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Abstract Background Circulating atherogenic index of plasma (AIP) levels has been proposed as a novel biomarker for dyslipidemia and as a predictor of insulin resistance (IR) risk. However, the association between AIP and the incidence of new-onset stroke, particularly in individuals with varying glucose metabolism status, remains ambiguous. Methods A total of 8727 participants aged 45 years or older without a history of stroke from the China Health and Retirement Longitudinal Study (CHARLS) were included in this study. The AIP was calculated using the formula log [Triglyceride (mg/dL) / High-density lipoprotein cholesterol (mg/dL)]. Participants were divided into four groups based on their baseline AIP levels: Q1 (AIP ≤ 0.122), Q2 (0.122 0.562). The primary endpoint was the occurrence of new-onset stroke events. The Kaplan–Meier curves, multivariate Cox proportional hazard models, and Restricted cubic spline analysis were applied to explore the association between baseline AIP levels and the risk of developing a stroke among individuals with varying glycemic metabolic states. Results During an average follow-up of 8.72 years, 734 participants (8.4%) had a first stroke event. The risk for stroke increased with each increasing quartile of baseline AIP levels. Kaplan–Meier curve analysis revealed a significant difference in stroke occurrence among the AIP groups in all participants, as well as in those with prediabetes mellitus (Pre-DM) and diabetes mellitus (DM) (all P values 0.05). Restricted cubic spline analysis also demonstrated that higher baseline AIP levels were associated with higher hazard ratios for stroke in all participants and those with glucose metabolism disorders. Conclusions An increase in baseline AIP levels was significantly associated with the risk of stroke in middle-aged and elderly individuals, and exhibited distinct characteristics depending on the individual’s glucose metabolism status.

Abstract Background Macrophages are key inflammatory immune cells that orchestrate the initiation and progression of autoimmune diseases. The characters of macrophage in diseases are determined by its phenotype in response to the local microenvironment. Ficolins have been confirmed as crucial contributors to autoimmune diseases, with Ficolin-2 being particularly elevated in patients with autoimmune diseases. However, whether Ficolin-A stimulates macrophage polarization is still poorly understood. Methods We investigated the transcriptomic expression profile of murine bone marrow-derived macrophages (BMDMs) stimulated with Ficolin-A using RNA-sequencing. To further confirm a distinct phenotype activated by Ficolin-A, quantitative RT-PCR and Luminex assay were performed in this study. Additionally, we assessed the activation of underlying cell signaling pathways triggered by Ficolin-A. Finally, the impact of Ficolin-A on macrophages were investigated in vivo through building Collagen-induced arthritis (CIA) and Dextran Sulfate Sodium Salt (DSS)-induced colitis mouse models with Fcna-/- mice. Results Ficolin-A activated macrophages into a pro-inflammatory phenotype distinct to LPS-, IFN-γ- and IFN-γ + LPS-induced phenotypes. The transcriptomic profile induced by Ficolin-A was primarily characterized by upregulation of interleukins, chemokines, iNOS, and Arginase 1, along with downregulation of CD86 and CD206, setting it apart from the M1 and M2 phenotypes. The activation effect of Ficolin-A on macrophages deteriorated the symptoms of CIA and DSS mouse models, and the deletion of Fcna significantly alleviated the severity of diseases in mice. Conclusion Our work used transcriptomic analysis by RNA-Seq to investigate the impact of Ficolin-A on macrophage polarization. Our findings demonstrate that Ficolin-A induces a novel pro-inflammatory phenotype distinct to the phenotypes activated by LPS, IFN-γ and IFN-γ + LPS on macrophages.

Abstract Background Drug resistance poses a significant challenge in cancer treatment, particularly as a leading cause of therapy failure. Cisplatin, the primary drug for lung adenocarcinoma (LUAD) chemotherapy, shows effective treatment outcomes. However, the development of resistance against cisplatin is a major obstacle. Therefore, identifying genes resistant to cisplatin and adopting personalized treatment could significantly improve patient outcomes. Methods By examining transcriptome data of cisplatin-resistant LUAD cells from the GEO database, 181 genes associated with cisplatin resistance were identified. Using univariate regression analysis, random forest and multivariate regression analyses, two prognostic genes, E2F7 and FAM83A, were identified. This study developed a prognostic model utilizing E2F7 and FAM83A as key indicators. The Cell Counting Kit 8 assay, Transwell assay, and flow cytometry were used to detect the effects of E2F7 on the proliferation, migration, invasiveness and apoptosis of A549/PC9 cells. Western blotting was used to determine the effect of E2F7 on AKT/mTOR signaling pathway. Results This study has pinpointed two crucial genes associated with cisplatin resistance, E2F7 and FAM83A, and developed a comprehensive model to assist in the diagnosis, prognosis, and evaluation of relapse risk in LUAD. Analysis revealed that patients at higher risk, according to these genetic markers, had elevated levels of immune checkpoints (PD-L1 and PD-L2). The prognostic and diagnosis values of E2F7 and FAM83A were further confirmed in clinical data. Furthermore, inhibiting E2F7 in lung cancer cells markedly reduced their proliferation, migration, invasion, and increased apoptosis. In vivo experiments corroborated these findings, showing reduced tumor growth and lung metastasis upon E2F7 suppression in lung cancer models. Conclusion Our study affirms the prognostic value of a model based on two DEGs, offering a reliable method for predicting the success of tumor immunotherapy in patients with LUAD. The diagnostic and predictive model based on these genes demonstrates excellent performance. In vitro, reducing E2F7 levels shows antitumor effects by blocking LUAD growth and progression. Further investigation into the molecular mechanisms has highlighted E2F7’s effect on the AKT/mTOR signaling pathway, underscoring its therapeutic potential. In the era of personalized medicine, this DEG-based model promises to guide clinical practice.

Abstract Excessive iron accumulation in the brain cortex increases the risk of cognitive deterioration. However, interregional relationships (defined as susceptibility connectivity) of local brain iron have not been explored, which could provide new insights into the underlying mechanisms of cognitive decline. Seventy-six healthy controls (HC), 58 participants with mild cognitive impairment due to probable Alzheimer’s disease (MCI-AD) and 66 participants with white matter hyperintensity (WMH) were included. We proposed a novel approach to construct a brain susceptibility network by using Kullback‒Leibler divergence similarity estimation from quantitative susceptibility mapping and further evaluated its topological organization. Moreover, sparse logistic regression (SLR) was applied to classify MCI-AD from HC and WMH with normal cognition (WMH-NC) from WMH with MCI (WMH-MCI).The altered susceptibility connectivity in the MCI-AD patients indicated that relatively more connectivity was involved in the default mode network (DMN)-related and visual network (VN)-related connectivity, while more altered DMN-related and subcortical network (SN)-related connectivity was found in the WMH-MCI patients. For the HC vs. MCI-AD classification, the features selected by the SLR were primarily distributed throughout the DMN-related and VN-related connectivity (accuracy = 76.12%). For the WMH-NC vs. WMH-MCI classification, the features with high appearance frequency were involved in SN-related and DMN-related connectivity (accuracy = 84.85%). The shared and specific patterns of the susceptibility network identified in both MCI-AD and WMH-MCI may provide a potential diagnostic biomarker for cognitive impairment, which could enhance the understanding of the relationships between brain iron burden and cognitive decline from a network perspective.

Abstract Background Nasopharyngeal carcinoma (NPC) is prevalent in southern China. EBV DNA is the most useful biomarker in NPC. However, the value of EBV DNA in posttreatment NPC patients infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) remains unclear. Methods Sixty-four eligible NPC patients were enrolled between December 2022 and February 2023. Patients who met the following criteria were included: had non-metastatic NPC, completed radical treatment, were first firstly infected with SARS-CoV-2 and their EBV DNA changed from undetectable to detectable. Results At the end of follow-up, 81.25% (52/64) of patients were confirmed not to relapse with undetectable EBV DNA (no-relapse). In addition, 18.75% (12/64) of patients experienced relapse with consistent detection of EBV DNA (yes-relapse). For all 64 patients, the average time from diagnosis of coronavirus disease 2019 (COVID-19) to detection of detectable EBV DNA was 35.41 days (2 to 139 days). For 52 no-relapse patients, the average time from EBV DNA changing from detectable to undetectable was 63.12 days (6 to 147 days). The levels of EBV DNA were greater in yes-relapse patients than that in no-relapse patients, and the average of EBV DNA levels were 1216 copies/ml and 53.18 copies/ml, respectively. Using 62.3 copies/mL as the threshold, the area under the curve for EBV DNA was 0.88 for distinguishing yes-relapse patients from no-relapse patients. The sensitivity and specificity were 81.97% (95% CI 0.71–0.95) and 86.67% (95% CI 0.70–0.95), respectively. Conclusion For NPC patients infected with SARS-CoV-2, EBV DNA alone is insufficient for monitoring relapse after radical therapy. Long-term follow-up and underlying mechanistic investigations of EBV DNA changes are urgently needed.

Abstract Background Patients with Alzheimer’s disease (AD) are often co-morbid with unprovoked seizures, making clinical diagnosis and management difficult. Although it has an important role in both AD and epilepsy, abnormal γ-aminobutyric acid (GABA)ergic transmission is recognized only as a compensative change for glutamatergic damage. Neuregulin 1 (NRG1)-ErbB4 signaling can promote GABA release and suppress epileptogenesis, but its effects on cognition in AD are still controversial. Methods Four-month-old APPswe/PS1dE9 mice (APP mice) were used as animal models in the early stage of AD in this study. Acute/chronic chemical-kindling epilepsy models were established with pentylenetetrazol. Electroencephalogram and Racine scores were performed to assess seizures. Behavioral tests were used to assess cognition and emotion. Electrophysiology, western blot and immunofluorescence were performed to detect the alterations in synapses, GABAergic system components and NRG1-ErbB4 signaling. Furthermore, NRG1 was administrated intracerebroventricularly into APP mice and then its antiepileptic and cognitive effects were evaluated. Results APP mice had increased susceptibility to epilepsy and resulting hippocampal synaptic damage and cognitive impairment. Electrophysiological analysis revealed decreased GABAergic transmission in the hippocampus. This abnormal GABAergic transmission involved a reduction in the number of parvalbumin interneurons (PV+ Ins) and decreased levels of GABA synthesis and transport. We also found impaired NRG1-ErbB4 signaling which mediated by PV+ Ins loss. And NRG1 administration could effectively reduce seizures and improve cognition in four-month-old APP mice. Conclusion Our results indicated that abnormal GABAergic transmission mediated hippocampal hyperexcitability, further excitation/inhibition imbalance, and promoted epileptogenesis in the early stage of AD. Appropriate NRG1 administration could down-regulate seizure susceptibility and rescue cognitive function. Our study provided a potential direction for intervening in the co-morbidity of AD and epilepsy.

The resonance enhanced InAs/GaSb type-II Superlattices (T2SLs) infrared detectors with diffraction rings is designed, and the photoelectric characteristics are calculated and studied in this paper. The diffraction rings are designed on the top surface of T2SLs detector to control the incident light inside the device by forming the resonant cavity. We designed the structure of the conventional PIN InAs/GaSb T2SLs photodetector, calculated the energy band structure of the absorption layer, and analyzed the influence of the thickness of the absorption layer on the photoelectric performance. It is proved that blindly increasing the thickness of the absorption layer cannot effectively improve the device performance. We further studied the quantum efficiency (QE) and electric field distribution of the device after adding the diffraction ring structure. The results show that the structure with diffraction rings can significantly improve the QE of the photodetector without increasing the dark current. The interaction between the diffraction ring and the metal contact layer will enhance the localization of the electric field and further increase the light absorption between the semiconductor layers.

Chitosan nanoparticles (NPs) possess great potential in biomedical fields. Orifice-induced hydrodynamic cavitation (HC) has been used for the enhancement of fabrication of size-controllable genipin-crosslinked chitosan (chitosan-genipin) NPs based on the emulsion cross-linking (ECLK). Experiments have been performed using various plate geometries, chitosan molecular weight and under different operational parameters such as inlet pressure (1–3.5 bar), outlet pressure (0–1.5 bar) and cross-linking temperature (40–70 °C). Orifice plate geometry was a crucial factor affecting the properties of NPs, and the optimized geometry of orifice plate was with single hole of 3.0 mm diameter. The size of NPs with polydispersity index of 0.359 was 312.6 nm at an optimized inlet pressure of 3.0 bar, and the maximum production yield reached 84.82 %. Chitosan with too high or too low initial molecular weight (e.g., chitosan oligosaccharide) was not applicable for producing ultra-fine and narrow-distributed NPs. There existed a non-linear monotonically-increasing relationship between cavitation number (Cv) and chitosan NP size. Scanning electron microscopy (SEM) test indicated that the prepared NPs were discrete with spherical shape. The study demonstrated the superiority of HC in reducing particle size and size distribution of NPs, and the energy efficiency of orifice type HC-processed ECLK was two orders of magnitude than that of ultrasonic horn or high shear homogenization-processed ECLK. In vitro drug-release studies showed that the fabricated NPs had great potential as a drug delivery system. The observations of this study can offer strong support for HC to enhance the fabrication of size-controllable chitosan-genipin NPs.

Summary: Background: Both defects in mismatch repair (dMMR) and high microsatellite instability (MSI-H) have been recognised as crucial biomarkers that guide treatment strategies and disease management in colorectal cancer (CRC). As MMR and MSI tests are being widely conducted, an increasing number of MSI-H tumours have been identified in CRCs with mismatch repair proficiency (pMMR). The objective of this study was to assess the clinical features of patients with pMMR/MSI-H CRC and elucidate the underlying molecular mechanism in these cases. Methods: From January 2015 to December 2018, 1684 cases of pMMR and 401 dMMR CRCs were enrolled. Of those patients, 93 pMMR/MSI-H were identified. The clinical phenotypes and prognosis were analysed. Frozen and paraffin-embedded tissue were available in 35 patients with pMMR/MSI-H, for which comprehensive genomic and transcriptomic analyses were performed. Findings: In comparison to pMMR/MSS CRCs, pMMR/MSI-H CRCs exhibited significantly less tumour progression and better long-term prognosis. The pMMR/MSI-H cohorts displayed a higher presence of CD8+ T cells and NK cells when compared to the pMMR/MSS group. Mutational signature analysis revealed that nearly all samples exhibited deficiencies in MMR genes, and we also identified deleterious mutations in MSH3-K383fs. Interpretation: This study revealed pMMR/MSI-H CRC as a distinct subgroup within CRC, which manifests diverse clinicopathological features and long-term prognostic outcomes. Distinct features in the tumour immune-microenvironment were observed in pMMR/MSI-H CRCs. Pathogenic deleterious mutations in MSH3-K383fs were frequently detected, suggesting another potential biomarker for identifying MSI-H. Funding: This work was supported by the Science and Technology Commission of Shanghai Municipality (20DZ1100101).

In recent years, environmental factors have received attention in the pathogenesis of neurodegenerative diseases. Other than genetic factors, the identification of environmental factors and modifiable risk factors may create opportunities to delay the onset or slow the progression of Lewy body disease. Researchers have made significant progress in understanding environmental and modifiable risk factors over the past 30 years. To date, despite the increasing number of articles assessing risk factors for Lewy body disease, few reviews have focused on their role in its onset. In this review, we reviewed the literature investigating the relationship between Lewy body disease and several environmental and other modifiable factors. We found that some air pollutants, exposure to some metals, and infection with some microorganisms may increase the risk of Lewy body disease. Coffee intake and the Mediterranean diet are protective factors. However, it is puzzling that low educational levels and smoking may have some protective effects. In addition, we proposed specific protocols for subsequent research directions on risk factors for neurodegenerative diseases and improved methods. By conducting additional case-control studies, we could explore the role of these factors in the etiopathogenesis of Lewy body disease, establishing a foundation for strategies aimed at preventing and reducing the onset and burden of the disease.

Abstract Objective To develop a clinical learning environment scale for Chinese nursing students and test its reliability and validity. Methods Based on Moos social environment theory, qualitative interviews and expert consultations were used to develop a pretest version of the Chinese Nursing Students’ Clinical Learning Environment Scale. With a convenience sampling method, 255 and 1582 Chinese nursing students were selected as the prediction and validation samples, respectively, from December 2022 to March 2023. Exploratory and confirmatory factor analyses were conducted to determine the construct validity. Results The scale consisted of 19 items. Exploratory factor analysis revealed three sub-scales, named goal orientation, interpersonal relation, and learning support, which explained 71.500% of the total variance. The results of the confirmatory factor analysis showed that the GFI was 0.848, the AGFI was 0.806, the RMSEA was 0.090, the RMR was 0.041, the NFI was 0.910, the IFI was 0.916, the CFI was 0.916, the PCFI was 0.798, and the PNFI was 0.793. The reliability values of the three dimensions were 0.870, 0.858, and 0.943, respectively, and the convergent validity values were 0.574, 0.603, and 0.625, respectively. Conclusion The reliability and validity of the dimensions of the Chinese Nursing Students’ Clinical Learning Environment Scale are acceptable, and the scale can be used as a useful tool for measuring the clinical learning environment of Chinese nursing students.

Abstract Background Microglia is the major contributor of post-stroke neuroinflammation cascade and the crucial cellular target for the treatment of ischemic stroke. Currently, the endogenous mechanism underlying microglial activation following ischemic stroke remains elusive. Serglycin (SRGN) is a proteoglycan expressed in immune cells. Up to now, the role of SRGN on microglial activation and ischemic stroke is largely unexplored. Methods Srgn knockout (KO), Cd44-KO and wild-type (WT) mice were subjected to middle cerebral artery occlusion (MCAO) to mimic ischemic stroke. Exogenous SRGN supplementation was achieved by stereotactic injection of recombinant mouse SRGN (rSRGN). Cerebral infarction was measured by 2,3,5-triphenyltetrazolium chloride (TTC) staining. Neurological functions were evaluated by the modified neurological severity score (mNSS) and grip strength. Microglial activation was detected by Iba1 immunostaining, morphological analysis and cytokines’ production. Neuronal death was examined by MAP2 immunostaining and FJB staining. Results The expression of SRGN and its receptor CD44 was significantly elevated in the ischemic mouse brains, especially in microglia. In addition, lipopolysaccharide (LPS) induced SRGN upregulation in microglia in vitro. rSRGN worsened ischemic brain injury in mice and amplified post-stroke neuroinflammation, while gene knockout of Srgn exerted reverse impacts. rSRGN promoted microglial proinflammatory activation both in vivo and in vitro, whereas Srgn-deficiency alleviated microglia-mediated inflammatory response. Moreover, the genetic deletion of Cd44 partially rescued rSRGN-induced excessed neuroinflammation and ischemic brain injury in mice. Mechanistically, SRGN boosted the activation of NF-κB signal, and increased glycolysis in microglia. Conclusion SRGN acts as a novel therapeutic target in microglia-boosted proinflammatory response following ischemic stroke.

Abstract HBV-miR-3 is encoded by HBV and takes part in pathogenesis of HBV-related liver disease. Whether HBV-miR-3 has a relationship with HBV replication and is predictive of PegIFN-α treatment response is still unknown. HBV-miR-3 quantification is based on qRT-PCR. The relationship of HBV-miR-3 and HBV replication, and predictive value of HBV-miR-3 were evaluated in a cohort of 650 HBeAg positive patients from a multi-center, randomized phase III clinical trial for the study of PegIFN-a2b. HBV-miR-3 is significantly positively related to HBVDNA, HBVpgRNA, HBeAg and HBsAg at baseline and at all the different time points during PegIFN-α treatment. Both univariate regression analyses and multivariate logistic regression analyses showed HBV-miR-3 is a predictor of HBeAg seroconversion in the patients treated with PegIFN-α at weeks of 0, 12, and 24. 70.0% of patients with HBV-miR-3 6log at week 12 no patient obtained HBeAg seroconversion. Conbination of HBV-miR-3 and HBeAg is more strongly predictive of HBeAg seroconversion (83.64%) at week 12. HBV-miR-3 is new biomarker for HBV replication and positively correlated to HBV replication. HBV-miR-3 is also an early predictor of HBeAg seroconversion in the patients treated with PegIFN-α.

Abstract Background Damage in the ischemic core and penumbra after stroke affects patient prognosis. Microglia immediately respond to ischemic insult and initiate immune inflammation, playing an important role in the cellular injury after stroke. However, the microglial heterogeneity and the mechanisms involved remain unclear. Methods We first performed single-cell RNA-sequencing (scRNA-seq) and spatial transcriptomics (ST) on middle cerebral artery occlusion (MCAO) mice from three time points to determine stroke-associated microglial subclusters and their spatial distributions. Furthermore, the expression of microglial subcluster-specific marker genes and the localization of different microglial subclusters were verified on MCAO mice through RNAscope and immunofluorescence. Gene set variation analysis (GSVA) was performed to reveal functional characteristics of microglia sub-clusters. Additionally, ingenuity pathway analysis (IPA) was used to explore upstream regulators of microglial subclusters, which was confirmed by immunofluorescence, RT-qPCR, shRNA-mediated knockdown, and targeted metabolomics. Finally, the infarct size, neurological deficits, and neuronal apoptosis were evaluated in MCAO mice after manipulation of specific microglial subcluster. Results We discovered stroke-associated microglial subclusters in the brains of MCAO mice. We also identified novel marker genes of these microglial subclusters and defined these cells as ischemic core-associated (ICAM) and ischemic penumbra-associated (IPAM) microglia, according to their spatial distribution. ICAM, induced by damage-associated molecular patterns, are probably fueled by glycolysis, and exhibit increased pro-inflammatory cytokines and chemokines production. BACH1 is a key transcription factor driving ICAM generation. In contrast, glucocorticoids, which are enriched in the penumbra, likely trigger IPAM formation, which are presumably powered by the citrate cycle and oxidative phosphorylation and are characterized by moderate pro-inflammatory responses, inflammation-alleviating metabolic features, and myelinotrophic properties. Conclusions ICAM could induce excessive neuroinflammation, aggravating brain injury, whereas IPAM probably exhibit neuroprotective features, which could be essential for the homeostasis and survival of cells in the penumbra. Our findings provide a biological basis for targeting specific microglial subclusters as a potential therapeutic strategy for ischemic stroke.

Abstract The TMEM63 family proteins (A, B, and C), calcium-permeable channels in animals that are preferentially activated by hypo-osmolality, have been implicated in various physiological functions. Deficiency of these channels would cause many diseases including hearing loss. However, their structures and physiological roles are not yet well understood. In this study, we determine the cryo-electron microscopy (cryo-EM) structure of the mouse TMEM63C at 3.56 Å, and revealed structural differences compared to TMEM63A, TMEM63B, and the plant orthologues OSCAs. Further structural guided mutagenesis and calcium imaging demonstrated the important roles of the coupling of TM0 and TM6 in channel activity. Additionally, we confirm that TMEM63C exists primarily as a monomer under physiological conditions, in contrast, TMEM63B is a mix of monomer and dimer in cells, suggesting that oligomerization is a regulatory mechanism for TMEM63 proteins.

Abstract Background Emerging evidence has shown that myeloid cells that infiltrate into the peri-infarct region may influence the progression of ischemic stroke by interacting with microglia. Properdin, which is typically secreted by immune cells such as neutrophils, monocytes, and T cells, has been found to possess damage-associated molecular patterns (DAMPs) properties and can perform functions unrelated to the complement pathway. However, the role of properdin in modulating microglia-mediated post-stroke neuroinflammation remains unclear. Methods Global and conditional (myeloid-specific) properdin-knockout mice were subjected to transient middle cerebral artery occlusion (tMCAO). Histopathological and behavioral tests were performed to assess ischemic brain injury in mice. Single-cell RNA sequencing and immunofluorescence staining were applied to explore the source and the expression level of properdin. The transcriptomic profile of properdin-activated primary microglia was depicted by transcriptome sequencing. Lentivirus was used for macrophage-inducible C-type lectin (Mincle) silencing in microglia. Conditioned medium from primary microglia was administered to primary cortex neurons to determine the neurotoxicity of microglia. A series of cellular and molecular biological techniques were used to evaluate the proinflammatory response, neuronal death, protein–protein interactions, and related signaling pathways, etc. Results The level of properdin was significantly increased, and brain-infiltrating neutrophils and macrophages were the main sources of properdin in the ischemic brain. Global and conditional myeloid knockout of properdin attenuated microglial overactivation and inflammatory responses at the acute stage of tMCAO in mice. Accordingly, treatment with recombinant properdin enhanced the production of proinflammatory cytokines and augmented microglia-potentiated neuronal death in primary culture. Mechanistically, recombinant properdin served as a novel ligand that activated Mincle receptors on microglia and downstream pathways to drive primary microglia-induced inflammatory responses. Intriguingly, properdin can directly bind to the microglial Mincle receptor to exert the above effects, while Mincle knockdown limits properdin-mediated microglial inflammation. Conclusion Properdin is a new medium by which infiltrating peripheral myeloid cells communicate with microglia, further activate microglia, and exacerbate brain injury in the ischemic brain, suggesting that targeted disruption of the interaction between properdin and Mincle on microglia or inhibition of their downstream signaling may improve the prognosis of ischemic stroke.

In recent years, tourism has flourished in ethnic areas of China as an important tool for rural revitalization and has become an important stimulus to promote the transformation of rural residents’ livelihood. However, rural residents in tourist villages in ethnic areas still face various livelihood risks, and academic literature has paid little attention to the mechanism’s substrate these household livelihood decision-making behaviors, and the differences in adaptive capacity and decision-making behaviors between mountainous minority villages and non-tourist villages are not sufficiently clear. Based on survey data of 284 rural residents in tourist and non-tourist villages in ethnic areas of western Sichuan, this study analyzed the adaptive capacity and differences of rural households using the comprehensive index method and Kruskal-Wallis test, and constructed a disordered multi-classification logistic regression model to explore the mechanism of rural residents’ livelihood behavior decisions. The results indicate that: (1) The adaptive capacity of rural residents in tourist villages in western Sichuan ethnic areas is slightly higher than that of non-tourist villages. (2) Tibetan households have the strongest adaptive capacity, and there is a significant difference between the adaptive capacity of Tibetan households and the rest of the minority households except Han Chinese. (3) The households with tourism-oriented livelihood strategy have the highest adaptive capacity, followed by households with tourism expansion livelihood strategy, while households with other types of livelihood strategies had the lowest livelihood adaptive capacity.(4) Compared to other types of livelihood strategies, when the policies are favorable and the ethnic culture is more primitive, rural residents are more inclined to choose tourism-oriented livelihood strategies, followed by tourism expansion livelihood strategies. When rural residents have higher adaptive capacity and more advantages in the market economy, they prefer tourism expansion strategies, followed by tourism-oriented strategies.

BackgroundLimited studies have explored the impact of the Omicron variant on SARS-CoV-2 infection, hospitalization, and associated factors among people living with HIV, particularly in China. The adjustment of preventive policies since December 2022 in China presents an opportunity to evaluate the real-world factors influencing SARS-CoV-2 infection and related hospitalization among people living with HIV. ObjectiveThis study aimed to investigate SARS-CoV-2 infection, hospitalization rates, and associated factors among people living with HIV following the adjustment of preventive policies from December 2022 to February 2023 in southeastern China. MethodsA cross-sectional telephone or web-based survey was conducted among people living with HIV in 5 cities in southeastern China from December 2022 to February 2023. Demographic information, SARS-CoV-2 infection and related hospitalization, and HIV-specific characteristics were collected from existing databases and special investigations. Multivariate logistic regression analyses were conducted to determine the associated factors for infection and hospitalization rates of SARS-CoV-2. Additionally, subgroup analyses were conducted for the association between vaccination and infection across different vaccination statuses and time since the last vaccination. ResultsAmong people living with HIV with a COVID-19 testing history, the SARS-CoV-2 infection rate was 67.13% (95% CI 65.81%-68.13%), whereas the hospitalization rate was 0.71% (95% CI 0.46%-0.97%). Factors such as age, latest CD4 cell count, latest HIV viral load, and transmission route were found to be associated with SARS-CoV-2 infection, while age, cancer, latest CD4 cell count, and latest HIV viral load were associated with SARS-CoV-2 hospitalization. In terms of SARS-CoV-2 vaccination, compared to unvaccinated people living with HIV, there was a lower infection rate among those who had been vaccinated for

Background Observational studies show that patients with chronic obstructive pulmonary disease (COPD) tend to be sedentary during leisure time. Physical activity (PA) may reduce the risk of COPD, but the causal relationship is unclear. We used a Mendelian randomisation (MR) method to elucidate the association of leisure sedentary behaviours (LSB) and PA with lung function and COPD.Methods Data on LSB (n=422 218), PA (n=608 595), COPD (n=299 929) and lung function (n=79 055) were obtained from the large-scale genome-wide association study. Causal inference used inverse variance-weighted, MR-Egger and weighted median. Sensitivity analysis was performed to assess heterogeneity and pleiotropy, and radial MR was used to distinguish outliers. The primary outcome was analysed by multifactorial MR adjusted for daily smoking.Results The inverse variance weighted analysis indicated that increased moderate-to-vigorous PA (MVPA) is associated with higher levels of forced vital capacity (FVC) (beta=0.27, 95% CI 0.12 to 0.42; p=3.51×10–4). For each increment of 2.8 hours in television watching, the odds of COPD were 2.25 times greater (OR=2.25; 95% CI 1.84 to 2.75; p=2.38×10–15). For early-onset COPD, the odds were 2.11 times greater (OR=2.11; 95% CI 1.56 to 2.85; p=1.06×10–6), and for late-onset COPD, the odds were 2.16 times greater (OR=2.16; 95% CI 1.64 to 2.84; p=3.12×10–8). Similarly, the odds of hospitalisation for COPD were 2.02 times greater with increased television watching (OR=2.02; 95% CI 1.59 to 2.55; p=4.68×10–9). Television watching was associated with lower FVC (beta=−0.19, 95% CI −0.28 to −0.10; p=1.54×10–5) and forced expiratory volume in the 1 s (FEV1) (beta=−0.16, 95% CI −0.25 to −0.08; p=1.21×10–4) levels. The results remained significant after adjustment for smoking.Conclusions Our study suggests a potential association with LSB, particularly television watching, is associated with higher odds of COPD and lower indices of lung function as measured continuously, including FEV1 and FVC. Conversely, an increase in MVPA is associated with higher indices of lung function, particularly reflected in increased FVC levels.

BackgroundThe underlying molecular pathways of idiopathic pulmonary fibrosis (IPF), a progressive lung condition with a high death rate, are still mostly unknown. By using microarray datasets, this study aims to identify new genetic targets for IPF and provide light on the genetic factors that contribute to the development of IPF.MethodWe conducted a comprehensive analysis of three independent IPF datasets from the Gene Expression Omnibus (GEO) database, employing R software for data handling and normalization. Our evaluation of the relationships between differentially expressed genes (DEGs) and IPF included differential expression analysis, expression quantitative trait loci (eQTL) analysis, and Mendelian Randomization(MR) analyses. Additionally, we used Gene Set Enrichment Analysis (GSEA) and Gene Ontology (GO)/Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis to explore the functional roles and pathways of these genes. Finally, we validated the results obtained for the target genes.ResultsWe identified 486 highly expressed genes and 468 lowly expressed genes that play important roles in IPF. MR analysis identified six significantly co-expressed genes associated with IPF, specifically C12orf75, SPP1, ZG16B, LIN7A, PPP1R14A, and TLR2. These genes participate in essential biological processes and pathways, including macrophage activation and neural system regulation. Additionally, CIBERSORT analysis indicated a unique immune cell distribution in IPF, emphasized the significance of immunological processes in the disease. The MR analysis was consistent with the results of the analysis of variance in the validation cohort, which strengthens the reliability of our MR findings.ConclusionOur findings provide new insights into the molecular basis of IPF and highlight the promise of therapeutic interventions. They emphasize the potential of targeting specific molecular pathways for the treatment of IPF, laying the foundation for further research and clinical work.

Heart failure is a continuously developing syndrome of cardiac insufficiency caused by diseases, which becomes a major disease endangering human health as well as one of the main causes of death in patients with cardiovascular diseases. The occurrence of heart failure is related to hemodynamic abnormalities, neuroendocrine hormones, myocardial damage, myocardial remodeling etc, lead to the clinical manifestations including dyspnea, fatigue and fluid retention with complex pathophysiological mechanisms. Currently available drugs such as cardiac glycoside, diuretic, angiotensin-converting enzyme inhibitor, vasodilator and β receptor blocker etc are widely used for the treatment of heart failure. In particular, natural products and related active ingredients have the characteristics of mild efficacy, low toxicity, multi-target comprehensive efficacy, and have obvious advantages in restoring cardiac function, reducing energy disorder and improving quality of life. In this review, we mainly focus on the recent advance including mechanisms and active ingredients of natural products for the treatment of heart failure, which will provide the inspiration for the development of more potent clinical drugs against heart failure.

Abstract Background Subjective cognitive decline (SCD) is a preclinical, asymptomatic stage of Alzheimer's disease (AD). Early identification and assessment of progressive SCD is crucial for preventing the onset of AD. Methods The study recruited 60 individuals diagnosed with SCD from the Alzheimer's Disease Neuroimaging Initiative (ADNI) database. Participants were divided into two groups: progressive SCD (pSCD, 23 individuals) and stable SCD (sSCD, 37 individuals) based on their progression to mild cognitive impairment (MCI) within 5 years. Cortical thickness, volumes of the hippocampus subfield, and subcortical regions were analyzed using T1‐weighted images and the FreeSurfer software. Network‐based statistics (NBS) were performed to compare structural covariance networks (SCNs) between the two groups. Results Results showed that the pSCD group showed significant atrophy of the hippocampal‐fimbria (p = .018) and cortical thinning in the left transverse temporal (cluster size 71.84 mm2, cluster‐wise corrected p value = .0004) and left middle temporal gyrus (cluster size 45.05 mm2, cluster‐wise corrected p value = .00639). The combination of these MRI features demonstrated high accuracy (AUC of 0.86, sensitivity of 78.3%, and specificity of 89.3%). NBS analysis revealed that pSCD individuals showed an increase in structural networks within the default mode network (DMN) and a decrease in structural connections between the somatomotor network (Motor) and DMN networks. Conclusion Our findings demonstrate that atrophy of the hippocampus and thinning of the cortex may serve as effective biomarkers for early identification of individuals at high risk of cognitive decline. Changes in connectivity within and outside of the DMN may play a crucial role in the pathophysiology of pSCD.

BackgroundIn recent years, the number and proportion of newly reported HIV/AIDS cases among older adults have increased dramatically. However, research on the pattern of temporal and spatial changes in newly reported HIV/AIDS among older adults remains limited. ObjectiveThis study analyzed the spatial and temporal distribution of HIV/AIDS cases and its influencing factors among older adults in Eastern China from 2004 to 2021, with the goal of improving HIV/AIDS prevention and intervention. MethodsWe extracted data on newly reported HIV/AIDS cases between 2004 and 2021 from a case-reporting system and used a Joinpoint regression model and an age-period-cohort model to analyze the temporal trends in HIV/AIDS prevalence. Spatial autocorrelation and geographically weighted regression models were used for spatial aggregation and influence factor analysis. ResultsA total of 12,376 participants with HIV/AIDS were included in the study. The newly reported HIV infections among older adults increased from 0.13 cases per 100,000 people in 2004 to 7.00 cases per 100,000 people in 2021. The average annual percent change in newly reported HIV infections was 28.0% (95% CI –21.6% to 34.8%). The results of the age-period-cohort model showed that age, period, and cohort factors affected the newly reported HIV infections among older adults. The newly reported HIV/AIDS cases among men who have sex with men (MSM) had spatial clustering, and the hotspots were mainly concentrated in Hangzhou. The disposable income of urban residents, illiteracy rate among people aged 15 years or older, and number of hospital beds per 1000 residents showed a positive association with the newly reported HIV infections among older MSM in the Zhejiang province. ConclusionsHIV/AIDS among older adults showed an increasing trend and was influenced by age, period, and cohort effects. Older MSM with HIV/AIDS showed regional clustering and was associated with factors such as the disposable income of urban residents, the illiteracy rate among people aged 15 years or older, and the number of hospital beds per 1000 people. Targeted prevention and control measures are needed to reduce HIV infection among those at higher risk.

Due to various factors, there is still a lack of effective neuroprotective agents for ischemic stroke in clinical practice. Neuroinflammation and neuronal apoptosis mediated by endoplasmic reticulum stress are some of the important pathological mechanisms in ischemic stroke. Linarin has been reported to have anti-inflammation, antioxidant, and anti-apoptotic effects in myocardial ischemia, osteoarthritis, and kidney disease. Whether it exerts neuroprotective functions in ischemic stroke has not been investigated. The results showed that linarin could reduce the infarct volume in cerebral ischemia animal models, improve the neurological function scores and suppress the expression of inflammatory factors mediating the NF-κB. Meanwhile, it could protect the neurons from OGD/R-induced-apoptosis, which was related to the PERK-eIF2α pathway. Our results suggested linarin could inhibit neuronal inflammation and apoptosis induced by endoplasmic reticulum stress. Furthermore, the neuroprotective effect of linarin may be related to the inhibition of AKR1B1. Our study offers new insight into protecting against ischemia-reperfusion injury by linarin treatment in stroke.

Multi-source data-fusion approaches have been developed for estimating regional precipitation. However, studies considering the specific upper limits of the improved gridded rainfall data for different fusion approaches are limited. Here, the potential ranges of accuracy improvement for satellite and reanalysis rainfall products were addressed using various machine learning fusion approaches, including multivariate linear regression (MLR), feedforward neural network (FNN), random forest (RF), and long short-term memory (LSTM), over the Chinese mainland. All four fusion methods reduce errors in the original precipitation products. The upper limits of accuracy improvement in terms of correlation coefficient (CC) and root mean square error (RMSE) were 30.65 and 15.27%, respectively. M-RF showed the best average CC (0.828) and RMSE (4.62 mm/day) in the four seasons. LSTM performed the best under light rainfall events, whereas MLR and RF exhibited better performance under moderate and heavy rainfall events, respectively. Overall, these results serve as a basis for the fusion approach and technique selection, based on the comprehensive validation in different climate zones, altitudes, and seasons over the Chinese mainland. HIGHLIGHTS Machine learning fusion approaches were used for precipitation product estimation.; Four different models were used: MLR, feedforward neural network, RF, and LSTM.; All four fusion methods reduced errors in the original precipitation products.; LSTM showed the best performance for light rainfall events.; MLR and RF performed better for moderate and heavy rainfall events.;

Abstract Fusarium oxysporum f. sp. cubense (Foc) causes Fusarium wilt of banana (Musa spp.), a notorious soil-borne vascular fungal disease threatening the global banana industry. Phytopathogens secrete effectors to suppress plant immunity. However, little is known about the effectors of Foc race 4 (Foc4). In this study, we built a streamlined screening system (candidate effector prediction, RNA-seq-based expression level analysis, and cell death manipulative activity assessment based on transient expression in Nicotiana benthamiana) to identify candidate virulence-related effectors. In total, 80 candidate effector genes (CEGs) differentially expressed during plant colonization were predicted; 12 out of 15 characterized CEGs, including FoSSP17, could suppress BAX-triggered programmed cell death (PCD) in N. benthamiana and were induced during the infection of plants. FoSSP17 encodes a novel protein conserved in the Fusarium genus. FoSSP17 gene deletion mutants were not affected in vegetative growth and conidiation but showed reduced virulence. Furthermore, the deletion mutants triggered higher expression levels of host defense-related genes including PR1, PR3, PR5, and PR10. Signal peptide activity assay and subcellular localization assay suggested that FoSSP17 is a conventional secretory protein that exerts cell-death-suppressive activity inside plant cells. In addition, FoSSP17 suppressed pattern-triggered immunity in plants by inhibiting reactive oxygen species (ROS) accumulation, reducing callose deposition, and suppressing the expression of NbLOX and NbERF1 genes related to jasmonic acid (JA)-pathway and ethylene (ET)-pathway, respectively. Overall, a systemic screening of Foc4 candidate effectors reveals that FoSSP17 contributes to the virulence of Foc4 and suppresses pattern-triggered immunity in plants.

Abstract Background Hypothyroidism (HT) and subclinical HT after radiotherapy is frequent in nasopharyngeal carcinoma (NPC) patients, results in negative impact on patients' quality of life. The percentage of thyroid volume receiving more than 40 Gy (V40) ≤ 85% was reported to be a useful dose constraint to adopt during intensity-modulated radiation therapy (IMRT) planning. This study aims to verify whether V40 ≤ 85% can be used as an effective dose constraint in IMRT planning in a randomized clinical trial. Methods This single-center 1:1 randomized clinical trial was conducted in Fujian province hospital between March 2018 and September 2022. All patients were treated with IMRT and randomized to induction chemo followed by concurrent chemo-IMRT or concurrent chemo-IMRT alone. Ninety-two clinically NPC patients were included in this study. The thyroid function tests were performed for all patients before and after radiation at regular intervals. Thyroid dose-constraint was defined as V40 ≤ 85%. The primary outcome in this study was subclinical HT. Results Median follow up was 34 months. Significant difference in the incidence of subclinical HT between the thyroid dose-constraint group and unrestricted group was observed (P = 0.023). The risk of subclinical HT in the thyroid dose-constraint group was lower than that in the unrestricted group (P = 0.022). Univariate and multivariate cox regression analysis indicated that thyroid dose-constraint was a protective effect of subclinical HT (HR = 0.408, 95% CI 0.184–0.904; HRadjusted = 0.361, 95% CI 0.155–0.841). Conclusion V40 ≤ 85% can be used as an effective dose constraint in IMRT planning to prevent radiation-induced subclinical HT.

To further clarify the proppant transport and placement law in multi-branched fractures induced by volume fracturing, proppant transport simulation experiments were performed with different fracture shapes, sand ratios, branched fracture opening time and injection sequence of proppants in varied particle sizes. The results show that the settled proppant height increases and the placement length decreases in main fractures as the fracturing fluid diverts gradually to the branched fractures at different positions. The flow rate in branched fractures is the main factor affecting their filling. The diverion to branched fractures leads to low flow rate and poor filling of far-wellbore branched fractures. The inclined fracture wall exerts a frictional force on the proppant to slow its settlement, thus enhancing the vertical proppant distribution in the fracture. The increase of sand ratio can improve the filling of near-wellbore main fracture and far-wellbore branched fracture and also increase the settled proppant height in main fracture. Due to the limitation of fracture height, when the sand ratio increases to a certain level, the increment of fracture filling decreases. When branched fracture is always open (or extends continuously), the supporting effect on the branched fractures is the best, but the proppant placement length within the main fractures is shorter. The fractures support effect is better when it is first closed and then opened (or extends in late stage) than when it is first opened and then closed (or extends in early stage). Injecting proppants with different particle sizes in a specific sequence can improve the placement lengths of main fracture and branched fracture. Injection of proppants in an ascending order of particle size improves the near-wellbore fracture filling, to a better extent than that in a descending order of particle size.

Abstract Background Obesity has been confirmed to be associated with infertility. However, the association between metabolically healthy obesity (MHO), a subset of obesity with no metabolic abnormalities, and female infertility has not yet been investigated. This study aimed to examine the association between MHO and the risk of female infertility among United States. Methods This study utilized a cross-sectional design and included 3542 women aged 20–45 years who were selected from the National Health and Nutrition Examination Survey (NHANES) 2013–2020 database. The association between MHO and the risk of infertility was evaluated using risk factor–adjusted logistic regression models. Results Higher BMI and WC were associated with increased infertility risk after adjusting for potential confounding factors (OR (95% CI): 1.04(1.02, 1.06), P = 0.001; OR (95% CI): 1.02 (1.01, 1.03), P

The shift towards green aviation necessitates the adoption of all-electric aircraft, marking an essential trend in the aviation industry. Distributed propulsion systems enhance aircraft flexibility and reliability, synchronously reducing performance demands and costs of single propulsion units compared to centralized propulsion system. The high reliability and lightweight characteristics of brushless DC motors have made them increasingly popular in distributed propulsion systems. Despite its advantage which helps to build efficient aircraft aerodynamic layout, there are more cables in the distributed propulsion system, which accounts for most of the weight of the aircraft. To address this, all-electric aircraft utilizes high-voltage power supply to reduce the current, so it uses SiC MOSFETs as power devices to improve its efficiency and heat dissipation. The speed controller in all-electric aircraft determines the efficiency and reliability of the propulsion unit. However, the traditional high-voltage speed controller poses challenges for aircraft maintenance because of high cost. Therefore, this paper emphasizes the significance of designing a low-cost, high-performance speed controller for all-electric aircraft. Challenges such as circuit interference, battery voltage fluctuation, and sampling noise affecting the high-voltage controller during operation are solved, respectively. First, to address the likelihood of mutual interference in the bridge arm, a self-bootstrapping voltage reduction drive mode is designed to turn off SiC MOSFET and enhance circuit anti-interference. Second, to solve the challenge of wide battery voltage fluctuation range and inconsistent controller output, an adaptive pulse width modulation (PWM) regulation mode for battery voltage is proposed, ensuring stable controller output. Finally, to counteract the impact of the comparator threshold on zero-crossing sampling, an electrical angle delay method based on delay compensation is designed to improve the efficiency of the brushless DC motor during operation. Experimental results show that the three solutions proposed in this paper are helpful to improve the anti-interference, stability, and efficiency of the controller in the high-voltage distributed electric propulsion system and contribute to reduce the cost and weight in the propulsion unit.

Background & Aims: Association studies have greatly refined the important role of the major histocompatibility complex (MHC) region in autoimmune hepatitis (AIH). However, the effects of human leucocyte antigen (HLA) polymorphisms on AIH are not well established. The aim of this study is to systematically characterise the association of MHC variants with AIH in our well-defined cohort of patients. Methods: We performed an imputation-based analysis on the extensive association observed within the MHC region using the Han-MHC reference panel, and tested the comprehensive associations of HLA polymorphisms with AIH in 1622 Chinese AIH type 1 patients and 10,466 population controls. Results: A total of 588 HLA variants were significantly associated with AIH, with HLA-B∗35:01 (p = 8.17 × 10−304; odds ratio [OR] = 7.32) contributing the strongest signal. Stepwise conditional analysis revealed additional independent signals at HLA-B∗08:01 (p = 1.35 × 10−33; OR = 4.26) and rs7765379 (p = 5.08 × 10−18; OR = 1.66). A strong link between the lead HLA variant and clinical phenotypes of AIH was observed: patients with HLA-B∗35:01 were less frequently positive for ANA and tended to have higher serum AST and ALT levels at diagnosis, but lower serum IgG levels. Conclusions: Our study reveals three novel and independent variants at HLA-B∗35:01, HLA-B∗08:01, and rs7765379 associated with AIH across the whole MHC region in the Han Chinese population. The findings illustrate the value of the MHC region in AIH and provide a new perspective for the immunogenetics of AIH. Impact and implications: This study revealed three novel and independent variants associated with autoimmune hepatitis across the whole major histocompatibility complex region in the Han Chinese population. These findings are significant in identifying autoantigens, providing insights into the activation of the autoimmune processes, and further advancing our understanding of the immunogenetic basis underlying autoimmune hepatitis.

Objectives This work aimed to analyse the risk factors for poor outcomes and mortality among patients with anterior large vessel occlusion (LVO) ischaemic stroke, despite successful recanalisation.Setting and participants This study conducted a secondary analysis among patients who underwent successful recanalisation in the CAPTURE trial. The trial took place between March 2018 and September 2020 at 21 sites in China. The CAPTURE trial enrolled patients who had an acute ischaemic stroke aged 18–80 years with LVO in anterior circulation.Interventions Thrombectomy was immediately performed using Neurohawk or the Solitaire FR after randomisation in CAPTURE trial. Rescue treatment was available for patients with severe residual stenosis caused by atherosclerosis.Primary and secondary outcome measures The primary goal was to predict poor 90-day survival or mortality within 90 days post-thrombectomy. Univariate analysis, using the χ2 test or Fisher’s exact test, was conducted for each selected factor. Subsequently, a multivariable analysis was performed on significant factors (p≤0.10) identified through univariate analysis using the backward selection logistic regression approach.Results Among the 207 recruited patients, 79 (38.2%) exhibited poor clinical outcomes, and 26 (12.6%) died within 90 days post-thrombectomy. Multivariate analysis revealed that the following factors were significantly associated with poor 90-day survival: age ≥67 years, internal carotid artery (ICA) occlusion (compared with middle cerebral artery (MCA) occlusion), initial National Institutes of Health Stroke Scale (NIHSS) score ≥17 and final modified Thrombolysis in Cerebral Infarction (mTICI) score 2b (compared with mTICI 3). Additionally, the following factors were significantly associated with mortality 90 days post-thrombectomy: initial NIHSS score ≥17, ICA occlusion (compared with MCA occlusion) and recanalisation with more than one pass.Conclusions Age, NIHSS score, occlusion site, mTICI score and the number of passes can be independently used to predict poor 90-day survival or mortality within 90 days post-thrombectomy.Trial registration number NCT04995757.

ABSTRACTObjective To understand the current situation and progress of nursing students’ professional self-concept, this review aimed to perform a general analysis of research related to the connotation of professional self-concept, measurement tools, influencing factors, effects, and intervention experiments.Methods Three databases (Web of Science, PubMed, and CNKI) were searched for relevant articles. Research articles that met specific criteria were included, with identified articles initially screened by title and keyword. Then the abstracts were screened for relevance, and the full text was read for validation before inclusion. Descriptive analysis was performed with relevant findings from data retrieved from various sources.Results Finally, 54 articles that met the criteria were included, which organised the connotation of self-concept of nursing speciality, and introduced six measurement scales, such as Professional Self-Concept of Nurses Instrument and Nurse’s Self-Concept Questionnaire. A total of 16 investigations on influencing factors were described, and the results showed that there were internal individual and external environmental factors. The professional self-concept was formed by analysing both factors. This paper described 17 effect surveys and found that professional self-concept had an important impact on students’ mental health, academic performance, and professional values, and so on. Eight intervention experiments including attribution training and hierarchical teaching were evaluated.Conclusions Research articles on the professional self-concept included in this review were rich. These articles clarified the basic connotation of the concept, developed relatively mature measurement tools, found many influencing factors and effects, and proposed effective intervention strategies. They were of great value for understanding the professional self-concept and could provide a reference for scholars to conduct relevant research and practice. It also presents research prospects in this field, aiming to inspire future research.

Abstract Background Anti-NMDA receptor (NMDAR) encephalitis is an autoimmune disease characterized by complex neuropsychiatric syndrome and cerebrospinal fluid (CSF) NMDAR antibodies. Triggering receptor expressed on myeloid cells 2 (TREM2) has been reported to be associated with inflammation of the central nervous system (CNS). Matrix metalloproteinase-9 (MMP9) and cluster of differentiation (CD44) were measured to evaluate blood‒brain barrier (BBB) permeability in anti-NMDAR encephalitis. The roles of microglial activation and BBB disruption in anti-NMDAR encephalitis are not well known. Findings In this work, we detected increased expression levels of CSF sTREM2, CSF and serum CD44, and serum MMP9 in anti-NMDAR encephalitis patients compared with controls. CSF sTREM2 levels were positively related to both CSF CD44 levels (r = 0.702, p

Magnetic resonance (MR) imaging is considered as a very powerful imaging modality in clinical examination, but the process of image acquisition and transmission will be affected by noise, resulting in the degradation of imaging quality. In this paper, based on the Laplacian prior sparsity constraint and the nonconvex second order total variation (TV) penalty, we propose a MR images denoising model which consists of three terms. Specifically, in the first term, we use the L2-norm as the fidelity term to control the proximity between the observed image and the recovered MR image. Then, we introduce the Laplacian sparse prior constraint as the second term to mitigate the staircase artifacts in the recovered image. In the third term, we adopt the nonconvex second-order TV penalty to preserve important textures and edges. Finally, we use the alternating direction method of multipliers to solve the corresponding minimization problem. Comparative experiments on clinical data demonstrate the effectiveness of our approach in terms of PSNR and SSIM values.

Abstract Aims Neutrophils play a pivotal in immunity and inflammation. We aim to investigate the prevalence of neutropenia in the United States. Methods In this cross-sectional study, participants from the National Health and Nutrition Examination Survey (NHANES) (2011–2018) were enrolled. Demographic information, hematologic measurements, smoking status of all participants were collected for all participants. All statistical analyses were performed utilizing the NHANES survey weights. Covariate-adjusted linear regression was used to compare hematologic indices in different population grouped by age, sex, ethnicity, and smoking. We also employed multivariate-logistic regression to estimate the weighted odds ratio with a 95% confidence interval and predict the neutropenia risk among. Results 32,102 participants from NHANES survey were included, represented 286.6 million multiracial population in the United States. Black participants had lower mean leukocyte count (mean difference (MD): 0.71 × 109/L; P

Abstract Stroke usually causes prolonged or lifelong disability, owing to the permanent loss of infarcted tissue. Although a variety of stem cell transplantation has been explored to improve neuronal defect behavior by enhancing neuroplasticity, it remains unknown whether the infarcted tissue can be reconstructed. We here cultured human cerebral organoids derived from human pluripotent stem cells (hPSCs) and transplanted them into the junction of the infarct core and the peri-infarct zone of NOD-SCID mice subjected to stroke. Months later, we found that the grafted organoids survived well in the infarcted core, differentiated into target neurons, repaired infarcted tissue, sent axons to distant brain targets, and integrated into the host neural circuit and thereby eliminated sensorimotor defect behaviors of stroke mice, whereas transplantation of dissociated single cells from organoids failed to repair the infarcted tissue. Our study offers a new strategy for reconstructing infarcted tissue via organoids transplantation thereby reversing stroke-induced disability.

Abstract Background Chronic cerebral ischemia induces white matter injury (WMI) contributing to cognitive decline. Both astrocytes and microglia play vital roles in the demyelination and remyelination processes, but the underlying mechanism remains unclear. This study aimed to explore the influence of the chemokine CXCL5 on WMI and cognitive decline in chronic cerebral ischemia and the underlying mechanism. Methods Bilateral carotid artery stenosis (BCAS) model was constructed to mimic chronic cerebral ischemia in 7–10 weeks old male mice. Astrocytic Cxcl5 conditional knockout (cKO) mice were constructed and mice with Cxcl5 overexpressing in astrocytes were generated by stereotactic injection of adeno-associated virus (AAV). WMI was evaluated by magnetic resonance imaging (MRI), electron microscopy, histological staining and western blotting. Cognitive function was examined by a series of neurobehavioral tests. The proliferation and differentiation of oligodendrocyte progenitor cells (OPCs), phagocytosis of microglia were analyzed via immunofluorescence staining, western blotting or flow cytometry. Results CXCL5 was significantly elevated in the corpus callosum (CC) and serum in BCAS model, mainly expressed in astrocytes, and Cxcl5 cKO mice displayed improved WMI and cognitive performance. Recombinant CXCL5 (rCXCL5) had no direct effect on the proliferation and differentiation of OPCs in vitro. Astrocytic specific Cxcl5 overexpression aggravated WMI and cognitive decline induced by chronic cerebral ischemia, while microglia depletion counteracted this effect. Recombinant CXCL5 remarkably hindered microglial phagocytosis of myelin debris, which was rescued by inhibition of CXCL5 receptor C-X-C motif chemokine receptor 2 (CXCR2). Conclusion Our study revealed that astrocyte-derived CXCL5 aggravated WMI and cognitive decline by inhibiting microglial phagocytosis of myelin debris, suggesting a novel astrocyte-microglia circuit mediated by CXCL5-CXCR2 signaling in chronic cerebral ischemia.

The UAV industry has witnessed an unprecedented boom in recent years. Among various kinds of UAV platforms, the vertical take-off and landing (VTOL) aircraft with fixed-wing configurations has received more and more attention due to its flexibility and long-distance flying abilities. However, due to the fact that the advance ratio of regular propeller systems during the cruise phase is significantly higher than that during the VTOL phase, a variable-pitch propeller system is proposed and designed which can be applied without additional propulsion mechanisms during both flying stages. Thus, a VTOL aircraft platform is proposed based on the propulsion system constructed of variable-pitch propellers, and appropriate control manners are precisely analyzed, especially during its VTOL phase. As a basic propulsion system, a nonlinear model for variable-pitch propellers is constructed, and an optimization-based control allocation module is developed because of its multi-solution and high-order characteristics. Finally, the objective function is designed according to the stability and energy consumption requirements. Simulation experiments demonstrate that the proposed controller is able to lower energy consumption and maintain the stability of the aircraft while tracking aggressive trajectories for large-scale VTOLs with noises at the same time.

In this paper, we investigate the effects of ambient air pollution (AAP) on the spread of influenza in an AAP-dependent dynamic influenza model. The value of this study lies in two aspects. Mathematically, we establish the threshold dynamics in the term of the basic reproduction number $ \mathcal{R}_0 $: If $ \mathcal{R}_0 < 1 $, the disease will go to extinction, while if $ \mathcal{R}_0 > 1 $, the disease will persist. Epidemiologically, based on the statistical data in Huaian, China, we find that, in order to control the prevalence of influenza, we must increase the vaccination rate, the recovery rate and the depletion rate, and decrease the rate of the vaccine wearing off, the uptake coefficient, the effect coefficient of AAP on transmission rate and the baseline rate. To put it simply, we must change our traveling plan and stay at home to reduce the contact rate or increase the close-contact distance and wear protective masks to reduce the influence of the AAP on the influenza transmission.

Abstract In this work, we develop a new type of mesoporous 2D N, B, and P codoped carbon network (NBP-CNW) arranged into high-order 3D nanotube arrays (NTAs), which are wrapped onto a flexible carbon fiber microelectrode, and this microelectrode is employed as a high-performance carbon-based nanocatalyst for electrochemical biosensing. The NBP-CNW-NTAs synthesized by a facile, controllable, ecofriendly and sustainable template strategy using ionic liquids as precursors possess a high structural stability, large surface area, abundant active sites, and effective charge transport pathways, which dramatically improve their electrocatalytic activity and durability in the redox reaction of cancer biomarker H2O2. Benefiting from these unique structural merits, superb electrochemical activity and good biocompatibility, the NBP-CNW-NTAs-modified microelectrode demonstrates excellent sensing performance toward H2O2 and is embedded in a homemade microfluidic electrochemical biosensor chip for the real-time tracking of H2O2 secreted from different live cancer cells with or without radiotherapy treatment, which provides a new strategy for distinguishing the types of cancer cells and evaluating the radiotherapeutic efficacy of cancer cells. Furthermore, the functional microelectrode is integrated into an implantable probe for the in situ detection of surgically resected human specimens to distinguish cancer tissues from normal tissues. These will be of vital significance for cancer diagnoses and therapy in clinical practice.

Abstract Ischemic stroke leads to white matter damage and neurological deficits. However, the characteristics of white matter injury and repair after stroke are unclear. Additionally, the precise molecular communications between microglia and white matter repair during the stroke rehabilitation phase remain elusive. In this current study, MRI DTI scan and immunofluorescence staining were performed to trace white matter and microglia in the mouse transient middle cerebral artery occlusion (tMCAO) stroke model. We found that the most serious white matter damage was on Day 7 after the ischemic stroke, then it recovered gradually from Day 7 to Day 30. Parallel to white matter recovery, we observed that microglia centered around the damaged myelin sheath and swallowed myelin debris in the ischemic areas. Then, microglia of the ischemic hemisphere were sorted by flow cytometry for RNA sequencing and subpopulation analysis. We found that CD11c+ microglia increased from Day 7 to Day 30, demonstrating high phagocytotic capabilities, myelin-supportive genes, and lipid metabolism associated genes. CD11c+ microglia population was partly depleted by the stereotactic injecting of rAAV2/6M-taCasp3 (rAAV2/6M-CMV-DIO-taCasp3-TEVp) into CD11c-cre mice. Selective depletion of CD11c+ microglia disrupted white matter repair, oligodendrocyte maturation, and functional recovery after stroke by Rotarod test, Adhesive Removal test, and Morris Water Maze test. These findings suggest that spontaneous white matter repair occurs after ischemic stroke, while CD11c+ microglia play critical roles in this white matter restorative progress.

Let $ \mu $ be a positive Borel measure on the interval $ [0, 1) $. The Hankel matrix $ \mathcal{H}_{\mu} = (\mu_{n, k})_{n, k\geq 0} $ with entries $ \mu_{n, k} = \mu_{n+k} $, where $ \mu_{n} = \int_{[0, 1)}t^nd\mu(t) $, formally induces the operator as follows: $ \mathcal{DH}_\mu(f)(z) = \sum\limits_{n = 0}^\infty\left(\sum\limits_{k = 0}^\infty \mu_{n,k}a_k\right)(n+1)z^n , \; z\in \mathbb{D}, $ where $ f(z) = \sum_{n = 0}^\infty a_nz^n $ is an analytic function in $ \mathbb{D} $. In this article, we characterize those positive Borel measures on $ [0, 1) $ such that $ \mathcal{DH}_\mu $ is bounded (resp., compact) from Bergman spaces $ \mathcal{A}^p $ into Hardy spaces $ H^q $, where $ 0 < p, q < \infty $.

BackgroundFatigue is a common source of distress for cancer survivors. The severity of cancer-related fatigue varies significantly, which may be due to individual differences in host factors.AimThis cross-sectional study aims to explore how demographic, oncological, sociological, psychological, and stress-related hormones levels interact to influence the distinct experiences of fatigue (Cancer-related fatigue [CRF] occurrence and fatigue degree).MethodsA cross-sectional study carried out at the oncology outpatient and ward department of Xiyuan Hospital of China Academy of Chinese Medical Sciences recruited 306 cancer patients between January 2021 to December 2021. General information, fatigue, psychological factors was evaluated by general information questionnaire, the Revised Piper’s Fatigue Scale-Chinese Version (RPFS-CV), and the self-report Hospital Anxiety and Depression Scale (HADS). Stress-related hormones were measured with chemiluminescent enzyme immunoassay (Zhengzhou Antobio).Results306 patients were included, 229 (74.8%) were diagnosed with CRF, including 94 (41.0%) with mild fatigue, 121 (52.8%) with moderate fatigue, and 14 (6.1%) with severe fatigue. Multivariate regression analysis showed that higher depression scores, aldosterone levels may increase the risk of CRF. Patients who are obese (Body mass index ≥ 28 kg/m2) may help to reduce the risk of CRF. Other contributing factors for increased levels of fatigue (p< 0.05) include being female, having anxiety, depression and high aldosterone levels.ConclusionThe research suggested that CRF was a common symptom in cancer survivors and pay attention to these influencing factors may help to better identify patients susceptible to fatigue and provide long-term, targeted interventions.

White matter hyperintensities (WMH) are widely observed in older adults and are closely associated with cognitive impairment. However, the underlying neuroimaging mechanisms of WMH-related cognitive dysfunction remain unknown. This study recruited 61 WMH individuals with mild cognitive impairment (WMH-MCI, n = 61), 48 WMH individuals with normal cognition (WMH-NC, n = 48) and 57 healthy control (HC, n = 57) in the final analyses. We constructed morphological networks by applying the Kullback-Leibler divergence to estimate interregional similarity in the distributions of regional gray matter volume. Based on morphological networks, graph theory was applied to explore topological properties, and their relationship to WMH-related cognitive impairment was assessed. There were no differences in small-worldness, global efficiency and local efficiency. The nodal local efficiency, degree centrality and betweenness centrality were altered mainly in the limbic network (LN) and default mode network (DMN). The rich-club analysis revealed that WMH-MCI subjects showed lower average strength of the feeder and local connections than HC (feeder connections: P = 0.034; local connections: P = 0.042). Altered morphological connectivity mediated the relationship between WMH and cognition, including language (total indirect effect: −0.010; 95 % CI: −0.024, −0.002) and executive (total indirect effect: −0.010; 95 % CI: −0.028, −0.002) function. The altered topological organization of morphological networks was mainly located in the DMN and LN and was associated with WMH-related cognitive impairment. The rich-club connection was relatively preserved, while the feeder and local connections declined. The results suggest that single-subject morphological networks may capture neurological dysfunction due to WMH and could be applied to the early imaging diagnostic protocol for WMH-related cognitive impairment.

ObjectiveMultiple myeloma (MM) is a highly characteristic tumor that is influenced by numerous factors that determine its prognosis. Studies indicate that the presence of circulating plasma cells (cPCs) is a detrimental factor that significantly impacts the prognosis of patients with MM.MethodsThis study retrospectively analyzed the prognostic value of cPCs quantified by 10-color flow cytometry in 145 newly diagnosed MM (NDMM) cases in the First Affiliated Hospital of Soochow University from November 2018 to February 2021. The study was approved by the Ethics Committee of the hospital (2021 No. 93).ResultsOf the 145 patients, 99 (68.2%) were detected cPCs. Through receiver operating characteristics (ROC) analysis, an optimal threshold of 0.165% was identified as a predictor for overall survival (OS). The median progression-free survival (PFS) was 33 months in patients with cPCs ≥0.165%, whereas those with cPCs

Synaptic dysfunction plays a crucial role in the pathogenesis of Alzheimer's disease (AD). α/β-hydrolase domain-containing 6 (ABHD6) contributes to synaptic dysfunctions, and ABHD6 inhibition has shown potential therapeutic value in neurological disorders. However, the role of ABHD6 in AD has not been fully defined. In this study, we demonstrated that adeno-associated virus (AAV) mediated shRNA targeting ABHD6 in hippocampal neurons attenuated synaptic dysfunction and memory impairment of APPswe/PS1dE9 (APP/PS1) mice, while it didn't affect the amyloid-beta (Aβ) levels and neuroinflammation in the brains. In addition, intraperitoneal injection of wwl70, a specific inhibitor of ABHD6, improved synaptic plasticity and memory function in APP/PS1 mice, which might attribute to the activation of endogenous cannabinoid signaling. Furthermore, wwl70 significantly decreased the Aβ levels and neuroinflammation in the hippocampus of AD mice, and enhanced Aβ phagocytized by microglia. In conclusion, for the first time our data have shown that ABHD6 inhibition might be a promising strategy for AD treatment, and wwl70 is a potential candidate for AD drug development pipeline.

The expansion in the repertoire of genes linked to thoracic aortic aneurysms (TAA) has revolutionised our understanding of the disease process. The clinical benefits of such progress are numerous, particularly helping our understanding of non-syndromic hereditary causes of TAA (HTAAD) and further refinement in the subclassification of disease. Furthermore, the understanding of aortic biomechanics and mechanical homeostasis has been significantly informed by the discovery of deleterious mutations and their effect on aortic phenotype. The drawbacks in genetic testing in TAA lie with the inability to translate genotype to accurate prognostication in the risk of thoracic aortic dissection (TAD), which is a life-threatening condition. Under current guidelines, there are no metrics by which those at risk for dissection with normal aortic diameters may undergo preventive surgery. Future research lies with more advanced genetic diagnosis of HTAAD and investigation of the diverse pathways involved in its pathophysiology, which will i) serve to improve our understanding of the underlying mechanisms, ii) improve guidelines for treatment and iii) prevent complications for HTAAD and sporadic aortopathies.