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In China, accompanying parents are a special group supporting inclusive preschool education for children with autism spectrum disorder (ASD). Although they lack professional knowledge and skills in children's education, they are required to accompany their children full-time to provide necessary and unique assistance. The present study aims to explore the experiences of accompanying parents of children with ASD in the context of Chinese inclusive preschool education. Semi-structured interviews and observations were conducted with 14 accompanying parents from an inclusive kindergarten. Results showed that the accompanying parents have transitioned across three roles -- from "caregivers" to "educators" to "right defenders." Each role transition resulted from their interaction with different elements in the environment and was aimed at increasing beneficial resources. Therefore, future policies and projects should improve the socioecological conditions of accompanying parents to promote inclusive preschool education in China.

Abstract Microorganisms consume and transform dissolved organic matter (DOM) into various forms. However, it remains unclear whether the ecological patterns and drivers of DOM chemodiversity are analogous to those of microbial communities. Here, a large-scale investigation is conducted along the Chinese coasts to resolve the intrinsic linkages among the complex intertidal DOM pools, microbial communities and environmental heterogeneity. The abundance of DOM molecular formulae best fits log-normal distribution and follows Taylor’s Law. Distance-decay relationships are observed for labile molecular formulae, while latitudinal diversity gradients are noted for recalcitrant molecular formulae. Latitudinal patterns are also observed for DOM molecular features. Negative cohesion, bacterial diversity, and molecular traits are the main drivers of DOM chemodiversity. Stochasticity analyses demonstrate that determinism dominantly shapes the DOM compositional variations. This study unveils the intrinsic mechanisms underlying the intertidal DOM chemodiversity and microbial communities from ecological perspectives, deepening our understanding of microbially driven chemical ecology.

In order to investigate the effect of curing time on the edible quality and oxidative characteristics of compound low-sodium yak meat products, in this experiment, complex low-sodium yak meat was selected to investigate the effects of curing time (12, 18, 24, 30 and 36 h) on the edible quality and oxidative characteristics. The results showed that prolonging the curing time significantly reduced the cooking loss (P

Abstract Background T cells play a pivotal role in chemotherapy-triggered anti-tumor effects. Emerging evidence underscores the link between impaired anti-tumor immune responses and resistance to paclitaxel therapy in triple-negative breast cancer (TNBC). Tumor-related endothelial cells (ECs) have potential immunoregulatory activity. However, how ECs regulate T cell activity during TNBC chemotherapy remains poorly understood. Methods Single-cell analysis of ECs in patients with TNBC receiving paclitaxel therapy was performed using an accessible single-cell RNA sequencing (scRNA-seq) dataset to identify key EC subtypes and their immune characteristics. An integrated analysis of a tumor-bearing mouse model, immunofluorescence, and a spatial transcriptome dataset revealed the spatial relationship between ECs, especially Tumor necrosis factor receptor (TNFR) 2+ ECs, and CD8+ T cells. RNA sequencing, CD8+ T cell proliferation assays, flow cytometry, and bioinformatic analyses were performed to explore the immunosuppressive function of TNFR2 in ECs. The downstream metabolic mechanism of TNFR2 was further investigated using RNA sequencing, cellular glycolysis assays, and western blotting. Results In this study, we identified an immunoregulatory EC subtype, characterized by enhanced TNFR2 expression in non-responders. By a mouse model of TNBC, we revealed a dynamic reduction in the proportion of the CD8+ T cell-contacting tumor vessels that could co-localize spatially with CD8+ T cells during chemotherapy and an increased expression of TNFR2 by ECs. TNFR2 suppresses glycolytic activity in ECs by activating NF-κB signaling in vitro. Tuning endothelial glycolysis enhances programmed death-ligand (PD-L) 1-dependent inhibitory capacity, thereby inducing CD8+ T cell suppression. In addition, TNFR2+ ECs showed a greater spatial affinity for exhausted CD8+ T cells than for non-exhausted CD8+ T cells. TNFR2 blockade restores impaired anti-tumor immunity in vivo, leading to the loss of PD-L1 expression by ECs and enhancement of CD8+ T cell infiltration into the tumors. Conclusions These findings reveal the suppression of CD8+ T cells by ECs in chemoresistance and indicate the critical role of TNFR2 in driving the immunosuppressive capacity of ECs via tuning glycolysis. Targeting endothelial TNFR2 may serve as a potent strategy for treating TNBC with paclitaxel.

Abstract Background Telemedicine is beneficial for improving treatment efficiency and reducing medical expenses of cancer patients. This study focuses on cancer patients participating in teleconsultations through a regional telemedicine platform in China, analyzes the consultation process, and provides references for the clinical application of telemedicine. Methods We collected information on teleconsultations of cancer patients conducted from 2015 to 2022 through the regional telemedicine platform. Utilizing SPSS 23.0 software, we conducted descriptive analysis to summarize the distribution of patient gender, age, region, and disease types. The ordinal logistic regression analysis was adopted to analyze the factors influencing the waiting time and consultation duration for teleconsultations. Results From 2015 to 2022, a total of 23,060 teleconsultations were conducted for cancer patients via regional telemedicine platform, with an average growth rate of 11.09%. The main types of consultations were for lung cancer, liver cancer, and breast cancer, accounting for 18.14%, 10.49%, and 9.46% respectively. 57.05% of teleconsultations had a waiting time of less than 24 h, while patient age, consultation expert level, and disease type were the main factors influencing the waiting time. 50.06% of teleconsultations had a duration of more than 20 min, and the inviting hospital level and the title of invited consultant were the main factors influencing the consultation duration. Conclusions In China, telemedicine has been widely employed in the clinical diagnosis and treatment of cancers, covering various types of oncological diseases. However, the waiting time for teleconsultations was generally more than 12 h, indicating the need to enhance consultation scheduling and allocate more expert resources to further optimize the efficiency of teleconsultations. Additionally, further exploration is required for remote health management of outpatients with cancers outside the hospital.

This study aimed to examine the impact of different low-sodium formulations on the quality and oxidative properties of yak meat products. Yak foreleg meat was utilized as the primary raw material, and various proportions of potassium chloride (KCl) and sodium pyrophosphate were incorporated to partially replace sodium chloride (NaCl) during the marination process. The objective was to assess the effects of these low-sodium composite salts on yield, edible quality, lipid oxidation, and protein oxidation of yak meat in sauce, while also determining the optimal ratio of composite substitutes for sodium salts. The findings revealed that an increasing substitution of sodium pyrophosphate and KCl resulted in a significant increase in product yield (P

Abstract Background Enlarged choroid plexus (ChP) volume has been reported in patients with Alzheimer’s disease (AD) and inversely correlated with cognitive performance. However, its clinical diagnostic and predictive value, and mechanisms by which ChP impacts the AD continuum remain unclear. Methods This prospective cohort study enrolled 607 participants [healthy control (HC): 110, mild cognitive impairment (MCI): 269, AD dementia: 228] from the Chinese Imaging, Biomarkers, and Lifestyle study between January 1, 2021, and December 31, 2022. Of the 497 patients on the AD continuum, 138 underwent lumbar puncture for cerebrospinal fluid (CSF) hallmark testing. The relationships between ChP volume and CSF pathological hallmarks (Aβ42, Aβ40, Aβ42/40, tTau, and pTau181), neuropsychological tests [Mini-Mental State Examination (MMSE), Montreal Cognitive Assessment (MoCA), Neuropsychiatric Inventory (NPI), and Activities of Daily Living (ADL) scores], and multimodal neuroimaging measures [gray matter volume, cortical thickness, and corrected cerebral blood flow (cCBF)] were analyzed using partial Spearman’s correlation. The mediating effects of four neuroimaging measures [ChP volume, hippocampal volume, lateral ventricular volume (LVV), and entorhinal cortical thickness (ECT)] on the relationship between CSF hallmarks and neuropsychological tests were examined. The ability of the four neuroimaging measures to identify cerebral Aβ42 changes or differentiate among patients with AD dementia, MCI and HCs was determined using receiver operating characteristic analysis, and their associations with neuropsychological test scores at baseline were evaluated by linear regression. Longitudinal associations between the rate of change in the four neuroimaging measures and neuropsychological tests scores were evaluated on the AD continuum using generalized linear mixed-effects models. Results The participants’ mean age was 65.99 ± 8.79 years. Patients with AD dementia exhibited the largest baseline ChP volume than the other groups (P

In order to study the interaction and antioxidant effects of the combination of natural extract and complex phosphate on the quality characteristics of yak mince during cold storage. In this study, rosemary, grape seed extract and complex phosphate were mixed at the ratio of 0.015%, 0.02% and 0.10%, and the edible quality, rheological properties, lipid oxidation and protein oxidation of yak meat were measured after the meat was refrigerated at 4 ℃ for 12, 24, 36, 48 and 60 h. The results showed that with the extension of refrigeration time, the pH of yak mince treated with rosemary, grape seed extract and complex phosphate decreased significantly, and the water retention increased significantly (P

In this paper, we analyze the global asymptotic behaviors of a mathematical susceptible-infected(SI) age-infection-structured human immunodeficiency virus(HIV) model with heterogeneous transmission. Mathematical analysis shows that the local and global dynamics are completely determined by the basic reproductive number R0. If R01, it shows that disease-free equilibrium is unstable and the unique endemic equilibrium is globally asymptotically stable. The proofs of global stability utilize Lyapunov functions. Besides, the numerical simulations are illustrated to support these theoretical results and sensitivity analysis of each parameter for R0 is performed by the method of partial rank correlation coefficient(PRCC).

Abstract Tumor dormancy is a stage in the growth and development of malignant cells and is one of the biological characteristics of malignant cells. Complex transitions involving dormant tumor cells between quiescent and proliferative states pose challenges for tumor eradication. This paper explores the biological features and molecular mechanisms of tumor dormancy and highlights emerging therapies. The strategies discussed promise innovative clinical potential against malignant tumors. Understanding the mechanisms of dormancy can help provide valuable insights into the diagnosis and treatment of malignant tumors to advance the fight against this world problem.

Abstract Purpose Illness cognition is an important mediator between psychological and behavioral adjustment and the quality of life for patients and their caregivers. Evidence related to illness cognition among parents of children with leukemia is limited. The purpose of this study is to explore the illness cognition status and associated factors in parents of children with leukemia. Methods A cross-sectional survey was conducted with the parents of 335 children with leukemia from three general children’s hospitals in China from January to December 2022. A parents’ version of the illness cognition questionnaire was used to collect data. This included three subscales: helplessness, acceptance, and perceived benefits. Results The mean scores of helplessness, acceptance and perceived benefits of parents regarding their children’s disease were 15.56 (4.60), 16.25 (4.41), and 19.96 (3.69) respectively. The multiple regression model indicated seven factors associated with the parents’ illness cognition (adjusted R [2] ranged from 0.182 to 0.134): four socio-demographic factors (parent’s age, role, education level, and family income) and three clinical factors (length of time spent each day caring for the child, the child’s age at diagnosis, and the duration of the disease). Conclusion This study reports on different levels of illness cognition and associated factors among parents of children with leukemia. The results may help pediatric oncology medical staff identify risk factors for poor psychological adjustment to children’s diseases. Parents may benefit from psychological support aimed at improving positive illness cognition.

Abstract The increasing incidence of autism spectrum disorder (ASD) worldwide poses serious social and family problems. Various risk factors for ASD are gradually being recognized, and there are also various options for the treatment of ASD. It is worth noting that dietary interventions have been shown to have a positive effect in terms of mitigating and preventing some psychiatric disorders, such as epilepsy, Parkinson's disease, and ASD, and they are gradually receiving attention as a safe adjuvant treatment. In this review, based on the current understanding of the pathogenic factors and intervention strategies for ASD, different dietary patterns that can be selected for children with ASD are discussed in depth. Moreover, a review was conducted on the use of dietary factors, such as natural products from food sources, prebiotics, and probiotics, as effective supplements to existing dietary patterns. As increasing evidence shows that maternal risk factors, such as obesity, diabetes, and hypertension, are associated with an increased risk of ASD in offspring, dietary suggestions are also made for pregnant woman with ASD‐related risk factors to counteract the impact of these risk factors. With compensation from food‐derived natural products, prebiotics, and probiotics, suitable dietary patterns can further enhance the effectiveness of dietary interventions for ASD. In addition, dietary recommendations for pregnant woman may reduce the potential impact of obesity, diabetes, and hypertension and may help to prevent the occurrence of ASD to the maximum extent possible.

Abstract This study developed a kind of PEG-crosslinked O-carboxymethyl chitosan (O-CMC–PEG) with various PEG content for food packaging. The crosslinking agent of isocyanate-terminated PEG was firstly synthesized by a simple condensation reaction between PEG and excess diisocyanate, then the crosslink between O-carboxymethyl chitosan (O-CMC) and crosslinking agent occurred under mild conditions to produce O-CMC–PEG with a crosslinked structure linked by urea bonds. FT-IR and 1H NMR techniques were utilized to confirm the chemical structures of the crosslinking agent and O-CMC–PEGs. Extensive research was conducted to investigate the impact of the PEG content (or crosslinking degree) on the physicochemical characteristics of the casted O-CMC–PEG films. The results illuminated that crosslinking and components compatibility could improve their tensile features and water vapor barrier performance, while high PEG content played the inverse effects due to the microphase separation between PEG and O-CMC segments. The in vitro degradation rate and water sensitivity primarily depended on the crosslinking degree in comparison with the PEG content. Furthermore, caused by the remaining –NH2 groups of O-CMC, the films demonstrated antibacterial activity against Escherichia coli and Staphylococcus aureus. When the PEG content was 6% (medium crosslinking degree), the prepared O-CMC–PEG−6% film possessed optimal tensile features, high water resistance, appropriate degradation rate, low water vapor transmission rate and fine broad-spectrum antibacterial capacity, manifesting a great potential for application in food packaging to extend the shelf life.

ObjectivesThis study aims to assess the predictive capability of synthetic MRI in assessing neurodevelopmental outcomes for extremely preterm neonates with low-grade Germinal Matrix-Intraventricular Hemorrhage (GMH-IVH). The study also investigates the potential enhancement of predictive performance by combining relaxation times from different brain regions.Materials and methodsIn this prospective study, 80 extremely preterm neonates with GMH-IVH underwent synthetic MRI around 38 weeks, between January 2020 and June 2022. Neurodevelopmental assessments at 18 months of corrected age categorized the infants into two groups: those without disability (n = 40) and those with disability (n = 40), with cognitive and motor outcome scores recorded. T1, T2 relaxation times, and Proton Density (PD) values were measured in different brain regions. Logistic regression analysis was utilized to correlate MRI values with neurodevelopmental outcome scores. Synthetic MRI metrics linked to disability were identified, and combined models with independent predictors were established. The predictability of synthetic MRI metrics in different brain regions and their combinations were evaluated and compared with internal validation using bootstrap resampling.ResultsElevated T1 and T2 relaxation times in the frontal white matter (FWM) and caudate were significantly associated with disability (p

Background: With the popularity of the internet, short videos have become an indispensable tool to obtain health information. However, avoiding health disinformation owing to the openness of the Internet is difficult for users. Disinformation may endanger the health and lives of users. Objective: With a focus on the process of identifying short videos' health disinformation and the factors affecting the accuracy of identification, this study aimed to investigate the identification methods, coping strategies, and the impact of short videos’ health disinformation on undergraduate nursing students. The findings will provide guidance to users on obtaining high-quality and healthy information, in addition to reducing health risks. Methods: Semi-structured in-depth interviews were conducted with 22 undergraduate nursing students in October 2022, and data were collected for collation and content analyses. Results: The techniques used to identify short videos that include health disinformation as well as how undergraduate nursing students perceived these videos' features are among the study's findings. The failure factors in identification, coping paths, and adverse impacts of short videos on health disinformation were analyzed. The platform, the material itself, and the students' individual characteristics all have an impact on their identifying behavior. Conclusions: Medical students continue to face many obstacles in identifying and responding to health disinformation through short videos. Preventing and stopping health disinformation not only requires individual efforts to improve health literacy and maintain rational thinking, it also requires the joint efforts of short video producers, relevant departments, and platforms.

Lung cancer persistently leads as the primary cause of morbidity and mortality among malignancies. A notable increase in the prevalence of lung adenocarcinoma has become evident in recent years. Although targeted therapies have shown in treating certain subsets of non-small cell lung cancers (NSCLC), a significant proportion of patients still face suboptimal therapeutic outcomes. Neuregulin-1 (NRG1), a critical member of the NRG gene family, initially drew interest due to its distribution within the nascent ventricular endocardium, showcasing an exclusive presence in the endocardium and myocardial microvessels. Recent research has highlighted NRG1’s pivotal role in the genesis and progression across a spectrum of tumors, influencing molecular perturbations across various tumor-associated signaling pathways. This review provides a concise overview of NRG1, including its expression patterns, configuration, and fusion partners. Additionally, we explore the unique features and potential therapeutic strategies for NRG1 fusion-positive occurrences within the context of NSCLC.

Objective To evaluate the effectiveness of machine learning (ML) models in predicting 5-year type 2 diabetes mellitus (T2DM) risk within the Chinese population by retrospectively analyzing annual health checkup records. Methods We included 46,247 patients (32,372 and 13,875 in training and validation sets, respectively) from a national health checkup center database. Univariate and multivariate Cox analyses were performed to identify factors influencing T2DM risk. Extreme Gradient Boosting (XGBoost), support vector machine (SVM), logistic regression (LR), and random forest (RF) models were trained to predict 5-year T2DM risk. Model performances were analyzed using receiver operating characteristic (ROC) curves for discrimination and calibration plots for prediction accuracy. Results Key variables included fasting plasma glucose, age, and sedentary time. The LR model showed good accuracy with respective areas under the ROC (AUCs) of 0.914 and 0.913 in training and validation sets; the RF model exhibited favorable AUCs of 0.998 and 0.838. In calibration analysis, the LR model displayed good fit for low-risk patients; the RF model exhibited satisfactory fit for low- and high-risk patients. Conclusions LR and RF models can effectively predict T2DM risk in the Chinese population. These models may help identify high-risk patients and guide interventions to prevent complications and disabilities.

The intrinsic resistance of MRSA coupled with biofilm antibiotic tolerance challenges the antibiotic treatment of MRSA biofilm infections. Phytochemical-based nanoplatform is a promising emerging approach for treatment of biofilm infection. However, their therapeutic efficacy was restricted by the low drug loading capacity and lack of selectivity. Herein, we constructed a surface charge adaptive phytochemical-based nanoparticle with high isoliquiritigenin (ISL) loading content for effective treatment of MRSA biofilm. A dimeric ISL prodrug (ISL-G2) bearing a lipase responsive ester bond was synthesized, and then encapsulated into the amphiphilic quaternized oligochitosan. The obtained ISL-G2 loaded NPs possessed positively charged surface, which allowed cis-aconityl-d-tyrosine (CA-Tyr) binding via electrostatic interaction to obtain ISL-G2@TMDCOS-Tyr NPs. The NPs maintained their negatively charged surface, thus prolonging the blood circulation time. In response to low pH in the biofilms, the fast removal of CA-Tyr led to a shift in their surface charge from negative to positive, which enhanced the accumulation and penetration of NPs in the biofilms. Sequentially, the pH-triggered release of d-tyrosine dispersed the biofilm and lipase-triggered released of ISL effectively kill biofilm MRSA. An in vivo study was performed on a MRSA biofilm infected wound model. This phytochemical-based system led to ∼2 log CFU (>99 %) reduction of biofilm MRSA as compared to untreated wound (P < 0.001) with negligible biotoxicity in mice. This phytochemical dimer nanoplatform shows great potential for long-term treatment of resistant bacterial infections.

Background: The predictive value of the methylation of Long non-coding RNA (lncRNA) metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) and H19 promoters in peripheral blood leukocytes as a non-invasive biomarker for the chemotherapy effect and prognosis gastric cancer (GC) is unclear. Methods: The DNA methylation of H19 and MALAT1 between chemotherapy-sensitive and non-sensitive groups and between groups with better and worse survival of GC was compared using regression analyses. Several predictive nomograms were constructed. The genetic alteration of MALAT1 and H19 and the association between gene expression and immune status in GC were also investigated using bioinformatics analysis. Results: Higher genetic methylations in peripheral blood were noticed in GC groups with poorer survival. The constructed nomograms presented strong predictive values for the chemotherapy effect and 3-year survival of disease-free survival, progression-free survival, and overall survival, with the area under the curve as 0.838, 0.838, 0.912, and 0.925, respectively. Significant correlations between MALAT1 or H19 expression and marker genes of immune checkpoints and immune pathways were noticed. The high infiltration of macrophages in H19-high and low infiltration of CD8+ T cells in MALAT1-high groups were associated with worse survival of GC. Conclusions: MALAT1 and H19 have the potential to predict the chemotherapy response and clinical outcomes of GC.

Abstract Background Clinically, hormone replacement therapy (HRT) is the main treatment for primary ovarian insufficiency (POI). However, HRT may increase the risk of both breast cancer and cardiovascular disease. Exosomes derived from human umbilical cord mesenchymal stem cell (hUC-MSC) have been gradually applied to the therapy of a variety of diseases through inflammation inhibition, immune regulation, and tissue repair functions. However, the application and study of hUC-MSC exosomes in POI remain limited. Methods Here, we first constructed four rat animal models: the POI-C model (the “cyclophosphamide-induced” POI model via intraperitoneal injection), the POI-B model (the “busulfan-induced” POI model), the POI-U model (the “cyclophosphamide-induced” POI model under ultrasonic guidance), and MS model (the “maternal separation model”). Second, we compared the body weight, ovarian index, status, Rat Grimace Scale, complications, and mortality rate of different POI rat models. Finally, a transabdominal ultrasound-guided injection of hUC-MSC exosomes was performed, and its therapeuticy effects on the POI animal models were evaluated, including changes in hormone levels, oestrous cycles, ovarian apoptosis levels, and fertility. In addition, we performed RNA-seq to explore the possible mechanism of hUC-MSC exosomes function. Results Compared with the POI-C, POI-B, and MS animal models, the POI-U model showed less fluctuation in weight, a lower ovarian index, fewer complications, a lower mortality rate, and a higher model success rate. Second, we successfully identified hUC-MSCs and their exosomes, and performed ultrasound-guided intraovarian hUC-MSCs exosomes injection. Finally, we confirmed that the ultrasound-guided exosome injection (termed POI-e) effectively improved ovarian hormone levels, the oestrous cycle, ovarian function, and fertility. Mechanically, hUC-MSCs may play a therapeutic role by regulating ovarian immune and metabolic functions. Conclusions In our study, we innovatively constructed an ultrasound-guided ovarian drug injection method to construct POI-U animal models and hUC-MSC exosomes injection. And we confirmed the therapeutic efficacy of hUC-MSC exosomes on the POI-U animal models. Our study will offer a better choice for new animal models of POI in the future and provides certain guidance for the hUC-MSCs exosome therapy in POI patients. Graphical abstract The schema of construction of different animal models, extraction and identifying hUC-MSCs and exosomes, therapy of ultrasound-guided hUC-MSCs exosome injection. Note: POI: premature ovarian insufficiency; hUC-MSCs: Human umbilical cord mesenchymal stem cells; POI-C: POI-cyclophosphamide; POI-B: POI-cyclophosphamide + Busulfan; POI-U: POI-Ultrasonic guidance cyclophosphamide injection; MS: POI-Maternal separation. POI-e: ultrasound-guided hUC-MSCs exosome injection; AMH: Anti-müllerian hormone; LH: Luteinizing hormone; FSH: Follicle-stimulating hormone; DA: dopamine; T: Testosterone; PRL: prolactin; GnRH: Gonadotropin-releasing hormone.

Abstract Background Platinum-etoposide chemotherapy combined with immune checkpoint inhibitors (ICIs) has been recommended as the first-line standard treatment for extensive-stage small-cell lung cancer (ES-SCLC). However, the effect of thoracic radiotherapy (TRT) on these patients is still unknown. This study aimed to evaluate the efficacy and safety of TRT for ES-SCLC patients who responded to first-line ICIs and chemotherapy (CHT). Methods Patients who received 4 to 6 cycles of ICIs and CHT as first-line therapy at three hospitals between 2018 and 2022 were included in the analysis. All patients were divided into two groups based on whether they received TRT as first-line treatment, and propensity score matching (PSM) was performed to ensure that the characteristics of two groups were well-balanced. The primary endpoints were overall survival (OS) and progression-free survival (PFS), and the secondary endpoint was toxic effects. Results A total of 276 patients were included, and the median follow-up time was 22.3 (range, 4.0-53.73) months. After PSM, 197 patients were further analysed, and 99 of whom received TRT. The baseline characteristics were well-balanced between patients in the TRT and non-TRT groups. There were significant differences in PFS between the TRT and non-TRT groups, with the median PFS of 10.76 and 7.63 months, respectively (P = 0.014). Significantly improved OS was observed in the TRT group (21.67 vs. 16.6 months, P = 0.009). In addition, the use of TRT was an independent prognostic factor for PFS and OS of ES-SCLC patients receiving ICIs plus CHT. In terms of safety, no significant increase of any grades adverse event (AE) (P = 0.874) and G3-4 AE (P = 0.909) was observed for patients receiving TRT. Radiation esophagitis, gastrointestinal and hematologic toxicities were the most common AEs in TRT group, which were tolerable. And high-dose radiotherapy was associated with higher incidence of pneumonitis. Conclusion Addition of TRT showed significant survival benefits and well tolerability in ES-SCLC patients receiving platinum-etoposide CHT and ICIs, which could be a feasible first-line treatment strategy for ES-SCLC patients.

Abstract Background Immunotherapy has significantly improved survival of esophageal squamous cell cancer (ESCC) patients, however the clinical benefit was limited to only a small portion of patients. This study aimed to perform a deep learning signature based on H&E-stained pathological specimens to accurately predict the clinical benefit of PD-1 inhibitors in ESCC patients. Methods ESCC patients receiving PD-1 inhibitors from Shandong Cancer Hospital were included. WSI images of H&E-stained histological specimens of included patients were collected, and randomly divided into training (70%) and validation (30%) sets. The labels of images were defined by the progression-free survival (PFS) with the interval of 4 months. The pretrained ViT model was used for patch-level model training, and all patches were projected into probabilities after linear classifier. Then the most predictive patches were passed to RNN for final patient-level prediction to construct ESCC-pathomics signature (ESCC-PS). Accuracy rate and survival analysis were performed to evaluate the performance of ViT-RNN survival model in validation cohort. Results 163 ESCC patients receiving PD-1 inhibitors were included for model training. There were 486,188 patches of 1024*1024 pixels from 324 WSI images of H&E-stained histological specimens after image pre-processing. There were 120 patients with 227 images in training cohort and 43 patients with 97 images in validation cohort, with balanced baseline characteristics between two groups. The ESCC-PS achieved an accuracy of 84.5% in the validation cohort, and could distinguish patients into three risk groups with the median PFS of 2.6, 4.5 and 12.9 months (P

Abstract Background Macrophages phenotypic deviation and immune imbalance play vital roles in pregnancy-associated diseases such as spontaneous miscarriage. Trophoblasts regulate phenotypic changes in macrophages, however, their underlying mechanism during pregnancy remains unclear. Therefore, this study aimed to elucidate the potential function of trophoblast-derived miRNAs (miR-410-5p) in macrophage polarization during pregnancy. Methods Patient decidual macrophage tissue samples in spontaneous abortion group and normal pregnancy group (those who had induced abortion for non-medical reasons) were collected at the Reproductive Medicine Center of Renmin Hospital of Wuhan University from April to December 2021. Furthermore, placental villi and decidua tissue samples were collected from patients who had experienced a spontaneous miscarriage and normal pregnant women for validation and subsequent experiments at the Shenzhen Zhongshan Obstetrics & Gynecology Hospital (formerly Shenzhen Zhongshan Urology Hospital), from March 2021 to September 2022. As an animal model, 36 female mice were randomly divided into six groups as follows: naive-control, lipopolysaccharide-model, agomir-negative control prevention, agomir-410-5p prevention, agomir-negative control treatment, and agomir-410-5p treatment groups. We analyzed the miR-410-5p expression in abortion tissue and plasma samples; and supplemented miR-410-5p to evaluate embryonic absorption in vivo. The main source of miR-410-5p at the maternal–fetal interface was analyzed, and the possible target gene, signal transducer and activator of transcription (STAT) 1, of miR-410-5p was predicted. The effect of miR-410-5p and STAT1 regulation on macrophage phenotype, oxidative metabolism, and mitochondrial membrane potential was analyzed in vitro. Results MiR-410-5p levels were lower in the spontaneous abortion group compared with the normal pregnancy group, and plasma miR-410-5p levels could predict pregnancy and spontaneous abortion. Prophylactic supplementation of miR-410-5p in pregnant mice reduced lipopolysaccharide-mediated embryonic absorption and downregulated the decidual macrophage pro-inflammatory phenotype. MiR-410-5p were mainly distributed in villi, and trophoblasts secreted exosomes-miR-410-5p at the maternal–fetal interface. After macrophages captured exosomes, the cells shifted to the tolerance phenotype. STAT1 was a potential target gene of miR-410-5p. MiR-410-5p bound to STAT1 mRNA, and inhibited the expression of STAT1 protein. STAT1 can drive macrophages to mature to a pro-inflammatory phenotype. MiR-410-5p competitive silencing of STAT1 can avoid macrophage immune disorders. Conclusion MiR-410-5p promotes M2 macrophage polarization by inhibiting STAT1, thus ensuring a healthy pregnancy. These findings are of great significance for diagnosing and preventing spontaneous miscarriage, providing a new perspective for further research in this field.

In this paper, we investigate the bifurcation results of the fractional Kirchhoff–Schrödinger–Poisson system \begin{equation*} \begin{cases} M([u]_s^2)(-\Delta)^s u+V(x)u+\phi(x) u=\lambda g(x)|u|^{p-1}u+|u|^{2_s^*-2}u~~&{\rm in}~\mathbb{R}^3, \\ (-\Delta)^t \phi(x)=u^2~~&{\rm in}~\mathbb{R}^3, \end{cases} \end{equation*} where $s,t\in(0,1)$ with $2t+4s>3$ and the potential function $V$ is a continuous function. We show that the existence of components of (weak) solutions of the above equation bifurcates out from the first eigenvalue $\lambda_1$ of the problem $$(-\Delta)^s u+V(x)u=\lambda g(x)u\quad\mbox{in }\mathbb R^3.$$ The main feature of this paper is the inclusion of a potentially degenerate Kirchhoff model, combined with the critical nonlinearity.

Abstract Background Hyperglycemia during pregnancy can affect fetal heart in many ways, including causing cardiac malformation, leading to hypertrophic cardiomyopathy and cardiac dysfunction. Echocardiographic evaluation can assist identify alterations in heart structure, morphology and function, enabling prompt monitoring and management. However, according to earlier research, the cardiac alterations are modest in hyperglycemic mothers’ fetuses, and might not be detectable using conventional methods and it is also unclear whether these changes are related to the metabolism of mothers. Fetal Heart Quantification (Fetal HQ) can assess ventricular geometry and function more sensitively and thoroughly, and identify sub-clinical cardiac dysfunction. The purpose of this study was to evaluate fetal heart by Fetal HQ in fetuses of hyperglycemic mothers who either had pre-gestational or gestational diabetes and to correlate them with maternal metabolic indices. Methods The fetuses of 25 gestational age-matched control mothers, 48 women with gestational diabetes mellitus (GDM), and 11 women with diabetes mellitus (DM) were included in the prospective case-control research. Using fetal echocardiography and speckle tracking echocardiography (STE), the heart of the fetus was evaluated. Differences in the groups’ anthropometric, metabolic, and cardiac parameters were examined. It was assessed whether maternal features, prenatal glucose, lipids, and maternal hemoglobin A1c (HbA1c) correlated with fetal cardiac parameters. Results The LV EDV and ESV were significantly higher in the GDM group as compared to the DM group (p

Abstract Background Acute respiratory distress syndrome (ARDS) is a disease with high mortality and morbidity. Regulator of G protein signaling protein 6 (RGS6), identified as a tumor suppressor gene, has received increasing attention owing to its close relationship with oxidative stress and inflammation. However, the association between ARDS and RGS6 has not been reported. Methods Congruously regulated G protein-coupled receptor (GPCR)-related genes and differentially expressed genes (DEGs) in an acute lung injury (ALI) model were identified, and functional enrichment analysis was conducted. In an in vivo study, the effects of RGS6 knockout were studied in a mouse model of ALI induced by lipopolysaccharide (LPS). HE staining, ELISA, and immunohistochemistry were used to evaluate pathological changes and the degree of inflammation. In vitro, qRT‒PCR, immunofluorescence staining, and western blotting were used to determine the dynamic changes in RGS6 expression in cells. The RGS6 overexpression plasmid was constructed for transfection. qRT‒PCR was used to assess proinflammatory factors transcription. Western blotting and flow cytometry were used to evaluate apoptosis and reactive oxygen species (ROS) production. Organoid culture was used to assess the stemness and self-renewal capacity of alveolar epithelial type II cells (AEC2s). Results A total of 110 congruously regulated genes (61 congruously upregulated and 49 congruously downregulated genes) were identified among GPCR-related genes and DEGs in the ALI model. RGS6 was downregulated in vivo and in vitro in the ALI model. RGS6 was expressed in the cytoplasm and accumulated in the nucleus after LPS stimulation. Compared with the control group, we found higher mortality, more pronounced body weight changes, more serious pulmonary edema and pathological damage, and more neutrophil infiltration in the RGS6 knockout group upon LPS stimulation in vivo. Moreover, AEC2s loss was significantly increased upon RGS6 knockout. Organoid culture assays showed slower alveolar organoid formation, fewer alveolar organoids, and impaired development of new structures after passaging upon RGS6 knockout. In addition, RGS6 overexpression decreased ROS production as well as proinflammatory factor transcription in macrophages and decreased apoptosis in epithelial cells. Conclusions RGS6 plays a protective role in ALI not only in early inflammatory responses but also in endogenous lung stem cell regeneration. Graphical Abstract

Background: Murine Nischarin and its human homolog IRAS are scaffold proteins highly expressed in the central nervous system (CNS). Nischarin was initially discovered as a tumor suppressor protein, and recent studies have also explored its potential value in the CNS. Research on IRAS has largely focused on its effect on opioid dependence. Although the role of Nischarin/IRAS in the physiological function and pathological process of the CNS has gradually attracted attention and the related research results are expected to be applied in clinical practice, there is no systematic review of the role and mechanisms of Nischarin/IRAS in the CNS so far. Aim of review: This review will systematically analyze the role and mechanism of Nischarin/IRAS in the CNS, and provide necessary references and possible targets for the treatment of neurological diseases, thereby broadening the direction of Nischarin/IRAS research and facilitating clinical translation. Key scientific concepts of review: The pathophysiological processes affected by dysregulation of Nischarin/IRAS expression in the CNS are mainly introduced, including spinal cord injury (SCI), opioid dependence, anxiety, depression, and autism. The molecular mechanisms such as factors regulating Nischarin/IRAS expression and signal transduction pathways regulated by Nischarin/IRAS are systematically summarized. Finally, the clinical application of Nischarin/IRAS has been prospected.

Summary: Background: This phase II prospective trial aimed to investigate the efficacy and safety of adebrelimab (PD-L1 antibody) plus first-line chemotherapy followed by sequential thoracic radiotherapy (TRT) combined with adebrelimab in extensive-stage small–cell lung cancer (ES-SCLC). Biomarkers associated with potential therapeutic effects were also explored. Methods: Patients with previously untreated ES-SCLC were enrolled at Shandong Cancer Hospital and Institute (Jinan, China). Patients received 4–6 cycles of adebrelimab (20 mg/kg, D1, Q3W) combined with EP/EC (etoposide, 100 mg/m2, D1-3, Q3W and cisplatin, 75 mg/m2, D1, Q3W or carboplatin, AUC = 5, D1, Q3W). Then patients with response sequentially underwent consolidative TRT (≥30 Gy in 10 fractions or ≥50 Gy in 25 fractions, involved-field irradiation), and maintenance adebrelimab until disease progression or intolerable adverse events (AEs). The primary endpoint was overall survival (OS). Genomic and circulating tumour DNA (ctDNA) profiling were also analyzed with tumour tissues and peripheral blood. This trial was registered with ClinicalTrials.gov, NCT04562337. Findings: From October 2020 to April 2023, 67 patients diagnosed with ES-SCLC were enrolled and received at least one dose of study treatment. All patients were included in the efficacy and safety analyses. 45 patients received sequential TRT as planned. The median OS and progression-free survival (PFS) was 21.4 months (95% CI: 17.2–not reached months) and 10.1 months (95% CI: 6.9–15.5 months), respectively. The confirmed objective response rate was 71.6% (48/67, 95% CI: 59.3–82.0%) and disease control rate was 89.6% (60/67, 95% CI: 79.7–95.7%). There were no treatment-related deaths. The most common grade 3 or higher treatment-related adverse events (TRAEs) were hematological toxicities. The incidence of any grade and G3+ pneumonitis was 25% (17/67) and 6% (4/67), respectively. No unexpected adverse events were observed. Patients without co-mutations of TP53/RB1 in both tissue and peripheral blood displayed longer PFS (tissue, P = 0.071; ctDNA, P = 0.060) and OS (tissue, P = 0.032; ctDNA, P = 0.031). Interpretation: Adebrelimab plus chemotherapy and sequential TRT as first-line therapy for ES-SCLC showed promising efficacy and acceptable safety. Funding: This study was funded by the National Natural Science Foundation of China (82172865), Jiangsu Hengrui Pharmaceuticals Co., Ltd. and Amoy Diagnostics Co., Ltd.

Introduction: Dilated cardiomyopathy (DCM) is a fatal myocardial condition with ventricular structural changes and functional deficits, leading to systolic dysfunction and heart failure (HF). DCM is a frequent complication in oncologic patients receiving Doxorubicin (Dox). Dox is a highly cardiotoxic drug, whereas its damaging spectrum affects most of the organs by multiple pathogenic cascades. Experimentally reproduced DCM/HF through Dox administrations has shed light on the pathogenic drivers of cardiotoxicity. Growth hormone (GH) releasing peptide 6 (GHRP-6) is a GH secretagogue with expanding and promising cardioprotective pharmacological properties. Here we examined whether GHRP-6 administration concomitant to Dox prevented the onset of DCM/HF and multiple organs damages in otherwise healthy rats.Methods: Myocardial changes were sequentially evaluated by transthoracic echocardiography. Autopsy was conducted at the end of the administration period when ventricular dilation was established. Semiquantitative histopathologic study included heart and other internal organs samples. Myocardial tissue fragments were also addressed for electron microscopy study, and characterization of the transcriptional expression ratio between Bcl-2 and Bax. Serum samples were destined for REDOX system balance assessment.Results and discussion: GHRP-6 administration in parallel to Dox prevented myocardial fibers consumption and ventricular dilation, accounting for an effective preservation of the LV systolic function. GHRP-6 also attenuated extracardiac toxicity preserving epithelial organs integrity, inhibiting interstitial fibrosis, and ultimately reducing morbidity and mortality. Mechanistically, GHRP-6 proved to sustain cellular antioxidant defense, upregulate prosurvival gene Bcl-2, and preserve cardiomyocyte mitochondrial integrity. These evidences contribute to pave potential avenues for the clinical use of GHRP-6 in Dox-treated subjects.

BackgroundSerum lipids were found to be correlated with chronic kidney disease and cardiovascular disease. Here, we aimed to research the potential causal associations between five serum lipid parameters and the risk of diabetic nephropathy using several Mendelian Randomization methods.MethodsGenetic data was obtained from the UK Biobank datasets. Causal effects were estimated using multiple MR methods. Heterogeneity and pleiotropy tests were performed.ResultsMR analysis revealed that HDL-C and TG exhibited causal associations with diabetic nephropathy (P

Abstract Objective It has been observed that the prognosis of patients with HER2‐positive metastatic breast cancer has improved significantly with HER2‐targeted agents. However, there is still a lack of evidence regarding first‐line anti‐HER2 treatment options for patients who have received adjuvant and/or neoadjuvant trastuzumab for HER2‐positive metastatic breast cancer. Besides, there are no reliable markers that can predict the efficacy of anti‐HER2 treatment in these patients. Methods Patients who have received adjuvant and/or neoadjuvant trastuzumab for HER2‐positive metastatic breast cancer were enrolled. Pyrotinib plus albumin‐bound paclitaxel were used as first‐line treatment. The primary endpoint was the objective response rate (ORR). The safety profile was also assessed. In order to explore predictive biomarkers using Olink technology, blood samples were collected dynamically. Results From December 2019 to August 2023, the first stage of the study involved 27 eligible patients. It has not yet reached the median PFS despite the median follow‐up being 17.8 months. Efficacy evaluation showed that the ORR was 92.6%, and the DCR was 100%. Adverse events of grade 3 or higher included diarrhoea (29.6%), leukopenia (11.1%), neutropenia (25.9%), oral mucositis (3.7%), and hand‐foot syndrome (3.7%). Toll‐like receptor 3 (TLR3) and Proto‐oncogene tyrosine‐protein kinase receptor (RET) were proteins with significant relevance to PFS in these patients. Conclusions This study demonstrates that pyrotinib plus albumin‐bound paclitaxel as a first‐line treatment regimen shows good efficacy and manageable safety for patients who have received adjuvant and/or neoadjuvant trastuzumab for HER2‐positive metastatic breast cancer. Besides, a significant association was identified between the expression levels of TLR3 and RET and the PFS in patients.

For a directed graph D, it's deemed rainbow connected if each arc is assigned a different color, so that all paths from the vertex u to the vertex v are rainbow connected. Rainbow connection number refers to how many colors are needed in D to achieve rainbow connectivity. Among ordered vertex pair (u,v) with arc coloring, if both arcs and internal vertices exhibit unique colors, it is referred to as a total colored graph. As the total rainbow connection number indicates, the smallest number of colors are required to total-color D. This paper focuses on investigating the rainbow connection number of the biorientation of a connected graph, as well as the total rainbow connection number.

Uniportal video-assisted thoracoscopic surgery (UVATS) segmentectomy has emerged as an effective approach for managing early-stage non-small-cell lung cancer (NSCLC). Compared to conventional open and thoracoscopic surgeries, this minimally invasive surgical technique offers multiple benefits, including reduced postoperative discomfort, shorter hospital stays, expedited recovery, fewer complications, and superior cosmetic outcomes. Particularly advantageous in preserving lung function, UVATS segmentectomy is a compelling option for patients with compromised lung capabilities or limited pulmonary reserve. Notably, it demonstrates promising oncological results in early-stage NSCLC, with long-term survival rates comparable to those of lobectomies. Skilled thoracic surgeons can ensure a safe and effective execution of UVATS despite the potential technical challenges posed by complex tumor locations that may hinder visibility and maneuverability within the thoracic cavity. This study provided a comprehensive review of the literature and existing studies on UVATS segmentectomies. It delves into the evolution of the technique, its current applications, and the balance between its benefits and limitations. This discussion extends the technical considerations, challenges, and prospects of UVATS segmentectomy. Furthermore, it aimed to update advancements in segmentectomy for treating early-stage NSCLC, offering in-depth insights to thoracic surgeons to inform more scientifically grounded and patient-specific surgical decisions.

Pulmonary mucinous adenocarcinoma (PMA), a distinct subtype of non-small cell lung cancer (NSCLC), is characterized by an abundance of mucin-producing cells. Although this subtype comprises a relatively small fraction of lung adenocarcinomas, PMA stands apart due to its unique clinical, pathological, and molecular features. This review comprehensively discusses the pathophysiology and etiology, clinical features, diagnostic methods, treatment strategies, prognosis, and future directions for PMA, drawing from relevant literature and existing studies. Advances in PMA treatment includes surgical intervention, targeted therapy, immunotherapy, and adjuvant therapy. Particularly, we discussed factors influencing the prognosis of PMAs, such as molecular markers, pathological features, and the impact of the latest treatment advances on prognosis. Moreover, we intended this review to be a comprehensive reference for diagnosing, treating, and assessing the prognosis of PMA, providing valuable guidance for clinical practice.

Abstract Anti‐virulence therapy that interferes with bacterial communication, known as “quorum sensing (QS)”, is a promising strategy for circumventing bacterial resistance. Using nanomaterials to regulate bacterial QS in anti‐virulence therapy has attracted much attention, which is mainly attributed to unique physicochemical properties and excellent designability of nanomaterials. However, bacterial QS is a dynamic and multistep process, and there are significant differences in the specific regulatory mechanisms and related influencing factors of nanomaterials in different steps of the QS process. An in‐depth understanding of the specific regulatory mechanisms and related influencing factors of nanomaterials in each step can significantly optimize QS regulatory activity and enhance the development of novel nanomaterials with better comprehensive performance. Therefore, this review focuses on the mechanisms by which nanomaterials regulate bacterial QS in the signal supply (including signal synthesis, secretion, and accumulation) and signal transduction cascade (including signal perception and response) processes. Moreover, based on the two key influencing factors (i.e., the nanomaterial itself and the environment), optimization strategies to enhance the QS regulatory activity are comprehensively summarized. Collectively, applying nanomaterials to regulate bacterial QS is a promising strategy for anti‐virulence therapy. This review provides reference and inspiration for further research on the anti‐virulence application of nanomaterials.

IntroductionPhysical and mental health problems among pilots affect their working state and impact flight safety. Although pilots’ physical and mental health problems have become increasingly prominent, their health has not been taken seriously. This study aimed to clarify challenges and support needs related to psychological and physical health among pilots to inform development of a more scientific and comprehensive physical and mental health system for civil aviation pilots.MethodsThis qualitative study recruited pilots from nine civil aviation companies. Focus group interviews via an online conference platform were conducted in August 2022. Colaizzi analysis was used to derive themes from the data and explore pilots’ experiences, challenges, and support needs.ResultsThe main sub-themes capturing pilots’ psychological and physical health challenges were: (1) imbalance between family life and work; (2) pressure from assessment and physical examination eligibility requirements; (3) pressure from worries about being infected with COVID-19; (4) nutrition deficiency during working hours; (5) changes in eating habits because of the COVID-19 pandemic; (6) sleep deprivation; (7) occupational diseases; (8) lack of support from the company in coping with stress; (9) pilots’ yearly examination standards; (10) support with sports equipment; (11) respecting planned rest time; and (12) isolation periods.DiscussionThe interviewed pilots experienced major psychological pressure from various sources, and their physical health condition was concerning. We offer several suggestions that could be addressed to improve pilots’ physical and mental health. However, more research is needed to compare standard health measures for pilots around the world in order to improve their physical and mental health and contribute to overall aviation safety.

Background: As emerging environmental contaminants, antibiotics pose potential threats to human health, in particular to pregnant women and infants. However, the potential harm of inadvertent antibiotic exposure (IAE) is often disregarded in light of the focus on intentional antibiotic use during pregnancy. Currently, little is known about the effects of IAE during pregnancy on fetal neural tube development. Methods: In this case-control study, we used questionnaire data from 855 subjects to investigate the effects of intentional antibiotic use in early pregnancy on neural tube defects (NTDs). Then we tested for placental antibiotics in mothers who had not intentionally used antibiotics, and the compounds were detected in 379 subjects; these were considered IAE cases. We assessed the association between IAE during pregnancy and fetal NTDs using both multivariable logistic and multi-pollutant exposure models. We also analyzed the correlation between maternal dietary habits and placental antibiotics to explore possible sources of IAE. Results: Only 50 of 855 participants (5.8%) intentionally used antibiotics and such use showed no significant association with NTD risk (odds ratio [OR] = 1.92, confidence interval [95%CI] = [0.66, 5.59]). However, 14 of 15 placental antibiotics were detected in 378 of 379 subjects (99.7%) and multivariable logistic analysis indicated that high levels of placental macrolides were significantly associated with increased NTD risk (4.42 [2.01–10.45]). Multi-pollutant exposure analysis suggested an increase in NTD risk with an increase in exposure to a mixture of placental antibiotics, among which macrolides were the most important contributor. In addition, the level of placental macrolides was positively correlated with the intake frequency of milk. Finally, mothers who drank river, well, or pond water had higher levels of placental macrolides than those who drank only tap water. Conclusions: Intentional antibiotic use during early pregnancy may not be associated with NTDs, while IAE during pregnancy is associated with higher NTD risk in offspring. Macrolides are crucial risk factors. Milk, and river, well, or pond water may be important sources of IAE.

Objectives: To investigate the association between neuropsychiatric symptoms (NPS) and nutritional status, and explore their shared regulatory brain regions on the Alzheimer’s disease (AD) continuum. Design: A longitudinal, observational cohort study. Setting: Data were collected from the Chinese Imaging, Biomarkers, and Lifestyle study between June 1, 2021 and December 31, 2022. Participants: Overall, 432 patients on the AD continuum, including amnestic mild cognitive impairment and AD dementia, were assessed at baseline, and only 165 patients completed the (10.37 ± 6.08) months’ follow-up. Measurements: The Mini-Nutritional Assessment (MNA) and Neuropsychiatric Inventory (NPI) were used to evaluate nutritional status and NPS, respectively. The corrected cerebral blood flow (cCBF) measured by pseudo-continuous arterial spin labeling of the dietary nutrition-related brain regions was analyzed. The association between the NPS at baseline and subsequent change in nutritional status and the association between the changes in the severity of NPS and nutritional status were examined using generalized linear mixed models. Results: Increased cCBF in the left putamen was associated with malnutrition, general NPS, affective symptoms, and hyperactivity (P < 0.05). The presence of general NPS (β = −1.317, P = 0.003), affective symptoms (β = −1.887, P < 0.001), and appetite/eating disorders (β = −1.714, P < 0.001) at baseline were associated with a decline in the MNA scores during follow-up. The higher scores of general NPI (β = −0.048), affective symptoms (β = −0.181), and appetite/eating disorders (β = −0.416; all P < 0.001) were longitudinally associated with lower MNA scores after adjusting for confounding factors. Conclusions: We found that baseline NPS were predictors of a decline in nutritional status on the AD continuum. The worse the severity of affective symptoms and appetite/eating disorders, the poorer the nutritional status. Furthermore, abnormal perfusion of the putamen may regulate the association between malnutrition and NPS, which suggests their potentially common neural regulatory basis.

The rapid advancement of mobile devices and human–machine interaction technologies has ushered in a new era for flexible touch panels as a novel input interface. This article reviews the historical evolution and technical progress of flexible touch panel technologies, from rudimentary single‐point touch to sophisticated grid‐free touch systems. Additionally, the working principles and mechanisms that underpin these advanced systems, including capacitive, resistive, piezoelectric, and triboelectric nanogenerator technologies, are explored. Following this, the integration of machine learning methods into these panels is discussed, offering new avenues for enhancing user experience and expanding functional capabilities. Various machine learning algorithms such as support vector machines, artificial neural networks, convolutional neural networks, and k‐nearest neighbors are examined for their potential applications in touch panel technologies. Finally, the challenges and prospects for the application of flexible touch panels fused with machine learning are discussed.

Abstract Objective To investigate the CBCT findings of the apical anatomy of immature maxillary central incisors. Methods CBCT images of 100 immature maxillary central incisors in Nolla 8 and 100 immature maxillary central incisors in Nolla 9 were collected. The mesiodistal and carniocaudal diameters of the apical foramen of immature maxillary central incisors were measured by software included with CBCT, as well as the mesiodistal, carniocaudal and facioligual diameters of the apical shadow. The apical shadow and apical foramen diameters were compared between Nolla 8 and Nolla 9. Data were analyzed using the MedCalc software package. Results For immature maxillary central incisors, the mesiodistal and facioligual diameters of the apical foramen were 2.75±0.68 mm and 3.28±0.74 mm in Nolla 8 and 1.50±0.51 mm and 1.92±0.79 mm in Nolla 9. The mesiodistal, facioligual and carniocaudal diameters of the apical shadow were 3.84±0.73 mm, 4.49±0.68 mm and 3.41±1.27 mm in Nolla 8 and 2.76±0.60 mm, 3.41±0.80 mm and 2.06±0.65 mm in Nolla 9, respectively. Conclusions The immature maxillary central incisors in Nolla 8 have a larger apical shadow and apical foramen than those in Nolla 9. The apical region of the maxillary central incisors in Nolla 8 was more likely to have a broad, blurred lamina dura. With the development of the apical foramen, the lamina dura in the apical region tended to be clear and sharp. Clinical significance To our knowledge, this is the first study to radiologically analyse the in vivo anatomy of the apical foramen and apical shadow of immature maxillary central incisors. The results of this study provide a more detailed understanding of the apical anatomy of the immature maxillary central incisor for the diagnosis and treatment of apical lesions.

Once China’s Tianwen-1 Mars probe arrived in a Mars orbit after a seven-month flight in the deep cold space environment, it would be urgently necessary to monitor its state and the surrounding environment. To address this issue, we developed a flexible deployable subsystem based on shape memory polymer composites (SMPC-FDS) with a large folding ratio, which incorporates a camera and two temperature telemetry points for monitoring the local state of the Mars orbiter and the deep space environment. Here, we report on the development, testing, and successful application of the SMPC-FDS. Before reaching its Mars remote-sensing orbit, the SMPC-FDS is designed to be in a folded state with high stiffness; after reaching orbit, it is in a deployed state with a large envelope. The transition from the folded state to the deployed state is achieved by electrically heating the shape memory polymer composites (SMPCs); during this process, the camera on the SMPC-FDS can capture the local state of the orbiter from multiple angles. Moreover, temperature telemetry points on the SMPC-FDS provide feedback on the environment temperature and the temperature change of the SMPCs during the energization process. By simulating a Mars on-orbit space environment, the engineering reliability of the SMPC-FDS was comprehensively verified in terms of the material properties, structural dynamic performance, and thermal vacuum deployment feasibility. Since the launch of Tianwen-1 on 23 July 2020, scientific data on the temperature environment around Tianwen-1 has been successfully acquired from the telemetry points on the SMPC-FDS, and the local state of the orbiter has been photographed in orbit, showing the national flag of China fixed on the orbiter.

Abstract Acetylation contributes to the bioactivity of numerous medicinally important natural products. However, little is known about the acetylation on sugar moieties. Here we report a saponin acetyltransferase from Astragalus membranaceus. AmAT7-3 is discovered through a stepwise gene mining approach and characterized as the xylose C3′/C4′-O-acetyltransferse of astragaloside IV (1). To elucidate its catalytic mechanism, complex crystal structures of AmAT7-3/1 and AmAT7-3A310G/1 are obtained, which reveal a large active pocket decided by a specific sequence AADAG. Combining with QM/MM computation, the regiospecificity of AmAT7-3 is determined by sugar positioning modulated by surrounding amino acids including #A310 and #L290. Furthermore, a small mutant library is built using semi-rational design, where variants A310G and A310W are found to catalyze specific C3′-O and C4′-O acetylation, respectively. AmAT7-3 and its variants are also employed to acetylate other bioactive saponins. This work expands the understanding of saponin acetyltransferases, and provide efficient catalytic tools for saponin acetylation.