Etiologic evaluation and pregnancy outcomes of fetal growth restriction (FGR) associated with structural malformations.

This study aimed to evaluate the etiology and pregnancy outcomes of fetuses underwent invasive prenatal diagnosis for fetal growth restriction (FGR) accompanied by structural malformations. Data from 130 pregnancies referred for prenatal diagnosis for FGR accompanied by structural malformations were obtained between July 2011 and July 2023. Traditional karyotyping was conducted for all the subjects. A total of 37 (28.5%) cases of chromosomal abnormalities were detected by karyotyping, including 30 cases of numerical anomalies and seven cases of unbalanced structural anomalies. Trisomy 18 was the most common abnormalities, accounting for 51.4%, significantly higher than any other chromosomal abnormality. The cohort was predominantly comprised of early-onset FGR (88.5%) compared to late-onset FGR (11.5%). The incidences of chromosomal abnormalities in this two groups were 29.6% (34/115) and 20.0% (3/15), respectively (p > 0.05). The majority (74.6%, 97/130) of the cohort were affected by a single system malformation, with chromosomal abnormalities found in 19.6% (19/97) of cases. In pregnancies of structural malformations involving two and multiple systems, the frequencies were 56.5% (13/23), and 50.0% (5/10), respectively. Single nucleotide polymorphism array (SNP array) was performed in parallel for 65 cases, revealing additional 7.7% cases of copy number variants (CNVs) compared to karyotyping. Polymerase chain reaction (PCR) was used for detection of cytomegalovirus (CMV) DNA in 92 cases. All fetuses with FGR associated with two or more system malformations were either terminated or stillborn, irrespective of chromosomal aberrations. Conversely, 71.8% of pregnancies with a single-system malformation and normal genetic testing results resulted in live births. Furthermore, two (2.2%) cases tested positive for CMV DNA, leading to one termination and one case of serious developmental disorder after birth. Our study suggests that structural malformations associated with FGR are more likely to affect a single organ system. When multiple systems are involved, the incidence of chromosomal abnormalities and termination rates are notably high. We advocate for the use of CMA and CMV DNA examinations in FGR cases undergo invasive prenatal diagnosis, as these tests can provide valuable insights for etiological exploration and pregnancy management guidance.

Advance in pathogenesis of sarcoidosis: Triggers and progression.

Sarcoidosis, a multisystemic immune disease, significantly impacts patients' quality of life. The complexity and diversity of its pathogenesis, coupled with limited comprehensive research, had hampered both diagnosis and treatment, resulting in an unsatisfactory prognosis for many patients. In recent years, the research had made surprising progress in the triggers of sarcoidosis (genetic inheritance, infection and environmental factors) and the abnormal regulations on immunity during the formation of granuloma. This review consolidated the latest findings on sarcoidosis research, providing a systematic exploration of advanced studies on triggers, immune-related regulatory mechanisms, and clinical applications. By synthesizing previous discoveries, we aimed to offer valuable insights for future research directions and the development of clinical diagnosis and treatment strategies.

Oxygen Vacancy and Bandgap Simultaneous Modulation to Achieve High Lithiophilicity and Mechanical Strength of Lithium Metal Anodes.

Metal oxides with conversion and alloying mechanisms are more competitive in suppressing lithium dendrites. However, it is difficult to simultaneously regulate the conversion and alloying reactions. Herein, conversion and alloying reactions are regulated by modulation of the zinc oxide bandgap and oxygen vacancies. State-of-the-art advanced characterization techniques from a microcosmic to a macrocosmic viewpoint, including neutron diffraction, synchrotron X-ray absorption spectroscopy, synchrotron X-ray microtomography, nanoindentation, and ultrasonic C-scan demonstrated the electrochemical gain benefit from plentiful oxygen vacancies and low bandgaps due to doping strategies. In addition, high mechanical strength 3D morphology and abundant mesopores assist in the uniform distribution of lithium ions. Consequently, the best-performed ZnO-2 offers impressive electrochemical properties, including symmetric Li cells with 2000 h and full cells with 81% capacity retention after 600 cycles. In addition to providing a promising strategy for improving the lithiophilicity and mechanical strength of metal oxide anodes, this work also sheds light on lithium metal batteries for practical applications.

An exosome-derived lncRNA signature identified by machine learning associated with prognosis and biomarkers for immunotherapy in ovarian cancer.

Background: Ovarian cancer (OC) has the highest mortality rate among gynecological malignancies. Current treatment options are limited and ineffective, prompting the discovery of reliable biomarkers. Exosome lncRNAs, carrying genetic information, are promising new markers. Previous studies only focused on exosome-related genes and employed the Lasso algorithm to construct prediction models, which are not robust. Methods: 420 OC patients from the TCGA datasets were divided into training and validation datasets. The GSE102037 dataset was used for external validation. LncRNAs associated with exosome-related genes were selected using Pearson analysis. Univariate COX regression analysis was used to filter prognosis-related lncRNAs. The overlapping lncRNAs were identified as candidate lncRNAs for machine learning. Based on 10 machine learning algorithms and 117 algorithm combinations, the optimal predictor combinations were selected according to the C index. The exosome-related LncRNA Signature (ERLS) model was constructed using multivariate COX regression. Based on the median risk score of the training datasets, the patients were divided into high- and low-risk groups. Kaplan-Meier survival analysis, the time-dependent ROC, immune cell infiltration, immunotherapy response, and immune checkpoints were analyzed. Results: 64 lncRNAs were subjected to a machine-learning process. Based on the stepCox (forward) combined Ridge algorithm, 20 lncRNA were selected to construct the ERLS model. Kaplan-Meier survival analysis showed that the high-risk group had a lower survival rate. The area under the curve (AUC) in predicting OS at 1, 3, and 5 years were 0.758, 0.816, and 0.827 in the entire TCGA cohort. xCell and ssGSEA analysis showed that the low-risk group had higher immune cell infiltration, which may contribute to the activation of cytolytic activity, inflammation promotion, and T-cell co-stimulation pathways. The low-risk group had higher expression levels of PDL1, CTLA4, and higher TMB. The ERLS model can predict response to anti-PD1 and anti-CTLA4 therapy. Patients with low expression of PDL1 or high expression of CTLA4 and low ERLS exhibited significantly better survival prospects, whereas patients with high ERLS and low levels of PDL1 or CTLA4 exhibited the poorest outcomes. Conclusion: Our study constructed an ERLS model that can predict prognostic risk and immunotherapy response, optimizing clinical management for OC patients.

Prognostic model development and molecular subtypes identification in bladder urothelial cancer by oxidative stress signatures.

BACKGROUND: Mounting studies indicate that oxidative stress (OS) significantly contributes to tumor progression. Our study focused on bladder urothelial cancer (BLCA), an escalating malignancy worldwide that is growing rapidly. Our objective was to verify the predictive precision of genes associated with overall survival (OS) by constructing a model that forecasts outcomes for bladder cancer and evaluates the prognostic importance of these genetic markers. METHODS: Transcriptomic data were obtained from TCGA-BLCA and GSE31684, which are components of the Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO), respectively. To delineate distinct molecular subtypes, we employed the non-negative matrix factorization (NMF)method. The significance of OS-associated genes in predicting outcomes was assessed using lasso regression, multivariate Cox analysis, and univariate Cox regression analysis. For external validation, we employed the GSE31684 dataset. CIBERSORT was utilized to examine the tumor immune microenvironment (TIME). A nomogram was created and verified using calibration and receiver operating characteristic (ROC) curves, which are based on risk signatures. We examined variations in clinical characteristics and tumor mutational burden (TMB) among groups classified as high-risk and low-risk. To evaluate the potential of immunotherapy, the immune phenomenon score (IPS) was computed based on the risk score. In the end, the pRRophetic algorithm was employed to forecast the IC50 values of chemotherapy medications. RESULTS: In our research, we examined the expression of 275 genes associated with OS in 19 healthy and 414 cancerous tissues of the bladder obtained from the TCGA database. As a result, a new risk signature was created that includes 4 genes associated with OS (RBPMS, CRYAB, P4HB, and PDGFRA). We found two separate groups, C1 and C2, that showed notable variations in immune cells and stromal score. According to the Kaplan-Meier analysis, patients classified as high-risk experienced a considerably reduced overall survival in comparison to those categorized as low-risk (P<0.001). The predictive capability of the model was indicated by the area under the curve (AUC) of the receiver operating characteristic (ROC) curve surpassing 0.6. Our model showed consistent distribution of samples from both the GEO database and TCGA data. Both the univariate and multivariate Cox regression analyses validated the importance of the risk score in relation to overall survival (P < 0.001). According to our research, patients with a lower risk profile may experience greater advantages from using a CTLA4 inhibitor, whereas patients with a higher risk profile demonstrated a higher level of responsiveness to Paclitaxel and Cisplatin. In addition, methotrexate exhibited a more positive outcome in patients with low risk compared to those with high risk. CONCLUSIONS: Our research introduces a novel model associated with OS gene signature in bladder cancer, which uncovers unique survival results. This model can assist in tailoring personalized treatment approaches and enhancing patient therapeutic effect in the management of bladder cancer.

Detailed mechanism study of volatile organic compound decomposition and oxidation removal based on a ReaxFF MD method.

Volatile organic compounds (VOCs) are typical air pollutants as well as gaseous wastes that contain energy. Utilization and disposition of VOCs is currently an important research hotspot in the field of atmospheric environment. In this paper, the thermal cracking and oxidation reaction processes of typical VOCs components were modelled and analyzed by combining molecular dynamics and detailed reaction mechanisms, focusing on the effects of temperature, oxygen and other conditions on the conversion of VOCs. The results of molecular dynamics studies show that improving temperature and reaction time benefit the decomposition of VOCs. High temperatures under an inert atmosphere can sufficiently crack the VOCs themselves, but other by-products are generated, which in turn cause secondary pollution. The activation energies derived by ReaxFF-MD calculation are 328 kJ mol-1, 147 kJ mol-1 and 121 kJ mol-1 for toluene, styrene and benzaldehyde respectively, which is consistent with experimental results. Under the oxygen atmosphere, the conversion rate of VOCs is greatly increased and the reaction temperature is significantly reduced. Meanwhile, the oxidation reaction fully converts VOCs into non-polluting products such as CO2 and H2O. Detailed kinetic studies show that initial oxidation of toluene molecules raised by hydrogen abstraction reaction is the dominant step during toluene oxidation, which significantly improved the decomposition efficiency of toluene.

Unraveling the atmospheric oxidation mechanism and kinetics of naphthalene: Insights from theoretical exploration.

Naphthalene, the most abundant polycyclic aromatic hydrocarbon in the atmosphere, significantly influences OH consumption and secondary organic aerosol (SOA) formation. Naphthoquinone (NQ) is a significant contributor to ring-retaining SOA from naphthalene degradation, impacting the redox properties and toxicity of ambient particles. However, inconsistencies persist regarding concentrations of its isomers, 1,2-NQ and 1,4-NQ. In present work, our theoretical investigation into naphthalene's reaction with OH and subsequent oxygenation unveils their role in SOA formation. The reaction kinetics of initial OH and subsequent O2 oxidation was extensively studied using high-level quantum chemical methods (DLPNO-CCSD(T)/aug-ccpVQZ//M052x-D3/6-311++G(d,p)) combined with RRKM/master equation simulations. The reactions mainly proceed through electrophilic addition and abstraction from the aromatic ring. The total rate coefficient of naphthalene + OH at 300 K and 1 atm from our calculation (7.2 × 10-12 cm3 molecule-1 s-1) agrees well with previous measurements (∼1 × 10-11 cm3 molecule-1 s-1). The computed branching ratios facilitate accurate product yield determination. The largest yield of 1-hydroxynaphthalen-1-yl radical (add1) producing the major precursor of RO2 is computed to be 93.8 % in the ambient environment. Our calculated total rate coefficient (5.2 × 10-16 cm3 molecule-1 s-1) for add1 + O2 closely matches that of limited experimental data (8.0 × 10-16 cm3 molecule-1 s-1). Peroxy radicals (RO2) generated from add1 + O2 include 4-cis/trans-(1-hydroxynaphthalen-1-yl)-peroxy radical (add1-4OOadd-cis/trans, 66.0 %/17.5 %), 2-cis/trans-(1-hydroxynaphthalen-1-yl)-peroxy radical (add1-2OOadd-cis/trans, 10.3 %/6.3 %). Regarding the debated predominance of 1,4-NQ (corresponding to the parent RO2, i.e., add1-4OOadd-cis/trans) and 1,2-NQ (corresponding to the parent RO2, i.e., add1-2OOadd-cis/trans) in the atmosphere, our findings substantiate the dominance of 1,4-NQ. This study also indicates potential weakening of 1,4-NQ's dominance due to competition from decomposition reactions of add1-4OOadd-cis/trans and add1-2OOadd-cis/trans. Precise reaction kinetics data are essential for characterizing SOA transformation derived from naphthalene and assessing their climatic impacts within modeling frameworks.

Experience of copy number variation sequencing applied in spontaneous abortion.

PURPOSE: We evaluated the value of copy number variation sequencing (CNV-seq) and quantitative fluorescence (QF)-PCR for analyzing chromosomal abnormalities (CA) in spontaneous abortion specimens. METHODS: A total of 650 products of conception (POCs) were collected from spontaneous abortion between April 2018 and May 2020. CNV-seq and QF-PCR were performed to determine the characteristics and frequencies of copy number variants (CNVs) with clinical significance. The clinical features of the patients were recorded. RESULTS: Clinically significant chromosomal abnormalities were identified in 355 (54.6%) POCs, of which 217 (33.4%) were autosomal trisomies, 42(6.5%) were chromosomal monosomies and 40 (6.2%) were pathogenic CNVs (pCNVs). Chromosomal trisomy occurs mainly on chromosomes 15, 16, 18, 21and 22. Monosomy X was not associated with the maternal or gestational age. The frequency of chromosomal abnormalities in miscarriages from women with a normal live birth history was 55.3%; it was 54.4% from women without a normal live birth history (P > 0.05). There were no significant differences among women without, with 1, and with ≥ 2 previous miscarriages regarding the rate of chromosomal abnormalities (P > 0.05); CNVs were less frequently detected in women with advanced maternal age than in women aged ≤ 29 and 30-34 years (P < 0.05). CONCLUSION: Chromosomal abnormalities are the most common cause of pregnancy loss, and maternal and gestational ages are strongly associated with fetal autosomal trisomy aberrations. Embryo chromosomal examination is recommended regardless of the gestational age, modes of conception or previous abortion status.

HPV prevalence and distribution characteristics in postmenopausal women from Nanjing, China.

BACKGROUND: Cervical cancer is strongly associated with human papillomavirus (HPV) infection. In this retrospective study, we analyzed the data of postmenopausal women who were tested for HPV in Nanjing First Hospital from 2019 to 2021. METHODS: We retrospectively analyzed the data of 14,608 postmenopausal women aged 45-90 years, who underwent HPV examination in Nanjing First Hospital between January 2019 and December 2021. All participants were tested for 23 HPV genotypes. We subsequently analyzed the infection rate and evaluated the distribution of HPV using the chi-square test. RESULTS: Our results showed that the HPV infection rate in postmenopausal women in Nanjing, China was 22.36%. In terms of age group, the infection rate was 19.54%, 24.30%, 26.58%, and 14.99% in those aged ≤ 50, 51-60, 61-70, and ≥ 71 years, respectively. The most common HPV subtypes were HPV52 (22.1 3%), HPV58 (15.86%), HPV53 (14.17%), HPV16 (12.61%), and HPV81 (11.66%), in that order. The single-HPV infection rate was 14.23%, and the multiple-genotype infection rate was 8.14% (1189/14,608). CONCLUSIONS: This study showed that in Nanjing, China, the different age groups of post-menopausal women could have different rates of HPV infection, and the most common types were HPV52, HPV58, HPV53, HPV16 and HPV81. These findings highlighted the importance of understanding the epidemiology of HPV infection in specific populations, such as postmenopausal women in Nanjing, China. The results could provide valuable information for healthcare professionals and policymakers to develop targeted prevention and screening strategies for reducing the burden of HPV-related diseases in this population.

Anthriscus sylvestris: An overview on Bioactive Compounds and Anticancer Mechanisms from a Traditional Medicinal Plant to Modern Investigation.

Anthriscus sylvestris (L.) Hoffm. Gen. is a biennial or perennial herb commonly found in China. It has a long history of use in traditional Chinese medicine to treat various ailments such as cough, gastric disorders, spleen deficiency, and limb weakness. Recently, its potential as an anticancer agent has gained considerable attention and has been the subject of extensive research focusing on extract efficacy, identification of active compounds, and proposed molecular mechanisms. Nevertheless, further high-quality research is still required to fully evaluate its potential as an anticancer drug. This review aims to comprehensively summarize the anticancer properties exhibited by the active components found in Anthriscus sylvestris. We conducted a comprehensive search, collation, and analysis of published articles on anticancer activity and active compounds of A. sylvestris using various databases that include, but are not limited to, PubMed, Web of Science, Science Direct and Google Scholar. The primary chemical composition of A. sylvestris consists of phenylpropanoids, flavonoids, steroids, fatty acids, and organic acids, showcasing an array of pharmacological activities like anticancer, antioxidant, anti-aging, and immunoregulatory properties. Thus, this review highlights the active compounds isolated from A. sylvestris extracts, which provide potential leads for the development of novel anticancer drugs and a better understanding of the plant's pharmacological effects, particularly its anticancer mechanism of action.

CRP, IL-1α, IL-1ß, and IL-6 levels and the risk of breast cancer: a two-sample Mendelian randomization study.

Epidemiological studies have reported a positive association between chronic inflammation and cancer risk. However, the causal association between chronic inflammation and breast cancer (BC) risk remains unclear. Here, we performed a Mendelian randomization study to investigate the etiological role of chronic inflammation in BC risk. We acquired data regarding C-reactive protein (CRP), interleukin (IL)-1a, IL-1b, and IL-6 expression and BC related to single nucleotide polymorphisms (SNPs) from two larger consortia (the genome-wide association studies and the Breast Cancer Association Consortium). Next, we conducted the two-sample Mendelian randomization study to investigate the relationship of the abovementioned inflammatory factors with the incidence of BC. We found that genetically predicted CRP, IL-6, and IL-1a levels did not increase BC incidence (odds ratio (OR)CRP 1.06, 95% confidence interval (CI) 0.98-1.12, P = 0.2059, ORIL-6 1.05, 95% CI 0.95-1.16, P = 0.3297 and ORIL-1a 1.01, 95% CI 0.99-1.03, P = 0.2167). However, in subgroup analysis, genetically predicted IL-1b levels increased ER + BC incidence (OR 1.15, 95% CI 1.03-1.27, P = 0.0088). Our study suggested that genetically predicted IL-1b levels were found to increase ER + BC susceptibility. However, due to the support of only one SNP, heterogeneity and pleiotropy tests cannot be performed, which deserves further research.

Genetic evaluation for twin pregnancies using karyotyping and single nucleotide polymorphism array analysis.

The study aimed to assess chromosomal abnormalities in twin pregnancies using karyotyping and SNP array analysis. The research involved 530 twin pregnancies from two prenatal diagnosis centers between October 2012 and October 2022. Two types of twin pregnancies were considered: monochorionic diamniotic (MCDA) and dichorionic diamniotic (DCDA), with a total of 177 MCDA and 353 DCDA cases. Chromosomal abnormalities were examined based on chorionic and amniotic sac properties and clinical indications. Among 42 twin pregnancies, 50 fetuses showed chromosomal abnormalities by karyotyping, with 35 cases of aneuploidy in DCDA and 10 in MCDA. Trisomy 21 was the most common aberration, affecting 15 fetuses in DCDA and 4 in MCDA. The rate of discordant karyotypes in MCDA and DCDA groups was 1.1% and 8.8%, respectively. Ultrasound abnormalities and advanced maternal age were frequent indications (55.3% and 39.2%, respectively). Aneuploidy frequencies in DCDA and MCDA pregnancies with advanced maternal age were 10.6% and 4.5%. Cardiac defects and increased nuchal translucency were common anomalies, with higher incidences of chromosomal abnormalities in DCDA (12.5% and 6.9%) and MCDA groups (23.5% and 3.7%). SNP array identified 1.6% clinically significant copy number variants in DCDA fetuses with ultrasound abnormalities, while no significant CNVs were found in MCDA pregnancies. Chromosomal aneuploidies were the primary abnormalities in twin pregnancies, with detectable abnormalities and clinically significant CNVs more likely in DCDA pregnancies, especially those with ultrasound abnormalities.

Kinetic Model for Denitration Reaction Process of Cylindrical Single-Base Gun Propellant.

As a new type of progressive energy release propellant, nitro gradiently distributed propellant (NGDP) was prepared by a denitration reaction between a denitration reagent and the propellant to remove the energy-containing functional group (-O-NO2) from the surface of the propellant. The kinetics of the denitration reaction determines distribution of the nitrate group in the surface layer of NGDP, which further affects the combustion progressivity. In this paper, the kinetic model for the denitration reaction process of the cylindrical single-base gun propellant was studied by the shrinking unreacted core model (SUC model). The energy change of the propellant particles before and after the denitration reaction was used to evaluate the denitration rates, which were used to fit the proposed SUC cylindrical model. The results show that the rate-controlling step of the denitration reaction process is largely dependent on the concentration of the denitration reagent. At low concentrations (the concentration of the denitration reagent was 6%), the denitration reaction process was controlled by the chemical reaction, and the activation energy was found to be 48.40 kJ·mol-1. When the concentration increased (the concentration of the denitration reagent was 15%), the rate-controlling step changed to a solid product layer diffusion control with an activation energy of 84.77 kJ·mol-1. The kinetic models obtained in this study can provide theoretical guidance for the controlled preparation of NGDP with good combustion progressivity.

Clinical Performance of a Dedicated Urine-Based Assay for the Detection of Human Papillomavirus and Cervical Intraepithelial Neoplasia.

Objective: The objective of this study is to assess the clinical performance of a urine-based high-risk human papillomavirus (hrHPV) test for the detection of cervical intraepithelial neoplasia grade 2 or higher (CIN2+). Methods: Between September and December 2021, women aged 20 to 65 years referred to colposcopy clinic were prospectively recruited at three clinical centers in China. Paired urine and cervical specimens from all enrolled women were obtained for hrHPV DNA fluorescence quantitative PCR test. The results of liquid-based cytology (LBC), colposcopy and diagnostic biopsies were collected. We evaluated the sensitivity and specificity for CIN and assessed the agreement/kappa value. Results: A total of 732 women (median age, 40 years) with valid results were included in the study, and 130 (17.8%) women were histologically confirmed as CIN2+. The sensitivity of urine and cervical test for CIN2+ and CIN3+ were 87.69% and 85.45%, respectively. The specificity of urine test performed better than cervical test in women with

New insights into the link between pro-environmental attitudes and household food waste behaviours in China: Moderating effect of shopping distance.

Environmental attitude, value and awareness are widely believed to help reach the goal of cutting global food waste, but these psychological and cognitive factors are not always good predictors of wasteful behaviours. Notably, it is still unclear how the role of pro-environmental attitude (PEA) in reducing household food waste (HFW) changes with grocery shopping distance. To this end, using 7319 households survey data from China, this study investigates the moderating effect of shopping distance on the link between PEA and HFW behaviour. The results of Tobit regressions show that PEA is an important predictor of actual HFW behaviour in the absence of the constraint of shopping distance. However, the expansion of shopping distance will weaken the positive role of PEA in reducing HFW. It indicates that, due to the temporal and financial constraints generated by shopping distance, there is a certain degree of hypothetical deviation between the wasteful behaviours that individuals actually exhibit and their stated PEA. Our findings, from the perspective of the moderating effect of shopping distance, explain why some individuals deviate from their stated PEA in HFW behaviour, which provides a new insight into the generation of 'attitude-behaviour' gap. Therefore, policy interventions that merely enhancing environmental education may have limited effect on reducing food waste; instead, the promotion of citizen environmental ethics should be combined with efforts to improve the accessibility of retail infrastructures.

Comparative metaproteomics reveal co-contribution of onion maggot and its gut microbiota to phoxim resistance.

Pesticide resistance inflicts significant economic losses on a global scale each year. To address this pressing issue, substantial efforts have been dedicated to unraveling the resistance mechanisms, particularly the newly discovered microbiota-derived pesticide resistance in recent decades. Previous research has predominantly focused on investigating microbiota-derived pesticide resistance from the perspective of the pest host, associated microbes, and their interactions. However, a gap remains in the quantification of the contribution by the pest host and associated microbes to this resistance. In this study, we investigated the toxicity of phoxim by examining one resistant and one sensitive Delia antiqua strain. We also explored the critical role of associated microbiota and host in conferring phoxim resistance. In addition, we used metaproteomics to compare the proteomic profile of the two D. antiqua strains. Lastly, we investigated the activity of detoxification enzymes in D. antiqua larvae and phoxim-degrading gut microbes, and assessed their respective contributions to phoxim resistance in D. antiqua. The results revealed contributions by D. antiqua and its gut bacteria to phoxim resistance. Metaproteomics showed that the two D. antiqua strains expressed different protein profiles. Detoxifying enzymes including Glutathione S-transferases, carboxylesterases, Superoxide Dismutase, Glutathione Peroxidase, and esterase B1 were overexpressed in the resistant strain and dominated in differentially expressed insect proteins. In addition, organophosphorus hydrolases combined with a group of ABC type transporters were overexpressed in the gut microbiota of resistant D. antiqua compared to the sensitive strain. 85.2% variation of the larval mortality resulting from phoxim treatment could be attributed to the combined effects of proteins from both from gut bacteria and D. antiqua, while the individual contribution of proteins from gut bacteria or D. antiqua alone accounted for less than 10% of the variation in larval mortality caused by phoxim. The activity of the overexpressed insect enzymes and the phoxim-degrading activity of gut bacteria in resistant D. antiqua larvae were further confirmed. This work enhances our understanding of microbiota-derived pesticide resistance and illuminates new strategies for controlling pesticide resistance in the context of insect-microbe mutualism.

Integrated analysis of single-cell RNA-seq and bulk RNA-seq unravels the heterogeneity of cancer-associated fibroblasts in TNBC.

BACKGROUND: The treatment of triple-negative breast cancer (TNBC) is one of the main focuses and key difficulties because of its heterogeneity, and the source of this heterogeneity is unclear. METHODS: Single-cell RNA (scRNA) and transcriptomics data of TNBC and normal breast samples were retrieved from Gene Expression Omnibus (GEO) database and TCGA-BRCA database. These cells were clustered using the t-SNE and UMAP method, and the marker genes for each cluster were found. We annotated the clusters using the published literature, CellMarker database and "SingleR" R package. RESULTS: A total of 1535 cells and 21785 genes from 6 TNBC patients and 2068 cells and 15868 genes from 3 normal breast tissues were used for downstream analyses. The scRNA data were divided into 14 clusters labeled into 8 cell types, including epithelial cells, immunocytes, CAFs/fibroblasts and etc. In the TNBC samples, CAFs were divided into three clusters and labelled as prCAFs, myCAFs and emCAFs, and the marker genes were DCN, FAP and RGS5, respectively. The prCAF subgroup is functionally characterized by promoting proliferation and multi drug resistance; myCAF subgroup is involved in constituting the extracellular matrix and collagen production, matrix composition and collagen production, and the emCAF functionally characterized by energy metabolism. CONCLUSIONS: TNBC has inter- and intra-tumor heterogeneity, and CAF is one of the sources of this heterogeneity. CD74, SASH3, CD2, TAGAP and CCR7 served as significant marker genes with prognostic and therapeutic value.

Prenatal diagnosis and genetic etiology analysis of talipes equinovarus by chromosomal microarray analysis.

BACKGROUND: With the advancement of molecular technology, fetal talipes equinovarus (TE) is believed to be not only associated with chromosome aneuploidy, but also related to chromosomal microdeletion and microduplication. The study aimed to explore the molecular etiology of fetal TE and provide more information for the clinical screening and genetic counseling of TE by Chromosomal Microarray Analysis (CMA). METHODS: This retrospectively study included 131 fetuses with TE identified by ultrasonography. Conventional karyotyping and SNP array analysis were performed for all the subjects. They were divided into isolated TE group (n = 55) and complex group (n = 76) according to structural anomalies. RESULTS: Among the total of 131 fetuses, karyotype analysis found 12(9.2%) abnormal results, while SNP array found 27 (20.6%) cases. Trisomy 18 was detected most frequently among abnormal karyotypes. The detection rate of SNP array was significantly higher than that of traditional chromosome karyotype analysis (P < 0.05). SNP array detected 15 (11.5%) cases of submicroscopic abnormalities that karyotype analysis did not find. The most common CNV was the 22q11.2 microdeletion. For both analyses, the overall detection rates were significantly higher in the complex TE group than in the isolated TE group (karyotype: P < 0.05; SNP array: P < 0.05). The incremental yield of chromosomal abnormalities in fetuses with unilateral TE (22.0%) was higher than in fetuses with bilateral TE (19.8%), but this difference was not statistically significant (P > 0.05). Abnormal chromosomes were most frequently detected in fetuses with TE plus cardiovascular system abnormalities. CONCLUSION: Fetal TE is related to chromosomal microdeletion or microduplication. Prenatal diagnosis is recommended for fetuses with TE, and CMA testing is preferred. CMA can improve the detection rate of chromosomal abnormalities associated with fetal TE, especially in pregnancies with complex TE.

Polyvalent passive vaccine candidates from egg yolk antibodies (IgY) of important outer membrane proteins (PF1380 and ExbB) of Pseudomonas fluorescens in fish.

Polyvalent antibodies can resist multiple bacterial species, and immunoglobulin Y (IgY) antibody can be economically prepared in large quantities from egg yolk; further, IgY polyvalent antibodies have application value in aquaculture. The outer membrane proteins (OMPs) PF1380 and ExbB of Pseudomonas fluorescens were expressed and purified, and the corresponding IgY antibodies were prepared. PF1380, ExbB, and the corresponding IgY antibodies could activate the innate immune responses of chicken and Carassius auratus. The passive immunization to C. auratus showed that the IgY antibodies of PF1380 and ExbB had an immune protection rate, down-regulated the expression of antioxidant-related factors (MDA, SOD, GSH-Px, and CAT) to reduce the antioxidant reaction, down-regulated the expression of inflammation-related genes (IL-6, IL-8, TNF-α, and IL-1ß) to reduce the inflammatory reaction, maintained the integrity of visceral tissue structure, and reduced apoptosis and damage of tissue cells in relation to P. fluorescens and Aeromonas hydrophila infections. Thus, the IgY antibodies of PF1380 and ExbB could be considered as passive polyvalent vaccine candidates in aquaculture.

Prenatal diagnosis of fetal digestive system malformations and pregnancy outcomes at a tertiary referral center in Fujian, China: A retrospective study.

Fetal digestive system malformations (DSMs) are correlated with chromosomal anomalies. The prenatal diagnosis of DSMs allows for timely treatment and reduces perinatal morbidity and mortality. However, genetic screening for fetal DSMs is rarely reported. This study aimed to investigate genetic etiology and pregnancy outcomes in cases of fetal DSM by analyzing correlations between DSM types and chromosomal anomalies. This retrospective single-center study included 126 fetuses in whom DSMs were detected via prenatal ultrasonography. Genetic etiology was investigated using conventional karyotyping, chromosome microarray analysis (CMA), and whole-exome sequencing (WES). DSMs were categorized as simple DSM (Group A), DSM combined with abnormal ultrasound soft markers (Group B), and DSM combined with comorbidities of other systems (Group C). Abnormal karyotypes were detected in 11/126 (8.7 %) fetuses. Four more pathogenic copy number variants (CNVs) were detected using CMA, increasing the detection rate to 11.9 %. The detection rates significantly differed between the three DSM types (1.78 %, 8.11 %, and 33.33 % in Groups A, B, and C, respectively). The overall adverse pregnancy outcome rate was 33.9 %, and 11.5 %, 23.5 %, and 81.3 %, (P < 0.001), respectively, in Groups A, B, and C. Out of 83 live births, three neonates died, 26 underwent postnatal surgery with 24 favorable outcomes, and 54 did not undergo surgery and were basically normal. Two neonates who underwent WES were diagnosed with CHD7-associated Charge syndrome and JAG1-associated Alagille syndrome, respectively. Our findings demonstrate that fetal DSM is closely related to chromosome aneuploidies, CNVs, and point mutations. The prognoses of most fetuses with simple DSM and those with comorbid abnormal ultrasound soft markers were favorable in the absence of chromosomal anomalies and severe structural malformations, provided they underwent timely surgery as neonates. These findings provide guidance for the prenatal diagnosis and clinical management of fetal DSMs and the genetic counseling of parents.