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Abstract Panax japonicus, an endangered species in China, is usually used as a traditional medicine with functions of hemostasis, pain relief, and detoxify. However, the seeds of P. japonicus are hard to germinate in natural conditions, and the molecular events and systematic changes occurring in seed germination are still largely unknown. In this study, we compared the seeds in different germination stages in terms of morphological features, antioxidant enzyme activities, and transcriptomics. The results indicated that sand storage at 25℃ for 120 d effectively released the seed dormancy of P. japonicus and promoted the seed germination. Moreover, sand storage treatment increased the antioxidant capacity of P. japonicus seeds through increasing the activities of SOD, POD, and CAT. The RNA-seq identified 28,908 differentially expressed genes (DEGs) between different germination stages, of which 1697 DEGs significantly changed throughout the whole germination process. Functional annotations showed that the seed germination of P. japonicus was mainly regulated by the DEGs related to pathways of ROS-scavenging metabolism, plant hormonal signal transduction, starch and sucrose metabolism, energy supply (glycolysis, pyruvate metabolism, and oxidative phosphorylation), and phenylpropanoid biosynthesis, as well as the transcription factors such as bHLHs, MYBs, WRKYs, and bZIPs. This study provides a foundation for unveiling molecular mechanisms underlying the seed germination and is beneficial for accelerating the development of P. japonicus industry.

Abstract For the clinical diagnosis of diseases and for basic biological research, it is crucial to develop a trustworthy and efficient method for detecting small extracellular vesicles (sEVs) in multiple experimental conditions. Here, we create a colorimetric assay that enables sensitive and precise sEVs identification without the need for pricey equipment. In this assay, the exonuclease III (Exo III)-assisted signal recycle is activated by the released single-strand DNA (ssDNA) from SMBs (streptavidin magnetic beads)-aptamer-ssDNA complex after identification of sEVs. By integrating with the strand displacement amplification (SDA) process, a significant amount of double-strand DNA products with G-rich tails is produced. The G-rich tails fold to G-quadruplex under the assistance of hemin to catalyze the oxidation of TMB, yielding a color change. The approach offers a broad detection range of 5 orders of magnitudes based on the signal recycles and SDA. In addition, single-stranded DNA binding protein (SSB) is exploited in this method to minimize the background signal from non-specific digestion of Exo-III, making the method a robust tool for sEVs detection and disease diagnosis.

Abstract Background Understanding resident physicians’ perceptions of competency-based medical education(CBME) may help improve approaches for implementing such education in standardized resident training (SRT). We conducted surveys of residents in China to identify their perceptions of CBME and determine the degree to which such education impacts their career plans. Methods Questionnaire contained a total of 24 questions, which were answered using multiple choice or yes/no, was distributed to residents who were undergoing SRT, regardless of specialty, at 7 accredited training bases located across six provinces of China. The survey aimed to investigate residents’ reasons for participating in SRT, perceptions of CBME, interest in receiving CBME-associated courses, and attitudes towards CBME. Results Overall, 441 residents completed the questionnaire.17.7% (78/441) responded “no clear objective” before the participated in SRT. Only 3.9% (17/441) fully understood the objectives, training contents, and assessment system of the current “competency-based” standardized training program for residents in China. Residents ranked clinical skills and patient care, interpersonal communication, and professionalism, as the three most important competencies. Most were interested in the CBME residency programs. 90.7% felt that implementing CBME could help them clarify their professional direction and improve their career planning. Conclusion Residents had positive perceptions of the incorporation of CBME into SRT. Administrators, educational leaders, and clinical faculty should seek to further publicize and increase the popularity of CBME.

This paper uses the physical information neural network (PINN) model to solve a 3D anisotropic steady-state heat conduction problem based on deep learning techniques. The model embeds the problem’s governing equations and boundary conditions into the neural network and treats the neural network’s output as the numerical solution of the partial differential equation. Then, the network is trained using the Adam optimizer on the training set. The output progressively converges toward the accurate solution of the equation. In the first numerical example, we demonstrate the convergence of the PINN by discussing the effect of the neural network’s number of layers, each hidden layer’s number of neurons, the initial learning rate and decay rate, the size of the training set, the mini-batch size, the amount of training points on the boundary, and the training steps on the relative error of the numerical solution, respectively. The numerical solutions are presented for three different examples. Thus, the effectiveness of the method is verified.

Due to the low computational efficiency of the Improved Element-Free Galerkin (IEFG) method, efficiently solving three-dimensional (3D) Laplace problems using meshless methods has been a longstanding research direction. In this study, we propose the Dimension Coupling Method (DCM) as a promising alternative approach to address this challenge. Based on the Dimensional Splitting Method (DSM), the DCM divides the 3D problem domain into a coupling of multiple two-dimensional (2D) problems which are handled via the IEFG method. We use the Finite Element Method (FEM) in the third direction to combine the 2D discretized equations, which has advantages over the Finite Difference Method (FDM) used in traditional methods. Our numerical verification demonstrates the DCM’s convergence and enhancement of computational speed without losing computational accuracy compared to the IEFG method. Therefore, this proposed method significantly reduces computational time and costs when solving 3D Laplace equations with natural or mixed boundary conditions in a dimensional splitting direction, and expands the applicability of the dimension splitting EFG method.

Objective Hypertension predicts the development of diabetes. However, there are still lacking high-quality studies on the correlation between mean arterial pressure (MAP) and incident diabetes. We aimed to explore the relationship between MAP and diabetes in Chinese adults.Design This is a secondary retrospective cohort study and the data were downloaded from the ‘DATADRYAD’ database (www.Datadryad.org).Participants The study included 210 418 adults without diabetes at baseline between 2010 and 2016 across 32 sites and 11 cities in China.Setting The target-independent and dependent variables were MAP measured at baseline and diabetes occurred during follow-up. Cox proportional hazards regression was used to explore the relationship between MAP and diabetes.Primary outcome measures The outcome was incident diabetes, which was defined as fasting blood glucose ≥7.00 mmol/L and/or self-reported diabetes during follow-up. Patients were censored either at the time of the diagnosis or at the last visit, whichever comes first.Results 3927 participants developed diabetes during a 5-year follow-up. After adjusting covariates, MAP positively correlated with diabetes (HR=1.008, 95% CI 1.005 to 1.011, p

Abstract Background Reliable quantification of the relationship between hypertension and diabetes risk is limited, especially among Chinese people. We aimed to investigate the association between hypertension and the risk of diabetes in a large cohort of the Chinese population. Methods This was a retrospective propensity score-matched cohort study among 211,809 Chinese adults without diabetes at baseline between 2010 and 2016. The target independent and dependent variable were hypertension at baseline and incident diabetes during follow-up respectively. The propensity score matching using a non-parsimonious multivariable logistic regression was conducted to balance the confounders between 28,711 hypertensive patients and 28,711 non-hypertensive participants. The doubly robust estimation method was used to investigate the association between hypertension and diabetes. Results In the propensity-score matching cohort, diabetes risk increased by 11.0% among hypertensive patients (HR = 1.110, 95% confidence interval (CI): 1.031–1.195, P = 0.00539). And diabetes risk dropped to 8.3% among hypertensive subjects after adjusting for the propensity score (HR = 1.083, 95%CI: 1.006–1.166, P = 0.03367). Compared to non-hypertensive participants with low propensity score, the risk of incident diabetes increased by 2.646 times among hypertensive patients with high propensity score (HR = 3.646, 95%CI: 2.635–5.045, P

Abstract Identifying individuals at high risk for incident diabetes could help achieve targeted delivery of interventional programs. We aimed to develop a personalized diabetes prediction nomogram for the 3-year risk of diabetes among Chinese adults. This retrospective cohort study was among 32,312 participants without diabetes at baseline. All participants were randomly stratified into training cohort (n = 16,219) and validation cohort (n = 16,093). The least absolute shrinkage and selection operator model was used to construct a nomogram and draw a formula for diabetes probability. 500 bootstraps performed the receiver operating characteristic (ROC) curve and decision curve analysis resamples to assess the nomogram's determination and clinical use, respectively. 155 and 141 participants developed diabetes in the training and validation cohort, respectively. The area under curve (AUC) of the nomogram was 0.9125 (95% CI, 0.8887–0.9364) and 0.9030 (95% CI, 0.8747–0.9313) for the training and validation cohort, respectively. We used 12,545 Japanese participants for external validation, its AUC was 0.8488 (95% CI, 0.8126–0.8850). The internal and external validation showed our nomogram had excellent prediction performance. In conclusion, we developed and validated a personalized prediction nomogram for 3-year risk of incident diabetes among Chinese adults, identifying individuals at high risk of developing diabetes.

Introduction: Renal cancer is one of the most common cancers in the world, but the effect of therapies on advanced renal cancer has not improved for decades. Ferroptosis is an emerging type of programmed cell death and has been proved to play a vital role in many kinds of cancers. However, the mechanisms of ferroptosis regulated by long noncoding RNA (lncRNA) in the context of renal cancer was still unknown. Methods: We used bioinformation analysis to identify SLC16A1-AS1 as a survival-related lncRNA in renal cancer. The expression levels of SLC16A1-AS1 and microRNA-143-3p (miR-143-3p) were detected by quantitative reverse transcription–polymerase chain reaction. Cell counting kit-8 assay, 5-bromo-2′-deoxyuridine proliferation assay, and colony-formation assay were performed to evaluate cell viability and proliferation. Wound-healing assay and transwell assay were used to examine cell invasive and migration capacity. Dual-luciferase reporter assay and RNA-binding protein immunoprecipitation were used to identify the interaction among SLC16A1-AS1, miR-143-3p, and the target protein solute carrier family 7 membrane 11 (SLC7A11). Reduced glutathione and glutathione and lipid peroxidation measurements were carried out to evaluate the level of ferroptosis, and the expression levels of ferroptosis-related proteins were analyzed by western blot. Results: Our study revealed that SLC16A1-AS1 has high expression and was associated with overall survival in renal cancer. Knockdown SLC16A1-AS1 inhibited cell viability, proliferation, and migration of renal cancer cells. Furthermore, it was demonstrated that SLC16A1-AS1 served as a sponge of miR-143-3p, and knockdown SLC16A1-AS1 significantly increased the enrichment of miR-143-3p. And then, SLC7A11 was identified as the target protein of miR-143-3p, and overexpression miR-143-3p remarkably inhibited the expression of SLC7A11. Moreover, knockdown SLC16A1-AS1 could aggravate this effect. Finally, through inhibiting SLC7A11 expression, silencing SLC16A1-AS1 induced ferroptosis via increasing miR-143-3p. Conclusion: The present results suggest that silencing lncRNA SLC16A1-AS1 can induce ferroptosis through miR-143-3p/SLC7A11 signaling in renal cancer. Our study provided a novel view into the pathogenesis and treatment strategy of RCC.

In order to obtain the numerical results of 3D convection-diffusion-reaction problems with variable coefficients efficiently, we select the improved element-free Galerkin (IEFG) method instead of the traditional element-free Galerkin (EFG) method by using the improved moving least-squares (MLS) approximation to obtain the shape function. For the governing equation of 3D convection-diffusion-reaction problems, we can derive the corresponding equivalent functional; then, the essential boundary conditions are imposed by applying the penalty method; thus, the equivalent integral weak form is obtained. By introducing the IMLS approximation, we can derive the final solved linear equations of the convection-diffusion-reaction problem. In numerical examples, the scale parameter and the penalty factor of the IEFG method for such problems are discussed, the convergence is proved numerically, and the calculation efficiency of the IEFG method are verified by four numerical examples.

Purpose: We aimed to establish and validate a risk assessment system that combines demographic and clinical variables to predict the 3-year risk of incident diabetes in Chinese adults.Methods: A 3-year cohort study was performed on 15,928 Chinese adults without diabetes at baseline. All participants were randomly divided into a training set (n = 7,940) and a validation set (n = 7,988). XGBoost method is an effective machine learning technique used to select the most important variables from candidate variables. And we further established a stepwise model based on the predictors chosen by the XGBoost model. The area under the receiver operating characteristic curve (AUC), decision curve and calibration analysis were used to assess discrimination, clinical use and calibration of the model, respectively. The external validation was performed on a cohort of 11,113 Japanese participants.Result: In the training and validation sets, 148 and 145 incident diabetes cases occurred. XGBoost methods selected the 10 most important variables from 15 candidate variables. Fasting plasma glucose (FPG), body mass index (BMI) and age were the top 3 important variables. And we further established a stepwise model and a prediction nomogram. The AUCs of the stepwise model were 0.933 and 0.910 in the training and validation sets, respectively. The Hosmer-Lemeshow test showed a perfect fit between the predicted diabetes risk and the observed diabetes risk (p = 0.068 for the training set, p = 0.165 for the validation set). Decision curve analysis presented the clinical use of the stepwise model and there was a wide range of alternative threshold probability spectrum. And there were almost no the interactions between these predictors (most P-values for interaction >0.05). Furthermore, the AUC for the external validation set was 0.830, and the Hosmer-Lemeshow test for the external validation set showed no statistically significant difference between the predicted diabetes risk and observed diabetes risk (P = 0.824).Conclusion: We established and validated a risk assessment system for characterizing the 3-year risk of incident diabetes.

The improved element-free Galerkin (IEFG) method is proposed in this paper for solving 3D Helmholtz equations. The improved moving least-squares (IMLS) approximation is used to establish the trial function, and the penalty technique is used to enforce the essential boundary conditions. Thus, the final discretized equations of the IEFG method for 3D Helmholtz equations can be derived by using the corresponding Galerkin weak form. The influences of the node distribution, the weight functions, the scale parameters of the influence domain, and the penalty factors on the computational accuracy of the solutions are analyzed, and the numerical results of three examples show that the proposed method in this paper can not only enhance the computational speed of the element-free Galerkin (EFG) method but also eliminate the phenomenon of the singular matrix.

Objectives: To study the operative outcomes of single-port laparoscopic hysterectomy in uteri greater than 500 g, using either laparoscopic assisted vaginal hysterectomy (LAVH) or laparoscopic supracervical hysterectomy (LSH). Materials and methods: 78 patients were included in a single institute by a single surgeon from March, 2013 to January, 2018. Results: The median uterine weight was 686.5 g. Larger uterine weight was correlated with longer operative time and greater estimated blood loss. Two types of operations were performed: LAVH (n = 55) or LSH (n = 23). There were no differences in operative time (150.2 ± 45.1 vs. 158.6 ± 82.1, P = 0.66) and estimated blood loss (365.8 ± 298.5 vs. 356.5 ± 46.6, ml, P = 0.94) between LAVH and LSH. However, patients in LAVH had more excess blood loss (>500 mL) compared with LSH (32.7% vs. 21.7%, P = 0.42). In the later study period, the operative time was shorter and complication rates were lower. Such differences were especially significant in the LAVH group. By multiple regression analysis, operative time was independently correlated with age, body mass index, estimated blood loss and uterine weight in LAVH. The correlation between operative time and uterine weight in LSH was attenuated by estimated blood loss. Estimated blood loss was the dominant factor correlated with longer operative time in LSH. Conclusions: Both LAVH and LSH could be feasible in uteri greater than 500 g. LSH appeared to have less complication and less blood loss than LAVH. Operative time was correlated significantly with bleeding amount. Therefore, better bleeding control and surgical experience were warrants for single-port laparoscopic hysterectomy in uteri greater than 500 g.

Background: Fertility‐sparing surgery (FSS) is an alternative choice of young patients who have not completed their family planning and still have fertility needs. The aims of this study were to compare the outcomes of early‐stage epithelial ovarian cancer (EOC) patients undergoing FSS and radical comprehensive staging surgery (RCS), and the suitability of FSS. Methods: A total of 1297 patients aged between 20 and 44 years with newly diagnosed early‐stage EOC were recruited from the Taiwan Cancer Registry database between 2009 and 2017. Site‐specific surgery codes were used to distinguish patients in FSS group or RCS group. Cancer‐specific survival (CSS) was evaluated using Kaplan–Meier method with log‐rank test and Cox regression model. Results: There were 401 and 896 patients in FSS and RCS group. Patients in FSS group were with younger age and mostly had Stage I disease. In contrast, patients in RCS group were older. There were more Stage II, high‐grade (Grade 3) disease, and adjuvant chemotherapy in RCS group. Stage and tumor grade were two independent factors correlating with CSS and the type of surgery showed no effect on CSS (HR: 1.09, 95% CI: 0.66–1.77, p = 0.73) in multivariable analysis. In multivariable analysis, the clear cell carcinoma group who underwent FSS demonstrated better CSS compared to those in the RCS group (HR: 0.28, 95% CI: 0.06–0.82, p = 0.04). A total of 17 women who underwent FSS developed second malignancies of the uterine corpus or contralateral ovary. Conclusion: FSS can be a safe alternative procedure in selected young patients of Stage I EOC who have fertility desire. Endometrial biopsy before or during FSS and regular surveillance to detect recurrence are mandatory for ovarian cancer patients undergoing FSS. [ABSTRACT FROM AUTHOR]

Objective: To share our experience of transition from multiport to single-site robotic surgery for benign gynecological conditions as well as to assess the selection criteria of candidates for robotic single-site supracervical hysterectomy (RSSH). Materials and methods: A retrospective review was conducted on patients undergoing robotic supracervical hysterectomy by a single surgeon in a single institute between June 2014 and December 2017. Patients who underwent additional procedures along with supracervical hysterectomy and who had unexpectant corpus malignancy proved pathologically were excluded from comparisons between patients undergoing RSSH and robotic multiport supracervical hysterectomy (RMSH). Results: Between June 2014 and December 2017, we accomplished 26 RSSH and 57 RMSH. There were no conversions, intraoperative complications, and readmissions within 30 days after surgery. In the RSSH group, the mean uterine weight was 264.6 ± 140.9 g with mean docking time of 15.8 ± 5.5 min, mean console time of 61.1 ± 35.6 min and mean operative time of 140.3 ± 34.4 min. In comparison to the RMSH group, the percentage of overweight/obese patients was lower (p = 0.018) and the uterine size was smaller (p

Point-of-care ultrasonography (POCUS) has become the most popular modality of testing for physicians in recent years and is used for improving the quality of care and increasing patient safety. However, POCUS is not always acceptable to all physicians. To address the benefits and importance of POCUS, numerous studies have examined the use of POCUS in clinical practice and even medical education. This article aims to highlight the effects of POCUS as an extension of the physical examination, and we present a case to address the reasons it should be performed. For a man experiencing abdominal pain immediately after his feeding jejunostomy tube was changed, there was high suspicion of small-bowel volvulus after a “whirlpool sign” was observed during the POCUS, whereby mesenteric vessels presented in a whirling or spiral shape. This impression was subsequently confirmed by computed tomography. Small-bowel volvulus is a rare complication of changing a feeding jejunostomy tube. The images submitted here add to the sparse evidence from the literature on the use of POCUS as an extension of the physical examination for evaluating abdominal pain. POCUS can be used after taking the patient’s history and conducting a physical examination. The observation of a whirlpool sign may indicate the presence of a volvulus that is life-threatening.

Abstract Background Short read DNA sequencing technologies have revolutionized genome assembly by providing high accuracy and throughput data at low cost. But it remains challenging to assemble short read data, particularly for large, complex and polyploid genomes. The linked read strategy has the potential to enhance the value of short reads for genome assembly because all reads originating from a single long molecule of DNA share a common barcode. However, the majority of studies to date that have employed linked reads were focused on human haplotype phasing and genome assembly. Results Here we describe a de novo maize B73 genome assembly generated via linked read technology which contains ~ 172,000 scaffolds with an N50 of 89 kb that cover 50% of the genome. Based on comparisons to the B73 reference genome, 91% of linked read contigs are accurately assembled. Because it was possible to identify errors with > 76% accuracy using machine learning, it may be possible to identify and potentially correct systematic errors. Complex polyploids represent one of the last grand challenges in genome assembly. Linked read technology was able to successfully resolve the two subgenomes of the recent allopolyploid, proso millet (Panicum miliaceum). Our assembly covers ~ 83% of the 1 Gb genome and consists of 30,819 scaffolds with an N50 of 912 kb. Conclusions Our analysis provides a framework for future de novo genome assemblies using linked reads, and we suggest computational strategies that if implemented have the potential to further improve linked read assemblies, particularly for repetitive genomes.

Background: Efficacy of sequential therapy with nucleos(t)ide analogues and interferons versus monotherapy in patients with hepatitis B e antigen (HBeAg)-positive chronic hepatitis B (CHB) remains unexplored. We aimed to assess efficacy and safety of sequential therapy with adefovir (ADV) or entecavir (ETV) followed by peginterferon (PEG-IFN) alfa-2a in Taiwanese patients with HBeAg-positive. Methods: This randomized, placebo-controlled, double-blind trial was conducted at nine sites in Taiwan from April 2010 to October 2013. Patients (N = 280) were randomized 1:1:1 to receive placebo, ETV or ADV alone for four weeks, combined with PEG-IFN alfa-2a for two weeks, then PEG-IFN alfa-2a alone for 46 weeks. The primary efficacy end point was HBeAg seroconversion at 48 weeks post-treatment. Results: No significant differences were observed among groups for HBeAg seroconversion (PEG-IFN alfa-2a+placebo, 36.3%; PEG-IFN alfa-2a+ETV, 29.5%; and PEG-IFN alfa-2a+ADV, 27.4%), HBeAg loss (37.4%, 32.2%, and 28.6%, respectively) or change in hepatitis B surface antigen (HBsAg) levels from baseline (−0.56 IU/mL, −0.60 IU/mL, and −0.41 IU/mL, respectively). However, hepatitis B virus DNA levels were higher with PEG-IFN alfa-2a+placebo than PEG-IFN alfa+ETV at week 64 (p = 0.0412), 76 (p = 0.0311), and 88 (p = 0.0113), and alanine aminotransferase (ALT) normalization rate was higher with PEG-IFN alfa-2a+placebo than PEG-IFN alfa-2a+ADV (p = 0.0283) or PEG-IFN alfa-2a+ETV (p = 0.0369) at week 88. Sub-analysis of results revealed an association between on-treatment HBsAg and ALT levels and efficacy 48 weeks post-treatment. Safety was comparable among treatment groups. Conclusion: Pre-therapy with ADV or ETV followed by PEG-IFN alfa-2a is not superior to PEG-IFN alfa-2a monotherapy in Taiwanese patients with HBeAg-positive CHB. Clinical trial ID: NCT: 00922207. Keywords: Chronic hepatitis B, Hepatitis B e antigen, Peginterferon alfa-2a, Adefovir, Entecavir

The 8th Biennial Meeting of the Asian Society of Gynecologic Oncology took place in Taipei, Taiwan in December 2023. The meeting aimed to advance the study, prevention, and treatment of gynecological cancer in Asia through scientific exchange, collaboration, and education. The event featured presentations on cutting-edge research and high-technology practices related to gynecological cancer. Notably, studies presented at the meeting showed that durvalumab plus carboplatin/paclitaxel followed by maintenance durvalumab improved survival rates in patients with recurrent or metastatic cervical cancer, and carboplatin/paclitaxel plus durvalumab followed by maintenance durvalumab with or without olaparib had a significant benefit in patients with advanced or recurrent endometrial cancer. The meeting also included symposia on various topics related to gynecologic oncology and featured social events such as a gala dinner and a laparoscopic surgery workshop. [Extracted from the article]

一對一數位學習觀念已逐漸被社會所接受，但對實際教學現場的影響仍十分有限；這是 因為將數位學習落實於教室，進而形成「數位學校」仍遭遇許多困難。研究團隊歷經十多年 發展，自 2009 年，以長期採納實踐的模式為主，探索並驗證學生、教師與家長投入數位學習 的意願與改變，逐步發展支援親師生的數位學習模式與平台，目標分別為：學生利用各式的 數位資源主動投入自主學習或同儕互動；教師發展與落實數位教學的能力與課程；家長善用 數位設備與資源來幫助學生。目前導入至數位學校已 6 年，發展全國第一所由家長為自己孩 子採購電腦的 BYOD 模式，並達成學生學科成就明顯提升、教師學與教的典範轉移與家長態 度從忐忑到信任等成果。後續將基於此成果與模式持續推廣與擴散。 Although the notion of one-to-one learning technology is a recent development, its impact on schools has thus far been limited. To develop a feasible model for digital schools based on one-to-one learning technology, the present study employed an adoption-based research methodology to investigate how students, teachers, and parents have engaged with digital learning platforms since 2009. Through the process of understanding their willingness to use digital learning platforms as well as reasons for changing for better learning and teaching, the researchers gradually developed digital learning models and corresponding platforms. The study objectives are described as follows: (1) to facilitate students’ active participation in self-directed learning and collaborative learning by using various digital resources; (2) to assist teachers in developing their capabilities for adopting digital teaching in classrooms; and (3) to assist parents in helping their children through appropriate use of digital devices. Based on these objectives, the present study established the first digital school in Taiwan using a bring-your-own-device model, where parents prepare personal tablet computers for their children. The results show that learning outcomes significantly improved among the students. In addition, the teachers transformed the paradigm of learning and teaching in classrooms, and the parents developed trust in digital learning. Based on these outcomes, the model designed in this study could be used in schools in the future.

Background/Aims: MicroRNAs (miRNAs, miRs) have emerged as important post-transcriptional regulators in various cancers. miR-543 has been reported to play critical roles in hepatocellular carcinoma and colorectal cancer, however, the role of miR-543 in the pathogenesis of prostate cancer has not been fully understood. Methods: Expression of miR-543 and Raf Kinase Inhibitory Protein (RKIP) in clinical prostate cancer specimens, two prostate cancer cell lines, namely LNCAP and C4-2B, were determined. The effects of miR-543 on proliferation and metastasis of tumor cells were also investigated with both in vitro and in vivo studies. Results: miR-543 was found to be negatively correlated with RKIP expression in clinical tumor samples and was significantly upregulated in metastatic prostate cancer cell line C4-2B compared with parental LNCAP cells. Further studies identified RKIP as a direct target of miR-543. Overexpression of miR-543 downregulated RKIP expression and promoted the proliferation and metastasis of cancer cells, whereas knockdown of miR-543 increased expression of RKIP and suppressed the proliferation and metastasis of cancer cells in vitro and in vivo. Conclusion: Our study demonstrates that miR-543 promotes the proliferation and metastasis of prostate cancer via targeting RKIP.

Summary: Twenty percent of breast cancer (BC) patients develop distant metastasis for which there is no cure. Mesenchymal stem/stromal cells (MSCs) in the tumor microenvironment were shown to stimulate metastasis, but the mechanisms are unclear. Here, we identified and quantified cancer cells engulfing stromal cells in clinical samples of BC metastasis by dual immunostaining for EZH2 and ALDH1 expression. Using flow cytometry and a microfluidic single-cell paring and retrieval platform, we show that MSC engulfment capacity is associated with BC cell metastatic potential and generates cells with mesenchymal-like, invasion, and stem cell traits. Whole-transcriptome analyses of selectively retrieved engulfing BC cells identify a gene signature of MSC engulfment consisting of WNT5A, MSR1, ELMO1, IL1RL2, ZPLD1, and SIRPB1. These results delineate a mechanism by which MSCs in the tumor microenvironment promote metastasis and provide a microfluidic platform with the potential to predict BC metastasis in clinical samples. : How MSCs in the tumor microenvironment promote breast cancer progression is unclear. Chen et al. find that aggressive breast cancer cells are able to engulf MSCs. Through the development of a microfluidic cell pairing platform, they discover that this process induces transcriptome changes in breast cancer cells and enhances distant metastasis. Keywords: breast cancer, metastasis, mesenchymal stem cell, MSC, cell fusion, cell engulfment, EZH2, microfluidics, microenvironment, single cell retrieval

In this retrospective study, we investigated adverse events and outcomes in patients treated with bevacizumab for ovarian, fallopian tube, or primary peritoneal cancers at a single hospital. We determined the cumulative incidences of various bevacizumab-related adverse events and the correlation between dose and adverse event incidences. We analyzed data from 154 patients that received 251 rounds of bevacizumab as first-line, first salvage, >2 salvage treatments. Adverse events of any grade were observed in 121 (78.6%) patients; at least one grade 3 or 4 adverse event occurred in 32 (20.8%) patients. The two most common events were proteinuria (38.3%) and hypertension (33.8%). The first-line treatment group displayed significantly higher frequencies of hypertension (52.7% vs. 18.9% vs. 15.5%, p < 0.001), wound complications (9.1% vs. 0% vs. 1.2%, p = 0.010), arthralgia (29.1% vs. 11.3% vs. 8.3%, p = 0.003), and reduced range of joint motion (14.5% vs. 5.7% vs. 3.6%, p = 0.046), compared to those in the first and >2 lines salvage groups, respectively (Kruskal–Wallis test). The cumulative incidences of all grades and grades 3/4 of hypertension cumulative incidence plateaued at around 30% for all grades and 10% for grades 3 and 4, at bevacizumab doses above 8080 and 3510 mg, respectively. The proteinuria cumulative incidence plateaued at around 35% for all grades and 3% for grades 3 and 4, at bevacizumab doses above 11,190 and 4530 mg, respectively. We concluded that, in this realistic clinical population, different kinds and higher cumulative incidences of adverse events were observed compared to those reported in previous clinical trials. Moreover, bevacizumab doses showed cumulative toxicity and plateau effects on hypertension and proteinuria.

Trichomonas vaginalis is a prevalent causative agent that causes trichomoniasis leading to uropathogenic inflammation in the host. The crucial role of the actin cytoskeleton in T. vaginalis cytoadherence has been established but the associated signaling has not been fully elucidated. The present study revealed that the T. vaginalis second messenger PIP2 is located in the recurrent flagellum of the less adherent isolate and is more abundant around the cell membrane of the adherent isolates. The T. vaginalis phosphatidylinositol-4-phosphate 5-kinase (TvPI4P5K) with conserved activity phosphorylating PI(4)P to PI(4, 5)P2 was highly expressed in the adherent isolate and partially colocalized with PIP2 on the plasma membrane but with discrete punctate signals in the cytoplasm. Plasma membrane PIP2 degradation by phospholipase C (PLC)-dependent pathway concomitant with increasing intracellular calcium during flagellate-amoeboid morphogenesis. This could be inhibited by Edelfosine or BAPTA simultaneously repressing parasite actin assembly, morphogenesis, and cytoadherence with inhibitory effects similar to the iron-depleted parasite, supporting the significance of PIP2 and iron in T. vaginalis colonization. Intriguingly, iron is required for the optimal expression and cell membrane trafficking of TvPI4P5K for in situ PIP2 production, which was diminished in the iron-depleted parasites. TvPI4P5K-mediated PIP2 signaling may coordinate with iron to modulate T. vaginalis contact-dependent cytolysis to influence host cell viability. These observations provide novel insights into T. vaginalis cytopathogenesis during the host-parasite interaction. Author summary: Signal transduction in T. vaginalis pathogenesis remains elusive despite elucidation of the distinctive actin-based cytoadherence of the adherent isolates. Herein, we identified a T. vaginalis phosphatidylinositol-4-phosphate 5-kinase (TvPI4P5K) which converts PI(4)P into PI(4, 5)P2. Differential TvPI4P5K expression and specific PIP2 localization in the T. vaginalis isolates with distinct cytoadherence suggest a potential link underlying PIP2 signaling and cytoskeleton behaviors in this parasite. In the parasite transforming from the flagellate into an amoeboid trophozoite, the plasma membrane PIP2 signal may be cleaved by a phospholipase C (PLC)-like pathway, thereafter increasing intracellular calcium, both of which are required for parasite actin assembly, morphogenesis, and cytoadherence. Moreover, environmental iron elicited TvPI4P5K and PIP2 expression and triggered TvPI4P5K translocation to the plasma membrane. PIP2 signaling also modulated the extracellular cytopathic effectors from the parasite to lyse host cells. Our study reveals the biological significance of PIP2 signal transduction in regulating T. vaginalis pathogenesis, which may be a potential therapeutic target. [ABSTRACT FROM AUTHOR]

Background: The prognosis of patients with acute coronary syndrome (ACS) varies greatly, and risk assessment models can help clinicians to identify and manage high-risk patients. While the Global Registry of Acute Coronary Events (GRACE) model is widely used, the clinical pathways for acute coronary syndromes (CPACS), which was constructed based on the Chinese population, and acute coronary treatment and intervention outcomes network (ACTION) have not yet been validated in the Chinese population. Methods: Patients with ACS who underwent coronary angiography or percutaneous coronary intervention from 2011 to 2020, were retrospectively recruited and the appropriate corresponding clinical indicators was obtained. The primary endpoint was in-hospital mortality. The performance of the GRACE, GRACE 2.0, ACTION, thrombolysis in myocardial infarction (TIMI) and CPACS risk models was evaluated and compared. Results: A total of 19,237 patients with ACS were included. Overall, in-hospital mortality was 2.2%. ACTION showed the highest accuracy in predicting discriminated risk (c-index 0.945, 95% confidence interval [CI] 0.922-0.955), but the calibration was not satisfactory. GRACE and GRACE 2.0 did not significantly differ in discrimination (p = 0.1480). GRACE showed the most accurate calibration in all patients and in the subgroup analysis of all models. CPACS (c-index 0.841, 95% CI 0.821-0.861) and TIMI (c-index 0.811, 95% CI 0.787-0.835) did not outperform (c-index 0.926, 95% CI 0.911-0.940). Conclusions: In contemporary Chinese ACS patients, the ACTION risk model's calibration is not satisfactory, although outperformed the gold standard GRACE model in predicting hospital mortality. The CPACS model developed for Chinese patients did not show better predictive performance than the GRACE model. [ABSTRACT FROM AUTHOR]