor microenvironmental characteristics and prognosis between HRD-positive and HRDnegative patients were analyzed.Results:Of the patients,25.1%(89/355)were HRD-positive.Compared to HRD-negative patients,HRDpositive patients had more somatic pathogenic homologous recombination repair(HRR)mutations,higher tumor mutation burden(TMB)(P<0.001),and fewer driver gene mutations(P<0.001).Furthermore,HRD-positive NSCLC had more amplifications in PI3K pathway and cell cycle genes,MET and MYC in epidermal growth factor receptor(EGFR)/anaplastic lymphoma kinase(ALK)mutant NSCLC,and more PIK3CA and AURKA in EGFR/ALK wild-type NSCLC.HRD-positive NSCLC displayed higher tumor proliferation and immunosuppression activity.HRD-negative NSCLC showed activated signatures of major histocompatibility complex(MHC)-II,interferon(IFN)-γand effector memory CD8+T cells.HRD-positive patients had a worse prognosis and shorter progressionfree survival(PFS)to targeted therapy(first-and third-generation EGFR-TKIs)(P=0.042).Additionally,HRDpositive,EGFR/ALK wild-type patients showed a numerically lower response to platinum-free immunotherapy regimens.Conclusions:Unique genomic and transcriptional characteristics were found in HRD-positive NSCLC.Poor prognosis and poor response to EGFR-TKIs and immunotherapy were observed in HRD-positive NSCLC.This study highlights potential actionable alterations in HRD-positive NSCLC,suggesting possible combinational therapeutic strategies for these patients.

Initial measurement of ultrafast charge exchange recombination spectroscopy on the EAST tokamak

Ultrafast charge exchange recombination spectroscopy(UF-CXRS)has been developed on the EAST tokamak(Yingying Li et al 2019 Fusion Eng.Des.146522)to measure fast evolutions of ion temperature and toroidal velocity.Here,we report the preliminary diagnostic measurements after relative sensitivity calibration.The measurement results show a much higher temporal resolution compared with conventional CXRS,benefiting from the usage of a prismcoupled,high-dispersion volume-phase holographic transmission grating and a high quantum efficiency,high-gain detector array.Utilizing the UF-CXRS diagnostic,the fast evolutions of the ion temperature and rotation velocity during a set of high-frequency small-amplitude edgelocalized modes(ELMs)are obtained on the EAST tokamak,which are then compared with the case of large-amplitude ELMs.

Physico−mathematical model of the voltage−current characteristics of light-emitting diodes with quantum wells based on the Sah−Noyce−Shockley recombination mechanism

Herein,a physical and mathematical model of the voltage−current characteristics of a p−n heterostructure with quantum wells(QWs)is prepared using the Sah−Noyce−Shockley(SNS)recombination mechanism to show the SNS recombination rate of the correction function of the distribution of QWs in the space charge region of diode configuration.A comparison of the model voltage−current characteristics(VCCs)with the experimental ones reveals their adequacy.The technological parameters of the structure of the VCC model are determined experimentally using a nondestructive capacitive approach for determining the impurity distribution profile in the active region of the diode structure with a profile depth resolution of up to 10Å.The correction function in the expression of the recombination rate shows the possibility of determining the derivative of the VCCs of structures with QWs with a nonideality factor of up to 4.

Features of Recombination Radiation of GaAs Type Semiconductors with the Participation of Fine Acceptor Levels in a Magnetic Field

Using the method of Picus and Beer invariants, general expressions are obtained for the total intensity I and the degree of circular polarization Рcirc.of the luminescence of GaAs-type semiconductors with the participation of shallow acceptor levels in a longitudinal magnetic field H. Special cases are analyzed depending on the value and direction of the magnetic field strength, as well as on the constants of the g-factor of the acceptor g1,g2and the conduction band electron ge. In the case of a strong magnetic field H// [100], [111], [110], a numerical calculation of the angular dependence of the quantities I and Рcirc.was performed for some critical values of g2/g1, at which Рcirc.exhibits a sharp anisotropy in the range from −100% to +100%, and the intensity of the crystal radiation along the magnetic field tends to a minimum value.

Association between homologous recombination deficiency and outcomes with platinum and platinum-free chemotherapy in patients with triple-negative breast cancer

Objective:The choice of chemotherapeutic regimen for triple-negative breast cancer(TNBC)remains controversial.Homologous recombination deficiency(HRD)has attracted increasing attention in informing chemotherapy treatment.This study was aimed at investigating the feasibility of HRD as a clinically actionable biomarker for platinum-containing and platinum-free therapy.Methods:Chinese patients with TNBC who received chemotherapy between May 1,2008 and March 31,2020 were retrospectively analyzed with a customized 3D-HRD panel.HRD positivity was defined by an HRD score≥30 or deleterious BRCA1/2 mutation.A total of 386 chemotherapy-treated patients with TNBC were screened from a surgical cohort(NCT01150513)and a metastatic cohort,and 189 patients with available clinical and tumor sequencing data were included.Results:In the entire cohort,49.2%(93/189)of patients were identified as HRD positive(40 with deleterious BRCA1/2 mutations and 53 with BRCA1/2 intact with an HRD score of≥30).In the first-line metastatic setting,platinum therapy was associated with longer median progression-free survival(mPFS)than platinum-free therapy[9.1 vs.3.0 months;hazard ratio(HR),0.43;95%confidence interval 0.22–0.84;P=0.01].Among HRD-positive patients,the mPFS was significantly longer in those treated with platinum rather than platinum-free therapy(13.6 vs.2.0 months;HR,0.11;P=0.001).Among patients administered a platinum-free regimen,HRD-negative patients showed a PFS significantly superior to that of HRD-positive patients(P=0.02;treatment-biomarker P-interaction=0.001).Similar results were observed in the BRCA1/2-intact subset.In the adjuvant setting,HRD-positive patients tended to benefit more from platinum chemotherapy than from platinum-free chemotherapy(P=0.05,P-interaction=0.02).Conclusions:HRD characterization may guide decision-making regarding the use of platinum treatment in patients with TNBC in both adjuvant and metastatic settings.

A novel color image encryption algorithm based on genetic recombination and the four-dimensional memristive hyperchaotic system

Recently, many image encryption algorithms based on chaos have been proposed. Most of the previous algorithms encrypt components R, G, and B of color images independently and neglect the high correlation between them. In the paper, a novel color image encryption algorithm is introduced. The 24 bit planes of components R, G, and B of the color plain image are obtained and recombined into 4 compound bit planes, and this can make the three components affect each other. A four-dimensional(4D) memristive hyperchaotic system generates the pseudorandom key streams and its initial values come from the SHA 256 hash value of the color plain image. The compound bit planes and key streams are confused according to the principles of genetic recombination, then confusion and diffusion as a union are applied to the bit planes,and the color cipher image is obtained. Experimental results and security analyses demonstrate that the proposed algorithm is secure and effective so that it may be adopted for secure communication.

Winter wheat yield improvement by genetic gain across different provinces in China

The replacement of winter wheat varieties has contributed significantly to yield improvement worldwide,with remarkable progress in China.Drawing on two sets of data,production yield from the National Bureau of Statistics of China and experimental yield from literature,this study aims to(1)illustrate the increasing patterns of production yield among different provinces from 1978 to 2018 in China,(2)explore the genetic gain in yield and yield relevant traits through the variety replacement based on experimental yield from 1937 to 2016 in China,and(3)compare the yield gap between experimental yield and production yield.The results show that both the production and experimental yields significantly increased along with the variety replacement.The national annual yield increase ratio for the production yield was 1.67%from 1978 to 2018,varying from 0.96%in Sichuan Province to 2.78%in Hebei Province;such ratio for the experimental yield was 1.13%from 1937 to 2016.The yield gap between experimental and production yields decreased from the 1970s to the 2010s.This study reveals significant increases in some yield components consequent to variety replacement,including thousand-grain weight,kernel number per spike,and grain number per square meter;however,no change is shown in spike number per square meter.The biomass and harvest index consistently and significantly increased,whereas the plant height decreased significantly.

Absolute dielectronic recombination rate coefficients of highly charged ions at the storage ring CSRm and CSRe

Dielectronic recombination(DR)is one of the dominant electron-ion recombination mechanisms for most highly charged ions(HCIs)in cosmic plasmas,and thus,it determines the charge state distribution and ionization balance therein.To reliably interpret spectra from cosmic sources and model the astrophysical plasmas,precise DR rate coefficients are required to build up an accurate understanding of the ionization balance of the sources.The main cooler storage ring(CSRm)and the experimental cooler storage ring(CSRe)at the Heavy-Ion Research Facility in Lanzhou(HIRFL)are both equipped with electron cooling devices,which provide an excellent experimental platform for electron-ion collision studies for HCIs.Here,the status of the DR experiments at the HIRFL-CSR is outlined,and the DR measurements with Na-like Kr25^(+)ions at the CSRm and CSRe are taken as examples.In addition,the plasma recombination rate coefficients for Ar12^(+),14^(+),Ca14^(+),16^(+),17^(+),Ni19^(+),and Kr25^(+)ions obtained at the HIRFL-CSR are provided.All the data presented in this paper are openly available at https://doi.org/10.57760/sciencedb.j00113.00092.

Genetically modified pigs:Emerging animal models for hereditary hearing loss

Hereditary hearing loss(HHL),a genetic disorder that impairs auditory function,significantly affects quality of life and incurs substantial economic losses for society.To investigate the underlying causes of HHL and evaluate therapeutic outcomes,appropriate animal models are necessary.Pigs have been extensively used as valuable large animal models in biomedical research.In this review,we highlight the advantages of pig models in terms of ear anatomy,inner ear morphology,and electrophysiological characteristics,as well as recent advancements in the development of distinct genetically modified porcine models of hearing loss.Additionally,we discuss the prospects,challenges,and recommendations regarding the use pig models in HHL research.Overall,this review provides insights and perspectives for future studies on HHL using porcine models.

AC Back Surface Recombination Velocity as Applied to Optimize the Base Thickness under Temperature of an (n+-p-p+) Bifacial Silicon Solar Cell, Back Illuminated by a Light with Long Wavelength

The bifacial silicon solar cell, placed at temperature (T) and illuminated from the back side by monochromatic light in frequency modulation (ω), is studied from the frequency dynamic diffusion equation, relative to the density of excess minority carriers in the base. The expressions of the dynamic recombination velocities of the minority carriers on the rear side of the base Sb1(D(ω, T);H) and Sb2(α, D(ω, T);H), are analyzed as a function of the dynamic diffusion coefficient (D(ω, T)), the absorption coefficient (α(λ)) and the thickness of the base (H). Thus their graphic representation makes it possible to go up, to the base optimum thickness (Hopt(ω, T)), for different temperature values and frequency ranges of modulation of monochromatic light, of strong penetration. The base optimum thickness (Hopt(ω, T)) decreases with temperature, regardless of the frequency range and allows the realization of the solar cell with few material (Si).

Genetic pathways in cerebral palsy:a review of the implications for precision diagnosis and understanding disease mechanisms

Ce rebral palsy is a diagnostic term utilized to describe a group of permanent disorders affecting movement and posture.Patients with cerebral palsy are often only capable of limited activity,resulting from non-progressive disturbances in the fetal or neonatal brain.These disturbances severely impact the child’s daily life and impose a substantial economic burden on the family.Although cerebral palsy encompasses various brain injuries leading to similar clinical outcomes,the unde rstanding of its etiological pathways remains incomplete owing to its complexity and heterogeneity.This review aims to summarize the current knowledge on the genetic factors influencing cerebral palsy development.It is now widely acknowledged that genetic mutations and alterations play a pivotal role in cerebral palsy development,which can be further influenced by environmental fa ctors.Des pite continuous research endeavors,the underlying fa ctors contributing to cerebral palsy remain are still elusive.However,significant progress has been made in genetic research that has markedly enhanced our comprehension of the genetic factors underlying cerebral palsy development.Moreove r,these genetic factors have been categorized based on the identified gene mutations in patients through clinical genotyping,including thrombosis,angiogenesis,mitochondrial and oxidative phosphorylation function,neuronal migration,and cellular autophagy.Furthermore,exploring targeted genotypes holds potential for precision treatment.In conclusion,advancements in genetic research have substantially improved our understanding of the genetic causes underlying cerebral palsy.These breakthroughs have the potential to pave the way for new treatments and therapies,consequently shaping the future of cerebral palsy research and its clinical management.The investigation of cerebral palsy genetics holds the potential to significantly advance treatments and management strategies.By elucidating the underlying cellular mechanisms,we can develop to rgeted interventions to optimize outcomes.A continued collaboration between researchers and clinicians is imperative to comprehensively unravel the intricate genetic etiology of cerebral palsy.

LociScan,a tool for screening genetic marker combinations for plant variety discrimination

To reduce the cost and increase the efficiency of plant genetic marker fingerprinting for variety discrimination,it is desirable to identify the optimal marker combinations.We describe a marker combination screening model based on the genetic algorithm(GA)and implemented in a software tool,Loci Scan.Ratio-based variety discrimination power provided the largest optimization space among multiple fitness functions.Among GA parameters,an increase in population size and generation number enlarged optimization depth but also calculation workload.Exhaustive algorithm afforded the same optimization depth as GA but vastly increased calculation time.In comparison with two other software tools,Loci Scan accommodated missing data,reduced calculation time,and offered more fitness functions.In large datasets,the sample size of training data exerted the strongest influence on calculation time,whereas the marker size of training data showed no effect,and target marker number had limited effect on analysis speed.

Allopolyploidization increases genetic recombination in the ancestral diploid D genome during wheat evolution

Genetic recombination produces new allelic combinations,thereby introducing variation for domestication.Allopolyploidization has increased the evolutionary potential of hexaploid common wheat by conferring the advantages of heterosis and gene redundancy,but whether a relationship exists between allopolyploidization and genetic recombination is currently unknown.To study the impact of allopolyploid ization on genetic recombination in the ancestral D genome of wheat,we generated new synthetic hexaploid wheats by crossing tetraploid Triticum turgidum with multiple diploid Aegilops tauschii accessions,with subsequent chromosome doubling,to simulate the evolutionary hexaploidization process.Using the DArT-Seq approach,we determined the genotypes of two new synthetic hexaploid wheats with their parents,F;plants in a diploid population(2 x,D_(1)D_(1)×D_(2)D_(2))and its new synthetic hexaploid wheatderived population(6 x,AABBD_(1)D_(1)×AABBD_(2)D_(2)).About 11%of detected SNP loci spanning the D genome of Ae.tauschii were eliminated after allohexaploidization,and the degree of segregation distortion was increased in their hexaploid offspring from the F_(1) generation.Based on codominant genotypes,the mean genetic interval length and recombination frequency between pairs of adjacent and linked SNPs on D genome of the hexaploid F;population were 2.3 fold greater than those in the diploid F_(2) population,and the recombination frequency of Ae.tauschii was increased by their hexaploidization with T.turgidum.In conclusion,allopolyploidization increases genetic recombination of the ancestral diploid D genome of wheat,and DNA elimination and increased segregation distortion also occur after allopolyploidization.Increased genetic recombination could have produced more new allelic combinations subject to natural or artificial selection,helping wheat to spread rapidly to become a major global crop and thereby accelerating the evolution of wheat via hexaploidization.

Genetic screening of liver cancer:State of the art

Liver cancer,primarily hepatocellular carcinoma,remains a global health challenge with rising incidence and limited therapeutic options.Genetic factors play a pivotal role in the development and progression of liver cancer.This state-of-the-art paper provides a comprehensive review of the current landscape of genetic screening strategies for liver cancer.We discuss the genetic underpinnings of liver cancer,emphasizing the critical role of risk-associated genetic variants,somatic mutations,and epigenetic alterations.We also explore the intricate interplay between environmental factors and genetics,highlighting how genetic screening can aid in risk stratification and early detection via using liquid biopsy,and advancements in high-throughput sequencing technologies.By synthesizing the latest research findings,we aim to provide a comprehensive overview of the state-of-the-art genetic screening methods for liver cancer,shedding light on their potential to revolutionize early detection,risk assessment,and targeted therapies in the fight against this devastating disease.

Age-specific heterogeneity of genetic susceptibility to cardiovascular disease might have opposite outcomes depending on the presence of prediabetes

Examining age-specific heterogeneity of susceptibility to cardiovascular disease is also essential in individuals without prediabetes to determine its relative size and direction compared to those with prediabetes.Of particular interest,age-specific heterogeneity in genetic susceptibility may exhibit opposite directions depending on the presence or absence of prediabetes.

Genetic and pathogenic characterization of new infectious bronchitis virus strains in the GVI-1 and GI-19 lineages isolated in central China

Avian infectious bronchitis(IB)is a highly contagious infectious disease caused by infectious bronchitis virus(IBV),which is prevalent in many countries worldwide and causes serious harm to the poultry industry.At present,many commercial IBV vaccines have been used for the prevention and control of IB;however,IB outbreaks occur frequently.In this study,two new strains of IBV,SX/2106 and SX/2204,were isolated from two flocks which were immunized with IBV H120 vaccine in central China.Phylogenetic and recombination analysis indicated that SX/2106,which was clustered into the GI-19 lineage,may be derived from recombination events of the GI-19 and GI-7 strains and the LDT3-A vaccine.Genetic analysis showed that SX/2204 belongs to the GVI-1 lineage,which may have originated from the recombination of the GI-13 and GVI-1 strains and the H120 vaccine.The virus cross-neutralization test showed that the antigenicity of SX/2106 and SX/2204 was different from H120.Animal experiments found that both SX/2106 and SX/2204 could replicate effectively in the lungs and kidneys of chickens and cause disease and death,and H120 immunization could not provide effective protection against the two IBV isolates.It is noteworthy that the pathogenicity of SX/2204 has significantly increased compared to the GVI-1 strains isolated previously,with a mortality rate up to 60%.Considering the continuous mutation and recombination of the IBV genome to produce new variant strains,it is important to continuously monitor epidemic strains and develop new vaccines for the prevention and control of IBV epidemics.

Effect of Environment and Genetic Recombination on Subspecies and Economic Trait Differentiation in the F_2 and F_3 Generations from indicajaponica Hybridization

indica and japonica are the two most important subspecies of Asian cultivated rice. Identifying mechanisms responsible for population differentiation in these subspecies is important for indica-japonica hybridization breeding. In this study, subspecies and economic trait differentiation patterns were analyzed using morphological and molecular （InDel and Intron Length Polymorphism） data in F2 and F3 populations derived from indica-japonica hybridization. Populations were grown in Liaoning and Guangdong provinces, China, with F3 populations generated from F2 populations using bulk harvesting （BM） and single-seed descent methods （SSD）. Segregation distortion was detected in F3-BM populations, but not in F3- SSD or in F2 populations. Superior performance was observed with respect to economic traits in Liaoning compared with that in Guangdong and 1 000-grain weight （KW）, seed setting rate （SSR） and grain yield per plant （GYP） were significantly correlated with indica and japonica subspecies types. Analysis of molecular and morphological data demonstrated that the environment is the main factor giving rise to population differentiation in indica-japonica hybridization. In addition, we also found that KW, SSR and GYP are related to subspecies characteristics and kinship, which is possibly a significant factor resulting in economic trait differentiation and determining environmental adaptability. Our study has provided new insights into the process of population differentiation in these subspecies to inform indica-japonica hybridization breeding.

Effect Study of the Recombinant Human Brain Natriuretic Peptide in Patients with Heart Failure Combined with Hypotension

Objective: This paper aims to investigate the effect of applying recombinant human brain natriuretic peptide in patients with heart failure combined with hypotension. Recombinant human brain natriuretic peptide is a synthetic polypeptide drug that is primarily used to treat acute heart failure. Its mechanism of action closely mimics that of human endogenous brain natriuretic peptide. By binding to receptors on cardiomyocytes, it exerts its pharmacological effects. Methods: For the study, 76 heart failure patients with hypotension were selected from our hospital between May 2022 and June 2023. These patients were divided into two groups: a control group and an observation group, each comprising 38 patients. The control group received dopamine treatment, while the observation group was treated with recombinant brain natriuretic peptide. The objective was to compare the effects of the treatments in both groups by analyzing cardiac function indices and levels of vasoactive substances to identify any significant differences in outcomes. Results: The overall response rate of the patients in the observation group and the control group was 94.74% and 73.68%, significantly higher as compared with the observation group (P 0.05). After the following treatment, BNP, ANNP and urine output in the observation group were significantly different compared with the control group, of the statistical significance (P Conclusion: For the treatment of heart failure patients with hypotension, the clinical application of recombinant human brain natriuretic peptide is the most ideal, and significantly improves the cardiac function of patients, which is worth popularizing.

Population genomic analysis reveals key genetic variations and the driving force for embryonic callus induction capability in maize

Genetic transformation has been an effective technology for improving the agronomic traits of maize.However,it is highly reliant on the use of embryonic callus(EC)and shows a serious genotype dependence.In this study,we performed genomic sequencing for 80 core maize germplasms and constructed a high-density genomic variation map using our newly developed pipeline(MQ2Gpipe).Based on the induction rate of EC(REC),these inbred lines were categorized into three subpopulations.The low-REC germplasms displayed more abundant genetic diversity than the high-REC germplasms.By integrating a genome-wide selective signature screen and region-based association analysis,we revealed 95.23 Mb of selective regions and 43 REC-associated variants.These variants had phenotypic variance explained values ranging between 21.46 and 49.46%.In total,103 candidate genes were identified within the linkage disequilibrium regions of these REC-associated loci.These genes mainly participate in regulation of the cell cycle,regulation of cytokinesis,and other functions,among which MYB15 and EMB2745 were located within the previously reported QTL for EC induction.Numerous leaf area-associated variants with large effects were closely linked to several REC-related loci,implying a potential synergistic selection of REC and leaf size during modern maize breeding.

Inbreeding and genetic load in a pair of sibling grouse species:Tetrastes sewersowi and T.bonasia

Genetic load and inbreeding are recognized as important factors to be considered in conservation programs.Elevated levels of both can increase the risk of population extinction by negatively impacting fitness-related characters in many species of plants and animals,including humans(inbreeding depression).Genomic tech-niques are increasingly used in measuring and understanding genetic load and inbreeding and their importance in evolution and conservation.We used whole genome resequencing data from two sibling grouse species in subarctic Eurasia to quantify both.We found a large range of inbreeding measured as FROH(fraction of runs of homozygosity)in individuals from different populations of Chinese Grouse(Tetrastes sewerzowi)and Hazel Grouse(T.bonasia).FROH estimated from genome-wide runs of homozygosity(ROH)ranged from 0.02 to 0.24 among Chinese Grouse populations and from 0.01 to 0.44 in Hazel Grouse.Individuals from a population of Chinese Grouse residing in the Qilian mountains and from the European populations of Hazel Grouse(including samples from Sweden,Germany and Northeast Poland)were the most inbred(FROH ranged from 0.10 to 0.23 and 0.11 to 0.44,respectively).These levels are comparable to other highly inbred populations of birds.Hazel Grouse from northern China and Chinese Grouse residing in the Qinghai-Tibetan Plateau showed relatively lower inbreeding levels.Comparisons of the ratio between deleterious missense mutations and synonymous mutations revealed higher levels in Chinese Grouse as compared to Hazel Grouse.These results are possibly explained by higher fixation rates,mutational melt down,in the range-restricted Chinese Grouse compared to the wide-ranging Hazel Grouse.However,when we compared the relatively more severe class of loss-of-function muta-tions,Hazel Grouse had slightly higher levels than Chinese Grouse,a result which may indicate that purifying selection(purging)has been more efficient in Chinese Grouse on this class of mutations.