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Abstract Background As online teaching gains prevalence in higher education, traditional face-to-face methods are encountering limitations in meeting the demands of medical ethics, the availability of experimental resources, and essential experimental conditions. Consequently, under the guidance of the BOPPPS (bridge-in, objective, preassessment, participatory learning, postassessment, summary) teaching model, the application of virtual simulation platform has become a new trend. The purpose of this study is to explore the effect of BOPPPS combined with virtual simulation experimental teaching on students’ scores and the evaluation of students’ participation, performance and teachers’ self-efficacy in preventive medicine experiment. Methods Students from Class 1 and Class 2 of 2019 preventive medicine major in Binzhou Medical University were selected as the research objects. The experimental group (class 2) (n = 51) received the teaching mode combined with BOPPPS and virtual simulation platform, while the control group (class 1) (n = 49) received the traditional experimental teaching method. After class, the experimental report scores, virtual simulation scores, students’ engagement scale (SES), Biggs questionnaires, and teachers’ sense of self-efficacy (TSES) questionnaires were analyzed. Results The experimental report results demonstrated a significant increase in the total score of the experimental group and the scores of each of the four individual experiments compared to the control group (P

Abstract This study aimed to elucidate the molecular mechanisms by which PLD2 controls apoptosis and edema in pancreatic cells via the Nrf2/NF-κB pathway. AR42J rat pancreatic cells were treated with 10 nM mitomycin to create an in vitro pancreatitis model (model group), with a control group receiving phosphate-buffered saline. Cells were transfected with a PLD2 overexpression plasmid using Lipofectamine 3000, forming the PLD2 overexpression group. PLD2 protein expression was assessed by Western blotting, and TNF-α, IL-6, and IL-10 levels were measured by RT-qPCR. Nrf2/NF-κB protein expressions were also analyzed. Apoptosis and necrosis were evaluated using Annexin V-FITC/PI staining and the LDH release test. Cell edema was assessed by cell volume, ion content, and membrane damage. Western blotting was used to analyze pan-apoptosis-related proteins. PLD2 expression was lower in the model group compared to controls (P

Abstract Background Different hormone receptor (HR) expression patterns have significant biological and therapeutic implications in patients with human epidermal growth factor receptor 2 (HER2)-positive breast cancer. However, the distinction between HR-positive /HER2-positive (HR+/HER2+) and HR-negative/HER2-positive (HR-/HER2+) subtypes remains unclear. Methods This retrospective study analyzed 828 patients with HER2-positive breast cancer at the First Affiliated Hospital of Xi’an Jiaotong University from 2012 to 2022. Baseline characteristics were compared by chi-square test. Survival outcomes were estimated by Kaplan-Meier method. Results In total, 56.3% (n = 466) had HR-positive and 43.7% (n = 362) had HR-negative disease. Comparatively, HR+/HER2 + breast cancers presented favorable clinicopathological features. At a median follow-up of 49 months, 199 disease-free survival (DFS) events and 99 deaths were observed. HR+/HER2 + patients had significantly better survival outcomes than HR-/HER2 + patients. HR-positive status was an independent protective factor for overall survival (OS) [P = 0.032; hazard ratio, 0.61; 95% confidence interval (CI), 0.39–0.96] and DFS (P = 0.001; hazard ratio, 0.61; 95% CI, 0.46–0.81). HR+/HER2 + patients were significantly less sensitive to neoadjuvant therapy than HR-/HER2 + patients. In the first-line treatment for HR+/HER2 + advanced breast cancer, receiving endocrine therapy significantly improved advanced-OS (P

Abstract Computer-aided diagnosis has been slow to develop in the field of oral ulcers. One of the major reasons for this is the lack of publicly available datasets. However, oral ulcers have cancerous lesions and their mortality rate is high. The ability to recognize oral ulcers at an early stage in a timely and effective manner is a very critical issue. In recent years, although there exists a small group of researchers working on these, the datasets are private. Therefore to address this challenge, in this paper a multi-tasking oral ulcer dataset (Autooral) containing two major tasks of lesion segmentation and classification is proposed and made publicly available. To the best of our knowledge, we are the first team to make publicly available an oral ulcer dataset with multi-tasking. In addition, we propose a novel modeling framework, HF-UNet, for segmenting oral ulcer lesion regions. Specifically, the proposed high-order focus interaction module (HFblock) performs acquisition of global properties and focus for acquisition of local properties through high-order attention. The proposed lesion localization module (LL-M) employs a novel hybrid sobel filter, which improves the recognition of ulcer edges. Experimental results on the proposed Autooral dataset show that our proposed HF-UNet segmentation of oral ulcers achieves a DSC value of about 0.80 and the inference memory occupies only 2029 MB. The proposed method guarantees a low running load while maintaining a high-performance segmentation capability. The proposed Autooral dataset and code are available from https://github.com/wurenkai/HF-UNet-and-Autooral-dataset .

Abstract Background Within the follicular fluid, extracellular vesicles (EVs) guide oocyte growth through their cargo microRNAs (miRNAs). Here, we investigated the role of EVs and their cargo miRNAs by linking the miRNAs found in EVs, derived from the fluid of an individual follicle, to the ability of its oocyte to become a blastocyst (competent) or not (non-competent). Methods Bovine antral follicles were dissected, categorized as small (2–4 mm) or large (5–8 mm) and the corresponding oocytes were subjected to individual maturation, fertilization and embryo culture to the blastocyst stage. Follicular fluid was pooled in 4 groups (4 replicates) based on follicle size and competence of the corresponding oocyte to produce a blastocyst. Follicular fluid-derived EVs were isolated, characterized, and subjected to miRNA-sequencing (Illumina Miseq) to assess differential expression (DE) in the 4 groups. Functional validation of the effect of miR-34c on embryo development was performed by supplementation of mimics and inhibitors during in vitro maturation (IVM). Results We identified 16 DE miRNAs linked to oocyte competence when follicular size was not considered. Within the large and small follicles, 46 DE miRNAs were driving blastocyst formation in each group. Comparison of EVs from competent small and large follicles revealed 90 DE miRNAs. Cell regulation, cell differentiation, cell cycle, and metabolic process regulation were the most enriched pathways targeted by the DE miRNAs from competent oocytes. We identified bta-miR-34c as the most abundant in follicular fluid containing competent oocytes. Supplementation of miR-34c mimic and inhibitor during IVM did not affect embryo development. However, blastocyst quality, as evidenced by higher cell numbers, was significantly improved following oocyte IVM in the presence of miR-34c mimics, while miR-34c inhibitors resulted in the opposite effect. Conclusion This study demonstrates the regulatory effect of miRNAs from follicular fluid-derived EVs on oocyte competence acquisition, providing a further basis for understanding the significance of miRNAs in oocyte maturation and embryonic development. Up-regulation of miR-34c in EVs from follicular fluid containing competent oocytes and the positive impact of miR-34c mimics added during IVM on the resulting blastocysts indicate its pivotal role in oocyte competence.

Dysbiosis of the intestinal microbiota is prevalent among patients with colorectal cancer (CRC). This study aims to explore the anticancer roles of the fecal microbiota in inhibiting the progression of colorectal cancer and possible mechanisms. The intestinal microbial dysbiosis in CRC mice was significantly ameliorated by fecal microbiota transplantation (FMT), as indicated by the restored ACE index and Shannon index. The diameter and number of cancerous foci were significantly decreased in CRC mice treated with FMT, along with the restoration of the intestinal mucosal structure and the lessening of the gland arrangement disorder. Key factors in oxidative stress (TXN1, TXNRD1, and HIF-1α); cell cycle regulators (IGF-1, BIRC5, CDK8, HDAC2, EGFR, and CTSL); and a critical transcription factor of the innate immune signal pathway (IRF5) were among the repressed oncogenic targets engaged in the FMT treatment of CRC. Correlation analysis revealed that their expressions were positively correlated with uncultured_bacterium_o_Mollicutes_RF39, Rikenellaceae_RC9_gut_group, and negatively correlated with Bacillus, Marvinbryantia, Roseburia, Angelakisella, Enterorhabdus, Bacteroides, Muribaculum, and genera of uncultured_bacterium_f_Eggerthellaceae, uncultured_bacterium_f_Xanthobacteraceae, Prevotellaceae_UCG-001, uncultured_bacterium_f_Erysipelotrichaceae, uncul-tured_bacterium_f_Lachnospiraceae, uncultured_bacterium_f_Ruminococcaceae, Eubacterium_coprostanoligenes_group, Ruminococcaceae_UCG-005, and uncultured_bacterium_f_Peptococcaceae. This study provides more evidence for the application of FMT in the clinical treatment of CRC.

We show how to prepare magnonic squeezed states in an optomagnomechanical system in which magnetostriction induced mechanical displacement couples to an optical cavity via radiation pressure. We discuss two scenarios depending on whether the magnomechanical coupling is linear or dispersive. We show that in both cases the strong mechanical squeezing obtained via two-tone driving of the optical cavity can be efficiently transferred to the magnon mode. In the linear coupling case, stationary magnon squeezing is achieved, while in the dispersive coupling case, a transient magnonic squeezed state is prepared in a two-step protocol. The proposed magnonic squeezed states find promising applications in quantum information processing and quantum sensing using magnons.

Background Neutrophil extracellular traps (NETs) are produced by polymorphonuclear neutrophils (PMNs) stimulated by interleukin-17 (IL-17) and tumor necrosis factor α (TNF-α). However, the level and role of NETs in oral lichen planus (OLP) remain poorly understood. Objective This study aimed to investigate the expression of NETs in OLP and explore the correlation between NETs and the levels of IL-17 and TNF-α. Methods The expression and distribution of NET-related proteins in tissue samples from each group were assessed using hematoxylin-eosin (HE) staining and immunofluorescence (IF). Additionally, the expression of NET-related proteins in peripheral blood samples from each group was evaluated using cell IF technique and fluorescence spectrophotometry. The relative formation level of NETs in each group was determined by fluorescence spectrophotometry via plasma co-culture. Furthermore, the levels of inflammatory cytokines IL-17 and TNF-α in plasma and culture supernatant were measured using enzyme-linked immunosorbent assay (ELISA). Results NET-related proteins were located in the subepithelial and lamina propria layers of OLP lesions. OLP had significantly higher expression of NET-related proteins in lesion tissues and peripheral blood compared to the healthy control (HC) group (p < 0.05). The rate of NETs formation in the erosive-stage OLP (EOLP) group was significantly higher than that in the HC group (p < 0.05), in contrast, no significant increase was observed in the non-erosive OLP (NEOLP) group (p > 0.05). Furthermore, the levels of IL-17 and TNF-α in the EOLP group were significantly elevated compared to those in the NEOLP group and HC group (p < 0.05), while the levels in the NEOLP group did not significantly differ from those in the HC group (p > 0.05). The rate of NETs formation showed a positive correlation with the levels of IL-17 and TNF-α in plasma. Conclusion The expression of NET-related proteins was upregulated in OLP lesion tissues and peripheral blood. Elevated levels of IL-17 and TNF-α in peripheral blood plasma positively correlated with the rate of NETs formation, suggesting that IL-17 and TNF-α mediate the formation of NETs in OLP patients, and may thereby contribute to the development of OLP.

Extracellular vesicles (EVs) contain microRNAs (miRNAs), which are important regulators of embryonic development. Nevertheless, little is known about the precise molecular processes controlling blastocyst development and quality. In a previous study, we identified bta-miR-665 as one of the miRNAs more abundantly present in extracellular vesicles of embryo-conditioned culture media of blastocysts compared to degenerate ones. Here, we investigated the effect and regulatory roles of bta-miR-665 in blastocyst development by supplementation of bta-miR-665 mimics or inhibitors to the culture media. Supplementation of bta-miR-665 mimics improved cleavage and blastocyst rate (P < 0.01), and blastocyst quality as indicated by increased inner cell mass rates and reduced apoptotic cell ratios (P < 0.01). Furthermore, supplementation of bta-miR-665 inhibitors had the opposite effect on these phenotypes. Low input transcriptome analysis and RT-qPCR revealed that bta-miR-665 acts on genes linked to microtubule formation and apoptosis/cell proliferation. These insights not only elucidate the important role of bta-miR-665 in embryo development, but also underscore its potential in improving reproductive efficiency in bovine embryo culture.

Abstract In this paper, we present a continuous-time algorithm with a dynamic event-triggered communication (DETC) mechanism for solving a class of distributed convex optimization problems that satisfy a metric subregularity condition. The proposed algorithm addresses the challenge of limited bandwidth in multi-agent systems by utilizing a continuous-time optimization approach with DETC. Furthermore, we prove that the distributed event-triggered algorithm converges exponentially to the optimal set, even without strong convexity conditions. Finally, we provide a comparison example to demonstrate the efficiency of our algorithm in communication resource-saving.

Abstract Flexible electro‐optical dual‐mode sensor fibers with capability of the perceiving and converting mechanical stimuli into digital‐visual signals show good prospects in smart human‐machine interaction interfaces. However, heavy mass, low stretchability, and lack of non‐contact sensing function seriously impede their practical application in wearable electronics. To address these challenges, a stretchable and self‐powered mechanoluminescent triboelectric nanogenerator fiber (MLTENGF) based on lightweight carbon nanotube fiber is successfully constructed. Taking advantage of their mechanoluminescent‐triboelectric synergistic effect, the well‐designed MLTENGF delivers an excellent enhancement electrical signal of 200% and an evident optical signal whether on land or underwater. More encouragingly, the MLTENGF device possesses outstanding stability with almost unchanged sensitivity after stretching for 200%. Furthermore, an extraordinary non‐contact sensing capability with a detection distance of up to 35 cm is achieved for the MLTENGF. As application demonstrations, MLTENGFs can be used for home security monitoring, intelligent zither, traffic vehicle collision avoidance, and underwater communication. Thus, this work accelerates the development of wearable electro‐optical textile electronics for smart human‐machine interaction interfaces.

Key Clinical Message Successful treatment by miniscrew‐assisted rapid expansion and clinical aligner therapy for an adult diagnosed with maxillary transverse deficiency (MTD) by clinical examinations and Yonsei transverse analysis. Abstract Adult orthodontic diagnosis and treatment with maxillary transverse deficiency (MTD) is challenging. Miniscrew‐assisted rapid palatal expansion (MARPE) is a fast and low‐risk method to expand the width of maxillary basal bone. This case report describes a 23‐year‐old female with mandible deviation and bilateral posterior teeth crossbite. She was diagnosed as MTD by the clinical examinations and Yonsei transverse analysis, and treated by the MARPE and clinical aligner therapy. After 26 months' treatment, cone‐beam computed tomography (CBCT) images showed that the width of maxillary basal bone increased by 3.8 mm, that of zygomatic arch and nasal bone increased by 1.0 and 1.9 mm, respectively, and the bilateral posterior teeth crossbite was corrected. Furthermore, the dental midline of lower arch was consistent with that of upper arch and face, the molars arrived Angle Class II and canines was Class I relationships, the profile was maintained, the facial asymmetry was improved. The results of seventeen‐month follow‐up showed that the effect of orthodontic treatment is very stable. This case report demonstrates that MARPE is the effective approach for patients with MTD and facial asymmetry, which provide the alternative for the treatment of similar cases.

Chlorinated polyfluorinated ether sulfonate, commercially known as F-53B, has been associated with adverse birth outcomes. However, the reproductive toxicology of F-53B on the placenta remains poorly understood. To address this gap, we examined the impact of F-53B on placental injury and its underlying molecular mechanisms in vivo. Pregnant C57BL/6 J female mice were randomly allocated to three groups: the control group, F-53B 0.8 µg/kg/day group, and F-53B 8 µg/kg/day group. After F-53B exposure through free drinking water from gestational day (GD) 0.5–14.5, the F-53B 8 µg/kg/day group exhibited significant increases in placental weights and distinctive histopathological alterations, including inflammatory cell infiltration, heightened syncytiotrophoblast knots, and a loosened trophoblastic basement membrane. Within the F-53B 8 µg/kg/day group, placental tissue exhibited increased apoptosis, as indicated by increased caspase3 activation. Furthermore, F-53B potentially induced the NF-κB signaling pathway activation through IκB-α phosphorylation. Subsequently, this activation upregulated the expression of inflammatory cytokines and components of the NLRP3 inflammasome, including activated caspase1, IL-1β, IL-18, and cleaved gasdermin D (GSDMD), ultimately leading to pyroptosis in the mouse placenta. Our findings reveal a pronounced inflammatory injury in the placenta due to F-53B exposure, suggesting potential reproductive toxicity at concentrations relevant to the human population. Further toxicological and epidemiological investigations are warranted to conclusively assess the reproductive health risks posed by F-53B.

Abstract Transfer RNA-derived small RNAs (tsRNAs) have been shown to be involved in early embryo development and repression of endogenous retroelements in embryos and stem cells. However, it is unknown whether tsRNAs also regulate embryo hatching. In this study, we mined the sequencing data of a previous experiment in which we demonstrated that the microRNA (miRNA) cargo of preimplantation embryonic extracellular vesicles (EVs) influences embryo development. We thus profiled the tsRNA cargo of EVs secreted by blastocysts and non-blastocysts. The majority of tsRNAs was identified as tRNA halves originating from the 5´ ends of tRNAs. Among the 148 differentially expressed tsRNAs, the 19 nt tRNA fragment (tRF) tDR-14:32-Glu-CTC-1 was found to be significantly up-regulated in EVs derived from non-blastocysts. RT-qPCR assays confirmed its significant up-regulation in non-blastocyst embryos and their conditioned medium compared to the blastocyst group (P

Abstract Background Fertility preservation treatment is increasingly essential for patients with apical endometrial hyperplasia (AEH) and early endometrial cancer (EEC) worldwide. Complete regression (CR) is the main endpoint of this treatment. Accurately predicting CR and implementing appropriate interventions during treatment are crucial for these patients. Methods We conducted a retrospective study involving 193 patients diagnosed with atypical AEH or EEC, enrolled from January 2012 to March 2022 at our center. We evaluated 24 clinical parameters as candidate predictors and employed LASSO regression to develop a prediction model for CR. Subsequently, a nomogram was constructed to predict CR after the treatment. We evaluated the performance of the nomogram using receiver operator characteristic (ROC) curve and decision curve analysis (DCA) to assess its predictive accuracy. Additionally, we employed cumulative curves to determine the CR rate among patients. Results Out of the 193 patients, 173 achieved CR after undergoing fertility preservation treatment. We categorized features with similar properties and provided a list of formulas based on their coefficients. The final model, named GLOBAL (including basic information, characteristics, blood pressure, glucose metabolism, lipid metabolism, immunohistochemistry, histological type, and medication), comprised eight variables identified using LASSO regression. A nomogram incorporating these eight risk factors was developed to predict CR. The GLOBAL model exhibited an AUC of 0.907 (95% CI 0.828–0.969). Calibration plots demonstrated a favorable agreement between the predicted probability by the GLOBAL model and actual observations in the cohort. The cumulative curve analysis revealed varying cumulative CR rates among patients in the eight subgroups. Categorized analysis demonstrated significant diversity in the effects of the GLOBAL model on CR among patients with different total points (p

Abstract Background Topical photodynamic therapy (PDT) has demonstrated encouraging results in the treatment of oral leukoplakia (OLK). However, data on the clinical efficacy of PDT in Chinese patients with OLK are still limited. Methods Fifty patients diagnosed with OLK were enrolled, including patients with various dysplastic tissues. All patients received topical PDT with 5-aminolevulinic acid (5-ALA) as a photosensitizer. Clinical efficacy was evaluated 4 weeks after treatment. Follow-up was performed every 3 months during the first year and every 6 months during the second year. Results The overall response rate was 68% (34/50): 12% (n = 6) complete and 56% (n = 28) partial responses. Aneuploidy was reduced in the patients with dysplastic lesions. Oral pain and local ulcers developed in 52% of the patients (n = 26). Patients with a long history of OLK including hyperplasia and dysplastic lesions, as well as those with non-homogenous lesions, were more likely to develop pain and ulcer. During follow-up, the recurrence rate of hyperplasia and dysplastic lesions was 32% (n = 16) and the malignant transformation rate of dysplastic lesions was 4% (n = 2). Lesions on the buccal mucosa were associated with recurrence (P = 0.044; OR: 0.108, 95% CI: 0.013–0.915). Conclusion Topical 5-ALA-mediated PDT is an effective treatment for OLK, particularly for homogenous leukoplakia, with few side effects. The buccal mucosa may be a protective factor that can reduce recurrence.

The sensitivity of the eye at night would lead to complete saturation of the eye during the day. Therefore, the sensitivity of the eye must be down-regulated during the day to maintain visual acuity. In the Drosophila eye, the opening of TRP and TRPL channels leads to an influx of Ca++ that triggers down-regulation of further responses to light, including the movement of the TRPL channel and Gα proteins out of signaling complexes found in actin-mediated microvillar extensions of the photoreceptor cells (the rhabdomere). The eye also exhibits a light entrained-circadian rhythm, and we have recently observed that one component of this rhythm (BDBT) becomes undetectable by antibodies after exposure to light even though immunoblot analyses still detect it in the eye. BDBT is necessary for normal circadian rhythms, and in several circadian and visual mutants this eye-specific oscillation of detection is lost. Many phototransduction signaling proteins (e.g., Rhodopsin, TRP channels and Gα) also become undetectable shortly after light exposure, most likely due to a light-induced compaction of the rhabdomeric microvilli. The circadian protein BDBT might be involved in light-induced changes in the rhabdomere, and if so this could indicate that circadian clocks contribute to the daily adaptations of the eye to light. Likewise, circadian oscillations of clock proteins are observed in photoreceptors of the mammalian eye and produce a circadian oscillation in the ERG. Disruption of circadian rhythms in the eyes of mammals causes neurodegeneration in the eye, demonstrating the importance of the rhythms for normal eye function.

Abstract Background To compared the clinical efficacy of two surgical methods, posterior laminectomy fusion fixation, and posterior single open-door laminoplasty, in treating multilevel cervical ossification of the posterior longitudinal ligament (OPLL). Methods The study retrospectively included 102 patients treated between December 2016 and December 2020. The patients were included into an observation group (56 cases) treated with total laminectomy and lateral screw fixation, and a control group (46 cases) treated with single open-door laminoplasty. Results After 24 months, both groups showed significant improvement in Japanese Orthopaedic Association (JOA) scores and Visual Analogue Scale (VAS) scores, indicating better clinical symptoms and functional recovery. There was no significant difference in preoperative JOA and VAS scores between the two groups (P > 0.05). At 24 months after surgery, there was no significant difference in JOA and VAS scores between the two groups (P > 0.05). However, the observation group had a significantly higher cervical curvature index (CCI) and lower range of motion (ROM) of the cervical spine compared to the control group (P

The Pan-Third Pole region comprises multiple nations affected by climate vulnerability and energy inequality, wherein promoting energy transitions in rural households would provide a path to combat climate change. Identifying the factors that drive rural household energy consumption and the transition is important. This study performed a micro-survey of 1060 rural households in five countries in the Pan-Third Pole region and empirically analyzed the relationships between off-farm income, energy consumption, and energy transitions. The off-farm income of rural households was found to have a significantly positive effect (p