Understanding the Roles of Thiophenol-Ligated Ag-Based Nanoclusters on TiO2 during the Catalytic Hydrogenation of Nitroarenes.

Elucidating the correlations between the core structure of atomically precise nanoclusters and their catalytic activities is fundamentalfor exploring highly efficient nanocatalysts. Herein, a series of Ag-based nanoclusters protected by 2,4-dimethylphenylthiophenol (specifically Ag4Pd2(SPhMe2)8 and Ag24M(SPhMe2)18 where M = Ag, Pd, and Pt) were synthesized and deposited on TiO2 supports as heterogeneous catalysts for the selective hydrogenation of nitroarenes with NaBH4 as the reductant. It was found that Ag4Pd2(SPhMe2)8 could spontaneously lose its ligands during catalysis, leading to the formation of polydispersed AgPd nanoparticles. This transformation endows the system with extraordinary activity for driving the hydrogenation of nitroarenes. However, the Ag24M (M = Ag, Pd, and Pt) systems, maintain their core structures during catalysis. They follow the generally reported ligand-mediated hydride-involved process, with catalytic activities depending on the central atom (Pt > Pd > Ag), which affects the hydride transferred from the nanoclusters to the reactant to regulate the catalysis.

The Gut Microbiota Mediates the Protective Effects of Spironolactone on Myocardial Infarction.

Myocardial infarction (MI) is a type of cardiovascular disease that influences millions of human beings worldwide and has a great rate of mortality and morbidity. Spironolactone has been used as a critical drug for the treatment of cardiac failure and it ameliorates cardiac dysfunction post-MI. Despite these findings, whether there is a relationship between the therapeutic effects of spironolactone and the gut microorganism after MI has not been determined. In our research, we used male C57BL/6 J mice to explore whether the gut microbiota mediates the beneficial function of spironolactone after myocardial infarction. We demonstrated that deletion of the gut microbiota eliminated the beneficial function of spironolactone in MI mice, displaying exacerbated cardiac dysfunction, cardiac infarct size. In addition, the gut microbiota was altered by spironolactone after sham or MI operation in mice. We also used male C57BL/6 J mice to investigate the function of a probiotic in the myocardial infarction. In summary, our findings reveal a precious role of the gut flora in the therapeutic function of spironolactone on MI.

Comparison of efficacy and safety of different suction pressure for speeding non-ventilated lung collapse in uniport video-assisted thoracoscopic surgery: a randomized-controlled trial.

BACKGROUND: The bronchial suction has been applied in speeding lung collapse. Low suction pressure may not speed lung collapse, but high pressure causes occult lung injury. The aim of the study was to explore efficacy and safety of different suction pressure for speeding lung collapse. METHODS: Eighty-four subjects undergoing uniport video-assisted thoracoscopic surgery (VATS) were randomly assigned for non-suction (Group 0), -10 cmH2O suction pressure (Group - 10), and - 30 cmH2O suction pressure (Group - 30). The primary outcome were the lung collapse scores (LCS) at 0 min (T0) after the visualization of the lung using a 10-point visual analogue scale and area under the curve (AUC) of LCS over time. The secondary outcomes included disconnection from the ventilator, the assessment of occult lung injury using NOS-3 expression, histologic scores of lung injury, and lung W/D weight ratio, intraoperative hypoxemia, the incidence of perioperative pulmonary complications. RESULTS: Both the LCS at T0 and AUC analysis showed that compared with Group 0, Group - 10 and Group - 30 significantly achieved good lung collapse (P < 0.05), but no difference between Group - 10 and Group - 30. Four patients in Group 0 were treated with disconnection maneuver. The assessment of occult lung injury showed no differences. CONCLUSIONS: Applying - 10 cmH2O suction pressure for 1 min when pleural incision is a relatively safe method to promote lung collapse without the occurrence of occult lung injury. TRIAL REGISTRATION: Chinese Clinical Trial Registry number, ChiCTR2200062991. Registered on 26/08/2022.

Analysis of microRNAs and the microRNA-messengerRNA regulatory network in chronic alcohol exposure.

Introduction: Chronic alcoholism is one of the most common neurological diseases in modern society. However, the key mechanisms underlying learning and memory impairments caused by chronic alcohol exposure remain unclear. In this study, a microRNA-messenger RNA (miRNA-mRNA) network was constructed to explore the potential function of key genes in chronic alcohol exposure, their effects on the hippocampus, and their mechanisms which facilitate brain injury in mice. Methods: The Morris water maze test was used to assess the learning ability of mice in each group. Mitochondrial ATPase activity and H2S levels in the hippocampi of mice were determined. Differentially expressed miRNAs and mRNAs in the mouse hippocampus were identified using second-generation sequencing. Using the TargetScan, miRTarBase, and miRDB databases, we predicted miRNA target genes and constructed a miRNA-mRNA regulatory network. Furthermore, using the Gene Ontology and KEGG databases we performed functional enrichment and protein-protein interaction analyses. Real-time quantitative polymerase chain reaction (qPCR) and other methods were employed to verify the mRNA expression of related genes. Results: The Morris water maze test revealed that mice exposed to chronic alcohol exhibited a significantly reduced learning ability compared to the control group (p < 0.05). Compared with the control group, the activity of mitochondrial ATPase in the hippocampal tissue of alcohol-treated mice was significantly decreased (p < 0.01), suggesting brain injury. In the model group, H2S significantly increased in the mice hippocampi (p < 0.01), indicating that chronic alcohol exposure could activate cystathionineß-synthase (CBS) and catalyze the mass formation of H2S, suggesting brain injury. A total of 208 differentially expressed miRNAs and 377 differentially expressed mRNAs were screened through bioinformatic analysis. Enrichment analysis indicated that the main pathways were involved in neurodegeneration and regulation of the Wnt signaling pathway. The PCR detected a significant downregulation in the expressions of FOS and EGR1 genes. Discussion: Consequently, chronic alcohol exposure may regulate the expression of FOS and EGR1 in the hippocampus through miR-222-3p, miR-132-3p, miR-212-3p, and miR-191-5p, reduce the activity of hippocampal mitochondrial ATPase, activate CBS, catalyze the large amount of H2S formation, and destroy the mitochondrial structure, resulting in decreased learning ability. Our findings revealed valuable genes and miRNAs for the study of chronic alcohol exposure.

Therapeutic effect of iridoid and xanthone glycosides components extracted from Swertia Mussotti on calculous cholecystitis and its clinical complications by targeting COX2.

Swertia Mussotti is used as febrifuge, analgesic and to treat calculous cholecystitis, however, the underling mechanism remains unclear. This study investigates the therapeutic effect of the active fraction named iridoid and xanthone glycoside (IXG) extracted from S. mussotii on six animal models related to calculous cholecystitis and its complications, and to explore its potential target proteins. Four main compounds including swertiamarin (STR), sweroside (SRS), gentiopicroside (GPS) and mangiferin (MGR) were identified from the IXG by UHPLC-TOF-MS. The in vivo experiments results confirmed that IXG significantly decreased the level of total bilirubin (TBIL), direct bilirubin (DBIL) and cyclooxygenase-2 (COX2) in calculous cholecystitis. IXG treatment dramatically reduced the number of twists and the time of clicking foot in 2nd phase induced by glacial acetic acid and formalin, however, no effect was showed on central pain established by hot plate test. IXG also significantly decreased the anal temperature induced by yeast and 2,4-dinitrophenol. These results indicated that IXG alleviate calculous cholecystitis and its clinical symptom. In addition, IXG suppressed the expression of Prostaglandin E2 (PGE2) in vitro. Mechanistically, COX2 was identified as the direct target of IXG in RAW264.7 cells, and downregulated the protein levels of COX2. The results confirmed that IXG ameliorates calculous cholecystitis and its clinical symptom (pain and fever) by suppressing the production of PGE2 through targeting COX2.

[Establishment of an Engineered Bacterial Membrane Biomimetic Nanodrug Delivery System and Its Role in the Treatment of Glioma]. / å·¥ç¨‹åŒ–ç»†èŒè†œä»¿ç”Ÿçº³ç±³è¯ç‰©é€’é€ç³»ç»Ÿçš„å»ºç«‹åŠåœ¨è„‘èƒ¶è´¨ç˜¤æ²»ç–—ä¸­çš„ä½œç”¨ç ”ç©¶.

Objective: To develop engineered bacterial membrane biomimetic nanoparticles, Angiopep-2 E. coli membrane (ANG-2 EM)@PDA-PEI-CpG (ANG-2 EM@PPC), for efficient targeted drug delivery in the treatment of glioma, and to provide theoretical and technical support for targeted glioma therapy. Methods: The expression of inaX-N-angiopep-2 engineered bacteria was constructed in the laboratory, and ANG-2 EM was obtained through lysozyme treatment and ultrafiltration centrifugation. ANG-2 EM@PPC was prepared by ultrasonication of bacterial membranes. Western blotting, agarose gel electrophoresis, and transmission electron microscopy (TEM) were used to verify the preparation. Particle size and Zeta potential were measured to investigate the stability of ANG-2 EM@PPC. Regarding cell experiments, CCK-8 assay was performed to determine the effect of ANG-2 EM@PPC on the survival rate of neutrophils. A flow chamber model was designed and constructed, and the uptake efficiency of neutrophils was measured by flow cytometry to investigate the hitchhiking efficiency of ANG 2 EM@PPC on neutrophils in inflammatory environment. Neutrophil death patterns were characterized by fluorescence microscopy, and flow cytometry and Western blotting were performed to examine neutrophil apoptotic bodies and the proportion of apoptotic bodies produced. Regarding animal experiments, a mouse model of in situ glioma was established and the inflammatory environment of tumor tissue was verified. The tumor model mice were divided into three groups, including DiR group, EM@PPC group, and ANG-2 EM@PPC group (all n=3), which were injected with DiR, ANG-2 EM@PDA-PEI-CpG, and EM@PDA-PEI-CpG via the tail vein, respectively (all at 10 mg/kg). Fluorescence images of organs and the brain were used to examine the distribution of the three formulations in vivo and in the brain. The tumor model mice were further divided into PBS group, PDA group, PC group, PPC group, EM@PPC group, and ANG-2 EM@PPC group (all n=4), which were injected with PBS, PDA, PC, PPC, EM@PPC, and ANG-2 EM@PPC injected via the tail vein, respectively (all at 10 mg/kg). Imaging was performed in vivo to observe tumor regression, and the survival rate and body mass of mice were measured to evaluate in vivo pharmacodynamics. TUNEL staining (brain tissue) and HE staining (brain, heart, liver, spleen, lung and kidney tissues) were performed to evaluate the therapeutic effect. Results: The results of TEM showed successful preparation of engineered bacterial membrane biomimetic nanoparticles, with PPC exhibiting a distinct shell-core structure and a shell thickness of about 8.2 nm. Due to the coating of ANG-2 EM, the shell thickness of ANG-2 EM@PPC increased to about 9.6 nm, with a clear bacterial membrane layer on the surface. Stability was maintained for at least one week. ANG-2 EM@PPC had no significant effect on the activity of neutrophils according to the findings from the CCK-8 assay. Flow cytometry showed that ANG-2 EM@PPC uptake is enhanced in activated neutrophils and hitchhiking on neutrophils was more efficient in the stationary state than that in the flowing condition. Compared with the EM@PPC group, the neutrophil hitchhiking ability of the ANG-2 EM@PPC group was enhanced (uptake efficiency 24.9% vs. 31.1%). Fluorescence microscopy showed that ANG-2 EM@PPC changed the death pathway of neutrophils from neutrophil extracellular traps-osis (NETosis) to apoptosis. Western blot confirmed the production of neutrophil apoptotic bodies, and flow cytometry showed that the production rate was as high as 77.7%. Animal experiments showed that there was no significant difference in the distribution of engineered bacterial membrane biomimetic nanoparticles in the organs (heart, liver, spleen, lungs, and kidney) in the DiR group, the EM@PPC gropu, and the ANG-2 EM@PPC group (P>0.05), but there was higher distribution in the brain tissue in EM@PPC and ANG-2 EM@PPC groups compared to the DiR group (P<0.05). Engineered bacterial membrane biomimetic nanoparticles crossed the blood-brain barrier (BBB), and exhibited high affinity to and internalization by neutrophils located in brain tumors. Compared with PBS, PDA, PC, and PPC groups, the survival rate and body mass of mice in the EM@PPC group were improved, tumor fluorescence intensity was weakened, and apoptotic cells were increased. These trends were even more prominent in the ANG-2 EM@PPC group. No abnormality was found in the HE staining of any group. Conclusion: An ANG-2 EM@PPC nanodelivery system with inflammation response characteristics was successfully prepared, capable of crossing BBB and targeting the tumor inflammatory microenvironment to improve the anti-glioma efficacy. This study provides a new drug delivery strategy for glioma treatment and offers a new idea for targeted drug delivery in the non-invasive inflammatory microenvironments in other central nervous system diseases.

Derivation and external validation of mass spectrometry-based proteomic model using machine learning algorithms to predict plaque rupture in patients with acute coronary syndrome.

BACKGROUND: A poor prognosis is associated with atherosclerotic plaque rupture (PR) despite after conventional therapy for patients with acute coronary syndrome (ACS). Timely identification of PR improves the risk stratification and prognosis of ACS patients. METHODS: A derivation cohort of 110 patients with ACS who underwent pre-intervention optical coherence tomography (OCT) were matched 1:1 to the PR and intact fibrous cap (IFC) groups according to traditional risk factors. Candidate PR proteins were identified via mass spectrometry (MS)-based proteomics using unbiased machine learning methods and were further validated by enzyme-linked immunosorbent assay (ELISA) in an external validation cohort of 85 patients with ACS. The performance of candidate biomakers was assessed using the receiver operating characteristic curve analysis. RESULTS: 1121 proteins were identified and 535 filtered proteins were used for analysis. Nine candidate proteins were screened by five machine learning algorithms. Three proteins (APOC3, RAB39A, and KNG1) were significantly different between the PR and IFC in validation cohort. The performance of plasm APOC3, RAB39A, and KNG1 for differentiating PR and IFC was superior to that of the conventional biomarkers and risk factors. CONCLUSION: The proteins (APOC3, RAB39A, and KNG1) serve as a potential novel diagnostic tool to identify PR in ACS patients.

Anterior High-Resolution Optical Coherence Tomography in the Diagnosis and Therapeutic Monitoring of Ocular Surface Squamous Neoplasia.

Ocular surface squamous neoplasia (OSSN) is the most common tumor of the ocular surface, ranging from mild dysplasia to invasive squamous carcinoma. Traditionally, the diagnosis of OSSN relies on histopathological confirmation followed by a full-thickness biopsy. However, in the past two decades, the therapeutic approach to OSSN has shifted from surgical intervention to topical chemotherapy regimens in clinical settings. This shift emphasizes the need for less invasive or non-invasive methods to diagnose ocular surface pathologies. Among various imaging devices, commercially available high-resolution optical coherence tomography (HR-OCT) has emerged as a powerful tool for the characterization of OSSN. HR-OCT provides an in vivo, cross-sectional view of ocular surface lesions, offering an "optical biopsy" for OSSN with high sensitivity and specificity. It provides valuable information in differentiating intraepithelial or invasive OSSN from other benign lesions. Additionally, HR-OCT can be used to monitor the response to topical chemotherapy and to detect subclinical OSSN during follow-up visits. In this article, the scanning protocol for image acquisition is presented, and image interpretation for OSSN is outlined. This standardized, practical, and reproducible approach is recommended in clinical workflows and is expected to assist clinicians in the management of OSSN.

ATF3 coordinates the survival and proliferation of cardiac macrophages and protects against ischemia-reperfusion injury.

Cardiac resident MerTK+ macrophages exert multiple protective roles after ischemic injury; however, the mechanisms regulating their fate are not fully understood. In the present study, we show that the GAS6-inducible transcription factor, activating transcription factor 3 (ATF3), prevents apoptosis of MerTK+ macrophages after ischemia-reperfusion (IR) injury by repressing the transcription of multiple genes involved in type I interferon expression (Ifih1 and Ifnb1) and apoptosis (Apaf1). Mice lacking ATF3 in cardiac macrophages or myeloid cells showed excessive loss of MerTK+ cardiac macrophages, poor angiogenesis and worse heart dysfunction after IR, which were rescued by the transfer of MerTK+ cardiac macrophages. GAS6 administration improved cardiac repair in an ATF3-dependent manner. Finally, we showed a negative association of GAS6 and ATF3 expression with the risk of major adverse cardiac events in patients with ischemic heart disease. These results indicate that the GAS6-ATF3 axis has a protective role against IR injury by regulating MerTK+ cardiac macrophage survival and/or proliferation.

Multifunctional Bone Regeneration Membrane with Flexibility, Electrical Stimulation Activity and Osteoinductive Activity.

The use of membrane-based guided bone regeneration techniques has great potential for single-stage reconstruction of critical-sized bone defects. Here, a multifunctional bone regeneration membrane combining flexible elasticity, electrical stimulation (ES) and osteoinductive activity is developed by in situ doping of MXene 2D nanomaterials with conductive functionality and ß-TCP particles into a Poly(lactic acid-carbonate (PDT) composite nano-absorbable membrane (P/T/MXene) via electrostatic spinning technique. The composite membrane has good feasibility due to its temperature sensitivity, elastic memory capacity, coordinated degradation profile and easy preparation process. In vitro experiments showed the P/T/MXene membrane effectively promoted the recruitment and osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs) under ES and enhanced the angiogenic capacity of endothelial cells, which synergistically promoted bone regeneration through neovascularization. In addition, an in vivo rat model of cranial bone defects further confirmed the bone regeneration efficacy of the P/T/MXene membrane. In conclusion, the developed P/T/MXene membrane can effectively promote bone regeneration through their synergistic multifunctional effects, suggesting the membranes have great potential for guiding tissue regeneration and providing guidance for the biomaterials design.

Dual-energy computed tomography with new virtual monoenergetic image reconstruction enhances prostate lesion image quality and improves the diagnostic efficacy for prostate cancer.

BACKGROUND: Prostate cancer is one of the most common malignant tumors in middle-aged and elderly men and carries significant prognostic implications, and recent studies suggest that dual-energy computed tomography (DECT) utilizing new virtual monoenergetic images can enhance cancer detection rates. This study aimed to assess the impact of virtual monoenergetic images reconstructed from DECT arterial phase scans on the image quality of prostate lesions and their diagnostic performance for prostate cancer. METHODS: We conducted a retrospective analysis of 83 patients with prostate cancer or prostatic hyperplasia who underwent DECT scans at Meizhou People's Hospital between July 2019 and December 2023. The variables analyzed included age, tumor diameter and serum prostate-specific antigen (PSA) levels, among others. We also compared CT values, signal-to-noise ratio (SNR), subjective image quality ratings, and contrast-to-noise ratio (CNR) between virtual monoenergetic images (40-100 keV) and conventional linear blending images. Receiver operating characteristic (ROC) curve analyses were performed to evaluate the diagnostic efficacy of virtual monoenergetic images (40 keV and 50 keV) compared to conventional images. RESULTS: Virtual monoenergetic images at 40 keV showed significantly higher CT values (168.19 ± 57.14) compared to conventional linear blending images (66.66 ± 15.5) for prostate cancer (P < 0.001). The 50 keV images also demonstrated elevated CT values (121.73 ± 39.21) compared to conventional images (P < 0.001). CNR values for the 40 keV (3.81 ± 2.13) and 50 keV (2.95 ± 1.50) groups were significantly higher than the conventional blending group (P < 0.001). Subjective evaluations indicated markedly better image quality scores for 40 keV (median score of 5) and 50 keV (median score of 5) images compared to conventional images (P < 0.05). ROC curve analysis revealed superior diagnostic accuracy for 40 keV (AUC: 0.910) and 50 keV (AUC: 0.910) images based on CT values compared to conventional images (AUC: 0.849). CONCLUSIONS: Virtual monoenergetic images reconstructed at 40 keV and 50 keV from DECT arterial phase scans substantially enhance the image quality of prostate lesions and improve diagnostic efficacy for prostate cancer.

Cancer-associated fibroblast-derived circFARP1 modulates non-small cell lung cancer invasion and metastasis through the circFARP1/miR-338-3p/SOX4 axis.

The pleiotropic effect of cancer-associated fibroblasts (CAFs) on tumour progression depends on the environment. circFARP1 is critical for CAFs-induced gemcitabine (GEM) resistance in pancreatic cancer. Its specific role and mechanism in non-small cell lung cancer (NSCLC) have not been reported yet. We prepared a cancer-associated fibroblasts-conditioned medium (CAF-CM) to incubate the A549 cells. Quantitative real-time polymerase chain reaction was used to detect RNA levels. We detected protein expression by immunohistochemistry, immunocytochemistry, western blot and immunofluorescence. We also detected the targeting impact between circFARP1, miR-338-3p and SRY-box transcription factor 4 (SOX4) by using dual-luciferase reporter and RNA pull-down assays. We determined cell proliferation, migration and invasion capabilities through Cell Counting Kit-8 and transwell assays. In addition, we measured tumour volume and weight in vivo by establishing a xenograft tumour model. CircFARP1 levels were remarkably high in the CAFs. The transfection experiments found that circFARP1 downregulation in CAFs caused migration, proliferation and invasion inhibition of CAFs and A549 cells, whereas inhibiting miR-38-3p or overexpressing SOX4 in CAFs could significantly reverse the inhibition. In vivo study in nude mice confirmed that CAFs could promote NSCLC tumour growth and knockdown of circFARP1 could inhibit tumour growth of NSCLC, whereas miR-38-3p downregulation or SOX4 overexpression could significantly reverse the inhibition. circFARP1 promotes NSCLC development by stimulating miR-338-3p/SOX4 signalling axis to regulate CAFs.

Glucose-responsive, self-healing, wet adhesive and multi-biofunctional hydrogels for diabetic wound healing.

Diabetic wounds are serious clinical complications which manifest wet condition due to the mass exudate, along with disturbed regulation of inflammation, severe oxidative stress and repetitive bacterial infection. Existing treatments for diabetic wounds remain unsatisfactory due to the lack of ideal dressings that encompass mechanical performance, adherence to moist tissue surfaces, quick repair, and diverse therapeutic benefits. Herein, we fabricated a wet adhesive, self-healing, glucose-responsive drug releasing hydrogel with efficient antimicrobial and pro-healing properties for diabetic wound treatment. PAE hydrogel was constructed with poly(acrylic acid-co-acrylamide) (AA-Am) integrated with a dynamic E-F crosslinker, which consisted of epigallocatechin gallate (EGCG) and 4-(2-acrylamidoethylcarbamoyl)-3-fluorophenylboronic acid (AFPBA). Due to the dynamic crosslinking nature of boronate esters, abundant catechol groups and hydrogen bonding, PAE hydrogel demonstrated excellent mechanical properties with about 1000 % elongation, robust adhesion to moist tissues, fast self-healing, and absorption of biofluids of 10 times of its own weight. Importantly, PAE hydrogel exhibited sustained and glucose-responsive release of EGCG. Together, the bioactive PAE hydrogel had effective antibacterial, antioxidative, and anti-inflammatory properties in vitro, and accelerated diabetic wound healing in rats via reducing tissue-inflammatory response, enhancing angiogenesis, and reprogramming of macrophages. Overall, this versatile hydrogel provides a straightforward solution for the treatment of diabetic wound, and shows potential for other wound-related application scenarios.

Predicting Conversion Time from Mild Cognitive Impairment to Dementia with Interval-Censored Models.

Background: Mild cognitive impairment (MCI) patients are at a high risk of developing Alzheimer's disease and related dementias (ADRD) at an estimated annual rate above 10%. It is clinically and practically important to accurately predict MCI-to-dementia conversion time. Objective: It is clinically and practically important to accurately predict MCI-to-dementia conversion time by using easily available clinical data. Methods: The dementia diagnosis often falls between two clinical visits, and such survival outcome is known as interval-censored data. We utilized the semi-parametric model and the random forest model for interval-censored data in conjunction with a variable selection approach to select important measures for predicting the conversion time from MCI to dementia. Two large AD cohort data sets were used to build, validate, and test the predictive model. Results: We found that the semi-parametric model can improve the prediction of the conversion time for patients with MCI-to-dementia conversion, and it also has good predictive performance for all patients. Conclusions: Interval-censored data should be analyzed by using the models that were developed for interval- censored data to improve the model performance.

The relationship between cardiometabolic index and pulmonary function among U.S. adults: insights from the National Health and Nutrition Examination Survey (2007-2012).

BACKGROUND: Previous findings have revealed that disorders of lipid metabolism may be a risk factor for pulmonary function damage; however, the combined effect of dyslipidemia and central obesity on pulmonary function is unclear. The cardiometabolic index (CMI) is a composite of serum lipids (triglyceride (TG)/high-density lipoprotein cholesterol (HDL-C)) and visceral fat parameters (waist-to-height ratio (WHtR)). This research aimed to investigate the link between CMI and pulmonary function, employing large-scale demographic data sourced from the National Health and Nutrition Examination Survey (NHANES) database. METHODS: This cross-sectional study used data involving 4125 adults aged 20 and above collected by NHANES between 2007 and 2012. We defined CMI as the exposure variable and measured outcomes using forced expiratory volume in one second (FEV1), forced vital capacity (FVC), and FEV1/FVC to evaluate pulmonary function. Weighted multiple linear regression models and subgroup analyses were employed to investigate separate relationships between CMI and pulmonary function. In addition, to investigate variations across different strata and evaluate the robustness of the findings, interaction tests and sensitivity analyses were conducted. RESULTS: Results from the weighted multiple linear regression analysis indicated a unit increase in log2-CMI was associated with a reduction of 82.63 mL in FEV1 and 112.92 mL in FVC. The negative association remained significant after transforming log2-CMI by quartile (Q). When the log2-CMI level reached Q4, ß coefficients (ß) were -128.49 (95% CI: -205.85, -51.13), -169.01 (95% CI: -266.72, -71.30), respectively. According to the interaction test findings, the negative association linking log2-CMI with FEV1 and FVC persists regardless of confounding factors including age, gender, BMI, physical activity (PA), and smoking status. A subsequent sensitivity analysis provided additional confirmation of the stability and reliability of the results. For females, the inflection points for the nonlinear relationships between log2-CMI and FEV1, as well as log2-CMI and FVC, were identified at 2.33 and 2.11, respectively. While in males, a consistent negative association was observed. CONCLUSIONS: Our findings suggest that higher CMI is associated with lower FEV1 and FVC. CMI may serve as a complementary consideration to the assessment and management of pulmonary function in clinical practice.

Innovation and challenges of artificial intelligence technology in personalized healthcare.

As the burgeoning field of Artificial Intelligence (AI) continues to permeate the fabric of healthcare, particularly in the realms of patient surveillance and telemedicine, a transformative era beckons. This manuscript endeavors to unravel the intricacies of recent AI advancements and their profound implications for reconceptualizing the delivery of medical care. Through the introduction of innovative instruments such as virtual assistant chatbots, wearable monitoring devices, predictive analytic models, personalized treatment regimens, and automated appointment systems, AI is not only amplifying the quality of care but also empowering patients and fostering a more interactive dynamic between the patient and the healthcare provider. Yet, this progressive infiltration of AI into the healthcare sphere grapples with a plethora of challenges hitherto unseen. The exigent issues of data security and privacy, the specter of algorithmic bias, the requisite adaptability of regulatory frameworks, and the matter of patient acceptance and trust in AI solutions demand immediate and thoughtful resolution .The importance of establishing stringent and far-reaching policies, ensuring technological impartiality, and cultivating patient confidence is paramount to ensure that AI-driven enhancements in healthcare service provision remain both ethically sound and efficient. In conclusion, we advocate for an expansion of research efforts aimed at navigating the ethical complexities inherent to a technology-evolving landscape, catalyzing policy innovation, and devising AI applications that are not only clinically effective but also earn the trust of the patient populace. By melding expertise across disciplines, we stand at the threshold of an era wherein AI's role in healthcare is both ethically unimpeachable and conducive to elevating the global health quotient.

Frameshift variants in C10orf71 cause dilated cardiomyopathy in human, mouse, and organoid models.

Research advances over the past 30 years have confirmed a critical role for genetics in the etiology of dilated cardiomyopathies (DCMs). However, full knowledge of the genetic architecture of DCM remains incomplete. We identified candidate DCM causal gene, C10orf71, in a large family with 8 patients with DCM by whole-exome sequencing. Four loss-of-function variants of C10orf71 were subsequently identified in an additional group of492 patients with sporadic DCM from 2 independent cohorts. C10orf71 was found to be an intrinsically disordered protein specifically expressed in cardiomyocytes. C10orf71-KO mice had abnormal heart morphogenesis during embryonic development and cardiac dysfunction as adults with altered expression and splicing of contractile cardiac genes. C10orf71-null cardiomyocytes exhibited impaired contractile function with unaffected sarcomere structure. Cardiomyocytes and heart organoids derived from human induced pluripotent stem cells with C10orf71 frameshift variants also had contractile defects with normal electrophysiological activity. A rescue study using a cardiac myosin activator, omecamtiv mecarbil, restored contractile function in C10orf71-KO mice. These data support C10orf71 as a causal gene for DCM by contributing to the contractile function of cardiomyocytes. Mutation-specific pathophysiology may suggest therapeutic targets and more individualized therapy.

Rapidly screening of pancreatic lipase inhibitors from Clematis tangutica using affinity ultrafiltration-HPLC-QTOFMS technique combined with targeted separation, in vitro validation, and molecular docking.

INTRODUCTION: Screening of novel pancreatic lipase inhibitors from complex natural products is a meaningful task. OBJECTIVES: Through accurately screening and separating pancreatic lipase inhibitors from Clematis tangutica (C. tangutica), to discover new leading compounds for slimming and accelerate the development and utilization of Tibetan medicine resources. METHODS: An integrated strategy that combines affinity ultrafiltration and high-performance liquid chromatography-quadrupole time-of-flight mass spectrometry (AU-HPLC-QTOFMS), targeted separation, in vitro validation, and molecular docking was developed to screen pancreatic lipase inhibitors from C. tangutica. The AU-HPLC-QTOFMS technique was performed to fish for the potential active substances. Macroporous resin, preparative liquid chromatography, and high-speed countercurrent chromatography were implemented for the accurate and targeted separation of active compounds. The inhibitory activities of target compounds to pancreatic lipase were detected by the inhibition experiments in vitro. The binding affinities and binding sites were analyzed using molecular docking. RESULTS: A total of eleven kinds of pancreatic lipase inhibitory substances were screened from C. tangutica. Seven triterpenoid saponins were screened for the first time as lipase inhibitors and successfully prepared with purities higher than 97%. Tanguticoside B, clematangoticoside J, hederoside H1, and rutin showed stronger inhibitory effects with IC50 values of 1.539 ± 0.048, 1.661 ± 0.092, 1.793 ± 0.069, and 1.792 ± 0.094 mmol/l. Moreover, they have the lowest ΔG values of -10.84, -9.97, -10.87, and -9.39 kcal/mol to pancreatic lipase. CONCLUSION: The integrated strategy using AU-HPLC-QTOFMS, targeted separation, in vitro validation, and molecular docking was feasible for rapidly screening and directionally isolating pancreatic lipase inhibitors from C. tangutica.

Integrated transcriptome and microRNA analysis reveals molecular responses to high-temperature stress in the liver of American shad (Alosa sapidissima).

BACKGROUND: Fish reproduction, development and growth are directly affected by temperature, investigating the regulatory mechanisms behind high temperature stress is helpful to construct a finer molecular network. In this study, we systematically analyzed the transcriptome and miRNA information of American shad (Alosa sapidissima) liver tissues at different cultivation temperatures of 24 â„ƒ (Low), 27 â„ƒ (Mid) and 30 â„ƒ (High) based on a high-throughput sequencing platform. RESULTS: The results showed that there were 1594 differentially expressed genes (DEGs) and 660 differentially expressed miRNAs (DEMs) in the LowLi vs. MidLi comparison group, 473 DEGs and 84 DEMs in the MidLi vs. HighLi group, 914 DEGs and 442 DEMs in the LowLi vs. HighLi group. These included some important genes and miRNAs such as calr, hsp90b1, hsp70, ssa-miR-125a-3p, ssa-miR-92b-5p, dre-miR-15a-3p and novel-m1018-5p. The DEGs were mainly enriched in the protein folding, processing and export pathways of the endoplasmic reticulum; the target genes of the DEMs were mainly enriched in the focal adhesion pathway. Furthermore, the association analysis revealed that the key genes were mainly enriched in the metabolic pathway. Interestingly, we found a significant increase in the number of genes and miRNAs involved in the regulation of heat stress during the temperature change from 24 °C to 27 °C. In addition, we examined the tissue expression characteristics of some key genes and miRNAs by qPCR, and found that calr, hsp90b1 and dre-miR-125b-2-3p were significantly highly expressed in the liver at 27 â„ƒ, while novel-m0481-5p, ssa-miR-125a-3p, ssa-miR-92b-5p, dre-miR-15a-3p and novel-m1018-5p had the highest expression in the heart at 30℃. Finally, the quantitative expression trends of 10 randomly selected DEGs and 10 DEMs were consistent with the sequencing data, indicating the reliability of the results. CONCLUSIONS: In summary, this study provides some fundamental data for subsequent in-depth research into the molecular regulatory mechanisms of A. sapidissima response to heat stress, and for the selective breeding of high temperature tolerant varieties.

Combined MediaPipe and YOLOv5 range of motion assessment system for spinal diseases and frozen shoulder.

Spinal diseases and frozen shoulder are prevalent health problems in Asian populations. Early assessment and treatment are very important to prevent the disease from getting worse and reduce pain. In the field of computer vision, it is a challenging problem to assess the range of motion. In order to realize efficient, real-time and accurate assessment of the range of motion, an assessment system combining MediaPipe and YOLOv5 technologies was proposed in this study. On this basis, Convolutional Block Attention Module (CBAM) is introduced into the YOLOv5 target detection model, which can enhance the extraction of feature information, suppress background interference, and improve the generalization ability of the model. In order to meet the requirements of large-scale computing, a client/server (C/S) framework structure is adopted. The evaluation results can be obtained quickly after the client uploads the image data, providing a convenient and practical solution. In addition, a game of "Picking Bayberries" was developed as an auxiliary treatment method to provide patients with interesting rehabilitation training.