Contribution of crosstalk of mesothelial and tumoral epithelial cells in pleural metastasis of lung cancer.

Background: Tumor metastasis commonly affects pleura in advanced lung cancer and results in malignant pleural effusion (MPE). MPE is related to poor prognosis, but without systematic investigation on different cell types and their crosstalk at single cell resolution. Methods: We conducted single-cell RNA-sequencing (scRNA-seq) of lung cancer patients with pleural effusion. Next, our data were integrated with 5 datasets derived from individuals under normal, non-malignant disease and lung carcinomatous conditions. Mesothelial cells were re-clustered and their interactions with epithelial cells were comprehensively analyzed. Taking advantage of inferred ligand-receptor pairs, a prediction model of prognosis was constructed. The co-culture of mesothelial cells and malignant epithelial cells in vitro and RNA-seq was performed. Epidermal growth factor receptor (EGFR) antagonist cetuximab was utilized to prevent the lung cancer cells' invasiveness. Spatial distribution of cells in lung adenocarcinoma patients' samples were also analyzed to validate our findings. Results: The most distinctive transcriptome profiles between tumor and control were revealed in mesothelial cells, which is the predominate cell type of pleura. Five subtypes were divided, including one predominately identified in MPE which was characterized by enriched cancer-related pathways (e.g., cell migration) along evolutionary trajectory from normal mesothelial cells. Cancer-associated mesothelial cells (CAMCs) exhibited varied interactions with different subtypes of malignant epithelial cells, and multiple ligands/receptors exhibited significant correlation with poor prognosis. Experimentally, mesothelial cells can increase the migration ability of lung cancer cells through co-culturing. EGFR was the only affected gene in cancer cells that exhibited interaction with mesothelial cells and was associated with poor prognosis. Using EGFR antagonist cetuximab prevented the lung cancer cells' increased invasiveness caused by mesothelial cells. Moreover, epithelial mitogen (EPGN)-EGFR interaction was supported through spatial distribution analysis, revealing the significant proximity between EPGN+ mesothelial cells and EGFR+ epithelial cells. Conclusions: Our findings highlighted the important role of mesothelial cells and their interactions with cancer cells in pleural metastasis of lung cancer, providing potential targets for treatment.

Med1 inhibits ferroptosis and alleviates liver injury in acute liver failure via Nrf2 activation.

BACKGROUND: Extensive hepatocyte mortality and the absence of specific medical therapy significantly contribute to the unfavorable prognosis of acute liver failure (ALF). Ferroptosis is a crucial form of cell death involved in ALF. In this study, we aimed to determine the impact of Mediator complex subunit 1 (Med1) on ferroptosis and its potential hepatoprotective effects in ALF. RESULTS: Med1 expression is diminished in the liver of lipopolysaccharide (LPS)/D-galactosamine (D-GalN)-induced ALF mice, as well as in hepatocytes damaged by H2O2 or TNF-α/D-GalN in vitro. Med1 overexpression mitigates liver injury and decreases the mortality rate of ALF mice by ferroptosis inhibition. The mechanism by which Med1 inhibits erastin-induced ferroptosis in hepatocytes involves the upregulation of nuclear factor erythroid 2-related factor 2 (Nrf2) and its downstream antioxidant genes heme oxygenase-1 (HO-1), glutamate cysteine ligase catalytic (GCLC), and NAD(P)H quinone oxidoreductase 1 (NQO1). Furthermore, Med1 overexpression suppresses the transcription of proinflammatory cytokines tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) in the liver of mice with LPS/D-GalN-induced ALF. CONCLUSION: Overall, our research findings indicate that Med1 suppresses ferroptosis and alleviates liver injury in LPS/D-GalN-induced ALF through the activation of Nrf2. These findings substantiate the therapeutic viability of targeting the Med1-Nrf2 axis as a means of treating individuals afflicted with ALF.

Highly Sensitive Weaving Sensor of Hybrid Graphene Nanoribbons and Carbon Nanotubes for Enhanced Pressure Sensing Function.

Carbon nanotubes (CNTs) hold great promise in next-generation sensors because of their remarkable physical properties. Yet, maintaining precise stacking configurations of CNTs to make full use of their remarkable properties is challenging because of their susceptibility to spontaneous reconstruction. Inspired by the weaving technology, we propose a CNT-graphene nanoribbon hybrid woven model that can maintain the specific structure of CNTs to achieve their elaborately designed function. In this study, comprehensive molecular dynamics simulations are carried out to investigate the thermal stability of the CNT-graphene hybrid woven model, as well as their potential for pressure sensing applications by utilizing the unique response of thermal transport to mechanical deformation at heterojunctions. The thermal stability is sensitive to the size of the graphene nanoribbon, and the woven structure remains stable from 200-500 K when its width is greater than 2.0 nm. Moreover, it is exciting that the sensors are effective at predicting the shapes of externally loaded objects through the analysis of the thermal conductivity distribution, which can be derived from the relationship between the thermal conduction and the pressure. Our findings shed light on the bottom-up functional design of nanomaterials and expand wider applications of high-performance nanosensors in other related fields.

The endocannabinoid system is involved in the anxiety-like behavior induced by dual-frequency 2.65/0.8 GHz electromagnetic radiation in mice.

As wireless communication devices gain popularity, concerns about the potential risks of environmental exposure to complex frequency electromagnetic radiation (EMR) on mental health have become a public health issue. Historically, EMR research has predominantly focused on single- frequency electromagnetic waves, neglecting the study of multi-frequency electromagnetic waves, which more accurately represent everyday life. To address these concerns, our study compared the emotional effects of single-frequency and dual-frequency EMR while exploring potential molecular mechanisms and intervention targets. Our results revealed that single-frequency EMR at 2.65 or 0.8 GHz did not induce anxiety-like behavior in mice. However, exposure to dual-frequency EMR at 2.65/0.8 GHz significantly led to anxiety-like behavior in mice. Further analysis of mouse sera revealed substantial increases in corticosterone and corticotrophin releasing hormone levels following exposure to 2.65/0.8 GHz EMR. Transcriptome sequencing indicated a significant decrease in the expression of Cnr1, encoding cannabinoid receptor 1 Type (CB1R), in the cerebral. This finding was consistently verified through western blot analysis, revealing a substantial reduction in CB1R content. Additionally, a significant decrease in the endocannabinoid 2-arachidonoylglycerol was observed in the cerebral cortex. Remarkably, administering the cannabinoid receptor agonist Win55-212-2 significantly alleviated the anxiety-like behavior, and the cannabinoid receptor antagonist AM251 effectively counteracted the anti-anxiety effects of Win55-212-2. In summary, our research confirmed that dual-frequency EMR is more likely to induce anxiety-like behavior in mice than single-frequency EMR, with implications for the hypothalamic-pituitary-adrenal axis and the endocannabinoid system. Furthermore, our findings suggest that Win55-212-2 may represent a novel avenue for researching and developing anti-EMR drugs.

Causal effect of gut microbiota of Defluviitaleaceae on the clinical pathway of "Influenza-Subacute Thyroiditis-Hypothyroidism".

Introduction: Hypothyroidism has been found to be influenced by gut microbiota. However, it remains unclear which a taxon of gut microbiota plays a key role in this function. Identifying the key bacteria affects hypothyroidism and through what mechanism will be helpful for the prevention of hypothyroidism through specific clinical pathways. Materials and methods: In Study A, 35 families and 130 genera of gut microbiota are used as exposures, with hypothyroidism as the outcome. The causal effect of the gut microbiota on hypothyroidism is estimated through two-sample Mendelian randomization. Combining the results of the two taxonomical levels, key taxa are selected, which in Study B are investigated for their causal association with multiple generally admitted causes of hypothyroidism and their more upstream factors. For validating and revealing the potential mechanism, enrichment analyses of the related genes and interacting transcription factors were performed. Results: In Study A, Defluviitaleaceae (OR: 0.043, 95% CI: 0.005-0.363, P = 0.018)/Defluviitaleaceae_UCG_011 (OR: 0.385, 95% CI: 0.172-0.865, P = 0.021) are significantly causally associated with hypothyroidism at both taxonomical levels. In Study B, Defluviitaleaceae family and Defluviitaleaceae_UCG_011 genus show the causal association with decreased thyroiditis (Family: OR: 0.174, 95% CI: 0.046-0.653, P = 0.029; Genus: OR: 0.139, 95% CI: 0.029-0.664, P = 0.043), decreased subacute thyroiditis (Family: OR: 0.028, 95% CI: 0.004-0.213, P = 0.007; Genus: OR: 0.018, 95% CI: 0.002-0.194, P = 0.013), decreased influenza (Family: OR: 0.818, 95% CI: 0.676-0.989, P = 0.038; Genus: OR: 0.792, 95% CI: 0.644-0.974, P = 0.027), and increased anti-influenza H3N2 IgG levels (Family: OR: 1.934, 95% CI: 1.123-3.332, P = 0.017; Genus: OR: 1.675, 95% CI: 0.953-2.943, P = 0.073). The results of the enrichment analysis are consistent with the findings and the suggested possible mechanisms. Conclusion: Defluviitaleaceae of the gut microbiota displays the probability of causally inhibiting the clinical pathway of "Influenza-Subacute Thyroiditis-Hypothyroidism" and acts as the potential probiotics to prevent influenza, subacute thyroiditis, and hypothyroidism.

Influence of cancer-directed surgery on the prognosis of liver metastases from gastric cancer

There are controversial about the application of cancer-directed surgery (CDS) in patients with liver metastases from gastric cancer, with improved responses to chemotherapy and targeted treatments, the role of CDS in metastatic gastric cancer to the liver needs to be revisited. This study aimed to evaluate the effect of CDS on patients with liver metastases from gastric cancer. Data for patients with liver metastases from gastric cancer were extracted from the population-based Surveillance, Epidemiology, and End Results (SEER) database. A total of 958 individuals were enrolled, 285 in the CDS group and 673 in the non-cancer guided surgery (Non-CDS) group. Following propensity score matching (PSM) analysis at 1:1 in the two groups,285 were included in the survival analysis for each group. Kaplan–Meier values and Cox proportional risk models were used to estimate the effect of CDS on patients' prognoses. Compared with the Non-CDS group, the CDS group significantly prolonged the median overall survival from 4 months (95% confidence interval [CI] 3–5) to 11 months (95% CI 8–12), p value < 0.001. Overall survival (OS) at 1 year was higher in the CDS group than in the Non-CDS group, at 44% (95 CI 38–50) and 25% (95 CI 20–30), respectively. OS at 3 years was also higher in the CDS group than in the Non-CDS group, at 24% (95 CI 19–29) and 6% (95 CI 3–9), respectively. Multivariate analysis showed that Non-CDS (hazard ratio[HR] = 2.26, 95% CI 1.88–2.72, p value < 0.001) was an adverse independent prognostic factor for patients (AU)

Multiple exposures to low-dose ionizing radiation induced the initiation and progression of pro-atherosclerotic phenotypes in mice and vascular endothelial cell damage.

OBJECTIVE: This study aimed to investigate the effects of low-dose radiation on the abdominal aorta of mice and vascular endothelial cells. METHODS: Wild-type and tumor-bearing mice were exposed to 15 sessions of low-dose irradiation, resulting in cumulative radiation doses of 187.5, 375, and 750 mGy. The effect on the cardiovascular system was assessed. Immunohistochemistry analyzed protein expressions of PAPP-A, CD62, P65, and COX-2 in the abdominal aorta. Microarray technology, Gene Ontology analysis, and pathway enrichment analysis evaluated gene expression changes in endothelial cells exposed to 375 mGy X-ray. Cell viability was assessed using the Cell Counting Kit 8 assay. Immunofluorescence staining measured γ-H2AX levels, and real-time polymerase chain reaction quantified mRNA levels of interleukin-6 (IL-6), ICAM-1, and Cx43. RESULTS: Hematoxylin and eosin staining revealed thickening of the inner membranes and irregular arrangement of smooth muscle cells in the media membrane at 375 and 750 mGy. Inflammation was observed in the inner membranes at 750 mGy, with a clear inflammatory response in the hearts of tumor-bearing mice. Immunohistochemistry indicated increased levels of PAPP-A, P65, and COX-2 post-irradiation. Microarray analysis showed 425 up-regulated and 235 down-regulated genes, associated with processes like endothelial cell-cell adhesion, IL-6, and NF-κB signaling. Cell Counting Kit 8 assay results indicated inhibited viability at 750 mGy in EA.hy926 cells. Immunofluorescence staining demonstrated a dose-dependent increase in γ-H2AX foci. Reverse transcription quantitative PCR results showed increased expression of IL6, ICAM-1, and Cx43 in EA.hy926 cells post 750 mGy X-ray exposure. CONCLUSION: Repeated low-dose ionizing radiation exposures triggered the development of pro-atherosclerotic phenotypes in mice and damage to vascular endothelial cells.

Thermal Property of Fullerene Fibers: One-Dimensional Material with Exceptional Thermal Performance.

The recent groundbreaking achievement in the synthesis of large-sized single crystal C60 monolayer, which is covalently bonded in a plane using C60 as building blocks. The asymmetric lattice structure endows it with anisotropic phonon modes and conductivity. If these C60 are arranged in form of 1D fiber, the improved manipulation of phonon conduction along the fiber axis could be anticipated. Here, thermal properties of C60-fiber, including thermal transfer along the C60-fiber axis and across the interlayer interface are investigated using molecular dynamic simulations. Taking advantage of the distinctively hollow spherical structure of C60 building blocks, the spherical structure deformation and encapsulation induced thermal reduction can be up to 56% and 80%, respectively. By applying external electronic fields in H2O@C60 model, its thermal conductivity decreases up to 60%, which realizes the contactless thermal regulation. ln particular, the thermal rectification phenomenon is discovered by inserting atoms/molecules in C60 with a rational designed mass-gradient, and its maximum thermal rectification factor is predicted to ≈45%. These investigations aim to achieve effective regulation of the thermal conductivity of C60-fibers. This work showcases the potential of C60-fiber in the realms of thermal management and thermal sensing, paving the way to C60-based functional materials.

Influence of cancer-directed surgery on the prognosis of liver metastases from gastric cancer.

There are controversial about the application of cancer-directed surgery (CDS) in patients with liver metastases from gastric cancer, with improved responses to chemotherapy and targeted treatments, the role of CDS in metastatic gastric cancer to the liver needs to be revisited. This study aimed to evaluate the effect of CDS on patients with liver metastases from gastric cancer. Data for patients with liver metastases from gastric cancer were extracted from the population-based Surveillance, Epidemiology, and End Results (SEER) database. A total of 958 individuals were enrolled, 285 in the CDS group and 673 in the non-cancer guided surgery (Non-CDS) group. Following propensity score matching (PSM) analysis at 1:1 in the two groups,285 were included in the survival analysis for each group. Kaplan-Meier values and Cox proportional risk models were used to estimate the effect of CDS on patients' prognoses. Compared with the Non-CDS group, the CDS group significantly prolonged the median overall survival from 4 months (95% confidence interval [CI] 3-5) to 11 months (95% CI 8-12), p value < 0.001. Overall survival (OS) at 1 year was higher in the CDS group than in the Non-CDS group, at 44% (95 CI 38-50) and 25% (95 CI 20-30), respectively. OS at 3 years was also higher in the CDS group than in the Non-CDS group, at 24% (95 CI 19-29) and 6% (95 CI 3-9), respectively. Multivariate analysis showed that Non-CDS (hazard ratio[HR] = 2.26, 95% CI 1.88-2.72, p value < 0.001) was an adverse independent prognostic factor for patients. This study concludes that CDS prolonged survival in patients with gastric cancer with liver metastases. Due to the lack of information on the quality of life, biomarkers, targeted therapies, and immunotherapy in the SEER database, the observed improved survival rates following CDS of hepatic metastasis from gastric cancer requires prospective studies that take these factors into account to properly address the survival advantages and impact on quality of life of such a method.

Mesenchymal stem cell-regulated miRNA-mRNA landscape in acute-on-chronic liver failure.

BACKGROUND: Acute-on-chronic liver failure (ACLF) is a major challenge in the field of hepatology. While mesenchymal stem cell (MSC) therapy can improve the prognosis of patients with ACLF, the molecular mechanisms through which MSCs attenuate ACLF remain poorly understood. We performed global miRNA and mRNA expression profiling via next-generation sequencing of liver tissues from MSC-treated ACLF mice to identify important signaling pathways and major factors implicated in ACLF alleviation by MSCs. METHODS: Carbon tetrachloride-induced ACLF mice were treated with saline or mouse bone marrow-derived MSCs. Mouse livers were subjected to miRNA and mRNA sequencing. Related signal transduction pathways were obtained through Gene Set Enrichment Analysis. Functional enrichment, protein-protein interaction, and immune infiltration analyses were performed for the differentially expressed miRNA target genes (DETs). Hub miRNA and mRNA associated with liver injury were analyzed using LASSO regression. The expression levels of hub genes were subjected to Pearson's correlation analysis and verified using RT-qPCR. The biological functions of hub genes were verified in vitro. RESULTS: The tricarboxylic acid cycle and peroxisome proliferator-activated receptor pathways were activated in the MSC-treated groups. The proportions of liver-infiltrating NK resting cells, M2 macrophages, follicular helper T cells, and other immune cells were altered after MSC treatment. The expression levels of six miRNAs and 10 transcripts correlated with the degree of liver injury. miR-27a-5p was downregulated in the mouse liver after MSC treatment, while its target gene E2f2 was upregulated. miR-27a-5p inhibited E2F2 expression, suppressed G1/S phase transition and proliferation of hepatocytes, in addition to promoting their apoptosis. CONCLUSIONS: This is the first comprehensive analysis of miRNA and mRNA expression in the liver tissue of ACLF mice after MSC treatment. The results revealed global changes in hepatic pathways and immune subpopulations. The miR-27a-5p/E2F2 axis emerged as a central regulator of the MSC-induced attenuation of ACLF. The current findings improve our understanding of the molecular mechanisms through which MSCs alleviate ACLF.

Mesenchymal Stem Cells Promote Polarization of M2 Macrophages in Mice with Acute-On-Chronic Liver Failure via Mertk/JAK1/STAT6 Signaling.

Acute-on-chronic liver failure (ACLF) is a severe disease with a high mortality. Macrophage-related inflammation plays a crucial role in ACLF development. Mesenchymal stem cells (MSCs) treatment was demonstrated to be beneficial in ACLF in our previous study; however, the underlying mechanisms remain unknown. Therefore, mouse bone marrow-derived MSCs were used to treat an ACLF mouse model or cocultured with RAW264.7/J774A.1 macrophages that were stimulated with LPS. Histological and serological parameters and survival were analyzed to evaluate efficacy. We detected changes of Mer tyrosine kinase (Mertk), JAK1/STAT6, inflammatory cytokines, and markers of macrophage polarization in vitro and in vivo. In ACLF mice, MSCs improved liver function and 48-h survival of ACLF mice and alleviated inflammatory injury by promoting M2 macrophage polarization and elevated Mertk expression levels in macrophages. This is significant, as Mertk regulates M2 macrophage polarization via the JAK1/STAT6 signaling pathway.

Assessing synchronous ovarian metastasis in gastric cancer patients using a clinical-radiomics nomogram based on baseline abdominal contrast-enhanced CT: a two-center study.

BACKGROUND: To build and validate a radiomics nomogram based on preoperative CT scans and clinical data for detecting synchronous ovarian metastasis (SOM) in female gastric cancer (GC) cases. METHODS: Pathologically confirmed GC cases in 2 cohorts were retrospectively enrolled. All cases had presurgical abdominal contrast-enhanced CT and pelvis contrast-enhanced MRI and pathological examinations for any suspicious ovarian lesions detected by MRI. Cohort 1 cases (n = 101) were included as the training set. Radiomics features were obtained to develop a radscore. A nomogram combining the radscore and clinical factors was built to detect SOM. The bootstrap method was carried out in cohort 1 as internal validation. External validation was carried out in cohort 2 (n = 46). Receiver operating characteristic (ROC) curve analysis, decision curve analysis (DCA) and the confusion matrix were utilized to assess the performances of the radscore, nomogram and subjective evaluation model. RESULTS: The nomogram, which combined age and the radscore, displayed a higher AUC than the radscore and subjective evaluation (0.910 vs 0.827 vs 0.773) in the training cohort. In the external validation cohort, the nomogram also had a higher AUC than the radscore and subjective evaluation (0.850 vs 0.790 vs 0.675). DCA and the confusion matrix confirmed the nomogram was superior to the radscore in both cohorts. CONCLUSIONS: This pilot study showed that a nomogram model combining the radscore and clinical characteristics is useful in detecting SOM in female GC cases. It may be applied to improve clinical treatment and is superior to subjective evaluation or the radscore alone.

Palmitic acid/expanded graphite/CuS composite phase change materials toward efficient thermal storage and photothermal conversion.

In this study, an expanded graphite (EG) with nano-CuS (EG/CuS) support material with a special morphology was prepared, with EG/CuS filled with different ratios of palmitic acid (PA). Finally, a PA/EG/CuS composite phase change thermal storage material with photothermal conversion performance was synthesized. The superb chemical and thermal stability of PA/EG/CuS was demonstrated by characterization and analysis of the experiments. EG, a multi-layer structured material, provides rich binding sites for PA and nano-CuS and constructs rich thermal conductivity paths, which effectively improves the thermal conductivity of PA/EG/CuS. It is noted that the maximum thermal conductivity of PA/EG/CuS reached 0.372 W m-1 K-1 and the maximum phase change thermal storage capacity reached 260.4 kJ kg-1, which proved the excellent thermal storage properties of PA/EG/CuS. In addition, PA/EG/CuS exhibits excellent photothermal conversion performance, and the experimental results demonstrated that the best photothermal conversion efficiency of PA/EG/CuS reached 81.4%. The PA/EG/CuS developed in this study provides a promising method for fabricating excellent conductive and low leakage composite phase change materials for solar energy utilization and energy storage.

The complete chloroplast genome sequence of Quercus kerrii (Fagaceae), and comparative analysis with related species.

Quercus kerrii Craib 1911 (section Cyclobalanopsis) is a widespread tree species in the tropical seasonal forests of southwest China and Northern Indo-China areas. In this study, we sequenced, assembled and annotated the complete chloroplast genome of Q. kerrii. The circular genome was 160,743 bp in length and had a GC content of 36.89%. The Q. kerrii chloroplast genome has a typical quadripartite structure, including two inverted repeat regions (length, 25,825 bp; GC content, 42.76%), a large single-copy region (length, 90,196 bp; GC content, 34.74%), and a small single-copy region (length, 18,897 bp; GC content, 30.60%). Genome annotation has indicated that the Q. kerrii chloroplast genome contained 131 genes, including 86 protein-coding genes, 37 tRNA, and eight rRNA. The phylogenetic tree showed that Q. kerrii had a close relationship with Q. schottkyana Rehder & E.H.Wilson 1916.

Influence of Material Removal Strategy on Machining Deformation of Aluminum Plates with Asymmetric Residual Stresses.

In this paper, the effects of material removal strategies and initial stress states on the machining deformation of aluminum alloy plates were investigated through a combination of finite element simulation and experiments. We developed different machining strategies described by Tm+Bn, which removal m mm materials form top and n mm materials from the bottom of the plate. The results demonstrate that the maximum deformation of structural components with the T10+B0 machining strategy could reach 1.94 mm, whereas with the T3+B7 machining strategy was only 0.065 mm, decreasing by more than 95%. The asymmetric initial stress state had a significant impact on the machining deformation of the thick plate. The machined deformation of thick plates increased with the increase in the initial stress state. The concavity of the thick plates changed with the T3+B7 machining strategy due to the asymmetry of the stress level. The deformation of frame parts was smaller when the frame opening was facing the high-stress level surface during machining than when it was facing the low-stress level. Moreover, the modeling results for the stress state and machining deformation were accurate and in good accordance with the experimental findings.

Protective effects of combined treatment with ciprofol and mild therapeutic hypothermia during cerebral ischemia-reperfusion injury.

Despite improvement in cardiopulmonary resuscitation (CPR) performance, cardiac arrest (CA) is still associated with poor prognosis. The high mortality rate is due to multi-organ dysfunction caused by cerebral ischemia and reperfusion injury (I/R). The guidelines for CPR suggest the use of therapeutic hypothermia (TH) as an effective treatment to decrease mortality and the only approach confirmed to reduce I/R injury. During TH, sedative agents (propofol) and analgesia agents (fentanyl) are commonly used to prevent shiver and pain. However, propofol has been associated with a number of serious adverse effects such as metabolic acidosis, cardiac asystole, myocardial failure, and death. In addition, mild TH alters the pharmacokinetics of agents (propofol and fentanyl) and reduces their systemic clearance. For CA patients undergoing TH, propofol can be overdosed, leading to delayed awakening, prolonged mechanical ventilation, and other subsequent complications. Ciprofol (HSK3486) is a novel anesthetic agent that is convenient and easy to administer intravenously outside the operating room. Ciprofol is rapidly metabolized and accumulates at low concentrations after continuous infusion in a stable circulatory system compared to propofol. Therefore, we hypothesized that treatment with HSK3486 and mild TH after CA could protect the brain and other organs.

Duration of Diabetes, Glycemic Control, and Risk of Heart Failure Among Adults With Diabetes: A Cohort Study.

CONTEXT: The influences of diabetes duration and glycemic control and their potential interplays on the risk of heart failure (HF) remain unclear. OBJECTIVE: This work aimed to investigate the association of diabetes duration and glycemic control with the risk of HF. METHODS: A total of 23 754 individuals with diabetes but without HF during the baseline recruitment of UK Biobank were included in this study. Duration of diabetes was self-reported, and the status of glycemic control was reflected by glycated hemoglobin A1c (HbA1c) levels. Their associations with incident HF were assessed using multivariate Cox models adjusting for traditional risk factors. RESULTS: Duration of diabetes and HbA1c levels both were positively associated with the risk of HF. The hazard ratios (HRs) (95% CI) for diabetes durations of 5 to less than 10, 10 to less than 15, and 15 years or more were 1.09 (0.97-1.23), 1.13 (0.97-1.30), and 1.32 (1.15-1.53), respectively (vs < 5 years); and the HRs for HbA1c of 53.0 to less than 58.5 mmol/mol (7.0% to < 7.5%), 58.5 to less than 63.9 mmol/mol (7.5% to < 8.0%), and 63.9 mmol/mol or greater (8.0%) were 1.15 (1.02-1.31), 1.07 (0.91-1.26), and 1.46 (1.30-1.65), respectively (vs < 53.0 mmol/mol [7.0%]). Individuals with the longest disease duration (≥ 15 years) and poorer glycemic control (HbA1c ≥ 63.9 mmol/mol [8.0%]) had a particularly higher risk of HF (P for interaction = .026). CONCLUSION: The risk of HF among individuals with diabetes increases with a longer duration of diabetes and increasing HbA1c levels. This finding may contribute to the individualized prevention of HF in patients with diabetes if being considered in clinical practices and policy-making.

Association of age at first birth and risk of non-alcoholic fatty liver disease in women: evidence from the NHANES.

BACKGROUND: Numerous studies have suggested that age at first birth (AFB) is inversely associated with metabolic diseases, but positively associated with liver cancer in women. Non-alcoholic fatty liver disease (NAFLD) is a canonical example of metabolic dysfunction and inflammation-based liver disease, while the association between AFB and the risk of NAFLD remains unclear. We aimed to investigate the association between AFB and the odds of NAFLD in women. METHODS: Women older than 20 years at the time of the survey were analyzed using National Health and Nutrition Examination Survey (NHANES) data from 1999 to 2018 in the US. AFB was obtained with self-administered questionnaires. NAFLD was diagnosed as fatty liver index (FLI) ≥ 60. Odds ratios (ORs) and 95% confidence intervals (CI) were estimated using logistic regression models. RESULTS: Of the 12,188 women included in this study, 5670 (46.5%) had NAFLD. Compared to individuals with AFB of 30-32 years old (reference group), the fully adjusted ORs and 95% CI in women with AFB < 18, 18-20, 21-23, and 24-26 years were 1.52 (95% CI 1.14, 2.03), 1.60 (95% CI 1.21, 2.11), 1.40 (95% CI 1.06, 1.84), and 1.33 (95% CI 1.01-1.76), respectively. Yet there was no significant difference between AFB of 27-29, 33-35, or > 35 years compared to the reference group. CONCLUSIONS: Women with younger AFB have higher odds of NAFLD in later life. Policymakers should consider focusing on those with earlier AFB for screening and prevention of NAFLD.

A Multi-Scale Study on Deformation and Failure Process of Metallic Structures in Extreme Environment.

It is a macro-micro model study for defect initiation, growth and crack propagation of metallic truss structure under high engine temperature and pressure conditions during the reentry atmosphere. Till now, the multi-scale simulation methods for these processes are still unclear. We explore the deformation and failure processes from macroscale to nanoscale using the Gas-Kinetic Unified Algorithm (GKUA) and all-atomic, molecular dynamic (MD) simulation method. The behaviors of the dislocations, defect evolution and crack propagation until failure for Aluminum-Magnesium (Al-Mg) alloy are considered with the different temperature background and strain fields. The results of distributions of temperature and strain field in the aerodynamic environment obtained by molecular dynamics simulations are in good agreement with those obtained from the macroscopic Boltzmann method. Compared to the tensile loading, the alloy structure is more sensitive to compression loading. The polycrystalline Al-Mg alloy has higher yield strength with a larger grain size. It is due to the translation of plastic deformation mode from grain boundary (GB) sliding to dislocation slip and the accumulation of dislocation line. Our findings have paved a new way to analyze and predict the metallic structural failure by micro-scale analysis under the aerodynamic thermal extreme environment of the reentry spacecraft on service expiration.