Search

Abstract Piercing-sucking pests are the most notorious group of pests for global agriculture. RNAi-mediated crop protection by foliar application is a promising approach in field trials. However, the effect of this approach on piercing-sucking pests is far from satisfactory due to the limited uptake and transport of double strand RNA (dsRNA) in plants. Therefore, there is an urgent need for more feasible and biocompatible dsRNA delivery approaches to better control piercing-sucking pests. Here, we report that foliar application of layered double hydroxide (LDH)-loaded dsRNA can effectively disrupt Panonychus citri at multiple developmental stages. MgAl-LDH-dsRNA targeting Chitinase (Chit) gene significantly promoted the RNAi efficiency and then increased the mortality of P. citri nymphs by enhancing dsRNA stability in gut, promoting the adhesion of dsRNA onto leaf surface, facilitating dsRNA internalization into leaf cells, and delivering dsRNA from the stem to the leaf via the vascular system of pomelo plants. Finally, this delivery pathway based on other metal elements such as iron (MgFe-LDH) was also found to significantly improve the protection against P. citri and the nymphs or larvae of Diaphorina citri and Aphis gossypii, two other important piercing-sucking hemipeteran pests, indicating the universality of nanoparticles LDH in promoting the RNAi efficiency and mortality of piercing-sucking pests. Collectively, this study provides insights into the synergistic mechanism for nano-dsRNA systemic translocation in plants, and proposes a potential eco-friendly control strategy for piercing-sucking pests. Graphical Abstract

Abstract Objective To analyse the influencing factors of vaccine hesitancy on HPV vaccination willingness of female college students in order to promote the promotion of HPV vaccine in female college student population. Methods From September-October 2022, a convenience sampling method was used to conduct a questionnaire survey among freshman female students from four higher vocational colleges in Henan Province, China. The survey comprised a general information questionnaire, as well as inquiries regarding vaccine hesitancy and willingness to receive the human papillomavirus (HPV) vaccine. In PSM analyses, vaccine-hesitant students were matched with non-vaccine-hesitant students at a 1:1 ratio; subsequently, both univariate and multivariatble logistic regression analyses were applied to assess the impact of vaccine hesitancy on female university students’ willingness to receive the HPV vaccine. Results The results revealed a vaccine hesitancy rate of 44.75% among female university students, with 82.9% expressing willingness to receive the HPV vaccine. The results of the multivariable ordinal logistic regression analysis indicated vaccine hesitancy is a risk factor for HPV vaccination intentions among female university students [OR = 4.38, 95% CI (2.74, 6.99), P

BackgroundCervical cancer is the fourth most common cancer among women, HPV vaccine can reduce the incidence of cervical cancer by approximately 70%. Sexual behavior is a direct risk factor for HPV infection, and sexually active college students, therefore, receive attention for HPV vaccination. This study aimed to investigate the awareness of HPV and its vaccine among college students in Zhengzhou, and to explore the factors influencing their awareness of HPV vaccine, to understand college students’ willingness to receive the vaccine. The findings of this study will lay a foundation for cervical cancer prevention.MethodsUsing a multistage random sampling method, 650 college students from four universities in Zhengzhou were selected. A self-administered questionnaire on the awareness of HPV and its vaccine, and willingness to receive HPV vaccination was carried out. Logistic regression was used to analyze the factors influencing students’ awareness of the HPV vaccine.Results58.0% of college students had heard of HPV, and 72.8% of college students had heard of HPV vaccine. Logistic regression showed that gender, major, grade, mean monthly consumption level, sexual history, and mother cervical cancer screening participation significantly influenced the awareness of HPV vaccine (p

Abstract This paper aims to investigate the internal structure of student academic resilience in language learning, to assess its global and dimensional levels and to examine the gender and age-related differences. Therefore, 1,653 English as a foreign language (EFL) learners, including junior and senior high school students were selected as participants to complete the questionnaires. The results of exploratory and confirmatory factor analyses unveiled a four-factorial structure of student academic resilience in English learning, including positive individual characteristics, family support, teacher support and peer support. In addition, there were no significant differences between male and female students in terms of academic resilience in English learning and its four subdimensions. Only the level of family support for junior high school students was significantly higher than that of senior high school students. The findings, implications, and limitations of language learning academic resilience were discussed.

Abstract Idiopathic pulmonary fibrosis (IPF) is a progressive and ultimately fatal interstitial lung disease, with limited therapeutic options available. Impaired autophagy resulting from aberrant TRB3/p62 protein‐protein interactions (PPIs) contributes to the progression of IPF. Restoration of autophagy by modulating the TRB3/p62 PPIs has rarely been reported for the treatment of IPF. Herein, peptide nanofibers are developed that specifically bind to TRB3 protein and explored their potential as a therapeutic approach for IPF. By conjugating with the self‐assembling fragment (Ac‐GFFY), a TRB3‐binding peptide motif A2 allows for the formation of nanofibers with a stable α‐helix secondary structure. The resulting peptide (Ac‐GFFY‐A2) nanofibers exhibit specific high‐affinity binding to TRB3 protein in saline buffer and better capacity of cellular uptake to A2 peptide. Furthermore, the TRB3‐targeting peptide nanofibers efficiently interfere with the aberrant TRB3/p62 PPIs in activated fibroblasts and fibrotic lung tissue of mice, thereby restoring autophagy dysfunction. The TRB3‐targeting peptide nanofibers inhibit myofibroblast differentiation, collagen production, and fibroblast migration in vitro is demonstrated, as well as bleomycin‐induced pulmonary fibrosis in vivo. This study provides a supramolecular method to modulate PPIs and highlights a promising strategy for treating IPF diseases by restoring autophagy.

Objective and rationale: The prevalence of depression among older adults residing in nursing homes has risen. While physical activity interventions based on the self-determination theory have been shown to reduce depressive symptoms among students and middle-aged adults, research in nursing home residents is scarce. This study aimed to investigate whether physical activity can alleviate depressive symptoms in nursing home residents over an extended period. Methods: Between September 2020 and August 2021, 46 nursing home residents in Shenyang were randomly assigned to either a control group (n = 23) or an intervention group (n = 23). The control group followed a standard physical activity programme, whereas the intervention group underwent a programme based on self-determination theory. Both groups were monitored for 24 weeks post-intervention. Depression scores were assessed using the Geriatric Depression Scale, sociodemographic data collected via a self-designed questionnaire, cognitive function evaluated using the Mini-Mental State Examination, and weight and body fat measured using the Omron KARADA Scan Body Composition and Scale. Results: Depression scores were measured at five time points: baseline (T0), weeks 12 (T1), and 24 (T2) of the intervention, and weeks 12 (T3) and 24 (T4) during follow-up. Both groups exhibited a trend of decline by more than five points. The intervention group demonstrated more favourable pre-to-post changes in depression scores compared to the control group. Conclusions: A physical activity intervention based on self-determination conceptual framework has been proven to be effective for nursing home residents with depressive symptoms, also aiding in the maintenance of their physical activity levels. This study offers a theoretical foundation for the development of intervention programmes by researchers and identifies potential intervention strategies for caregivers in nursing homes. Trial Registration: The Chinese Clinical Trial Registry (ChiCTR2200060598) (June 5, 2022).

BackgroundEpidemiological studies have shown that early-life nutritional deficiencies are associated with an increased risk of diseases later in life. This study aimed to explore the correlation between famine exposure during the early stages of life and cataracts.MethodsWe included 5,931 participants from the Chinese Longitudinal Healthy Longevity Survey (CLHLS) 2018 cross-sectional data in our study. Subjects were categorized into three groups by their age during the famine: adulthood group, school age famine exposure group, and teenage famine exposure group. Utilizing binary logistic regression models, we investigated the relationship between early-life famine exposure and cataracts.ResultsCompared to the adulthood group, both the school age exposure group (OR = 2.49, 95%CI = 1.89–3.27) and teenage exposure group (OR = 1.45, 95%CI = 1.20–1.76) had a heightened risk of developing cataracts in elderly stage. And the sex differences in the impact of famine during early years on elderly cataract risk were observed, particularly indicating a higher risk among women who experienced childhood famine compared to men with similar exposure.ConclusionFamine exposure during the early stages of life is associated with a heightened risk of developing cataracts in old age. To prevent cataracts in elderly individuals, particularly in females, measures should be taken to address nutritional deficiencies in these specific periods.

Psychological stress represents a prevalent societal concern, particularly evident during crises such as epidemics, which exacerbate various forms of psychological strain. Prompt mitigation of psychological stress holds potential for enhancing quality of life and fostering societal advancement. In this study, drawing inspiration from the International Emotion Picture Library, we crafted four virtual reality (VR) scenes augmented with five emblematic animals, resulting in 20 VR scenarios for psychological stress assessment. Fifteen participants engaged in the test, which was preceded by the completion of the World Health Organization Quality of Life Questionnaire (WHOQOL-BREF). Throughout the test, EEG and heart rate data were meticulously recorded. Following each scenario, participants completed the Self-Assessment Manikin (SAM) scale, culminating in the formation of the VR psychological stress reduction dataset. We meticulously analyze the SAM scale. For EEG data, we devised a deep learning model leveraging a hybrid CNN-LSTM architecture for signal classification. The model was evaluated on both the publicly available DEAP dataset and our collected DSRP dataset, yielding superior performance. Leveraging the dataset amassed in this study, we scrutinize the alleviative impact of VR on human psychological stress, providing foundational insights for VR-based psychological stress reduction research. Moreover, the EEG classification model proposed herein enhances the categorization of EEG signals, thereby advancing the domain of emotion recognition grounded in EEG technology.

Phenylalanine ammonia-lyase (PAL, EC 4.3.1.5) catalyzes the deamination of phenylalanine, which is the initial step in the biosynthesis of phenylpropanoids. It serves as a crucial enzyme that facilitates the transfer of carbon from primary to secondary metabolism in plants. Duckweed is regarded as a promising chassis plant in synthetic biology research and application, due to its being rich in secondary metabolites and other advantages. The genes encoding PAL in Spirodela polyrhiza (L.) Schleid, the giant duckweed, were investigated in this study. Three SpPAL genes (SpPAL1–SpPAL3) were identified and cloned. All of them were successfully expressed in E. coli, and their recombinant proteins all showed PAL activity. In addition, SpPAL1 and SpPAL2 proteins could also utilize tyrosine as substrate, although the activity was low. A qRT-PCR analysis demonstrated that the expression of SpPAL3 was most pronounced in young fronds. It was found that the expression of SpPAL1 and SpPAL3 was significantly induced by MeJA treatment. Overexpression of SpPAL3 in Lemna turionifera inhibited the growth of fronds and adventitious roots in the transgenic plants, indicating the importance of SpPAL3 in duckweed besides its involvement in the secondary metabolism.

ObjectiveTo understand the current status of self-regulatory fatigue among gynecologic cancer chemotherapy patients and explore influencing factorsMethodsUsing convenient sampling, a total of 232 gynecological cancer chemotherapy patients from two tertiary hospitals in Zhengzhou, Henan, China, were selected as study subjects from February 2023 to April 2023. General information questionnaire, Self-Regulatory Fatigue Scale (SRF-S), Strategies Used by People to Promote Health (SUPPH) Scale, Connor-Davidson resilience scale (CD-RISC) and Perceived Social Support Scale (PSSS) were employed for data collection. The data were analyzed using SPSS 26.0 software. Chi-square test and binary logistic regression were executed to explore the correlates of self-regulatory fatigue, the significance level (α) was set at 0.05.ResultsThe self-regulatory fatigue score of the 232 patients was 44 (36, 56). Binary logistic regression analyses revealed significant associations, demonstrating that residing in urban areas (OR=0.241, P=0.015), having no comorbidities (OR=0.158, P=0.015), increased perceived social support (OR=0.937, P=0.001), strong self-efficacy (OR=0.959, P=0.021), and heightened psychological resilience (OR=0.895, P

Summary: The gut must perform a dual role of protecting the host against toxins and pathogens while harboring mutualistic microbiota. Previous studies suggested that the NADPH oxidase Duox contributes to intestinal homeostasis in Drosophila by producing reactive oxygen species (ROS) in the gut that stimulate epithelial renewal. We find instead that the ROS generated by Duox in the Malpighian tubules leads to the production of Upd3, which enters the gut and stimulates stem cell proliferation. We describe in Drosophila the existence of a countercurrent flow system, which pushes tubule-derived Upd3 to the anterior part of the gut and stimulates epithelial renewal at a distance. Thus, our paper clarifies the role of Duox in gut homeostasis and describes the existence of retrograde fluid flow in the gut, collectively revealing a fascinating example of inter-organ communication.

Background: Sepsis is a life-threatening disease characterized by multiple organ failure due to excessive activation of the inflammatory response and cytokine storm. Despite recent advances in the clinical use of anti-cytokine biologics, sepsis treatment efficacy and improvements in mortality remain unsatisfactory, largely due to the mechanistic complexity of immune regulation and cytokine interactions.Methods: In this study, a broad-spectrum anti-inflammatory and endotoxin neutralization strategy was developed based on autologous “cryo-shocked” neutrophils (CS-Neus) for the management of sepsis. Neutrophils were frozen to death using a novel liquid nitrogen “cryo-shock” strategy. The CS-Neus retained the source cell membrane structure and functions related to inflammatory site targeting, broad-spectrum inflammatory cytokines, and endotoxin (LPS) neutralizing properties. This strategy aimed to disable harmful pro-inflammatory functions of neutrophils, such as cytokine secretion. Autologous cell-based therapy strategies were employed to avoid immune rejection and enhance treatment safety.Results: In both LPS-induced sepsis mouse models and clinical patient-derived blood samples, CS-Neus treatment significantly ameliorated cytokine storms by removing inflammatory cytokines and endotoxin. The therapy showed notable anti-inflammatory therapeutic effects and improved the survival rate of mice.Discussion: The results of this study demonstrate the potential of autologous “cryo-shocked” neutrophils as a promising therapeutic approach for managing sepsis. By targeting inflammatory organs and exhibiting anti-inflammatory activity, CS-Neus offer a novel strategy to combat the complexities of sepsis treatment. Further research and clinical trials are needed to validate the efficacy and safety of this approach in broader populations and settings.

Accurate identification of the source of water gushing in closed coal mines and correct division of water gushing modes are of great significance for scientific disposal of water resources waste and water environment pollution caused by closed coal mine drainage. A comprehensive method for water inflow characterization, source identification, and model research for closed coal mines by multivariate analysis of “water quantity–hydrochemistry–microorganism–hydrogeological conditions” is proposed. The method is based on the dynamic monitoring data of water inflow and the water chemical and microbial indexes of several closed coal mines in the Songzao mining area of Chongqing in a hydrological year. Water quality analysis methods, such as flow dynamic analysis of water inflow and flow–rainfall hydro-logical series correlation function, descriptive statistics of water chemical indexes, and the Pearson correla-tion function of water chemical indexes between mine water samples are also used as bases. The method is further coupled with the hydrogeological conditions of the mining area. Results show that there are three types of fluctuations in the response of water inflow from closed coal mines to rainfall: sudden rise and slow drop, slow rise and slow drop, and stable. The difference in water inflow source and water diversion medium is the main reason for the dynamic change in mine water inflow and the temporal and spatial differences in its response to rainfall. It also causes the characteristics of large variability in TDS, pH, chemical correlation degree, and microbial content of mine water. Based on water source identification, four types, rainfall infiltration type, aquifer release type, old empty water overflow type, and compound type, of water gushing modes of closed coal mines in mining areas are proposed. The multivariate comprehensive analysis method identifies the source of water inrush from closed coal mines in karst mining areas effectively, deepens the understanding of the characteristics of water inrush from closed coal mines, and provides theoretical support for the scientific prevention and control of closed coal mine water inrush in Songzao mining area and the coordinated development of environment and resources.

Abstract Background The TNM staging system cannot accurately predict the prognosis of postoperative gastric signet ring cell carcinoma (GSRC) given its unique biological behavior, epidemiological features, and various prognostic factors. Therefore, a reliable postoperative prognostic evaluation system for GSRC is required. This study aimed to establish a nomogram to predict the overall survival (OS) rate of postoperative patients with GSRC and validate it in the real world. Methods Clinical data of postoperative patients with GSRC from 2002 to 2014 were collected from the Surveillance, Epidemiology, and End Results database and randomly assigned to training and internal validation sets at a 7:3 ratio. The external validation set used data from 124 postoperative patients with GSRC who were admitted to the Affiliated Tumor Hospital of Harbin Medical University between 2002 and 2014. The independent risk factors affecting OS were screened using univariate and multivariate analyses to construct a nomogram. The performance of the model was evaluated using the C-index, receiver operating characteristic curve (ROC), calibration curve, decision analysis (DCA) curve, and adjuvant chemotherapy decision analysis. Results Univariate/multivariate analysis indicated that age, stage, T, M, regional nodes optimized (RNE), and lymph node metastasis rate (LNMR) were independent risk factors affecting prognosis. The C-indices of the training, internal validation, and external validation sets are 0.741, 0.741, and 0.786, respectively. The ROC curves for the first, third, and fifth years in three sets had higher areas under the curves, (training set, 0.782, 0.864, 0.883; internal validation set, 0.781, 0.863, 0.877; external validation set, 0.819, 0.863, 0.835). The calibration curve showed high consistency between the nomogram-predicted 1-, 3-, and 5-year OS and the actual OS in the three queues. The DCA curve indicated that applying the nomogram enhanced the net clinical benefits. The nomogram effectively distinguished patients in each subgroup into high- and low-risk groups. Adjuvant chemotherapy can significantly improve OS in high-risk group (P = 0.034), while the presence or absence of adjuvant chemotherapy in low-risk group has no significant impact on OS (P = 0.192). Conclusions The nomogram can effectively predict the OS of patients with GSRC and may help doctors make personalized prognostic judgments and clinical treatment decisions.

Ductile iron is a heterogeneous material. The presence of spherical graphite and a hard and brittle structure makes the surface of the workpiece easily form pits and crack defects under harsh grinding conditions, which seriously affects the service life and service performance of the workpiece. The new assisted grinding process based on the electroplastic effect is expected to avoid the surface defects of ductile iron. By comparing the surface roughness and microstructure of conventional grinding and electroplastic-assisted grinding, the superiority of electroplastic-assisted grinding surface quality is confirmed. Further discussion is presented on the impact of grinding parameters on the workpiece’s surface quality under the same electrical parameters. The results show that the sensitivity of surface roughness to grinding parameters from strong to weak is grinding wheel speed, feed speed and grinding depth. The optimal combination of grinding parameters is determined as a grinding wheel speed of 30 m/s, a feed speed of 0.5 m/min and a grinding depth of 10 μm.

Dicranopteris dichotoma is a pioneer herbaceous plant species that is tolerant to barrenness and drought. Mapping its biomass spatial distribution is valuable for understanding its important role in reducing soil erosion and restoring ecosystems. This research selected Luodihe watershed in Changting County, Fujian Province, China, where soil erosion has been a severe problem for a long time, as a case study to explore the method to estimate biomass, including total and aboveground biomass, through the integration of field measurements, handheld laser scanning (HLS), and airborne laser scanning (ALS) data. A stepwise regression model and an allometric equation form model were used to develop biomass estimation models based on Lidar-derived variables at typical areas and at a regional scale. The results indicate that at typical areas, both total and aboveground biomass were best estimated using an allometric equation form model when HLS-derived height and density variables were extracted from a window size of 6 m × 6 m, with the coefficients of determination (R2) of 0.64 and 0.58 and relative root mean square error (rRMSE) of 28.2% and 35.8%, respectively. When connecting HLS-estimated biomass with ALS-derived variables at a regional scale, total and aboveground biomass were effectively predicted with rRMSE values of 17.68% and 17.91%, respectively. The HLS data played an important role in linking field measurements and ALS data. This research provides a valuable method to map Dicranopteris biomass distribution using ALS data when other remotely sensed data cannot effectively estimate the understory vegetation biomass. The estimated biomass spatial pattern will be helpful to understand the role of Dicranopteris in reducing soil erosion and improving the degraded ecosystem.

Glioblastoma multiforme, a highly aggressive and lethal brain tumor, is a substantial clinical challenge and a focus of increasing concern globally. Hematological toxicity and drug resistance of first-line drugs underscore the necessity for new anti-glioma drug development. Here, 43 anthracenyl skeleton compounds as p53 activator XI-011 analogs were designed, synthesized, and evaluated for their cytotoxic effects. Five compounds (13d, 13e, 14a, 14b, and 14n) exhibited good anti-glioma activity against U87 cells, with IC50 values lower than 2 μM. Notably, 13e showed the best anti-glioma activity, with an IC50 value up to 0.53 μM, providing a promising lead compound for new anti-glioma drug development. Mechanistic analyses showed that 13e suppressed the MDM4 protein expression, upregulated the p53 protein level, and induced cell cycle arrest at G2/M phase and apoptosis based on Western blot and flow cytometry assays.

The main aim of this article is using the elementary method and the number of the solutions of some congruence equations modulo an odd prime $ p $, to study the calculating problem of the sixth power mean of one kind generalized two-term exponential sums, and give a sharp asymptotic formula for it.

Hepatocellular carcinoma is one of the leading cancers worldwide and is a potential consequence of fibrosis. Therefore, the identification of key cellular and molecular mechanisms involved in liver fibrosis is an important goal for the development of new strategies to control liver-related diseases. Here, single-cell RNA sequencing data (GSE136103 and GES181483) of clinical liver non-parenchymal cells were analyzed to identify cellular and molecular mechanisms of liver fibrosis. The proportion of endothelial subpopulations in cirrhotic livers was significantly higher than that in healthy livers. Gene ontology and gene set enrichment analysis of differentially expressed genes in the endothelial subgroups revealed that extracellular matrix (ECM)-related pathways were significantly enriched. Since anthrax toxin receptor 2 (ANTXR2) interacts with the ECM, the expression of ANTXR2 in the liver endothelium was analyzed. ANTXR2 expression in the liver endothelium of wild-type (WT) mice significantly decreased after a 4-time sequential injection of carbon tetrachloride (CCl4) to induce liver fibrosis. Next, conditional knockout mice selectively lacking Antxr2 in endothelial cells were generated. After endothelial-specific Antxr2 knockout mice were subjected to the CCl4 model, the degree of liver fibrosis in the knockout group was significantly more severe than that in the control group. In addition, ANTXR2 in human umbilical vein endothelial cells promoted matrix metalloproteinase 2 (MMP2) activation to degrade the ECM in vitro. Finally, endothelial-specific overexpression of Antxr2 alleviated the development of liver fibrosis following adeno-associated virus treatment. Collectively, these results suggested that endothelial ANTXR2 plays a protective role in liver fibrosis. This function of ANTXR2 may be achieved by promoting MMP2 activation to degrade the ECM.

Head pose estimation plays a pivotal role in various applications, including augmented reality and human–computer interaction within intelligent museum environments. Head pose estimation conventionally relies on hard labels. However, acquiring the “ground truth” through subjective means introduces an element of uncertainty into the labels for head pose estimation. The introduction of soft labels offers a potential remedy for this uncertainty. However, existing head pose estimation methods based on soft labels neglect the asymmetry of head pose. After careful observation, two types of asymmetry have been identified in human head pose: within angle and between angle asymmetry. Taking these two characteristics into account, we have devised a Double Asymmetric Distribution Learning (DADL) network model for the precise estimation of head pose angles. This model employs distinct soft label distribution mechanisms to capture within-angle and between-angle nuances in head pose variations. Thereby enhancing the interpretability, generalization capability, and classification accuracy of head pose estimation models. Extensive experiments were conducted on various widely recognized benchmarks, including the AFLW2000 and BIWI datasets. The results substantiate substantial advantages of our model over conventional approaches.

Abstract Background Renal fibrosis is the final development pathway and the most common pathological manifestation of chronic kidney disease. Epigenetic alteration is a significant intrinsic factor contributing to the development of renal fibrosis. SET domain‐containing 2 (SETD2) is the sole histone H3K36 trimethyltransferase, catalysing H3K36 trimethylation. There is evidence that SETD2‐mediated epigenetic alterations are implicated in many diseases. However, it is unclear what role SETD2 plays in the development of renal fibrosis. Methods Kidney tissues from mice as well as HK2 cells were used as research subjects. Clinical databases of patients with renal fibrosis were analysed to investigate whether SETD2 expression is reduced in the occurrence of renal fibrosis. SETD2 and Von Hippel–Lindau (VHL) double‐knockout mice were used to further investigate the role of SETD2 in renal fibrosis. Renal tubular epithelial cells isolated from mice were used for RNA sequencing and chromatin immunoprecipitation sequencing to search for molecular signalling pathways and key molecules leading to renal fibrosis in mice. Molecular and cell biology experiments were conducted to analyse and validate the role of SETD2 in the development of renal fibrosis. Finally, rescue experiments were performed to determine the molecular mechanism of SETD2 deficiency in the development of renal fibrosis. Results SETD2 deficiency leads to severe renal fibrosis in VHL‐deficient mice. Mechanically, SETD2 maintains the transcriptional level of Smad7, a negative feedback factor of the transforming growth factor‐β (TGF‐β)/Smad signalling pathway, thereby preventing the activation of the TGF‐β/Smad signalling pathway. Deletion of SETD2 leads to reduced Smad7 expression, which results in activation of the TGF‐β/Smad signalling pathway and ultimately renal fibrosis in the absence of VHL. Conclusions Our findings reveal the role of SETD2‐mediated H3K36me3 of Smad7 in regulating the TGF‐β/Smad signalling pathway in renal fibrogenesis and provide an innovative insight into SETD2 as a potential therapeutic target for the treatment of renal fibrosis.

BackgroundThe management of acne requires the consideration of its severity; however, a universally adopted evaluation system for clinical practice is lacking. Artificial intelligence (AI) evaluation systems hold the promise of enhancing the efficiency and reproducibility of assessments. Artificial intelligence (AI) evaluation systems offer the potential to enhance the efficiency and reproducibility of assessments in this domain. While the identification of skin lesions represents a crucial component of acne evaluation, existing AI systems often overlook lesion identification or fail to integrate it with severity assessment. This study aimed to develop an AI-powered acne grading system and compare its performance with physician image-based scoring.MethodsA total of 1,501 acne patients were included in the study, and standardized pictures were obtained using the VISIA system. The initial evaluation involved 40 stratified sampled frontal photos assessed by seven dermatologists. Subsequently, the three doctors with the highest inter-rater agreement annotated the remaining 1,461 images, which served as the dataset for the development of the AI system. The dataset was randomly divided into two groups: 276 images were allocated for training the acne lesion identification platform, and 1,185 images were used to assess the severity of acne.ResultsThe average precision of our model for skin lesion identification was 0.507 and the average recall was 0.775. The AI severity grading system achieved good agreement with the true label (linear weighted kappa = 0.652). After integrating the lesion identification results into the severity assessment with fixed weights and learnable weights, the kappa rose to 0.737 and 0.696, respectively, and the entire evaluation on a Linux workstation with a Tesla K40m GPU took less than 0.1s per picture.ConclusionThis study developed a system that detects various types of acne lesions and correlates them well with acne severity grading, and the good accuracy and efficiency make this approach potentially an effective clinical decision support tool.

The characteristics of post-cathode plasma maintained by a self-made DC short glow-discharge plasma generator with grid electrodes were measured by optical emission spectroscopy. The discharge existed in an abnormal glow discharge mode at a voltage of 250–400 V and a helium pressure of 3–15 Torr and a discharge gap of 3 mm. The results indicate that the intensity distribution of helium atom spectral lines in the post-cathode space differs from that in the post-anode space. The temperature of electron excitation in the post-cathode plasma reaches its peak of 1500–3000K at 5–6 mm from the grid cathode. The difference in the intensity distributions of helium atom spectral lines in the post-cathode and post-anode spaces is associated with electron generation mechanism in these cases.

Background and objective Osimertinib is a third-generation epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) capable of overcoming non-small cell lung cancer (NSCLC) with EGFR T790M mutation. Although the addition of bevacizumab to 1st generation EGFR-TKIs confers a significant improvement in progression-free survival (PFS) in treatment-naive EGFR mutant NSCLC patients, osimertinib plus bevacizumab combination failed to show prolongation in the phase 2 study WJOG8715L. Data of such combination in Chinese patients are still lacking. This study aimed to explore the efficacy of the addition of bevacizumab to osimertinib as second-line therapy in real-world data, and to evaluate the role of anti-angiogenesis plus osimertinib combination therapeutic strategies in pretreated Chinese NSCLC patients with acquired EGFR T790M mutation. Methods A total of 42 advanced NSCLC patients with acquired EGFR T790M mutation after prior EGFR-TKIs treatment were collected between January 2020 to August 2021, with 16 cases treated with osimertinib plus bevacizumab and 26 cases treated with osimertinib. The treatment effect of patients were analyzed. Results The objective response rate (ORR) in combination group and osimertinib group were 43.8% and 50.0% respectively (P=0.694). No statistically significant difference in median PFS (14.0 mon vs 13.0 mon, P=0.797) and overall survival (OS) (29.0 mon vs 26.0 mon, P=0.544) between the combination group and osimertinib group were observed. Prior history of bevacizumab was identified as an independent predictor of PFS (P=0.045) and OS (P=0.023). Conclusion Our study demonstrated that adding bevacizumab to osimertinib could not show advantages in PFS and OS in pretreated NSCLC patients harboring EGFR T790M-mutation.

Abstract Background Cervical cancer is the fourth most common cancer in women. Up to 99% of cervical cancer cases are associated with high-risk human papillomavirus (HPV). Sexual behavior is a direct risk factor for HPV infection, and sexually active college students, therefore, receive attention for HPV vaccination. At present, most Chinese studies lack of in-depth research on influencing factors, and are limited to cervical cancer, HPV, or HPV vaccine, without comprehensive consideration. This study investigated Chinese college students’ cervical cancer prevention and treatment knowledge level, and explored the influencing factors, and understood their willingness to receive HPV vaccination. The findings of this study will lay a foundation for promoting the early screening of cervical cancer and vaccination process. Methods A total of 800 college students from four universities in Zhengzhou, China were selected by multistage random sampling method. A self-administered questionnaire on the knowledge of cervical cancer prevention and treatment, and willingness to receive HPV vaccination was carried out. A logistic regression model was conducted to analyze factors influencing knowledge of cervical cancer prevention and treatment among college students. Results Up to 87.9% of college students said they had heard of cervical cancer. The proportion of college students with good knowledge of cervical cancer prevention and treatment was 46.7%. Logistic regression showed that gender, major, grade, level of education, the father's level of education, premarital sex attitude, and mother cervical cancer screening participation had a significant influence on cervical cancer prevention and treatment knowledge level (P

Abstract Background Complex epithelial neoplasms of the ovary (CENO), an uncommon pathological histotype in ovarian cancer, comprises adenosquamous carcinoma and adenocarcinoma with metaplasia. Owing to the rarity of relevant reports, there are currently no statistics on outcomes based on large samples. Meanwhile high-grade serous ovarian cancer (HGSOC) is the most common histotype in ovarian cancer which has a recognized first-line treatment regimen and poor prognosis. Thus, we aimed to determine the characteristics, prognosis, and independent predictors of survival for CENO, compare them with those of HGSOC and construct prognostic predictive models and nomograms. Methods We used the Surveillance, Epidemiology, and End Results (SEER) database to determine patients diagnosed with CENO or HGSOC from 2000 to 2017. Clinical, demographic, and treatment characteristics were compared between these groups. Propensity score matching, Cox risk regression analysis, Kaplan–Meier survival curves, and the Least Absolute Shrinkage and Selection Operator regression analysis were employed for analyzing the data. Results Here, 31,567 patients with HGSOC and 216 patients with CENO between 2000 and 2017 in the SEER database were enrolled. Age

BackgroundIt is critical to minimize nurse turnover to improve the quality of care and patient safety. In-depth investigation is required to better understand the factors related to nurses' turnover intentions.AimThis study aimed to determine the relationships between burnout, general wellbeing, and psychological detachment with turnover intention among nurses in China.MethodsA cross-sectional survey using convenience sampling was conducted in one hospital in China between January 2023 and March 2023. A total of 536 nurses were surveyed using the General Wellbeing Schedule (GWB), the Maslach Burnout Inventory scale (MBI), the Psychological Detachment scale, and the Turnover Intention scale. The collected data were analyzed using SPSS 26.0 statistical software. The chi-square test and binary logistic regression analysis were used to explore the factors related to turnover intention.ResultsOur data demonstrated that the turnover intention scores were 13 (10, 15.75), with 56% of nurses exhibiting a high level of turnover intention. Binary logistic regression analysis results indicated that being on a contract (OR = 4.385, 95% CI = 2.196–8.754), working in the pediatrics (OR = 2.392, 95% CI = 1.267–4.514) or obstetrics (OR = 2.423, 95% CI = 1.145–5.126) department, and experiencing burnout (OR = 1.024, 95% CI = 1.008–1.041) were associated with a heightened level of turnover intention. Conversely, organizational satisfaction (OR = 0.162, 95% CI = 0.033–0.787) and general wellbeing (OR = 0.967, 95% CI = 0.946–0.989) were identified as factors that hindered the intention to leave.ConclusionsFindings from this study suggest that nurses were employed on a contract basis, working in pediatric or obstetric departments, expressing dissatisfaction with the organization, reporting low general wellbeing, and experiencing high levels of burnout that require special attention. The identification of these risk factors can inform targeted interventions and support programs aimed at improving the wellbeing and retention of nurses in these settings.

Lung metastasis of breast cancer is closely associated with patient morbidity and mortality, which correlates with myeloid cells in the lung microenvironment. However, the heterogeneity and specificity of metastasis-associated myeloid cells have not been fully established in lung metastasis. Here, by integrating and analyzing single-cell transcriptomics, we found that myeloid subpopulations (Tppp3+ monocytes, Isg15+ macrophages, Ifit3+ neutrophils, and Il12b+ DCs) play critical roles in the formation and development of the metastatic niche. Gene enrichment analyses indicate that several tumor-promoting pathways should be responsible for the process, including angiogenesis (Anxa1 and Anxa2 by Tppp3+ monocytes), immunosuppression (Isg15 and Cxcl10 by Isg15+ macrophages; Il12b and Ccl22 by Il12b+ DCs), and tumor growth and metastasis (Isg15 and Isg20 by Ifit3+ neutrophils). Furthermore, we have validated these subpopulations in lung microenvironment of MMTV-PyVT transgenic mice and verified their association with poor progression of human breast cancer. Also, our results elucidated a crosstalk network among four myeloid subpopulations by cell-cell communication analysis. This study, therefore, highlights the crucial role of myeloid cells in lung metastasis and provides insights into underlying molecular mechanisms, which pave the way for therapeutic interventions in breast cancer metastasis to lung.

Background & Aims: Immune checkpoint inhibitors (ICIs) alone or in combination with other ICIs or vascular endothelial growth factor pathway inhibitors are therapeutic options in unresectable/metastatic hepatocellular carcinoma (HCC). Whether antibiotic (ATB) exposure affects outcome remains unclear. Methods: This study retrospectively analysed an FDA database including 4,098 patients receiving ICI (n = 842) either as monotherapy (n = 258) or in combination (n = 584), tyrosine kinase inhibitor (TKI) (n = 1,968), vascular endothelial growth factor pathway inhibitors (n = 480), or placebo (n = 808) as part of nine international clinical trials. Exposure to ATB within 30 days before or after treatment initiation was correlated with overall survival (OS) and progression-free survival (PFS) across therapeutic modality before and after inverse probability of treatment weighting (IPTW). Results: Of 4,098 patients with unresectable/metastatic HCC, of which 39% were of hepatitis B aetiology and 21% were of hepatitis C aetiology, 83% were males with a median age of 64 years (range 18–88), a European Collaborative Oncology Group performance status of 0 (60%), and Child–Pugh A class (98%). Overall, ATB exposure (n = 620, 15%) was associated with shorter median PFS (3.6 months in ATB-exposed vs. 4.2 months; hazard ratio [HR] 1.29; 95% CI 1.22, 1.36) and OS (8.7 months in ATB-exposed vs. 10.6 months; HR 1.36; 95% CI 1.29, 1.43). In IPTW analyses, ATB was associated with shorter PFS in patients treated with ICI (HR 1.52; 95% CI 1.34, 1.73), TKI (HR 1.29; 95% CI 1.19, 1.39), and placebo (HR 1.23; 95% CI 1.11, 1.37). Similar results were observed in IPTW analyses of OS in patients treated with ICI (HR 1.22; 95% CI 1.08, 1.38), TKI (HR 1.40; 95% CI 1.30, 1.52), and placebo (HR 1.40; 95% CI 1.25, 1.57). Conclusions: Unlike other malignancies where the detrimental effect of ATB may be more prominent in ICI recipients, ATB is associated with worse outcomes in this study across different therapies for HCC including placebo. Whether ATB is causally linked to worse outcomes through disruption of the gut–liver axis remains to be demonstrated in translational studies. Impact and Implications: A growing body of evidence suggests the host microbiome, frequently altered by antibiotic treatment, as an important outcome predictor in the context of immune checkpoint inhibitor therapy. In this study, we analysed the effects of early antibiotic exposure on outcomes in almost 4,100 patients with hepatocellular carcinoma treated within nine multicentre clinical trials. Interestingly, early exposure to antibiotic treatment was associated with worse outcomes not only in patients treated with immune checkpoint inhibitors but also in those treated with tyrosine kinase inhibitors and placebo. This is in contrast to data published in other malignancies, where the detrimental effect of antibiotic treatment may be more prominent in immune checkpoint inhibitor recipients, highlighting the uniqueness of hepatocellular carcinoma given the complex interplay between cirrhosis, cancer, risk of infection, and the pleiotropic effect of molecular therapies for this disease.

Introduction: We measure for the first time the associations between subjective patient experiences of feeling “high” and treatment outcomes during real-time Cannabis flower consumption sessions.Methods: Our study uses data from the mobile health app, Releaf App™, through which 1,882 people tracked the effects of Cannabis flower on a multitude of health conditions during 16,480 medical cannabis self-administration sessions recorded between 6/5/2016 and 3/11/2021. Session-level reported information included plant phenotypes, modes of administration, potencies, baseline and post-administration symptom intensity levels, total dose used, and real-time side effect experiences.Results: Patients reported feeling high in 49% of cannabis treatment sessions. Using individual patient-level fixed effects regression models and controlling for plant phenotype, consumption mode, tetrahydrocannabinol (THC) and cannabidiol (CBD) potencies, dose, and starting symptom level, our results show that, as compared to sessions in which individuals did not report feeling high, reporting feeling high was associated with a 7.7% decrease in symptom severity from a mean reduction of −3.82 on a 0 to 10 analog scale (coefficient = −0.295, p < 0.001) with evidence of a 14.4 percentage point increase (p < 0.001) in negative side effect reporting and a 4.4 percentage point (p < 0.01) increase in positive side effect reporting. Tetrahydrocannabinol (THC) levels and dose were the strongest statistical predictors of reporting feeling high, while the use of a vaporizer was the strongest inhibitor of feeling high. In symptom-specific models, the association between feeling high and symptom relief remained for people treating pain (p < 0.001), anxiety (p < 0.001), depression (p < 0.01) and fatigue (p < 0.01), but was insignificant, though still negative, for people treating insomnia. Although gender and pre-app cannabis experience did not appear to affect the relationship between high and symptom relief, the relationship was larger in magnitude and more statistically significant among patients aged 40 or less.Discussion: The study results suggest clinicians and policymakers should be aware that feeling high is associated with improved symptom relief but increased negative side effects, and factors such as mode of consumption, product potency, and dose can be used to adjust treatment outcomes for the individual patient.

High temperatures accelerate the accumulation of storage material in seeds, often leading to defects in grain filling. However, the mechanisms regulating grain filling at high temperatures remain unknown. Here, we want to explore the quality factors influenced by the environment and have identified a LATE EMBROYGENESIS ABUNDANT gene, OsLEA1b, a heat-stress-responsive gene in rice grain filling. OsLEA1b is highly expressed in the endosperm, and its coding protein localizes to the nucleus and cytoplasm. Knock-out mutants of OsLEA1b had abnormal compound starch granules in endosperm cells and chalky endosperm with significantly decreased grain weight and grain number per panicle. The oslea1b mutants exhibited a lower proportion of short starch chains with degrees of polymerization values from 6 to 13 and a higher proportion of chains with degrees from 14 to 48, as well as significantly lower contents of starch, protein, and lipid compared to the wild type. The difference was exacerbated under high temperature conditions. Moreover, OsLEA1b was induced by drought stress. The survival rate of oslea1b mutants decreased significantly under drought stress treatment, with significant increase in ROS levels. These results indicate that OsLEA1b regulates starch biosynthesis and influences rice grain quality, especially under high temperatures. This provides a valuable resource for genetic improvement in rice grain quality.

The main purpose of this paper is to study the calculating problem of one kind hybrid power mean involving the cubic Gauss sums and Kloosterman sums, and using the elementary methods, analytic methods and the properties of the classical Gauss sums to give some interesting calculating formula for them. At the same time, the paper also provides an effective calculating method for the study of the hybrid power mean involving the k-th Gauss sums and Kloosterman sums.

Abstract Background Kisspeptin is the leading upstream regulator of pulsatile and surge Gonadotrophin-Releasing Hormone secretion (GnRH) in the hypothalamus, which acts as the key governor of the hypothalamic-pituitary-ovary axis. Main text Exogenous kisspeptin or its receptor agonist can stimulate GnRH release and subsequent physiological gonadotropin secretion in humans. Based on the role of kisspeptin in the hypothalamus, a broad application of kisspeptin and its receptor agonist has been recently uncovered in humans, including central control of ovulation, oocyte maturation (particularly in women at a high risk of ovarian hyperstimulation syndrome), test for GnRH neuronal function, and gatekeepers of puberty onset. In addition, the kisspeptin analogs, such as TAK-448, showed promising agonistic activity in healthy women as well as in women with hypothalamic amenorrhoea or polycystic ovary syndrome. Conclusion More clinical trials should focus on the therapeutic effect of kisspeptin, its receptor agonist and antagonist in women with reproductive disorders, such as hypothalamic amenorrhoea, polycystic ovary syndrome, and endometriosis.

BackgroundIndividuals with autism spectrum disorder (ASD) often have different social characteristics and particular sensory processing patterns, and these sensory behaviors may affect their social functioning. The objective of our study is to investigate the sensory profiles of children with ASD and their association with social behavior. Specifically, we aim to identify the predictive role of sensory processing in social functioning.MethodsThe Short Sensory Profile (SSP) was utilized to analyze sensory differences between ASD children and their peers. The Social Responsiveness Scale (SRS) and other clinical scales were employed to assess the social functioning of children with ASD. Additionally, the predictive ability of sensory perception on social performance was discussed using random forest and support vector machine (SVM) models.ResultsThe SSP scores of ASD children were lower than those of the control group, and there was a significant negative correlation between SSP scores and clinical scale scores (P < 0.05). The random forest and SVM models, using all the features, showed higher sensitivity, while the random forest model with 7-feature factors had the highest specificity. The area under the receiver operating characteristic (ROC) curve (AUC) for all the models was higher than 0.8.ConclusionAutistic children in our study have different patterns of sensory processing than their peers, which are significantly related to their patterns of social functioning. Sensory features can serve as a good predictor of social functioning in individuals with ASD.

Background: One of the features of tumor immunity is the immunosuppressive tumor microenvironment (TME). In this study, TME gene signatures were used to define the characteristics of Cervical squamous cell carcinoma (CESC) immune subtypes and construct a new prognostic model.Methods: Single sample gene set enrichment analysis (ssGSEA) was used to quantify pathway activity. RNA-seq of 291 CESC were obtained from the Cancer Genome Atlas (TCGA) database as a training set. Microarray-based data of 400 cases of CESC were obtained from the Gene Expression Compilation (GEO) database as an independent validation set. 29 TME related gene signatures were consulted from previous study. Consensus Cluster Plus was employed to identify molecular subtype. Univariate cox regression analysis and random survival forest (RSF) were used to establish the immune-related gene risk model based on the TCGA data set of CESC, and the accuracy of prognosis prediction was verified by GEO data set. ESTIMATE algorithm was used to perform immune and matrix scores on the data set.Results: three molecular subtypes (C1, C2, C3) were screened in TCGA-CESC on account of 29 TME gene signatures. Among, C3 with better survival outcome had higher immune related gene signatures, while C1 with worse prognosis time had enhanced matrix related features. Increased immune infiltration, inhibition of tumor related pathways, widespread genomic mutations and prone immunotherapy were observed in C3. Furthermore, a five immune genes signature was constructed and predicted overall survival for CESC, which successfully validated in GSE44001 dataset. A positive phenomenon was observed between five hub genes expressions and methylation. Similarly, high group enriched in matrix related features, while immune related gene signatures were enriched in low group. Immune cell, immune checkpoints genes expression levels were negatively, while most TME gene signatures were positively correlated with Risk Score. In addition, high group was more sensitive to drug resistance.Conclusion: This work identified three distinct immune subtypes and a five genes signature for predicting prognosis in CESC patients, which provided a promising treatment strategy for CESC.

Objectives: We measure for the first time how commercially available Cannabis flower products affect feelings of fatigue. Methods: A total of 1,224 people recorded 3,922 Cannabis flower self-administration sessions between June 6, 2016, and August 7, 2019, using the Releaf App. Usage sessions included real-time subjective changes in fatigue intensity levels prior to and following Cannabis consumption, Cannabis flower characteristics (labeled phenotype, cannabinoid potency levels), combustion method, and any potential experienced side effects. Results: On average, 91.94% of people experienced decreased fatigue following consumption with an average symptom intensity reduction of 3.48 points on a 0–10 visual analog scale (SD = 2.70, d = 1.60, p < 0.001). While labeled plant phenotypes (“C. indica,” “C. sativa,” or “hybrid”) did not differ in symptom relief, people that used joints to combust the flower reported greater symptom relief than pipe or vaporizer users. Across cannabinoid levels, tetrahydrocannabinol, and cannabidiol levels were generally not associated with changes in symptom intensity levels. Cannabis use was associated with several negative side effects that correspond to increased feelings of fatigue (e.g., feeling unmotivated, couch-locked) among a minority of users (

BackgroundSmall cell carcinoma of ovary (SCCO) is a rare and aggressive cancer primarily reported in the form of case reports. Due to limited epidemiological and prognostic analyses based on large populations, SCCO has varied considerably without prognostic models and a recognized first-line treatment strategy. The study aimed to compare the clinical characteristics, treatment methods, and prognosis of SCCO and high-grade serous ovarian cancer (HGSOC), the most prevalent subtype of ovarian cancer, in a large sample and develop a predictive model for these two subtypes.MethodsData from the Surveillance, Epidemiology, and End Results program were analyzed for patients with SCCO or HGSOC from 2000 to 2017. Clinical, demographic, and treatment characteristics were compared between the two groups. Propensity-score matching, Cox risk regression analysis, and Kaplan-Meier survival curves were used to assess the data. Finally, a nomogram was developed to predict the patient survival time.ResultsA total of 32,185 women, including 31,979 (99.4%) diagnosed with HGSOC and 206 (0.6%) diagnosed with SCCO, were identified. Age ≤ 51 years, single, median house income less than $70,000, early stage, and unilateral disease were more common characteristics of patients with SCCO than those with HGSOC. Patients with SCCO were more likely to receive radiotherapy (6.8% vs. 0.8%, p

Research questionIs there an association between intrauterine hematoma (IUH), vanishing twin syndrome (VTS), and subsequent complications in twin pregnancies after in vitro fertilization (IVF)? What are the risk factors for these complications?DesignWomen who presented with two live gestational sacs following double embryo transfer were included. Patients with systematic diseases, artificial fetal reduction, and incomplete data were excluded. Further stratification of IUH pregnancies was performed according to IUH-related characteristics (i.e., volume, changing pattern, and relationship with fetal cardiac activities). The primary outcome was the incidence of VTS, while adverse outcomes in the surviving singleton and the gestational age of VTS were secondary outcomes.ResultsThe incidence of IUH was 13.8%. A total of 1,078 twin pregnancies including 539 IUH pregnancies and 539 non-IUH pregnancies were included. IUH pregnancy was associated with higher risks of VTS (26.9% vs. 18.7%, p = 0.001) as well as a higher incidence of preterm birth (p = 0.001, crude OR = 1.98, 95% CI 1.28–3.09, adjusted OR = 1.19, 95% CI 1.09–1.24), threatened abortion (p < 0.001, crude OR = 9.12, 95% CI 2.90–28.69, adjusted OR = 6.63, 95% CI 1.69–14.67), and postpartum hemorrhage (p = 0.024, crude OR = 3.13, 95% CI 1.09–8.99, adjusted OR = 1.16, 95% CI 1.08–1.32) in the surviving singleton. There was no significant difference in risks of other complications. The absence of fetal cardiac activities at the diagnosis of IUH predicted VTS (p < 0.001, crude OR 4.67, 95% CI 3.67–5.78, adjusted OR 3.33, 95% CI 1.56–5.14) and fetal loss at smaller gestational age (7.81 ± 2.10 vs. 11.39 ± 5.60 weeks, p < 0.001), while an IUH with an increasing volume did not increase the risk of VTS but might induce threatened abortion in the surviving fetus (p < 0.001, crude OR 1.84, 95% CI 1.32–2.55, adjusted OR 1.72, 95% CI 1.13–2.13).ConclusionsIUH was a risk factor for VTS in twin pregnancies following double embryo transfer and elevated the risks of threatened abortion, preterm birth, and postpartum hemorrhage in the surviving singleton. The absence of fetal cardiac activities at the diagnosis of IUH elevated the risks of VTS, while an IUH with an increasing volume was associated with threatened abortion without elevating the risks of VTS. An IUH diagnosed before the presence of fetal cardiac activities also resulted in an earlier miscarriage. The study suggests that attention be paid to twin pregnancies with first-trimester IUH to prevent VTS and subsequent adverse perinatal outcomes.HighlightsFirst-trimester intrauterine hematoma (IUH) following double embryo transfer is associated with a higher incidence of vanishing twin syndrome (VTS) and elevated subsequent risk of threatened abortion, preterm birth, and postpartum hemorrhage in the surviving singleton. Other perinatal outcomes were not associated with the diagnosis of first-trimester IUH. The absence of fetal cardiac activities at the diagnosis of IUH was of predictive value toward VTS, while an IUH with an increasing size was associated with threatened abortion without elevating the risk of VTS. Incomplete fetal cardiac activities and earlier detection of an IUH might also predict miscarriage at smaller gestational age.

Increasing evidence indicates that miRNAs play crucial regulatory roles in various physiological processes of insects, including systemic metabolism. However, the molecular mechanisms of how specific miRNAs regulate energy metabolic homeostasis remain largely unknown. In the present study, we found that an evolutionarily conserved miR-275/305 cluster was essential for maintaining energy metabolic homeostasis in response to dietary yeast stimulation in Bactrocera dorsalis. Depletion of miR-275 and miR-305 by the CRISPR/Cas9 system significantly reduced triglyceride and glycogen contents, elevated total sugar levels, and impaired flight capacity. Combined in vivo and in vitro experiments, we demonstrated that miR-275 and miR-305 can bind to the 3’UTR regions of SLC2A1 and GLIS2 to repress their expression, respectively. RNAi-mediated knockdown of these two genes partially rescued metabolic phenotypes caused by inhibiting miR-275 and miR-305. Furthermore, we further illustrated that the miR-275/305 cluster acting as a regulator of the metabolic axis was controlled by the insulin signaling pathway. In conclusion, our work combined genetic and physiological approaches to clarify the molecular mechanism of metabolic homeostasis in response to different dietary stimulations and provided a reference for deciphering the potential targets of physiologically important miRNAs in a non-model organism. Author summary Metabolic homeostasis is critical for the fundamental physiological processes of organisms, and its dysregulation leads to severe metabolic and physiological diseases, such as obesity and insulin resistance. miRNA is a type of endogenous non-coding RNA that participates in multiple biological processes directly or indirectly. In the present study, we found the involvement of the miR-275/305 cluster in energy metabolism in female B. dorsalis and revealed the related post-transcriptional regulatory mechanisms. The miR-275/305 cluster expression positively responded to dietary yeast stimulation, and its knockdown had a profound impact on the triglyceride, glycogen, and glucose metabolisms at the adult stage of B. dorsalis. Furthermore, we uncovered that the miR-275/305 cluster mainly functions through negatively regulating the transcription of the SLC2A1/GLIS2, eventually ensuring normal metabolic physiology. Further, this miRNA-target axis was under the control of the conserved insulin signaling pathway. Therefore, our findings provide novel insight into the molecular basis of the metabolic adaptation to nutrient availability in B. dorsalis.

Introduction: Renal interstitial fibrosis is a common pathophysiological change in the chronic kidney disease (CKD). Nicotinamide adenine dinucleotide (NAD)-dependent deacetylase sirtuin 6 (SIRT6) is demonstrated to protect against kidney injury. Vitamin B3 is the mostly used form of NAD precursors. However, the role of SIRT6 overexpression in renal interstitial fibrosis of CKD and the association between dietary vitamin B3 intake and renal function remain to be elucidated.Methods: Wild-type (WT) and SIRT6-transgene (SIRT6-Tg) mice were given with high-adenine diets to establish CKD model. HK2 cells were exposed to transforming growth factor β1 (TGF-β1) in vitro to explore related mechanism. Population data from Multi-Ethnic Study of Atherosclerosis (MESA) was used to examine the association between dietary vitamin B3 intake and renal function decline.Results: Compared to WT mice, SIRT6-Tg mice exhibited alleviated renal interstitial fibrosis as evidenced by reduced collagen deposit, collagen I and α-smooth muscle actin expression. Renal function was also improved in SIRT6-Tg mice. Homeodomain interacting protein kinase 2 (HIPK2) was induced during the fibrogenesis in CKD, while HIPK2 was downregulated after SIRT6 overexpression. Further assay in vitro confirmed that SIRT6 depletion exacerbated epithelial-to-mesenchymal transition of HK2 cells, which might be linked with HIPK2 upregulation. HIPK2 was inhibited by SIRT6 in the post-transcriptional level. Population study indicated that higher dietary vitamin B3 intake was independently correlated with a lower risk of estimate glomerular filtration rate decline in those ≥65 years old during follow-up.Conclusion: SIRT6/HIPK2 axis serves as a promising target of renal interstitial fibrosis in CKD. Dietary vitamin B3 intake is beneficial for renal function in the old people.

The Little Ice Age (LIA) during the Ming and Qing dynasties was the most abnormal climate event in China for nearly 2,000 years. During this period, the climate was relatively cold and various natural disasters frequently took place. By locating and compiling related historical documents, we aimed to quantitatively and systematically analyze the spatial–temporal variations in the natural disasters in the ancient Huizhou region (hereinafter referred to as Huizhou region or Huizhou) during the Ming and Qing dynasties (1368–1911; all dates are in AD, unless otherwise mentioned). The results show that (1) flood and drought disasters, the major types of disasters in this area during the Ming and Qing dynasties, occurred 422 times, accounting for 79.6% of the natural disasters, (2) there was a significant correlation of occurrence frequency of flood plus drought disasters and the total natural disasters on a certain time scale. In addition to flood and drought disasters, other disasters (hailstorms, windstorms, frosts, and earthquakes) occurred more frequently in the Qing dynasty (1644–1911) than in the Ming dynasty (1368–1644). The occurrence frequency of natural disasters had a fluctuant variation pattern over time, with peaks emerging about once a century. The peaks of natural disasters were mainly concentrated at 1471–1490, 1571–1590, 1671–1690, 1751–1770, and 1851–1870, which is supported by the wavelet analysis, (3) the most frequent natural disasters took place in Wuyuan, followed by Jixi, Shexian, Xiuning, Qimen, and Yixian. More droughts occurred in Jixi and Yixian, while more floods occurred in Wuyuan, Shexian, and Qimen, more hailstorms occurred in Wuyuan and Jixi, more frost disasters occurred in Wuyuan, Jixi, and Qimen, and more earthquakes occurred in Wuyuan and Jixi. The occurrence frequency of wind disasters was not high in any of the counties, (4) flood and drought disasters in the Huizhou region exhibited obvious stage characteristics during the Ming and Qing dynasties, and they changed gradually from droughts to floods, among which the transition from slight drought to slight flooding was the most obvious during 1811–1911, and (5) overall, slight flooding and slight drought situations accounted for the largest percentage of drought and flood disasters in this area during the Ming and Qing dynasties. Among these, slight flooding mainly occurred in Shexian and Qimen; severe flooding mainly occurred in Wuyuan; slight drought mainly occurred in Yixian; and severe drought mainly occurred in Jixi.

The composition of gut microbiota is not a static state in humans but fluctuates in response to changes in environments, diet, and lifestyle factors. Here, we explored differences in gut microbiota between populations worked offshore and onshore and further studied microbiota-associated variables in offshore workers (OFWs). We investigated the gut microbiota of 168 healthy subjects (offshore: 145 and onshore: 23) using 16S rRNA sequencing. Our results indicated that the marine environment caused significant changes in intestinal microbial structure, which was mainly reflected in the increase in bacterial diversity, changes in composition, and the emergence of more specific bacteria in OFWs. In addition, characteristics of gut microbiota in OFWs were further explored, and the genus Holdemanella was considered a potential contributor to the stable state of health. Besides, some dietary factors, namely, duck, mutton, dairy products, and algae vegetables were identified as the gut microbial covariates in the OFWs cohort and were positively correlated with the genus Holdemanella. This suggests the positive intervention of diet on Holdemanella. Our data highlight, for the first time to our knowledge, that the marine geographical environment plays an important role in shaping the gut mycobiome composition. And diet could be considered as the targeted intervention that alters the composition of the microbiome to improve host health.

Recent research has unveiled the critical roles of self-efficacy and buoyancy in teachers' work engagement. However, there has been limited research on the intricate links between teacher self-efficacy, buoyancy and engagement in the online English as a foreign language (EFL) teaching context. To address the underexplored relationships among these variables, the current study adopted a quantitative approach to verify the direct and indirect paths from online EFL teacher self-efficacy to engagement via the mediating effect of teacher buoyancy. We invited 978 Chinese high school EFL teachers to take part in the current study and answer questions about their self-efficacy, buoyancy and work engagement. The results of the structural equation modelling indicate that teacher self-efficacy could directly and indirectly predict online EFL teacher work engagement via the mediation of teacher buoyancy. The results of this study shed light on ways of improving EFL teachers' online teaching experience and educational outcomes.

Abstract Background Duckweed is considered a promising feedstock for bioethanol production due to its high biomass and starch production. The starch content can be promoted by plant growth regulators after the vegetative reproduction being inhibited. Maleic hydrazide (MH) has been reported to inhibit plant growth, meantime to increase biomass and starch content in some plants. However, the molecular explanation on the mechanism of MH action is still unclear. Results To know the effect and action mode of MH on the growth and starch accumulation in Spirodela polyrrhiza 7498, the plants were treated with different concentrations of MH. Our results showed a substantial inhibition of the growth in both fronds and roots, and increase in starch contents of plants after MH treatment. And with 75 µg/mL MH treatment and on the 8th day of the experiment, starch content was the highest, about 40 mg/g fresh weight, which is about 20-fold higher than the control. The I2-KI staining and TEM results confirmed that 75 µg/mL MH-treated fronds possessed more starch and big starch granules than that of the control. No significant difference for both in the photosynthetic pigment content and the chlorophyll fluorescence parameters of PII was found. Differentially expressed transcripts were analyzed in S. polyrrhiza 7498 after 75 µg/mL MH treatment. The results showed that the expression of some genes related to auxin response reaction was down-regulated; while, expression of some genes involved in carbon fixation, C4 pathway of photosynthesis, starch biosynthesis and ABA signal transduction pathway was up-regulated. Conclusion The results provide novel insights into the underlying mechanisms of growth inhibition and starch accumulation by MH treatment, and provide a selective way for the improvement of starch production in duckweed.

In order to reveal the change law of permeability of high-temperature granite under thermal shock, the permeability of granite specimens at different temperatures was investigated under four cooling conditions: natural cooling in air and thermal shock cooling in water (20 ℃, 60 ℃, 100 ℃). The change rule was analyzed, and the thermal shock damage at different cooling temperatures was quantitatively characterized with the help of the 'thermal shock factor'. The research results show that the increase in the permeability of specimen under thermal shock is exponentially related to the increase in rock temperature; cooling medium and the temperature difference between high-temperature rocks and the convective heat transfer coefficient together affect the rate of heat exchange during thermal shock process and then affect the result of thermal shock damage; the thermal shock factor can be used as a physical quantity to measure thermal shock damage ability; and the penetration of granite after thermal shock damage increases monotonously with the thermal shock factor to a threshold, after which the permeability of specimen increases greatly with the increase of the thermal shock factor.

Increasing evidence shows that lncRNAs, an important kind of endogenous regulator, are involved in the regulation of follicular development and female fertility, but the mechanism remain largely unknown. In this study, we found that SDNOR, a recently identified antiapoptotic lncRNA, is a potential multifunctional regulator in porcine follicular granulosa cells (GCs) through RNA-seq and multi-dimension analyses. SDNOR-mediated regulatory networks were established and identified that SOX9, a transcription factor inhibited by SDNOR, mediates SDNOR’s regulation of the transcription of downstream targets. Functional analyses showed that loss of SDNOR significantly impairs GC morphology, inhibits cell proliferation and viability, reduces E2/P4 index, and suppresses the expression of crucial markers, including PCNA, Ki67, CDK2, CYP11A1, CYP19A1, and StAR. Additionally, after the detection of ROS, SOD, GSH-Px, and MDA, we found that SDNOR elevates the resistance of GCs to oxidative stress (OS) and also inhibits OS-induced apoptosis. Notably, GCs with high SDNOR levels are insensitive to oxidative stress, leading to lower apoptosis rates and higher environmental adaptability. In summary, our findings reveal the regulation of porcine GCs in response to oxidative stress from the perspective of lncRNA and demonstrate that SDNOR is an essential antioxidative lncRNA for maintaining the normal state and function of GCs.

Insects face immune challenges posed by invading and indigenous bacteria. They rely on the immune system to clear these microorganisms. However, the immune response can be harmful to the host. Therefore, fine-tuning the immune response to maintain tissue homeostasis is of great importance to the survival of insects. The Nub gene of the OCT/POU family regulates the intestinal IMD pathway. However, the role of the Nub gene in regulating host microbiota remains unstudied. Here, a combination of bioinformatic tools, RNA interference, and qPCR methods were adopted to study BdNub gene function in Bactrocera dorsalis gut immune system. It’s found that BdNubX1, BdNubX2, and antimicrobial peptides (AMPs), including Diptcin (Dpt), Cecropin (Cec), AttcinA (Att A), AttcinB (Att B) and AttcinC (Att C) are significantly up-regulated in Tephritidae fruit fly Bactrocera dorsalis after gut infection. Silencing BdNubX1 leads to down-regulated AMPs expression, while BdNubX2 RNAi leads to increased expression of AMPs. These results indicate that BdNubX1 is a positive regulatory gene of the IMD pathway, while BdNubX2 negatively regulates IMD pathway activity. Further studies also revealed that BdNubX1 and BdNubX2 are associated with gut microbiota composition, possibly through regulation of IMD pathway activity. Our results prove that the Nub gene is evolutionarily conserved and participates in maintaining gut microbiota homeostasis.

Immune checkpoint inhibitor (ICI) has been proven to be a major breakthrough in the treatment of various tumor types. Despite the favorable results in terms of oncological outcomes, these treatments have been associated with a variety of immune-related adverse events (irAEs). Myasthenia gravis (MG) is one of rare but life-threatening irAEs, with acute onset and rapid progression after ICI initiation. Early diagnosis and active treatment are crucial. Herein, we review recent literatures to provide guidance to frequently asked questions concerning the diagnosis and management of ICI-MG.

Abstract Background The incidence of ductal carcinoma in situ (DCIS) has increased substantially since the introduction of mammography screening. Nevertheless, little is known about the natural history of preclinical DCIS in the absence of biopsy or complete excision. Methods Two well-established population models evaluated six possible DCIS natural history submodels. The submodels assumed 30%, 50%, or 80% of breast lesions progress from undetectable DCIS to preclinical screen-detectable DCIS; each model additionally allowed or prohibited DCIS regression. Preclinical screen-detectable DCIS could also progress to clinical DCIS or invasive breast cancer (IBC). Applying US population screening dissemination patterns, the models projected age-specific DCIS and IBC incidence that were compared to Surveillance, Epidemiology, and End Results data. Models estimated mean sojourn time (MST) in the preclinical screen-detectable DCIS state, overdiagnosis, and the risk of progression from preclinical screen-detectable DCIS. Results Without biopsy and surgical excision, the majority of DCIS (64–100%) in the preclinical screen-detectable state progressed to IBC in submodels assuming no DCIS regression (36–100% in submodels allowing for DCIS regression). DCIS overdiagnosis differed substantially between models and submodels, 3.1–65.8%. IBC overdiagnosis ranged 1.3–2.4%. Submodels assuming DCIS regression resulted in a higher DCIS overdiagnosis than submodels without DCIS regression. MST for progressive DCIS varied between 0.2 and 2.5 years. Conclusions Our findings suggest that the majority of screen-detectable but unbiopsied preclinical DCIS lesions progress to IBC and that the MST is relatively short. Nevertheless, due to the heterogeneity of DCIS, more research is needed to understand the progression of DCIS by grades and molecular subtypes.