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Abstract We previously identified CLDN6 as a pivotal tumor suppressor in breast cancer and unexpectedly discovered that overexpression of CLDN6 resulted in characteristic ultrastructural alterations of ferroptosis. However, the exact mechanism by which CLDN6 triggers ferroptosis is still elusive in breast cancer. Our study showed that CLDN6 was associated with ferroptosis in breast cancer patients. The integration of CLDN6 and ferroptosis demonstrated remarkable predictive prognostic performance. We observed that CLDN6 triggers NRF2-mediated ferroptosis in vitro and in vivo. Mechanistically, CLDN6 enhanced nuclear export of NRF2 by regulating the PBK-dependent AKT/GSK3β/FYN axis. Further CLDN6 recruited PBK to the cell membrane through the endosomal pathway and bound with the DLG1/PBK complex, thereby promoted the degradation of PBK by the UPS. This study elucidates the previously unrecognized mechanism of CLDN6 triggering NRF2-mediated ferroptosis through recruiting DLG1/PBK complex. This study provides a reliable biomarker for predicting prognosis and is anticipated to guide the selection of therapies targeting ferroptosis in breast cancer.

Abstract This study aimed to investigate the regulatory effects of the long non-coding RNA (lncRNA) MISATO family member 2 (MSTO2P) on non-small cell lung cancer (NSCLC) cell viability, invasion, and migration, as well as the underlying mechanism. Quantitative real-time polymerase chain reaction (qRT-PCR) was used to analyze the expression levels of MSTO2P. The effects of MSTO2P on cell viability, invasion, and migration were assessed using cell counting kit-8 (CCK-8), Transwell invasion, and wound healing assays in A549 and H1229 cells. A human phospho-kinase array kit was employed to identify potential phosphorylated kinases or signaling nodes affected by MSTO2P. The interaction between MSTO2P and β-catenin was evaluated using RNA pull-down and RNA immunoprecipitation (RIP) assays. A xenograft tumor mouse model was established to evaluate tumor growth. The results demonstrated that MSTO2P expression was elevated in NSCLC tissues and cells compared to normal counterparts. Silencing MSTO2P inhibited the viability, invasion, and migration of A549 and H1229 cells. MSTO2P interacted with β-catenin, thereby activating the Wnt/β-catenin pathway. Overexpression of MSTO2P or β-catenin promoted the viability, invasion, and migration of A549 and H1229 cells, effects that were reversed by treatment with XAV-939. In vivo studies showed that silencing MSTO2P suppressed tumor growth. In conclusion, MSTO2P promoted NSCLC cell viability, invasion, and migration by regulating the Wnt/β-catenin pathway, suggesting that MSTO2P may be a potential therapeutic target for NSCLC.

Abstract Previous deep learning-based brain network research has made significant progress in understanding the pathophysiology of schizophrenia. However, it ignores the three-dimensional spatial characteristics of EEG signals and cannot dynamically learn the interactions between nodes. To address this issue, a schizophrenia classification model based on a three-dimensional adaptive graph convolutional neural network (3D-AGCN) is proposed. Each subject’s EEG data is divided into various segment lengths and frequency bands for the experiment. The attention mechanism is then used to integrate the node features in the spatial, feature, and frequency band dimensions. The resulting adaptive brain functional network features are then constructed and fed into the GAT + GCN model. This adaptive approach eliminates the human-specified criteria for feature selection and brain network construction. The trial results demonstrated that, when using a 6-second segment length and time-domain and frequency-domain features, patients with first-episode schizophrenia achieved the highest classification accuracy of 87.64% This method outperforms other feature selection and brain network modeling approaches, providing new insights and directions for the early diagnosis and recognition of schizophrenia.

Abstract Background Nutrition and its associated inflammation have been acknowledged as vital factors in the etiopathogenesis of non-alcoholic fatty liver disease (NAFLD) and liver fibrosis. The nutritional risk index (NRI) has been widely recognized as a valid indicator of nutritional status in several diseases, including osteoporosis and cardiovascular disease. However, the role of NRI in NAFLD and liver fibrosis remains unclear. Methods Participants were selected from the National Health and Nutrition Examination Survey data for the 2017–2018 cycle. Association between NRI and both NAFLD and liver fibrosis was evaluated using multiple logistic regression and restricted cubic spline (RCS) analysis. Mediation analysis was employed to assess the influence of inflammation on the association between NRI and both NAFLD and liver fibrosis. Results Compared to their respective control groups, individuals with NAFLD and liver fibrosis exhibited higher NRI levels. Multiple logistic regression analyses indicated that NRI was positively associated with the odds of NAFLD and liver fibrosis across both continuous scales and quantile groups, with adjustments for relevant covariables. The RCS model demonstrated a dose-response effect between NRI and the odds of NAFLD, but not with liver fibrosis. Receiver operating characteristic (ROC) analysis revealed the area under the ROC curves of 0.798 and 0.775 for NAFLD and liver fibrosis, respectively. Mediation analysis showed that inflammation accounted for 3.139% of the effect of NRI on the odds of NAFLD, suggesting inflammation might partially mediate the impact of NRI on NAFLD. Conclusions Our findings indicate that NRI may serve as a potential associated marker for these liver diseases, underscoring the importance of nutritional status in their etiopathogenesis.

ObjectiveTo explore the relationships between internet gaming disorder (IGD), interpersonal needs, loneliness, and depression in adolescents through the construction of a chain mediation model, to clarify the underlying mechanisms of these associations, and to provid a theoretical basis for depression prevention and intervention.MethodsBased on the data of the 7th Population Census, using convenient sampling method 1 106 adolescents aged between 10‒19 years in South China (176), North China (147), Central China (332), and East China (451) were selected to conduct a cross-sectional survey, with a ratio of 1∶1∶1.5∶2.5. The survey was conducted with a questionnaire consisting of general information (sex, age, grade, parents’ education level), the Chinese version of the IGDS9-SF, the INQ-15, the short-form of the ULS-8 and the PHQ-9 were used to evaluate the depression status of adolescents. Spearman correlation analysis was used to explore the correlation between the variables. A multiple-mediator model was constructed using IBM SPSS Statistics 22.0 PROCESS to examine the mediating effects of interpersonal needs and loneliness on the relationship between IGD and depression. The significance of the chain mediating effect was tested using the Bootstrap method.ResultsOverall, 39.06% (432/1 106) adolescents experienced depression. The incidence of depression among adolescents with smoking and without smoking was 62.50% and 38.36%, respectively. Similarly, the incidence of depression among adolescents with alcohol consuming and without alcohol consuming was 61.94% and 35.94%, respectively. There were statistically significant differences between IGD, interpersonal needs, loneliness, and depression (P

Background Post-stroke fatigue (PSF) is a common complication experienced by stroke survivors. These individuals often confront psychological challenges such as depression and anxiety, along with significant obstacles like reduced quality of life (QoL) and limitations in activities of daily living (ADLs). Such challenges can profoundly affect their overall recovery and well-being. Despite its prevalence, the associated factors contributing to PSF remain poorly understood. This study aims to primarily investigate these associated factors, while also examining the interrelationships among PSF, depression level, QoL, and ADLs, highlighting the need for a better understanding of these complex interactions. Methods This cross-sectional study involved 271 stroke survivors and was conducted at the Department of Neurology, Second Affiliated Hospital of Guizhou University of Traditional Chinese Medicine, China, from September 2023 to January 2024. Participants independently completed the Fatigue Severity Scale (FSS), Patient Health Questionnaire-9 (PHQ-9), and the Short Version of the Stroke-Specific Quality of Life Scale (SV-SS-QoL) as part of a convenience sampling method, while medical professionals assessed the Barthel Index (BI) using the same sampling framework. Multivariable linear regression analyses were employed to determine the factors associated with the persistence of PSF. Results The mean FSS score was 35.04 ± 11.60, while the average score for the SV-SS-QoL was 34.28 ± 9.51, and the BI score averaged 77.79 ± 25.90. Approximately 45.8% of participants (n = 124) experienced PSF. The mean score on the PHQ-9 was 7.63 ± 6.13. A significant negative correlation was identified between fatigue and both QoL and ADLs (P

IntroductionThe infralimbic cortex (IL), a critical subregion within the ventromedial prefrontal cortex (vmPFC), modulates emotion, memory, and social functions via robust projections to the basolateral amygdala (BLA). However, the afferent brain regions that innervate BLA-projecting IL neurons (IL-BLA PNs) and their efferent targets have not been systematically characterized.MethodsWe employed tracing techniques integrating adeno-associated virus (AAV) and monosynaptic rabies to systematically investigate the presynaptic inputs and axonal outputs of IL-BLA PNs.ResultsOur findings revealed widespread synaptic inputs to IL-BLA PNs from subcortical areas, with the strongest inputs originating from the dorsomedial thalamus (MD) and anterior medial thalamus (AM) in the thalamic region, as well as from the ventral hippocampus (vHPC) and piriform cortex (Pir) in the limbic system. Sparse labeling of the virus demonstrated that IL-BLA PNs collateralize to innervate various subcortical regions, including the horizontal diagonal band (HDB), lateral preoptic area (LPO), ventral pallidum (VP), and lateral hypothalamus (LH).DiscussionThis work establishes essential theoretical frameworks for the functional investigation and targeted intervention in neurological disorders.

The development of a precise and sensitive electrochemical sensor is essential in the field of medical diagnostics in order to identify gemcitabine, a chemotherapy drug that is commonly used to treat breast cancer. This work presents a novel electrochemical sensor based on a reduced graphene oxide (rGO) nanocomposite and a zirconium-based metal-organic framework (Zr-MOF) with terephthalic acid as a ligand. Gemcitabine (GEM), a chemotherapy medication used to treat breast cancer, is detected with remarkable sensitivity and selectivity by the Zr-MOF-rGO modified graphene paste electrode (GrPE) sensor. By combining the strong structure and active sites of Zr-MOF with the large surface area and electrical conductivity of rGO, the sensor's design maximizes electron transfer rates and GEM adsorption capacity. The sensor outperforms current GEM sensors with its wide linear detection range (0.5–490 μM) and low detection limit (0.008 μM). The sensor's long-term analytical applicability is confirmed by stability and reusability studies, which produced accuracy rates surpassing 94 % and RSD values below 4.21 % in recovery trials using spiked human blood serum and urine samples. Overall, the results of this investigation show that the Zr-MOF-rGO/GrPE electrode has the potential to be a useful platform for the detection of gemcitabine in patients with breast cancer.

Abstract Background Bile acids (BAs) are steroid-derived molecules with important roles in digestion, the maintenance of host metabolism, and immunomodulation. Primary BAs are synthesized by the host, while secondary BAs are produced by the gut microbiome through transformation of the former. The regulation of microbial production of secondary BAs is not well understood, particularly the production of 7-dehydroxylated BAs, which are the most potent agonists for host BA receptors. The 7-dehydroxylation of cholic acid (CA) is well established and is linked to the expression of a bile acid-inducible (bai) operon responsible for this process. However, little to no 7-dehydroxylation has been reported for other host-derived BAs (e.g., chenodeoxycholic acid, CDCA or ursodeoxycholic acid, UDCA). Results Here, we demonstrate that the 7-dehydroxylation of CDCA and UDCA by the human isolate Clostridium scindens is induced when CA is present, suggesting that CA-dependent transcriptional regulation is required for substantial 7-dehydroxylation of these primary BAs. This is supported by the finding that UDCA alone does not promote expression of bai genes. CDCA upregulates expression of the bai genes but the expression is greater when CA is present. In contrast, the murine isolate Extibacter muris exhibits a distinct response; CA did not induce significant 7-dehydroxylation of primary BAs, whereas BA 7-dehydroxylation was promoted upon addition of germ-free mouse cecal content in vitro. However, E. muris was found to 7-dehydroxylate in vivo. Conclusions The distinct expression responses amongst strains indicate that bai genes are regulated differently. CA promoted bai operon gene expression and the 7-dehydroxylating activity in C. scindens strains. Conversely, the in vitro activity of E. muris was promoted only after the addition of cecal content and the isolate did not alter bai gene expression in response to CA. The accessory gene baiJ was only upregulated in the C. scindens ATCC 35704 strain, implying mechanistic differences amongst isolates. Interestingly, the human-derived C. scindens strains were also capable of 7-dehydroxylating murine bile acids (muricholic acids) to a limited extent. This study shows novel 7-dehydroxylation activity in vitro resulting from the presence of CA and suggests distinct bai gene expression across bacterial species.

Abstract Background Breast cancer (BC) ranks as the third most fatal malignant tumor worldwide, with a strong reliance on fatty acid metabolism. CLDN6, a candidate BC suppressor gene, was previously identified as a regulator of fatty acid biosynthesis; however, the underlying mechanism remains elusive. In this research, we aim to clarify the specific mechanism through which CLDN6 modulates fatty acid anabolism and its impact on BC growth and metastasis. Methods Cell function assays, tumor xenograft mouse models, and lung metastasis mouse models were conducted to evaluate BC growth and metastasis. Human palmitic acid assay, triglyceride assay, Nile red staining, and oil red O staining were employed to investigate fatty acid anabolism. Reverse transcription polymerase chain reaction (RT–PCR), western blot, immunohistochemistry (IHC) assay, nuclear fractionation, immunofluorescence (IF), immunoprecipitation and acyl–biotin exchange (IP-ABE), chromatin immunoprecipitation (ChIP), dual luciferase reporter assay, and co-immunoprecipitation (Co-IP) were applied to elucidate the underlying molecular mechanism. Moreover, tissue microarrays of BC were analyzed to explore the clinical implications. Results We identified that CLDN6 inhibited BC growth and metastasis by impeding RAS palmitoylation both in vitro and in vivo. We proposed a unique theory suggesting that CLDN6 suppressed RAS palmitoylation through SREBP1-modulated de novo palmitic acid synthesis. Mechanistically, CLDN6 interacted with MAGI2 to prevent KLF5 from entering the nucleus, thereby restraining SREBF1 transcription. The downregulation of SREBP1 reduced de novo palmitic acid synthesis, hindering RAS palmitoylation and subsequent endosomal sorting complex required for transport (ESCRT)-mediated plasma membrane localization required for RAS oncogenic activation. Besides, targeting inhibition of RAS palmitoylation synergized with CLDN6 to repress BC progression. Conclusions Our findings provide compelling evidence that CLDN6 suppresses the palmitic acid-induced RAS palmitoylation through the MAGI2/KLF5/SREBP1 axis, thereby impeding BC malignant progression. These results propose a new insight that monitoring CLDN6 expression alongside targeting inhibition of palmitic acid-mediated palmitoylation could be a viable strategy for treating oncogenic RAS-driven BC. Graphical Abstract

Abstract Objective To study the effects of chemotherapy on cognitive function in breast cancer patients, and to investigate the relationship of MemTrax test of memory and related functions to the FACT-Cog functional self-assessment for the evaluation and management of chemobrain. Methods In this prospective cohort study, clinical information of pathologically confirmed female breast cancer patients who decided to receive chemotherapy were collected in a questionnaire which was developed for this study and provided as a supplementary file. The FACT-Cog self-assessment and MemTrax test were administered before and after the chemotherapy treatments. Patients with chemobrain were identified using published criteria based on FACT-Cog scores, and MemTrax scores from chemobrain patients were analyzed. Results Fifty-six patients participated in this study, of which 41 participants completed 4 or more cycles of chemotherapy and were included in the final analyses here. Using the reported high end of minimal clinical differences (10.6 points) of FACT-Cog before and after chemotherapy, 18 patients suffered from chemobrain in this study. In these 18 chemobrain patients, no cognitive impairments were detected by MemTrax, which paradoxically demonstrated an improvement in the normal cognitive range. Conclusion The cognitive impairment induced by chemotherapy in breast cancer patients is detectable by the FACT-Cog in a Chinese cohort but is not detected by the MemTrax memory test. The fact that the more objective MemTrax could not detect the impairment could alleviate patients’ concerns which in turn would be beneficial for patients’ mental health.

Abstract In plants, the conserved plant-specific photoreceptor UV RESISTANCE LOCUS 8 (UVR8) perceives ultraviolet-B (UV-B) light and mediates UV-B-induced photomorphogenesis and stress acclimation. In this study, we reveal that UV-B light treatment shortens seedlings, increases stem thickness, and enhances UV-B stress tolerance in rice (Oryza sativa) via its two UV-B photoreceptors OsUVR8a and OsUVR8b. Although the rice and Arabidopsis (Arabidopsis thaliana) UVR8 (AtUVR8) photoreceptors all form monomers in response to UV-B light, OsUVR8a, and OsUVR8b function is only partially conserved with respect to AtUVR8 in UV-B-induced photomorphogenesis and stress acclimation. UV-B light and CONSTITUTIVELY PHOTOMORPHOGENIC 1 (COP1) promote the nuclear accumulation of AtUVR8; by contrast, OsUVR8a and OsUVR8b constitutively localize to the nucleus via their own nuclear localization signals, independently of UV-B light and the RING-finger mutation of OsCOP1. We show that OsCOP1 negatively regulates UV-B responses, and shows weak interaction with OsUVR8s, which is ascribed to the N terminus of OsCOP1, which is conserved in several monocots. Furthermore, transcriptome analysis demonstrates that UV-B-responsive gene expression differs globally between Arabidopsis and rice, illuminating the evolutionary divergence of UV-B light signaling pathways between monocot and dicot plants.

Background: Fatigue following a stroke, known as post-stroke fatigue (PSF), is a frequent complication experienced by individuals recovering from a stroke, with its incidence steadily increasing over time. The long-term presence of PSF significantly hinders the rehabilitation process and quality of life for these individuals. However, the most effective intervention strategies for PSF remain unclear. Therefore, it is crucial to implement appropriate intervention strategies at an early stage to prevent and manage PSF, thereby mitigating its negative impacts and promoting recovery in stroke survivors. Objective: This scoping review aimed to explore and chart the interventions available for managing post-stroke fatigue in individuals recovering from stroke, providing healthcare professionals with evidence to guide the development of optimal treatments. Design: A scoping review. Data Sources: This review conducted a systematic search across six databases¾PubMed, Web of Science, Cochrane Library, Scopus and CINAHL (via EBSCO), and CNKI, for articles published from 10 January 2012 to early May 2024. Review Methods: This review followed the PRISMA-ScR reporting guidelines. Studies were selected based on the PCC framework, focusing on specific participants, concepts, and contexts. Exclusion criteria included ongoing studies without results, articles without full text, posters, reviews, and protocols. Tables and narrative descriptions were used to present relevant information on the interventions and their outcomes during the review process. Results: Twenty-seven studies were included, categorizing interventions for post-stroke fatigue into ten types: pharmacological treatments, physical activity, physical therapy, cognitive behavioral therapy, respiratory training, music therapy, mindfulness-based stress reduction, health education management, Traditional Chinese Medicine, and environmental enrichment. Conclusion: The interventions for post-stroke fatigue have demonstrated positive effects in alleviating fatigue symptoms among stroke survivors. However, some approaches have limitations, and the most effective treatment strategy remains unclear. The multidisciplinary collaboration between nurses and healthcare professionals plays a critical role in managing post-stroke fatigue by providing patients with education on fatigue prevention and treatment, along with personalized care plans, including one-on-one or group interventions. Future research should focus on increasing sample sizes and conducting multicenter trials to identify the most effective intervention strategies for managing post-stroke fatigue.

IntroductionA multimodal persistent topological feature extraction and classification method is proposed to enhance the recognition accuracy of first-episode schizophrenia patients. This approach addresses the limitations of traditional higher-order brain network analyses that rely on single persistent features (e.g., persistent images).MethodsThe study utilized resting-state EEG data from 198 subjects recruited at Huilongguan Hospital in Beijing, comprising 102 males and 96 females, with a mean age of 30 years and mean education of 14 years. Persistent topological features were extracted using adaptive thresholding during persistent homology (PH) filtrations. The distribution of these features was visualized through heatmaps and persistence entropies, while the generation process was elucidated using Betti curves and persistence landscapes.ResultsThe classification performance of the multimodal persistent topological features was assessed using various machine learning classifiers. The classifier yielding the highest performance was selected for comparison with traditional brain network features derived from graph theory and single persistent topological features. The results revealed significant topological changes in first-episode schizophrenia patients throughout the persistent homology filtering compared to healthy subjects. The univariate feature selection algorithm achieved a classification accuracy of 94.6% with a combination of attributes meeting the criterion of AC ≥ 0.6.DiscussionThe proposed method demonstrates clinical significance for the early identification and diagnosis of first-episode schizophrenia patients, offering a new research perspective for constructing higher-order functional connectivity networks and extracting topological structure features.

Abstract Background Childhood obesity is increasingly recognized as a major public health challenge worldwide, and excessive sedentary screen time is emerging as a key risk factor. This study aimed to assess the recreational screen sedentary time of Chinese primary school-aged children and investigate the relationship between screen-related family factors and the outcome variable. Methods Our study used data from a cross-sectional survey collected from fifth-grade students and their parents in Beijing, China, from April to May 2018 (n = 2,373). The questions included basic demographic information, family socioeconomic status, students’ and parents’ sedentary and exercising habits, within-family communicational factors, and health belief patterns. The recreational screen sedentary time of the children was compared across demographic groups. The study employed multivariate linear regression models to examine associations between children’s screen time and various family factors, as well as the moderating effect of overall family communication. Results Our findings revealed an average daily recreational screen sedentary time of 2.4 h among participants. Screen time significantly varied across demographic categories, including children’s sex, age, residence, parents’ education, household income, family size, and primary family member. After adjustment, the proportion of child-owned digital devices (p

Abstract Spinal cord injury (SCI) remains a formidable challenge, lacking effective treatments. Following SCI, neural stem cells (NSCs) migrate to SCI sites, offering a potential avenue for nerve regeneration, but the effectiveness of this intrinsic repair mechanism remains suboptimal. Salidroside has demonstrated pro-repair attributes in various pathological conditions, including arthritis and cerebral ischemia, and the ability to curtail early-stage inflammation following SCI. However, the specific role of salidroside in the late-stage repair processes of SCI remains less defined. In this investigation, we observed that continuous salidroside treatment in SCI mice improved motor function recovery. Immunofluorescence-staining corroborated salidroside’s capacity to stimulate nerve regeneration and remyelination, suppress glial scar hyperplasia, reduce the activation of neurotoxic A1 astrocytes, and facilitate NSCs migration towards the injured region. Mechanistically, in vitro experiments elucidated salidroside’s significant role in restraining astrocyte proliferation and A1 polarization. It was further established that A1 astrocytes hinder NSCs proliferation while inducing their differentiation into astrocytes. Salidroside effectively ameliorated this inhibition of NSCs proliferation through diminishing c-Jun N-terminal kinase (JNK) pathway phosphorylation and restored their differentiation into neurons by suppressing the signal transducer and activator of transcription 3 (STAT3) pathway. In summary, our findings suggest that salidroside holds promise as a therapeutic agent for traumatic SCI treatment.

Hypertension (HT) can induce aortic dissection (AD) by increasing the tension of the aortic wall and promoting tissue degradation, and continuous HT may increase the risk of aortic-related death. It is a significant factor in poor prognosis for AD and the most important controllable factor. Research has shown that blood pressure management after AD can reduce the incidence rate and mortality of AD, so controlling HT is an important goal and means of AD treatment. This article reviews the research progress on the impact of AD on blood pressure, the significance and methods of blood pressure management after AD, with the hope of providing reference for the treatment of AD patients and benefiting them.

Non-alcoholic fatty liver disease (NAFLD) is the most common chronic liver disease worldwide, and its prevalence is rapidly increasing. Antioxidants, lipid-lowering medications, and lifestyle interventions are the most commonly used treatment options for NAFLD, but their efficacy in inhibiting steatosis progression is limited and their long-term ineffectiveness and adverse effects have been widely reported. Therefore, it is important to gain a deeper understanding of the pathogenesis of NAFLD and to identify more effective therapeutic approaches. Mitochondrial homeostasis governs cellular redox biology, lipid metabolism, and cell death, all of which are crucial to control hepatic function. Recent findings have indicated that disruption of mitochondrial homeostasis occurs in the early stage of NAFLD and mitochondrial dysfunction reinforces disease progression. In this review, we summarize the physical roles of the mitochondria and describe their response and dysfunction in the context of NAFLD. We also discuss the drug targets associated with the mitochondria that are currently in the clinical trial phase of exploration. From our findings, we hope that the mitochondria may be a promising therapeutic target for the treatment of NAFLD.

Background: During the COVID-19 pandemic, numerous studies focused on mental health, but few considered both positive and negative aspects within the dual-factor model of psychological well-being. In China, a highly populous country, limited evidence exists regarding mental health and its associated factors following the surge and decline of COVID-19 cases after the loosening of COVID-19 control measures. This study aims to investigate the mental health status of Chinese residents in the aftermath of the pandemic and factors influencing positive and negative indicators using the System-Based Model of Stress. Methods: A cross-sectional online survey of 1,026 participants was conducted in China from March 2–31, 2023, using quota sampling. Structural equation modeling (SEM) was performed to test the conceptual model, where social support, perceived susceptibility, perceived severity, pandemic-related events, coping style, and concern about COVID-19 were considered as predictors, and psychological distress and subjective well-being as outcomes. Results: The results revealed high prevalence rates of psychological distress (23 %) with either of anxiety (15 %) or depression (20 %), and poor subjective well-being (23 %) among Chinese residents after the COVID-19 pandemic. Social support was negatively correlated with psychological distress, and negative coping style, pandemic-related events, and concern about COVID-19 were positively correlated with psychological distress. Moreover, social support was positively correlated with subjective well-being, and negative coping style and pandemic-related events were negatively correlated with subjective well-being. Conclusions: These findings enhance our understanding of the differing correlates of positive and negative mental health, suggesting targeted psychological interventions for post-pandemic and future public health events.

Cannabinoids and the endocannabinoid system (ECS) have been intensively studied for their neuroregulatory roles in the central nervous system (CNS), especially in regulating learning and memory. However, many experimental and clinical studies obtained conflicting results indicating a complex network of interaction underlying the regulation of learning and memory by different cannabinoids and the ECS. The ECS influences neuronal synaptic communications, and therefore may exert different regulation via their different impact on other neurotransmitters. The monoaminergic system includes a variety of neurotransmitters, such as dopamine, norepinephrine, and serotonin, which play important roles in regulating mood, cognition, and reward. The interaction among cannabinoids, ECS and the monoaminergic system has drawn particular attention, especially their contributions to learning and memory. In this review, we summarized the current understanding of how cannabinoids, ECS and the monoaminergic system contribute to the process of learning and memory, and discussed the influences of monoaminergic neurotransmission by cannabinoids and ECS during this process.

Abstract Macroautophagy/autophagy is a lysosome-dependent catabolic process induced by various cellular stress conditions, maintaining the homeostasis of cells, tissues and organs. Autophagy is a series of membrane-related events involving multiple autophagy-related (ATG) proteins. Most studies to date have focused on various signaling pathways affecting ATG proteins to control autophagy. However, mounting evidence reveals that the actin cytoskeleton acts on autophagy-associated membranes to regulate different events of autophagy. The actin cytoskeleton assists in vesicle formation and provides the mechanical forces for cellular activities that involve membrane deformation. Although the interaction between the actin cytoskeleton and membrane makes the role of actin in autophagy recognized, how the actin cytoskeleton is recruited and assembles on membranes during autophagy needs to be detailed. Nucleation-promoting factors (NPFs) activate the Arp2/3 complex to produce actin cytoskeleton. In this review, we summarize the important roles of the actin cytoskeleton in autophagy regulation and focus on the effect of NPFs on actin cytoskeleton assembly during autophagy, providing new insights into the occurrence and regulatory mechanisms of autophagy. Video Abstract

Osteoarthritis (OA) has emerged as a significant health concern among the elderly population, with increasing attention paid to ferroptosis-induced OA in recent years. However, the prolonged use of nonsteroidal anti-inflammatory drugs or corticosteroids can lead to a series of side effects and limited therapeutic efficacy. This study aimed to employ the Mannich condensation reaction between epigallocatechin-3-gallate (EGCG) and selenomethionine (SeMet) to efficiently synthesize polyphenol-based nanodrugs in aqueous media for treating OA. Molecular biology experiments demonstrated that EGCG-based nanodrugs (ES NDs) could effectively reduce glutathione peroxidase 4 (GPX4) inactivation, abnormal Fe2+ accumulation, and lipid peroxidation induced by oxidative stress, which ameliorated the metabolic disorder of chondrocytes and other multiple pathological processes triggered by ferroptosis. Moreover, imaging and histopathological analysis of the destabilization of the medial meniscus model in mice confirmed that ES NDs exhibiting significant therapeutic effects in relieving OA. The intra-articular delivery of ES NDs represents a promising approach for treating OA and other joint inflammatory diseases.

In the trend of spectrometer miniaturization, the design of combining computational imaging with the metasurfaces has been proved to be an efficient and feasible solution. Nevertheless, determining the optimal filter array design remains a compelling subject for ongoing research. A computational microspectrometer consisting of a planar array of broadband optical filters is proposed, which are formed by low-loss freeform dielectric metasurfaces. Diverse metasurface designs are obtained by using binary graph generation technology, and rich spectral responses are obtained. The final performance of microspectrometer depends on the trade-offs between reconstruction time, relative error, footprint, and resolution. To optimize these trade-offs, we have improved the existing freeform metasurface design scheme and optimized the filter array design. Simulation results show the proposed microspectrometer can successfully reconstruct the spectra over the 380 to 680 nm spectral range with a resolution of 1 nm. In summary, we propose an integrated design including meta-pixel design, filter combinations and simulation test flow, which leads to an impressive performance microspectrometer.

Abstract Outpatient care patterns have changed markedly during the COVID-19 pandemic. In this population-based retrospective cohort study, we compared the frequency of outpatient care (whether in-person or virtual) and continuity of care for all community-dwelling adults in Alberta between March 1, 2019 and February 29, 2020 (pre-pandemic) versus March 1, 2020 to February 28, 2021 (pandemic). We calculated provider continuity using Breslau’s Usual Provider Continuity (UPC) for patients with at least 2 outpatient encounters. In 2019–20, 594,350 (98.4%) of 603,877 community-dwelling adults with ambulatory care sensitive conditions (ACSC) had $$\ge$$ ≥ 1 outpatient visit (median 8 visits, mean UPC score 0.61, SD 0.23), compared to 566,569 (98.6%) of 574,613 (median 8 visits, mean UPC score 0.67, SD 0.23) during the first year of the pandemic. Similar patterns were seen for adults without ACSC: 2,207,710 (93.9%) of 2,350,147 had $$\ge$$ ≥ 1 outpatient visit (median 3 visits, mean UPC score 0.61, SD 0.24) pre-pandemic compared to 2,113,239 (93.5%, median 4 visits, mean UPC 0.67, SD 0.24) in the first year of the pandemic. Thus, the COVID-19 pandemic did not impact frequency of follow-up while continuity of care improved both for patients with or without ACSC in Alberta, Canada.

ObjectiveTo understand the health information needs of chronic disease inpatients and the current utilization of community health resources， and to analyze the influencing factors， so as to provide basis for personalized and high-quality health education for chronic disease inpatients and to guide them to make full use of community health resources.MethodsFrom November 2020 to February 2021， we conducted a face-to-face multi-center clinical epidemiological survey with paper questionnaire in three general hospitals of Shanghai. The study included 404 inpatients with diabetes， hypertension， coronary heart disease， chronic respiratory diseases， cancer and other chronic diseases.Results94.01% of the 404 respondents had different needs for disease or health related information， and there was no significant difference between patients of different ages， genders and educational backgrounds in their needs for health knowledge. Among these patients， only 39.11% of them participated in the establishment of a card for chronic disease management in the community or signed for a family doctor. The participation rate of male patients was lower than that of female patients （P

Summary: M2 macrophages are associated with the prognosis of bladder cancer. CLDN6 has been linked to immune infiltration and is crucial for predicting the prognosis in multi-tumor. The effect of CLDN6 on M2 macrophages in bladder cancer remains elusive. Here, we compared a total of 40 machine learning algorithms, then selected optimal algorithm to develop M2 macrophages-related signature (MMRS) based on the identified M2 macrophages related module. MMRS predicted the prognosis better than other models and associated to immunotherapy response. CLDN6, as an important variable in MMRS, was an independent factor for poor prognosis. We found that CLDN6 was highly expressed and affected immune infiltration, immunotherapy response, and M2 macrophages polarization. Meanwhile, CLDN6 promoted the growth of bladder cancer and enhanced the carcinogenic effect by inducing polarization of M2 macrophages. In total, CLDN6 is an independent risk factor in MMRS to predict the prognosis of bladder cancer.

Parkinson’s disease (PD) is featured by movement impairments, including tremors, bradykinesia, muscle stiffness, and imbalance. PD is also associated with many non-motor symptoms, such as cognitive impairments, dementia, and mental disorders. Previous studies identify the associations between PD progression and factors such as α-synuclein aggregation, mitochondrial dysfunction, inflammation, and cell death. The cannabinoid type-2 receptor (CB2 receptor) is a transmembrane G-protein-coupled receptor and has been extensively studied as part of the endocannabinoid system. CB2 receptor is recently emerged as a promising target for anti-inflammatory treatment for neurodegenerative diseases. It is reported to modulate mitochondrial function, oxidative stress, iron transport, and neuroinflammation that contribute to neuronal cell death. Additionally, CB2 receptor possesses the potential to provide feedback on electrophysiological processes, offering new possibilities for PD treatment. This review summarized the mechanisms underlying PD pathogenesis. We also discussed the potential regulatory role played by CB2 receptor in PD.

Excessive copper concentration in the soil will cause certain harm to human body and the environment, so it is of great significance to explore the inversion of heavy metal copper content. In this study, 43 soil samples in the typical iron tailings area of Tangshan were taken as examples, and the reflectance spectrum and content information of copper in the soil were measured at the same time. After a variety of spectral transformations, the correlation analysis method (CA) and the continuous projection method (SPA) were carried out. The characteristic wavebands of soil copper content were selected, and then the inversion model of copper content was established using multiple linear regression (MLR) and partial least square regression (PLSR) algorithms, and the inversion results of various spectral data were obtained. The results show that the spectrum data after the second-order differential processing has the best inversion effect. Among the two inversion models of CA-PLSR and SPA-MLR, the inversion accuracy of SPA-MLR is relatively accurate; after the second-order differential spectrum transformation te SPA-MLR model has more advantages in estimating soil copper content.

Abstract Background As a breast cancer suppressor gene, CLDN6 overexpression was found to inhibit breast cancer metastasis in our previous studies, but the specific mechanism remains unclear. This study aimed to clarify the role and mechanism of CLDN6 in inhibiting breast cancer metastasis. Methods Western blot, immunofluorescence and transmission electron microscopy were performed to detect autophagy. Wound healing, transwell assays and lung metastasis mouse models were used to examine breast cancer metastasis. Phalloidin staining and immunofluorescent staining were used to observe actin cytoskeleton. mRNA seq, RT-PCR, western blot, chromatin immunoprecipitation, dual luciferase reporter assay, co-immunoprecipitation and immunofluorescence were performed to define the molecular mechanism. The expression levels and clinical implication of CLDN6, WIP and LC3 in breast cancer tissues were evaluated using immunohistochemistry. Results We demonstrated that CLDN6 inhibited breast cancer metastasis through autophagy in vitro and vivo. We unraveled a novel mechanism that CLDN6 regulated autophagy via WIP-dependent actin cytoskeleton assembly. Through its PDZ-binding motif, overexpressed CLDN6 interacted with JNK and upregulated JNK/c-Jun pathway. C-Jun promoted WIP expression at the transcriptional level. Notably, we observed c-Jun transcriptionally upregulated CLDN6 expression, and there was a positive feedback loop between CLDN6 and JNK/c-Jun. Finally, we found that CLDN6, WIP and LC3 expression correlated with each other, and WIP expression was significantly associated with lymph node metastasis of breast cancer patients. Conclusions The data provide a new insight into the inhibitory effects of CLDN6-mediated autophagy on breast cancer metastasis, and revealed the new mechanism of CLDN6 regulating autophagy through WIP-dependent actin cytoskeleton. Our findings enrich the theoretical basis for CLDN6 as a potential biomarker for breast cancer diagnosis and therapy.

ObjectiveTo investigate the condom use of men who have sex with men （MSM） in Shanghai， the information motivation behavioral skills model （IMB） theory was used to introduce psychosocial factors and study the relevant factors of consistent condom use （CCU） in this population.MethodsA cross-sectional study of 547 MSM in four districts of Shanghai was conducted by snowball sampling. The structural equation model based on psychosocial optimization was constructed and validated using the data collected by structured questionnaires.ResultsAmong the 547 respondents， the proportion of CCU in the past six months was 45.5%. Comparing the fitness of the initial model with that of the adjusted model， we found that the fitness of the adjusted model was good.ConclusionThe proportion of CCU among MSM in Shanghai is relatively low； In addition， information and motivation do not directly affect the CCU of this population； Only behavioral skills have a direct effect on CCU. Finally， social psychological measures should be emphasized for this population， and comprehensive and multi-level strategies should be formulated to control the spread of HIV in this population.

Compared with conventional lenses, metalenses can offer smaller form factor, light weight and new functionality, and have become the focus of the recent investigations of metasurface. To date, quite a lot of studies have been reported for chromatic aberration correction of metalenses. Noting most work was carried out to satisfy the required group delay or dispersion by introducing sophisticated and integrated nanopillars, which are obtained using computationally intensive global search algorithms. Generally, the design is time-consuming. Here, we propose an alternative scheme, where metalens that corrects the chromatic aberration can be designed by optimizing the spectral degree of freedom C(ω), rather than relying on time-consuming algorithms. The proposed metalens is compatible with the complementary metal oxide semiconductor (CMOS) fabrication process. The numerically demonstrated metalens with a diameter of 200 μm and a numerical aperture (NA) of 0.24 has a small focal length fractional change (FLFC) of 4.1% over the wavelength of 9∼12 μm with an average efficiency of 51.7% in transmission mode. Moreover, the effect of fabrication deviations on the performance of the metalens is analyzed, showing critical dimension (CD) bias, sidewall angle and pillar height all have different levels of influence on the performance of the metalens.

Silicon nitride (SiN) is emerging as a material of choice for photonic integrated circuits (PICs) due to its ultralow optical losses, absence of two-photon absorption in telecommunication bands, strong Kerr nonlinearity and high-power handling capability. These properties make SiN particularly well-suited for applications such as delay lines, chip-scale frequency combs and narrow-linewidth lasers, especially when implemented with thick SiN waveguides, which is achieved through low-pressure chemical vapor deposition (LPCVD). However, a significant challenge arises when the LPCVD SiN film thickness exceeds 300 nm on an 8-inch wafer, as this can result in cracking due to high stress. In this work, we successfully develop a damascene process to fabricate 800 nm-thick SiN photonics devices on an 8-inch wafer in a pilot line, overcoming cracking challenges. The resulting 2 × 2 multimode interference (MMI) coupler exhibits low excess loss (−0.1 dB) and imbalance (0.06 dB) at the wavelength of 1310 nm. Furthermore, the dispersion-engineered SiN micro-ring resonator exhibits a quality (Q) factor exceeding 1 × 106, enabling the generation of optical frequency combs. Our demonstration of photonics devices utilizing the photonics damascene process sets the stage for high-volume manufacturing and widespread deployment.

Abstract Ultraviolet-B (UV-B) light is an intrinsic part of sunlight that reaches the earth’s surface, and affects plant survival and adaptation. How plants respond to UV-B light is regulated by the wavelength, intensity and duration of UV-B radiation, and is also regulated by photosynthetically active radiation perceived by phytochrome and cryptochrome photoreceptors. Non-damaging UV-B light promotes plant photomorphogenesis and UV-B acclimation which enhances plant tolerance against UV-B stress. However, high-level UV-B radiation induces DNA damage, generates reactive oxygen species (ROS) and impairs photosynthesis. Plants have evolved efficient mechanisms to utilize informational UV-B signal, and protect themselves from UV-B stress. UV RESISTANCE LOCUS8 (UVR8) is a conserved plant-specific UV-B photoreceptor. It interacts with CONSTITUTIVELY PHOTOMORPHOGENIC1 (COP1) to initiate UV-B-specific light signaling and regulate UV-B responsive gene expression. A set of transcription factors such as ELONGATED HYPOCOTYL5 (HY5) function downstream of the UVR8-COP1 module to promote seedling de-etiolation for photomorphogenic development and biosynthesis of sunscreen flavonoids for UV-B stress tolerance. In addition to UVR8 signaling pathways, plants subjected to damaging UV-B radiation initiate stress protection and repair mechanisms through UVR8-independent pathways. In this review, we summarize the emerging mechanisms underlying UV-B stress acclimation and protection in plants, primarily revealed in the model plant Arabidopsis thaliana.

Due to a large number of mutations in the spike protein and immune escape, the Omicron variant (B.1.1.529) has become a predominant variant of concern (VOC) strain. To prevent the disease, we developed a candidate inactivated vaccine (Omicron COVID-19 Vaccine (Vero Cell), Inactivated). To evaluate the safety of the vaccine, we tested the repeat-dose toxicity in Sprague-Dawley (SD) rats. The doses were administered randomly to three groups: physiological saline solution (control), aluminum adjuvant in PBS solution adjuvant (adjuvant group), and low-dose and high-dose omicron vaccines (vaccine group) for 6 weeks. The SD rats were allowed to recover for 4 weeks after withdrawal. We evaluated the physiological condition of the rats, including their ophthalmological condition, body weight, food intake, body temperature, blood biochemistry, urine, neutralizing antibody, inflammation at the injection site, and organs weight. In summary, no dose-dependent adverse toxicological changes were observed, and a recovery trend was obvious, which proved the preclinical safety of the candidate omicron vaccine and provided evidence for clinical trials in humans.

Metabolomics analysis reveals that inosine monophosphate, a purine metabolite, promotes myelopoiesis and contributes to severe acute pancreatitis in db/db mice.

In order to solve the problems of high labor intensity, low efficiency of manual operation and lack of supporting machinery in the fruit harvesting of modern orchards, a self-propelled orchard multi-station harvesting equipment was designed in combination with the fruit tree dwarf anvil wide-row dense planting mode and agronomic planting requirements. The whole machine structure and working principle of the self-propelled orchard multi-station harvesting equipment were expounded. According to the environmental conditions of mountainous orchards, the crawler chassis structure was designed, and the working speed was 0~2 km/h. The operating platform including left extension platform and right extension platform was designed according to the difference of fruit tree row spacing, and the working width of the operating platform was 1500~2700 mm. In order to improve the working efficiency and ensure the same picking speed of upper and lower operators, the picking operation mode of "two sides, two heights and six stations" was proposed by comparing the difference in the working flexibility between the operator on the platform and the operator on the ground during the operation of the machine, and the in-and-out channels of fruit boxes and the automatic collection and packing device were designed. The front and rear unobstructed fruit box access system was composed of the front loading and unloading mechanism, the rear loading and unloading mechanism and the fruit box slide rail, which was convenient for the empty fruit box to enter the fruit loading station of the working platform from the front and unloading from the rear after the fruit was filled. Six sub-conveyor belts were designed to handle apples harvested by six non interacting operators at the same time. The prototype was test in the field, and the packing uniform distribution coefficient calculation method was proposed to evaluate the uniformity of fruit packing, and the performance of the prototype was comprehensively evaluated in combination with the fruit damage rate and packing speed. The results showed that, the designed self-propelled orchard multi-station harvesting equipment could synchronize with the six stations manual harvesting speed. At the same time, with the help of the expansion platform, the apple picking range covered the entire canopy of the fruit tree. The prototype worked smoothly, and the speed of each conveyor belt was in good coordination with manual picking, and there was no apple congestion occurred. The apple harvest damage rate was 4.67%, the packing uniform distribution coefficient was 1.475, and the packing speed was 72.9 apples per minute, which could meet the requirements of orchard harvest operation.

Identifying desirable genotypes with the best performance in diverse environments is a perpetual aim of plant breeding, and the interaction between genotype and environment (G × E) always plays a key role. This study was conducted to elucidate the genetic behaviour of different hybrid combinations at various densities in diverse environments. According to a line × tester design, 32 hybrid combinations were obtained from 16 inbred individuals crossed with two testers and planted at three locations at three density levels (45,000, 67,500 and 90,000 plants ha−1) during 2014−2017. Genotype (G), environment (E) and the interaction of genotype and environment (G × E) significantly affected grain yield at different densities. Increasing planting density enhanced grain yield and improved the efficiency of germplasm screening, where the effect of location on grain yield at different densities was larger than that of year and the GCA was larger than the SCA. Finally, four inbred lines (KB102, KB081, KA105, and KB106) with a high GCA, environmental adaptability, and several combinations using them as parents have been approved in ShannXi Province and National of China. In conclusion, the evaluation of combining ability at multiple densities and locations can effectively screen inbred lines and improve breeding efficiency.

Abstract Background Oncostatin M receptor (OSMR), as one of the receptors for oncostatin M (OSM), has previously been shown to mediate the stimulatory role of OSM in osteoclastogenesis and bone resorption. However, it remains to be clarified whether and how OSMR affects the differentiation of osteoblasts. Methods The expression level of OSMR during osteoblast and adipocyte differentiation was examined. The role of OSMR in the differentiation was investigated using in vitro gain-of-function and loss-of-function experiments. The mechanisms by which OSMR regulates bone cell differentiation were explored. Finally, in vivo function of OSMR in cell fate determination and bone homeostasis was studied after transplantation of OSMR-silenced bone marrow stromal cells (BMSCs) to the marrow of ovariectomized mice. Results OSMR was regulated during osteogenic and adipogenic differentiation of marrow stromal progenitor cells and increased in the metaphysis of ovariectomized mice. OSMR suppressed osteogenic differentiation and stimulated adipogenic differentiation of progenitor cells. Mechanistic investigations showed that OSMR inhibited extracellular signal-regulated kinase (ERK) and autophagy signaling. The downregulation of autophagy, which was mediated by ERK inhibition, suppressed osteogenic differentiation of progenitor cells. Additionally, inactivation of ERK/autophagy signaling attenuated the stimulation of osteogenic differentiation induced by Osmr siRNA. Furthermore, transplantation of BMSCs in which OSMR was silenced to the marrow of mice promoted osteoblast differentiation, attenuated fat accumulation and osteoclast differentiation, and thereby relieved the osteopenic phenotype in the ovariectomized mice. Conclusions Our study has for the first time established the direct role of OSMR in regulating osteogenic differentiation of marrow stromal progenitor cells through ERK-mediated autophagy signaling. OSMR thus contributes to bone homeostasis through dual regulation of osteoblasts and osteoclasts. It also suggests that OSMR may be a potential target for the treatment of metabolic disorders such as osteoporosis.

Abstract Background AKI is related to severe adverse outcomes and mortality with Coronavirus Disease 2019 (COVID-19) patients, that early diagnosed and intervened is imperative. Neutrophil gelatinase-associated lipocalin (NGAL) is one of the most promising biomarkers for detection of acute kidney injury (AKI), but current detection methods are inadequacy, so more rapid, convenient and accuracy methods are needed to detect NGAL for early diagnosis of AKI. Herein, we established a rapid, reliable and accuracy lateral flow immunoassay (LFIA) based on europium nanoparticles (EU-NPS) for the detection of NGAL in human urine specimens. Methods A double-antibody sandwich immunofluorescent assay using europium doped nanoparticles was employed and the NGAL monoclonal antibodies (MAbs) conjugate as labels were generated by optimizing electric fusion parameters. Eighty-three urine samples were used to evaluate the clinical application efficiency of this method. Results The quantitative detection range of NGAL in AKI was 1-3000 ng/mL, and the detection sensitization was 0.36 ng/mL. The coefficient of variation (CV) of intra-assay and inter-assay were 2.57-4.98 % and 4.11-7.83 %, respectively. Meanwhile, the correlation coefficient between europium nanoparticles-based lateral fluorescence immunoassays (EU-NPS-LFIA) and ARCHITECT analyzer was significant (R2 = 0.9829, n = 83, p

Background Because the impact of changes in how outpatient care was delivered during the COVID‐19 pandemic is uncertain, we designed this study to examine the frequency and type of outpatient visits between March 1, 2019 to February 29, 2020 (prepandemic) and from March 1, 2020 to February 28, 2021 (pandemic) and specifically compared outcomes after virtual versus in‐person outpatient visits during the pandemic. Methods and Results Population‐based retrospective cohort study of all 3.8 million adults in Alberta, Canada. We examined all physician visits and 30‐ and 90‐day outcomes, with a focus on those adults with the cardiovascular ambulatory‐care sensitive conditions heart failure, hypertension, and diabetes. Our primary outcome was emergency department visit or hospitalization, evaluated using survival analysis accounting for competing risk of death. Although in‐person outpatient visits decreased by 38.9% in the year after March 1, 2020 (10 142 184 versus 16 592 599 in the prior year), the introduction of virtual visits (7 152 147; 41.4% of total) meant that total outpatient visits increased by 4.1% in the first year of the pandemic for Albertan adults. Outpatient visit frequency (albeit 41.4% virtual, 58.6% in‐person) and prescribing patterns were stable in the first year after pandemic onset for patients with the cardiovascular ambulatory‐care sensitive conditions we examined, but laboratory test frequency declined by 20% (serum creatinine) to 47% (glycosylated hemoglobin). In the first year of the pandemic, virtual outpatient visits were associated with fewer subsequent emergency department visits or hospitalizations (compared with in‐person visits) for patients with heart failure (adjusted hazard ratio [aHR], 0.90 [95% CI, 0.85–0.96] at 30 days and 0.96 [95% CI, 0.92–1.00] at 90 days), hypertension (aHR, 0.88 [95% CI, 0.85–0.91] and 0.93 [95% CI, 0.91–0.95] at 30 and 90 days), or diabetes (aHR, 0.90 [95% CI, 0.87–0.93] and 0.93 [95% CI, 0.91–0.95] at 30 and 90 days). Conclusions The adoption and rapid uptake of virtual outpatient care during the COVID‐19 pandemic did not negatively impact frequency of follow‐up, prescribing, or short‐term outcomes, and could have potentially positively impacted some of these for adults with heart failure, diabetes, or hypertension in a setting where there was an active reimbursement policy for virtual visits. Given declines in laboratory monitoring and screening activities, further research is needed to evaluate whether long‐term outcomes will differ.

Solution-processable polyimide (PI) materials are attractive for applications in future flexible optoelectronics, owing to their excellent thermal and chemical resistance, inherent flexibility, and superior dielectric properties. They are widely integrated and investigated in various semiconductor devices. Here, the unique characteristics of PIs and their applications in optoelectronics are analyzed and summarized. A general introduction from the material aspect is given, followed by detailing the PI applications in multiple devices, including field-effect transistors, capacitors, photodetectors, and memory devices. In this review, the uniqueness and potential of PIs for next-generation optoelectronics are fully demonstrated, and the underlying challenges are proposed.

The DTacP-sIPV-Hib combination vaccine can replace the single-component acellular pertussis, diphtheria, tetanus, polio, and Haemophilus influenzae type B vaccines. In this study, we evaluated the safety and immunogenicity of a newly developed DTacP-sIPV-Hib combination vaccine in animal models. We used 40 mice and 46 cynomolgus monkeys to evaluate acute and long-term toxicity. Thirty-six guinea pigs were used for sensitization assessment. For immunogenicity assessment, 50 NIH mice and 50 rats were equally randomized to receive 3 doses of 3 different batches of the tested vaccine at an interval of 21 d, or physiological saline solution (0.5 mL). Orbital blood was collected at an interval of 21 d post inoculation to detect related antibody titers or neutralizing antibody titers against poliovirus. Gross autopsy and histopathological examination revealed no abnormal toxicity or irritation in mice and cynomolgus monkeys. Sensitization assessment in guinea pigs indicated the lack of evident allergic symptoms in the high- and low-dose vaccine groups within 30 min after repeated stimulation. The DTacP-sIPV-Hib combination vaccine induced significant immune responses in mice, rats, and cynomolgus monkeys, with 100% seroconversion rates after 3 doses. The DTacP-sIPV-Hib combination vaccine is safe and immunogenic in animal models. Three doses of the vaccine elicited satisfactory antibody responses in mice, rats, and cynomolgus monkeys.

Non-alcoholic fatty liver disease (NAFLD) occurs in 25% of the global population and manifests as lipid deposition, hepatocyte injury, activation of Kupffer and stellate cells, and steatohepatitis. Predominantly expressed in hepatocytes, the augmenter of liver regeneration (ALR) is a key factor in liver regulation that can alleviate fatty liver disease and protect the liver from abnormal liver lipid metabolism. ALR has three isoforms (15-, 21-, and 23-kDa), amongst which 23-kDa ALR is the most extensively studied. The 23-kDa ALR isoform is a sulfhydryl oxidase that resides primarily in the mitochondrial intermembrane space (IMS), whereby it protects the liver against various types of injury. In this review, we describe the role of ALR in regulating hepatocytes in the context of NAFLD. We also discuss questions about ALR that remain to be explored in the future. In conclusion, ALR appears to be a promising therapeutic target for treating NAFLD.

This article describes a master oscillator and power amplifier (MOPA) system with a single longitudinal mode (SLM) and high-repetition-frequency Pr3+:YLF active medium that was end-pumped by two 444 nm laser diodes. The Pr3+:YLF MOPA laser system produced a maximum pulse energy of 13.5 μJ with a pulse width of 130.2 ns at a pulse repetition frequency of 20 kHz, translating to a peak power of around 103.7 W. The Pr3+:YLF MOPA laser system’s output wavelength was 639.7 nm, and the line-width of its laser spectra was roughly 168 MHz. Additionally, at the highest output level, the laser beam quality did not decrease much due to amplification.

We create a rate equation theoretical model of a continuous-wave end-pumped Pr3+:YLF SLM laser that characterizes the output properties of a single-longitudinal-mode (SLM) green laser. After inserting two Fabry–Perot (F–P) etalons with thicknesses of 0.3 mm and 0.5 mm and angles of 1.42° and 0.69° into the cavity, a single-longitudinal-mode green laser was generated. The maximum output power in single-longitudinal mode was 183 mW. The maximum absorbed pump power was 6.2 W. The corresponding linewidth is about 18 MHz. This work presents a simple method for generating a single-longitudinal-mode laser in the green spectral region, providing a practical approach for various green-laser-related applications.

Abstract Background Risk factors that predispose the development of severe community-acquired pneumonia (CAP) among pediatric CAP patients of different age ranges are yet to be identified. Methods We retrospectively analyzed pediatric in-patients ( 1 for all). CHD, low albumin, proteinuria, abnormal chest x-ray were independent risks factors across different age groups, whereas birth or feeding history, history of pneumonia, cyanosis or dyspnea on admission, and RSV infection were independent risk factors for only younger kids (

Fertilization is the main strategy to accelerate vegetation restoration and improve the rhizosphere microbial community in the northeast China. However, the responses of rhizosphere microbial community structure, specific microbial community and symbiotic pattern to manure fertilization in grassland (alfalfa only) are not well clear. In this study, the variation of bacterial community structures in R_Manure (extracted liquid of fermented cow manure), E_Manure (extracted residue of fermented cow manure), F_Manure (full fermented cow manure), and Control (without fermented cow manure) collected from the rhizosphere microbial community of alfalfa were analyzed by the application of an Illumina HiSeq high-throughput sequencing technique. A total of 62,862 microbial operational taxonomic units (OTUs) were detected and derived from 21 phyla of known bacteria. The dominant bacteria in the rhizosphere include Proteobacteria (70.20%), Acidobacteria (1.24%), Actinobacteria (2.11%), Bacteroidetes (6.15%), Firmicutes (4.21%), and Chlorofexi (2.13%) accounting for 86% of the dominant phyla in all treatments. At the genus level, the dominant genus include NB1-j, Lysobacter, Alphaproteobacteria, Subgroup_6, Actinomarinales, Saccharimonadales, Aneurinibacillus, MO-CFX2, SBR1031, Caldilineaceae, and so on with the average relative abundance (RA) of 1.76%, 1.52%, 1.30%, 1.24%, 1.61%, 2.39%, 1.36%, 1.42%, 1.27%, and 1.03%, respectively. Bacterial diversities and community structures were significantly differentiated by different treatments of fertilization. The results of community structure composition showed that R_Manure treatment significantly increased the population abundance of Firmicutes, Chlorofexi, and Patescibacteria by 34.32%, 6.85%, and 2.70%, and decreased the population abundance of Proteobacteria and Actinobacteria by 16.83% and 1.04%, respectively. In addition, it showed that all treatments significantly resulted in an increase or decrease at the genus level. R_Manure had the higher richness and diversity of the bacterial community, with the greatest topology attributes of the co-occurrence networks. Through the analysis of the molecular ecological network (MENA), the co-occurrence networks had a shorter average path distance and diameter in R_Manure than in others, implying more stability to environmental changes. Redundancy analysis (RDA) showed that the ratio of carbon and nitrogen (C/N) was the main factor affecting rhizosphere microbial community composition while driving distinct rhizosphere bacterial community and its co-occurrence networks. The R_Manure associated with more C/N had relatively complex microbial co-occurrence network with a large number of nodes and edges, while the microbial network of others associated with less C/N had fewer taxa with loose mutual interactions. These results suggested that organic fertilizer with high C/N can regulate the rhizosphere microorganism, while high C/N can determine bacterial community structures, specific bacterial taxa, and their relationships with the nodule size of alfalfa. These significant changes can be used to evaluate soil fertility and fertilizer management in the artificial grassland system, while the potential biological indicators of the rhizosphere microbial community will play an important role in future eco-agriculture.

Objective To study the effect of miR-29b on lipopolysaccharide(LPS)-induced apoptosis of human bronchial epithelial cell line 16HBE. Methods 16HBE cells were divided into control group, LPS group (LPS treatment), transfection mimics control group, transfection miR-29b mimics group. MTT assay for proliferation, flow cytometry was used for apoptosis; Western blot was used for checking the expression of cleaved cysteinyl aspartate specific proteins 3(c-caspase-3), cleaved cysteinyl aspartate specific proteinase 12(c-caspase-12), glucose-regulated protein 78(GRP78) and CCAAT/enhancer-binding protein C/EBP (CHOP) protein. Human bronchial epithelial cells 16HBE were co-transfected with miR-29b mimics and pcDNA-CHOP, the proliferation and apoptosis were also determined using the above method. Results Compared with the control group, the cell proliferation- activity and apoptosis rate of the LPS group decreased, and the protein expression level of c-caspase-3, c-caspase-12, GRP78, and CHOP all increased. Compared with the LPS+NC group, the LPS+miR-29b group showed an increased cell proliferation, decreased apoptosis and decreased expression of c-caspase-3, c-caspase-12, GRP78, and CHOP protein. pcDNA-CHOP reversed the effects of miR-29b mimics on the proliferation and apoptosis of bronchial epithelial cells under LPS conditions. Conclusions miR-29b inhibits 16HBE apoptosis induced by LPS; the mechanism might be related to the inhibition of endoplasmic reticulum stress.