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Abstract Asthenoteratozoospermia is a major cause of male infertility. Thus far, the identified related genes can explain only a small share of asthenoteratozoospermia cases, suggesting the involvement of other genes. The transmembrane protein TMEM232 is highly expressed in mouse testes. In the present study, to determine its function of TMEM232 in testes, we constructed a Tmem232-null mouse model using CRISPR–Cas9 technology. Tmem232 knockout (KO) male mice was completely infertile, and their sperm were immotile, with morphological defects of the flagellum. Electron microscopy revealed an aberrant midpiece-principal junction and the loss of the fourth outer microtubule doublet in the sperm of Tmem232 −/− mice. Sperm cells presented an 8 + 2 conformation and an irregular arrangement of the mitochondrial sheath. Proteomic analysis revealed altered expression of proteins related to flagellar motility, sperm capacitation, the integrity and stability of sperm structure, especially an upregulated expression of multiple ribosome components in TMEM232-deficient spermatids. Additionally, TMEM232 was observed to be involved in autophagy by interacting with autophagy-related proteins, such as ATG14, to regulate ribosome homeostasis during spermiogenesis. These results suggest that TMEM232, as a potential scaffold protein involving in the correct assembly, distribution, and stability maintenance of certain functional complexes by recruiting key intracellular proteins, is essential for the formation of a highly structured flagellum and plays an important role in the autophagic elimination of cytosolic ribosomes to provide energy for sperm motility.

Abstract Aim The aim of this review is to evaluate and summarize the evidence for preoperative visit-care of transcatheter aortic valve replacement (TAVR) and to provide evidence-based support for clinical intervention. Design The review presents an evidence summary report, following the standard of the Fudan University Center for Evidence-based Nursing. Methods Literature related to preoperative visit-care for transcatheter aortic valve replacement have been retrieved based on the “6S” pyramid model of evidence. The types of literature included systematic reviews, expert consensus, evidence summary, and guidelines. Data sources Up To Date, Cochrane Library, Joanna Briggs Institute, National Institute for Health and Care Excellence, Medlive, American Heart Association, Registered Nurses Association of Ontario, Scottish Intercollegiate Guidelines Network, European Society of Cardiology, American College of Cardiology, PubMed, CINAHL, Wanfang database, VIP database, Chinese biomedical literature database, CNKI. The search period is limited to the time when each database was established until February 2024. Results A total of 18 articles were included in this review, consisting of 1 systematic review, 1 evidence summary, 3 guidelines and 13 expert consensuses. This review summarized 30 pieces of the best evidence for preoperative visit-care for transcatheter aortic valve replacement, encompassing three evidence themes: multidisciplinary team collaboration, preoperative assessment, and preoperative education. Conclusion The study has established an ideal foundation of evidence for preoperative visit-care in TAVR. However, throughout the particular application process, it was crucial to assess the feasibility and relevance of the evidence in clinical practice by taking into account elements such as the application setting, recommendations from experts with diverse expertise, and the preferences of the patients.

Abstract Background Preoperative visit-care for transcatheter aortic valve replacement (TAVR) plays a crucial role in improving the quality of care and patient safety. However, preoperative care for TAVR patients is still in its early stages in China, with the care often being experience-based. The application of relevant evidence in nursing practice is necessary. Little is known regarding the facilitators and barriers to apply and compliance to the evidences about preoperative visit-care for TAVR in nursing. Methods The Nurse’s Compliance Checklist was used to investigate the evidence-based compliance of nurses (n = 21) who worked in the TAVR team in the evidence-based implementation setting. Meanwhile, an Evidence-Based Practice Beliefs Scale, and Influencing Factors Checklist were used to investigate all nurses (n = 66) who work in the same setting. Stakeholders (Middle and senior-level nursing administrators, frontline clinical nurses, and patients) interview was carried out to further disclose the barriers and facilitators in the process of evidence-based practice. Results The results of this study showed that only 1 evidence implemented fully (100%) by nurses, 3 evidences with 0% implementation rate, and implementation rate of the other evidences were 9.5∼71.4%. The overall score of nurses’ evidence-based nursing belief level was (3.52 ± 0.82). Three domains of barriers were identified: the Context Domain included lack of nursing procedures, inadequate health education materials, insufficient training; the Practitioner Domain included insufficient attention, lack of relevant knowledge, high work pressure and uncertainty of expected results, and Patient Domain included lack of relational knowledge. Facilitating factors included leadership support, nurse’ high evidence-based nursing belief, high executive ability and enthusiasm for learning. Conclusion The study indicated that the nurses’ compliance of evidence-based practice in preoperative visit-care for TAVR was in lower level. There were some factors influencing the application of the evidences. The study revealed potential modifiable barriers to the successful implementation of evidence-based preoperative visit-care, including a lack of preoperative visit- care routine, related knowledge and training. Leadership support and nurse training should be considered to improve nurses’ compliance with evidence-based practice.

Abstract Compensation and intracellular storage of PD-L1 may compromise the efficacy of antibody drugs targeting the conformational blockade of PD1/PD-L1 on the cell surface. Alternative therapies aiming to reduce the overall cellular abundance of PD-L1 thus might overcome resistance to conventional immune checkpoint blockade. Here we show by bioinformatics analysis that colon adenocarcinoma (COAD) with high microsatellite instability (MSI-H) presents the most promising potential for this therapeutic intervention, and that overall PD-L1 abundance could be controlled via HSC70-mediated lysosomal degradation. Proteomic and metabolomic analyses of mice COAD with MSI-H in situ unveil a prominent acidic tumor microenvironment. To harness these properties, an artificial protein, IgP β, is engineered using pH-responsive peptidic foldamers. This features customized peptide patterns and designed molecular function to facilitate interaction between neoplastic PD-L1 and HSC70. IgP β effectively reduces neoplastic PD-L1 levels via HSC70-mediated lysosomal degradation, thereby persistently revitalizing the action of tumor-infiltrating CD8 + T cells. Notably, the anti-tumor effect of lysosomal-degradation-based therapy surpasses that of antibody-based immune checkpoint blockade for MSI-H COAD in multiple mouse models. The presented strategy expands the use of peptidic foldamers in discovering artificial protein drugs for targeted cancer immunotherapy.

Objective: This study aimed to explore the determinants influencing training transfer and evaluate how those factors change over time among nurses who graduated from clinical nurse specialist training to provide a theoretical basis for improving the training transfer of clinical nurse specialists (CNSs). Methods: A quantitative longitudinal survey with four rounds of data collection was utilized to measure the influencing aspects of training transfer from June 2018 to December 2019. A total of 46 new CNSs participated in this study, including 30 and 16 nurses receiving training programs for CNSs in Infusion, Wound and Ostomy. The factor influencing training transfer (FITT) questionnaire was used to collect data for the first month (time 1), the third month (time 2), the sixth month (time 3), and the first year (time 4) after training. This questionnaire contains 53 items divided into five dimensions, including managerial support (20 items); hindrance in the organization (6 items); the validity of the training program (10 items); organizational and personal facilitators (11 items); and personal attitudes towards training transfer (6 items). Results: The influencing factors of CNSs transfer decreased over time, with managerial support, hindrance in the organization, the validity of the training program, and personal attitudes towards training transfer changing statistically over time (P

BackgroundChronic heart failure has become a serious threat to the health of the global population, and self-management is key to treating chronic heart failure. The emergence of mobile health (mHealth) provides new ideas for the self-management of chronic heart failure in which the informal caregiver plays an important role. Current research has mainly studied the experiences with using mHealth among patients with chronic heart failure from the perspective of individual patients, and there is a lack of research from the dichotomous perspective. ObjectiveThe aim of this study was to explore the experiences with mHealth use among patients with chronic heart failure and their informal caregivers from a dichotomous perspective. MethodsThis descriptive phenomenological study from a post-positivist perspective used a dyadic interview method, and face-to-face semistructured interviews were conducted with patients with chronic heart failure and their informal caregivers. Data were collected and managed using NVivo 12 software, and data analysis used thematic analysis to identify and interpret participants’ experiences and perspectives. The thematic analysis included familiarizing ourselves with the data, generating initial codes, searching for themes, reviewing themes, defining and naming themes, and producing the report. ResultsA total of 14 dyads of patients with chronic heart failure and their informal caregivers (13 men and 15 women) participated in this study, including 3 couples and 11 parent-child pairs. We constructed 4 key themes and their subthemes related to the experiences with mHealth use: (1) opposing experiences with mHealth as human interaction or trauma (great experience with mHealth use; trauma), (2) supplement instead of replacement (it is useful but better as a reference; offline is unavoidable sometimes), (3) both agreement and disagreement over who should be the adopter of mHealth (achieving consensus regarding who should adopt mHealth; conflict occurs when considering patients as the adopter of mHealth), (4) for better mHealth (applying mHealth with caution; suggestions for improved mHealth). ConclusionsThis study reported that the experiences with mHealth use among patients with chronic heart failure and their informal caregivers were mixed, and it highlighted the human touch of mHealth and the importance of network security. These results featured mHealth as a complement to offline hospitals rather than a replacement. In the context of modern or changing Chinese culture, we encourage patients to use mHealth by themselves and their informal caregivers to provide help when necessary. In addition, we need to use mHealth carefully, and future mHealth designs should focus more on ease of use and be oriented more toward older adults.

ABSTRACT Guanine nucleotides are required for growth and viability of cells due to their structural role in DNA and RNA, and their regulatory roles in translation, signal transduction, and cell division. The natural antibiotic mycophenolic acid (MPA) targets the rate-limiting step in de novo guanine nucleotide biosynthesis executed by inosine-5´-monophosphate dehydrogenase (IMPDH). MPA is used clinically as an immunosuppressant, but whether in vivo inhibition of bacterial IMPDH (GuaB) is a valid antibacterial strategy is controversial. Here, we describe the discovery of extremely potent small molecule GuaB inhibitors (GuaBi) specific to pathogenic bacteria with a low frequency of on-target spontaneous resistance and bactericidal efficacy in vivo against Acinetobacter baumannii mouse models of infection. The spectrum of GuaBi activity includes multidrug-resistant pathogens that are a critical priority of new antibiotic development. Co-crystal structures of A. baumannii, Staphylococcus aureus, and Escherichia coli GuaB proteins bound to inhibitors show comparable binding modes of GuaBi across species and identifies key binding site residues that are predictive of whole-cell activity across both Gram-positive and Gram-negative clades of Bacteria. The clear in vivo efficacy of these small molecule GuaB inhibitors in a model of A. baumannii infection validates GuaB as an essential antibiotic target.IMPORTANCEThe emergence of multidrug-resistant bacteria worldwide has renewed interest in discovering antibiotics with novel mechanism of action. For the first time ever, we demonstrate that pharmacological inhibition of de novo guanine biosynthesis is bactericidal in a mouse model of Acinetobacter baumannii infection. Structural analyses of novel inhibitors explain differences in biochemical and whole-cell activity across bacterial clades and underscore why this discovery may have broad translational impact on treatment of the most recalcitrant bacterial infections.

ABSTRACT Discrete element method is widely used to study grain particles; however, there is a lack of research on the mathematical model parameters of rice straw particles in the crushing simulation process. To determine suitable parameter settings for crushing of rice straw particles in the simulation process, a twin-screw rice straw crushing test device was built using rice straw particles as the research object. Through actual tests, the parameters of the Ab-T10 crushing models of rice straw particles with five different moisture contents were calibrated, and the crushing characteristics of the rice straw particles were analyzed. The Ab-T10 crushing models with calibrated parameters were verified by comparing the probability of the particle-size distribution (t10) between the simulation and actual tests. The results show that the crushing probability and t10 of rice straw increase with the increase in accumulated contact specific energy and decrease with the increase in rice straw moisture content. The minimum value of the fitting parameter between the simulated and measured values is 0.9654, which indicates that the calibrated Ab-T10 crushing model can accurately simulate the rice straw particle-crushing process. This study provides a reference for the analysis of crushing in subsequent rice straw pulping.

Abstract Pralsetinib, a potent and selective inhibitor of oncogenic RET fusion and RET mutant proteins, is a substrate of the drug metabolizing enzyme CYP3A4 and a substrate of the efflux transporter P‐gp based on in vitro data. Therefore, its pharmacokinetics (PKs) may be affected by co‐administration of potent CYP3A4 inhibitors and inducers, P‐gp inhibitors, and combined CYP3A4 and P‐gp inhibitors. With the frequent overlap between CYP3A4 and P‐gp substrates/inhibitors, pralsetinib is a challenging and representative example of the need to more quantitatively characterize transporter‐enzyme interplay. A physiologically‐based PK (PBPK) model for pralsetinib was developed to understand the victim drug–drug interaction (DDI) risk for pralsetinib. The key parameters driving the magnitude of pralsetinib DDIs, the P‐gp intrinsic clearance and the fraction metabolized by CYP3A4, were determined from PBPK simulations that best captured observed DDIs from three clinical studies. Sensitivity analyses and scenario simulations were also conducted to ensure these key parameters were determined with sound mechanistic rationale based on current knowledge, including the worst‐case scenarios. The verified pralsetinib PBPK model was then applied to predict the effect of other inhibitors and inducers on the PKs of pralsetinib. This work highlights the challenges in understanding DDIs when enzyme‐transporter interplay occurs, and demonstrates an important strategy for differentiating enzyme/transporter contributions to enable PBPK predictions for untested scenarios and to inform labeling.

Genetics is an important basic course in the field of life science, and the cultivation of students’ practical ability should be emphasized in the experimental teaching of genetics. How to let students have more time to participate in the experimental practice within the limited class hours? Our genetics experimental teaching team has developed innovative teaching models on the basis of traditional teaching models. In order to improve students’ independent thinking and practical ability and cultivate their interest in scientific research and scientific accomplishment, experimental teaching is carried out through the learning mode of teachers’ questions raised before class, students’ experimental plans designed before class and students’ experimental tasks completed. Through questionnaires distributed after class, this paper investigates students’ opinions and suggestions on innovative teaching mode, hoping to give full play to the role of ‘innovative teaching mode’ in genetics experimental teaching through interaction and continuous improvement between teachers and students, so as to lay a foundation for improving students’ comprehensive ability and cultivating innovative talents.

Summary: The resected pⅢA-N2 non-small-cell lung cancer (NSCLC) patients who could benefit from postoperative radiotherapy (PORT) are not well-defined. The study explored the role of PORT on EGFR mutant and wild-type NSCLC patients. We retrospectively searched for resected pIIIA-N2 lung adenocarcinoma patients who underwent EGFR mutation testing. 80 patients with EGFR wild-type and 85 patients with EGFR mutation were included. 62 patients received PORT. In overall population, the median disease-free survival (DFS) was improved in PORT arm compared to non-PORT arm (22.9 vs. 16.1 months; p = 0.036), along with higher 2-year locoregional recurrence-free survival (LRFS) rate (88.3% vs. 69.3%; p = 0.004). In EGFR wild-type patients, PORT was associated with a longer median DFS (23.3 vs. 17.2 months; p = 0.044), and a higher 2-year LRFS rate (86.8% vs. 61.9%; p = 0.012). In EGFR mutant patients, PORT was not significantly correlated with improved survival outcomes. EGFR wild-type may a biomarker to identify the cohort that benefits from PORT.

Abstract Sirtuins, which are NAD+-dependent class III histone deacetylases, are involved in various biological processes, including DNA damage repair, immune inflammation, oxidative stress, mitochondrial homeostasis, autophagy, and apoptosis. Sirtuins are essential regulators of cellular function and organismal health. Increasing evidence suggests that the development of age-related diseases, including kidney diseases, is associated with aberrant expression of sirtuins, and that regulation of sirtuins expression and activity can effectively improve kidney function and delay the progression of kidney disease. In this review, we summarise current studies highlighting the role of sirtuins in renal diseases. First, we discuss sirtuin family members and their main mechanisms of action. We then outline the possible roles of sirtuins in various cell types in kidney diseases. Finally, we summarise the compounds that activate or inhibit sirtuin activity and that consequently ameliorate renal diseases. In conclusion, targeted modulation of sirtuins is a potential therapeutic strategy for kidney diseases. Video Abstract

Abstract Vaccination is a valid strategy to prevent and control newly emerging and reemerging infectious diseases in humans and animals. However, synthetic and recombinant antigens are poor immunogenic to stimulate efficient and protective host immune response. Immunostimulants are indispensable factors of vaccines, which can promote to trigger fast, robust, and long-lasting immune responses. Importantly, immunotherapy with immunostimulants is increasing proved to be an effective and promising treatment of cancer, which could enhance the function of the immune system against tumor cells. Pattern recognition receptors (PRRs) play vital roles in inflammation and are central to innate and adaptive immune responses. Toll-like receptors (TLRs)-targeting immunostimulants have become one of the hotspots in adjuvant research and cancer therapy. Bacterial-origin immunoreactive molecules are usually the ligands of PRRs, which could be fast recognized by PRRs and activate immune response to eliminate pathogens. Varieties of bacterial immunoreactive molecules and bacterial component-mimicking molecules have been successfully used in vaccines and clinical therapy so far. This work provides a comprehensive review of the development, current state, mechanisms, and applications of bacterial-origin immunostimulants. The exploration of bacterial immunoreactive molecules, along with their corresponding mechanisms, holds immense significance in deepening our understanding of bacterial pathogenicity and in the development of promising immunostimulants.

Abstract Mosunetuzumab is a CD3/CD20 bispecific antibody. As an on‐target effect, transient elevation of interleukin‐6 (IL‐6) occurs in early treatment cycles. A physiologically‐based pharmacokinetic (PBPK) model was developed to assess potential drug interaction caused by IL‐6 enzyme suppression on cytochrome P450 3A (CYP3A) during mosunetuzumab treatment. The model's performance in predicting IL‐6 CYP3A suppression and subsequent drug–drug interactions (DDIs) was verified using existing clinical data of DDIs caused by chronic and transient IL‐6 elevation. Sensitivity analyses were performed for a complete DDI risk assessment. The IL‐6 concentration‐ and time‐dependent CYP3A suppression during mosunetuzumab treatment was simulated using PBPK model with incorporation of in vitro IL‐6 inhibition data. At clinically approved doses/regimens, the DDI at maximum CYP3A suppression was predicted to be a midazolam maximum drug concentration in plasma (Cmax) and area under the plasma drug concentration–time curve (AUC) ratio of 1.17 and 1.37, respectively. At the 95th percentile of IL‐6 concentration level or when gut CYP3A suppression was considered, the predicted DDI risk for mosunetuzumab remained low (

Abstract Background Cardiac implantable electronic devices (CIEDs) has proven to be an invaluable tool in the practice of cardiology. Patients who have undergone CIED surgery with local anesthesia may result in fear, insecurity and suffering. Some studies have put efforts on ways to improve intraoperative experience of patients with local anesthesia, but researches concerning experiences of CIED patients during surgery is in its infancy. Methods Based on semi-structured and in-depth interviews, a qualitative design was conducted in a tertiary general hospital in China from May 2022 to July 2023.Purposeful sampling of 17 patients received CIED surgery and 20 medical staff were interviewed. Thematic analysis with an inductive approach was used to identify dominant themes. Results Four themes emerged from the data: (1) Safety and success is priority; (2) Humanistic Caring is a must yet be lacking; (3) Paradox of surgery information given; (4) Ways to improve surgery experiences in the operation. Conclusions Intraoperative care is significant for CIED surgery. To improve care experience during surgery, healthcare professionals should pay attention to patients’ safety and the factors that affecting humanistic caring in clinical practice. In addition, information support should consider information-seeking styles and personal needs. Besides, the four approaches presented in this study are effective to improve the intraoperative care experience.

BackgroundFamilies of children with congenital heart disease (CHD) face tremendous stressors in the process of coping with the disease, which threatens the health of families of children with CHD. Studies have shown that nursing interventions focusing on family stress management can improve parents’ ability to cope with illness and promote family health. At present, there is no measuring tool for family stressors of CHD.MethodsThe items of the scale were generated through qualitative interviews and a literature review. Initial items were evaluated by seven experts to determine content validity. Factor analysis and reliability testing were conducted with a convenience sample of 670 family members. The criterion-related validity of the scale was calculated using scores on the Self-Rating Anxiety Scale (SAS).ResultsThe CHD Children’s Family Stressor Scale consisted of six dimensions and 41 items. In the exploratory factor analysis, the cumulative explained variance of the six factors was 61.085%. In the confirmatory factor analysis, the six factors in the EFA were well validated, indicating that the model fits well. The correlation coefficient between CHD Children’s Family Stressor Scale and SAS was r = 0.504 (p

Urinary tract infections (UTIs) represent a significant challenge in clinical practice, with recurrent forms (rUTIs) posing a continual threat to patient health. Escherichia coli (E. coli) is the primary culprit in a vast majority of UTIs, both community-acquired and hospital-acquired, underscoring its clinical importance. Among different mediators of pathogenesis, toxin-antitoxin (TA) systems are emerging as the most prominent. The type II TA system, prevalent in prokaryotes, emerges as a critical player in stress response, biofilm formation, and cell dormancy. ccdAB, the first identified type II TA module, is renowned for maintaining plasmid stability. This paper aims to unravel the physiological role of the ccdAB in rUTIs caused by E. coli, delving into bacterial characteristics crucial for understanding and managing this disease. We investigated UPEC-induced rUTIs, examining changes in type II TA distribution and number, phylogenetic distribution, and Multi-Locus Sequence Typing (MLST) using polymerase chain reaction (PCR). Furthermore, our findings revealed that the induction of ccdB expression in E. coli BL21 (DE3) inhibited bacterial growth, observed that the expression of both ccdAB and ccdB in E. coli BL21 (DE3) led to an increase in biofilm formation, and confirmed that ccdAB plays a role in the development of persistent bacteria in urinary tract infections. Our findings could pave the way for novel therapeutic approaches targeting these systems, potentially reducing the prevalence of rUTIs. Through this investigation, we hope to contribute significantly to the global effort to combat the persistent challenge of rUTIs.

Background: Endometrial cancer (EC) is the leading gynecological cancer worldwide, yet current EC screening approaches are not satisfying. The purpose of this retrospective study was to evaluate the feasibility and capability of DNA methylation analysis in cervical Papanicolaou (Pap) brush samples for EC detection. Methods: We used quantitative methylation-sensitive PCR (qMS-PCR) to determine the methylation status of candidate genes in EC tissue samples, as well as cervical Pap brushes. The ability of RASSF1A and HIST1H4F to serve as diagnostic markers for EC was then examined in cervical Pap brush samples from women with endometrial lesions of varying degrees of severity. Results: Methylated RASSF1A and HIST1H4F were found in EC tissues. Further, methylation of the two genes was also observed in cervical Pap smear samples from EC patients. Methylation levels of RASSF1A and HIST1H4F increased as endometrial lesions progressed, and cervical Pap brush samples from women affected by EC exhibited significantly higher levels of methylated RASSF1A and HIST1H4F compared to noncancerous controls ( P

Pulmonary sarcomatoid carcinoma (PSC) represents a rare and highly aggressive variant of lung cancer, characterized by its recalcitrance to conventional therapeutic modalities and the attendant dismal prognosis it confers. Recent breakthroughs in immunotherapy have presented novel prospects for PSC patients; nevertheless, the utility of neoadjuvant/conversional immunotherapy in the context of PSC remains ambiguous. In this report, we present a middle-aged male presenting with Stage III PSC, notable for its high expression of the programmed death-ligand 1 (PD-L1), initially deemed as non-resectable for sizeable tumor mass and multiple lymph nodes metastases. The patient underwent a transformation to a resectable state after a regimen of three cycles of platinum-based chemotherapy plus immunotherapy. Following definitive surgical resection, the individual realized a pathological complete response (pCR), culminating in a significant prolongation of event-free survival (EFS). This case underscores the viability of employing immunochemotherapy as a neoadjuvant/conversional strategy for chosen cases of PSC.

Abstract Inability to meet nutrition needs resulting from multiple diseases‐related, and individual factors contribute significantly to malnutrition and poor disease outcome among cancer patients. Strategies capable of delivering metabolically efficient nutrients with less digestive and metabolic stress without adding bulk to the diet of patients may be suitable for dealing with cancer‐related malnutrition and quality of life (QoL). We sought to test the hypothesis that peptide supplementation could attenuate weight loss and improve QoL among brain cancer patients compared to conventionally treated controls. In a non‐blind pilot study, brain cancer patients received 9 g soybean peptide supplementation twice per day (peptide group, n = 9) and compared with conventional treatment (control group, n = 10) over two chemotherapy cycles of 42 days. Compared to the controls, soypeptide supplementation attenuated weight loss with 5.4% increase in weight. Moreover, QoL, assessed using the European Organization for Research and Treatment of Cancer QLQ‐C30, revealed that physical (8.1 ± 15.6, p

Abstract Background Extravillous trophoblasts (EVTs) are essential cells during the formation of the placenta, with the major function of invading the maternal decidua, anchoring the developing placenta to the uterus, remodeling uterine arteries, and regulating immune responses to prevent rejection. During early pregnancy, the decidua undergoes a hypoxic and acidic microenvironment, which has been shown to participate in tumor cell migration, invasion, growth, and angiogenesis. Nevertheless, the mechanisms by which EVTs sense and respond to the acidic microenvironment, thereby executing their functions, remain poorly understood. Methods The effects of G protein-coupled receptor 65 (GPR65) on cell adhesion and other cellular functions were tested using JAR spheroids, mouse blastocysts, and HTR-8/SVneo cells. Specifically, we employed HTR-8/SVneo cells for gene overexpression and silencing to investigate the underlying mechanism of GPR65's impact on trophoblast cell function under acidic conditions. Additionally, villus tissue samples obtained from early pregnancy loss patients were utilized to explore the potential association between GPR65 and its related signaling pathway molecules with the disease. Results This study identified GPR65 expression widely in trophoblasts, with the highest level in EVTs. Importantly, optimal GPR65 levels are required for maintaining normal adhesion, migration, and invasion, whereas overexpression of GPR65 inhibits these functions by activating the cAMP-ERK signaling pathway, upregulating myosin light chain kinase (MYLK) and MYLK3 expression, and subsequently downregulating fibronectin. Consistently, elevated expression of GPR65, MYLK, and MYLK3 is observed in patients suffering from early pregnancy loss. Conclusions This work offers insights into the suppressive effects of GPR65 on EVT function under acidic conditions and highlights a putative target for therapeutic intervention in early pregnancy complications. Video Abstract

The investigation into the spatial distribution of living woody (LWD) and coarse woody debris (CWD) within forests represents a fundamental methodology for probing the inherent mechanisms governing coexistence and mortality within forest ecosystems. Here, a complete spatial randomness (CSR) null model was employed to scrutinize the spatial pattern, while canonical correspondence analysis (CCA) and the Torus-translation test (TTT) were utilized to elucidate the distribution patterns of LWD and CWD within warm-temperate deciduous broadleaf secondary forests in Dongling Mountains plot, northern China. The results reveal that both LWD and CWD exhibit an aggregated distribution as the predominant pattern in the Dongling Mountains plot, with the proportion and intensity of aggregation diminishing as spatial scale increases. Specifically, the aggregation intensity g0–10 demonstrates a significant negative correlation with abundance and maximum diameter at breast height (DBH). Notably, the g0–10 of LWD manifests a stronger correlation with the maximum DBH, whereas the g0–10 of CWD exhibits a greater association with the mortality rate. CCA outcomes suggest that elevation, convexity, and aspect significantly impact LWD distribution, whereas CWD distribution shows substantial negative correlations with elevation, convexity, slope, and aspect. TTT findings indicate that ecosystems characterized by a substantial presence of LWD also display a notable prevalence of CWD. Additionally, the majority of species exhibit no habitat preference, displaying neutral habitat connections and low ecological niche differentiation within the sampled plot.

A thorough comprehension of distribution features of ecosystem services (ESs) and the influencing mechanisms can offer scientific guidance for the ecosystem management of small watersheds. We analyzed the spatial distribution patterns, interrelationships, and service hotspots of ESs across pixel and administrative scales using a multi-level statistical analysis approach in the Ashi River Basin. Through the quantitative calculation of the InVEST model, the findings revealed a decrease in soil retention, water yield, total nitrogen and phosphorus export, carbon storage, and habitat quality, while an increase in food production was observed during the period from 1995 to 2015. Through the geographical detector, the spatial heterogeneity of most individual ESs was influenced by land use patterns. Through redundancy analysis, terrain factors had the highest contribution rate to the integral ESs. Socio-economic factors and climate factors also drove the ESs’ amount and spatial distribution. At the pixel scale and administrative scale, there were distinctions in the correlations between all ESs, reflected by the fact that the relationships between ESs at the administrative scale were generally weaker and no more significant than at the pixel scale. Based on the number and distribution of hotspots in ESs and the clustering results of influencing factors, the framework of ecosystem zoning was constructed. This basin was divided into three ecological zones, and the management policies were formulated according to the ecological environment. This study clarifies the internal and mutual connection between ESs and influencing factors across two scales, thus contributing to the advancement of management strategies for ecological conservation and socio-economic development within the context of small watersheds.

The endometrium is an important part of women’s bodies for menstruation and pregnancy. Various proteins are widely expressed on the surface of endometrial cells, and glycosylation is an important post-translational modification of proteins. Glycosylation modification is closely related not only to endometrial receptivity but also to common diseases related to endometrial receptivity. Glycosylation can improve endometrial receptivity, promote embryo localization and trophoblast cell adhesion and invasion, and contribute to successful implantation. Two diseases related to endometrial receptivity include endometriosis and endometrial cancer. As a common benign disease in women, endometriosis is often accompanied by an increased menstrual volume, prolonged menstrual periods, progressive and aggravated dysmenorrhea, and may be accompanied by infertility. Protein glycosylation modification of the endometrial surface indicates the severity of the disease and may be an important pathogenesis of endometriosis. In cancer, glycosylation modifications on the surface of tumor cells can be a marker to distinguish the type and severity of endometrial cancer. This review highlights the role of protein glycosylation in embryo–maternal endometrial dialogue and explores its potential mechanisms in diseases related to endometrial receptivity, which could provide a new clinical approach for their diagnosis and treatment.

Abstract Objective The coronavirus disease 2019 was a global public health emergency in later years (from 2020 to early 2022), and androgens have been associated with infection and prognostic outcomes. However, the relationship between low serum testosterone levels and prognostic outcomes remains inconclusive. This systematic review aimed to investigate the relationship between serum testosterone levels and prognostic outcomes in patients with COVID-19. Methods We searched PubMed, MEDLINE, EMBASE and Web of Science electronic databases for all literature from January 1, 2020, to September 1, 2022. In addition, we also searched literature manually. The search terms were COVID-19, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), androgens, and testosterone. There were no language restrictions for retrieval. Results Our search identified 2285 articles, resulting in a full-text analysis of 16 studies, including 12 cohort studies and four case-control studies. Low serum testosterone levels were observed to be statistically associated with a higher probability of intensive care unit (ICU) admission in seven studies. In eight studies, higher hospital mortality was associated with lower serum testosterone levels. Six studies found that low serum testosterone levels were associated with a statistically significant difference in lung function impairment. Only four studies found that among living patients, those with lower serum testosterone levels had longer hospital stays. All but one of the included studies had a low risk of bias. Conclusions Based on available data, low serum testosterone levels are associated with higher rates of ICU admission, hospital mortality, risk of lung failure, inflammatory markers, and longer hospital stays in patients with COVID-19 compared with those having normal serum testosterone levels.

Grain number per spike (GNS) is a crucial component of grain yield and plays a significant role in improving wheat yield. To identify quantitative trait loci (QTL) associated with GNS, a recombinant inbred line (RIL) population derived from the cross of Zhongkemai 13F10 and Chuanmai 42 was employed to conduct QTL mapping across eight environments. Based on the bulked segregant exome sequencing (BSE-Seq), genomic regions associated with GNS were detected on chromosomes 5A and 6A. According to the constructed genetic maps, two major QTL QGns.cib-5A (LOD = 4.35–8.16, PVE = 8.46–14.43%) and QGns.cib-6A (LOD = 3.82–30.80, PVE = 5.44–12.38%) were detected in five and four environments, respectively. QGns.cib-6A is a QTL cluster for other seven yield-related traits. QGns.cib-5A and QGns.cib-6A were further validated using linked Kompetitive Allele Specific PCR (KASP) markers in different genetic backgrounds. QGns.cib-5A exhibited pleiotropic effects on productive tiller number (PTN), spike length (SL), fertile spikelet number per spike (FSN), and ratio of grain length to grain width (GL/GW) but did not significantly affect thousand grain weight (TGW). Haplotype analysis revealed that QGns.cib-5A and QGns.cib-6A were the targets of artificial selection during wheat improvement. Candidate genes for QGns.cib-5A and QGns.cib-6A were predicted by analyzing gene annotation, spatiotemporal expression patterns, and orthologous and sequence differences. These findings will be valuable for fine mapping and map-based cloning of genes underlying QGns.cib-5A and QGns.cib-6A.

To realize the coordinated development of urbanization and ecological environment is a research hotspot in recent years. There is a very complicated relationship between them. Understanding their relationship is key to realize their coordinated development. In this paper, the long-term dynamic balance behavior between urbanization and ecological environment was studied by means of long-term equilibrium model and error correction model (ECM) based on the data of Shandong Province. In order to comprehensively reflect urbanization and ecological environment, this paper employed comprehensive evaluation model to construct comprehensive index of urbanization and ecological environment respectively, and used coupling coordination degree (CDE) and relative development degree model (RDE) to study the dynamic changes of the two. The results showed that: (1) The relationship between urbanization and ecological environment in Shandong Province is becoming more and more harmonious, and the coupling coordination type between them has gradually developed from extremely uncoupling (EUC) type to highly coupling (HC) type; (2) In the long run, there is a long-term equilibrium relationship between urbanization and ecological environment in Shandong Province, and this equilibrium can be achieved through short-term dynamic adjustment. Therefore, a correct understanding of the short-term and long-term development laws between them can provide the corresponding theoretical basis for policy makers, and shorten the time for urbanization and ecological environment to reach an equilibrium state.

In this study, a series of potential ligands for the treatment of AD were synthesised and characterised as novel harmine derivatives modified at position 9 with benzyl piperazinyl. In vitro studies revealed that the majority of the derivatives exhibited moderate to potent inhibition against hAChE and Aβ1 − 42 aggregation. Notably, compounds 13 and 17d displayed potent drug − likeness and ADMET properties, demonstrating remarkable inhibitory activities towards AChE (IC50 = 58.76 nM and 89.38 nM, respectively) as well as Aβ aggregation (IC50 = 9.31 μM and 13.82 μM, respectively). More importantly, compounds 13 and 17d showed exceptional neuroprotective effects against Aβ1 − 42−induced SH − SY5Y damage, while maintaining low toxicity in SH − SY5Y cells. Further exploration of the mechanism through kinetic studies and molecular modelling confirmed that compound 13 could interact with both the CAS and the PAS of AChE. These findings suggested that harmine derivatives hold great potential as dual − targeted candidates for treating AD.

Objective: This study aimed to evaluate the impact of pre-operative education tailored to percutaneous coronary intervention (PCI) patients’ information-seeking styles on pre-operative anxiety and depression. Methods: A single-blind randomized control trial was conducted. A total of 114 participants were recruited from the cardiology department in a tertiary hospital in Kunming, Southwest China from April to September 2020 and randomly allocated to the intervention group (n = 57) or control group (n = 57). All patients received oral pre-operative education as well as printed pre-operative education manuals and divided into monitors or blunters by the Chinese Version of the Monitoring Subscale of the Miller Behavioral Style Scale (C-MMBSS). The intervention group received pre-operative education tailored to information-seeking styles, while the control group received routine education. Anxiety and depression were measured at baseline and 1 h before the operation. Satisfaction with pre-operative education and length of stay were assessed at discharge. Results: A total of 104 participants completed the study (52 participants in each group). Pre-operative education tailored to information-seeking styles was beneficial for reducing pre-operative anxiety (P

Based on the data of Sichuan Province from 2007 to 2021, the extreme climate events in Sichuan Province was identified by statistical method, and the coupling coordination degree of water resources-climate system and separate water resource system was analyzed. Based on the difference of coupling coordination degree under these two systems, the influence mechanism of extreme climate factors on the water resource system is analyzed. The results show that the extreme climate types in Sichuan Province gradually transition from extreme drought to extreme precipitation and from extreme low temperature to extreme high temperature. When climate factors are not considered, the coupling coordination degree of the water resource system is generally improved and the distribution is more concentrated. Moreover, the influence of climate factors on the water resource system is not a simple linear relationship.

Internal pore defects are inevitable during laser powder bed fusion (LPBF), which have a significant impact on the mechanical properties of the parts. Therefore, detecting pores and obtaining their morphology will contribute to the quality of LPBF parts. Currently, supervised models are used for defect image detection, which requires a large amount of LPBF sample data, image labeling, and computing power equipment during the training process, resulting in high detection costs. This study extensively collected LPBF sample data and proposed a method for pore defect classification by obtaining its morphological features while detecting pore defects in optical microscopy (OM) images under various conditions. Compared with other advanced models, the proposed method achieves better detection accuracy on pore defect datasets with limited data. In addition, quickly detecting pore defects in a large number of labeling ground truth images will also contribute to the development of deep learning. In terms of image segmentation, the average accuracy scores of this method in the test images exceed 85%. The research results indicate that the algorithm proposed in this paper is suitable for quickly and accurately identifying pore defects from optical microscopy images.

Sirtuins are a family of NAD+ III-dependent histone deacetylases that consists of seven family members, Sirt1-Sirt7, which regulate various signalling pathways and are involved in many critical biological processes of kidney diseases. Traditional Chinese medicine (TCM), as an essential part of the global healthcare system, has multi-component and multi-pathway therapeutic characteristics and plays a role in preventing and controlling various diseases. Through ongoing collaboration with modern medicine, TCM has recently achieved many remarkable advancements in theoretical investigation, mechanistic research, and clinical applications related to kidney diseases. Therefore, a comprehensive and systematic summary of TCM that focuses on sirtuins as the intervention target for kidney diseases is necessary. This review introduces the relationship between abnormal sirtuins levels and common kidney diseases, such as diabetic kidney disease and acute kidney injury. Based on the standard biological processes, such as inflammation, oxidative stress, autophagy, mitochondrial homeostasis, and fibrosis, which are underlying kidney diseases, comprehensively describes the roles and regulatory effects of TCM targeting the sirtuins family in various kidney diseases.

Diabetic kidney disease (DKD) is a major microvascular complication of diabetes and a leading cause of end-stage renal disease worldwide. Autophagy plays an important role in maintaining cellular homeostasis in renal physiology. In DKD, the accumulation of advanced glycation end products induces decreased renal autophagy-related protein expression and transcription factor EB (TFEB) nuclear transfer, leading to impaired autophagy and lysosomal function and blockage of autophagic flux. This accelerates renal resident cell injury and apoptosis, mediates macrophage infiltration and phenotypic changes, ultimately leading to aggravated proteinuria and fibrosis in DKD. Natural polyphenols show promise in treating DKD by regulating autophagy and promoting nuclear transfer of TFEB and lysosomal repair. This review summarizes the characteristics of autophagy in DKD, and the potential application and mechanisms of some known natural polyphenols as autophagy regulators in DKD, with the goal of contributing to a deeper understanding of natural polyphenol mechanisms in the treatment of DKD and promoting the development of their applications. Finally, we point out the limitations of polyphenols in current DKD research and provide an outlook for their future research.

Diabetic nephropathy (DN) often leads to end-stage renal disease. Oxidative stress demonstrates a crucial act in the onset and progression of DN, which triggers various pathological processes while promoting the activation of inflammation and forming a vicious oxidative stress-inflammation cycle that induces podocyte injury, extracellular matrix accumulation, glomerulosclerosis, epithelial-mesenchymal transition, renal tubular atrophy, and proteinuria. Conventional treatments for DN have limited efficacy. Polyphenols, as antioxidants, are widely used in DN with multiple targets and fewer adverse effects. This review reveals the oxidative stress and oxidative stress-associated inflammation in DN that led to pathological damage to renal cells, including podocytes, endothelial cells, mesangial cells, and renal tubular epithelial cells. It demonstrates the potent antioxidant and anti-inflammatory properties by targeting Nrf2, SIRT1, HMGB1, NF-κB, and NLRP3 of polyphenols, including quercetin, resveratrol, curcumin, and phenolic acid. However, there remains a long way to a comprehensive understanding of molecular mechanisms and applications for the clinical therapy of polyphenols.

BackgroundPD-1/PD-L1 immune checkpoint inhibitors are currently the most commonly utilized agents in clinical practice, which elicit an immunostimulatory response to combat malignancies. However, all these inhibitors are currently administered via injection using antibody-based therapies, while there is a growing need for oral alternatives.MethodsThis study has developed and synthesized exosome-wrapped gold–peptide nanocomplexes with low immunogenicity, which can target PD-L1 and activate antitumor immunity in vivo through oral absorption. The SuperPDL1exo was characterized by transmission electron microscopy (TEM), dynamic light scattering (DLS), Fourier transform infrared (FTIR), X-ray photoelectron spectroscopy (XPS), and gel silver staining. The transmembrane ability of SuperPDL1exo was evaluated by flow cytometry and immunofluorescence. Cell viability was determined using the Cell Counting Kit-8 (CCK-8) assay. ELISA experiments were conducted to detect serum and tissue inflammatory factors, as well as serum biochemical indicators. Tissue sections were stained with H&E for the evaluation of the safety of SuperPDL1exo. An MC38 colon cancer model was established in immunocompetent C56BL/6 mice to evaluate the effects of SuperPDL1exo on tumor growth in vivo. Immunohistochemistry (IHC) staining was performed to detect cytotoxicity factors such as perforin and granzymes.ResultsFirst, SuperPDL1 was successfully synthesized, and milk exosome membranes were encapsulated through ultrasound, repeated freeze–thaw cycles, and extrusion, resulting in the synthesis of SuperPDL1exo. Multiple characterization results confirmed the successful synthesis of SuperPDL1exo nanoparticles. Furthermore, our data demonstrated that SuperPDL1exo exhibited excellent colloidal stability and superior cell transmembrane ability. In vitro and in vivo experiments revealed that SuperPDL1exo did not cause damage to multiple systemic organs, demonstrating its good biocompatibility. Finally, in the MC38 colon cancer mouse model, it was discovered that SuperPDL1exo could inhibit the progression of colon cancer, and this tumor-suppressive effect was mediated through the activation of tumor-specific cytotoxic T lymphocyte (CTL)-related immune responses.ConclusionThis study has successfully designed and synthesized an oral nanotherapeutic, SuperPDL1exo, which demonstrates small particle size, excellent colloidal stability, transmembrane ability in tumor cells, and biocompatibility. In vivo experiments have shown that it effectively activates T-cell immunity and exerts antitumor effects.

IntroductionThe combination of a PD-L1 inhibitor plus carboplatin/cisplatin and etoposide (EC/EP) has become a new standard first-line treatment for extensive-stage small-cell lung cancer (ES-SCLC). Combining concurrent palliative hypofractionated radiotherapy of the thorax (HFRT) and immunochemotherapy may have a synergistic effect. In this study, we explored an optimal model of combination radiotherapy with immunochemotherapy as first-line treatment of ES-SCLC.Patients and methodsIn this multicenter single-arm phase 2 trial, patients with ES-SCLC received atezolizumab with EC/EP for two cycles (induction phase), then, those who did not progress received concurrent palliative HFRT and two cycles of atezolizumab with EC/EP (combination phase). Afterward they received atezolizumab every 3 weeks for a maximum of 2 years after study enrolment (maintenance phase). Prophylactic cranial irradiation (PCI) was recommended. The primary endpoints were safety and tolerance; the second endpoints were progression-free survival (PFS).ResultsForty patients were enrolled, and all had completed palliative HFRT and four cycles of immunochemotherapy. There were seven grade 3 adverse events (3 decreased neutrophil count, 1 anemia, 2 pneumonitis, 1 esoenteritis), two grade 4 adverse events (2 decreased white cell count) and no grade 5 toxicities. The pneumonitis rate was 12.5% (three grade 2 and two grade 3 events). At the median follow-up of 14.2 months (range, 6.8–28.7), the median PFS was 8.6 months (95%CI, 6.1–11.1).ConclusionThe addition of concurrent hypofractionated thoracic radiotherapy to first-line immunochemotherapy for ES-SCLC was well tolerated and showed promising clinical efficacy. Additional randomized trials are needed to validate benefits.Clinical trial registrationhttps://clinicaltrials.gov/ (NCT 04636762).

The investigation into the spatial patterns of living woody (LWD) and coarse woody debris (CWD) in warm-temperate deciduous broadleaved secondary forests serves as a foundational exploration of the mechanisms governing coexistence and mortality in forest ecosystems. The complete spatial randomness null model (CSR) was employed to analyze spatial distribution patterns, with the independent component null model (IC) and canonical correspondence analysis (CCA) utilized to elucidate spatial correlations and topographic influences. All three models were applied to LWD and CWD across various size classes within a 20-hectare plot in the Dongling Mountains. The study’s findings indicate that both LWD and CWD predominantly exhibited aggregated patterns, transitioning to a random distribution as the size class increased. Both increasing abundance and maximum diameter at breast height (DBH) also have a significant influence on the distribution of species. Notably, rare species exhibited higher aggregation compared to common and abundant species. The spatial correlation results between LWD and CWD across various size classes predominantly showed positive correlations and uncorrelated patterns within the sampled plots. CCA analysis further revealed that elevation, convexity, slope, and aspect significantly influenced the spatial patterns of LWD and CWD across different size classes. Within the sample site, trees display a tendency to grow and die in clusters. Biotic factors have a more significant influence on species distribution than abiotic factors.

En este estudio se utilizó un nuevo tipo de floculante microbiano combinado con coagulante de cloruro férrico de polialuminio (PAFC) en el experimento de coagulación-floculación de agua de limo de carbón. Se investigaron los efectos de la dosis de PAFC, la dosis de biofloculante y el pH sobre la turbidez y la demanda química de oxígeno (COD) del agua de limo de carbón. Los resultados mostraron que las mejores condiciones para eliminar la turbidez del agua de limo y la COD mediante la prueba de factor único fueron las siguientes: la dosis de PAFC fue de 37.5 mg/l, la dosis de biofloculante fue de 0.75 mg/l y el pH fue de 7.0. A través de la prueba ortogonal se identificó que los factores más influyentes para la turbidez y eliminación de COD son el pH y la dosis de PAFC, respectivamente. La mejor condición de la coagulación-floculación fue con una dosis de PAFC de 50.0 mg/l, una dosis de biofloculante de 0.5 mg/l y el pH de 7.0. Bajo esta condición, se obtuvo una eficiencia de remoción de turbidez del 93.2 % y una eficiencia de remoción de COD del 47.2 %.

BackgroundUniversal COVID-19 vaccination programs are now recommended in several countries and represent the most effective preventive measure against COVID-19. However, some reports suggest that vaccination may cause infertility or have adverse effects on pregnancy. Conflicting reports have led to vaccine hesitancy in women planning pregnancy.PurposeTo determine whether vaccination against COVID-19 affects in vitro fertilization (IVF) outcomes, we conducted a meta-analysis.MethodA systematic search was conducted using PubMed, Embase, MEDLINE, and Web of Science databases for all published literature on COVID-19 vaccines and outcomes of IVF. International Prospective Register of Systematic Reviews registration was completed on September 13, 2022 (CRD42022359771).ResultsWe analyzed 20 studies totaling 18,877 individual cases undergoing IVF. COVID-19 vaccination had significant effect on clinical and ongoing pregnancy rate (risk ratio (RR): 0.97; 95% confidence interval (CI): 0.94–0.99; RR: 0.93; 95% CI: 0.87–0.99). These outcomes did not differ between vaccinated and unvaccinated individuals: biochemical pregnancy rate (RR: 0.95; 95% CI: 0.88–1.03), implantation rate (RR: 1.02; 95%CI: 0.97–1.07; P = 0.41), the number of oocytes (mean difference (MD): 0.12; 95% CI: −0.65–0.88) and MII/mature oocytes recovered (MD: 0.27; 95% CI: −0.36–0.90), blastocysts rate (MD: 0.01; 95% CI: −0.04, 0.06), and fertilization rate (MD: 1.08; 95% CI: −0.57, 2.73).ConclusionOur findings suggest that vaccination against COVID-19 does not adversely affect the biochemical pregnancy rates; number of oocytes and MII/mature oocytes obtained; implantation, blastocysts; and fertilization rates in women undergoing IVF treatment. Subgroup analysis showed that the mRNA vaccine had no statistical significance on all indexes (clinical, biochemical, or ongoing pregnancy rates; implantation, blastocysts, or fertilization rates; and the number of oocytes and MII/mature oocytes). The findings of this meta-analysis are anticipated to increase the willingness of women planning IVF treatment to receive COVID-19 vaccination and provide evidence-based medical guidance for the development and implementation of guidelines.Systematic review registrationhttps://www.crd.york.ac.uk/PROSPERO/, identifier: CRD42022359771.

The Sox transcription factor family plays an important role in various biological processes such as animal sex determination and multiple organ development. We used online databases to analyze the gene structure, chemical characteristics, and evolutionary relationship of Sox family genes through bioinformatics, and we studied the expression profiles and regulatory mechanisms of Sox family genes. A total of 29 rainbow trout Sox genes were identified. The phylogenetic analysis found that Sox genes of rainbow trout were clustered in seven subfamilies (B1, B2, C, D, E, F and H), and the gene structure of each subfamily was relatively conserved. Furthermore, Sox1, Sox4, Sox6, Sox8, Sox9, Sox11, Sox17, Sox18, and Sox19 developed into two copies, which might be the result of teleost fish-specific genome replication. Multiple HMG box domain alignments indicated that the motifs for all Sox sequences are conserved. Gene expression studies reveal that Sox expression is tissue-specific and that multiple Sox genes are involved in rainbow trout gonad and central nervous system development. Our study provides valuable information on the evolution of teleosts, and will also help to further research the functional characteristics of Sox genes.

The dried roots of the perennial herb Angelica sinensis (Oliv.) Diels (AS) are commonly used as medicinal and edible resources. In commercial planting, early bolting and flowering (EB) of ca. 60% in the medicine formation period reduces root yield and quality, becoming a significant bottleneck in agricultural production. In the cultivation process, summer bolting (SB) occurs from June to July, and autumn bolting (AB) occurs in September. The AB root is often mistaken for the AS root due to its similar morphological characteristics. Few studies have involved whether the root of AB could be used as herbal medicine. This study explored and compared the accumulation dynamics of primary and secondary metabolites in AS and EB roots during the vegetative growth stage (from May to September) by light microscopy, ultraviolet spectrometry, and HPLC methods. Under a microscope, the amount of free starch granules and oil chamber in the AS root increased. On the contrary, they decreased further from EB-Jul to EB-Sep. By comparison, the wall of the xylem vessel was slightly thickened and stacked, and the cell walls of parenchyma and root cortex tissue were thickened in the EB root. Early underground bolting reduces soluble sugar, soluble protein, free amino acids, total C element, total N element, ferulic acid, and ligustilide accumulation, accompanied by the lignification of the root during the vegetative growth stage. Furthermore, a total of 55 root samples from different bolting types of AS root (29 samples), SB root (14 samples), and AB root (12 samples) were collected from Gansu Province during the harvesting period (October). The later the bolting occurred, the less difference there was between unbolted and bolted roots in terms of morphological appearance and efficacy components. Fourier transform infrared spectroscopy with the attenuated total reflection mode (ATR-FTIR) provides a “holistic” spectroscopic fingerprinting of all compositions in the tested sample. The ATR-FTIR spectrum of the AB root was similar to that of the AS root. However, the number and location of absorption peaks in the spectra of SB were different, and only one strong absorption peak at 1021 cm−1 was regarded as the characteristic peak of C-O stretching vibration in lignin. The ATR-FTIR spectra can be effectively differentiated based on their various characteristics using orthogonal partial least squares discrimination analysis (OPLS-DA). Results were assessed using multiple statistical techniques, including Spearman’s correlation, principal component analysis (PCA), partial least squares discriminant analysis (PLS-DA), and OPLS-DA. Among these methods, the ATR-FTIR data demonstrated the most effective outcomes in differentiating between viable and non-viable roots for their application in herbal medicine. Essential substances are ferulic acid and flavonoid, which are much more abundant in the AB root. It provides a material basis for the pharmacological action of the AB roots and a theoretical basis for improving their availability.

Habitat heterogeneity caused by topographic variations at the local scale is the environmental basis for the establishment and evolution of biodiversity and biomass patterns. The similarities and distinctions between the effects of microtopographic variables on living wood (LWD) and dead wood (CWD) remain unknown. In the present study, the response mechanisms of biomass and species diversity patterns of living wood (LWD) and coarse woody debris (CWD) to microtopographic parameters were quantified in a warm temperate secondary forest located in Dongling Mountain, China. This quantification was achieved using a generalized additive model on a completely mapped 20-hectare permanent plot. The evaluation of biomass and species diversity of woody plants was carried out by utilizing the total basal area of all individuals and the species richness within each 20 m × 20 m quadrat as a standard. The results indicate that there are notable disparities in the influence of microtopographic elements on the LWD and CWD. In the case of LWD, microtopography accounts for 22.90% of the variation in total basal area, with convexity making a greater relative contribution than elevation, slope, and aspect. Additionally, microtopography explains 46.20% of the variation in species richness, with aspect making a greater relative contribution than elevation, convexity, and slope. Nevertheless, the influence of microtopography on CWD may only account for a deviation of 10.20% in the total basal area and 4.95% in the species richness; aspect and slope have been identified as the primary drivers in this regard. The inclusion of microtopographic factors in the model resulted in a 23.10% increase in the explanatory deviations of LWD biomass and an 8.70% increase in the explanatory deviations of CWD biomass. The findings suggest that topographic considerations have a greater impact on the biomass distribution of LWD compared to that of CWD. Conversely, the biomass of CWD is more influenced by the species richness. The presence of microtopography plays a vital role in determining the spatial distribution of species and biomass at local scales, reflecting the multiple response mechanisms and growth strategies of vegetation in response to redistribution in water, soil, and light.

Metal FDM technology overcomes the problems of high cost, high energy consumption and high material requirements of traditional metal additive manufacturing by combining FDM and powder metallurgy and realizes the low-cost manufacturing of complex metal parts. In this work, 15-5PH stainless steel granules with a powder content of 90% and suitable for metal FDM were developed. The flowability and formability of the feedstock were investigated and the parts were printed. A two-step (solvent and thermal) debinding process is used to remove the binder from the green part. After being kept at 75 °C in cyclohexane for 24 h, the solvent debinding rate reached 98.7%. Following thermal debinding, the material’s weight decreased by slightly more than 10%. Sintering was conducted at 1300 °C, 1375 °C and 1390 °C in a hydrogen atmosphere. The results show that the shrinkage of the sintered components in the X-Y-Z direction remains quite consistent, with values ranging from 13.26% to 19.58% between 1300 °C and 1390 °C. After sintering at 1390 °C, the material exhibited a relative density of 95.83%, a hardness of 101.63 HRBW and a remarkable tensile strength of 770 MPa. This work realizes the production of metal parts using 15-5PH granules’ extrusion additive manufacturing, providing a method for the low-cost preparation of metal parts. And it provides a useful reference for the debinding and sintering process settings of metal FDM. In addition, it also enriches the selection range of materials for metal FDM.

In order to identify the effects of the slope and precipitation intensity on the soil runoff depth and runoff rate, different tillage patterns (slope-ridge direction, horizontal slope-ridge direction, no-ridge farming) and different slopes (3° and 5°) were set up, and five typical rainfalls from June to September 2021 were selected, to dynamically monitor the soil-erosion dynamics of the test plots under different rainfall intensities. The results show that cross-slope-ridge cropping has a retention effect on runoff, which effectively inhibits the ineffective loss of rainfall confluence. Among these results, the variation range in the soil runoff depth under cross-slope-ridge treatment conditions was 0.11~0.94 mm, while that under the slope-ridge treatment and no-ridge treatment conditions was increased to 1.44~12.49 mm and 3.45~14.96 mm, respectively. It found that the loss of soil nutrients was significantly higher in the slope-ridge direction and in the no-ridge farming condition than in the horizontal slope-ridge direction. It is worth noting that, as the slope of the cultivated land increases, the erosive capacity of the precipitation runoff for the soil phosphorus increases, while the carrying capacity of the soil nitrogen decreases, and the correlation analysis results confirm that the corresponding relationship between the free diffusion capacity of the soil ammonium nitrogen and soil erosion is weaker than that between the nitrate nitrogen and soil erosion. The effects of single factors, such as the slope, ridge direction, and precipitation intensity of the cultivated land, have a significant impact on the soil water- and fertilizer-loss process, while the influence effect of the multi-factor coupling process on soil erosion is weakened. It was confirmed that the erosion process of rainfall runoff on soil nitrogen and phosphorus loss in slope cultivated land is the result of multi-factor action, and the artificial modification of the tillage mode can effectively regulate the effect of farmland water and fertilizer loss.

Abstract Background Aberrant DNA methylation may offer opportunities in revolutionizing cancer screening and diagnosis. We sought to identify a non-invasive DNA methylation-based screening approach using cell-free DNA (cfDNA) for early detection of hepatocellular carcinoma (HCC). Methods Differentially, DNA methylation blocks were determined by comparing methylation profiles of biopsy-proven HCC, liver cirrhosis, and normal tissue samples with high throughput DNA bisulfite sequencing. A multi-layer HCC screening model was subsequently constructed based on tissue-derived differentially methylated blocks (DMBs). This model was tested in a cohort consisting of 120 HCC, 92 liver cirrhotic, and 290 healthy plasma samples including 65 hepatitis B surface antigen-seropositive (HBsAg+) samples, independently validated in a cohort consisting of 67 HCC, 111 liver cirrhotic, and 242 healthy plasma samples including 56 HBsAg+ samples. Results Based on methylation profiling of tissue samples, 2321 DMBs were identified, which were subsequently used to construct a cfDNA-based HCC screening model, achieved a sensitivity of 86% and specificity of 98% in the training cohort and a sensitivity of 84% and specificity of 96% in the independent validation cohort. This model obtained a sensitivity of 76% in 37 early-stage HCC (Barcelona clinical liver cancer [BCLC] stage 0-A) patients. The screening model can effectively discriminate HCC patients from non-HCC controls, including liver cirrhotic patients, asymptomatic HBsAg+ and healthy individuals, achieving an AUC of 0.957(95% CI 0.939–0.975), whereas serum α-fetoprotein (AFP) only achieved an AUC of 0.803 (95% CI 0.758–0.847). Besides detecting patients with early-stage HCC from non-HCC controls, this model showed high capacity for distinguishing early-stage HCC from a high risk population (AUC=0.934; 95% CI 0.905–0.963), also significantly outperforming AFP. Furthermore, our model also showed superior performance in distinguishing HCC with normal AFP (< 20ng ml−1) from high risk population (AUC=0.93; 95% CI 0.892–0.969). Conclusions We have developed a sensitive blood-based non-invasive HCC screening model which can effectively distinguish early-stage HCC patients from high risk population and demonstrated its performance through an independent validation cohort. Trial registration The study was approved by the ethic committee of The Second Xiangya Hospital of Central South University (KYLL2018072) and Chongqing University Cancer Hospital (2019167). The study is registered at ClinicalTrials.gov(# NCT04383353 ).

IntroductionThe treatment response to neoadjuvant immunochemotherapy varies among patients with potentially resectable non-small cell lung cancers (NSCLC) and may have severe immune-related adverse effects. We are currently unable to accurately predict therapeutic response. We aimed to develop a radiomics-based nomogram to predict a major pathological response (MPR) of potentially resectable NSCLC to neoadjuvant immunochemotherapy using pretreatment computed tomography (CT) images and clinical characteristics.MethodsA total of 89 eligible participants were included and randomly divided into training (N=64) and validation (N=25) sets. Radiomic features were extracted from tumor volumes of interest in pretreatment CT images. Following data dimension reduction, feature selection, and radiomic signature building, a radiomics-clinical combined nomogram was developed using logistic regression analysis.ResultsThe radiomics-clinical combined model achieved excellent discriminative performance, with AUCs of 0.84 (95% CI, 0.74-0.93) and 0.81(95% CI, 0.63-0.98) and accuracies of 80% and 80% in the training and validation sets, respectively. Decision curves analysis (DCA) indicated that the radiomics-clinical combined nomogram was clinically valuable.DiscussionThe constructed nomogram was able to predict MPR to neoadjuvant immunochemotherapy with a high degree of accuracy and robustness, suggesting that it is a convenient tool for assisting with the individualized management of patients with potentially resectable NSCLC.

Artemisinin, an antimalarial traditional Chinese herb, is isolated from Artemisia annua. L, and has shown fewer side effects. Several pieces of evidence have demonstrated that artemisinin and its derivatives exhibited therapeutic effects on diseases like malaria, cancer, immune disorders, and inflammatory diseases. Additionally, the antimalarial drugs demonstrated antioxidant and anti-inflammatory activities, regulating the immune system and autophagy and modulating glycolipid metabolism properties, suggesting an alternative for managing kidney disease. This review assessed the pharmacological activities of artemisinin. It summarized the critical outcomes and probable mechanism of artemisinins in treating kidney diseases, including inflammatory, oxidative stress, autophagy, mitochondrial homeostasis, endoplasmic reticulum stress, glycolipid metabolism, insulin resistance, diabetic nephropathy, lupus nephritis, membranous nephropathy, IgA nephropathy, and acute kidney injury, suggesting the therapeutic potential of artemisinin and its derivatives in managing kidney diseases, especially the podocyte-associated kidney diseases.

Various intractable inflammatory diseases caused by disorders of immune systems have pressed heavily on public health. Innate and adaptive immune cells as well as secreted cytokines and chemokines are commanders to mediate our immune systems. Therefore, restoring normal immunomodulatory responses of immune cells is crucial for the treatment of inflammatory diseases. Mesenchymal stem cell derived extracellular vesicles (MSC-EVs) are nano-sized double-membraned vesicles acting as paracrine effectors of MSCs. MSC-EVs, containing a variety of therapeutic agents, have shown great potential in immune modulation. Herein, we discuss the novel regulatory functions of MSC-EVs from different sources in the activities of innate and adaptive immune cells like macrophages, granulocytes, mast cells, natural killer (NK) cells, dendritic cells (DCs) and lymphocytes. Then, we summarize the latest clinical trials of MSC-EVs in inflammatory diseases. Furthermore, we prospect the research trend of MSC-EVs in the field of immune modulation. Despite the fact that the research on the role of MSC-EVs in regulating immune cells is in infancy, this cell-free therapy based on MSC-EVs still offers a promising solution for the treatment of inflammatory diseases.