Taz/Tead1 Promotes Alternative Macrophage Activation and Kidney Fibrosis via Transcriptional Upregulation of Smad3.

Macrophage alternative activation is involved in kidney fibrosis. Previous researches have documented that the transcriptional regulators Yes-associated protein (Yap)/transcriptional coactivator with PDZ-binding motif (Taz) are linked to organ fibrosis. However, limited knowledge exists regarding the function and mechanisms of their downstream molecules in regulating macrophage activation and kidney fibrosis. In this paper, we observed that the Hippo pathway was suppressed in macrophages derived from fibrotic kidneys in mice. Knockout of Taz or Tead1 in macrophages inhibited the alternative activation of macrophages and reduced kidney fibrosis. Additionally, by using bone marrow-derived macrophages (BMDMs), we investigated that knockout of Taz or Tead1 in macrophages impeded both cell proliferation and migration. Moreover, deletion of Tead1 reduces p-Smad3 and Smad3 abundance in macrophages. And chromatin immunoprecipitation (ChIP) assays showed that Tead1 could directly bind to the promoter region of Smad3. Collectively, these results indicate that Tead1 knockout in macrophages could reduce TGFß1-induced phosphorylation Smad3 via transcriptional downregulation of Smad3, thus suppressing macrophage alternative activation and IRI-induced kidney fibrosis.

Eu3+-functionalized covalent organic framework for ratiometric fluorescence detection and adsorption of tetracycline and information steganography.

Functional materials with organic/inorganic composites as the main matrix and rare earth ion complexes as the guest have shown a very broad application prospect for antibiotic sensors. However, Eu3+-complex often relies on a single fluorescence response signal, which is susceptible to changes in the detection environment and cannot simultaneously detect and remove tetracycline (TC). Herein, green fluorescent covalent two-dimensional organic framework (COF-TD) is synthesized, followed by modification of Eu3+ to synthesize COF-TD@Eu3+. In the ratiometric sensor, Eu3+ serves as the recognition site and specific response probe for TC, while COF-TD is the fluorescence reference and carrier for Eu3+. Due to the antenna effect, TC enhances the red fluorescence of Eu3+, while the green fluorescence of COF-TD remains almost stable. Based on the change of fluorescence intensity and fluorescence color from green to red, the efficient ratiometric sensing can be finished in 1 min. The developed method shows high sensitivity with a detection limit of 0.3 µM and high selectivity to TC which makes the method applicable to detect TC in traditional Chinese medicine preparations. In addition, due to the high specific surface area of COFs and specific adsorption sites, COF-TD@Eu3+ also shows good performance for TC removal. The findings show that the maximum adsorption capacity is 137.3 mg g-1 and the adsorption equilibrium is reached in 30 min. Smartphone assisted COF-TD@Eu3+ for both ratiometric fluorescence detection and detecting the absorption of TC is proposed for the first time. The molecular cryptosteganography that transforms the selective response of COF-TD@Eu3+ to binary strings is anticipated to advance utilization of nanomaterials in logic sensing and information safety.

Top coal drawing law for an extra thick coal seam under the single round group drawing method.

To solve the problems of poor top coal drawing, lagging collapse, and difficulty in parallel operation of mining and drawing in extra-thick coal seams, considering the 8222 working face of the Tashan Mine as the engineering background, we first investigate the basic problems of fully mechanized top coal drawing mining in extra-thick coal seams using the single-round group drawing method (GDM). We then analyze the drawing law of top coal with different thicknesses under the single-round GDM from the aspects of top coal recovery (TCR) and drawing efficiency, coal loss mechanism, and the relation between TCR and gangue content (GC), providing a basis for determining the process parameters of GDM. Results indicate that as the top coal thickness increases, the number of drawing openings considerably influences drawing efficiency and top coal loss. And there is a notable thickness effect of the number of drawing openings on the top coal loss. There is a quantitative relationship among TCR, cumulative GC (CGC) and instantaneous GC (IGC), and CGC and TCR can be predicted based on the IGC. Consequently, theoretical analysis and numerical simulation results indicate that the optimal IGC threshold at the coal drawing openings between 31.2 and 40%. Through optimizing the coal drawing method and strictly controlling the IGC at the coal drawing openings on-site, the measured working face TCR increased from 75.25 to 90.12%, and CGC was controlled at approximately 9%. Meanwhile, the average coordination efficiency of mining and drawing time reaches 68.2%, effectively ensuring the construction of a coal mine with an annual output of 15 million tons.

Current state and influencing factors in airbag management among emergency department nurses: A multicenter study.

BACKGROUND: The emergency department (ED) plays a critical role in establishing artificial airways and implementing mechanical ventilation. Managing airbags in the ED presents a prime opportunity to mitigate the risk of ventilator-associated pneumonia. Nonetheless, existing research has largely overlooked the understanding, beliefs, and practical dimensions of airway airbag management among ED nurses, with a predominant focus on intensive care unit nurses. AIM: To investigate the current status of ED nurses' knowledge, beliefs, and practical behaviors in airway airbag management and their influencing factors. METHODS: A survey was conducted from July 10th to August 10th, 2023, using convenience sampling on 520 ED nurses from 15 tertiary hospitals and 5 sary hospitals in Shanghai. Pathway analysis was utilized to analyze the influencing factors. RESULTS: The scores for ED nurses' airway airbag management knowledge were 60.26 ± 23.00, belief was 88.65 ± 13.36, and behavior was 75.10 ± 19.84. The main influencing factors of airbag management knowledge included participation in specialized nurse or mechanical ventilation training, department, and work experience in the department. Influencing factors of airbag management belief comprised knowledge, department, and participation in specialized nurse or mechanical ventilation training. Primary influencing factors of airbag management behavior included knowledge, belief, department, participation in specialized nurse or mechanical ventilation training, and professional title. The belief in airbag management among ED nurses acted as a partial mediator between knowledge and behavior, with a total effect value of 0.513, and an indirect effect of 0.085, constituting 16.6% of the total effect. CONCLUSION: ED nurses exhibit a positive attitude toward airbag management with relatively standardized practices, yet there remains room for improvement in their knowledge levels. Nursing managers should implement interventions tailored to the characteristics of ED nurses' airbag management knowledge, beliefs, and practices to enhance their airbag management proficiency.

Enhanced Hybrid Vision Transformer with Multi-Scale Feature Integration and Patch Dropping for Facial Expression Recognition.

Convolutional neural networks (CNNs) have made significant progress in the field of facial expression recognition (FER). However, due to challenges such as occlusion, lighting variations, and changes in head pose, facial expression recognition in real-world environments remains highly challenging. At the same time, methods solely based on CNN heavily rely on local spatial features, lack global information, and struggle to balance the relationship between computational complexity and recognition accuracy. Consequently, the CNN-based models still fall short in their ability to address FER adequately. To address these issues, we propose a lightweight facial expression recognition method based on a hybrid vision transformer. This method captures multi-scale facial features through an improved attention module, achieving richer feature integration, enhancing the network's perception of key facial expression regions, and improving feature extraction capabilities. Additionally, to further enhance the model's performance, we have designed the patch dropping (PD) module. This module aims to emulate the attention allocation mechanism of the human visual system for local features, guiding the network to focus on the most discriminative features, reducing the influence of irrelevant features, and intuitively lowering computational costs. Extensive experiments demonstrate that our approach significantly outperforms other methods, achieving an accuracy of 86.51% on RAF-DB and nearly 70% on FER2013, with a model size of only 3.64 MB. These results demonstrate that our method provides a new perspective for the field of facial expression recognition.

Morvan's syndrome with hypercoagulable condition in a patient positive for anti-CASPR2 antibodies: A case report.

RATIONALE: The phenomenon of hypercoagulability has not been previously documented in individuals with Morvan's syndrome, especially in those associated with contactin-associated protein-like receptor 2 (CASPR2). PATIENT CONCERNS: A previously healthy 32-year-old Chinese male was admitted to the hospital with central and peripheral neurologic symptoms. The patient was tested positive for anti-CASPR2 antibodies, and also presented with an activated coagulation state on admission, characterized by a low activated partial thromboplastin time and a high platelet count. With gradual improvement of clinical symptoms, activated partial thromboplastin time, and platelet count returned to normal. Simultaneously, anti-CASPR2 antibody titers significantly decreased and eventually became undetectable. DIAGNOSES: The patient was diagnosed as Morvan's syndrome with positive anti-CASPAR2 antibodies accompanied with hypercoagulable state. INTERVENTIONS: Plasmapheresis was administered to improve the symptoms combined with prednisolone acetate therapy. OUTCOMES: The patient experienced complete resolution of all symptoms during hospitalization and generally recovery after 2 months of discharge. LESSONS: Emphasis should be directed towards hypercoagulability in individuals diagnosed with Morvan's syndrome, particularly those presenting with positive anti-CASPR2 antibodies. Anticoagulant therapy may represent a novel therapeutic approach for individuals afflicted with Morvan's syndrome and exhibiting positivity for anti-CASPR2 antibodies.

Concurrent manipulation of competitive mechanisms to construct glutathione-stabilized gold nanocluster-based dual-channel molecular classifier for metal ions detection and information steganography.

Understanding charge transport in metal ion-mediated glutathione-stabilized gold nanoclusters (GSH-Au NCs) has proved difficult due to the presence of various competitive mechanisms, such as electron transfer (ET) and aggregation induction effect (AIE). In this paper, we present a dual-channel fluorescence (FL) and second-order Rayleigh scattering (SRS) sensing method for high-throughput classification of metal ions, relying on the competition between ET and AIE using GSH-Au NCs. The SRS signals show significant enhancement when Pb2+, Ag+, Al3+, Cu2+, Fe3+, and Hg2+ are present, as a result of the aggregation of GSH-Au NCs. Notably, the fluorescence signal exhibits the opposite trend. The FL intensities of GSH-Au NCs are enhanced by Pb2+, Ag+, and Al3+ through the AIE mechanism, while they are quenched by Cu2+, Fe3+, and Hg2+, which is dominated by the ET mechanism. By employing principal component analysis and hierarchical cluster analysis, these signals are transformed into unique fingerprints and Euclidean distances, respectively, enabling successful distinction of six metal ions and their mixtures with a low detection limit of 30 nM. This new strategy has successfully addressed interference from impurities in the testing of real water samples, demonstrating its strong ability to detect multiple metal ions. Impressively, we have achieved molecular cryptosteganography, which involves encoding, storing, and concealing information by transforming the selective response of GSH-Au NCs to binary strings. This research is anticipated to advance utilization of nanomaterials in logic sensing and information safety, bridging the gap between molecular sensors and information systems.

Isomerization reactions of metal vinylidene units.

Isomerization reactions of unsaturated molecules offer an efficient strategy in atom-economical synthesis. Although isomerization reactions of unsaturated organic and organometallic compounds, such as alkenes, alkynes, and metal carbynes, have been achieved, those of metal vinylidene units that contain cumulated double bonds have never been reported. Herein, we inaugurally discovered isomerization reactions of metal vinylidene units via protonation and deprotonation reactions of metal carbenes. Experimental and theoretical investigations indicate that the electrical characteristics of substituents on the rings play a crucial role in controlling the formation of metal vinylidene units. The isomerization reactions of metal vinylidene units were driven by thermodynamic forces. Moreover, one of the angles at metal vinylidenes was found as 126.9°, representing the smallest angle in metal vinylidenes and the first cyclic 4d transition metal (Ru) vinylidene complex was successfully isolated. These investigations unveil novel structures and reactivity for metal vinylidenes, offering a fresh perspective on the isomerization reactions of unsaturated molecules containing cumulative unsaturated bonds.

Dynamic interfacial electrostatic energy harvesting via a single wire.

Spontaneously occurred electrostatic breakdown releases enormous energy, but harnessing the energy remains a notable challenge due to its irregularity and instantaneity. Here, we propose a revolutionary method that effectively harvests the energy of dynamic interfacial electrostatic breakdown by simply imbedding a conductive wire (diameter, 25 micrometers) beneath dielectric materials to regulate the originally chaotic and distributed electrostatic energy resulted from contact electrification into aggregation, effectively transforming mechanical energy into electricity. A point-charge physical model is proposed to explain the power generation process and output characteristics, guide structural design, and enhance output performance. Furthermore, a quantified triboelectric series including 72 dielectric material pairs is established for materials choice and optimization. In addition, a high voltage of over 10 kilovolts is achieved using polytetrafluoroethylene and polyethylene terephthalate. This work opens a door for effectively using electrostatic energy, offering promising applications ranging from novel high-voltage power sources, smart clothing, and internet of things.

A Multi-Scale Natural Scene Text Detection Method Based on Attention Feature Extraction and Cascade Feature Fusion.

Scene text detection is an important research field in computer vision, playing a crucial role in various application scenarios. However, existing scene text detection methods often fail to achieve satisfactory results when faced with text instances of different sizes, shapes, and complex backgrounds. To address the challenge of detecting diverse texts in natural scenes, this paper proposes a multi-scale natural scene text detection method based on attention feature extraction and cascaded feature fusion. This method combines global and local attention through an improved attention feature fusion module (DSAF) to capture text features of different scales, enhancing the network's perception of text regions and improving its feature extraction capabilities. Simultaneously, an improved cascaded feature fusion module (PFFM) is used to fully integrate the extracted feature maps, expanding the receptive field of features and enriching the expressive ability of the feature maps. Finally, to address the cascaded feature maps, a lightweight subspace attention module (SAM) is introduced to partition the concatenated feature maps into several sub-space feature maps, facilitating spatial information interaction among features of different scales. In this paper, comparative experiments are conducted on the ICDAR2015, Total-Text, and MSRA-TD500 datasets, and comparisons are made with some existing scene text detection methods. The results show that the proposed method achieves good performance in terms of accuracy, recall, and F-score, thus verifying its effectiveness and practicality.

Intervention Research of Narrative Nursing on the Psychological Problems of the Caregivers Under the Normalization of the Epidemic.

Objective: The research aims to investigate the impact of narrative nursing on the psychological well-being of nursing personnel in the context of the normalization of epidemic. Methods: A cohort of 170 frontline nursing staff at our institution was selected for this clinical study from January 1st to October 31st of 2023. The Symptom Checklist-90 (SCL-90) was employed to evaluate the psychological health of these frontline nursing personnel, compared to the standard norms for nurses in mainland China. Employing a randomized selection method, the cohort was divided into two groups: a control group (85 cases) receiving conventional nursing care and a research group (85 cases) receiving narrative nursing care. The duration of nursing intervention in both groups was set at 12 weeks. Various aspects of psychological well-being, work-related stress, psychological resilience, post-traumatic stress disorder, occupational burnout, job satisfaction, and coping strategies were assessed both before and after the nursing intervention. Results: Among the positive projects of 170 frontline nursing personnel, 32 exhibited positive symptoms, resulting in a positive rate of 18.82%. With the exception of the paranoia dimension score, the scores for other dimensions in the SCL-90 scale within the clinical group were notably higher than those observed in the norm group (P < .05). Among the ten items with the highest frequency of positive symptoms, anxiety, obsessive-compulsive symptoms, and hostility were identified as the most prevalent psychological health issues among frontline nursing personnel. Post-nursing intervention, the research group exhibited lower scores in dimensions other than paranoia in the SCL-90 scale compared to the control group (P < .05). The research group also displayed lower scores in SAS, SDS, SRQ, PCL-C, MBI-HSS and higher scores in CD-RISC and JWS post-intervention (P < .05). In the post-nursing intervention phase, the research group demonstrated lower scores in negative coping and higher scores in positive coping as per the SCSQ scale in comparison to the control group (P < .05). Conclusions: Amidst the ongoing normalization of the epidemic, the psychological well-being of frontline nursing staff was lower than the established norms for nurses in mainland China. Notably, somatization, anxiety, and depression emerged as predominant manifestations. Narrative nursing was identified as an effective intervention to enhance nursing personnel's psychological well-being and coping strategies, ultimately regulating negative emotions, reducing post-traumatic stress disorder and occupational burnout, reducing stress levels, and enhancing job satisfaction and psychological resilience.

Blood chromium and lung function among Chinese young adults: A comprehensive analysis based on epidemiology and metabolomics.

Chromium (Cr) exposure is associated with various respiratory system diseases, but there are limited studies investigating its impact on lung function in young adults. The Cr exposure-related metabolomic changes are not well elucidated. This study recruited 608 students from a university in Shandong Province, China in 2019. We used cohort design fitted with linear mixed-effects models to assess the association between blood Cr concentration and lung function. In addition, we performed metabolomic and lipidomic analyses of baseline serum samples (N = 582) using liquid chromatography-mass spectrometry. Two-step statistical analysis (analysis of variance and mixed-linear effect model) was used to evaluate the effect of blood Cr exposure on metabolites. We found that blood Cr was associated with decreased lung function in young adults. Each 2-fold increase in blood Cr concentrations was significantly associated with decreased FEV1 and FVC by 35.26 mL (95 % CI: -60.75, -9.78) and 38.56 mL (95 % CI: -66.60, -10.51), respectively. In the metabolomics analysis, blood Cr exposure was significantly associated with 14 key metabolites. The changed metabolites were mainly enriched in six pathways including lipid metabolism, amino acid metabolism, and cofactor vitamin metabolism. Blood Cr may affect lung function through oxidative stress and inflammation related pathways.

Lung-Specific mRNA Delivery Enabled by Sulfonium Lipid Nanoparticles.

Among various mRNA carrier systems, lipid nanoparticles (LNPs) stand out as the most clinically advanced. While current clinical trials of mRNA/LNP therapeutics mainly address liver diseases, the potential of mRNA therapy extends far beyond─yet to be unraveled. To fully unlock the promises of mRNA therapy, there is an urgent need to develop safe and effective LNP systems that can target extrahepatic organs. Here, we report on the development of sulfonium lipid nanoparticles (sLNPs) for systemic mRNA delivery to the lungs. sLNP effectively and specifically delivered mRNA to the lungs following intravenous administration in mice. No evidence of lung and systemic inflammation or toxicity in major organs was induced by sLNP. Our findings demonstrated that the newly developed lung-specific sLNP platform is both safe and efficacious. It holds great promise for advancing the development of new mRNA-based therapies for the treatment of lung-associated diseases and conditions.

Probabilistic Scatter Plots for visualizing carbohydrate and lipid metabolism states in Non-Alcoholic Fatty Liver Disease.

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) is characterized by dysregulated carbohydrate and lipid metabolism, which are its primary features. However, traditional biochemical markers pose challenges for accurate quantification and visualization of metabolic states. This study introduces a novel states-based approach for accurate NAFLD assessment. METHODS: Joint probabilistic distributions of triglycerides and glycemia were constructed using dual-indicator Probabilistic Scatter Plots based on clinical data (healthy controls: n = 1978; NAFLD patients: n = 471). Patterns of metabolic dysregulation were revealed through comparison against healthy profiles. Self-organizing feature mapping (SOFM) clustered the distributions into four dominant states. RESULTS: Healthy scatter plots demonstrated a distinct progression of sub-states ranging from very healthy to sub-healthy. In contrast, NAFLD plots exhibited shifted probability centers and outward divergence. SOFM clustering classified the states into: mild; moderate and severe lipid metabolism disorders; and carbohydrate metabolism disorders. CONCLUSIONS: Probabilistic Scatter Plots, when combined with SOFM clustering, facilitate a states-based quantification of NAFLD metabolic dysregulation. This method integrates multi-dimensional biochemical indicators and their distributions into a cohesive framework, enabling precise and intuitive visualization for personalized diagnosis and monitoring of prognostic developments.

Dopamine-modified cobalt spinel nanoparticles as an active catalyst for the acidic oxygen evolution reaction.

The development of efficient non-noble metal electrocatalysts for the oxygen evolution reaction (OER) under acidic conditions remains a critical challenge. Herein, we report a N-doped carbonaceous component-engineered Co3O4 (NCEC) catalyst synthesized via the sol-gel method. Dopamine hydrochloride (DA)-derived nitrogen-doped carbonaceous components were found to boost the OER performance of Co3O4. The optimized catalyst can reach an overpotential as low as 330 mV in 1 M H2SO4 at a current density of 10 mA cm-2 and maintains a good long-term stability of 60 hours. In particular, we found that the thermodynamic overpotential was inversely proportional to the content of oxidized N and pyridinic N, whereas it was directly proportional to the pyrrolic-N content. Our experiments and density functional theory (DFT) calculations confirm that the optimized catalyst exhibits enhanced charge transfer and the oxidized N species on Co3O4 is responsible for the high catalytic activity. Our study suggests that the performance of NCEC in acidic media can be further optimized by enhancing the content of oxidized N species.

Aqueous Topological Synthesis of Au@semiconductor Core-Shell Nanocrystals with Morphology and Composition Engineering.

Core-shell nanocrystals (C-S NCs) are an essential class of materials whose structural engineering has attracted wide attention due to their tunable optical and electrical properties, especially noble metal@semiconductor (NMS) C-S NCs with flexible plasmon-exciton coupling. Due to their diverse critical applications, especially aqueous biological applications, herein we propose an aqueous topological strategy enabled by cation exchange reactions (CER) to synthesize various plasmonic Au@semiconductor C-S NCs, in which environmentally friendly triphenylphosphine (TPP) is used as an initiator instead of inflammable tributyl phosphine (TBP). The introduction of the milder, solid TPP facilitated a new aqueous CER strategy for synthesizing Au@semiconductor NCs with tailored chalcogenide compositions and morphologies. For example, the as-synthesized Au@ZnS C-S NRs had better absorption and biocompatibility and exhibited excellent photodynamic therapy efficacy.

Association of Serum Unsaturated Fatty Acid Patterns with the Risk of Diabetic Nephropathy.

Introduction: Unsaturated fatty acids play an essential role in the progression of diabetic nephropathy (DN). However, previous studies were mainly focused on the role of individual unsaturated fatty acid. The serum unsaturated fatty acid patterns (FAPs) in patients with DN remain to be determined. Methods: A total of 135 patients with DN (DN group) and 322 patients with type II diabetes without nephropathy (non-DN group) were included in this study. Clinical data, serum levels of unsaturated fatty acids, and other laboratory indicators were collected. Multivariate logistic regression was applied to identify risk factors for serum unsaturated fatty acid level in both groups. Serum unsaturated fatty acids were subjected to factor analysis to identify distinct FAPs. Multivariable logistic regression was employed to assess the risk of DN associated with different serum FAPs. Results: After adjusting for confounders, three types of unsaturated fatty acid including C20:5 (eicosapentaenoic acid [EPA]), C22:6 (docosahexaenoic acid [DHA]), and C22:5 n-3 (docosapentaenoic acid n-3) were significantly associated with DN in the population. The odds ratios (ORs) (95% confidence interval [CI]) of DN were 0.583 (0.374, 0.908), 0.826 (0.716, 0.954), and 0.513 (0.298, 0.883), respectively. Factor analysis revealed five major FAPs, among which FAP2 (enriched with EPA and DHA) exhibited a significant inverse association with DN. In the multivariate-adjusted model, the OR (95% CI) was 0.678 (0.493, 0.933). Additionally, a combination of DHA and EPA enriched in FAP2 further decreased extracellular matrix production induced by transforming growth factor beta 1 in podocytes and tubular cells. Conclusions: Our findings suggest that FAP2 which is enriched with DHA and EPA is associated with a reduced risk of DN. This highlights the potential of targeting FAP2 for the patients with DN.

The association between non-alcoholic fatty liver disease and urinary incontinence among adult females in the United States.

BACKGROUND AND OBJECTIVES: Non-alcoholic fatty liver disease (NAFLD) and urinary incontinence (UI) are both highly prevalent and age-related diseases. Nevertheless, the link between NAFLD and UI is unclear. Hence, the study was designed to evaluate the association between the NAFLD and UI (including UI types) in a nationally representative sample of United States (US) female adults. METHODS: We conducted this study used data from U.S. female adults in the National Health and Nutrition Examination Survey (NHANES) 2017-March 2020 (pre-pandemic) cycles. The diagnosis of NAFLD is based on Vibration controlled transient elastography (VCTE) and absence of know liver diseases and significant alcohol consumption. The diagnosis and types of UI were assessment using a self-report questionnaire. Multivariable logistic regression models were used to analyze the association between NALFD and UI. Stratified analyses based on age, obesity, race, educational level, married status, PIR, and smoking status were conducted. RESULTS: Of the 2149 participants, the mean (95% CI) age was 53.9 (52.7-55.0), 686 (61.1%) were Non-Hispanic White. UI was significantly more common in participants with NAFLD [490 (64.7%)] than those without NAFLD [552 (44.9%)]. Adjusted for age, race/ethnicity, marital status, educational level, family poverty income ratio (PIR) status, alanine aminotransferase (ALT), aspartate aminotransferase (AST), smoking status, obesity, type 2 diabetes mellitus (T2DM), hypertension and insulin resistance (IR) in a multivariable logistic regression model, NALFD were associated with UI [OR: 1.93, 95%CI 1.23-3.02, P = 0.01] and urge UI [OR: 1.55, 95%CI 1.03-2.33, P = 0.03], while patients with NAFLD did not show an increased odds in stress UI and mixed UI when compared with those without NAFLD subject (P > 0.05). In the subgroup analyses, NAFLD remained significantly associated with UI, particularly among those participants without obesity (OR: 2.69, 95% CI 1.84-4.00) and aged ≥ 60 years (OR: 2.20, 95% CI 1.38-3.51). CONCLUSIONS: Among US female adults, NAFLD has a strong positive correlation with UI. Given that NAFLD is a modifiable disease, these results may help clinicians to target female patients with NAFLD for treatments and interventions that may help prevent the occurrence of UI and reduce the symptoms of UI.

Tumor-neutrophil cross talk orchestrates the tumor microenvironment to determine the bladder cancer progression.

The immune landscape of bladder cancer progression is not fully understood, and effective therapies are lacking in advanced bladder cancer. Here, we visualized that bladder cancer cells recruited neutrophils by secreting interleukin-8 (IL-8); in turn, neutrophils played dual functions in bladder cancer, including hepatocyte growth factor (HGF) release and CCL3highPD-L1high super-immunosuppressive subset formation. Mechanistically, c-Fos was identified as the mediator of HGF up-regulating IL-8 transcription in bladder cancer cells, which was central to the positive feedback of neutrophil recruitment. Clinically, compared with serum IL-8, urine IL-8 was a better biomarker for bladder cancer prognosis and clinical benefit of immune checkpoint blockade (ICB). Additionally, targeting neutrophils or hepatocyte growth factor receptor (MET) signaling combined with ICB inhibited bladder cancer progression and boosted the antitumor effect of CD8+ T cells in mice. These findings reveal the mechanism by which tumor-neutrophil cross talk orchestrates the bladder cancer microenvironment and provide combination strategies, which may have broad impacts on patients suffering from malignancies enriched with neutrophils.

Vascular endothelial-derived SPARCL1 exacerbates viral pneumonia through pro-inflammatory macrophage activation.

Inflammation induced by lung infection is a double-edged sword, moderating both anti-viral and immune pathogenesis effects; the mechanism of the latter is not fully understood. Previous studies suggest the vasculature is involved in tissue injury. Here, we report that expression of Sparcl1, a secreted matricellular protein, is upregulated in pulmonary capillary endothelial cells (EC) during influenza-induced lung injury. Endothelial overexpression of SPARCL1 promotes detrimental lung inflammation, with SPARCL1 inducing 'M1-like' macrophages and related pro-inflammatory cytokines, while SPARCL1 deletion alleviates these effects. Mechanistically, SPARCL1 functions through TLR4 on macrophages in vitro, while TLR4 inhibition in vivo ameliorates excessive inflammation caused by endothelial Sparcl1 overexpression. Finally, SPARCL1 expression is increased in lung ECs from COVID-19 patients when compared with healthy donors, while fatal COVID-19 correlates with higher circulating SPARCL1 protein levels in the plasma. Our results thus implicate SPARCL1 as a potential prognosis biomarker for deadly COVID-19 pneumonia and as a therapeutic target for taming hyperinflammation in pneumonia.