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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.

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.

Gas control in the upper corner of the natural coal mining face with high gas is always a difficult problem that troubles the safe production of the working face. Among them, a high gas-prone natural coal mining face with ground air leakage is more likely to cause gas and CO to exceed limits in the corner of the working surface and is difficult to control. The traditional treatment methods often have some problems; for example, it is easy to increase air leakage in the gob with the method of gas extraction in the gob, which is not conducive to the prevention and control of spontaneous combustion of coal in the gob. At present, the more effective method is the pressure-equalization method. However, the pressure-equalization measures need to establish a complex pressure-equalization system, and close cooperation between the systems is required; once the system power fails or equipment failure occurs, the pressure-equalization state changes randomly, and it is easy to cause gas over-limits and other faults. Therefore, this paper presents a new method to control gas in the gob of a coal seam by pumping the gob of the upper-adjacent layer, using the negative pressure of pumping, and balancing the negative pressure of the upper-adjacent layer and the gob of the coal seam to form a new pressure-equalization relationship. This method can prevent the toxic and harmful gases in the goaf of the upper-adjacent layer from escaping into the passageway of the gob of the local coal seam, reduce the air leakage in the goaf, and benefit the gas control and spontaneous coal combustion prevention in the goaf.

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.

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.

Rodents have been confirmed as hosts of various vector-borne zoonotic pathogens and are important for the maintenance of these microbes in nature. However, surveillance for zoonotic pathogens is limited for many wild rodent species in China, so our knowledge of pathogen ecology, genetic diversity, and the risk of cross-species transmission to humans is limited. In this study, 165 spleen samples of Daurian ground squirrels (Spermophilus dauricus) were collected from Weichang Manchu and the Mongolian Autonomous County of Hebei Province, China, and Rickettsia, Bartonella, and Anaplasma were identified by DNA detection using polymerase chain reaction (PCR). Sequence analysis identified eight bacterial pathogens: R. raoultii, R. sibirica, Candidatus R. longicornii, B. washoensis, B. grahamii, B. jaculi, A. capra, and Candidatus Anaplasma cinensis. Co-infection of B. grahamii and R. raoultii in one sample was observed. Our results demonstrated the genetic diversity of bacteria in Daurian ground squirrels and contributed to the distribution of these pathogens. Six species, A. capra, R. raoultii, R. sibirica, Candidatus R. longicornii, B. washoensis, and B. grahamii, are known to be pathogenic to humans, indicating a potential public health risk to the local human population, especially to herders who frequently have close contact with Daurian ground squirrels and are thus exposed to their ectoparasites. [ABSTRACT FROM AUTHOR]

Introduction: Laparoendoscopic single-site inguinal lymphadenectomy (LESS-IL), a minimally invasive technique, has been reported in patients with vulvar or vaginal cancer regarding its safety and feasibility. However, the long-term outcomes, especially oncologic outcomes, are still lacking. We aimed to evaluate the long-term outcomes of LESS-IL to confirm its safety further. Patients and Methods: Data were prospectively collected from patients with vulvar or vaginal cancer who underwent LESS-IL at our institution between July 2018 and June 2021. The patients were followed up for at least 12 months. All procedures were performed according to treatment standards. Short- and long-term complications and oncologic outcomes were analysed. Results: A total of 16 patients undergoing 28 LESS-IL procedures were identified, amongst whom 4 underwent unilateral LESS-IL. The median numbers of excised groin lymph nodes were 9.0 (6.5-11.8) and 10.5 (8.3-12.0) in each left and right groin, respectively. Short-term complications occurred in 4 (25%) patients, including 18.7% lymphocele and 6.3% wound infection. Long-term complications regarding lower-limb lymphoedema appeared in 6 (37.5%) patients. Most short- and long-term complications were Clavien-Dindo 1 or 2, accounting for 90% of all post-operative issues. After a median follow-up of 27 (21.3-35.8) months, only 1 (6.3%) patient had isolated inguinal recurrence at 13 months postoperatively. No local or distant recurrence occurred. Conclusion: Our results suggest that LESS-IL is associated with little incidence of complications and promising oncologic outcomes, further demonstrating the safety and feasibility of the LESS-IL technique in patients requiring IL. [ABSTRACT FROM AUTHOR]

Background: Dogs and cats are the hosts of many vector-borne human pathogens that can be transmitted to humans. Given their direct and intimate contact with humans, companion dogs and cats are considered direct sentinels of vector-borne human pathogens. However, limited information is currently available regarding canine and feline zoonotic pathogens in China. This study detected canine and feline vector-borne human pathogens to better understand the potential risk to humans. Methods: Blood samples were collected from 275 domestic companion animals (117 dogs and 158 cats) living in Tianjin city, China, and the presence of DNA from Anaplasma, Babesia, Bartonella, and Rickettsia was detected by seminested polymerase chain reaction (PCR). The PCR products of the expected size were sequenced, and these newly generated sequences were subjected to BLASTN, nucleotide identity, and phylogenetic analyses. Results: A total of 24 blood samples tested positive for vector-borne pathogens in companion dogs and cats in Tianjin city, China, with a relatively low positive rate of 8.7%. Specifically, seven human pathogens, including Rickettsia raoultii, Candidatus Rickettsia jingxinensis, Rickettsia sibirica, Rickettsia felis, Babesia venatorum, Bartonella tribocorum, and Bartonella Henselae, were identified. In addition, Anaplasma ovis with zoonotic potential and Candidatus A. cinensis were detected. Conclusion: Our results indicate substantial genetic diversity in the vector-borne human pathogens circulating in companion dogs and cats. Interventions based on "One Health" should be taken to reduce the potential risks of contracting infection from companion dogs and cats in Tianjin, China. [ABSTRACT FROM AUTHOR]

Background: The interrelation between intestinal polyps, metabolic syndrome (MetS), and colorectal cancer (CRC) is a critical area of study. This research focuses on pinpointing potential molecular targets to understand the link between intestinal polyp formation, metabolic irregularities, and CRC progression. Methods: We examined clinical samples from patients with intestinal polyps coexisting with MetS and compared them with samples from patients with standard intestinal polyps. Transcriptome sequencing and public database analysis were employed to identify significant pathways and genes. These targets were then validated through immunohistochemistry (IHC). Following the RNA interference of key target expression, a series of experiments, including the cell counting kit-8 assay, colony formation, wound healing, and Transwell assays, were conducted. Results: Comparative analysis revealed 75 up-regulated and 61 down-regulated differentially expressed genes (DEGs) in the MetS polyp group vs. the control. Kyoto encyclopedia of genes and genomes (KEGG) pathway enrichment suggested these DEGs were primarily associated with cell cycle and mitosis. Integration with comparative toxicogenomics database (CTD) and the cancer genome atlas (TCGA) databases highlighted 44 key CRC-related genes. Protein interaction networks indicated connections of purkinje cell protein 4 (PCP4), olfactomedin 1 (OLFM1), fibronectin 1 (FN1), and transforming growth factor beta 3 (TGF-β3) with the mitogen-activated protein kinase (MAPK) pathway. Tumor correlation studies suggested higher risk associations with FN1, PCP4, and TGF-β3, while OLFM1 was identified as a lower risk gene. Immunohistochemical analysis revealed a decrease in OLFM1 in MetS-associated intestinal polyps. Upon interference with OLFM1 in polyp epithelial cells, there was a significant enhancement in cell proliferation, colony formation, and cell migration and invasion capabilities. Conclusion: Our study highlights a significant decrease in OLFM1 expression in MetS-associated intestinal polyps. And, this reduction in OLFM1 is associated with enhanced cell proliferation, colony formation, and increased cell migration and invasion capabilities. These findings underscore the reduced OLFM1 expression in MetS-associated intestinal polyps may play a crucial role in promoting tumorigenic processes in colorectal pathology. Further research on OLFM1 may provide valuable insights into understanding and targeting MetS-associated intestinal polyps. [ABSTRACT FROM AUTHOR]

Background: Endovascular treatment for patients with symptomatic nonacute middle cerebral artery occlusion remains clinically challenging, and proof of a beneficial effect on functional outcome is lacking. We aim to evaluate the effectiveness and safety of endovascular recanalization for patients with symptomatic nonacute middle cerebral artery occlusion. Methods: Ninety‐eight patients with symptomatic atherosclerotic nonacute middle cerebral artery occlusion were divided into drug treatment groups (42) and endovascular treatment groups (56). The rate of recanalization, peri‐procedural complications, and follow‐up results were evaluated. Results: Among the 56 patients who received endovascular treatment, 53 (94.6%) achieved successful recanalization. The rate of peri‐procedural complications was 7.1% (4/56), and the death rate was 1.8% (1/56). Any stroke within 90 days was 7.1% (4/56). Among the 42 patients in drug treatment group, any stroke within 90 days was 19.0% (8/42), death rate was 0. Conclusion: Among patients with symptomatic nonacute middle cerebral artery occlusion with a short length of occlusion and a moderate‐to‐good collateral circulation, endovascular treatment seems to be safe. And endovascular treatment could reduce the recurrence rate of stroke. [ABSTRACT FROM AUTHOR]

Abstract Currently, collaborative distribution models have not reached the optimal state of carbon emissions. The cost of additional low-carbon expenditures and the problem of carbon data verification have led to the lack of motivation for reducing emissions among collaborative distribution enterprises. Therefore, how to incentivize them to adopt the low-carbon model is crucial for achieving low-carbon goal. By relying on a government-led digital platform, this paper designs a dual low-carbon incentive strategy to encourage enterprise-alliance to adopt a low-carbon distribution model. In this paper, we first construct an evolutionary game model of the government, enterprise-alliance and end-users; then we explore the conditions of the three-party equilibrium evolution strategy by solving the model and analyzing the stability; and finally, we conduct simulation validation and results analysis with the help of MATLAB. In summary, we found that government punishment is more effective at regulating enterprise-alliance than reward. End-users’ behavior is affected by the costs they need to bear, and they no longer support enterprise-alliance to carry out collaborative low-carbon distribution above a certain threshold.

Abstract Background Tuberculosis (TB) remains a global public health event of great concern, however epidemic data on TB covering entire areas during the special period of the COVID-19 epidemic have rarely been reported. We compared the dissemination and multidrug-resistance patterns of Mycobacterium tuberculosis complex (MTBC) in the main urban area of Luoyang City, China (including six municipal jurisdictions) and nine county and township areas under its jurisdiction, aimed to establish the epidemiology of TB in this region and to provide reference for precision anti-TB in places with similar settings. Methods From 2020 to 2022, sputum samples were collected from 18,504 patients with confirmed, suspected and unexcluded TB in 10 designated TB medical institutions. Insertion sequence 6110 was amplified by PCR (rpoB gene detection if necessary) to confirm the presence of MTBC. PCR-positive specimens were analyzed by multicolor melting curve analysis to detect multidrug resistance. Results Among the 18,504 specimens, 2675 (14.5%) were MTBC positive. The positive rate was higher in the main urban area than in the county and township areas (29.8% vs. 10.9%, p 60 years were the largest group infected with MTBC in the main urban area, compared with individuals aged

Abstract Nuclear factor erythroid 2-related factor 2 (NRF2) hyperactivation has been established as an oncogenic driver in a variety of human cancers, including non-small cell lung cancer (NSCLC). However, despite massive efforts, no specific therapy is currently available to target NRF2 hyperactivation. Here, we identify peptidylprolyl isomerase A (PPIA) is required for NRF2 protein stability. Ablation of PPIA promotes NRF2 protein degradation and blocks NRF2-driven growth in NSCLC cells. Mechanistically, PPIA physically binds to NRF2 and blocks the access of ubiquitin/Kelch Like ECH Associated Protein 1 (KEAP1) to NRF2, thus preventing ubiquitin-mediated degradation. Our X-ray co-crystal structure reveals that PPIA directly interacts with a NRF2 interdomain linker via a trans-proline 174-harboring hydrophobic sequence. We further demonstrate that an FDA-approved drug, cyclosporin A (CsA), impairs the interaction of NRF2 with PPIA, inducing NRF2 ubiquitination and degradation. Interestingly, CsA interrupts glutamine metabolism mediated by the NRF2/KLF5/SLC1A5 pathway, consequently suppressing the growth of NRF2-hyperactivated NSCLC cells. CsA and a glutaminase inhibitor combination therapy significantly retard tumor progression in NSCLC patient-derived xenograft (PDX) models with NRF2 hyperactivation. Our study demonstrates that targeting NRF2 protein stability is an actionable therapeutic approach to treat NRF2-hyperactivated NSCLC.

Sarcasm represents a language form where a discrepancy lies between the literal meanings and implied intention. Sarcasm detection is challenging with unimodal text without clearly understanding the context, based on which multimodal information is introduced to benefit detection. However, current approaches only focus on modeling text–image incongruity at the token level and use the incongruity as the key to detection, ignoring the significance of the overall multimodal features and textual semantics during processing. Moreover, semantic information from other samples with a similar manner of expression also facilitates sarcasm detection. In this work, a semantic enhancement framework is proposed to address image–text congruity by modeling textual and visual information at the multi-scale and multi-span token level. The efficacy of textual semantics in multimodal sarcasm detection is pronounced. Aiming to bridge the cross-modal semantic gap, semantic enhancement is performed by using a multiple contrastive learning strategy. Experiments were conducted on a benchmark dataset. Our model outperforms the latest baseline by 1.87% in terms of the F1-score and 1% in terms of accuracy.

Obstructive sleep apnea hypopnea syndrome (OSAHS) in adults is a common sleep-breathing disorder closely associated with hypertension, diabetes, cardiovascular diseases, and other health concerns. Despite its widespread impact on global health, the screening and diagnosis of OSAHS is still not widely available in clinical practice. In this context, the U.S. Preventive Services Task Force (USPSTF) has recently released updated recommendations for adult OSAHS screening to help more people identify and treat potential sleep-breathing disorders. This article interprets the latest recommendations and consider the practical situation in China, providing reference for OSAHS screening of adults in China.

Abstract Quantum effects in photosynthetic energy transport in nature, especially for the typical Fenna-Matthews-Olson (FMO) complexes, are extensively studied in quantum biology. Such energy transport processes can be investigated as open quantum systems that blend the quantum coherence and environmental noise, and have been experimentally simulated on a few quantum devices. However, the existing experiments always lack a solid quantum simulation for the FMO energy transport due to their constraints to map a variety of issues in actual FMO complexes that have rich biological meanings. Here we successfully map the full coupling profile of the seven-site FMO structure by comprehensive characterisation and precise control of the evanescent coupling of the three-dimensional waveguide array. By applying a stochastic dynamical modulation on each waveguide, we introduce the base site energy and the dephasing term in coloured noise to faithfully simulate the power spectral density of the FMO complexes. We show our photonic model well interprets the phenomena including reorganisation energy, vibrational assistance, exciton transfer and energy localisation. We further experimentally demonstrate the existence of an optimal transport efficiency at certain dephasing strength, providing a window to closely investigate environment-assisted quantum transport.

Highlights A strategy based on metal-organic decomposition is proposed to enhance the tube-tube interactions of carbon nanotubes (CNTs). The robust tube-tube interactions of CNTs enhance both EMI shielding performance and mechanical properties of CNT film. This innovative approach provides an effective way to obtain high-performance CNT film.

Background: Ovarian cancer, as a highly malignant tumor, features the critical involvement of tumor-associated fibroblasts in the ovarian cancer tissue microenvironment. However, due to the apparent heterogeneity within fibroblast subpopulations, the specific functions of these subpopulations in the ovarian cancer tissue microenvironment remain insufficiently elucidated. Methods: In this study, we integrated single-cell sequencing data from 32 ovarian cancer samples derived from four distinct cohorts and 3226 bulk RNA-seq data from GEO and TCGA-OV cohorts. Utilizing computational frameworks such as Seurat, Monocle 2, Cellchat, and others, we analyzed the characteristics of the ovarian cancer tissue microenvironment, focusing particularly on fibroblast subpopulations and their differentiation trajectories. Employing the CIBERSORTX computational framework, we assessed various cellular components within the ovarian cancer tissue microenvironment and evaluated their associations with ovarian cancer prognosis. Additionally, we conducted Mendelian randomization analysis based on cis-eQTL to investigate causal relationships between gene expression and ovarian cancer. Results: Through integrative analysis, we identified 13 major cell types present in ovarian cancer tissues, including CD8+ T cells, malignant cells, and fibroblasts. Analysis of the tumor microenvironment (TME) cell proportions revealed a significant increase in the proportion of CD8+ T cells and CD4+ T cells in tumor tissues compared to normal tissues, while fibroblasts predominated in normal tissues. Further subgroup analysis of fibroblasts identified seven subgroups, with the MMP11+Fib subgroup showing the highest activity in the TGFβ signaling pathway. Single-cell analysis suggested that oxidative phosphorylation could be a key pathway driving fibroblast differentiation, and the ATRNL1+KCN + Fib subgroup exhibited chromosomal copy number variations. Prognostic analysis using a large sample size indicated that high infiltration of MMP11+ fibroblasts was associated with poor prognosis in ovarian cancer. SMR analysis identified 132 fibroblast differentiation-related genes, which were linked to pathways such as platinum drug resistance. Conclusions: In the context of ovarian cancer, fibroblasts expressing MMP11 emerge as the primary drivers of the TGF-beta signaling pathway. Their presence correlates with an increased risk of adverse ovarian prognoses. Additionally, the genetic regulation governing the differentiation of fibroblasts associated with ovarian cancer correlates with the emergence of drug resistance.