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Abstract Background Gender equality and the gender income gap in medicine are long-standing global problems. Although gender-related differences have been widely studied in developed countries, they remain unclear in underdeveloped regions. In 2010, China initiated a national compulsory service program (CSP) to train qualified general practitioners in rural and remote areas. This study aimed to evaluate gender income differences for early career CSP and non-CSP (NCSP) graduates in underdeveloped areas. Methods A cohort study was conducted with 3620 CSP and NCSP graduates from four medical universities in Central and Western China. Baseline surveys and six follow-up surveys were conducted between 2015 and 2022. Incomes, including monthly mean income and proportion of performance-based income, were measured as the key outcome variables. Multivariate linear regression models were used to identify the gender income gap. Results NCSP graduates had higher average monthly incomes than CSP graduates. In the seventh year after graduation, the average monthly income for NCSP graduates was 7859 CNY while was 5379 CNY for CSP graduates. After controlling for demographic characteristics, the gender monthly income gap for CSP graduates was expanded from the fourth year (3.0%) to the sixth year (5.9%) after graduation, and that for NCSP graduates was expanded from the fifth year (11.9%) to the seventh year (16.3%) after graduation. Regarding performance-based income, it was 58.9% for NCSP graduates and 45.8% for CSP graduates in the seventh year after graduation. After controlling for performance-based income proportion, the gender income gap was reduced from 5.9 to 4.0% in the sixth year after graduation for CSP graduates, and from 16.3 to 14.4% for NCSP graduates in the seventh year after graduation. Conclusion An extensive and ever-increasing gender income gap exists among young doctors in the early stages of their careers in underdeveloped areas of China. The high proportion of performance-based income among men is one of the main explanations for the observed difference. A more explicit compensation system must be established to enhance support for female health workers.

Abstract Epidermal growth factor receptor (EGFR) is reportedly overexpressed in most esophageal squamous cell carcinoma (ESCC) patients, but anti-EGFR treatments offer limited survival benefits. Our preclinical data showed the promising antitumor activity of afatinib in EGFR-overexpressing ESCC. This proof-of-concept, phase II trial assessed the efficacy and safety of afatinib in pretreated metastatic ESCC patients (n = 41) with EGFR overexpression (NCT03940976). The study met its primary endpoint, with a confirmed objective response rate (ORR) of 39% in 38 efficacy-evaluable patients and a median overall survival of 7.8 months, with a manageable toxicity profile. Transcriptome analysis of pretreatment tumors revealed that neurotrophic receptor tyrosine kinase 2 (NTRK2) was negatively associated with afatinib sensitivity and might serve as a predictive biomarker, irrespective of EGFR expression. Notably, knocking down or inhibiting NTRK2 sensitized ESCC cells to afatinib treatment. Our study provides novel findings on the molecular factors underlying afatinib resistance and indicates that afatinib has the potential to become an important treatment for metastatic ESCC patients.

Abstract Background Cryptosporidium parvum is an apicomplexan zoonotic parasite causing the diarrheal illness cryptosporidiosis in humans and animals. To invade the host intestinal epithelial cells, parasitic proteins expressed on the surface of sporozoites interact with host cells to facilitate the formation of parasitophorous vacuole for the parasite to reside and develop. The gp40 of C. parvum, named Cpgp40 and located on the surface of sporozoites, was proven to participate in the process of host cell invasion. Methods We utilized the purified Cpgp40 as a bait to obtain host cell proteins interacting with Cpgp40 through the glutathione S-transferase (GST) pull-down method. In vitro analysis, through bimolecular fluorescence complementation assay (BiFC) and coimmunoprecipitation (Co-IP), confirmed the solid interaction between Cpgp40 and ENO1. In addition, by using protein mutation and parasite infection rate analysis, it was demonstrated that ENO1 plays an important role in the C. parvum invasion of HCT-8 cells. Results To illustrate the functional activity of Cpgp40 interacting with host cells, we identified the alpha-enolase protein (ENO1) from HCT-8 cells, which showed direct interaction with Cpgp40. The mRNA level of ENO1 gene was significantly decreased at 3 and 24 h after C. parvum infection. Antibodies and siRNA specific to ENO1 showed the ability to neutralize C. parvum infection in vitro, which indicated the participation of ENO1 during the parasite invasion of HCT-8 cells. In addition, we further demonstrated that ENO1 protein was involved in the regulation of cytoplasmic matrix of HCT-8 cells during C. parvum invasion. Functional study of the protein mutation illustrated that ENO1 was also required for the endogenous development of C. parvum. Conclusions In this study, we utilized the purified Cpgp40 as a bait to obtain host cell proteins ENO1 interacting with Cpgp40. Functional studies illustrated that the host cell protein ENO1 was involved in the regulation of tight junction and adherent junction proteins during C. parvum invasion and was required for endogenous development of C. parvum. Graphical Abstract

Abstract DNA methylation (5mC) is a repressive gene regulatory mark widespread in vertebrate genomes, yet the developmental dynamics in which 5mC patterns are established vary across species. While mammals undergo two rounds of global 5mC erasure, teleosts, for example, exhibit localized maternal-to-paternal 5mC remodeling. Here, we studied 5mC dynamics during the embryonic development of sea lamprey, a jawless vertebrate which occupies a critical phylogenetic position as the sister group of the jawed vertebrates. We employed 5mC quantification in lamprey embryos and tissues, and discovered large-scale maternal-to-paternal epigenome remodeling that affects ~30% of the embryonic genome and is predominantly associated with partially methylated domains. We further demonstrate that sequences eliminated during programmed genome rearrangement (PGR), are hypermethylated in sperm prior to the onset of PGR. Our study thus unveils important insights into the evolutionary origins of vertebrate 5mC reprogramming, and how this process might participate in diverse developmental strategies.

The aim of this study was to evaluate the mutation spectrum of homologous recombination repair (HRR) genes and its association with tumor immune infiltration and prognosis in triple-negative breast cancer (TNBC). TNBC patients (434 patients from Ruijin cohort) were evaluated with targeted next-generating sequencing for mutations in HRR genes. The frequencies of mutations were compared with public reference cohorts (320 TNBC patients from METABRIC, 105 from TCGA, and 225 from MSKCC 2018). Associations between mutation status and tumor immune infiltration and prognosis were analyzed. HRR genes mutations were seen in 21.89% patients, with BRCA1/2 mutations significantly enriched in tumors with breast/ovarian cancer family history (P = 0.025) and high Ki-67 levels (P = 0.018). HRR genes mutations were not related with recurrence-free survival (RFS) (adjusted P = 0.070) and overall survival (OS) (adjusted P = 0.318) for TNBC patients, regardless of carboplatin treatment (P > 0.05). Moreover, tumor immune infiltration and PD-L1 expression was positively associated with HRR or BRCA1/2 mutation (all P < 0.001). Patients with both HRR mutation and high CD8+ T cell counts had the best RFS and OS, whereas patients with no HRR mutation and low CD8+ T cell counts had the worst outcomes (RFS P < 0.001, OS P = 0.019). High frequency of HRR gene mutations was found in early TNBC, with no prognostic significance. Immune infiltration and PD-L1 expression was positively associated with HRR mutation, and both HRR mutation and high CD8+ T cell infiltration levels were associated with superior disease outcome.

Objectives The aim of this study was to assess the quality of tuberculosis (TB) care for the whole course and assess factors that affect completing treatment.Design This is an observational retrospective study using chart abstraction for the whole course of TB care conducted at two underserved provinces in China.Setting The study was conducted from June 2021 to July 2021. All medical records (outpatient and inpatient) for the whole course (6–8 months) of patients with TB newly registered from July 2020 to December 2020 were reviewed and abstracted using predetermined checklists.Participants A total of 268 outpatient medical records and 126 inpatient records were included.Primary and secondary outcome measures The primary outcome included diagnostic quality, treatment quality and management quality. The secondary outcome was completing treatment.Results For diagnostic quality, 94.2% of the diagnosis were based on adequate evidence. For treatment quality, 240 (91.6%) outpatients and 100 (85.5%) inpatients took the standard chemotherapy regimens. 234 (87.3%) patients completed treatment. 85.1% of the inpatients prescribed with second-line drugs were inappropriate. For management quality, 128 (47.9%) patients received midterm assessments, but only 47 (19.7%) received sufficient services for the whole course. Patients with TB symptoms were 1.8 times more likely to complete treatment (p=0.011).Conclusion Patients with TB received high-quality diagnosis and treatment services, but low-quality whole-course management. Integration of medical and public health services should be strengthened to improve whole-course quality.

Diabetic kidney disease (DKD) is one of the chronic microvascular complications caused by diabetes, which is characterized by persistent albuminuria and/or progressive decline of estimated glomerular filtration rate (eGFR), and has been the major cause of dialysis around the world. At present, although the treatments for DKD including lifestyle modification, glycemic control and even using of Sodium-glucose cotransporter 2 (SGLT2) inhibitors can relieve kidney damage caused to a certain extent, there is still a lack of effective treatment schemes that can prevent DKD progressing to ESRD. It is urgent to find new complementary and effective therapeutic agents. Growing animal researches have shown that mitophagy makes a great difference to the pathogenesis of DKD, therefore, exploration of new drugs that target the restoration of mitophagy maybe a potential perspective treatment for DKD. The use of Chinese botanical drugs (CBD) has been identified to be an effective treatment option for DKD. There is growing concern on the molecular mechanism of CBD for treatment of DKD by regulating mitophagy. In this review, we highlight the current findings regarding the function of mitophagy in the pathological damages and progression of DKD and summarize the contributions of CBD that ameliorate renal injuries in DKD by interfering with mitophagy, which will help us further explain the mechanism of CBD in treatment for DKD and explore potential therapeutic strategies for DKD.

Accurate wind power prediction helps to stabilize the operation of the power system, improve the utilization rate of renewable energy, reduce dependence on traditional energy, and achieve sustainable energy development. An ultra short-term wind power prediction method integrating EMD-EncoderForest-TCN is proposed to address the difficulty of predicting wind power due to frequent changes in wind speed. Firstly, the time-series input data of the model is decomposed into high-frequency and low-frequency components using Empirical Mode Decomposition. Then, based on the EncoderForest model and TCN model, differential information extraction is performed on the low-frequency and high-frequency components. The EncoderForest model regularizes low-frequency information and captures trend patterns in the data. The TCN model models the high-frequency components of time series to capture complex patterns and structures in wind power. Finally, based on convolutional neural networks, the output results of each part are calculated to achieve accurate prediction of wind power. Based on the operational data of an actual wind farm, conduct a case study analysis. The results show that the proposed model can achieve accurate prediction of short-term wind power, with a prediction accuracy improvement of 2.57%.

Abstract Motivated by the unexplored potential of in vitro neural systems for computing and by the corresponding need of versatile, scalable interfaces for multimodal interaction, an accurate, modular, fully customizable, and portable recording/stimulation solution that can be easily fabricated, robustly operated, and broadly disseminated is presented. This approach entails a reconfigurable platform that works across multiple industry standards and that enables a complete signal chain, from neural substrates sampled through micro‐electrode arrays (MEAs) to data acquisition, downstream analysis, and cloud storage. Built‐in modularity supports the seamless integration of electrical/optical stimulation and fluidic interfaces. Custom MEA fabrication leverages maskless photolithography, favoring the rapid prototyping of a variety of configurations, spatial topologies, and constitutive materials. Through a dedicated analysis and management software suite, the utility and robustness of this system are demonstrated across neural cultures and applications, including embryonic stem cell‐derived and primary neurons, organotypic brain slices, 3D engineered tissue mimics, concurrent calcium imaging, and long‐term recording. Overall, this technology, termed “mind in vitro” to underscore the computing inspiration, provides an end‐to‐end solution that can be widely deployed due to its affordable (>10× cost reduction) and open‐source nature, catering to the expanding needs of both conventional and unconventional electrophysiology.

The tumor-associated macrophages (TAM) play a crucial role in lung adenocarcinoma (LUAD), which can cause the proliferation, migration and invasion of tumor cells. In particular, TAMs mainly regulate changes in the tumor microenvironment thereby contributing to tumorigenesis and progression. Recently, an increasing number of studies are using single-cell RNA (Sc-RNA) sequencing to investigate changes in the composition and transcriptomics of the tumor microenvironment. We obtained Sc-RNA sequencing data of LUAD from GEO database and transcriptome data with clinical information of LUAD patients from TCGA database. A group of important genes in the state transition of TAMs was identified by analyzing TAMs at the single-cell level, while 5 TAM-related prognostic genes were obtained by omics data integration, and a prognostic model was constructed. GOBP analysis revealed that TAM-related genes were mainly enriched in tumor-promoting and immunosuppression-related pathways. After ROC analysis, it was found that the AUC of the prognosis model reached 0.751, with well predictive effectiveness. The 5 unique genes, HLA-DMB, HMGN3, ID3, PEBP1, and TUBA1B, was finally identified through synthesized analysis. The transcriptional characteristics of 5 genes were determined through GEPIA2 database and RT-qPCR. The increased expression of TUBA1B in advanced LUAD may serve as a prognostic indicator, while low expression of PEBP1 in LUAD may have the potential to become a therapeutic target.

Electricity is the lifeblood of modern society. However, the predominant source of electricity generation still relies on non-renewable fossil fuels, whose combustion releases greenhouse gases contributing to global warming. The increasing demand for energy and escalating environmental concerns necessitate proactive measures to develop innovative green energy technologies capable of both cooling the Earth and generating electricity. Here, we look forward to an interdisciplinary power system integrating solar absorbers, radiative coolers, and thermoelectric generators. This system can simultaneously harvest thermal energy from the sun and from cold space, thereby transforming the challenges posed by global warming into opportunities for the production of clean electricity. We underscore recent advancements in this field and address key challenges while also exploring forward-looking opportunities in the foreseeable future. The proposed integrated energy technology achieves uninterrupted power supply through the unrestricted capture of thermal energy, offering a robust alternative pathway for next-generation sustainable energy technologies.

Helicobacter pylori infection is associated with the risk of gastrointestinal (GI) cancers; however, its impact on immunotherapy for GI cancers remains uncertain. In this study, we included 10,122 patients who underwent 13C-urea breath tests. Among 636 patients with Epstein-Barr virus–negative microsatellite-stable gastric cancer (GC) who were treated with anti-PD-1/PD-L1 therapy, H. pylori–positive patients exhibited significantly longer immune-related progression-free survival (irPFS) compared with H. pylori–negative patients (6.97 months versus 5.03 months, p

Summary: Background: Although the antibody–drug conjugates (ADCs) have significantly improved the survival outcomes of patients with human epidermal receptor 2 (HER2)-expressing gastric or gastroesophageal junction (G/GEJ) cancer, the efficacy of ADC used as a single agent is limited. Therefore, it is necessary to investigate effective and safe combination regimens. Preclinical data indicated a synergetic antitumour effect of RC48 and programmed cell death protein 1 (PD-1) inhibitors. We aimed to evaluate the safety and efficacy of RC48 plus toripalimab in patients with HER2-expressing G/GEJ cancer and other solid tumours. Methods: This was a open-label, multicentre, phase 1 trial performed at three hospitals in China. Eligible patients had advanced G/GEJ cancer or other solid tumours with HER2 IHC≥1 or ISH positivity and were refractory to at least one line of treatment, or standard treatment was intolerable or unavailable for these patients. This study followed a “3 + 3” design with predefined RC48 dosages of 2.0 mg/kg and 2.5 mg/kg plus toripalimab 3 mg/kg, once every 2 weeks (q2w). The primary objectives were to evaluate the safety and determine the recommended phase II dose (RP2D), and the secondary objectives included assessing the pharmacokinetics (PK) and preliminary efficacy. This study was registered with ClinicalTrials.gov, NCT04280341. Findings: Between July 13, 2020 and August 30, 2022, 56 patients, including 30 patients with G/GEJ cancer and 26 patients with other solid tumours, were enrolled and received RC48 plus toripalimab (n = 7 for RC48 2.0 mg/kg, toripalimab 3 mg/kg, q2w; n = 49 for RC48 2.5 mg/kg, toripalimab 3 mg/kg, q2w). No dose-limiting toxic effects occurred. The RP2D was declared as RC48 2.5 mg/kg plus toripalimab 3 mg/kg, q2w. The most common grade 3 adverse events were a decreased neutrophil count (n = 13), and a decreased white blood cell count (n = 7). The efficacy assessment was completed for 52 patients. Among patients with G/GEJ cancer (n = 30), the confirmed objective response rate (ORR) was 43% (12/28, 95% CI 25, 63), median progression-free survival (PFS) was 6.2 months (95% CI 4.0, 6.9), median overall survival (OS) was 16.8 months (95% CI 7.2, NE). The ORR of patients with G/GEJ cancer receiving RP2D (n = 24) reached 50% (11/22, 95% CI 28, 72), with median PFS of 5.1 months (95% CI 1.4, 7.3) and median OS of 14.0 months (95% CI 6.3, NE). Among patients with G/GEJ cancer who received RP2D, a clinical benefit was observed in both HER2-positive and low HER2 expressing populations, with an ORR of 56% (5/9, 95% CI 21, 86) vs. 46% (6/13, 95% CI 19, 75), median PFS of 7.8 months (95% CI 0.9, NE) vs. 5.1 months (95% CI 1.2, 6.9), median OS of NE months (95% CI 4.3, NE) vs. 14.0 months (95% CI 5.1, NE), respectively. Antitumour activity was also observed for other solid tumours, including breast cancer (5/13) and endometrial carcinoma (1/1). Interpretation: Our findings suggested that RC48 plus toripalimab had a manageable safety profile and showed encouraging efficacy in pretreated patients with HER2-positive and low HER2-expressing G/GEJ cancer. The findings of our phase 1 clinical trial support further investigation of HER2-targeted ADC plus immunotherapy in HER2-expressing G/GEJ cancer and pancancer treatment in the future. Funding: Beijing Municipal Medical Research Institutes, Beijing Medical Research Institute (Z200015).

Bisphenol A (BPA) is easily enriched in many human-disturbed watersheds, particularly lakes with poor water mobility, which is posing a threat to aquatic biota. While previous studies have focused on the concentration of BPA in water and its toxicity to aquatic organisms, a small amount of measured data is not enough to reveal the temporal and spatial distribution and threats of BPA, and estimate the ecological risk in watersheds. Therefore, we collected 164 measured BPA data points from Taihu Lake to develop machine learning models using random forest (RF), support vector machine (SVM) and least square regression (LSR) and created month-by-month watershed prediction maps in temperate lakes to estimate the spatiotemporal distribution and threats of BPA. Due to RF's superior robustness to noisy data, the RF model exhibits the best performance among the three algorithms. The RF model showed acceptable predictive performance on the modeling dataset (coefficients of determination and root-mean-square error for the training set were 0.927 and 17.499, respectively, and 0.607, 39.645 for the validation set, respectively). The maps indicated that areas susceptible to anthropogenic activities were more severely polluted by BPA, and rainy climate may favor the migration of BPA to aquatic ecosystems. The model was also applied to predict 42 data points of BPA collected from Dianchi Lake, and the results showed that most predicted data were within a factor of 10 of the measured data, but the prediction accuracy of the model has declined. The ecological risks in the two lakes were evaluated and attention should be paid to the regions with higher risks. Our study provided a novel idea for comprehensive monitoring of an unconventional trace pollutant with endocrine disrupting effects in aquatic ecosystems and analyzing their spatiotemporal distribution, which will contribute to the scientific assessment of the ecological risk of BPA.

This paper thoroughly examines the time distribution, author collaboration, research institutions, research hotspots, theme clustering, and research changes and trends based on 345 CNKI literatures in the field of blended learning for Business English majors in China from 2012 to 2022. It reveals that: Research on blended learning for Business English majors in China from 2012 to 2022 can be divided into Steady Start Stage (2012–2017), Rapid Growth Stage (2018–2020) and Stable Development Stage (2021–2022). High-frequency keywords such as blended teaching mode, MOOC, flipped classroom, SPOC, etc. are hotspots of current scholars' attention. The themes of research on blended learning of business English majors in China mainly include Teaching Reform of Business English Majors, Exploration of Blended Teaching Mode and Design, and Application of Internet Teaching Platform. “Teaching Reform”, “Online and Offline”, “Application of Smart Platform” are the current research frontier issues in the development of blended learning for Business English majors in China. In general, China's research on blended learning for business English majors has achieved fruitful results under China's policies. Future research should concentrate on the construction of a technology environment for blended learning between learners, a variety of intelligent learning tools and mobile devices, and should be steadily bolstered in the field of blended learning for business English majors, particularly in practical application, effectiveness analysis, distance education, training and continuing education, innovation education, etc.

Initial public offerings and mergers and acquisitions represent important opportunities for investors to exit and harvest their entrepreneurial success. Some firms are acquired shortly after their initial public offerings. This exit strategy is known as a double exit. In addition, issuing firms may choose to reincorporate in Delaware during their IPOs. In this study, we use hand-collected data from 1993 to 2020 to investigate whether and to what extent Delaware reincorporation may affect the M&As in the post-IPO stage. We use a Cox proportional hazard model to test the relation between Delaware reincorporation and the likelihood of being acquired for our sample IPOs. Recognizing that Delaware reincorporation is not a random decision, we adopt a Heckman switching regression method to estimate the relation between Delaware reincorporation and takeover premiums and announcement returns. We report that IPO firms choosing to reincorporate in Delaware experience a higher likelihood of being acquired compared to those IPO firms choosing to remain incorporated in their home states. We further document that IPO firms choosing to reincorporate in Delaware receive lower premiums in acquisitions, and experience lower abnormal returns on announcements.

With the acceleration of transportation infrastructure and the densification of transportation networks, there has been an increase in bridge pile construction near oil and gas pipelines. Selecting bridge pile construction methods with minimal impact and reducing the adverse effects of bridge pile construction on nearby oil and gas pipelines are of great importance. This paper uses FLAC3D 6.0 software to simulate and analyze the impact of two different pile construction methods, rotary drilling and impact drilling, on adjacent oil pipelines. The results show that the horizontal displacement of oil pipelines during rotary drilling construction is nearly 90% lower than that of the traditional impact drilling method, and the axial stress is reduced by nearly 85%. Furthermore, numerical simulations of rotary drilling under different conditions were conducted to analyze and summarize the patterns of how different conditions affect construction vibration and stress. This study provides a reference for bridge pile construction near oil and gas pipelines or important buildings.

Insulin-like growth factors (IGFs) play central roles in the growth and development of vertebrates. Blotched snakehead (Channa maculata), an economically significant fish, exhibits obvious sexual dimorphism and achieves sexual maturity in one year. However, the role of IGFs in C. maculata remains unknown. Three IGF genes were identified in C. maculata, designated as CmIGF1-1, CmIGF1-2, and CmIGF2. The cDNA sequences of these genes are 1184, 655, and 695 bp, encoding putative proteins of 168, 131, and 215 amino acids, respectively, and all three proteins contain a conserved IGF domain. Quantitative real-time PCR (qPCR) revealed the predominant expression of CmIGFs in the liver of adult fish, with higher expression levels observed in males. Notably, CmIGF1-1, CmIGF1-2, and CmIGF2 displayed analogous expression profiles in the liver across various developmental stages, peaking at 365 days after hatching (dah). Subsequently, 600 individuals at 75 dah, at an early developmental stage, were randomly divided equally into six groups and reared in aerated 2 m × 2 m × 2 m cement ponds at 26.0 ± 1.0 °C. Following a one-week acclimatization period, fish without observed abnormalities were intraperitoneally injected with either 17α-ethynylestradiol (EE2) or 17α-methyltestosterone (MT) at a dose of 10 μg/g body weight. Three groups underwent short-term hormone treatment, and the remaining three groups underwent long-term hormone treatment, which included five injections at two-week intervals over ten weeks. The analysis of CmIGFs expression levels in the liver under different hormone treatments revealed that EE2 suppressed the expression of CmIGF1-1 and CmIGF1-2 while promoting CmIGF2 expression. In females, MT up-regulated the expression of CmIGF1-1 and CmIGF2 in a time-dependent manner, but consistently inhibited CmIGF2 expression. In males, MT promoted the expression of CmIGFs in a time-dependent manner, reaching peak levels for CmIGF1-1, CmIGF1-2, and CmIGF2 after 8, 10, and 2 weeks of injection, respectively. Additionally, CmIGF1 and CmIGF2 might exhibit a complementary relationship, with a compensatory increase in CmIGF2 expression in response to low CmIGF1 concentration. These findings highlight the potential key role of IGFs upon growth and their regulation by sex steroid hormones in C. maculata, providing a crucial foundation for future research aimed at elucidating the molecular mechanisms underlying the growth dimorphism between female and male blotched snakeheads.

Figla is one of the earliest expressed genes in the oocyte during ovarian development. In this study, Figla was characterized in C. maculata, one of the main aquaculture species in China, and designated as CmFigla. The length of CmFigla cDNA was 1303 bp, encoding 197 amino acids that contained a conserved bHLH domain. CmFigla revealed a female-biased expression patterns in the gonads of adult fish, and CmFigla expression was far higher in ovaries than that in testes at all gonadal development stages, especially at 60~180 days post-fertilization (dpf). Furthermore, a noteworthy inverse relationship was observed between CmFigla expression and the methylation of its promoter in the adult gonads. Gonads at 90 dpf were used for in situ hybridization (ISH), and CmFigla transcripts were mainly concentrated in oogonia and the primary oocytes in ovaries, but undetectable in the testes. These results indicated that Figla would play vital roles in the ovarian development in C. maculata. Additionally, the frame-shift mutations of CmFigla were successfully constructed through the CRISPR/Cas9 system, which established a positive foundation for further investigation on the role of Figla in the ovarian development of C. maculata. Our study provides valuable clues for exploring the regulatory mechanism of Figla in the fish ovarian development and maintenance, which would be useful for the sex control and reproduction of fish in aquaculture.

Despite the rising awareness that mobile technologies can be used as viable options for additional support for intercultural learning, few studies have been conducted to explore the feasibility of using mobile apps to develop intercultural competence (IC) from the perspectives of learners' acceptance and user experiences. This study applied a mixed-method approach to investigate factors affecting university students' acceptance of using mobile apps to develop their IC. Quantitative survey data were collected from 671 Chinese university students using measures developed based on the extended technology acceptance model. The results of structural equation modeling indicated that students' perceived usefulness (PU) of mobile apps supporting IC development positively influenced their mobile application efficacy, subjective norms, and perceived enjoyment. Additionally, their perceived ease of use (PEU) concerning the apps was positively associated with their mobile application efficacy, perceived enjoyment, and previous experiences, while being negatively associated with mobile application anxiety. PU and PEU were also found to be positively related to students' attitudes towards and behavioral intention to use apps for intercultural learning. Qualitative interviews were subsequently conducted with six students to investigate the underlying reasons for the predictors identified quantitatively following their actual use of three recommended apps over three consecutive weeks. The results of content analysis uncovered a range of categories that provided further insights into the statistical findings. Implications of the findings were discussed in the context of technology-enhancing intercultural education.

Amidst the challenges posed by the Covid-19 pandemic, this study investigates the impact of Problem-based Language Learning (PBLL) using DingTalk on enhancing Business English Writing skills among Chinese undergraduates. Employing a mixed-method approach, the research involved two phases. In the quantitative phase, a twelve-week quasi-experimental study was conducted. The control group received traditional Business English Writing instruction, while the experimental group utilized the PBLL + DingTalk method. Analysis of pre-test and post-test scores using SPSS 27.0 revealed a significant improvement in the experimental group's writing abilities, with their post-test scores averaging 5.3275 points higher than the control group. In the qualitative phase, semi-structured interviews were conducted with students from the experimental group. Participants expressed high engagement, motivation, and satisfaction with the PBLL + DingTalk approach, highlighting its effectiveness in interactive problem-solving and technology integration. This study demonstrates the effectiveness of PBLL + DingTalk in improving Business English Writing skills among Chinese undergraduates, even during challenging circumstances like the Covid-19 pandemic. The combination of quantitative results and qualitative insights underscores its practical impact and relevance for language educators, emphasizing the importance of innovative teaching methods in adapting to evolving educational landscapes.

Culturally authentic literature is widely recognized for its efficacy in developing children's multicultural awareness and intercultural understanding. Through systematic examination and analysis of 53 Children's picture books featuring China and its culture published in North America, this study investigated the extent to which the selected books were culturally authentic, and how these books would exert their functions as multicultural literature for readers. The results revealed that most books portrayed cultural elements authentically, while a number of books contained incorrect, stereotyped or outdated information. The mismatch of some cultural elements in illustrations with the storylines was especially notable. The ways in which the selected books would play their roles as windows and mirrors for multicultural education, and the implications drawn for writers, illustrators, and publishers of multicultural children's books were discussed.

At present, safe and effective treatment drugs are urgently needed for diabetic kidney disease (DKD). Circulating protein biomarkers with causal genetic evidence represent promising drug targets, which provides an opportunity to identify new therapeutic targets. Summary data from two protein quantitative trait loci studies are presented, one involving 4,907 plasma proteins data from 35,559 individuals and the other encompassing 4,657 plasma proteins among 7,213 European Americans. Summary statistics for DKD were obtained from a large genome-wide association study (3,345 cases and 2,372 controls) and the FinnGen study (3,676 cases and 283,456 controls). Mendelian randomization (MR) analysis was conducted to examine the potential targets for DKD. The colocalization analysis was used to detect whether the potential proteins exist in the shared causal variants. To enhance the credibility of the results, external validation was conducted. Additionally, enrichment analysis, assessment of protein druggability, and the protein-protein interaction networks were used to further enrich the research findings. The proteome-wide MR analyses identified 21 blood proteins that may causally be associated with DKD. Colocalization analysis further supported a causal relationship between 12 proteins and DKD, with external validation confirming 4 of these proteins, and TGFBI was affirmed through two separate group data sets. These results indicate that targeting these four proteins could be a promising approach for treating DKD, andwarrant further clinical investigations. [ABSTRACT FROM AUTHOR]