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Abstract Purpose The primary objectives of this trial were aimed at exploring the pharmacokinetic profiles and the human bioequivalence of an intravenous liposomal injection of doxorubicin hydrochloride in comparison with a reference formulation in Chinese patients diagnosed with metastatic breast cancer. Methods To achieve these goals, the trial employed a randomized, open-label, two-formulation crossover dosing strategy among Chinese patients with metastatic breast cancer. Pharmacokinetic (PK) evaluation was conducted through the collection of blood samples, and the liquid chromatography tandem mass spectrometry (LC/MS/MS) method was leveraged to quantify plasma concentrations of both liposome-encapsulated doxorubicin and non-encapsulated doxorubicin in patients. Throughout the trial, all adverse events observed in the patients were meticulously assessed. Results The results indicated that the maximum concentration (Cmax), AUC from time zero to the last measurable concentration (AUC0-t), and AUC extrapolated to infinity (AUC0-∞) of in vivo non-encapsulated doxorubicin after administration of both formulations fell within the 80.00%–125.00% range at a 90% confidence interval. Conclusion These findings strongly indicated that the tested formulations were bioequivalent to the reference formulation. The results also demonstrated that both formulations were well-tolerated, further establishing their safety profile in the context of metastatic breast cancer treatment. Trial registration Chinadrugtrials.org.cn Identifier: CTR20200878.

Abstract Owing to their synergistic interactions, dual-atom catalysts (DACs) with well-defined active sites are attracting increasing attention. However, more experimental research and theoretical investigations are needed to further construct explicit dual-atom sites and understand the synergy that facilitates multistep catalytic reactions. Herein, we precisely design a series of asymmetric selenium-based dual-atom catalysts that comprise heteronuclear SeN2–MN2 (M = Fe, Mn, Co, Ni, Cu, Mo, etc.) active sites for the efficient oxygen reduction reaction (ORR). Spectroscopic characterisation and theoretical calculations revealed that heteronuclear selenium atoms can efficiently polarise the charge distribution of other metal atoms through short-range regulation. In addition, compared with the Se or Fe single-atom sites, the SeFe dual-atom sites facilitate a reduction in the conversion energy barrier from *O to *OH via the coadsorption of *O intermediates. Among these designed selenium-based dual-atom catalysts, selenium-iron dual-atom catalysts achieves superior alkaline ORR performance, with a half-wave potential of 0.926 V vs. a reversible hydrogen electrode. In addition, the SeN2–FeN2-based Zn–air battery has a high specific capacity (764.8 mAh g−1) and a maximum power density (287.2 mW cm−2). This work may provide a good perspective for designing heteronuclear DACs to improve ORR efficiency.

Probiotics participate in various physiological activities and contribute to body health. However, their viability and bioefficacy are adversely affected by gastrointestinal harsh conditions, such as gastric acid, bile salts and various enzymes. Fortunately, encapsulation based on various nanomaterials shows tremendous potential to protect probiotics. In this review, we introduced some novel encapsulation technologies involving nanomaterials in view of predesigned stability and viability, selective adhesion, smart release and colonization, and efficacy exertion of encapsulated probiotics. Furthermore, the interactions between encapsulated probiotics and the gastrointestinal tract were summarized and analyzed, with highlighting the regulatory mechanisms of encapsulated probiotics on intestinal mechanical barrier, chemical barrier, biological barrier and immune barrier. This review would benefit the food and pharmaceutical industries in preparation and utilization of multifunctional encapsulated probiotics.

Abstract Double-atom catalysts (DACs) have opened distinctive paradigms in the field of rapidly developing atomic catalysis owing to their great potential for promoting catalytic performance in various reaction systems. However, increasing the loading and extending the service life of metal active centres represents a considerable challenge for the efficient utilization of DACs. Here, we rationally design asymmetric nitrogen, sulfur-coordinated diatomic iron centres on highly defective nitrogen-doped carbon nanosheets (denoted A-Fe2S1N5/SNC, A: asymmetric), which possess the atomic configuration of the N2S1Fe-FeN3 moiety. The abundant defects and low-electronegativity heteroatoms in the carbon-based framework endow A-Fe2S1N5/SNC with a high loading of 6.72 wt%. Furthermore, A-Fe2S1N5/SNC has a low overpotential of 193 mV for the oxygen evolution reaction (OER) at 10 mA cm−2, outperforming commercial RuO2 catalysts. In addition, A-Fe2S1N5/SNC exhibits extraordinary stability, maintaining > 97% activity for over 2000 hours during the OER process. This work provides a practical scheme for simultaneously balancing the activity and stability of DACs towards electrocatalysis applications.

Abstract The analysis of people's daily activities has played a crucial role in various applications, such as urban geography, activity prediction, and homogeneous population detection. However, limited studies have explored changes in the residents’ activity patterns in a particular region across various periods. To explore the changes, a methodological framework of sequence visualization analysis based on machine learning that extracts the activity patterns across various periods using sequence analysis, visualizes the activity patterns by calculating the frequency of different activities at time points and categorizes them through graphical similarity, and then compares the activity patterns in terms of activity and demographic characteristics is proposed. Empirical testing on the New York Metropolitan data of the National Household Travel Survey (NHTS) is conducted for 2001, 2009, and 2017. The findings reveal significant intra‐similarities, inter‐differences, and distinct changes in activity patterns across three periods for different social populations in the New York Metropolitan. From the perspective of information analysis, this work is anticipated to enhance the understanding of travel needs for diverse social populations in a particular region, thereby facilitating targeted policy adjustments for the departments concerned.

Abstract This study aimed to investigate the potential correlation between the perfusion parameters of brain arteriovenous malformations (bAVMs) as determined by multiphase CT angiography and bAVM rupture. Based on the occurrence of bAVM-related hemorrhage, 480 diagnosed bAVM patients were divided into hemorrhage (n = 220) and non-hemorrhage (n = 260) groups in this retrospective multi-center study spanning 2010 to 2020. On initial rupture CT images, the bAVM nidus and major draining vein were segmented, and time-density curves were extracted to compute perfusion parameters including mean transit time (MTT), time to peak (TTP), blood volume (BV), and blood flow (BF). To examine the potential correlation between these parameters and bAVM rupture, logistic regression was utilized to analyze multifactorial data and compare differences between the two groups. The ruptured group demonstrated a bAVM nidus characterized by an increased BF, a shorter TTP and MTT, and a higher peak density. The veins that were draining exhibited a reduced TTP, MTT, and peak density. A nidus TTP of less than 4s was identified by the multifactorial analysis as a critical risk factor for bAVM rupture. The statistical results highlight the noteworthy correlation between nidus TTP and bAVM rupture, presenting an original framework for assessing the risk of rupture.

Background Periodontitis is not always satisfactorily treated with conventional scaling and root planing, and adjunctive use of antibiotics is required in clinical practice. Therefore, it is important for clinicians to understand the diversity and the antibiotic resistance of subgingival microbiota when exposed to different antibiotics. Materials and Methods In this study, subgingival plaques were collected from 10 periodontitis patients and 11 periodontally healthy volunteers, and their microbiota response to selective pressure of four antibiotics (amoxicillin, metronidazole, clindamycin, and tetracycline) were evaluated through 16S rRNA gene amplicon and metagenomic sequencing analysis. Additionally, sensitive and resistant strains were isolated and cultured in vitro for resistance evaluation. Results Cultivation of subgingival microbiota revealed the oral microbiota from periodontitis patients were more resistant to antibiotics than that of healthy. Significant differences were also observed for the microbial community between with and without antibiotics (especially amoxicillin and tetracycline) treated in periodontitis group. Conclusion Overall, after the two antibiotics (amoxicillin and tetracycline) exposed, the oral subgingival microbiota in periodontitis patients exhibited different diversity and composition. Streptococcus may account for oral biofilm-specific antibiotic resistance in periodontitis. This provides information for personalized treatment of periodontitis.

Abstract Mutations in the nuclear envelope (NE) protein lamin A/C (encoded by LMNA), cause a severe form of dilated cardiomyopathy (DCM) with early-onset life-threatening arrhythmias. However, molecular mechanisms underlying increased arrhythmogenesis in LMNA-related DCM (LMNA-DCM) remain largely unknown. Here we show that a frameshift mutation in LMNA causes abnormal Ca2+ handling, arrhythmias and disformed NE in LMNA-DCM patient-specific iPSC-derived cardiomyocytes (iPSC-CMs). Mechanistically, lamin A interacts with sirtuin 1 (SIRT1) where mutant lamin A/C accelerates degradation of SIRT1, leading to mitochondrial dysfunction and oxidative stress. Elevated reactive oxygen species (ROS) then activates the Ca2+/calmodulin-dependent protein kinase II (CaMKII)-ryanodine receptor 2 (RYR2) pathway and aggravates the accumulation of SUN1 in mutant iPSC-CMs, contributing to arrhythmias and NE deformation, respectively. Taken together, the lamin A/C deficiency-mediated ROS disorder is revealed as central to LMNA-DCM development. Manipulation of impaired SIRT1 activity and excessive oxidative stress is a potential future therapeutic strategy for LMNA-DCM.

Close-range sensing has yet to attain the status of being a dependable source for in situ forest information as the conventional field inventory. Each solution has its advantages and disadvantages in terms of accuracy, completeness, and efficiency. For a forest area, Terrestrial Laser Scanning (TLS) has the highest data quality, but is limited to static perspectives and lack the efficiency. Mobile Mapping Systems (MMS) systems gain on the efficiency but compromise the data quality. More recently, under-canopy UAV caught attentions for its potential to leverage the advantages of both TLS and MMS systems. This study demonstrates the feasibility of autonomous forest in situ investigation using an autonomous under-canopy UAV Laser Scanning (ULS) system, and evaluates the performance of such system in deriving key forest and tree attributes through a comparison with other close-range sensing systems such as the TLS and the Personal Laser Scanning (PLS). The under-canopy ULS system uses an onboard LiDAR sensor to aid its self-traverse in an unknown forest environment and to collect point cloud data during its movement inside the forest. Key factors influencing the systems’ overall performance were investigated via various experiments. The point cloud data collected by the under canopy autonomous ULS system deliver similar stem capturing capacity as TLS in single layer forest stands with less undergrowth. The RMSEs of the DBH estimates were 0.81 cm (3.80%), 4.12cm (19.92%), and 5.13cm (22.01%), respectively. The RMSEs of the stem curve estimates were 1.27 cm (5.48%), 3.97 cm (17.63%), and 5.18 cm (22.49%), respectively. The geometric accuracy and the completeness of the point cloud significantly improved when the trajectory was densified. More studies on autonomous route planning in complex unknown forest is required to improve the system mobility, data quality, and the applicability of such systems in future practical forest in situ observations.

With the fast-paced growth of underground engineering, the performance demands for construction materials are increasing. It is essential to explore the performance optimization of bentonite-based materials from admixture and material property’s view. In this paper, the rheological and filtration properties were selected as the key indices of the bentonite slurry performance. The synergistic effect of bentonite particle size and content, carboxymethyl starch (CMS), and Na2CO3 content on bentonite slurry performance were investigated by conducting the rheology measurement and filtration test. Rheological behaviour, parameters, and filtration loss of the bentonite slurry with different factors were obtained. Range analysis was employed to evaluate the effect degree of each factor on the slurry performance, and an optimal bentonite-based slurry ratio was presented. Results showed that bentonite slurry exhibited shear-thinning characteristic as the bentonite content and CMS content increased, and bentonite particle size decreased. Excessive addition of Na2CO3 weakened the shear-thinning characteristic. The rheological parameters of the bentonite slurry were positively correlated with the bentonite and CMS contents and negatively correlated with the bentonite particle size. An addition of 0.5 %–1.5 % Na2CO3 resulted in the largest rheological parameter. The bentonite content had the greatest impact on the rheological parameters and filtration loss, followed by the particle size. The influences of the Na2CO3 and CMS contents were relatively weak, but the effect of the CMS content on filtration loss was stronger than that of the Na2CO3 content. An optimal ratio of bentonite-based slurry was presented for engineering reference: the bentonite particle size range of 10–23 μm, bentonite content range of 10 %–15 %, Na2CO3 content range of 0.5 %–0.8 %, and CMS content range of 0.1 %–0.8 %.

Calcium- and integrin-binding protein 1 (CIB1) has a diverse role in many different cell types and processes, including calcium signaling, migration, adhesion, proliferation, and survival. It is associated with cancer, cardiovascular disease and male infertility. Here, CRISPR/Cas9 genome-editing technology was employed to establish a CIB1 knockout human embryonic stem cell line, which exhibited normal pluripotency and karyotype.

Brugada syndrome (BrS) is a hereditary arrhythmia syndrome characterized by right bundle branch block on an electrocardiogram and persistent ST-segment elevation in the right precordial leads. In this study, we describe the establishment of an induced pluripotent stem cell (iPSC) line derived from a BrS patient carrying the novel heterogeneous missense mutation (c.3118G>C; p.G1040R) in the sodium channel protein type 5 subunit alpha (SCN5A) gene. Skin fibroblasts underwent reprogramming using a non-integrated Sendai viral method. Generated iPSC line exhibited embryonic stem cell-like morphology, maintained a normal karyotype, expressed pluripotency markers, and demonstrated the capacity to differentiate into three germ layers.

This paper provides a historical overview of research on language teachers' beliefs and emotions, examining how studies on teacher emotions have influenced research on beliefs and classroom practices. Using bibliometric analysis, we mapped trends and paradigms in the literature, focusing on significant developments in this field. Our findings reveal a notable increase in publications on language teacher beliefs, particularly since 2018, indicating growing academic interest. Highly cited studies predominantly emphasize the emotional aspects of teaching, signaling a broader shift in research focus from cognitive to emotional dimensions, commonly referred to as the “emotional turn.” The analysis also identifies influential authors and institutions, with the USA, China, and the UK leading in contributions. Research themes have evolved over time, moving from foundational beliefs and teaching practices to more complex areas like teacher psychology, with particular attention to emotional regulation, identity, and agency in language teaching. Finally, we offer insights for future research, aiming to further explore the intricate relationship between teachers' beliefs and emotions.

This meta-analytic review examines the relationships between foreign language teachers’ burnout and two key factors: (1) job satisfaction and (2) emotion regulation. The analysis incorporates data from 14 studies with 3,812 participants to quantify these relationships and explore potential moderating factors. The results indicate a significant negative correlation between burnout and job satisfaction, as well as a strong negative correlation between burnout and emotion regulation. Moderator analyses reveal that country, educational setting, and education stage significantly influence these relationships. However, continuous moderators such as gender distribution and publication year did not significantly affect the outcomes. These findings underscore the importance of considering contextual factors in addressing burnout among foreign language teachers and suggest targeted interventions to enhance emotion regulation and job satisfaction in this population.

Abstract A promising new therapy option for acute kidney injury (AKI) is mesenchymal stem cells (MSCs). However, there are several limitations to the use of MSCs, such as low rates of survival, limited homing capacity, and unclear differentiation. In search of better therapeutic strategies, we explored all-trans retinoic acid (ATRA) pretreatment of MSCs to observe whether it could improve the therapeutic efficacy of AKI. We established a renal ischemia/reperfusion injury model and treated mice with ATRA-pretreated MSCs via tail vein injection. We found that AKI mice treated with ATRA-MSCs significantly improved renal function compared with DMSO-MSCs treatment. RNA sequencing screened that hyaluronic acid (HA) production from MSCs promoted by ATRA. Further validation by chromatin immunoprecipitation experiments verified that retinoic acid receptor RARα/RXRγ was a potential transcription factor for hyaluronic acid synthase 2. Additionally, an in vitro hypoxia/reoxygenation model was established using human proximal tubular epithelial cells (HK-2). After co-culturing HK-2 cells with ATRA-pretreated MSCs, we observed that HA binds to cluster determinant 44 (CD44) and activates the PI3K/AKT pathway, which enhances the anti-inflammatory, anti-apoptotic, and proliferative repair effects of MSCs in AKI. Inhibition of the HA/CD44 axis effectively reverses the renal repair effect of ATRA-pretreated MSCs. Taken together, our study suggests that ATRA pretreatment promotes HA production by MSCs and activates the PI3K/AKT pathway in renal tubular epithelial cells, thereby enhancing the efficacy of MSCs against AKI.

Abstract Interplay between innate and adaptive immune cells is important for the antitumor immune response. However, the tumor microenvironment may turn immune suppressive, and tumor associated macrophages are playing a role in this transition. Here, we show that CD276, expressed on tumor-associated macrophages (TAM), play a role in diminishing the immune response against tumors. Using a model of tumors induced by N-butyl-N-(4-hydroxybutyl) nitrosamine in BLCA male mice we show that genetic ablation of CD276 in TAMs blocks efferocytosis and enhances the expression of the major histocompatibility complex class II (MHCII) of TAMs. This in turn increases CD4 + and cytotoxic CD8 + T cell infiltration of the tumor. Combined single cell RNA sequencing and functional experiments reveal that CD276 activates the lysosomal signaling pathway and the transcription factor JUN to regulate the expression of AXL and MerTK, resulting in enhanced efferocytosis in TAMs. Proving the principle, we show that simultaneous blockade of CD276 and PD-1 restrain tumor growth better than any of the components as a single intervention. Taken together, our study supports a role for CD276 in efferocytosis by TAMs, which is potentially targetable for combination immune therapy.

Abstract Early warning of existing bridges is now predominated by deterministic methods. However, these methods face challenges in expressing uncertain factors (such as wind load, temperature load, and other variables, etc.). These problems directly impact the timeliness and accuracy of bridge early warning. This study develops an innovative method for bridge dynamic early warning with high versatility and accuracy. Long short-term memory network model (LSTM), expectation maximization (EM) and Gaussian mixture model (GMM) were employed in the proposed method. Firstly, the LSTM model is used to predict the measured monitoring data (such as deflection, strain, cable force, etc.) in real time to obtain the predicted results. Next, the number of clusters for the EM-GMM model is determined using the Calinski-Harabasz (CH) index. The method aims to comprehensively consider the internal cohesion of the clustering, ensuring accurate and reliable clustering results. Then, the EM-GMM model is used to cluster the random influence error and the predicted value, which can get the probabilistic prediction result of each corresponding random influence error. On this basis, the dynamic early warning interval under 95% confidence level is constructed. This facilitates early warning and decision-making for potential structural abnormalities. Finally, the accuracy and practicability of the method are verified by the comparison of engineering applications and existing specifications. The results demonstrate that the probabilistic early warning method considering the uncertain factors in the complex service environment can accurately achieve the dynamic early warning of bridges.

Abstract Warning and controlling the water invasion in water-driving reservoirs is significant because water invasion will seriously hamper well productivity and gas recovery. Unfortunately, there are few comprehensive methods to control water invasion. First, we establish and verify a water invasion model of reservoir scale. Then, a new workflow for warning and controlling the water invasion is proposed using the numerical simulation method. The workflow first judges the water invasion characteristics, determines the water invasion index based on the production data, and then controls the water invasion by finding and closing the perforation layer of serious water production. Finally, the optimal water control scheme is obtained by comparing water and gas production. The results show that the accuracy of the geological reserves of the established water invasion model is 99% and has a good pressure fitting result. The early warning chart for the gas reservoir in the west of Amu Darya B area is drawn, including the early warning pressure and the level 1, level 2, and level 3 early warning water–gas ratio, which is convenient for field application. For the water-driving wells west of area B, the early warning value of the water–gas ratio increases with the increase of gas production rate during fixed production and decreases with the increase of bottom hole pressure during constant pressure production. Closing the harmful perforation from the water-finding study will significantly reduce the water while retaining the gas production. After water control technology, water production decreased by 90.9%, while gas production decreased by only 9.7%.

The primary payload onboard the Gaofen-3-02 (GF3-02) satellite is a C-band Synthetic Aperture Radar (SAR) capable of achieving a maximum resolution of 1 m. This instrument is critical to monitor the marine environment, particularly for tracking sea surface wind speeds, an important marine environmental parameter. In this study, we utilized 192 sets of GF3-02 SAR data, acquired in Quad-Polarization Strip I (QPSI) mode in March 2022, to retrieve sea surface wind speeds. Prior to wind speed retrieval for vertical-vertical (VV) polarization, radiometric calibration accuracy was analyzed, yielding good performance. The results showed a bias and root mean square errors (RMSEs) of 0.02 m/s and 1.36 m/s, respectively, when compared to the European Centre for Medium-Range Weather Forecasts (ECMWF) Reanalysis V5 (ERA5) data. For horizontal–horizontal (HH) polarization, two types of polarization ratio (PR) models were introduced based on the GF3-02 SAR data. Combining these refitted PR models with CMOD5.N, the results for HH polarization exhibited a bias of −0.18 m/s and an RMSE of 1.25 m/s in comparison to the ERA5 data. Regarding vertical–horizontal (VH) polarization, two linear models based on both measured normalized radar cross sections (NRCSs) and denoised NRCSs were developed. The findings indicate that denoising significantly enhances the accuracy of wind speed measurements for VH polarization when dealing with low wind speeds. When compared against buoy data, the wind speed retrieval results demonstrated a bias of 0.23 m/s and an RMSE of 1.77 m/s. Finally, a comparative analysis of the above retrieval results across all three polarizations was conducted to further understand their respective performances.

Resilience and flow are crucial in language education, yet most research focuses on formal learning environments, with limited studies on their impact in informal settings. This study explores the relationship between basic psychological needs and engagement in the context of informal digital English learning (IDLE). Using a mixed-methods design, data were collected from 512 Chinese EFL learners. Structural equation modeling and NVivo analysis were applied to quantitative and qualitative data, respectively. The findings reveal that resilience fully mediates the relationship between basic psychological needs and engagement, serving as an adaptability enhancer, persistence promoter, stress buffer, self-efficacy builder, and emotional regulation facilitator. Conversely, flow partially mediates this relationship, though perceived competence does not significantly predict flow in this context. Building on this, flow contributes as an intrinsic motivation driver, positive cycle creator, external pressure mitigator, and efficiency enhancer. This research underscores the important role of resilience and flow in IDLE among Chinese university EFL students. By highlighting these mediating roles, the study provides valuable insights for enhancing the effectiveness of IDLE experiences, contributing to the broader discourse on language education in the digital age.

Objective: To investigate a case of neurodevelopmental disorder caused by mutation of FBXW7.Methods: Clinical data were collected from the patient, trio-WES (whole-exome sequencing) was performed on the patient and his parents (trio), and the results were verified by Sanger sequencing. RESULTS: The patient was a 2-year and 1-month old male who presented with facial dysmorphism (prominent forehead, ocular hypertelorism, and low nasal bridge), global developmental delay, language impairment, hypertonia, labial hemangioma, hydrocele, and overgrowth. The trio-WES confirmed that the child had a pathogenic de novo FBXW7 gene variant, c.1612C>T (p.G1n538*), a heretofore unreported locus.Conclusion: This case of developmental delay, hypotonia, and impaired language (OMIM: #620012) related to a mutation in FBXW7, is a rare genetic disorder, newly identified in recent years, and seldom reported. The presence of hypertonia, labial hemangioma, and hydrocele in this child suggests significant phenotypic heterogeneity of the disease, and the discovery of new mutant loci enriches the spectrum of pathogenic variants of the disease.

Birds are sensitive to environmental changes and can drive range shifts rapidly due to their high mobility. Though previous studies have examined the associations between species traits and range shifts, whether species traits could still explain heterogeneity in shift directions remains poorly explored. Here, we compiled new bird records of China from 2000 to 2019 and analyzed species traits associated with apparent shift directions. We collected 350 provincial-level new records of birds belonging to 67 families of 22 orders. Of these, 32 are threatened, with 3 critically endangered, 11 endangered, and 18 vulnerable. Provinces in western China (i.e., Yunnan and Xizang) had relatively higher species richness of new recorded birds; this pattern was also reflected in the phylogenetic diversity we observed. In addition, provinces in northern China (i.e., Tianjin, Shandong, and Beijing) had relatively higher richness-controlled phylogenetic diversity. Phylogenetic overdispersion of new recorded bird communities was observed in 61.29% of provinces (19 of 31). The main shift directions indicated by new bird records were northward (with nearly 50% of birds moving NW, N and NE). Migration, hand-wing index (HWI), body mass, and range size are the four key factors that most significantly influence the shift directions in bird species, suggesting that bird movement toward newly suitable areas varies with species-specific traits. Together, these results demonstrate the importance of considering species ecological traits when predicting shift directions of birds.

Objective: To assess the changes in QRS duration (△QRSd) before and after primary percutaneous coronary intervention(PPCI) regarding the relation of left ventricular ejection fraction (LVEF) in patients after a first acute ST segment elevation myocardial infarction (STEMI) treated with primary percutaneous coronary intervention (PPCI). Methods: A total of 244 patients with STEMI were enrolled, and clinical, biochemical, and angiographic parameters were compared between two groups based on LVEF at 6 months post-discharge. QRS duration (QRSd) was analyzed in relation to LVEF, and feature selection using least absolute shrinkage and selection operator(LASSO) regression was performed. Logistic regression analysis and receiver operating characteristic (ROC) curve evaluation were conducted to identify predictors and assess model efficacy. Results: Significant differences were observed between the two groups in terms of various parameters, including age, time from symptom onset to balloon dilation (STB), N-terminal pro B-type natriuretic peptide (NT-proBNP) levels, Left ventricular end-diastolic volume(LVEDV) at baseline, left ventricular end-systolic volume(LVESV)at baseline, left ventricular end-diastolic diameter (LVDD)at baseline and six months, hospital length of stay(days), ST-segment resolution (STR), the left anterior descending artery as the infarction-related artery (IRA-LAD), frequency of TIMI 3 flow post PPCI, thrombus aspiration and/or intracoronary thrombolysis, the use of tirofiban, and the number of implanted stents(stents).In addition, postoperative QRSd and △QRSd were significantly higher in patients with left ventricular systolic dysfunction(LVSD). LASSO regression selected six variables as predictors of postoperative LVEF. Logistic regression analysis identified age, STB, NT-proBNP, LVESV at baseline,△QRSd, and stents, as independent factors associated with LVSD within six months for patients with a first occurrence of STEMI. The models achieved AUC values of 0.906 (using ΔQRSd),0.922(using 6 variables excluding ΔQRSd) and 0.962 (using 6 variables). Conclusion: This study identified ΔQRSd as a potential predictor of LVSD in patients with STEMI. The developed models showed good efficacy in predicting postoperative LVEF changes. These findings may contribute to risk stratification and individualized management strategies for STEMI patients.

Abstract Background Hypertension influences the inflammatory pathological changes in the retina. The function of the inflammasomes is significant. To see if Sirtuin 1 (SIRT1) regulates angiotensin II (Ang II)-induced hypertensive retinopathy and inflammation by modulating NOD-like receptor thermal protein domain associated protein 3 (NLRP3) inflammasome activation and the potential protective effects of fucoidan (FO) in mouse retinal vascular endothelial cells (mRECs) and mice retina. Methods The diagnosis of hypertensive retinopathy was made after three weeks of Ang II infusion (3000 ng/kg/min). One day prior to the commencement of Ang II infusion, the mice were treatment with NLRP3 inhibitor MCC950 (10 mg/kg/day, intraperitoneal injections) or FO (300 mg/kg/day, oral gavage). A blood pressure was recorded. Hematoxylin and eosin (H&E) staining was used to conduct pathological alterations, dihydroethidium bromide (DHE) was utilized to assess oxidative stress damage in the retina, and fluorescence angiography was used to identify vascular disorders in the eye. Using immunohistochemical labeling, NLRP3 expression was found. Reactive protein and mRNA expression levels in mouse retina and cells were assessed using Western blot and real-time quantitative polymerase chain reaction (RT-qPCR). Results NLRP3 inflammasome activation and SIRT1 decrease were brought about by Ang II infusion. Retinopathy and dysfunction were lessened by MCC950 target-induced NLRP3 inflammasome activation, while overexpression of SIRT1 had the opposite impact on NLRP3 inflammasome activation, indicating that SIRT1 functions as an upstream regulator of NLRP3 activity. FO may improve SIRT1 expression and decrease NLRP3 activation in retinopathy and dysfunction brought on by Ang II, and the effects were consistent across both in vivo and in vitro models. Conclusions SIRT1 adversely regulates the NLRP3 inflammasome pathway, which in turn increases Ang II-induced inflammation and hypertensive retinopathy. FO may mitigate Ang II-induced retinopathy and dysfunction via modulating the expression of SIRT1/NLRP3. This implies practical approaches to the management of hypertensive retinopathy.

Abstract Existing studies have underscored the pivotal role of N-acetyltransferase 10 (NAT10) in various cancers. However, the outcomes of protein-protein interactions between NAT10 and its protein partners in head and neck squamous cell carcinoma (HNSCC) remain unexplored. In this study, we identified a significant upregulation of RNA-binding protein with serine-rich domain 1 (RNPS1) in HNSCC, where RNPS1 inhibits the ubiquitination degradation of NAT10 by E3 ubiquitin ligase, zinc finger SWIM domain-containing protein 6 (ZSWIM6), through direct protein interaction, thereby promoting high NAT10 expression in HNSCC. This upregulated NAT10 stability mediates the enhancement of specific tRNA ac4C modifications, subsequently boosting the translation process of genes involved in pathways such as IL-6 signaling, IL-8 signaling, and PTEN signaling that play roles in regulating HNSCC malignant progression, ultimately influencing the survival and prognosis of HNSCC patients. Additionally, we pioneered the development of TRMC-seq, leading to the discovery of novel tRNA-ac4C modification sites, thereby providing a potent sequencing tool for tRNA-ac4C research. Our findings expand the repertoire of tRNA ac4C modifications and identify a role of tRNA ac4C in the regulation of mRNA translation in HNSCC.

Due to the small scale and short lifetimes of mode-2 internal solitary waves (ISWs), they are seldom observed by satellite images. This study investigated the optical remote sensing imaging characteristics of mode-2 ISWs through physical simulation experiments, proposed a method for identifying mode-2 ISWs in optical remote sensing images, and conducted multisource optical remote sensing observation of mode-2 ISWs in the northern South China Sea (SCS). We have gathered over 10 000 images from seven optical remote sensing satellites, including Terra/Aqua, Gaofen-1/6, HJ-2A/B, and CBERS-04. A total of 342 mode-2 ISWs events were identified, exhibiting primary concentrations near Dongsha Atoll and the northern Heng–Chun Ridge in the northeastern SCS, as well as the Shenhu–Yitong Shoals in the northwestern SCS. Most mode-2 ISWs were observed within the 150–400 m water depth range along the continental shelf. The mode-2 ISWs primarily propagate in a northwestern direction, with propagation speeds approximately half that of the mode-1 ISWs. In the case of the northern Heng–Chun Ridge, mode-2 ISWs tended to propagate in a southwest direction. This study underscores the significant potential of high-resolution optical remote sensing satellites in observing mode-2 ISW and provides a new direction for studying mode-2 ISW.

Tensions between policies and practices have long been studied. When the Breaking Five-Only Policy was issued in October 2020 in China, it was a cause for controversy and debate among scholars and educators. Take the publications-only or S/SCI paper supremacy policy, for example; the proposed policy encourages scholars and educators to publish their papers in domestic journals instead of international or S/SCI-indexed journals. However, scholars and educators have reported that it is even more challenging to publish in domestic journals for various reasons. We thus examined this dilemma by comparing journal metrics of 12 Chinese journals and 12 English ones in the same field. Specifically, we studied how academic publications had been measured in terms of statistics and parameters, including the title ranks, funds, and university ranks of the authors, typically in the Chinese context. We set up different hypotheses, analyzed the data, reported the quantitative findings, and tested the proposed hypotheses. Then, we discussed our results and argued that coercive and authoritarian accountability, quantity over quality, and ever-increased involution are major forces that drive the audit culture with regard to academic performance in the Chinese context. We concluded the paper with hidden tensions between the policy and reality and advocated for continued efforts for policy implementation and reform.

Abstract Imitation is an important learning heuristic in animal and human societies. Previous explorations report that the fate of individuals with cooperative strategies is sensitive to the protocol of imitation, leading to a conundrum about how different styles of imitation quantitatively impact the evolution of cooperation. Here, we take a different perspective on the personal and external social information required by imitation. We develop a general model of imitation dynamics with incomplete information in networked systems, which unifies classical update rules including the death-birth and pairwise-comparison rule on complex networks. Under pairwise interactions, we find that collective cooperation is most promoted if individuals neglect personal information. If personal information is considered, cooperators evolve more readily with more external information. Intriguingly, when interactions take place in groups on networks with low degrees of clustering, using more personal and less external information better facilitates cooperation. Our unifying perspective uncovers intuition by examining the rate and range of competition induced by different information situations.

Introduction: Human enterovirus D68 (EV-D68), which belongs to enteroviruses of the small RNA family, is a type of enterovirus that can cause acute respiratory tract infection and central nervous system diseases. This study systematically analysed and summarized EV-D68 antibody studies in databases and identified the seropositivity rates of different regions, ages, and sexes. Methods: Meta-analysis was performed using STATA 16.0 software. I2 and Q tests were used to analyse the heterogeneity of the included studies. Meta-regression analysis was performed for different groups, and Egger’s linear regression analysis was used to evaluate publication bias. Results: The results of multiple studies indicated that the serological prevalence range of EV-D68 antibody was 17.78–96.69%. The results of the meta-analysis showed that the seropositivity rate of EV-D68 antibody was 76% (95% confidence interval [CI]: 67–84%), among which that of the Chinese population was 74% (95% CI: 61–86%) and that of other countries was 79% (95% CI: 65–91%). At the same time, a subgroup analysis was conducted. The seroprevalence of EV-D68 antibody was related to age but not sex or region. Conclusion: The seropositivity rate was lower in the below 5-year age group; however, it gradually increased with age. The results of this study showed that EV-D68 infection was widespread in the population, and the current clinical infection situation could not reflect the actual epidemic situation of the virus, among which children under 5 years old were vulnerable to infection, which should be given greater attention for epidemic prevention and control.

A Diffuse Leptomeningeal Glioneuronal Tumor (DLGNT), a rare entity as classified in the World Health Organization’s Fifth Edition of the Classification of Tumors of the Central Nervous System (WHO CNS5), is characterized by oligodendrocyte-like cells with MAPK pathway alterations. This report details the case of a 29-year-old female presenting with unique radiological features: extensive spinal cord dissemination involving both parenchyma and leptomeninges, without intracranial involvement. Near-total resection (NTR) was performed, revealing H3K27me3 positivity, a molecular characteristic not previously reported in DLGNTs. We also review recent studies to expand the understanding of DLGNT’s clinical, imaging, and molecular profiles, aiming to assist radiologists and clinicians in accurate diagnosis and timely management.

Globally, lung cancer stands as the leading type of cancer in terms of incidence and is the major source of mortality attributed to cancer. We have outlined the molecular biomarkers for lung cancer that are available clinically. Circulating tumor cells (CTCs) spread from the original location, circulate in the bloodstream, extravasate, and metastasize, forming secondary tumors by invading and establishing a favorable environment. CTC analysis is considered a common liquid biopsy method for lung cancer. We have enumerated both in vivo and ex vivo techniques for CTC separation and enrichment, examined the advantages and limitations of these methods, and also discussed the detection of CTCs in other bodily fluids. We have evaluated the value of CTCs, as well as CTCs in conjunction with other biomarkers, for their utility in the early detection and prognostic assessment of patients with lung cancer. CTCs engage with diverse cells of the metastatic process, interfering with the interaction between CTCs and various cells in metastasis, potentially halting metastasis and enhancing patient prognosis.

Objective: Acute liver and kidney injury is the most common complication after aortic surgery, which seriously affects the survival and safety of perioperative patients. The presence of chronic preoperative liver and renal insufficiency, presence of preoperative blood inflammation indicators, duration of intraoperative extracorporeal circulation, and volume of red blood cell transfusion are the main influencing factors for acute postoperative liver and kidney injuries. In recent years, with the research progress on oxidative stress, a growing body of evidence has demonstrated that oxidative stress may cause tissue damage after ischemia–reperfusion (IR). However, the impact of the oxidative stress of distal tissues caused by IR on liver and renal cells after arterial surgeries has not yet been elucidated. Methods: New Zealand white rabbits were used for the experiments and were divided into three groups. Among them, two groups were fed high-fat feed to establish a white rabbit model of hypertriglyceridemia, whereas the control group was provided with ordinary feed. In the experiment, white rabbits were subjected to occlusion of the infrarenal aorta abdominalis to simulate IR of the lower limbs. The effects of high triglyceride levels after the arterial IR of the lower limbs were investigated using the contents of reactive oxygen species (ROS) and malondialdehyde (MDA), a fat metabolite, in ischemic muscle tissues and blood tissues. One of the groups receiving high-fat feed received intervention with reduced glutathione (GSH) before IR of the lower limbs. Pathological studies were performed to identify the expression levels of inflammatory factors and inflammatory cells in liver and renal cells as well as cell apoptosis. The effects of GSH administration before IR on reducing the oxidative stress in adipose tissues and alleviating liver and kidney damage after stress response were investigated. Results: After IR, the increases in ROS and MDA in ischemic muscle tissues and blood tissues were higher in white rabbits with high triglyceride levels than in those that only received ordinary feed or received intervention with GSH. In addition, for white rabbits with high triglyceride levels, the TNF-α expression levels in the liver increased after IR. Moreover, a considerable increase in the expression of TNF-α, IL-6, macrophages, and T lymphocytes were observed in renal cells. A large number of inflammatory cells and the formation of immune complexes were also noted in the glomeruli; in addition, cell apoptosis was promoted. Conclusion: This study showed that high triglyceride levels enhanced the oxidative stress response and increased ROS production in New Zealand white rabbits after arterial IR of the lower limbs. High ROS levels activated the expression of inflammatory factors and inflammatory cells in the liver and kidney, which affected cell functions and promoted apoptosis. At high triglyceride levels, GSH downregulated ROS production in oxidative stress after IR, thereby protecting liver and kidney functions.

Objectives This study aims to investigate the impact of digital engagement on urban-rural disparities in depressive symptoms among Chinese women. Methods Using a dataset from the China Family Panel Studies (CFPS) wave 2020, this study analyzes the impact of digital engagement on the urban-rural disparity in women's depressive symptoms using multiple linear regression and recentered influence function (RIF) models. Furthermore, the extent to which digital engagement affects the urban-rural disparity in women's depressive symptoms was calculated using the RIF decomposition method. Results Analysis showed that rural women had significantly higher levels of depressive symptoms compared to urban women; digital engagement significantly reduced women's depressive symptoms levels and mitigated the urban-rural disparity for women with moderate to high levels of depressive symptoms, and the mitigating effect was stronger for the highly depressed sample, but still widened the urban-rural disparity in women's depressive symptoms overall. In addition, the results of the RIF decomposition showed that digital engagement explained 28.28% of the urban-rural disparity in women's depressive symptoms. Conclusion There is a significant disparity in depressive symptoms levels between urban and rural women in China. Digital engagement reduces women's depressive symptoms, but it also widens the depressive symptoms disparity between urban and rural women overall. Digital engagement is potentially positive for reducing women's depressive symptoms.

Introduction: Glaucoma, a principal cause of irreversible vision loss, is characterized by intricate optic neuropathy involving significant immune mechanisms. This study seeks to elucidate the molecular and immune complexities of glaucoma, aiming to improve our understanding of its pathogenesis.Methods: Gene expression profiles from glaucoma patients were analyzed to identify immune-related differentially expressed genes (DEGs). Techniques used were weighted gene co-expression network analysis (WGCNA) for network building, machine learning algorithms for biomarker identification, establishment of subclusters related to immune reactions, and single-sample gene set enrichment analysis (ssGSEA) to explore hub genes’ relationships with immune cell infiltration and immune pathway activation. Validation was performed using an NMDA-induced excitotoxicity model and RT-qPCR for hub gene expression measurement.Results: The study identified 409 DEGs differentiating healthy individuals from glaucoma patients, highlighting the immune response’s significance in disease progression. Immune cell infiltration analysis revealed elevated levels of activated dendritic cells, natural killer cells, monocytes, and immature dendritic cells in glaucoma samples. Three hub genes, CD40LG, TEK, and MDK, were validated as potential diagnostic biomarkers for high-risk glaucoma patients, showing increased expression in the NMDA-induced excitotoxicity model.Discussion: The findings propose the three identified immune-related genes (IRGs) as novel diagnostic markers for glaucoma, offering new insights into the disease's pathogenesis and potential therapeutic targets. The strong correlation between these IRGs and immune responses underscores the intricate role of immunity in glaucoma, suggesting a shift in the approach to its diagnosis and treatment.

BackgroundThe dysregulated immune response to sepsis still remains unclear. Stratification of sepsis patients into endotypes based on immune indicators is important for the future development of personalized therapies. We aimed to evaluate the immune landscape of sepsis and the use of immune clusters for identifying sepsis endotypes.MethodsThe indicators involved in innate, cellular, and humoral immune cells, inhibitory immune cells, and cytokines were simultaneously assessed in 90 sepsis patients and 40 healthy controls. Unsupervised k-means cluster analysis of immune indicator data were used to identify patient clusters, and a random forest approach was used to build a prediction model for classifying sepsis endotypes.ResultsWe depicted that the impairment of innate and adaptive immunity accompanying increased inflammation was the most prominent feature in patients with sepsis. However, using immune indicators for distinguishing sepsis from bacteremia was difficult, most likely due to the considerable heterogeneity in sepsis patients. Cluster analysis of sepsis patients identified three immune clusters with different survival rates. Cluster 1 (36.7%) could be distinguished from the other clusters as being an “effector-type” cluster, whereas cluster 2 (34.4%) was a “potential-type” cluster, and cluster 3 (28.9%) was a “dysregulation-type” cluster, which showed the lowest survival rate. In addition, we established a prediction model based on immune indicator data, which accurately classified sepsis patients into three immune endotypes.ConclusionWe depicted the immune landscape of patients with sepsis and identified three distinct immune endotypes with different survival rates. Cluster membership could be predicted with a model based on immune data.

Cellular collective motion in confluent epithelial monolayers is involved in many processes such as embryo development, carcinoma invasion, and wound healing. The development of new chemical strategies to achieve large-scale control of cells’ collective motion is essential for biomedical applications. Here a series of DNA nanostructures with different dimensions were synthesized and their influences on cells’ collective migration and packing behaviors in epithelial monolayers were investigated. We found that the framed DNA nanoassemblies effectively reduced the cells’ speed by increasing the rigidity of cells, while the lipid-DNA micelles had a more pronounced effect on cells’ projection area and shape factor. These DNA nanostructures all significantly enhanced the dependence of cells’ speed on their shape factor. Our results indicate that cells’ mobility in monolayers can be manipulated by chemical intercellular interactions without any genetic intervention. This may provide a new chemical strategy for tissue engineering and tumor therapy.

Abstract Background Mutations in the cardiac sodium channel gene SCN5A cause Brugada syndrome (BrS), an arrhythmic disorder that is a leading cause of sudden death and lacks effective treatment. An association between SCN5A and Wnt/β-catenin signaling has been recently established. However, the role of Wnt/β-catenin signaling in BrS and underlying mechanisms remains unknown. Methods Three healthy control subjects and one BrS patient carrying a novel frameshift mutation (T1788fs) in the SCN5A gene were recruited in this study. Control and BrS patient-specific induced pluripotent stem cells (iPSCs) were generated from skin fibroblasts using nonintegrated Sendai virus. All iPSCs were differentiated into cardiomyocytes using monolayer-based differentiation protocol. Action potentials and sodium currents were recorded from control and BrS iPSC-derived cardiomyocytes (iPSC-CMs) by single-cell patch clamp. Results BrS iPSC-CMs exhibited increased burden of arrhythmias and abnormal action potential profile featured by slower depolarization, decreased action potential amplitude, and increased beating interval variation. Moreover, BrS iPSC-CMs showed cardiac sodium channel (Nav1.5) loss-of-function as compared to control iPSC-CMs. Interestingly, the electrophysiological abnormalities and Nav1.5 loss-of-function observed in BrS iPSC-CMs were accompanied by aberrant activation of Wnt/β-catenin signaling. Notably, inhibition of Wnt/β-catenin significantly rescued Nav1.5 defects and arrhythmic phenotype in BrS iPSC-CMs. Mechanistically, SCN5A-encoded Nav1.5 interacts with β-catenin, and reduced expression of Nav1.5 leads to re-localization of β-catenin in BrS iPSC-CMs, which aberrantly activates Wnt/β-catenin signaling to suppress SCN5A transcription. Conclusions Our findings suggest that aberrant activation of Wnt/β-catenin signaling contributes to the pathogenesis of SCN5A-related BrS and point to Wnt/β-catenin as a potential therapeutic target.

The composition of the gut microbiota varies among end-stage renal disease (ESRD) patients on the basis of their mode of renal replacement therapy (RRT), with notably more pronounced dysbiosis occurring in those undergoing hemodialysis (HD). Interventions such as dialysis catheters, unstable hemodynamics, strict dietary restrictions, and pharmacotherapy significantly alter the intestinal microenvironment, thus disrupting the gut microbiota composition in HD patients. The gut microbiota may influence HD-related complications, including cardiovascular disease (CVD), infections, anemia, and malnutrition, through mechanisms such as bacterial translocation, immune regulation, and the production of gut microbial metabolites, thereby affecting both the quality of life and the prognosis of patients. This review focuses on alterations in the gut microbiota and its metabolites in HD patients. Additionally, understanding the impact of the gut microbiota on the complications of HD could provide insights into the development of novel treatment strategies to prevent or alleviate complications in HD patients.

Teaching satisfaction and resilience play important roles in the education field, but most research focuses on higher education, with few scholars studying their impact on language teaching within the context of middle school education. In this sense, this study employs a mixed-methods research design, selecting 375 Chinese middle school English teachers to investigate the roles of teaching satisfaction and resilience in the relationship between self-efficacy and teachers’ well-being. A structural equation modeling approach and NVivo were utilized to analyze quantitative data and qualitative data, respectively. Quantitative results reveal that both teaching satisfaction and resilience mediate the relationship between self-efficacy and teachers’ well-being. Qualitative interviews reveal that teaching satisfaction primarily enhances job commitment, reduces job stress, improves student relationships, and increases professional growth. Meanwhile, resilience plays a crucial role in stress management, positive adaptation, and emotional regulation. This research offers insightful implications for improving teachers’ well-being and contributes significantly to the broader discourse on foreign language teacher education.

Abstract In this work, an ultrathin acoustic metamaterial formed by space-coiled water channels with a rubber coating is proposed for underwater sound absorption. The proposed metamaterial achieves perfect sound absorption ( $$\alpha$$ α > 0.99) at 181 Hz, which has a deep subwavelength thickness ( $$\lambda {/}162$$ λ / 162 ). The theoretical prediction is consistent with the numerical simulation, which demonstrate the broadband low-frequency sound absorption performance of the proposed super absorber. The introduction of rubber coating leads to a significant decrease of the effective sound speed in the water channel, resulting in the phenomenon of slow-sound propagation. From the perspective of numerical simulations and acoustic impedance analysis, it is proved that the rubber coating on the channel boundary causes slow-sound propagation with inherent dissipation, which is the key to meet the impedance matching condition and achieve perfect low-frequency sound absorption. Parametric studies are also carried out to investigate the effect of specific structural and material parameters on sound absorption. By tailoring key geometric parameters, an ultra-broadband underwater sound absorber is constructed, with a perfect absorption range of 365–900 Hz and a deep subwavelength thickness of 33 mm. This work paves a new way for designing underwater acoustic metamaterials and controlling underwater acoustic waves.

Abstract Herein, we report a mild, operationally simple, multicatalytic method for the synthesis of β,γ-unsaturated ketones via allylic acylation of alkenes. Specifically, the method combines N‑heterocyclic carbene catalysis, hydrogen atom transfer catalysis, and photoredox catalysis for cross-coupling reactions between a wide range of feedstock carboxylic acids and readily available olefins to afford structurally diverse β,γ-unsaturated ketones without olefin transposition. The method could be used to install acyl groups on highly functionalized natural-product-derived compounds with no need for substrate pre-activation, and C–H functionalization proceed with excellent site selectivity. To demonstrate the potential applications of the method, we convert a representative coupling product into various useful olefin synthons.

Abstract Background Although human-induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs) are a promising cell resource for cardiovascular research, these cells exhibit an immature phenotype that hampers their potential applications. The inwardly rectifying potassium channel Kir2.1, encoded by the KCNJ2 gene, has been thought as an important target for promoting electrical maturation of iPSC-CMs. However, a comprehensive characterization of morphological and functional changes in iPSC-CMs overexpressing KCNJ2 (KCNJ2 OE) is still lacking. Methods iPSC-CMs were generated using a 2D in vitro monolayer differentiation protocol. Human KCNJ2 construct with green fluorescent protein (GFP) tag was created and overexpressed in iPSC-CMs via lentiviral transduction. The mixture of iPSC-CMs and mesenchymal cells was cocultured with decellularized natural heart matrix for generation of 3D human engineered heart tissues (EHTs). Results We showed that mRNA expression level of KCNJ2 in iPSC-CMs was dramatically lower than that in human left ventricular tissues. KCNJ2 OE iPSC-CMs yielded significantly increased protein expression of Kir2.1 and current density of Kir2.1-encoded IK1. The larger IK1 linked to a quiescent phenotype that required pacing to elicit action potentials in KCNJ2 OE iPSC-CMs, which can be reversed by IK1 blocker BaCl2. KCNJ2 OE also led to significantly hyperpolarized maximal diastolic potential (MDP), shortened action potential duration (APD) and increased maximal upstroke velocity. The enhanced electrophysiological maturation in KCNJ2 OE iPSC-CMs was accompanied by improvements in Ca2+ signaling, mitochondrial energy metabolism and transcriptomic profile. Notably, KCNJ2 OE iPSC-CMs exhibited enlarged cell size and more elongated and stretched shape, indicating a morphological phenotype toward structural maturation. Drug testing using hERG blocker E-4031 revealed that a more stable MDP in KCNJ2 OE iPSC-CMs allowed for obtaining significant drug response of APD prolongation in a concentration-dependent manner. Moreover, KCNJ2 OE iPSC-CMs formed more mature human EHTs with better tissue structure and cell junction. Conclusions Overexpression of KCNJ2 can robustly enhance maturation of iPSC-CMs in electrophysiology, Ca2+ signaling, metabolism, transcriptomic profile, cardiomyocyte structure and tissue engineering, thus providing more accurate cellular model for elucidating cellular and molecular mechanisms of cardiovascular diseases, screening drug-induced cardiotoxicity, and developing personalized and precision cardiovascular medicine.

Abstract Background Severe fever with thrombocytopenia syndrome (SFTS) is an emerging infectious disease, which is caused by severe fever with thrombocytopenia syndrome virus (SFTSV) with high fatality. Recently, the incidence of SFTS increased obviously in Jiangsu Province. However, the systematic and complete analysis of spatiotemporal patterns and clusters coupled with epidemiological characteristics of SFTS have not been reported so far. Methods Data on SFTS cases were collected during 2011–2021. The changing epidemiological characteristics of SFTS were analyzed by adopting descriptive statistical methods. GeoDa 1.18 was applied for spatial autocorrelation analysis, and SaTScan 10.0 was used to identify spatio-temporal clustering of cases. The results were visualized in ArcMap. Results The annual incidence of SFTS increased in Jiangsu Province from 2011 to 2021. Most cases (72.4%) occurred during May and August with the obvious peak months. Elderly farmers accounted for most cases, among which both males and females were susceptible. The spatial autocorrelation and spatio-temporal clustering analysis indicated that the distribution of SFTS was not random but clustered in space and time. The most likely cluster was observed in the western region of Jiangsu Province and covered one county (Xuyi county) (Relative risk = 8.18, Log likelihood ratio = 122.645, P

Abstract Focused ion beam (FIB) is an effective tool for precise nanoscale fabrication. It has recently been employed to tailor defect engineering in functional nanomaterials such as two-dimensional transition metal dichalcogenides (TMDCs), providing desirable properties in TMDC-based optoelectronic devices. However, the damage caused by the FIB irradiation and milling process to these delicate, atomically thin materials, especially in extended areas beyond the FIB target, has not yet been fully characterised. Understanding the correlation between lateral ion beam effects and optical properties of 2D TMDCs is crucial in designing and fabricating high-performance optoelectronic devices. In this work, we investigate lateral damage in large-area monolayer WS2 caused by the gallium focused ion beam milling process. Three distinct zones away from the milling location are identified and characterised via steady-state photoluminescence (PL) and Raman spectroscopy. The emission in these three zones have different wavelengths and decay lifetimes. An unexpected bright ring-shaped emission around the milled location has also been revealed by time-resolved PL spectroscopy with high spatial resolution. Our findings open up new avenues for tailoring the optical properties of TMDCs by charge and defect engineering via focused ion beam lithography. Furthermore, our study provides evidence that while some localised damage is inevitable, distant destruction can be eliminated by reducing the ion beam current. It paves the way for the use of FIB to create nanostructures in 2D TMDCs, as well as the design and realisation of optoelectrical devices on a wafer scale.

Objective: To use etomidate in combination with different opioids (sufentanil, fentanyl, and dezocine) to compare several anesthesia options from the aspects of the patient's index of consciousness (IoC). Methods: This was a prospective pilot study of consecutive patients who were scheduled for elective painless gastroscopy at PLA Strategic Force Characteristic Medical Center, Beijing, China, between December 2020 and May 2022. The patients were randomized to control (etomidate), S (sufentanil ​+ ​etomidate), F (fentanyl ​+ ​etomidate), and D (dezocine ​+ ​etimidate). IoC was measured before anesthesia (T1), opioids (T2), etomidate (T3), the start of endoscopy (T4), drug withdrawal (T5), OAA/S ​> ​2 (T6), and OAA/S ​> ​4) (T7). The primary outcome was the observation of IoC at T6 and T7. The adverse reaction and recovery time were secondary outcomes. Results: With 20 patients in each group, there were no differences in the operation and awakening times among the four groups (P ​> ​0.05). Compared with group C, the IoC values of groups S and F at T5, T6, and T7 were increased after drug administration (P ​

PCIF1 can mediate the methylation of N6,2′-O-dimethyladenosine (m6Am) in mRNA. Yet, the detailed interplay between PCIF1 and the potential cofactors and its pathological significance remain elusive. Here, we demonstrated that PCIF1-mediated cap mRNA m6Am modification promoted head and neck squamous cell carcinoma progression both in vitro and in vivo. CTBP2 was identified as a cofactor of PCIF1 to catalyze m6Am deposition on mRNA. CLIP-Seq data demonstrated that CTBP2 bound to similar mRNAs as compared with PCIF1. We then used the m6Am-Seq method to profile the mRNA m6Am site at single-base resolution and found that mRNA of TET2, a well-known tumor suppressor, was a major target substrate of the PCIF1-CTBP2 complex. Mechanistically, knockout of CTBP2 reduced PCIF1 occupancy on TET2 mRNA, and the PCIF1-CTBP2 complex negatively regulated the translation of TET2 mRNA. Collectively, our study demonstrates the oncogenic function of the epitranscriptome regulator PCIF1-CTBP2 complex, highlighting the importance of the m6Am modification in tumor progression.