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Embodied cognition posits that processing concepts requires sensorimotor activation. Previous research has shown that perceived power is spatially embodied along the vertical axis. However, it is unclear whether such mapping applies equally in the two languages of bilinguals. Using event-related potentials, we compared spatial embodiment correlates in participants reporting the source of auditory words as being presented from above or below their sitting position. English bilinguals responded faster for congruent presentations of high-power words (presented above) but not for congruent presentations of low-power words (presented below) in both languages. Low-power words together also failed to modulate N400 amplitude or interact with language. However, follow-up analyses on high-power words showed congruency effects on N400 amplitude in Chinese but not in English. Finally, English controls showed no effect. This suggests that spatial embodiment differs across languages in bilinguals, but the roles of culture and proficiency require further research.

Abstract Schizophrenia is a common and serious heterogeneous mental disorder that has a significant health and economic impact on families and society. As the prevalence of schizophrenia increases each year, public awareness of the disorder is growing. However, it remains unclear whether the quality of information presented in these videos is satisfactory. Therefore, a comprehensive assessment of the quality and content of schizophrenia-related videos on video-sharing platforms is necessary. We screened 123 schizophrenia-related videos from the video-sharing platform TikTok that met the criteria, and evaluated and analyzed them. First, the basic information provided in the videos was recorded and analyzed. The source and content type of each video was then determined. The educational content and quality of all videos were then evaluated using three rating instruments, Modified DISCERN, Global Quality Scale, and Journal of the American Medical Association (JAMA). Videos from different sources were also compared to see if they were statistically different in terms of educational content and quality. We identified 4 categories of content for the videos. The science introduction category had the largest number of 50, and the least number of videos was etiology and causation at 15. Six categories of sources of videos were also identified: the for-profit organizations category has the lowest number of 10, the health professionals category has the highest number of 45. There was a significant correlation between video source and duration (P = 0.014). The JAMA score was significantly positively correlated with the number of video likes (r = 0.721, P

Abstract The long-term use of aspirin for preventing cardiovascular disease has been recommended for decades. However, there is currently uncertainty regarding the long-term effects of aspirin use on the risk of all-cause, cardiovascular, and cancer mortality in cancer patients. The aim of this work was to analyze the connection between the prophylactic use of low-dose aspirin and the risk of all-cause death, cardiovascular death, and carcinoma death in carcinoma patients in the United States. A cohort study was conducted using National Health and Nutrition Examination Survey (NHANES) data (2011–2012, 2013–2014, 2015–2016, and 2017–2018) and associated mortality data. The 95% confidence intervals (CIs) and hazard ratios (HRs) between non-aspirin use and prophylactic low-dose aspirin use and the risk of death were measured via Cox proportional hazard regression models. A total of 1819 participants were included in the present research, of whom 945 were nonaspirin users and 874 were prophylactic aspirin users. Compared with non-aspirin users, prophylactic low-dose aspirin users had a decreased risk of all-cause death (HR = 0.647, 95% CI = 0.489–0.857). There was no statistically significant difference in the risk of cardiovascular death (HR = 0.623, 95% CI = 0.362–1.074) or cancer death (HR = 0.709, 95% CI = 0.410–1.226). Prophylactic use of low-dose aspirin may lower all-cause mortality in individuals with cancer but does not have a substantial effect on cardiovascular risk or cancer-specific mortality in this patient population.

Abstract Cucumis melo L., commonly known as melon, is a crucial horticultural crop. The selection and breeding of superior melon germplasm resources play a pivotal role in enhancing its marketability. However, current methods for melon appearance phenotypic analysis rely primarily on expert judgment and intricate manual measurements, which are not only inefficient but also costly. Therefore, to expedite the breeding process of melon, we analyzed the images of 117 melon varieties from two annual years utilizing artificial intelligence (AI) technology. By integrating the semantic segmentation model Dual Attention Network (DANet), the object detection model RTMDet, the keypoint detection model RTMPose, and the Mobile-Friendly Segment Anything Model (MobileSAM), a deep learning algorithm framework was constructed, capable of efficiently and accurately segmenting melon fruit and pedicel. On this basis, a series of feature extraction algorithms were designed, successfully obtaining 11 phenotypic traits of melon. Linear fitting verification results of selected traits demonstrated a high correlation between the algorithm-predicted values and manually measured true values, thereby validating the feasibility and accuracy of the algorithm. Moreover, cluster analysis using all traits revealed a high consistency between the classification results and genotypes. Finally, a user-friendly software was developed to achieve rapid and automatic acquisition of melon phenotypes, providing an efficient and robust tool for melon breeding, as well as facilitating in-depth research into the correlation between melon genotypes and phenotypes.

Abstract Seasonal epidemics of influenza viruses are responsible for a significant global public health burden. Vaccination remains the most effective way to prevent infection; however, due to the persistence of antigenic drift, vaccines must be updated annually. The selection of vaccine strains occurs months in advance of the influenza season to allow adequate time for production in eggs. RNA vaccines offer the potential to accelerate production and improve efficacy of influenza vaccines. We leveraged the nucleoside-modified RNA (modRNA) platform technology and lipid nanoparticle formulation process of the COVID-19 mRNA vaccine (BNT162b2; Comirnaty®) to create modRNA vaccines encoding hemagglutinin (HA) (modRNA-HA) for seasonal human influenza strains and evaluated their preclinical immunogenicity and toxicity. In mice, a monovalent modRNA vaccine encoding an H1 HA demonstrated robust antibody responses, HA-specific Th1-type CD4+ T cell responses, and HA-specific CD8+ T cell responses. In rhesus and cynomolgus macaques, the vaccine exhibited durable functional antibody responses and HA-specific IFN-γ+ CD4+ T cell responses. Immunization of mice with monovalent, trivalent, and quadrivalent modRNA-HA vaccines generated functional antibody responses targeting the seasonal influenza virus(es) encoded in the vaccines that were greater than, or similar to, those of a licensed quadrivalent influenza vaccine. Monovalent and quadrivalent modRNA-HA vaccines were well-tolerated by Wistar Han rats, with no evidence of systemic toxicity. These nonclinical immunogenicity and safety data support further evaluation of the modRNA-HA vaccines in clinical studies.

Abstract Significant pharmacokinetic (PK) differences exist between different forms of valproic acid (VPA), such as syrup and sustained‐release (SR) tablets. This study aimed to develop a population pharmacokinetic (PopPK) model for VPA in children with epilepsy and offer dose adjustment recommendation for switching dosage forms as needed. The study collected 1411 VPA steady‐state trough concentrations (Ctrough) from 617 children with epilepsy. Using NONMEM software, a PopPK model was developed, employing a stepwise approach to identify possible variables such as demographic information and concomitant medications. The final model underwent internal and external evaluation via graphical and statistical methods. Moreover, Monte Carlo simulations were used to generate a dose tailoring strategy for typical patients weighting 20–50 kg. As a result, the PK characteristics of VPA were described using a one‐compartment model with first‐order absorption. The absorption rate constant (ka) was set at 2.64 and 0.46 h−1 for syrup and SR tablets. Body weight and sex were identified as significant factors affecting VPA's pharmacokinetics. The final PopPK model demonstrated acceptable prediction performance and stability during internal and external evaluation. For children taking syrup, a daily dose of 25 mg/kg resulted in the highest probability of achieving the desired target Ctrough, while a dose of 20 mg/kg/day was appropriate for those taking SR tablets. In conclusion, we established a PopPK model for VPA in children with epilepsy to tailor VPA dosage when switching between syrup and SR tablets, aiming to improve plasma VPA concentrations fluctuations.

Abstract Background Pharmacogenetics/pharmacogenomics (PGx) focuses on the genetic variation that causes the heterogeneity of pharmacokinetics and drug response among individuals and has the potential to predict individual efficacy and/or side effects. This study aims to investigate and understand the implementation of genetic testing for the personalized medication (GTPM) in children's hospitals in Mainland China. Methods A survey was conducted on 50 children's hospitals from 31 provinces, municipalities, and autonomous regions across Mainland China, and statistical analysis and recommendations were made. Results Questionnaire response was rate of 76.0% (38/50). Data from 15 hospitals conducting GTPM were included in this study, but only 6 hospitals had offered PGx tests for no less than five drug-related genes, and only 5 hospitals had covered more than ten drugs, which was a small scale overall. 20.0% of the laboratories did not conduct internal quality control, and 33.3% did not participate in inter-laboratory quality assessment. 46.7% of the practitioners did not receive external training. The primary goal for GTPM was to optimize drug dosage in the 15 hospitals, while the main challenge for GTPM was the implementation cost. Conclusion Although GTPM in pediatrics has made major progress in Mainland China in recent years, there were still various problems in terms of software, hardware configuration, personnel allocation, business scale, quality control, and result interpretation. This requires joint efforts of health administration, medical insurance departments, researchers, and hospitals to promote and improve GTPM.

Abstract Background Traditional Chinese medicine (TCM) has been hailed as a rich source of medicine, but many types of herbs and their functions still need to be rapidly discovered and elucidated. HerboChip, a target-based drug screening platform, is an array of different fractions deriving from herbal extracts. This study was designed to identify effective components from TCM that interact with vascular endothelial growth factor (VEGF) as a target using HerboChip. Methods Selected TCMs that are traditionally used as remedies for cancer prevention and wound healing were determined and extracted with 50% ethanol. Biotinylated-VEGF was hybridized with over 500 chips coated with different HPLC-separated fractions from TCM extracts and straptavidin-Cy5 was applied to identify plant extracts containing VEGF-binding fractions. Cytotoxicity of selected herbal extracts and their activities on VEGF-mediated angiogenic functions were evaluated. Results Over 500 chips were screened within a week, and ten positive hits were identified. The interaction of the identified herbal extracts with VEGF was confirmed in cultured endothelial cells. The identified herbs promoted or inhibited VEGF-mediated cell proliferation, migration and tube formation. Results from western blotting analysis demonstrated the identified herbal extracts significantly affected VEGF-triggered phosphorylations of eNOS, Akt and Erk. Five TCMs demonstrated potentiating activities on the VEGF response and five TCMs revealed suppressive activities. Conclusions The current results demonstrated the applicability of the HerboChip platform and systematically elucidated the activity of selected TCMs on angiogenesis and its related signal transduction mechanisms.

Abstract Lung cancer has emerged as a major global public health concern. With growing public interest in lung cancer, online searches for related information have surged. However, a comprehensive evaluation of the credibility, quality, and value of lung cancer-related videos on digital media platforms remains unexamined. This study aimed to assess the informational quality and content of lung cancer-related videos on Douyin and Bilibili. A total of 200 lung cancer-related videos that met the criteria were selected from Douyin and Bilibili for evaluation and analysis. The first step involved recording and analyzing the basic information provided in the videos. Subsequently, the source and type of content for each video were identified. All videos’ educational content and quality were then evaluated using JAMA, GQS, and Modified DISCERN. Douyin videos were found to be more popular in terms of likes, comments, favorites, and shares, whereas Bilibili videos were longer in duration (P

Abstract Background CD19-targeted chimeric antigen receptor T (CAR-T) cell therapy stands out as a revolutionary intervention, exhibiting remarkable remission rates in patients with refractory/relapsed (R/R) B-cell malignancies. However, the potential side effects of therapy, particularly cytokine release syndrome (CRS) and infections, pose significant challenges due to their overlapping clinical features. Promptly distinguishing between CRS and infection post CD19 target CAR-T cell infusion (CTI) remains a clinical dilemma. Our study aimed to analyze the incidence of infections and identify key indicators for early infection detection in febrile patients within 30 days post-CTI for B-cell malignancies. Methods In this retrospective cohort study, a cohort of 104 consecutive patients with R/R B-cell malignancies who underwent CAR-T therapy was reviewed. Clinical data including age, gender, CRS, ICANS, treatment history, infection incidence, and treatment responses were collected. Serum biomarkers procalcitonin (PCT), interleukin-6 (IL-6), and C-reactive protein (CRP) levels were analyzed using chemiluminescent assays. Statistical analyses employed Pearson’s Chi-square test, t-test, Mann–Whitney U-test, Kaplan–Meier survival analysis, Cox proportional hazards regression model, Spearman rank correlation, and receiver operating characteristic (ROC) curve analysis to evaluate diagnostic accuracy and develop predictive models through multivariate logistic regression. Results In this study, 38 patients (36.5%) experienced infections (30 bacterial, 5 fungal, and 3 viral) within the first 30 days of CAR T-cell infusion. In general, bacterial, fungal, and viral infections were detected at a median of 7, 8, and 9 days, respectively, after CAR T-cell infusion. Prior allogeneic hematopoietic cell transplantation (HCT) was an independent risk factor for infection (Hazard Ratio [HR]: 4.432 [1.262–15.565], P = 0.020). Furthermore, CRS was an independent risk factor for both infection ((HR: 2.903 [1.577–5.345], P

Abstract Background Mild cognitive impairment has received widespread attention as a high-risk population for Alzheimer’s disease, and many studies have developed or validated predictive models to assess it. However, the performance of the model development remains unknown. Objective The objective of this review was to provide an overview of prediction models for the risk of Alzheimer’s disease dementia in older adults with mild cognitive impairment. Method PubMed, EMBASE, Web of Science, and MEDLINE were systematically searched up to October 19, 2023. We included cohort studies in which risk prediction models for Alzheimer’s disease dementia in older adults with mild cognitive impairment were developed or validated. The Predictive Model Risk of Bias Assessment Tool (PROBAST) was employed to assess model bias and applicability. Random-effects models combined model AUCs and calculated (approximate) 95% prediction intervals for estimations. Heterogeneity across studies was evaluated using the I 2 statistic, and subgroup analyses were conducted to investigate sources of heterogeneity. Additionally, funnel plot analysis was utilized to identify publication bias. Results The analysis included 16 studies involving 9290 participants. Frequency analysis of predictors showed that 14 appeared at least twice and more, with age, functional activities questionnaire, and Mini-mental State Examination scores of cognitive functioning being the most common predictors. From the studies, only two models were externally validated. Eleven studies ultimately used machine learning, and four used traditional modelling methods. However, we found that in many of the studies, there were problems with insufficient sample sizes, missing important methodological information, lack of model presentation, and all of the models were rated as having a high or unclear risk of bias. The average AUC of the 15 best-developed predictive models was 0.87 (95% CI: 0.83, 0.90). Discussion Most published predictive modelling studies are deficient in rigour, resulting in a high risk of bias. Upcoming research should concentrate on enhancing methodological rigour and conducting external validation of models predicting Alzheimer’s disease dementia. We also emphasize the importance of following the scientific method and transparent reporting to improve the accuracy, generalizability and reproducibility of study results. Registration This systematic review was registered in PROSPERO (Registration ID: CRD42023468780).

Introduction Elderly patients are at a high risk of postoperative delirium (POD), leading to increased postoperative morbidity and mortality. The use of dexmedetomidine and depth of anaesthesia may influence POD. This study aims to determine the effects of dexmedetomidine infusion versus normal saline placebo during light versus deep anaesthesia on POD among elderly patients undergoing major non-cardiac surgery.Methods and analysis This prospective, multicentre, randomised, controlled, factorial trial will be conducted at three tertiary hospitals in Jiangsu, China. We will recruit a total of 420 patients who are at least 60 years old and undergoing major non-cardiac surgery (thoracic, abdominal, urology, orthopaedic and spine surgery) under general anaesthesia. Patients will be randomised (1:1:1:1) to receive one of four anaesthesia regimens: (1) dexmedetomidine and light anaesthesia, (2) dexmedetomidine and deep anaesthesia, (3) placebo and light anaesthesia or (4) placebo and deep anaesthesia. Dexmedetomidine will be infused at 0.5 µg/kg/h throughout surgery, and intraoperative bispectral index target will be 55 for light anaesthesia and 40 for deep anaesthesia. The primary outcome is the occurrence of POD during the first 7 days postoperatively or until hospital discharge, assessed using the 3-min Confusion Assessment Method two times per day. The secondary outcomes include days with POD, type of POD, pain scores at rest and on movement at 24 and 48 hours postoperatively, patient-controlled intravenous fentanyl consumption during 0–24 and 24–48 hours postoperatively, hypotension, bradycardia, postoperative nausea and vomiting, non-delirium complications, length of postoperative hospital stay, 30-day cognitive function and 30-day mortality. Data will be analysed on a modified intention-to-treat basis.Ethics and dissemination This trial was approved by the Ethics Committee of the First Affiliated Hospital of Soochow University and each participating centre. The trial results will be published in a peer-reviewed journal.Trial registration Chinese Clinical Trial Registry (ChiCTR2300073271)

Introduction and Objectives: The increasing incidence of hepatocellular carcinoma (HCC) in China is an urgent issue, necessitating early diagnosis and treatment. This study aimed to develop personalized predictive models by combining machine learning (ML) technology with a demographic, medical history, and noninvasive biomarker data. These models can enhance the decision-making capabilities of physicians for HCC in hepatitis B virus (HBV)-related cirrhosis patients with low serum alpha-fetoprotein (AFP) levels. Patients and Methods: A total of 6,980 patients treated between January 2012 and December 2018 were included. Pre-treatment laboratory tests and clinical data were obtained. The significant risk factors for HCC were identified, and the relative risk of each variable affecting its diagnosis was calculated using ML and univariate regression analysis. The data set was then randomly partitioned into validation (20 %) and training sets (80 %) to develop the ML models. Results: Twelve independent risk factors for HCC were identified using Gaussian naïve Bayes, extreme gradient boosting (XGBoost), random forest, and least absolute shrinkage and selection operation regression models. Multivariate analysis revealed that male sex, age >60 years, alkaline phosphate >150 U/L, AFP >25 ng/mL, carcinoembryonic antigen >5 ng/mL, and fibrinogen >4 g/L were the risk factors, whereas hypertension, calcium 6.8 μmol/L, hemoglobin 40 U/L were the protective factors in HCC patients. Based on these factors, a nomogram was constructed, showing an area under the curve (AUC) of 0.746 (sensitivity = 0.710, specificity=0.646), which was significantly higher than AFP AUC of 0.658 (sensitivity = 0.462, specificity=0.766). Compared with several ML algorithms, the XGBoost model had an AUC of 0.832 (sensitivity = 0.745, specificity=0.766) and an independent validation AUC of 0.829 (sensitivity = 0.766, specificity = 0.737), making it the top-performing model in both sets. The external validation results have proven the accuracy of the XGBoost model. Conclusions: The proposed XGBoost demonstrated a promising ability for individualized prediction of HCC in HBV-related cirrhosis patients with low-level AFP.

BackgroundAs individuals age, they commonly experience reduced physical activity and cognitive decline. While evidence, there is limited trajectory research on their concurrent progression and interrelation in individuals over 55 years old.MethodsThe data was collected from 5,765 individuals aged over 55 years who participated in the China Health and Retirement Longitudinal Study (CHARLS) between 2011 and 2020. Physical activity was measured by IPAQ, cognitive function by episodic memory, and mental intactness score. Separate sets of group-based trajectory models were fitted to identify physical activity trajectories and cognitive function trajectories. Multivariate logistic regression was used to estimate the association between baseline characteristics and each set of trajectories. Group-based dual trajectory modeling (GBDTM) was applied to quantify these associations.ResultsGBDTM identified three distinct trajectory groups for physical activity and cognitive outcomes. The physical activity trajectories were classified as “Persistently low physical activity” (74.2%), “Decreasing physical activity” (13.7%), and “Rising physical activity” (12.1%). Similarly, cognitive function trajectories were categorized as “Persistently low cognitive function” (22.2%), “Persistently moderate cognitive function” (37.9%), and “Persistently high cognitive function” (39.9%). Notably, 15.6% of participants followed the trajectories of “Persistently low physical activity” and “Persistently low cognitive function.” The presence of a severe decline in physical activity was associated with an increased likelihood of poor cognitive function and vice versa. Age, sex, education, residential status, BMI, and visual impairment were identified as significant predictors for physical activity and cognitive decline.ConclusionThis study found that the GBDTM can determine the consistent trajectories of physical activity and cognitive function trajectories that persistently decline in individuals over 55 years. Analyses of predictive factors can be instrumental in promoting physical activity and delaying cognitive decline.

BackgroundOlder adults with cognitive impairment can experience poor oral health due to reduced self-care ability, yet the impact of various oral health indicators on the cognitive ability remains unclear. We investigated the relationship between oral health indicators and mild cognitive impairment (MCI) in older adults.MethodsA cross-sectional study of 234 older adults aged 65 years or over was performed form January to March 2023 at health screening departments of hospitals. This study used the Mini-mental State Examination (MMSE), Montreal Cognitive Assessment (MoCA), Activities of Daily Living (ADL), Clinical Dementia Rating (CDR), and Hachinski Ischemic Score (HIS) to measure MCI. Two qualified dentists performed clinical oral examinations (number of teeth lost, dental caries, removable dentures, periodontitis). The other oral health status was measured by subjective assessment questionnaires, and the oral health-related quality of life (OHRQoL) was assessed by Geriatric Oral Health Assessment Index (GOHAI).ResultsOf the 234 older adults, 166 had MCI and 68 had normal cognitive ability. The univariate analyses revealed that older adults with poor oral health indicators of dental caries, mastication ability, oral and maxillofacial pain, self-perceived oral health status and OHRQoL had lower cognitive levels. The stepwise logistic regression analysis observed that higher education level (OR = 0.06, 95%CI = 0.007, 0.567) and OHRQoL score (OR = 0.92, 95%CI = 0.878, 0.963) were negatively associated with the presence of MCI. The area under the ROC curve (AUC) of MCI was 0.675 (95% CI: 0.600, 0.749) with a low sensitivity of 41.6% and a moderate specificity of 86.8%.ConclusionOHRQoL was found to be associated with MCI, implying that OHRQoL may be important in cognitive decline. The GOHAI scale can be used to more easily assess the oral health of older adults, which is important for the timely detection of poor oral status to delay cognitive decline.

Abstract Infectious intracranial aneurysm (IIA) and embolic cerebral infarction are well‐known devastating complications of children suffering infective endocarditis. In this report, we describe a successfully embolized IIA concurrent with bilateral middle cerebral artery (MCA) occlusion. Unfortunately, a newly formed IIA located in the contralateral MCA bifurcation ruptured at the seventh day following embolization. A 6‐month‐old female child was admitted to hospital 3 days following acute right limb mobility disorder. An interventional surgery history of congenital heart disease was confirmed. She was immediately started on antibiotic therapy and the computed tomography agiography (CTA) scan showed occlusion of the upper branch of the left MCA. Unfortunately an IIA was located in the distal artery region (DAR) of the ipsilateral anterior cerebral artery. Angiography (digital subtraction angiography) was performed and the DAR IIA was embolized by OnyX‐18 with Magic 1.2 Fr. microcatheter. On the sixth day, magnetic resonance imaging during the hospital stay showed reduced infarction area with no other special sign. Desperately, a major seizure with opisthotonos attacked the baby on the seventh day after embolization. An immediate CTA scan showed massive hematoma in the right basal ganglia and a ruptured bifurcate aneurysm of the right MCA. The parents refused positive treatment and discharged in considering the critical situation. It should be noted that IIA can be fast formed anywhere in cerebral artery and dynamic angio‐image should be performed as supervision.

Background: The widespread clinical use of lacosamide (LCM) has revealed significant individual differences in clinical response, with various reported influencing factors. However, it remains unclear how genetic factors related to the disposition and clinical response of LCM, as well as drug–drug interactions (DDIs), exert their influence on pediatric patients with epilepsy. Objectives: To evaluate the impact of genetic variations and DDIs on plasma LCM concentrations and clinical response. Design: Patients with epilepsy treated with LCM from June 2021 to March 2023 in the Children’s Hospital of Nanjing Medical University were included in the analysis. Methods: The demographic information and laboratory examination data were obtained from the hospital information system. For the pharmacogenetic study, the left-over blood specimens, collected for routine plasma LCM concentration monitoring, were used to perform genotyping analysis for the selected 26 single nucleotide polymorphisms from 14 genes. The trough concentration/daily dose ( C 0 /D) ratio and efficacy outcomes were compared. Results: Patients achieved 90.1% and 68.9% responder rates in LCM mono- and add-on therapy, respectively. The genetic variant in the CYP2C19 *2 (rs4244285) was associated with a better responsive treatment outcome (odds ratio: 1.82; 95% confidence interval: 1.05–3.15; p = 0.031). In monotherapy, 36% of patients were CYP2C19 normal metabolizers (NMs), 49% were intermediate metabolizers (IMs), and 15% were poor metabolizers (PMs) carrying CYP2C19 *2 or *3. Of note, the C 0 /D ratios of IMs and PMs were 9.1% and 39.6% higher than those of NMs, respectively. Similar results were in the add-on therapy group, and we also observed a substantial decrease in the C 0 /D ratio when patients were concomitant with sodium channel blockers (SCBs). Conclusion: This study was the first to confirm that CYP2C19 *2 or *3 variants impact the disposition and treatment response of LCM in children with epilepsy. Moreover, concomitant with SCBs, particularly oxcarbazepine, also decreased plasma LCM concentration.

BackgroundThe main challenges faced when using sirolimus in children with vascular anomalies (VAs) still include significant pharmacokinetic (PK) variability, uncertainty in the target concentration range, as well as inconsistencies in initial dosing and dosing frequency. The aim of this study is to establish a new population pharmacokinetic (PPK) model for children with VAs to guide the individualized use of sirolimus.MethodsA PPK study was performed using data from children with VAs who received sirolimus between July 2017 and April 2022. A nonlinear mixed-effect modeling with a one-compartment model structure was applied. Monte Carlo simulation was employed to propose specific dosing recommendations to achieve the target trough concentrations (Ctrough) of 5–15 ng/mL.ResultsIn total, 134 blood concentrations from 49 pediatric patients were used to characterize the sirolimus pharmacokinetics. Covariate analysis identified body weight (BW) as a significant factor affecting clearance (CL) in the final PPK model. The typical clearance rate and distribution volume, standardized to a BW of 16 kg, were 4.06 L/h (4% relative standard error, RSE) and 155 L (26% RSE), respectively. Optimal dosing regimens were simulated for different BWs. For a twice-daily regimen, the recommended doses were 0.05, 0.06, 0.07, and 0.08 mg/kg/day for BW of

Abstract BackgroundPersonality has an impact on the health-related quality of life (HRQoL) of older adults. However, the relationship and mechanisms of the 2 variables are controversial, and few studies have been conducted on older adults. ObjectiveThe aim of this study was to explore the relationship between personality and HRQoL and the mediating and moderating roles of sleep quality and place of residence in this relationship. MethodsA total of 4123 adults 60 years and older were from the Psychology and Behavior Investigation of Chinese Residents survey. Participants were asked to complete the Big Five Inventory, the Brief version of the Pittsburgh Sleep Quality Index, and EQ-5D-5L. A backpropagation neural network was used to explore the order of factors contributing to HRQoL. Path analysis was performed to evaluate the mediation hypothesis. ResultsAs of August 31, 2022, we enrolled 4123 older adults 60 years and older. Neuroticism and extraversion were strong influencing factors of HRQoL (normalized importance >50%). The results of the mediation analysis suggested that neuroticism and extraversion may enhance and diminish, respectively, HRQoL (index: β=−.262, PPPPPPP ConclusionsThis study sheds light on the potential mechanisms of personality and HRQoL among older Chinese adults and can help health care providers and relevant departments take reasonable measures to promote healthy aging.

The content and density of traffic signs directly affect the operation of urban road traffic and drivers. To overcome the limitations of quantitative research on the density threshold of traffic signs on urban roads, a real vehicle experiment was conducted to record the psychological characteristics of drivers. Four psychological parameters of drivers—pupil area, fixation intensity, heart rate change rate, and heart rate variability—were explored. Subsequently, principal component analysis was used to present a new index, S, divided into 5 grade scales, to represent the driving visual comfort level. The information entropy theory was applied to quantify the amount of information on road traffic signs that are included in driving tests, and a regression relationship between the traffic sign information and comfort index S was established. The visual psychological load thresholds for different comfort levels were −2.289≤S

Background: Chemotherapy plus immunotherapy has become the standard first-line treatment of advanced or metastatic esophageal squamous cell carcinoma (ESCC), but median duration of response is only 7.0–8.3 months and progression-free survival (PFS, ∼6 months) is still far from satisfactory. We aim to evaluate whether early involvement of radiotherapy might improve the treatment outcome if objective response to first-line chemo-immunotherapy was observed in locally advanced or metastatic ESCC. Methods: Patients were retrospectively collected from 3 institutions in China. Patients with histopathologically confirmed diagnoses of locally advanced or metastatic ESCC were identified, who objectively responded to first-line chemo-immunotherapy (complete or partial response, or stable disease) and also received radiotherapy of primary lesions with radiation dose of over 40 Gy, with or without radiotherapy of metastatic lesions before the first disease progression. Results: A total of 72 eligible patients were identified. With median follow-up duration of 14.6 (range, 7.1–34.8) months, median progression-free survival (PFS) and overall survival (OS) were 13.5 (95 % CI,10.4-NA) months and 31.8 (95 % CI, 23.0-NA) months, respectively. Median duration from initiation of chemo-immunotherapy to radiotherapy was 2.9 (range, 0–15.1) months. Besides lower tumor burden as a significant factor of better treatment outcome, radiation dose ≥ 50 Gy was associated with superior PFS, while OS might be mainly related to tumor response to the induction chemo-immunotherapy. A low incidence of Grade 3 or above treatment-related adverse events were observed (19 %), and no treatment-related death occurred. Conclusion: Our multi-center retrospective study showed survival benefit brought by early involvement of radiotherapy after first-line chemo-immunotherapy for patients with locally advanced or metastatic ESCC. However, further investigation is warranted in future prospective, controlled trials to assess the value of radio-immunotherapy in advanced or metastatic ESCC.

Abstract Molecular ferroelectrics are attracting great interest due to their light weight, mechanical flexibility, low cost, ease of processing and environmental friendliness. These advantages make molecular ferroelectrics viable alternatives or supplements to inorganic ceramics and polymer ferroelectrics. It is expected that molecular ferroelectrics with good performance can be fabricated, which in turns calls for effective chemical design strategies in crystal engineering. To achieve so, we propose a hydrogen bond modification method by introducing the hydroxyl group, and successfully boost the phase transition temperature (T c) by at least 336 K. As a result, the molecular ferroelectric 1-hydroxy-3-adamantanammonium tetrafluoroborate [(HaaOH)BF4] can maintain ferroelectricity until 528 K, a T c value much larger than that of BTO (390 K). Meanwhile, micro-domain patterns, in stable state for 2 years, can be directly written on the film of (HaaOH)BF4. In this respect, hydrogen bond modification is a feasible and effective strategy for designing molecular ferroelectrics with high T c and stable ferroelectric domains. Such an organic molecule with varied modification sites and the precise crystal engineering can provide an efficient route to enrich high-T c ferroelectrics with various physical properties.

There are many fields involved in China’s industry, and the carbon reduction is urgent. Oxy-fuel combustion is the core process of carbon capture in combustion. Coupling fluidized preheating activation with industrial kilns oxy-fuel combustion is a new way to expand fuel adaptability and achieve carbon capture during combustion. This study uses a small-scale fluidized bed continuous feeding experimental platform to investigate the effect of C/CO2 molar ratio (CC ratio) on the fluidized preheating activation characteristics of raw semi-char (RC) by adjusting the feeding rate at a temperature of 1 050 ℃ and CO2 fluidized rate of 0.17 m/s. The gas composition and low calorific value are analyzed, and the CO2 reduction ratio is calculated. The specific surface area, pore structure and carbon frame structure of fine particle activated semi-char (FC) and large particle activated semi-char (LC) are characterized. The reactivity of RC and FC is evaluated using a high-temperature tubular furnace thermobalance at 1 300 ℃. The results show that the use of fluidized preheating activation technology has achieved the resource utilization of CO2 and produced rich-CO fuel gas. When the CC ratio increases from 1 to 4, the CO+H2 volume fraction in the gas increases from 69.24% to 79.08%, and the highest CO volume fraction of 68.96%, the CO2 volume fraction decreases from 29.48% to 20.13%, and the CO2 reduction rate increases from 50.37% to 57.56%. The low calorific value of fuel gas increases from 8.69 MJ/m3 to 9.83 MJ/m3, which is 1.55−1.88 times higher than the low calorific value of the fuel gas produced by the project as described in the reference. The produced fuel gas in this study is conducive to the ignition and stable combustion of the kiln system. As the CC ratio increases, the specific surface area of FC and LC first increases and then decreases. The highest specific surface areas of FC and LC are 291.21 m2/g and 477.15 m2/g, respectively, which are 48 and 78 times higher than the RC. FC and LC have rich microporous structures, and the degree of graphitization decreases while the active sites increase. The microporous area accounts for 54.93%−68.42% of the specific surface area. In comparison, LC has a higher specific surface area and incremental pore volume mainly due to its longer residence time in the reactor, which promotes the development of pores and forms a large number of micropores. The reactivity index R0.5 and the average mass reaction rate of FC obtained under different CC ratios are higher than the RC, which reveals the good reaction characteristics of FC. It can be predicted that FC will achieve an efficient conversion during the high-temperature gas-solid activated thermal fuel combustion process. This research proposes a new route of fluidized oxy-fuel preheating activation for carbon-based fuels coupled with oxy-fuel combustion of gas-solid activated fuel with high-temperature. The influence of CC ratio on the characteristics of semi-char at CO2 atmosphere with fluidized preheating activation technology is obtained. The positive role of CO2 as a carbon and oxygen carrier is revealed. The research results provide a data support for the application of fluidized preheating activation technology in the industrial kiln oxy-fuel combustion industry.

Abstract Background Stress is a recognized risk factor for cognitive decline, which triggers neuroinflammation involving microglial activation. However, the specific mechanism for microglial activation under stress and affects learning and memory remains unclear. Methods The chronic stress mouse model was utilized to explore the relationship between microglial activation and spatial memory impairment. The effect of hippocampal hyperglycemia on microglial activation was evaluated through hippocampal glucose-infusion and the incubation of BV2 cells with high glucose. The gain-and loss-of-function experiments were conducted to investigate the role of GLUT1 in microglial proinflammatory activation. An adeno-associated virus (AAV) was employed to specifically knockdown of GLUT1 in hippocampal microglia to assess its impact on stressed-mice. Results Herein, we found that chronic stress induced remarkable hippocampal microglial proinflammatory activation and neuroinflammation, which were involved in the development of stress-related spatial learning and memory impairment. Mechanistically, elevated hippocampal glucose level post-stress was revealed to be a key regulator of proinflammatory microglial activation via specifically increasing the expression of microglial GLUT1. GLUT1 overexpression promoted microglial proinflammatory phenotype while inhibiting GLUT1 function mitigated this effect under high glucose. Furthermore, specific downregulation of hippocampal microglial GLUT1 in stressed-mice relieved microglial proinflammatory activation, neuroinflammation, and spatial learning and memory injury. Finally, the NF-κB signaling pathway was demonstrated to be involved in the regulatory effect of GLUT1 on microglia. Conclusions We demonstrate that elevated glucose and GLUT1 expression induce microglia proinflammatory activation, contributing to stress-associated spatial memory dysfunction. These findings highlight significant interplay between metabolism and inflammation, presenting a possible therapeutic target for stress-related cognitive disorders.

Abstract Objective The present study aims to explore the influencing factors of the scientific fitness literacy of nurses and provide a strategic basis for literacy improvement. Methods A questionnaire on the influencing factors of scientific fitness literacy of nurses was designed by the group conducting the present study; the questionnaire was based on the socioecology model and the questionnaire preparation method. The general data questionnaire and the questionnaire on the influencing factors of scientific fitness literacy of nurses were adopted to investigate nurses in tertiary hospitals in order to analyze and discuss the influencing factors of their scientific fitness literacy. Results (1) The questionnaire on the influencing factors of the scientific fitness literacy of nurses comprised five dimensions and 36 items. The overall item-content validity index was 0.833–1.000, the scale-content validity index was 0.974, and the overall Cronbach’s α coefficient was 0.955; (2) the results of the pairwise Pearson correlation analysis showed that all five dimensions were positively correlated with the scientific fitness literacy of nurses; and (3) the results of the multiple linear regression analysis revealed that five dimensions, as well as the existence of exercise habits in daily life, had a significant impact on the scientific fitness literacy of nurses (P

Background/Aims Four-week treatment of linvencorvir (RO7049389) was generally safe and well tolerated, and showed anti-viral activity in chronic hepatitis B (CHB) patients. This study evaluated the efficacy, safety, and pharmacokinetics of 48-week treatment with linvencorvir plus standard of care (SoC) in CHB patients. Methods This was a multicentre, non-randomized, non-controlled, open-label phase 2 study enrolling three cohorts: nucleos(t)ide analogue (NUC)-suppressed patients received linvencorvir plus NUC (Cohort A, n=32); treatment-naïve patients received linvencorvir plus NUC without (Cohort B, n=10) or with (Cohort C, n=30) pegylated interferon-α (Peg-IFN-α). Treatment duration was 48 weeks, followed by NUC alone for 24 weeks. Results 68 patients completed the study. No patient achieved functional cure (sustained HBsAg loss and unquantifiable HBV DNA). By Week 48, 89% of treatment-naïve patients (10/10 Cohort B; 24/28 Cohort C) reached unquantifiable HBV DNA. Unquantifiable HBV RNA was achieved in 92% of patients with quantifiable baseline HBV RNA (14/15 Cohort A, 8/8 Cohort B, 22/25 Cohort C) at Week 48 along with partially sustained HBV RNA responses in treatment-naïve patients during follow-up period. Pronounced reductions in HBeAg and HBcrAg were observed in treatment-naïve patients, while HBsAg decline was only observed in Cohort C. Most adverse events were grade 1–2, and no linvencorvir-related serious adverse events were reported. Conclusions 48-week linvencorvir plus SoC was generally safe and well tolerated, and resulted in potent HBV DNA and RNA suppression. However, 48-week linvencorvir plus NUC with or without Peg-IFN did not result in the achievement of functional cure in any patient.

Abstract Background Non‐small cell lung cancer (NSCLC) is a type of lung cancer that occurs in the cells of the respiratory tract, and its development is influenced by the regulation of circular RNAs (circRNAs). However, the role of circRNA carboxypeptidase A4 (circCPA4) in the progression of NSCLC and the underlying mechanism remain relatively clear. Methods The study utilized both real‐time quantitative polymerase chain reaction (RT‐qPCR) and western blot techniques to evaluate the levels of circCPA4, microRNA‐145‐5p (miR‐145‐5p), alanine, serine, or cysteine‐preferring transporter 2 (ASCT2). To assess cell proliferation, cell counting kit‐8 (CCK8) and 5‐ethynyl‐2′‐deoxyuridine (EdU) assays were performed. Apoptosis was determined using flow cytometry, while cell migration and invasive capacity were evaluated through transwell and wound‐healing assays. Intracellular levels of glutamine, glutamate, and α‐KG were measured using specific kits. The relationship between miR‐145‐5p and circCPA4 or ASCT2 was confirmed using dual‐luciferase reporter assay and RNA immunoprecipitation assay. Results CircCPA4 and ASCT2 RNA levels were elevated, while miR‐145‐5p was downregulated in both NSCLC tissues and cells. Depletion of circCPA4 significantly inhibited NSCLC cell proliferation, migration, invasion, and intracellular levels of glutamine, glutamate, and α‐KG, and promoted apoptosis. Moreover, circCPA4 knockdown delayed tumor growth in vivo. Furthermore, circCPA4 was found to bind to miR‐145‐5p, thereby regulating the progression of NSCLC in vitro. ASCT2 was also identified as a downstream target of miR‐145‐5p, and its upregulation rescued the effects of miR‐145‐5p overexpression on NSCLC cell processes. Conclusion CircCPA4 knockdown inhibited tumor property of NSCLC cells by modulating the miR‐145‐5p/ASCT2 axis.

Abstract Background No study has comparing hepatitis B virus (HBV) relapse rates among patients with both cancer and hepatitis B e antigen (HBeAg)-negative chronic hepatitis B (CHB) who completed anti-viral prophylaxis for chemotherapy and then stopped taking entecavir or tenofovir alafenamide (TAF). Methods A total of 227 HBeAg-negative cancer patients without cirrhosis who previously took entecavir (n = 144) or TAF (n = 83) for antiviral prophylaxis were enrolled. Results The cumulative incidence of virological and clinical relapse at 2 years was 37% and 10.4%, respectively, in the entecavir group, and 46.7% and 19.5%, respectively, in the TAF group. The multivariate analysis revealed that the use of hematologic malignancy, TAF use, and high-viremia group at baseline were independent risk factors for virological relapse, and use of rituximab, TAF use, higher FIB-4 index and high-viremia group at baseline were independent risk factors for clinical relapse. After propensity score-matching, the patients who discontinued TAF therapy still exhibited higher virological (P = 0.031) and clinical relapse rates (P = 0.012) than did those who discontinued entecavir therapy. The patients were allocated to high- (> 2000 IU/mL), moderate- (between 20 and 2000 IU/mL) and low- (

Abstract Toluene treatment has received extensive attention, and ozone synergistic catalytic oxidation was thought to be a potential method to degrade VOCs (violate organic compounds) due to its low reaction temperature and high catalytic efficiency. A series of bimetal/Cord monolithic catalysts were prepared by impregnation with cordierite, including MnxCu5−x/Cord, MnxCo5−x/Cord and CuxCo5−x/Cord (x = 1, 2, 3, 4). Analysis of textural properties, structures and morphology characteristics on the prepared catalysts were conducted to evaluate their performance on toluene conversion. Effects of active component ratio, ozone addition and space velocity on the catalytic oxidation of toluene were investigated. Results showed that MnxCo5−x/Cord was the best among the three bimetal catalysts, and toluene conversion and mineralization rates reached 100 and 96% under the condition of Mn2Co3/Cord with 3.0 g/m3 O3 at the space velocity of 12,000 h−1. Ozone addition in the catalytic oxidation of toluene by MnxCo5−x/Cord could efficiently avoid the 40% reduction of the specific surface area of catalysts, because it could lower the optimal temperature from 300 to 100 °C. (Co/Mn)(Co/Mn)2O4 diffraction peaks in XRD spectra indicated all the four MnxCo1−x/Cord catalysts had a spinel structure, and diffraction peak intensity of spinel reached the largest at the ratio of Mn:Co = 2:3. Toluene conversion rate increased with rising ozone concentration because intermediate products generated by toluene degradation might react with excess ozone to generate free radicals like ·OH, which would improve the toluene mineralization rate of Mn2Co3/Cord catalyst. This study would provide a theoretical support for its industrial application.

Abstract Integrating CYP2D6 genotyping and therapeutic drug monitoring (TDM) is crucial for guiding individualized atomoxetine therapy in children with attention-deficit/hyperactivity disorder (ADHD). The aim of this retrospective study was (1) to investigate the link between the efficacy and tolerability of atomoxetine in children with ADHD and plasma atomoxetine concentrations based on their CYP2D6 genotypes; (2) to offer TDM reference range recommendations for atomoxetine based on the CYP2D6 genotypes of children receiving different dosage regimens. This retrospective study covered children and adolescents with ADHD between the ages of 6 and 60% of enrolled children belonged to the CYP2D6 extensive metabolizer (EM), while

Abstract We show that lattice dislocations of topological iron-based superconductors such as FeTe1−x Se x will intrinsically trap non-Abelian Majorana quasiparticles, in the absence of any external magnetic field. Our theory is motivated by the recent experimental observations of normal-state weak topology and surface magnetism that coexist with superconductivity in FeTe1−x Se x , the combination of which naturally achieves an emergent second-order topological superconductivity in a two-dimensional subsystem spanned by screw or edge dislocations. This exemplifies a new embedded higher-order topological phase in class D, where Majorana zero modes appear around the “corners” of a low-dimensional embedded subsystem, instead of those of the full crystal. A nested domain wall theory is developed to understand the origin of these defect Majorana zero modes. When the surface magnetism is absent, we further find that s ± pairing symmetry itself is capable of inducing a different type of class-DIII embedded higher-order topology with defect-bound Majorana Kramers pairs. We also provide detailed discussions on the real-world material candidates for our proposals, including FeTe1−x Se x , LiFeAs, β-PdBi2, and heterostructures of bismuth, etc. Our work establishes lattice defects as a new venue to achieve high-temperature topological quantum information processing.

Abstract Background Racial/ethnic disparities in the HIV care continuum have been well documented in the US, with especially striking inequalities in viral suppression rates between White and Black persons with HIV (PWH). The South is considered an epicenter of the HIV epidemic in the US, with the largest population of PWH living in Florida. It is unclear whether any disparities in viral suppression or immune reconstitution—a clinical outcome highly correlated with overall prognosis—have changed over time or are homogenous geographically. In this analysis, we 1) investigate longitudinal trends in viral suppression and immune reconstitution among PWH in Florida, 2) examine the impact of socio-ecological factors on the association between race/ethnicity and clinical outcomes, 3) explore spatial and temporal variations in disparities in clinical outcomes. Methods Data were obtained from the Florida Department of Health for 42,369 PWH enrolled in the Ryan White program during 2008-2020. We linked the data to county-level socio-ecological variables available from County Health Rankings. GEE models were fit to assess the effect of race/ethnicity on immune reconstitution and viral suppression longitudinally. Poisson Bayesian hierarchical models were fit to analyze geographic variations in racial/ethnic disparities while adjusting for socio-ecological factors. Results Proportions of PWH who experienced viral suppression and immune reconstitution rose by 60% and 45%, respectively, from 2008-2020. Odds of immune reconstitution and viral suppression were significantly higher among White [odds ratio =2.34, 95% credible interval=2.14-2.56; 1.95 (1.85-2.05)], and Hispanic [1.70 (1.54-1.87); 2.18(2.07-2.31)] PWH, compared with Black PWH. These findings remained unchanged after accounting for socio-ecological factors. Rural and urban counties in north-central Florida saw the largest racial/ethnic disparities. Conclusions There is persistent, spatially heterogeneous, racial/ethnic disparity in HIV clinical outcomes in Florida. This disparity could not be explained by socio-ecological factors, suggesting that further research on modifiable factors that can improve HIV outcomes among Black and Hispanic PWH in Florida is needed.

Porcine deltacoronavirus (PDCoV) is an emerging porcine enteropathogenic coronavirus that causes acute watery diarrhoea in piglets, resulting in significant economic losses to the global swine industry. However, the underlying mechanism of PDCoV infection is not well defined, which seriously hinders the development of effective drugs and vaccines. Integrins (ITG) are heterodimeric transmembrane glycoproteins that play important roles in the life cycle of many viruses. In the current study, the viral entry pathways of PDCoV were explored and the role of ITGαVβ3 was investigated during PDCoV infection. Our results showed that the lysosomal acidification inhibitor bafilomycin-A1 (Baf-A1) significantly reduced PDCoV infection, while exogenous protease facilitated PDCoV infection and even allowed PDCoV entry to bypass the endosomal pathway, suggesting PDCoV entry into cells via the endocytic pathway and the exogenous protease-mediated pathway simultaneously. Furthermore, ITGαVβ3 was identified to be involved in PDCoV infection, especially during viral entry stages. PDCoV infection triggers the activation of the focal adhesion kinase (FAK)-phosphatidylinositol 3-kinase (PI3K)-serine/threonine-specific protein kinase (AKT) signalling pathway, and this activation is ITGαVβ3-dependent, suggesting that the activation of the FAK-PI3K-AKT signalling pathway during PDCoV infection is mediated by ITGαVβ3. Our results further demonstrated that PDCoV infection induced the expression of inflammatory cytokines, which was mediated by activation of the ITGαVβ3-FAK-PI3K-AKT-nuclear transcription factor-κB (NF-κB) signalling pathway. Overall, the results revealed that ITGαVβ3 is an essential host factor for PDCoV infection and can serve as a supplementary receptor to facilitate PDCoV infection, which can help us to explore the molecular mechanism of PDCoV infection.

Clostridioides difficile sequence type (ST) 35 has been found in humans and animals worldwide. However, its genomic epidemiology and clonal transmission have not been explored in detail. In this study, 176 C. difficile ST35 isolates from six countries were sequenced. Genomic diversity, clonal transmission and epidemiological data were analyzed. Sporulation and virulence capacities were measured. Four ribotypes (RT) were identified including RT046 (97.2%), RT656 (1.1%), RT427 (0.6%), and RT AI-78 (1.1%). Phylogenetic analysis of 176 ST35 genomes, along with 50 publicly available genomes, revealed two distinctive lineages without time-, region-, or source-dependent distribution. However, the distribution of antimicrobial resistance genes differed significantly between the two lineages. Nosocomial and communal transmission occurred in humans with the isolates differed by ≤ two core-genome single-nucleotide polymorphism (cgSNPs) and clonal circulation was found in pigs with the isolates differed by ≤ four cgSNPs. Notably, interspecies clonal transmission was identified among three patients with community acquired C. difficile infection and pigs with epidemiological links, differed by ≤ nine cgSNPs. Toxin B (TcdB) concentrations were significantly higher in human isolates compared to pig isolates, and ST35 isolates exhibited stronger sporulation capacities than other STs. Our study provided new genomic insights and epidemiological evidence of C. difficile ST35 intraspecies and interspecies clonal transmission, which can also be facilitated by its strong sporulation capacity.

ABSTRACTThe lithium niobate on insulator devices confine the light field to submicron size in monocrystalline lithium niobate, to achieve ultra-strong electro-optical interaction and nonlinear optical interaction, and thus extend the frontiers of the photonic research in the past decade. Such devices are manufactured using nano-fabrication technology over the thin-film lithium niobate wafer, which usually stands on a silica insulator layer above the substrate material, including low-loss waveguides, electro-optical modulators, domain engineered structures, high-Q microring resonators and electrical filters etc., and lead to breakthroughs in optical communication, microwave photonics and quantum integration.

Abstract Fine roots and absorptive roots play key roles in acquiring resources throughout soil profiles and determining plant functions along environmental gradients. Yet, the geographical pattern of carbon allocation in fine roots, particularly in absorptive roots, and their relations with plant sizes and evironment are less understood. We sampled 243 xerophytic shrubs from 63 species distributed along the latitudinal gradient (23°N to 32°N) in dry valleys of southwest China and synthetically measured biomass fractions of plant organs, especially fine roots and absorptive roots (1st to 3rd root order). We identified latitudinal patterns of biomass allocation fractions of organs and their relationships with plant sizes and environmental factors. The latitudinal patterns of both absorptive root and fine‐root fractions followed weak unimodal distributions; stem biomass fraction increased with the latitude, while the leaf biomass fraction decreased. The fraction of fine‐root biomass had negative relationships with plant height and root depth. The fractions of root, fine root, and absorptive root biomass were largely explained by soil moisture. Furthermore, fraction of fine‐root biomass increased in a relatively humid environment. Overall, soil moisture was the most important factor in driving latitudinal patterns of biomass fraction. Our study highlighted that functional redistribution of root system biomass was the critical adaptive strategy along a latitudinal gradient.

Spiral ganglia neurons (SGNs) impairment can cause deafness. One important therapeutic approach involves utilizing stem cells to restore impaired auditory circuitry. Nevertheless, the inadequate implementation of research methodologies poses a challenge in accurately assessing the functionality of derived cells within the circuit. Here, we describe a novel method for converting human embryonic stem cells (hESCs) into otic neurons (ONs) and assess their functional connectivity using an optogenetic approach with cells or an organotypic slice of rat cochlear nucleus (CN) in coculture. Embryonic stem cell-derived otic neurons (eONs) exhibited SGN marker expression and generated functional synaptic connection when cocultured with cochlear nucleus neurons (CNNs). Synapsin 1 and VGLUT expression are found in the cochlear nucleus of brain slices, where eONs projected processes during the coculture of eONs and CN brain slices. Action potential spikes and I Na+ /I K+ of CNNs increased in tandem with light stimulations to eONs. These findings provide further evidence that eONs may be a candidate source to treat SGN-deafness.

Chimeric antigen receptor T (CAR-T) cell therapy targeting T cell tumors still faces many challenges, one of which is its fratricide due to the target gene expressed on CAR-T cells. Despite this, these CAR-T cells can be expanded in vitro by extending the culture time and effectively eliminating malignant T cells. However, the mechanisms underlying CAR-T cell survival in cell subpopulations, the molecules involved, and their regulation are still unknown. We performed single-cell transcriptome profiling to investigate the fratricidal CAR-T products (CD26 CAR-Ts and CD44v6 CAR-Ts) targeting T cells, taking CD19 CAR-Ts targeting B cells from the same donor as a control. Compared with CD19 CAR-Ts, fratricidal CAR-T cells exhibit no unique cell subpopulation, but have more exhausted T cells, fewer cytotoxic T cells, and more T cell receptor (TCR) clonal amplification. Furthermore, we observed that fratricidal CAR-T cell survival was accompanied by target gene expression. Gene expression results suggest that fratricidal CAR-T cells may downregulate their human leukocyte antigen (HLA) molecules to evade T cell recognition. Single-cell regulatory network analysis and suppression experiments revealed that exhaustion mediated by critical regulatory factors may contribute to fratricidal CAR-T cell survival. Together, these data provide valuable and first-time insights into the survival of fratricidal CAR-T cells.

Background: Postoperative sleep disturbance (PSD) occurs frequently in patients who undergo major abdominal surgical procedures. Dexmedetomidine is a promising agent to improve the quality of sleep for surgical patients. We designed this trial to investigate the effects of two different doses of intraoperative dexmedetomidine on the occurrence of PSD in elderly patients who have major abdominal surgery. Methods: In this randomized, double-blind, controlled trial, 210 elderly patients aged ≥65 years will be randomized, with an allocation ratio of 1:1:1, to two dexmedetomidine groups (intraoperative infusion of 0.3 or 0.6 μg/kg/h) and a normal saline placebo group. The primary endpoint is the occurrence of PSD on the first night after surgery, assessed using the Athens Insomnia Scale. The secondary endpoints are (1) the incidence of PSD during the 2nd, 3rd, 5th, 7th, and 30th nights postoperatively; (2) pain at rest and on movement at 24 and 48 h postoperatively, assessed using the Numerical Rating Scale; (3) the incidence of postoperative delirium during 0–7 days postoperatively or until hospital discharge, assessed using the 3-min Confusion Assessment Method; (4) depressive symptoms during 0–7 days postoperatively or until hospital discharge, assessed using the 15-items Geriatric Depression Scale; and (5) quality of recovery on postoperative days 1, 2, and 3, assessed using the 15-items Quality of Recovery Scale. Patients' sleep data will also be collected by Xiaomi Mi Band 7 for further analysis. Discussion: The findings of this trial will provide clinical evidence for improving the quality of sleep among elderly patients undergoing major abdominal surgery. Ethics and dissemination: This trial was approved by the Ethics Committee of the First Affiliated Hospital of Soochow University (No. 2023-160). The results will be published in a peer-reviewed journal. Trial registration: Chinese Clinical Trial Registry (ChiCTR2300073163).

Abstract Finite-momentum Cooper pairing is an unconventional form of superconductivity that is widely believed to require finite magnetization. Altermagnetism is an emerging magnetic phase with highly anisotropic spin-splitting of specific symmetries, but zero net magnetization. Here, we study Cooper pairing in metallic altermagnets connected to conventional s-wave superconductors. Remarkably, we find that the Cooper pairs induced in the altermagnets acquire a finite center-of-mass momentum, despite the zero net magnetization in the system. This anomalous Cooper-pair momentum strongly depends on the propagation direction and exhibits unusual symmetric patterns. Furthermore, it yields several unique features: (i) highly orientation-dependent oscillations in the order parameter, (ii) controllable 0-π transitions in the Josephson supercurrent, (iii) large-oblique-angle Cooper-pair transfer trajectories in junctions parallel with the direction where spin splitting vanishes, and (iv) distinct Fraunhofer patterns in junctions oriented along different directions. Finally, we discuss the implementation of our predictions in candidate materials such as RuO2 and KRu4O8.

We examined new Allacta materials from Yunnan and Hainan Province, China, and discovered new species using both morphological and molecular species delimitation (ABGD) methods. Five new species are described: A. bifolium Li & Wang, sp. nov., A. hemiptera Li & Wang, sp. nov., A. lunulara Li & Wang, sp. nov., A. redacta Li & Wang, sp. nov., and A. unicaudata Li & Wang, sp. nov. All five species are placed under the hamifera species group. An updated key and checklist of Allacta species from China are provided.

Abstract Objective To evaluate the effectiveness and safety of perampanel (PER) monotherapy (MT) or add‐on therapy (AT) in Chinese children with epilepsy, as well as to evaluate the data from routine therapeutic drug monitoring (TDM) of PER for these pediatric patients. Methods This retrospective and observational study was carried out on children with epilepsy (n = 340) from 2020 to 2022 at the Children's Hospital of Nanjing Medical University. Outcome measures were the responder rate (50% or greater seizure reduction), long‐term efficacy, and tolerability (number and types of adverse events) in MT and AT groups. Concentrations of plasma PER obtained from these patients, if available, were analyzed too. Results A total of 279 patients achieved at least 3 months of therapy, and 58.1% responded to PER therapy. 53 of the responders were seizure‐free (32.7%). The retention rate dropped from 88.0% at 3 months to 40.6% at 12 months after treatment. Patients with MT achieved better seizure control than those with AT (P < 0.001). Intriguingly, PER exerted a very weak effect on patients who took more than 2 ASMs or were diagnosed with drug‐resistant epilepsy. There were no significant differences in tolerability between the two groups. In addition, 179 patients were routinely monitored for PER, and the trough concentrations (C0) for these patients ranged from 30.0 to 992.0 ng/mL. However, no significant difference in C0 was observed between responders and nonresponders (333 ng/mL vs 325.5 ng/mL, P = 0.264). Significance This study provides effectiveness and safety data on Chinese children with epilepsy treated with PER either as MT or as AT. The efficacy of patients receiving MT was much better than cases administered with more than 2 ASMs or diagnosed with drug‐resistant epilepsy. In addition, no association was found between the plasma PER concentration and efficacy or safety. Plain Language Summary The study reports the effects of perampanel on seizures and adverse effects in Chinese patients with epilepsy younger than 18 years. Seizures decreased in 58.1% of patients (responders); in a third of these responders, seizures stopped. After treatment was started, 88% of patients were still on perampanel at 3 months and 40.6% at 12 months. People who were treated with perampanel only were more likely to respond than those who received perampanel and other antiseizure treatments, although perampanel was tolerated equally well in these groups. Plasma perampanel concentration did not predict seizure response or adverse effects.

Abstract Understanding the pairing symmetry is a crucial theoretical aspect in the study of unconventional superconductivity for interpreting experimental results. Here we study superconductivity of electron systems with both spin and pseudospin-1/2 degrees of freedom. By solving linearized gap equations, we derive a weak coupling criterion for the even-parity spin-singlet pseudospin-triplet pairing. It can generally mix with the on-site s-wave pairing since both of them belong to the same symmetry representation (A 1g ) and their mixture could naturally give rise to anisotropic intra-band pairing gap functions with or without nodes. This may directly explain why some of the iron-chalcogenide superconductors are fully gapped (e.g. FeSe thin film) and some have nodes (e.g. LaFePO and LiFeP). We also find that the anisotropy of gap functions can be enhanced when the principal rotation symmetry is spontaneously broken in the normal state such as nematicity, and the energetic stabilization of pseudospin-triplet pairings indicates the coexistence of nematicity and superconductivity. This could be potentially applied to bulk FeSe, where gap anisotropy has been experimentally observed.

Abstract Understanding the adverse effects of tunnel crossing active faults on tunnel structures is crucial for ensuring their safe operation and construction. This paper presents the results of a series of model tests conducted at a scale of 1:40 using a fault sliding test box. Three sets of fault comparison tests were carried out, namely: (1) the tunnel does not cross the fault, (2) the spring stiffness is reduced, and (3) the model is not reinforced. The objective was to study the failure characteristics of tunnels crossing active faults. The findings reveal that when the hanging wall moves downwards, cracks appear on the surrounding rock surface of the hanging wall, specifically above the tunnel lining crossing the fault. The lining is significantly damaged within the range of − 30–+ 30 cm. All points of axial force exhibit an increasing compression trend. The section of axial force and bending moment near the fault fracture surface is notably larger than that far from the fault fracture surface. The safety factor of the entire structure decreases sharply after dislocation, making the tunnel more susceptible to cracking at various locations such as the vault, arch waist, left and right arch feet, and inverted arch. It has been proven that the shear compression of the fracture surface during fault dislocation is the main cause of longitudinal through cracks in the lining. The use of springs with higher stiffness effectively ensures the reciprocating dislocation of the upper and foot walls, with long duration and large displacement, providing a better simulation of the dislocation of active faults.

Abstract Milling quality (MQ) and grain shape (GS) of rice (Oryza sativa L.) are correlated traits, both determine farmers’ final profit. More than one population under multiple environments may provide valuable information for breeding selection on these MQ-GS correlations. However, suitable analytical methods for reciprocal introgression lines with linkage map for this kind of correlation remains unclear. In this study, our major tasks were (1) to provide a set of reciprocal introgression lines (composed of two BC2RIL populations) suitable for mapping by linkage mapping using markers/bins with physical positions; (2) to test the mapping effects of different methods by using MQ-GS correlation dissection as sample case; (3) to perform genetic and breeding simulation on pyramiding favorite alleles of QTLs for representative MQ-GS traits. Finally, with four analysis methods and data collected under five environments, we identified about 28.4 loci on average for MQ-GS traits. Notably, 52.3% of these loci were commonly detected by different methods and eight loci were novel. There were also nine regions harboring loci for different MQ-GS traits which may be underlying the MQ-GS correlations. Background independent (BI) loci were also found for each MQ and GS trait. All these information may provide useful resources for rice molecular breeding.

Background Community health services play an effective role in delaying the progression of diabetes and managing diabetes complications. Previous studies have suggested that the subjective experiences of visits to community health centers by patients with diabetes contributes to their improved health outcomes. However, few studies have evaluated the correlation of glycemic control outcomes with specific service processes and objective experiences of programs received by diabetic patients in the community health service centers. Objective To explore the correlation between the community health service experiences and glycemic control outcomes in patients with diabetes mellitus. Methods A cross-sectional survey design and multi-stage, cluster random sampling method was used to select six community health service centers in the central urban area of Guangzhou, with one family doctor team randomly selected from each center. A total of 336 patients with diabetes who visited the corresponding family doctor teams from September to November 2019 were recruited as the study subjects. A questionnaire was conducted to collect baseline information, fasting plasma glucose (FPG) level, and Primary Care Assessment Tool (PCAT) scores. The glycemic control outcomes of patients were assessed based on the FPG level, and their experiences of community health services were assessed based on the PCAT scores. Logistic regression models were used to evaluate the effect of community health service experiences on glycemic control outcomes in diabetic patients. Results The glycemic control rate of the included diabetic patients was 73.2% (246/336). The total PCAT score and the scores for each dimension of PCAT with good glycemic control outcomes were higher than those of patients with poor glycemic control outcomes, and the difference was statistically significant (P

Abstract Background Inflammatory bowel disease (IBD) is a global health concern with varying levels and trends across countries and regions. Understanding these differences is crucial for effective prevention and treatment strategies. Methods Using data from the 2019 Global Burden of Disease study, we examine IBD incidence, mortality, and disability-adjusted life years (DALYs) rates in 198 countries from 1990 to 2019. To assess changes in the burden of IBD, estimated annual percentage changes (EAPC) were calculated, and a Bayesian age-period-cohort model was used to predict the future 30-year trends of IBD. Results In 2019, there were 405,000 new IBD cases globally (95% uncertainty interval (UI) 361,000 to 457,000), with 41,000 deaths (95% UI 35,000 to 45,000) and 1.62million DALYs (95% UI 1.36–1.92million). The global age-standardized incidence rate in 2019 was 4.97 per 100,000 person-years (95% UI 4.43 to 5.59), with a mortality rate of 0.54 (95% UI 0.46 to 0.59) and DALYs rate of 20.15 (95% UI 16.86 to 23.71). From 1990 to 2019, EAPC values for incidence, mortality, and DALYs rates were − 0.60 (95% UI − 0.73 to − 0.48), − 0.69 (95% UI − 0.81 to − 0.57), and − 1.04 (95% UI − 1.06 to − 1.01), respectively. Overall, the burden of IBD has shown a slow decline in recent years. In SDI stratification, regions with higher initial SDI (high-income North America and Central Europe) witnessed decreasing incidence and mortality rates with increasing SDI, while regions with lower initial SDI (South Asia, Oceania, and Latin America) experienced a rapid rise in incidence but a decrease in mortality with increasing SDI. Predictions using a Bayesian model showed lower new cases and deaths from 2020 to 2050 than reference values, while the slope of the predicted incidence-time curve closely paralleled that of the 2019 data. Conclusion Increasing cases, deaths, and DALYs highlight the sustained burden of IBD on public health. Developed countries have stabilized or declining incidence rates but face high prevalence and societal burden. Emerging and developing countries experience rising incidence. Understanding these changes aids policymakers in effectively addressing IBD challenges in different regions and economic contexts.

Abstract Lenvatinib has been approved as one of the first‐line treatments for advanced hepatocellular carcinoma (HCC) due to its high treatment efficacy being non‐inferior to sorafenib. Previous studies have shown well‐controlled viremia contributes to the prognosis of HCC patients receiving first‐line sorafenib; hence, we postulated this association might also exist in HCC patients with lenvatinib treatment. From April 2018 to December 2021, 201 unresectable HCC patients with first‐line lenvatinib treatment in our institute were assessed. High‐effect nucleoside analogues were administered for hepatitis B virus (HBV) control, while direct‐acting antivirals were used for hepatitis C virus (HCV) elimination. Based on our previous study, well‐controlled viremia was defined as patients who had undetectable viremia, or who had been receiving antivirals at least 6 months before lenvatinib. This study enrolled 129 patients, including 85 patients with HBV‐related HCC (HBV‐HCC) and 44 patients with HCV‐related HCC (HCV‐HCC), respectively. Progression‐free survival (PFS) and overall survival (OS) rates between the two groups were not different. Before administration of lenvatinib, 57.1% of the HBV‐HCC patients and 88.4% of the HCV‐HCC patients had well‐controlled viremia, and their PFS (8.8 vs. 3.1 months, p

AIM: To investigate the role of reactive oxygen species (ROS) in epithelial–mesenchymal transition (EMT) and apoptosis of human lens epithelial cells (HLECs). METHODS: Flow cytometry was used to assess ROS production after transforming growth factor β2 (TGF-β2) induction. Apoptosis of HLECs after H2O2 and TGF-β2 interference with or without ROS scavenger N-acetylcysteine (NAC) were assessed by flow cytometry. The corresponding protein expression levels of the EMT marker α-smooth muscle actin (α-SMA), the extracellular matrix (ECM), marker fibronectin (Fn), and apoptosis-associated proteins were detected by using Western blotting in the presence of an ROS scavenger (NAC). Wound-healing and Transwell assays were used to assess the migration capability of HLECs. RESULTS: TGF-β2 stimulates ROS production within 8h in HLECs. Additionally, TGF-β2 induced HLECs cell apoptosis, EMT/ECM synthesis protein markers expression, and pro-apoptotic proteins production; nonetheless, NAC treatment prevented these responses. Similarly, TGF-β2 promoted HLECs cell migration, whereas NAC inhibited cell migration. We further determined that although ROS initiated apoptosis, it only induced the accumulation of the EMT marker α-SMA protein, but not COL-1 or Fn. CONCLUSION: ROS contribute to TGF-β2-induced EMT/ECM synthesis and cell apoptosis of HLECs; however, ROS alone are not sufficient for EMT/ECM synthesis.