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Abstract With climate change and anthropic influence on the coastal ecosystems, mangrove ecosystems are disappearing at an alarming rate. Accordingly, it becomes important to track, study, record and store the mangrove microbial community considering their ecological importance and potential for biotechnological applications. Here, we provide information on mangrove fungal community composition and diversity in mangrove ecosystems with different plant species and from various locations differing in relation to anthropic influences. We describe twelve newly assembled genomes, including four chromosomal-level genomes of fungal isolates from the mangrove ecosystems coupled with functional annotations. We envisage that these data will be of value for future studies including comparative genome analysis and large-scale temporal and/or spatial research to elucidate the potential mechanisms by which mangrove fungal communities assemble and evolve. We further anticipate that the genomes represent valuable resources for bioprospecting related to industrial or clinical uses.

Abstract Background To compare the surgical outcomes of the inverted internal limiting membrane (ILM) flap technique and ILM insertion for macular hole (MH) without retinal detachment in eyes with extremely high myopia. Methods In this retrospective study, we analyzed 22 eyes with an axial length ≥ 30.0 mm that had underwent MH surgery between April 2015 and August 2021. The surgical procedures involved either an inverted ILM flap or ILM insertion. The outcomes were compared between the two techniques. Closure of the MH was confirmed by optical coherence tomography (OCT). The best-corrected visual acuity (BCVA) was measured before and after surgery. Associated complications were documented. Results The median of axial length was 30.64 mm (range, 30.0-34.42). The MH closed in 100% (22/22) eyes and did not recur with a median follow-up of 12.5 months. For the inverted ILM flap technique, the median BCVA improved significantly from 0.80 logarithm of the minimum angle of resolution (logMAR) (range, 0.40-2.00) before surgery to 0.70 logMAR (range, 0.09–1.52) after surgery (p = 0.002). In addition, the median of final BCVA was better for the inverted ILM flap than ILM insertion (0.7 logMAR V.S. 1.00 logMAR; p = 0.016). Conclusions In eyes with extremely high myopia, despite comparable effects on MH closure for both ILM insertion and the inverted ILM flap, the later technique achieved significantly better visual outcomes.

Abstract Background Brain metastasis is one of the main causes of recurrence and death in non-small cell lung cancer (NSCLC). Although radiotherapy is the main local therapy for brain metastasis, it is inevitable that some cancer cells become resistant to radiation. Microglia, as macrophages colonized in the brain, play an important role in the tumor microenvironment. Radiotherapy could activate microglia to polarize into both the M1 and M2 phenotypes. Therefore, searching for crosstalk molecules within the microenvironment that can specifically regulate the polarization of microglia is a potential strategy for improving radiation resistance. Methods We used databases to detect the expression of MIF in NSCLC and its relationship with prognosis. We analyzed the effects of targeted blockade of the MIF/CD74 axis on the polarization and function of microglia during radiotherapy using flow cytometry. The mouse model of brain metastasis was used to assess the effect of targeted blockade of MIF/CD74 axis on the growth of brain metastasis. Result Our findings reveals that the macrophage migration inhibitory factor (MIF) was highly expressed in NSCLC and is associated with the prognosis of NSCLC. Mechanistically, we demonstrated CD74 inhibition reversed radiation-induced AKT phosphorylation in microglia and promoted the M1 polarization in combination of radiation. Additionally, blocking the MIF-CD74 interaction between NSCLC and microglia promoted microglia M1 polarization. Furthermore, radiation improved tumor hypoxia to decrease HIF-1α dependent MIF secretion by NSCLC. MIF inhibition enhanced radiosensitivity for brain metastasis via synergistically promoting microglia M1 polarization in vivo. Conclusions Our study revealed that targeting the MIF-CD74 axis promoted microglia M1 polarization and synergized with radiotherapy for brain metastasis in NSCLC.

Abstract Background The interplay between exosomes and the tumor microenvironment (TME) remains unclear. We investigated the influence of exosomes on the TME in hepatocellular carcinoma (HCC), focusing on their mRNA expression profile. Methods mRNA expression profiles of exosomes were obtained from exoRBase. RNA sequencing data from HCC patients’ tumors were acquired from The Cancer Genome Atlas (TCGA) and the International Cancer Genome Consortium (ICGC). An exosome mRNA-related risk score model of prognostic value was established. The patients in the two databases were divided into high- and low-risk groups based on the median risk score value, and used to validate one another. Functional enrichment analysis was performed based on a differential gene prognosis model (DGPM). CIBERSORT was used to assess the abundance of immune cells in the TME. The correlation between the expression levels of immune checkpoint-related genes and DGPM was analyzed alongside the prediction value to drug sensitivity. Results A prognostic exosome mRNA-related 4-gene signature (DYNC1H1, PRKDC, CCDC88A, and ADAMTS5) was constructed and validated. A prognostic nomogram had prognostic ability for HCC. The genes for this model are involved in extracellular matrix, extracellular matrix (ECM)-receptor interaction, and the PI3K-Akt signaling pathway. Expression of genes here had a positive correlation with immune cell infiltration in the TME. Conclusions Our study results demonstrate that an exosome mRNA-related risk model can be established in HCC, highlighting the functional significance of the molecules in prognosis and risk stratification.

Reprocessing of gastrointestinal (GI) endoscopes and accessories is an essential part of patient safety and quality control in GI endoscopy centers. However, current endoscopic reprocessing guidelines or procedures are not adequate to ensure patient-safe endoscopy. Approximately 5.4 % of the clinically used duodenoscopes remain contaminated with high-concern microorganisms. Thus, the Digestive Endoscopy Society of Taiwan (DEST) sets standards for the reprocessing of GI endoscopes and accessories in endoscopy centers. DEST organized a task force working group using the guideline-revision process. These guidelines contain principles and instructions of step-by-step for endoscope reprocessing. The updated guidelines were established after a thorough review of the existing global and local guidelines, systematic reviews, and health technology assessments of clinical effectiveness. This guideline aims to provide detailed recommendations for endoscope reprocessing to ensure adequate quality control in endoscopy centers.

Abstract The new energy industry is strongly supported by the state, and accurate forecasting of stock price can lead to better understanding of its development. However, factors such as cost and ease of use of new energy, as well as economic situation and policy environment, have led to continuous changes in its stock price and increased stock price volatility. By calculating the Lyapunov index and observing the Poincaré surface of the section, we find that the sample of the China Securities Index Green Power 50 Index has chaotic characteristics, and the data indicate strong volatility and uncertainty. This study proposes a new method of stock price index prediction, namely, EWT-S-ALOSVR. Empirical wavelet decomposition extracts features from multiple factors affecting stock prices to form multiple sub-columns with features, significantly reducing the complexity of the stock price series. Support vector regression is well suited for dealing with nonlinear stock price series, and the support vector machine model parameters are selected using random wandering and picking elites via Ant Lion Optimization, making stock price prediction more accurate.

Abstract Background Continuous and noninvasive hemoglobin (Hb) monitoring during surgery is essential for anesthesiologists to make transfusions decisions. The aim of this study was to investigate the feasibility and accuracy of noninvasive and continuous Hb monitoring using transesophageal descending aortic photoplethysmography (dPPG) in porcine model. Methods Nineteen landrace pigs, aged 3 to 5 months and weighing 30 to 50 kg, were enrolled in this study. A homemade oximetry sensor, including red (660 nm) and infrared (940 nm) lights, was placed in the esophagus for dPPG signal detection to pair with the corresponding reference Hb values (Hbi−STAT) measured by blood gas analysis. The decrease and increase changes in Hb concentration were achieved by hemodilution and transfusion. Metrics, including alternating current (AC), direct current (DC), and AC/DC for both red and infrared light were extracted from the dPPG signal. A receiver operating characteristic (ROC) curve was built to evaluate the performance of dPPG metrics in predicting the Hb “trigger threshold” of transfusion (Hb 100 g/L). Agreement and trending ability between Hb measured by dPPG (HbdPPG) and by blood gas analysis were analyzed by Bland-Altman method and polar plot graph. Error grid analysis was also performed to evaluate clinical significance of HbdPPG measurement. Results The dPPG signal was successfully detected in all of the enrolled experimental pigs, without the occurrence of a continuous loss of dPPG signal for 2 min during the entire measurement. A total of 376 pairs of dPPG signal and Hbi−STAT were acquired. ACred/DCred and ACinf/DCinf had moderate correlations with Hbi−STAT, and the correlation coefficients were 0.790 and 0.782, respectively. The areas under the ROC curve for ACred/DCred and ACinf/DCinf in predicting Hbi−STAT < 60 g/L were 0.85 and 0.75, in predicting Hbi−STAT > 100 g/L were 0.90 and 0.83, respectively. Bland-Altman analysis and polar plot showed a small bias (1.69 g/L) but a wide limit of agreement (-26.02–29.40 g/L) and a poor trend ability between HbdPPG and Hbi−STAT. Clinical significance analysis showed that 82% of the data lay within the Zone A, 18% within the Zone B, and 0% within the Zone C. Conclusion It is feasible to establish a noninvasive and continuous Hb monitoring by transesophageal dPPG signal. The ACred/DCred extracted from the dPPG signal could provide a sensitive prediction of the Hb threshold for transfusion. The Hb concentration measured by dPPG signal has a moderate correlation with that measured by blood gas analysis. This animal study may provide an experimental basis for the development of bedside HbdPPG monitoring in the future.

Abstract Inhibition of epigenetic regulators by small molecules is an attractive strategy for cancer treatment. Recently, we characterised the role of lysine methyltransferase 9 (KMT9) in prostate, lung, and colon cancer. Our observation that the enzymatic activity was required for tumour cell proliferation identified KMT9 as a potential therapeutic target. Here, we report the development of a potent and selective KMT9 inhibitor (compound 4, KMI169) with cellular activity through structure-based drug design. KMI169 functions as a bi-substrate inhibitor targeting the SAM and substrate binding pockets of KMT9 and exhibits high potency, selectivity, and cellular target engagement. KMT9 inhibition selectively downregulates target genes involved in cell cycle regulation and impairs proliferation of tumours cells including castration- and enzalutamide-resistant prostate cancer cells. KMI169 represents a valuable tool to probe cellular KMT9 functions and paves the way for the development of clinical candidate inhibitors as therapeutic options to treat malignancies such as therapy-resistant prostate cancer.

Abstract Background This study aims to investigate the relationship between gestational metabolic syndrome (GMS) and the Chinese Healthy Eating Index (CHEI) in mid-pregnancy, and to identify potentially beneficial or high-risk dietary habits. We have developed a mid-pregnancy version of CHEI-2022, adapting the Chinese Healthy Eating Index to align with the food quantity recommendations outlined in the 2022 Dietary Guidelines for Chinese Residents for mid-pregnancy. Methods Using the inclusion and exclusion criteria, data from 2411 mid-pregnant individuals were collected through interviews. The Total CHEI score and its component scores were determined through analysis of responses from the food frequency questionnaire. GMS diagnosis involved conducting physical examinations and performing blood biochemical tests. A logistic regression model was employed to analyze the relationship between GMS or related indices and both the total CHEI score and its component scores. Results The study identified an overall GMS prevalence of 21.65% (522 out of 2411 participants). During mid-pregnancy, participants diagnosed with GMS exhibited higher BMI, FBG, 1hPBG, 2hPBG, TC, TG, HDL, SBP, as well as higher educational levels and daily activity, compared to those without GMS (P

Abstract Acute myeloid leukemia (AML) with CEBPA bZIP in-frame mutations (CEBPA bZIP-inf) is classified within the favorable-risk group by the 2022 European LeukemiaNet (ELN-2022). However, heterogeneous clinical outcomes are still observed in these patients. In this study, we aimed to investigate the mutation profiles and transcriptomic patterns associated with poor outcomes in patients with CEBPA bZIP-inf. One hundred and thirteen CEBPA bZIP-inf patients were identified in a cohort of 887 AML patients homogeneously treated with intensive chemotherapy. Concurrent WT1 or DNMT3A mutations significantly predicted worse survival in AML patients with CEBPA bZIP-inf. RNA-sequencing analysis revealed an enrichment of interferon (IFN) signaling and metabolic pathways in those with a shorter event-free survival (EFS). CEBPA bZIP-inf patients with a shorter EFS had higher expression of IFN-stimulated genes (IRF2, IRF5, OAS2, and IFI35). Genes in mitochondrial complexes I (NDUFA12 and NDUFB6) and V (ATP5PB and ATP5IF1) were overexpressed and were associated with poorer survival, and the results were independently validated in the TARGET AML cohort. In conclusion, concurrent WT1 or DNMT3A mutations and a dysregulated immune and metabolic state were correlated with poor survival in patients with CEBPA bZIP-inf, and upfront allogeneic transplantation may be indicated for better long-term disease control.

Abstract Our study presents a 319-gene panel targeting inherited retinal dystrophy (IRD) genes. Through a multi-center retrospective cohort study, we validated the assay’s effectiveness and clinical utility and characterized the mutation spectrum of Taiwanese IRD patients. Between January 2018 and May 2022, 493 patients in 425 unrelated families, all initially suspected of having IRD without prior genetic diagnoses, underwent detailed ophthalmic and physical examinations (with extra-ocular features recorded) and genetic testing with our customized panel. Disease-causing variants were identified by segregation analysis and clinical interpretation, with validation via Sanger sequencing. We achieved a read depth of >200× for 94.2% of the targeted 1.2 Mb region. 68.5% (291/425) of the probands received molecular diagnoses, with 53.9% (229/425) resolved cases. Retinitis pigmentosa (RP) is the most prevalent initial clinical impression (64.2%), and 90.8% of the cohort have the five most prevalent phenotypes (RP, cone-rod syndrome, Usher’s syndrome, Leber’s congenital amaurosis, Bietti crystalline dystrophy). The most commonly mutated genes of probands that received molecular diagnosis are USH2A (13.7% of the cohort), EYS (11.3%), CYP4V2 (4.8%), ABCA4 (4.5%), RPGR (3.4%), and RP1 (3.1%), collectively accounted for 40.8% of diagnoses. We identify 87 unique unreported variants previously not associated with IRD and refine clinical diagnoses for 21 patients (7.22% of positive cases). We developed a customized gene panel and tested it on the largest Taiwanese cohort, showing that it provides excellent coverage for diverse IRD phenotypes.

BackgroundTelehealth has emerged as a popular channel for providing outpatient services in many countries. However, the majority of telehealth systems focus on operational functions and offer only a sectional patient journey at most. Experiences with incorporating longitudinal real-world medical record data into telehealth are valuable but have not been widely shared. The feasibility and usability of such a telehealth platform, with comprehensive, real-world data via a live feed, for cancer patient care are yet to be studied. ObjectiveThe primary purpose of this study is to understand the feasibility and usability of cancer patient care using a telehealth platform with longitudinal, real-world data via a live feed as a supplement to hospital electronic medical record systems specifically from physician’s perspective. MethodsA telehealth platform was constructed and launched for both physicians and patients. Real-world data were collected and curated using a comprehensive data model. Physician activities on the platform were recorded as system logs and analyzed. In February 2023, a survey was conducted among the platform’s registered physicians to assess the specific areas of patient care and to quantify their before and after experiences, including the number of patients managed, time spent, dropout rate, visit rate, and follow-up data. Descriptive and inferential statistical analyses were performed on the data sets. ResultsOver a period of 15 months, 16,035 unique users (13,888 patients, 1539 friends and family members, and 174 physician groups with 608 individuals) registered on the platform. More than 382,000 messages including text, reminders, and pictures were generated by physicians when communicating with patients. The survey was completed by 78 group leaders (45% of the 174 physician groups). Of the participants, 84% (65.6/78; SD 8.7) reported a positive experience, with efficient communication, remote supervision, quicker response to questions, adverse event prevention, more complete follow-up data, patient risk reduction, cross-organization collaboration, and a reduction in in-person visits. The majority of the participants (59/78, 76% to 76/78, 97.4%) estimated improvements in time spent, number of patients managed, the drop-off rate, and access to medical history, with the average ranging from 57% to 105%. When compared with prior platforms, responses from physicians indicated better experiences in terms of time spent, the drop-off rate, and medical history, while the number of patients managed did not significantly change. ConclusionsThis study suggests that a telehealth platform, equipped with comprehensive, real-world data via a live feed, is feasible and effective for cancer patient care. It enhances inpatient management by improving time efficiencies, reducing drop-off rates, and providing easy access to medical history. Moreover, it fosters a positive experience in physician-patient interactions.

Abstract Temozolomide (TMZ) represents the cornerstone of therapy for glioblastoma (GBM). However, acquisition of resistance limits its therapeutic potential. The human kinome is an undisputable source of druggable targets, still, current knowledge remains confined to a limited fraction of it, with a multitude of under‐investigated proteins yet to be characterized. Here, following a kinome‐wide RNAi screen, pantothenate kinase 4 (PANK4) isuncovered as a modulator of TMZ resistance in GBM. Validation of PANK4 across various TMZ‐resistant GBM cell models, patient‐derived GBM cell lines, tissue samples, as well as in vivo studies, corroborates the potential translational significance of these findings. Moreover, PANK4 expression is induced during TMZ treatment, and its expression is associated with a worse clinical outcome. Furthermore, a Tandem Mass Tag (TMT)‐based quantitative proteomic approach, reveals that PANK4 abrogation leads to a significant downregulation of a host of proteins with central roles in cellular detoxification and cellular response to oxidative stress. More specifically, as cells undergo genotoxic stress during TMZ exposure, PANK4 depletion represents a crucial event that can lead to accumulation of intracellular reactive oxygen species (ROS) and subsequent cell death. Collectively, a previously unreported role for PANK4 in mediating therapeutic resistance to TMZ in GBM is unveiled.

BackgroundObservational studies and some experimental investigations have indicated that gut microbiota are closely associated with the incidence and progression of chronic renal failure. However, the causal relationship between gut microbiota and chronic renal failure remains unclear. The present study employs a two-sample Mendelian randomization approach to infer the causal relationship between gut microbiota and chronic renal failure at the genetic level. This research aims to determine whether there is a causal effect of gut microbiota on the risk of chronic renal failure, aiming to provide new evidence to support targeted gut therapy for the treatment of chronic renal failure.MethodsEmploying genome-wide association study (GWAS) data from the public MiBioGen and IEU OpenGWAS platform, a two-sample Mendelian randomization analysis was conducted. The causal relationship between gut microbiota and chronic renal failure was inferred using five different methods: Inverse Variance Weighted, MR-Egger, Weighted Median, Simple Mode, and Weighted Mode. The study incorporated sensitivity analyses that encompassed evaluations for pleiotropy and heterogeneity. Subsequently, the results of the Mendelian randomization analysis underwent a stringent correction for multiple testing, employing the False Discovery Rate method to enhance the validity of our findings.ResultsAccording to the results from the Inverse Variance Weighted method, seven bacterial genera show a significant association with the outcome variable chronic renal failure. Of these, Ruminococcus (gauvreauii group) (OR = 0.82, 95% CI = 0.71–0.94, p = 0.004) may act as a protective factor against chronic renal failure, while the genera Escherichia-Shigella (OR = 1.22, 95% CI = 1.08–1.38, p = 0.001), Lactococcus (OR = 1.1, 95% CI = 1.02–1.19, p = 0.013), Odoribacter (OR = 1.23, 95% CI = 1.03–1.49, p = 0.026), Enterorhabdus (OR = 1.14, 95% CI = 1.00–1.29, p = 0.047), Eubacterium (eligens group) (OR = 1.18, 95% CI = 1.02–1.37, p = 0.024), and Howardella (OR = 1.18, 95% CI = 1.09–1.28, p

Precise traffic prediction is crucial in the domain of intelligent transportation. However, the task of accurately predicting traffic has struggled to keep pace with escalating application demands. One of the main reasons for this difficulty is the neglect of the dependence of surrounding spatial data on traffic information. In this study, we introduce a novel framework that incorporates the surrounding spatial data from the road network into the analysis of existing sensor graphs. We delve into an innovative method for traffic prediction by employing a heterogeneous graph that integrates the surrounding spatial information from the road network. The method is based on the common observation that traffic conditions are closely associated with surrounding spatial information, which can be analyzed utilizing heterogeneous graphs. Consequently, we propose a new framework, the heterogeneous attentive spatial–temporal network (HASTN). This framework constructs a heterogeneous graph that merges road networks with surrounding geographic features and employs attention mechanisms to learn traffic patterns. Our method achieves promising results on public datasets as well as a dataset we proposed. Additionally, we employ spatial information to analyze the impact of road traffic patterns on attention. This research offers a fresh perspective on addressing traffic prediction problems by integrating spatial information.

本研究依據學業情緒的控制—價值理論（Control-Value Theory, CVT）與認知—動機模式（cognitive-motivational model），採用前瞻性縱貫設計，解釋學習者的控制—價值評估如何互動，並透過愉悅／無聊情緒對動機涉入產生影響。據此，本研究首先考驗「控制評估→愉悅／無聊→動機涉入」的中介效果，以檢驗愉悅／無聊是否扮演中介變項角色；其次，以價值評估為調節變項，解釋價值評估是否調節上述的中介效果。本研究以468位臺灣七年級生為對象，進行為期3年，共包含三次的施測，蒐集資料以結構方程模式進行中介與條件化間接效果分析。研究指出：一、控制評估會透過愉悅／無聊進而對動機涉入產生中介效果，支持學業情緒的確為控制評估與動機涉入之中介變項；二、價值評估會調節上述中介效果：當學習者對數學學習的價值評估程度愈高時，學習者對數習學習的控制評估透過愉悅／無聊對動機涉入的正向間接效果則愈強，此結果支持控制—價值評估之互動觀點。 The academic emotion theory encompasses two main models: the control-value theory (CVT) and the cognitive motivational model. These models are used to examine the factors that precede and follow academic emotion (Pekrun et al., 2002). According to the CVT, academic emotions are closely related to how students perceive their control over learning and value achievement. When students perceive control and achievement, they experience positive emotions, such as enjoyment, hope, and pride, and their negative emotions, such as anxiety, hopelessness, or boredom, are reduced (Pekrun et al., 2002; Shao et al., 2020). The cognitive motivational model suggests that academic emotions affect learning and achievement through cognitive and motivational mechanisms, such as engagement (Pekrun et al., 2002). In summary, appraisals of control and value indirectly influence motivational engagement by shaping academic emotions. According to the CVT, academic emotions are not simply the result of control appraisal and value appraisal added together but rather a multiplicative function of these two factors. For instance, the effect of control appraisal on positive emotions, such as enjoyment, hope, and pride, is expected to be much stronger for students who have a higher value appraisal of academic study and achievement. Control appraisal and value appraisal interact for determining achievement-related emotions. Except for a few studies (Bieg et al., 2013; Goetz et al., 2010; Putwain et al., 2018; Shao et al., 2020), research so far has focused on investigating the separate (unique) effects (i.e., additive effects), rather than the interactive effects (i.e., synergistic effects), of control-value appraisals on academic emotions, learning, and achievement among students (Nagengast et al., 2011; Trautwein et al., 2012). Additionally, few studies in Taiwan have examined whether control appraisal and value appraisal have synergistic interaction effects on motivational engagement among students through academic emotions. In this study, we focused on two specific academic emotions: enjoyment and boredom. These emotions are frequently experienced in relation to achievement (Lüfteneggerr et al., 2016; Pekrun et al., 2002). Enjoyment is defined as a pleasant activating emotion, whereas boredom is defined as an unpleasant deactivating emotion. Both of these emotions are activity-related emotions (Pekrun, 2006). Additionally, researchers in the field of educational psychology often use motivational involvement as an external indicator of motivation. Motivational involvement refers to the learning strategies and actions adopted by students that contribute to their success in achieving learning goals (Pintrich & Schunk, 2008). Several studies have used indicators such as effort, persistence, and challenge-seeking and help-seeking behaviors to measure motivational engagement (Pintrich & Schunk, 2008). Accordingly, we integrated the CVT and the cognitive-motivational model to examine how control and value appraisal interact with the motivational engagement of students through enjoyment and boredom. The present study has two objectives. First, to construct mediation models to investigate the relationship between control appraisal, enjoyment/boredom, and motivational engagement (i.e., the indirect effects of control appraisal→ enjoyment/boredom→ motivational engagement). Second, to explore whether these mediation relationships can be moderated by value appraisal. Two research questions guided the research: (1) Does control appraisal have indirect effects on motivational engagement through the feelings of enjoyment and boredom? (2) Does value appraisal moderate the aforementioned mediation effects? In research question 1, we hypothesize that control appraisal exerts positive predictive effects on enjoyment and motivational engagement but has negative predictive effects on boredom. We also hypothesize that motivational engagement is positively predicted by enjoyment but is negatively predicted by boredom (research hypothesis 1-1). Furthermore, we hypothesize that enjoyment/boredom mediates the relationship between control appraisal and motivational engagement. In other words, control appraisal promotes enjoyment but reduces boredom, which in turn increases motivational engagement (research hypothesis 1-2). In research question 2, we hypothesize that value appraisal moderates the positive indirect effects of “control appraisal→enjoyment/boredom→ motivational engagement” (research hypothesis 2). Students from 18 seventh-grade classes in Taiwanese junior high schools were recruited in the present study. The study had a prospectivel ongitudinal design with three measurement waves to evaluate control-value appraisals, enjoyment, boredom, and motivational engagement. The first, second, and third measurements were conducted in October 2019 (T1), October 2020 (T2), and October 2021 (T3), respectively. Initially, 468 students volunteered to participate (with written parental consent) in this study. However, data from 18 participants were not included in the analyses because these participants were not present for all sessions. The final sample comprised 468 students (212 boys and 256 girls). Methodologically, three theoretical models were constructed: two mediation models and a conditional indirect effect model. These models were used to test the relationships between control-value appraisal, enjoyment/boredom, and motivational engagement. Collected data were analyzed using structural equation modeling to test both the mediation effects and conditional indirect effects. Additionally, prior achievement, prior enjoyment/boredom, prior motivational engagement, and gender were treated as control variables. In research hypothesis 1, the observed data support two mediation models. These models suggest that control appraisal influences enjoyment/boredom, which in turn influences motivational engagement. Specifically, control appraisal positively predicts enjoyment (and negatively predicts boredom), leading to increased motivational engagement. In research hypothesis 2, value appraisal moderates the positive indirect effects of “control appraisal→ (+) enjoyment→ (+) motivational engagement” and “control appraisal→ (−) boredom→ (−) motivational engagement.” When the level of value appraisal increases, the effects of control appraisal on enjoyment/boredom and subsequently on motivational engagement increase. Two main conclusions can be drawn from the aforementioned results. First, our results support the hypothesis that academic emotions (i.e., enjoyment and boredom) play mediating roles between control appraisal and motivational engagement. Second, our finding suggests that value appraisal moderates the aforementioned mediations. When the level of value appraisal increases, the influence of control appraisal on enjoyment/boredom and subsequently on motivational engagement increases. This result supports the interaction effects of control-value appraisals.

Abstract Background Impairment of cerebral autoregulation (CA) has been observed in patients undergoing cardiopulmonary bypass (CPB), but little is known about its risks and associations with outcomes. The cerebral oximetry index (COx), which is a moving linear correlation coefficient between regional cerebral oxygen saturation (rScO2) and mean blood pressure (MAP), may reflect CA function. When COx approaches 1, it implies that CA is damaged, whereas the CA is functional when the COx value approaches 0. The objective of this study was to analyze the incidence and risks of impaired CA, based on COx assessment, in patients undergoing total aortic arch replacement under systemic moderate hypothermia and circulatory arrest of the lower body (MHCA). We also evaluated the association between impaired CA and patient outcomes. Methods One hundred and fifty-four adult patients who underwent total aortic arch replacement with stented elephant trunk implantation under MHCA at our hospital were retrospectively analyzed. Patients were defined as having new-onset impaired CA if pre-CPB COx 0.3. Pre- and intraoperative factors were tested for independent association with impaired CA. Postoperative outcomes were compared between patients with normal and impaired CA. Results In our 154 patients, 46(29.9%) developed new-onset impaired CA after CPB. Multivariable analysis revealed a prolonged low rScO2 (rScO2

Herpes zoster (HZ) is an infectious disease caused by the reactivation of varicella zoster virus (VZV), with 68% of cases occurring in adults over 50 years of age. HZ/su (Shingrix®) was approved by the Food and Drug Administration in 2017 for the prevention of HZ in individuals ≥ 50 years of age and showed very good protection from HZ. However, due to the use of the adjuvant AS01B, adverse reactions caused by Shingrix are a concern. Aluminum hydroxide is the most commonly used adjuvant and is widely used in a variety of vaccines. We developed a recombinant zoster vaccine (code: LZ901) consisting of a tetramer of VZV glycoprotein E (gE) and a human Fc fusion protein expressed in CHO cells, an immune complex-like molecule that can be adsorbed with an aluminum hydroxide adjuvant. We compared the immunogenicity of LZ901 with that of HZ/su in BALB/c mice. The results showed that LZ901 induced levels of gE-specific IgG antibodies comparable to those induced by HZ/su, and the results of FAMA titers further demonstrated their similar neutralizing antibody abilities. Most importantly, LZ901 induced higher levels of cell-mediated immunity (CMI) (which plays a decisive role in the efficacy of zoster vaccines) than HZ/su in BALB/c mice. The numbers of cytokine-producing T cells in LZ901-vaccinated mice were significantly greater than those in v-vaccinated mice, and the proportions of CD4+ and CD8+ T cells producing at least two types of cytokines in LZ901-vaccinated mice were significantly greater than those in HZ/su-vaccinated mice.

Tendon Sheath Giant Cell Tumor (TGCT) is a benign tumor that primarily grows within joints and bursae. However, it has a high postoperative recurrence rate, ranging from 15% to 45%. Although radiotherapy may reduce this recurrence rate, its applicability as a standard treatment is still controversial. Furthermore, the pathogenic mechanisms of TGCT are not clear, which limits the development of effective treatment methods. The unpredictable growth and high recurrence rate of TGCT adds to the challenges of disease management. Currently, our understanding of TGCT mainly depends on pathological slice analysis due to a lack of stable cell models. In this study, we first reviewed the medical records of two female TGCT patients who had undergone radiotherapy. Then, by combining bioinformatics and machine learning, we interpreted the pathogenesis of TGCT and its associations with other diseases from multiple perspectives. Based on a deep analysis of the case data, we provided empirical support for postoperative radiotherapy in TGCT patients. Additionally, our further analysis revealed the signaling pathways of differentially expressed genes in TGCT, as well as its potential associations with osteoarthritis and synovial sarcomas.

BackgroundThe immune response to hepatitis B vaccine may be influenced by numerous factors, and patients with non/low response re-exposed to hepatitis B virus remain susceptible. Thus, a better understanding of the underlying mechanisms of non/low immune response in infants born to Hepatitis B surface antigen (HBsAg)-positive mothers is essential.Methods100 infants born to HBsAg-positive mothers from 2015 to 2020 were enrolled in the study, further divided into the non/low response group (n=13) and the moderate strong response group (n=87) based on the quantification of hepatitis B surface antibody at 12 months of age. The differential expression of 48 immune-related cytokines in the two groups was compared and analyzed in detail. The key cytokines were further identified and clinically predictive models were developed.ResultsWe found that 13 cytokines were lowly expressed and one cytokine was highly expressed in the non/low response group, compared with the moderate strong response group at birth. In addition, 9 cytokines were lowly expressed and one cytokine was highly expressed in the non/low response group at 12 months of age. Furthermore, we found that IL-5 and HGF were promising predictors for predicting the immunization response to hepatitis B vaccine in infants, and the combination of the two cytokines showed the best predictive efficiency, with an area under the curve (AUC) value of 0.844.ConclusionThe present study provides a theoretical basis on cytokines for developing and implementing effective immunotherapies against non/low immune response in infants born to HBsAg-positive mothers.

Plasmablastic lymphoma (PBL) is an aggressive non-Hodgkin lymphoma associated with HIV infection and immunodeficiency. However, PBL can also be seen immunocompetent individuals in recent studies. PBL was characterized by distinct clinical and pathological features, such as plasmablastic morphology and universal expression of plasma cell markers. The clinicopathologic features were different between HIV-negative and HIV-positive patients. Gene expression analysis identified the unique molecular feature in PBL, including frequent c-MYC rearrangement and downregulation of BCR signaling pathway. Despite the recent advances in the treatment of PBL, the prognosis of PBL patients remains dismal. The objectives of this review are to summarize the current knowledge on the epidemiology, molecular profiles, clinical and pathological features, differential diagnosis, treatment strategies, prognostic factors, and potential novel therapeutic approaches in PBL patients.

Drawing on the associative network memory theory (ANMT), this study aims to investigate the impact of social media marketing activities (SMMAs) on brand equity (BE) of luxury brands through the mediating role of brand image (BI) and the moderating role of word of mouth (WOM). This study employs a cross-sectional design to collect data from online adult users of Weibo in China. Data are analyzed in SmartPLS (v. 4.0.8.4) to evaluate the measurement model and the structural model. Findings of this study reveal that SMMAs have a significant positive impact on BI and BE. Besides, BI partially mediates the relationship between SMMAs and BE. Moreover, WOM moderates the association between SMMAs and BE such that the association is more potent at high levels of WOM and vice versa. This is one of the few studies that investigate the role of SMMAs on BE in the context of luxury brands, mediated by BI. Also, this is the first study that explores the moderating role of WOM in the relationship between SMMAs and BE through the mediating role of BI.

ABSTRACT The increasing prevalence of hypervirulent (hv) and carbapenem-resistant (CR) Klebsiella pneumoniae (Kp) highlights the importance of timely and accurate differential diagnosis for epidemiological investigation and clinical management. A multiplex quantitative real-time PCR (qRT-PCR) assay for the simultaneous identification of hvKp and CR-Kp was developed and validated with excellent performance in sensitivity and specificity. Generally, the gltA gene for Kp, the iucA, rmpA and rmpA2 genes for hvKp, and the Klebsiella pneumoniae carbapenemases (KPC) gene for CR-Kp were included in the qRT-PCR assay. The detection limits for classic Kp (cKp), CR-cKp, hvKp, and CR-hvKp strains could all reach 50 genome equivalent copies and 20 CFUs per reaction with high accuracy (R 2 > 0.99) and reliability (CV values < 3%). Detection results from 84 Kp positive clinical samples showed 31 hvKp with 8 CR-hvKp and 53 cKp with 1 CR-cKp strains. The presence of virulence-associated factors for the identified hvKp and KPC genes for CR-Kp was confirmed by previously developed conventional PCR and antimicrobial susceptibility tests, respectively. Furthermore, the qRT-PCR identified hvKp strains showed mortality rates of ≥40% in the outbred murine infection model, while no death for the identified cKp strains. These results indicated that our multiplex qRT-PCR assay could accurately identify hvKp and CR-Kp strains, which will be of great use for the rapid and accurate diagnosis in a clinical setting and the surveillance of the circulating Kp. IMPORTANCE Globally, the increasing number of hypervirulent Klebsiella pneumoniae (hvKp) and carbapenem-resistant Kp (CR-Kp) infections poses a huge public health challenge with high morbidity and mortality. Worrisomely, due to the mobility of elements carrying virulence and drug-resistance genes, the increasing prevalence of CR-hvKp has also been found with an overwhelming mortality rate in recent years. However, the current detection methods for hvKp and CR-Kp have many disadvantages, such as long turnaround time, complex operation, low sensitivity, and specificity. Herein, a more sensitive, rapid, single-reaction, and multiplex quantitative real-time PCR was developed and validated to differentiate the circulating lineages of Kp with excellent performance in sensitivity and specificity, providing a useful tool for the differential diagnosis and the surveillance of the circulating Kp.

Abstract Xrv proteins are a group of regulators in Xanthomonas spp., belonging to the histone-like nucleoid-structuring (H-NS) proteins of Gram-negative bacteria. The rice bacterial leaf streak pathogen Xanthomonas oryzae pv. oryzicola (Xoc) harbors three Xrv proteins, the XrvA, XrvB, and XrvC. Here, we report that in Xoc, the XrvB but not XrvA and XrvC is involved in negative regulation of the type III secretion system (T3SS) encoded by hrp genes. As with other Xanthomonas spp., the T3SS is an essential virulence determinant of Xoc and the expression of the hrp genes in Xoc is controlled by the HrpG/HrpX regulatory cascade. HrpG positively regulates the expression of HrpX, which in turn activates the transcription of the hrp genes. We provide evidences to demonstrate that the XrvB binds to the promoter region of hrpG and represses its transcription. Furthermore, we found that XrvB production was induced in the Xoc cells cultured in a nutrient-rich medium compared to a hrp-inducing minimal medium. We also found that in Xoc, the hrpG expression level is inversely correlated with the content of XrvB, and XrvB occupancy at hrpG promoter region is positively correlated with XrvB levels. Our data suggest that XrvB is a determinative factor controlling the expression levels of HrpG. In addition, mutation analysis revealed that the Xoc XrvB also plays positive roles in regulating bacterial growth, cell motility, and stress tolerance. Our findings provide important insights into the molecular mechanism of T3SS expression regulation in Xoc.

Abstract In this paper, a new reverse half-discrete Mulholland-type inequality with the nonhomogeneous kernel of the form h ( v ( x ) ln n ) $h(v(x)\ln n)$ and the best possible constant factor is obtained by using the weight functions and the technique of real analysis. The equivalent reverses are considered. As corollaries, we deduce some new equivalent reverse inequalities with the homogeneous kernel of the form k λ ( v ( x ) , ln n ) $k_{\lambda }(v(x),\ln n)$ . A few particular cases are provided. Our new reverse half-discrete Mulholland-type inequality which has a nonhomogeneous kernel is more general than in the previous homogeneous kernel work. The harmonized integration will have more applications.

This study is to explore underlying mechanism of skin wound healing by snakehead fish soup using rat and cell models. We assessed skin wound changes after administering wild and farmed snakehead fish soup intragastrically, then using CCK-8 and scratch tests to evaluate cell proliferation and migration, last assessed vessel tubule formation by HUVEC cells. The results showed that the skin wound healing rates of rats after 14 days of intragastrical administration of farmed and wild snakehead fish soup were 52.71% and 57.76%, respectively, which were substantially greater than the control group (39.84%). With the administration of the soups, the collagen tissue on the skin wound was more homogenous and thicker, and type I collagen was denser. Additionally, interleukin-6 level in rat serum during wound healing was significantly lower, while cyclin-D1 and fibroblast growth factor-2 levels were higher. Furthermore, the soups (particularly at 50 μg/mL) significantly increased the proliferation and migration rates of both the HACAT and NIH3T3 cells, and considerably promoted the tubule formation of HUVEC cells. The findings confirm that the soup can promote skin wound healing and the underlying mechanism involves multiple roles including anti-inflammation, cell proliferation, vessel tubule formation, and collagen expression.

This study focuses on constructions that are vulnerable to fire hazards during wildfire events, and these constructions are known as ‘exposures’, which are an increasingly significant area of disaster research. A key challenge lies in estimating dynamically and comprehensively the risk that individuals are exposed to during wildfire spread. Here, ‘exposure risk’ denotes the potential threat to exposed constructions from fires within a future timeframe. This paper introduces a novel method that integrates a spatiotemporal knowledge graph with wildfire spread data and an exposure risk analysis model to address this issue. This approach enables the semantic integration of varied and heterogeneous spatiotemporal data, capturing the dynamic nature of wildfire propagation for precise risk analysis. Empirical tests are employed for the study area of Xichang, Sichuan Province, using real-world data to validate the method’s efficacy in merging multiple data sources and enhancing the accuracy of exposure risk analysis. Notably, this approach also reduces the time complexity from O (m×n×p) to O (m×n).

Background: CpxAR is a two-component system that allows bacteria to reorganize envelope structures in response to extracellular stimuli. CpxAR negatively affects type 1 fimbriae expression in Klebsiella pneumoniae CG43, a hypervirulent strain. The involvement of CpxAR in the regulation of type 3 fimbriae expression was investigated. Methods: cpxAR, cpxA, and cpxR gene-specific deletion mutants were generated. The deletion effects on the expression of type 1 and type 3 fimbriae were analyzed via measuring the promoter activity, mannose sensitive yeast agglutination activity, biofilm formation, and the production of the major pilins FimA and MrkA respectively. RNA sequencing analysis of CG43S3, ΔcpxAR, ΔcpxR and Δfur was employed to study the regulatory mechanism influencing the expression of type 3 fimbriae. Results: Deletion of cpxAR increased type 1 and type 3 fimbrial expression. Comparative transcriptomic analysis showed that the expression of oxidative stress-responsive enzymes, type 1 and type 3 fimbriae, and iron acquisition and homeostasis control systems were differentially affected by cpxAR or cpxR deletion. Subsequent analysis revealed that the small RNA RyhB negatively affects the expression of type 3 fimbriae, while CpxAR positively controls ryhB expression. Finally, the site-directed mutation of the predicted interacting sequences of RyhB with the mRNA of MrkA attenuated the RyhB repression of type 3 fimbriae. Conclusion: CpxAR negatively regulates the expression of type 3 fimbriae by modulating cellular iron levels thereafter activating the expression of RyhB. The activated RyhB represses the expression of type 3 fimbriae by base-pairing binding to the 5′region of mrkA mRNA.

Abstract Background Efforts to precisely assess tumor-specific T-cell immune responses still face major challenges, and the potential molecular mechanisms mediating hepatocellular carcinoma (HCC) microenvironment imbalance after incomplete radiofrequency ablation (iRFA) are unclear. This study aimed to provide further insight into the integrated transcriptomic and proteogenomic landscape and identify a new target involved in HCC progression following iRFA. Methods Peripheral blood and matched tissue samples were collected from 10 RFA-treated HCC patients. Multiplex immunostaining and flow cytometry were used to assess local and systemic immune responses. Differentially expressed genes (DEGs) and differentially expressed proteins (DEPs) were explored via transcriptomic and proteogenomic analyses. Proteinase-3 (PRTN3) was identified in these analyses. And then, the ability of PRTN3 to predict overall survival (OS) was assessed in 70 HCC patients with early recurrence after RFA. In vitro CCK-8, wound healing and transwell assays were conducted to observe interactions between Kupffer cells (KCs) and HCC cells induced by PRTN3. The protein levels of multiple oncogenic factors and signaling pathway components were detected by western blotting. A xenograft mouse model was built to observe the tumorigenic effect of PRTN3 overexpression on HCC. Results Multiplex immunostaining revealed no immediate significant change in local immune cell counts in periablational tumor tissues after 30 min of iRFA. Flow cytometry showed significantly increased levels of CD4+ T cells, CD4+CD8+ T cells, and CD4+CD25+CD127− Tregs and significantly decreased the levels of CD16+CD56+ natural killer cells on day 5 after cRFA (p

Abstract. Background:. Ischemic acute kidney injury (AKI) is a common syndrome associated with considerable mortality and healthcare costs. Up to now, the underlying pathogenesis of ischemic AKI remains incompletely understood, and specific strategies for early diagnosis and treatment of ischemic AKI are still lacking. Here, this study aimed to define the transcriptomic landscape of AKI patients through single-cell RNA sequencing (scRNA-seq) analysis in kidneys. Methods:. In this study, scRNA-seq technology was applied to kidneys from two ischemic AKI patients, and three human public scRNA-seq datasets were collected as controls. Differentially expressed genes (DEGs) and cell clusters of kidneys were determined. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis, as well as the ligand–receptor interaction between cells, were performed. We also validated several DEGs expression in kidneys from human ischemic AKI and ischemia/reperfusion (I/R) injury induced AKI mice through immunohistochemistry staining. Results:. 15 distinct cell clusters were determined in kidney from subjects of ischemic AKI and control. The injured proximal tubules (PT) displayed a proapoptotic and proinflammatory phenotype. PT cells of ischemic AKI had up-regulation of novel pro-apoptotic genes including USP47, RASSF4, EBAG9, IER3, SASH1, SEPTIN7, and NUB1, which have not been reported in ischemic AKI previously. Several hub genes were validated in kidneys from human AKI and renal I/R injury mice, respectively. Furthermore, PT highly expressed DEGs enriched in endoplasmic reticulum stress, autophagy, and retinoic acid-inducible gene I (RIG-I) signaling. DEGs overexpressed in other tubular cells were primarily enriched in nucleotide-binding and oligomerization domain (NOD)-like receptor signaling, estrogen signaling, interleukin (IL)-12 signaling, and IL-17 signaling. Overexpressed genes in kidney-resident immune cells including macrophages, natural killer T (NKT) cells, monocytes, and dendritic cells were associated with leukocyte activation, chemotaxis, cell adhesion, and complement activation. In addition, the ligand–receptor interactions analysis revealed prominent communications between macrophages and monocytes with other cells in the process of ischemic AKI. Conclusion:. Together, this study reveals distinct cell-specific transcriptomic atlas of kidney in ischemic AKI patients, altered signaling pathways, and potential cell–cell crosstalk in the development of AKI. These data reveal new insights into the pathogenesis and potential therapeutic strategies in ischemic AKI.