Integrated transcriptome and microRNA analysis reveals molecular responses to high-temperature stress in the liver of American shad (Alosa sapidissima).

BACKGROUND: Fish reproduction, development and growth are directly affected by temperature, investigating the regulatory mechanisms behind high temperature stress is helpful to construct a finer molecular network. In this study, we systematically analyzed the transcriptome and miRNA information of American shad (Alosa sapidissima) liver tissues at different cultivation temperatures of 24 â„ƒ (Low), 27 â„ƒ (Mid) and 30 â„ƒ (High) based on a high-throughput sequencing platform. RESULTS: The results showed that there were 1594 differentially expressed genes (DEGs) and 660 differentially expressed miRNAs (DEMs) in the LowLi vs. MidLi comparison group, 473 DEGs and 84 DEMs in the MidLi vs. HighLi group, 914 DEGs and 442 DEMs in the LowLi vs. HighLi group. These included some important genes and miRNAs such as calr, hsp90b1, hsp70, ssa-miR-125a-3p, ssa-miR-92b-5p, dre-miR-15a-3p and novel-m1018-5p. The DEGs were mainly enriched in the protein folding, processing and export pathways of the endoplasmic reticulum; the target genes of the DEMs were mainly enriched in the focal adhesion pathway. Furthermore, the association analysis revealed that the key genes were mainly enriched in the metabolic pathway. Interestingly, we found a significant increase in the number of genes and miRNAs involved in the regulation of heat stress during the temperature change from 24 °C to 27 °C. In addition, we examined the tissue expression characteristics of some key genes and miRNAs by qPCR, and found that calr, hsp90b1 and dre-miR-125b-2-3p were significantly highly expressed in the liver at 27 â„ƒ, while novel-m0481-5p, ssa-miR-125a-3p, ssa-miR-92b-5p, dre-miR-15a-3p and novel-m1018-5p had the highest expression in the heart at 30℃. Finally, the quantitative expression trends of 10 randomly selected DEGs and 10 DEMs were consistent with the sequencing data, indicating the reliability of the results. CONCLUSIONS: In summary, this study provides some fundamental data for subsequent in-depth research into the molecular regulatory mechanisms of A. sapidissima response to heat stress, and for the selective breeding of high temperature tolerant varieties.

Relationship and mechanisms between internet use and physical exercise among middle- and younger-aged groups.

The "Internet Plus" era has established a closer connection between sports and individuals. This study used data from the 2018 China Family Panel Studies and focused on the middle- and younger-aged population aged 15 to 59 years. Employing a negative binomial regression model, this study empirically analyzed the impact of Internet use on physical exercise and its internal mechanisms among this population. The findings revealed that (1) Internet use significantly promoted physical exercise in the middle- and younger-aged population, with the frequency of physical exercise increasing to 1.549 times the original value; (2) The positive effects of the internet on physical exercise outweighed the negative effects, with online learning and entertainment enhancing physical exercise and online socialization limiting it. Specifically, online learning and entertainment increased the frequency of physical exercise among the middle- and younger-aged population by 0.063 and 0.018, respectively. Online socialization reduced the frequency by 0.023; and (3) The influence of internet use on physical exercise varies; significantly, it positively affects the exercise frequency among individuals over 35 years old and shows a positive correlation with employment status, including both employed individuals and those out of the labor market. The positive role of Internet use in encouraging physical exercise participation among the middle- and young-aged groups should be valued and enhanced.

A single-cell sequence analysis of mouse subcutaneous white adipose tissue reveals dynamic changes during weaning.

Adipose tissue development begins in the fetal period, and continues to expand after birth. Dysregulation of adipose tissue during weaning may predispose individuals to lifelong metabolic disorders. However, the developmental remodeling of adipose tissue during weaning remains largely unexplored. Here we comprehensively compare the changes in mouse subcutaneous white adipose tissue from 7 days after birth to 7 days after weaning using single-cell RNA sequencing along with other molecular and histologic assays. We characterize the developmental trajectory of preadipocytes and indicate the commitment of preadipocytes with beige potential during weaning. Meanwhile, we find immune cells unique to weaning period, whose expression of extracellular matrix proteins implies potential regulation on preadipocyte. Finally, the strongest cell-cell interaction during weaning determined by the TGFß ligand-receptor pairs is between preadipocytes and endotheliocytes. Our results provide a detailed and unbiased cellular landscape and offer insights into the potential regulation of adipose tissue remodeling during weaning.

Biocontrol potential and growth-promoting effect of endophytic fungus Talaromyces muroii SD1-4 against potato leaf spot disease caused by Alternaria alternata.

BACKGROUND: Alternaria alternata is the primary pathogen of potato leaf spot disease, resulting in significant potato yield losses globally. Endophytic microorganism-based biological control, especially using microorganisms from host plants, has emerged as a promising and eco-friendly approach for managing plant diseases. Therefore, this study aimed to isolate, identify and characterize the endophytic fungi from healthy potato leaves which had great antifungal activity to the potato leaf spot pathogen of A. alternata in vitro and in vivo. RESULTS: An endophytic fungal strain SD1-4 was isolated from healthy potato leaves and was identified as Talaromyces muroii through morphological and sequencing analysis. The strain SD1-4 exhibited potent antifungal activity against the potato leaf spot pathogen A. alternata Lill, with a hyphal inhibition rate of 69.19%. Microscopic and scanning electron microscope observations revealed that the strain SD1-4 grew parallel to, coiled around, shrunk and deformed the mycelia of A. alternata Lill. Additionally, the enzyme activities of chitinase and ß-1, 3-glucanase significantly increased in the hyphae of A. alternata Lill when co-cultured with the strain SD1-4, indicating severe impairment of the cell wall function of A. alternata Lill. Furthermore, the mycelial growth and conidial germination of A. alternata Lill were significantly suppressed by the aseptic filtrate of the strain SD1-4, with inhibition rates of 79.00% and 80.67%, respectively. Decrease of leaf spot disease index from 78.36 to 37.03 was also observed in potato plants treated with the strain SD1-4, along with the significantly increased plant growth characters including plant height, root length, fresh weight, dry weight, chlorophyll content and photosynthetic rate of potato seedlings. CONCLUSION: The endophyte fungus of T. muroii SD1-4 isolated from healthy potato leaves in the present study showed high biocontrol potential against potato leaf spot disease caused by A. alternata via direct parasitism or antifungal metabolites, and had positive roles in promoting potato plant growth.

Identification method for a fractional-order system in terms of equivalent dynamic properties.

In this paper, we introduce an efficient method for identifying fractional dynamic systems using extended sparse regression and cross-validation techniques. The former identifies equations that fit the data with varying candidate functions, while the latter determines the optimal equation with the fewest terms yet ensuring accuracy. The identified optimal equation is expected to share the same dynamic properties as the original fractional system. Unlike previous studies focusing on efficiently computing fractional terms, this strategy addresses dynamic analysis from a data perspective. Importantly, in the proposed method, we treat the fractional order as a variable to account for its impact on the dynamic properties of the identified equation. This treatment enables the identified equation to successfully capture dynamic behaviors when the fractional order changes. We validate the effectiveness of the method using three classical fractional-order systems as well as an energy harvesting system. Interestingly, we find that, although the identified equations do not contain non-local terms like the original fractional-order systems, they exhibit the same stochastic P-bifurcation phenomena. In other words, we construct an equivalent equation without memory properties, sharing the dynamic properties with the original system.

The health implications of cumulative exposure to contextual (dis)advantage: Methodological and substantive advances from a unique data linkage.

Deleterious neighborhood conditions are associated with poor health, yet the health impact of cumulative lifetime exposure to neighborhood disadvantage is understudied. Using up to five decades of residential histories for 4,177 adult participants in the Survey of Health of Wisconsin (SHOW) and spatio-temporally linked neighborhood conditions, we develop four operational approaches to characterizing cumulative neighborhood (dis)advantage over the life course. We estimated their associations with self-reported general health and compared to estimates using neighborhood (dis)advantage at time of study enrollment. When cumulative exposures were assessed with the most granular temporal scale (Approach 4), neighborhood transport constraints (OR = 1.21, 95% CI: 1.08, 1.36), residential turnover (OR = 1.20, 95% CI: 1.07, 1.34), education deficit (OR = 1.17, 95% CI: 1.04, 1.32), racial segregation (OR = 1.20, 95% CI: 1.04, 1.38) and median household income (OR = 0.85, 95% CI: 0.75, 0.97) were significantly associated with risk of fair or poor health. For composite neighborhood disadvantage, cumulative exposures had a stronger association (OR = 1.05, 95% CI: 1.02, 1.08) than the cross-sectional exposure (OR = 1.03, 95% CI: 1.01, 1.06). Single point-in-time neighborhood measures underestimate the neighborhood and health relationship, underscoring the importance of a life course approach to cumulative exposure measurement.

Immune response regulation by transduced mesenchymal stem cells with decorin gene on bleomycin-induced lung injury, fibrosis, and inflammation.

BACKGROUND: Pulmonary fibrosis is a pathological hallmark of lung injury. It is an aggressive disease that replaces normal lung parenchyma by fibrotic tissue. The transforming growth factor-beta-mothers against decapentaplegic homolog 3 (TGF-ß1-Smad3) signaling pathway plays a key role in regulating lung fibrosis. Decorin (DCN), a small leucine-rich proteoglycan, has a modulatory effect on the immune system by reversibly binding with TGF-ß and reducing its bioavailability. Mesenchymal stem cell (MSC) therapy is a new strategy that has an immune-modulatory capacity. OBJECTIVE: The aim of this study was to introduce a new therapeutic approach to harness remodeling in injured lung. MATERIAL AND METHODS: Bone marrow MSCs were isolated and transduced by decorin gene. Lung injury was induced by bleomycin and mice were treated with MSCs, MSCs-decorin, and decorin. Then, oxidative stress biomarkers, remodeling biomarkers, bronchoalveolar lavage cells, and histopathology study were conducted. RESULTS: Reduced catalase and superoxide dismutase increased due to treatments. Elevated malondialdehyde, hydroxyproline, TGF-ß levels, and polymorphonuclear cells count decreased in the treated groups. Additionally, the histopathology of lung tissues showed controlled inflammation and fibrosis. CONCLUSION: Transfected decorin gene to MSCs and used cell therapy could control remodeling and bleomycin-induced lung injury.

Investigation of film Physical properties under various starch thermal treatments with emphasis on Retrogradation effects.

This study investigated the changes in the physical properties of cornstarch-based films as they were retrogradely aged at different temperatures. Using a casting method, the films were fabricated, and their effects on the mechanical properties, thermal stability, barrier properties, and essential properties were analyzed. With prolonged aging and retrogradation periods, reductions in film thickness, solubility, water content, and water vapor permeability of 5.35%, 9.92%, 29.61%, and 20.94%, respectively, were observed. In addition, the surface roughness decreased by 44.46% for Rq (root-mean-square roughness) and 45.61% for Ra (arithmetic average roughness), while the elongation at break decreased by 72.64%. Conversely, the tensile strength, maximum degradation rate, and maximum degradation temperature increased by 116.98%, 99.5%, and 3.21%, respectively. These results provide a fundamental understanding of the changes that occur in the properties of cornstarch-based films during aging and retrogradation.

Quantitative Assessment of Acute Intracranial Clot and Collaterals on High Resolution Magnetic Resonance Imaging.

INTRODUCTION: There has been an increasing demand for imaging methods that provide a comprehensive evaluation of intracranial clot and collateral circulation, which are helpful for clinical decision-making and predicting functional outcomes. We aimed to quantitatively evaluate acute intracranial clot burden and collaterals on high-resolution magnetic resonance imaging (HR-MRI). METHODS: We analyzed acute ischemic stroke patients with internal carotid artery or middle cerebral artery occlusion in a prospective multicenter study. The clot burden was scored on a scale of 0-10 based on the clot location on HR-MRI. The collateral score was assigned on a scale of 0-3 using the minimum intensity projection from HR-MRI. Uni- and multivariable logistic regression analyses were performed to assess their correlation with clinical outcome (modified Rankin Scale >2 at 90 days). Thresholds were defined to dichotomize into low and high score groups and predictive performances were assessed for clinical and radiologic outcomes. RESULTS: Ninety-nine patients (mean age of 60.77 ± 11.54 years) were included in the analysis. The interobserver correlation was 0.89 (95% CI: 0.77-0.95) for the clot burden score and 0.78 (95% CI: 0.53-0.90) for the collateral score. Multivariable logistic regression analysis demonstrated that the collateral score (odds ratio: 0.41, 95% CI: 0.19-0.90) was significantly associated with clinical outcomes. A better functional outcome was observed in the group with clot burden scores greater than 7 (p=0.011). A smaller final infarct size and a higher diffusion-weighted imaging-Alberta Stroke Program Early Computed Tomography Score were observed in the group with collateral scores greater than 1 (all p<0.05). CONCLUSIONS: HR-MRI offers a new tool for quantitative assessment of clot burden and collaterals simultaneously in future clinical practices and research endeavors.

ULI-ssDRIP-seq revealed R-loop dynamics during vertebrate early embryogenesis.

R-loop, a chromatin structure containing one RNA:DNA hybrid and one unpaired single-stranded DNA, plays multiple biological roles. However, due to technical limitations, the landscapes and potential functions of R-loops during embryogenesis remain elusive. Here, we developed a quantitative and high-resolution ultra-low input R-loop profiling method, named ULI-ssDRIP-seq, which can map global R-loops with as few as 1000 cells. By using ULI-ssDRIP-seq, we reveal the R-loop dynamics in the zebrafish from gametes to early embryos. In oocytes, the R-loop level is relatively low in most regions of the nuclear genome, except maternal-inherited rDNA and mitochondrial genome. The correlation between R-loop and CG methylation dynamics during early development is relatively weak. Furthermore, either up- or down-regulation of global R-loops by knockdown or overexpression of RNase H1 causes a delay of embryonic development with dramatic expression changes in zygotic and maternal genes. This study provides comprehensive R-loop landscapes during early vertebrate embryogenesis and demonstrates the implication of R-loops in embryonic development.

Development of a novel staging classification for Siewert II adenocarcinoma of the esophagogastric junction after neoadjuvant chemotherapy.

BACKGROUND: Stage classification for Siewert II adenocarcinoma of the esophagogastric junction (AEG) treated with neoadjuvant chemotherapy (NAC) has not been established. AIM: To investigate the optimal stage classification for Siewert II AEG with NAC. METHODS: A nomogram was established based on Cox regression model that analyzed variables associated with overall survival (OS) and disease-specific survival (DSS). The nomogram performance in terms of discrimination and calibration ability was evaluated using the likelihood-ratio test, Akaike information criterion, Harrell concordance index, time-receiver operating characteristic curve, and decision curve analysis. RESULTS: Data from 725 patients with Siewert type II AEG who underwent neoadjuvant therapy and gastrectomy were obtained from the Surveillance, Epidemiology, and End Results database. Univariate and multivariate analyses revealed that sex, marital status, race, ypT stage, and ypN stage were independent prognostic factors of OS, whereas sex, race, ypT stage, and ypN stage were independent prognostic factors for DSS. These factors were incorporated into the OS and DSS nomograms. Our novel nomogram model performed better in terms of OS and DSS prediction compared to the 8th American Joint Committee of Cancer pathological staging system for esophageal and gastric cancer. Finally, a user-friendly web application was developed for clinical use. CONCLUSION: The nomogram established specifically for patients with Siewert type II AEG receiving NAC demonstrated good prognostic performance. Validation using external data is warranted before its widespread clinical application.

An appearance quality classification method for Auricularia auricula based on deep learning.

The intelligent appearance quality classification method for Auricularia auricula is of great significance to promote this industry. This paper proposes an appearance quality classification method for Auricularia auricula based on the improved Faster Region-based Convolutional Neural Networks (improved Faster RCNN) framework. The original Faster RCNN is improved by establishing a multiscale feature fusion detection model to improve the accuracy and real-time performance of the model. The multiscale feature fusion detection model makes full use of shallow feature information to complete target detection. It fuses shallow features with rich detailed information with deep features rich in strong semantic information. Since the fusion algorithm directly uses the existing information of the feature extraction network, there is no additional calculation. The fused features contain more original detailed feature information. Therefore, the improved Faster RCNN can improve the final detection rate without sacrificing speed. By comparing with the original Faster RCNN model, the mean average precision (mAP) of the improved Faster RCNN is increased by 2.13%. The average precision (AP) of the first-level Auricularia auricula is almost unchanged at a high level. The AP of the second-level Auricularia auricula is increased by nearly 5%. And the third-level Auricularia auricula AP is increased by 1%. The improved Faster RCNN improves the frames per second from 6.81 of the original Faster RCNN to 13.5. Meanwhile, the influence of complex environment and image resolution on the Auricularia auricula detection is explored.

Eutrophication impacts the distribution and functional traits of viral communities in lakes.

Viruses play a crucial role in aquatic ecosystems by regulating microbial composition and impacting biogeochemical cycling. While the response of viral diversity to the trophic status has been preliminarily explored in lake ecosystems, there is limited integrated exploration of the biogeography of viruses, host associations, and the auxiliary metabolic genes (AMGs), particularly for plateau lakes. Therefore, this research investigated the viral biogeography, virus-host association, and AMGs in the surface waters of 11 lakes varying in trophic levels (eutrophic and oligo-mesotrophic) in the Yunnan-Guizhou plateau region of China. A total of 73,105 viral operational taxonomic units were obtained from 11 samples, with 84.8 % remaining unannotated at the family level, indicating a predominance of novel viruses within these lakes. The most abundant viral family was Kyanoviridae (24.4 %), recognized as a common cyanophage. The vast majority of cyanobacteria and several eukaryotic algae were predicted as hosts for the viruses, with a lytic lifestyle predominating the life strategy of these cyanophages, implying the potential influence of the virus on algae. The viral community structure significantly correlated with both trophic status and the bacterial community. The structure equation model analysis revealed chlorophyll a was the primary factor affecting viral communities. Moreover, numerous AMGs linked to carbon metabolism, phosphorus metabolism, sulfur metabolism, and photosynthesis were found in these lakes, some of which showed virus preference for the trophic statuses, suggesting a vital role of the virus in driving biogeochemical cycling in the lake crossing different nutrient levels. In addition, a restricted presence of viruses was found to infect humans or harbor antibiotic resistance genes in the lakes, suggesting a subtle yet potential link to human health. Overall, these findings offer insights into the response of viral communities to eutrophication and their potential role in biogeochemical cycling and controlling algal propagation.

Experimental Study on Mechanical Properties and Permeability Characteristics of Calcareous Mudstone under Different Confining Pressures.

Calcareous mudstone, a type of red-bed soft rock, is prevalent in the surrounding rock of the Central Yunnan Water Diversion Project (CYWDP) in Yunnan Province, China, significantly impacting both construction and operation. The mechanical properties of calcareous mudstone vary with depth. This study investigates its mechanical properties, permeability characteristics, energy evolution, and macro- and micro-failure characteristics during deformation using triaxial compression tests under different confining pressures. Results reveal distinct stage characteristics in the stress-strain behavior, permeability, and energy evolution of calcareous mudstone. Crack propagation, permeability evolution, and energy dissipation are closely linked, elucidating the deformation and failure process, with fluid pressure playing a crucial role. The confining pressure σ3 increased from 2 MPa to 4 MPa and 6 MPa, while the peak stress σc (Pw = 1 MPa) of the calcareous mudstone increased by 84.49% and 24.89%, respectively. Conversely, the permeability at σc decreased from 11.25 × 10-17 m2 to 8.99 × 10-17 m2 and 5.72 × 10-17 m2, while the dissipative energy at σc increased from 12.39 kJ/m3 to 21.14 kJ/m3 and 42.51 kJ/m3. In comparison to those without fluid pressure (Pw = 0), the value of σc at Pw = 1 MPa was reduced by 36.61%, 23.23%, and 20.67% when σ3 was 2, 4, and 6 MPa, respectively. Increasing confining pressure augments characteristic stresses, deformation and failure energy, and ductility, while reducing permeability, crack propagation, and width. These findings enhance our understanding of calcareous mudstone properties at varying depths in tunnel construction scenarios.

Electronic symptom monitoring after lung cancer surgery: establishing a core set of patient-reported outcomes for surgical oncology care in a longitudinal cohort study.

BACKGROUND: Electronic symptom monitoring via patient-reported outcome in surgical oncology is limited owing to lengthy instruments and non-specific items in common patient-reported outcome instruments. To establish electronic symptom monitoring through a clinically relevant and fit-for-purpose core set of patient-reported outcome in patients undergoing lung cancer surgery. MATERIALS AND METHODS: One qualitative (Cohort 1) and two prospective studies (Cohorts 2 and 3) were conducted between 2018 and 2023. Patients undergoing lung cancer surgery were recruited. Items of symptoms and daily functioning were generated through extensive interviews in Cohort 1 and incorporated into a smartphone-based platform to establish the electronic Perioperative Symptom Assessment for Lung surgery (ePSA-Lung). This tool was finalized and validated in Cohort 2. Patients in Cohort 3 were longitudinally monitored for the first year post-surgery using the validated ePSA-Lung. RESULTS: In total, 1,037 patients scheduled for lung cancer surgery were recruited. The 11-item draft PSA-Lung was generated based on qualitative interview with 39 patients and input from a Delphi study involving 42 experts. A 9-item ePSA-Lung was finalized by assessing 223 patients in the validation cohort; the results supported the instrument's understandability, reliability, sensitivity, and surgical specificity. In Cohort 3 (n=775), compliance ranged from 63.21% to 84.76% during the one-year follow-up after discharge. Coughing, shortness of breath, and disturbed sleep were the most severe symptoms after discharge. Longitudinally, patients who underwent single-port video-assisted thoracic surgery had a lower symptom burden than those who underwent multi-port video-assisted thoracic surgery or thoracotomy (all symptoms, P<0.001). CONCLUSION: The ePSA-Lung is valid, concise, and clinically applicable as it supports electronic symptom monitoring in surgical oncology care. The need for long-term extensive care was identified for patients after discharge, even in early-stage cancer with potential curative treatment.

Risk factors for tubal patency and their impact on pregnancy rate after partial salpingectomy and end-to-end anastomosis. / è¾“åµç®¡éƒ¨åˆ†åˆ‡é™¤æœ¯è”åˆç«¯ç«¯å»åˆæœ¯åŽå½±å“æ‚£è€ è¾“åµç®¡é€šç• æ€§å’Œå¦Šå¨ çš„ç›¸å ³å› ç´ åˆ†æž.

OBJECTIVES: To explore the risk factors for tubal patency after partial salpingectomy and end-to-end anastomosis, and their impact on pregnancy outcomes. METHODS: A total of 300 patients with tubal pregnancy who underwent partial salpingectomy and end-to-end anastomosis in Zhengzhou Maternal and Child Health Hospital from January 2020 to April 2023. Hysterosalpingography was performed after surgical treatment to examine the tubal patency. Lasso-Logistic regression was used to analyze the risk factors for postoperative tubal patency, and Spearman's correlation was used to analyze the impact of each risk factor on the pregnancy rate. RESULTS: Hysterosalpingography showed that the fallopian tube was not obstructed in 225 cases (unobstructed group), the tube was not completely patent (n=54) or blocked (n=21) (obstructed group). Univariate analysis showed that age, diameter of the tubal pregnancy sac, location of tubal pregnancy, timing of surgery, pelvic adhesion, anastomotic method, length of remaining tubal, history of pelvic surgery, number of intraoperative electrocoagulation, intraoperative blood loss, and experience of surgeons were factors affecting postoperative tubal patency (all P<0.01). Lasso regression analysis identified location of tubal pregnancy, pelvic adhesion, anastomotic surgical method, length of remaining tubal, history of pelvic surgery, number of intraoperative electrocoagulation, and experience of surgeons as influencing factors. Multivariate Logistic regression analysis showed that tubal isthmus pregnancy, pelvic adhesion, open anastomosis surgery, history of pelvic surgery, and number of intraoperative electrocoagulation were independent risk factors for postoperative tubal patency, while length of remaining tubal and surgeon's work experience were independent protective factors for postoperative tubal patency (all P<0.01). A total of 295 patients were followed up of 1 year, 192 cases (65.08%) were pregnant, including 172 cases of intrauterine pregnancy (89.58%) and 20 cases of ectopic pregnancy (10.42%). Spearman correlation analysis showed that tubal isthmus pregnancy, pelvic adhesion, open abdominal anastomosis surgery, pelvic surgery history, and times of intraoperative electrocoagulation were negatively correlated with postoperative pregnancy, while the remaining tubal length and years of surgeon's working experience were positively correlated with postoperative pregnancy rate (all P<0.01). CONCLUSIONS: For the tubal patency of patients after partial salpingectomy combined with end-to-end anastomosis, the history of tubal isthmus pregnancy, pelvic adhesion, open abdominal anastomosis, pelvic surgery, and the number of intraoperative electrocoagulation are independent risk factors, which are negatively correlated with postoperative pregnancy. The remaining tubal length and the surgeon's work experience are independent protective factors, which are positively correlated with postoperative pregnancy.

Analysis of CCND3 mutations in diffuse large B-cell lymphoma.

Diffuse large B-cell lymphoma (DLBCL), accounts for 30-40% of newly diagnosed lymphomas, has an overall cure rate of approximately 60%. Despite previous reports suggesting a negative prognostic association between CCND3 mutations and Burkitt lymphoma, their prognostic implications in DLBCL remain controversial. To investigate this, we evaluated CCND3 mutation status in 2059 DLBCL patient samples from four database (integrated cohort) and additional 167 DLBCL patient samples in our center (JSPH cohort). The mutation was identified in 5.5% (113/2059) of the cases in the integrated cohort, with 86% (97/113) found in exon 5. Furthermore, P284, R271, I290 and Q276 are described as CCND3 mutation hotspots. CCND3 mutation was associated with decreased overall survival (OS) in the integrated cohort (P = 0.0407). Further subgroup analysis revealed that patients diagnosed as EZB subtype DLBCL by LymphGen algorithm with CCND3 mutations had poorer OS than patients diagnosed as EZB subtype without CCND3 mutations (P = 0.0140). Using the next-generation sequencing (NGS) in the JSPH cohort, it was found that both cell cycle and DNA replication pathways were highly upregulated in patients with CCND3 mutations. Our results suggest that CCND3 mutations can serve as a novel prognostic factor in DLBCL pathogenesis. Consequently, the development of personalized therapeutic strategies for DLBCL patients with CCND3 mutations might enhance their prognosis.

Bone marrow mesenchymal stem cell-derived exosomal miR-221-3p promotes angiogenesis and wound healing in diabetes via the downregulation of forkhead box P1.

AIM: Impaired wound healing in patients with diabetes can develop into nonhealing ulcerations. Because bone marrow mesenchymal stem cells (BMSCs) exosomes can promote wound healing, this study aims to investigate the mechanism of BMSCs-isolated exosomal miR-221-3p in angiogenesis and diabetic wound healing. METHODS: To mimic diabetes in vitro, human umbilical vein endothelial cells (HUVECs) were subjected to high glucose (HG). Exosomes were derived from BMSCs and identified by transmission electron microscopy (TEM), western blot analysis and dynamic light scattering (DLS). The ability to differentiate BMSCs was assessed via Oil red O staining, alkaline phosphatase (ALP) staining and alizarin red staining. The ability to internalise PKH26-labelled exosomes was assessed using confocal microscopy. Migration, cell viability and angiogenesis were tested by scratch, MTT and tube formation assays separately. The miRNA and protein levels were analysed by quantitative reverse transcriptase polymerase chain reaction (qRT-PCR) or western blotting. The relationship among miR-221-3p, FOXP1 and SPRY1 was determined using the dual-luciferase reporter, ChIP and RIP assays. RESULTS: Exosomal miR-221-3p was successfully isolated from BMSCs and delivered into HUVECs. HG was found to suppress the angiogenesis, cell viability and migration of HUVECs and exosomal miR-221-3p separated from BMSCs inhibited the above phenomenon. FOXP1 could transcriptionally upregulate SPRY1, and the silencing of FOXP1 reversed the HG-stimulated angiogenesis inhibition, cell viability and migration in HUVECs via the downregulation of SPRY1. Meanwhile, miR-221-3p directly targeted FOXP1 and the overexpression of FOXP1 reversed the positive effect of exosomal miR-221-3p on HUVEC angiogenesis. CONCLUSION: Exosomal miR-221-3p isolated from BMSCs promoted angiogenesis in diabetic wounds through the mediation of the FOXP1/SPRY1 axis. Furthermore, the findings of this study can provide new insights into probing strategies against diabetes.

Improved efficacy and safety of zanubrutinib versus ibrutinib in patients with relapsed/refractory chronic lymphocytic leukemia (R/R CLL) in China: a subgroup of ALPINE.

Chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) has different epidemiology in Chinese vs. Western patients, but there are few studies of CLL/SLL in large populations of Chinese patients. ALPINE is a global phase 3 trial investigating Bruton tyrosine kinase inhibitors zanubrutinib vs. ibrutinib to treat relapsed/refractory (R/R) CLL/SLL. Here we report results from the subgroup of Chinese patients. Adults with R/R CLL/SLL were randomized 1:1 to receive zanubrutinib (160 mg twice-daily) or ibrutinib (420 mg once-daily) until disease progression or unacceptable toxicity. Endpoints included overall response rate (ORR), progression-free survival (PFS), overall survival (OS), and safety. Data were analyzed descriptively. Ninety patients were randomized in China (zanubrutinib, n = 47; ibrutinib, n = 43). Baseline characteristics were balanced between groups, with fewer male patients in the zanubrutinib vs. ibrutinib group (55.3% vs. 69.8%). Median age was 60.5 years, 11% had del(17p) mutation, and 32% had tumor protein 53 (TP53) mutation. With median 25.3 months follow-up, ORR was 80.9% with zanubrutinib vs. 72.1% with ibrutinib. PFS was improved with zanubrutinib vs. ibrutinib (HR = 0.34 [95% CI, 0.15, 0.77]), and the HR for OS was 0.45 (95% CI, 0.14, 1.50). Rates of Grade ≥ 3 treatment-emergent adverse events (TEAEs; 64.4% vs. 72.1%), AEs leading to discontinuation (6.4% vs. 14.0%), and serious TEAEs (35.6% vs. 51.2%) were lower with zanubrutinib vs. ibrutinib. Zanubrutinib demonstrated improved ORR, PFS, and OS vs. ibrutinib and a more favorable safety profile in patients with R/R CLL/SLL in China. These results are consistent with the full global population of ALPINE. ClinicalTrials.gov: NCT03734016, registered November 7, 2018.