The relationship between Geriatric Nutritional Risk Index (GNRI) and in-hospital mortality in critically ill patients with Acute Kidney Injury (AKI).

BACKGROUND: The role of the geriatric nutritional risk index (GNRI) as a prognostic factor in intensive care unit (ICU) patients with acute kidney injury (AKI) remains uncertain. OBJECTIVES: The aim of this study was to investigate the impact of the GNRI on mortality outcomes in critically ill patients with AKI. METHODS: For this retrospective study, we included 12,058 patients who were diagnosed with AKI based on ICD-9 codes from the eICU Collaborative Research Database. Based on the values of GNRI, nutrition-related risks were categorized into four groups: major risk (GNRI < 82), moderate risk (82 ≤ GNRI < 92), low risk (92 ≤ GNRI < 98), and no risk (GNRI ≥ 98). Multivariate analysis was used to evaluate the relationship between GNRI and outcomes. RESULTS: Patients with higher nutrition-related risk tended to be older, female, had lower blood pressure, lower body mass index, and more comorbidities. Multivariate analysis showed GNRI scores were associated with in-hospital mortality. (Major risk vs. No risk: OR, 95% CI: 1.90, 1.54-2.33, P < 0.001, P for trend < 0.001). Moreover, increased nutrition-related risk was negatively associated with the length of hospital stay (Coefficient: -0.033; P < 0.001) and the length of ICU stay (Coefficient: -0.108; P < 0.001). The association between GNRI scores and the risks of in-hospital mortality was consistent in all subgroups. CONCLUSIONS: GNRI serves as a significant nutrition assessment tool that is pivotal to predicting the prognosis of critically ill patients with AKI.

High-order diffraction for optical superfocusing.

High-order diffraction (HOD) from optical microstructures is undesirable in many applications because of the accompanying ghosting patterns and loss of efficiency. In contrast to suppressing HOD with subwavelength structures that challenge the fabrication of large-scale devices, managing HOD is less developed due to the lack of an efficient method for independently manipulating HOD. Here, we report independent manipulation of HODs, which are unexploited for subdiffraction-limit focusing in diffractive lenses, through an analytical formula that correlates the diffraction order and the width of each zone. The large spatial frequencies offered by the HODs enable our lenses to reduce the lateral focal size down to 0.44 λ even without any subwavelength feature (indispensable in most high-NA diffractive lenses), facilitating large-scale manufacture. Experimentally, we demonstrate high-order lens-based confocal imaging with a center-to-center dry resolution of 190 nm, the highest among visible-light confocal microscopies, and laser-ablation lithography with achieved direct-writing resolution of 400 nm (0.385 λ).

[Effect of Pterostilbene Regulating Nuclear Factor E2-Related Factor 2 on Apoptosis of Colon Cancer Cells in Vitro].

Objective To investigate the effects of pterostilbene on human colon cancer LoVo cells and study the regulatory mechanism of nuclear factor E2-related factor 2 (Nrf2) in the process of pterostilbene acting on LoVo cells. Methods LoVo cells were treated with different concentrations (5,10,20,40,60,80,100 µmol/L) of pterostilbene.Cell viability,migration,invasion,and apoptosis were examined by CCK-8,scratch,Transwell,and TUNEL assays,respectively.The mitochondrial membrane potential was measured by the mitochondrial membrane potential assay kit with JC-1.The reactive oxygen species level was measured by 2',7'-dichlorofluorescein diacetate.The protein levels of Nrf2,phosphorylated Nrf2,heme oxygenase 1,and apoptotic proteins (Bcl2 and Bax) were determined by Western blotting.In addition,cell viability,Nrf2 expression,and apoptosis rate were determined after co-application of the Nrf2-specific agonist sulforaphane. Results Compared with the control group,40,60,80,100 µmol/L pterostilbene reduced the viability of LoVo cells (P=0.014,P<0.001,P<0.001,P<0.001).Pterostilbene at 5,10,20 µmol/L did not show effects on cell viability but inhibited cell migration (P=0.008,P<0.001,P<0.001) and invasion (all P<0.001).Pterostilbene at 40,60,80 µmol/L increased apoptosis (P=0.014,P<0.001,P<0.001),promoted mitochondrial membrane potential depolarization (P=0.026,P<0.001,P<0.001) and reactive oxygen species accumulation (all P<0.001),and down-regulated the expression of phosphorylated Nrf2 (P=0.030,P<0.001,P<0.001),heme oxygenase 1 (P=0.015,P<0.001,P<0.001),and Bcl2 (P=0.039,P<0.001,P<0.001) in LoVo cells.Pterostilbene at 60,80 µmol/L down-regulated Nrf2 expression (P=0.001,P<0.001) and up-regulated Bax expression (both P<0.001).The application of sulforaphane reversed the effects of pterostilbene on cell viability (P<0.001),apoptosis (P<0.001),and Nrf2 expression (P=0.022). Conclusion Pterostilbene is a compound that can effectively inhibit colon cancer cells by inhibiting the Nrf2 pathway.

Dual-target inhibitors based on acetylcholinesterase: Novel agents for Alzheimer's disease.

Alzheimer's disease (AD) is the most common form of dementia among the elderly, accounting for 60 %-70 % of cases. At present, the pathogenesis of this condition remains unclear, but the hydrolysis of acetylcholine (ACh) is thought to play a role. Acetylcholinesterase (AChE) can break down ACh transmission from the presynaptic membrane and stop neurotransmitters' excitatory effect on the postsynaptic membrane, which plays a key role in nerve conduction. Acetylcholinesterase inhibitors (AChEIs) can delay the hydrolysis of acetylcholine (ACh), which represents a key strategy for treating AD. Due to its complex etiology, AD has proven challenging to treat. Various inhibitors and antagonists targeting key enzymes and proteins implicated in the disease's pathogenesis have been explored as potential therapeutic agents. These include Glycogen Synthase Kinase 3ß (GSK-3ß) inhibitors, ß-site APP Cleaving Enzyme (BACE-1) inhibitors, Monoamine Oxidase (MAO) inhibitors, Phosphodiesterase inhibitors (PDEs), N-methyl--aspartic Acid (NMDA) antagonists, Histamine 3 receptor antagonists (H3R), Serotonin receptor subtype 4 (5-HT4R) antagonists, Sigma1 receptor antagonists (S1R) and soluble Epoxide Hydrolase (sEH) inhibitors. The drug development strategy of multi-target-directed ligands (MTDLs) offers unique advantages in the treatment of complex diseases. On the one hand, it can synergistically enhance the therapeutic efficacy of single-target drugs. On the other hand, it can also reduce the side effects. In this review, we discuss the design strategy of dual inhibitors based on acetylcholinesterase and the structure-activity relationship of these drugs.

Heat-dependent properties of methane diffusion in coal: an experimental study and mechanistic analysis.

Coalbed methane thermodynamic extraction, as an emerging ECBM recovery method, can effectively improve gas recovery rates. And clarifying methane diffusion and migration law in coal under thermal stimulation is crucial for the selection of its process parameters. Based on laboratory methane adsorption-release experiments, the evolution law of methane diffusion characteristics with temperature and pressure was studied, and the control mechanism of heat-dependent methane diffusion behavior was explored. The results show that both thermal stimulation and high adsorption pressure accelerated the methane diffusion rate in coal. Adsorption pressure had little effect on methane diffusion percentage, but thermal stimulation promoted a significant increase in diffusion percentage and improved the net methane yield. The influence mechanisms of adsorption pressure and thermal stimulation on methane diffusion characteristics are elucidated in relation to the amount and proportion of methane-activated molecules in the diffusion process. The constant diffusion coefficient of methane is heat-dependent, based on which a diffusion model is derived to accurately predict the methane release process in coal. Additionally, temperature has a more important effect on transient diffusion coefficient than pressure. Thermal stimulation leads to a net increase rather than a decrease in diffusion coefficient in the early diffusion stages and can also accelerate the attenuation of diffusion coefficient, with this intensifying effect becoming more pronounced at higher temperatures. The research results can provide some reference for the determination of coal seam gas content and the selection of heat injection process parameters.

Angiopoietin-like 4 is a potential biomarker for diabetic kidney disease in type 2 diabetes patients.

AIMS/INTRODUCTION: The association between serum angiopoietin-like 4 (ANGPTL4) levels and the severity of diabetic kidney disease (DKD) in patients with type 2 diabetes mellitus remains unclear. METHODS: A total of 1,115 type 2 diabetes mellitus patients were analyzed in this cross-sectional study. DKD index included DKD stages defined by estimated glomerular filtration rate, the albuminuria grades and DKD risk management grades. Serum levels of ANGPTL4 and other biomarkers were detected. Multivariable-adjusted linear and logistic analyses were used to study the association between ANGPTL4 and DKD. The protein levels of ANGPTL4 were assessed in the kidney. Renal tubular cells were stimulated with glucose to study ANGPTL4 expression. RESULTS: Compared with the participants in the third or fourth quantile of ANGPTL4, those in the first or second quantile of ANGPTL4 were younger, with lower glycated hemoglobin, triglycerides and urinary albumin creatinine ratio (all P < 0.05). There was a negative nonlinear relationship between ANGPTL4 and estimated glomerular filtration rate in type 2 diabetes mellitus patients. One standard deviation increased serum ANGPTL4 levels, the odds ratio of having DKD was 1.40 (95% confidence interval 1.08-1.80). The mediation analysis showed that triglycerides did not mediate the association between ANGPTL4 and DKD. Furthermore, ANGPTL4 could be the strongest among multiple panels of biomarkers in its association of DKD. Compared with mice at 8 weeks-of-age, db/db mice at 18 weeks-of-age had increased ANGPTL4 expression in glomeruli and tubular segments. In vitro, glucose could stimulate ANGPTL4 expression in tubular cells in a dose-dependent manner. CONCLUSIONS: ANGPTL4 could be a potential marker and therapeutic target for DKD treatment.

Structure-Based Discovery of Symmetric Disulfides from Garlic Extract as Pseudomonas aeruginosa Quorum Sensing Inhibitors.

Microorganisms are the most common cause of food spoilage. Pseudomonas aeruginosa is a common foodborne pathogen that causes food spoilage and poses a serious threat to food safety. As a crucial target in antitoxicity strategies, the quorum sensing (QS) system shows promising potential for further development. The garlic extract diallyl disulfide exhibits inhibitory activity against the QS system of P. aeruginosa, with disulfide bonds serving as the active component. However, the biological activity of other symmetric disulfides has not been investigated in this capacity. The study synthesized 39 disulfide bond-containing analogs and evaluated their activity as quorum sensing inhibitors (QSIs). The results showed that p-hydroxyphenyl substitution can replace the allyl groups while maintaining strong biological activity. The virulence factors production was reduced by compound 2i, with the strongest inhibitory effect being observed on elastase production. Synergistic inhibition was observed in the presence of antibiotics like ciprofloxacin and tobramycin. 2i successfully inhibited P. aeruginosa infection in the Galleria mellonella larvae model. Primary mechanism studies using transcriptome, surface plasmon resonance and molecular docking suggested that 2i inhibits the QS system by targeting the LasR protein. Thus, compound 2i could be used in developing QSIs for the control of P. aeruginosa infections.

Magnetic resonance imaging-based radiomics model for preoperative assessment of risk stratification in endometrial cancer.

BACKGROUND: Preoperative risk stratification is significant for the management of endometrial cancer (EC) patients. Radiomics based on magnetic resonance imaging (MRI) in combination with clinical features may be useful to predict the risk grade of EC. AIM: To construct machine learning models to predict preoperative risk stratification of patients with EC based on radiomics features extracted from MRI. METHODS: The study comprised 112 EC patients. The participants were randomly separated into training and validation groups with a 7:3 ratio. Logistic regression analysis was applied to uncover independent clinical predictors. These predictors were then used to create a clinical nomogram. Extracted radiomics features from the T2-weighted imaging and diffusion weighted imaging sequences of MRI images, the Mann-Whitney U test, Pearson test, and least absolute shrinkage and selection operator analysis were employed to evaluate the relevant radiomic features, which were subsequently utilized to generate a radiomic signature. Seven machine learning strategies were used to construct radiomic models that relied on the screening features. The logistic regression method was used to construct a composite nomogram that incorporated both the radiomic signature and clinical independent risk indicators. RESULTS: Having an accuracy of 0.82 along with an area under the curve (AUC) of 0.915 [95% confidence interval (CI): 0.806-0.986], the random forest method trained on radiomics characteristics performed better than expected. The predictive accuracy of radiomics prediction models surpassed that of both the clinical nomogram (AUC: 0.75, 95%CI: 0.611-0.899) and the combined nomogram (AUC: 0.869, 95%CI: 0.702-0.986) that integrated clinical parameters and radiomic signature. CONCLUSION: The MRI-based radiomics model may be an effective tool for preoperative risk grade prediction in EC patients.

In-Hospital Mortality and Treatment in Patients With Acute Coronary Syndrome With and Without Standard Modifiable Cardiovascular Risk Factors: Findings From the CCC-ACS Project.

BACKGROUND: Patients with acute coronary syndrome without standard modifiable cardiovascular risk factors (SMuRFs; hypertension, smoking, dyslipidemia, diabetes) have not been well studied, with little known about their characteristics, quality of care, or outcomes. We sought to systematically analyze patients with ACS without SMuRFs, especially to evaluate the effectiveness of guideline-directed medical therapy for these patients. METHODS AND RESULTS: In the CCC-ACS (Improving Care for Cardiovascular Disease in China-Acute Coronary Syndrome) project (2014-2019), we examined the presence and absence of SMuRFs and features among 89 462 patients with initial acute coronary syndrome. The main outcome was in-hospital all-cause mortality. Among eligible patients, 11.0% had none of the SMuRFs (SMuRF-less). SMuRF-less patients had higher in-hospital mortality (unadjusted hazard ratio [HR], 1.49 [95% CI, 1.19-1.87]). After adjustment for clinical characteristics and treatments, the associations between SMuRF status and in-hospital mortality persisted (adjusted HR, 1.35 [95% CI, 1.07-1.70]). Guideline-directed optimal medical therapy (receiving angiotensin-converting enzyme inhibitors/angiotensin receptor blockers, ß-blockers, and statins) was not associated with lower mortality (adjusted HR, 0.98 [95% CI, 0.58-1.67]) in SMuRF-less patients, unlike the association in patients with SMuRFs (adjusted HR, 0.80 [95% CI, 0.66-0.98]). Sensitivity analyses were consistent with these results. CONCLUSIONS: SMuRF-less patients were associated with an increased risk of in-hospital mortality. Guideline-directed medical therapy was less effective in SMuRF-less patients than in patients with SMuRFs. Dedicated studies are needed to confirm the optimal therapy for SMuRF-less patients. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT02306616.

Herbicidal Sorbicillinoid Analogs Cause Lignin Accumulation in Aspergillus aculeatus TE-65L.

Five new sorbicillinoid derivatives, including (±)-aspersorbicillin A [(±)-1], a pair of enantiomers at C-9, and aspersorbicillins B-D (2-4), together with two known analogs (5 and 6) were isolated from the endophytic fungus Aspergillus aculeatus TE-65L. Their structures including absolute configurations were determined by detailed spectroscopic analyses and electronic circular dichroism calculations. The herbicidal activity of sorbicillinoids on the germ and radicle elongation of various weed types was reported for the first time. Compound 1 displayed significant herbicidal activity against Eleusine indica germ elongation (IC50 = 28.8 µg/mL), while compound 6 inhibited radicle elongation (IC50 = 25.6 µg/mL). Both were stronger than those of glyphosate (66.2 and 30.9 µg/mL, respectively). Further transcriptomic and LC-MS/MS metabolomic analysis indicated that 6 induced the transcriptional expressions of genes related to the lignin biosynthetic pathway, resulting in lignin accumulation. Transmission electron microscopy confirmed the cell wall thickening of seeds treated with 6, suggesting weed growth inhibition. This study reveals new lead compounds for fabricating natural herbicides and expands the agricultural use of sorbicillinoid analogs.

Combined effect of intermittent hemostasis and a modified external hemorrhage control device in a lethal swine model.

Background: Non-compressible torso hemorrhage (NCTH) presents the ultimate challenge in pre-hospital care. While external hemorrhage control devices (EHCDs) such as the Abdominal Aortic and Junctional Tourniquet (AAJT) and SAM Junctional Tourniquet (SJT) have been invented, the current design and application strategy requires further improvement. Therefore, researchers devised a novel apparatus named Modified EHCD (M-EHCD) and implemented intermittent hemostasis (IH) as a preventive measure against ischemia-reperfusion injury. The objective of this study was to ascertain the combined effect of M-EHCD and IH on the hemostatic effect of NCTH. Methods: Eighteen swine were randomized to M-EHCD, AAJT or SJT. The NCTH model was established by inducing Class Ⅲ hemorrhagic shock and performing a hemi-transection of common femoral artery (CFA). EHCDs were rapidly fastened since the onset of free bleeding (T0min). The IH strategy was implemented by fully releasing M-EHCD at T40min, T70min and T100min, respectively, whereas AAJT and SJT maintained continuous hemostasis (CH) until T120min. All groups underwent CFA bridging at T110min, and EHCDs were removed at T120min. Reperfusion lasted for 60 min, after which euthanasia was performed. Hemodynamics, intra-vesical pressure (IVP), and blood samples were collected periodically. Histological examinations were also conducted. Results: M-EHCD demonstrated the fastest application time (M-EHCD: 26.38 ± 6.32s vs. SJT: 30.84 ± 5.62s vs. AAJT: 54.28 ± 5.45s, P < 0.001) and reduced free blood loss (M-EHCD: 17.77 ± 9.85g vs. SJT: 51.80 ± 33.70g vs. AAJT: 115.20 ± 61.36g, P = 0.011) compared to SJT and AAJT. M-EHCD exhibited inhibitory effects on heart rate (M-EHCD: 91.83 ± 31.61bpm vs. AAJT: 129.00 ± 32.32bpm vs. SJT: 135.17 ± 21.24bpm, P = 0.041) and shock index. The device's external pressure was lowest in M-EHCD and highest in SJT (P = 0.001). The resultant increase in IVP were still the lowest in M-EHCD (M-EHCD: -0.07 ± 0.45 mmHg vs. AAJT: 27.04 ± 5.03 mmHg vs. SJT: 5.58 ± 2.55 mmHg, P < 0.001). Furthermore, M-EHCD caused the least colonic injury (M-EHCD: 1.17 ± 0.41 vs. AAJT: 2.17 ± 0.41 vs. SJT: 2.17 ± 0.41, P = 0.001). The removal of M-EHCD showed the slightest impact on pH (P < 0.001), while AAJT group was more susceptible to the lethal triad based on the arterial lactate and thrombelastogram results. Conclusions: M-EHCD + IH protected the organs and reduced the risk of the lethal triad by decreasing disruptions to IVP, hemodynamics, acid-base equilibrium and coagulation. M-EHCD + IH was superior to the hemostatic safety and efficacy of AAJT/SJT + CH.

Case report: Germline BRCA 2 mutation in primary peritoneal carcinoma: a rare malignancy.

Background: Primary peritoneal carcinoma (PPC) is a rare malignancy. Clinically, its histological morphology resembles that of epithelial ovarian tumors (EOC), often leading to misdiagnosis. Diagnosis and treatment of PPC are time-sensitive because of the rapidly progressive nature of the disease. Case report: Herein, we report the case of a 54-year-old woman who was initially diagnosed with ovarian cancer; however, extensive workup showed evidence of Müllerian PPC origin. Furthermore, the patient harbored a targetable BRCA mutation. Conclusion: The patient was treated with the BRCA-targeting agents and had a good prognosis after surgery.

Trajectories of Remnant Cholesterol are Associated with Diabetic Foot Ulcer in Adult Patients with Type 2 Diabetes: A Retrospective Cohort Study.

Objective: This study aimed to investigate the potential association between long-term variations in remnant cholesterol (RC) levels and the development of diabetic foot ulcers (DFU) in participants with type 2 diabetes (T2D). Methods: This was a retrospective cohort study. Variation in RC was assessed by the following metrics: mean, standard deviation (SD), coefficient of variation (CV) and trajectories pattern of RC. To identify RC trajectories, we employed the latent class mixture model. The primary endpoint was the development of DFU, and the time-to-event data were analyzed using Cox regression. Results: A total of 1874 patients with T2D were included, with a median follow-up duration of 4.7 years. Among them, 129 individuals (6.9%) developed DFU. The proportion of DFU was significantly higher in the U-shaped group compared to the median group (P for trend < 0.001). Upon adjustment for confounding variables, the U-shaped trajectory correlated with a higher risk of DFU, demonstrating a hazard ratio (HR) of 2.57 (95% CI, 1.54-4.27). Subgroup analysis showed the U-shaped trajectory had a higher DFU risk regardless of gender (HR=2.40 and 2.81, respectively), glycemic control (HR=1.89 and 7.41, respectively), smoking (HR=2.36 and 2.93, respectively), or hypertension (HR=2.30 and 2.97, respectively). No association was found between mean, SD and CV of RC and DFU. Conclusion: A U-shape trajectory of RC was independently associated with an elevated risk of DFU among patients with T2D.

Taking Photoacoustic Force into Account in Liquid-Phase Peak Force Infrared Microscopy.

The microscopic structure of the material's solid-liquid interface significantly influences its physicochemical properties. Peak force infrared microscopy (PFIR) is a powerful technique for analyzing these interfaces at the nanoscale, revealing crucial structure-activity relationships. PFIR is recognized for its explicit photothermal signal generation mechanism but tends to overlook other photoinduced forces, which can disturb the obtained infrared spectra, thereby reducing spectral signal-to-noise ratio (SNR) and sensitivity. We have developed a multiphysics-coupled theoretical model to assess the magnitudes of various photoinduced forces in PFIR experiments and have found that the magnitude of the photoacoustic force is comparable to that of the photothermal expansion force in a liquid environment. Our calculations show that through simple modulation of the pulse waveform it is possible to effectively suppress the photoacoustic interference, thereby improving the SNR and sensitivity of PFIR. This work aims to alert researchers to the potential for strong photoacoustic interference in liquid-phase PFIR measurements and enhance the performance of PFIR by clarifying the photoinduced forces entangled in the signals.

Effect of different processing steps in the production of beer fish on volatile flavor profile and their precursors determined by HS-GC-IMS, HPLC, E-nose, and E-tongue.

Beer fish is characterized by its distinctive spicy flavor and strong beer aroma. Currently, there is a lack of comprehensive research analyzing the changes in taste and volatile compounds that occur during the processing of beer fish. Thus, this study used HS-GC-IMS, electronic tongue, and electronic nose to investigate the changes in flavor components during various processing stages of beer fish. The obtained results were subsequently analyzed using multivariate statistical analysis. The results showed that the final beer fish product (SF) had the greatest amount of free amino acids (888.28 mg/100 g), with alanine, glutamic acid, and glycine contributing to the taste of SF. The inosine monophosphate (IMP) content of beer fish meat varied noticeably depending on processing stages, with deep-fried fish (FF) having the greatest IMP content (61.93 mg/100 g), followed by the final product (SF) and ultrasonic-cured fish (UF). A total of 67 volatiles were detected by GC-IMS, mainly consisting of aldehydes, ketones, and alcohols, of which aldehydes accounted for >37%, which had a great influence on the volatile flavor of beer fish. The flavor components' composition varied noticeably depending on the stage of processing. PLS-DA model screened 35 volatile flavor components (VIP > 1) as markers; the most significant differences were 1-propanethiol, isoamyl alcohol, ethanol, and eucalyptol. Ultrasonic processing, frying, and soaking sauce can significantly improve the formation of flavor compounds, resulting in a notable enhancement of the final beer fish's umami taste and overall flavor quality.

Glucocorticoid therapy in pancreatic portal hypertension associated with autoimmune pancreatitis: A case report.

BACKGROUND: Autoimmune pancreatitis (AIP) is a chronic form of pancreatitis characterized by diffused enlargement of the pancreas and irregular stenosis of the main pancreatic duct. Some studies have reported that AIP can cause hemorrhage of gastric varices (GV) related to portal hypertension (PH). However, such cases are rare. In addition, the association of PH with AIP is unclear. At the same time, the efficacy and duration of glucocorticoid therapy is also controversial. CASE SUMMARY: In this case, we reported a case of GV in pancreatic PH associated with AIP. Enhanced abdominal computed tomography (CT) suggested splenic vein (SV) and superior mesenteric vein (SMV) thromboses. The patient received a long-term glucocorticoid therapy, that the initial dose of 40 mg is reduced weekly by 5 mg, and then reduced to 5 mg for long-term maintenance. CT and gastroscopic examination after 8 mo of treatment indicated that SV and SMV were recanalized, pancreatic stiffness and swelling were ameliorated, and the GV almost completely disappeared. CONCLUSION: Long-term glucocorticoid therapy can alleviate the development of GV in patients with AIP and has potential reversibility.

Remimazolam Alleviates Ventilator-Induced Lung Injury by Activating TSPO to Inhibit Macrophage Pyroptosis.

BACKGROUND: Macrophages are activated in ventilator-induced lung injury (VILI), accompanied by macrophage pyroptosis. Remimazolam (Re) plays a role in inhibiting macrophage activation. In this study, we aimed to investigate the mechanism of Re in VILI. METHODS: A VILI model (20 mL/kg mechanical ventilation) was created using C57BL/6 mice. Alveolar macrophages were isolated from bronchoalveolar lavage fluid (BALF) and received mechanical stretching to simulate the mechanical ventilation in vitro. VILI model mice were treated with Re (16 mg/kg) to assess the alveolar structure, wet/dry (W/D) weight ratio, endothelial barrier antigen (EBA) permeability index, BALF protein content, inflammatory factors, macrophage pyroptosis, pyroptosis-related factors, and translocator protein (TSPO) level using a series of biological experiments. Whether Re alleviated macrophage pyroptosis by regulating TSPO was determined by rescue experiments. RESULTS: Re alleviated VILI, as evidenced by improvement of abnormal morphology of lung tissues during VILI and decreases in the lung W/D weight ratio, lung EBA permeability index, and BALF protein content. Re attenuated pulmonary inflammation and macrophage pyroptosis during VILI via down-regulation of inflammatory factors (myeloperoxidase, malondialchehyche, 8-hydroxy-2 deoxyguanosine, interleukin-6, tumor necrosis factor-α, macrophage inflammatory protein-2, interleukin-1ß, and interleukin-18), and pyroptosis factors (cleaved gasdermin D (GSDMD)/GSDMD value, NOD-like receptor thermal protein domain associated protein 3 (NLRP3), and caspase-1). Re activated TSPO in macrophages. TSPO overexpression rescued the cell stretch-inhibited macrophage viability and cell stretch-induced macrophage pyroptosis. CONCLUSION: Re alleviates VILI by activating TSPO to inhibit macrophage pyroptosis.

Integrated Analysis of Clinical Outcome of Mesenchymal Stem Cell-related Genes in Pan-cancer.

Background: Although the application of mesenchymal stem cells (MSCs) in engineered medicine, such as tissue regeneration, is well known, new evidence is emerging that shows that MSCs can also promote cancer progression, metastasis, and drug resistance. However, no large-scale cohort analysis of MSCs has been conducted to reveal their impact on the prognosis of cancer patients. Objectives: We propose the MSC score as a novel surrogate for poor prognosis in pan-cancer. Methods: We used single sample gene set enrichment analysis to quantify MSC-related genes into a signature score and identify the signature score as a potential independent prognostic marker for cancer using multivariate Cox regression analysis. TIDE algorithm and neural network were utilized to assess the predictive accuracy of MSC-related genes for immunotherapy. Results: MSC-related gene expression significantly differed between normal and tumor samples across the 33 cancer types. Cox regression analysis suggested the MSC score as an independent prognostic marker for kidney renal papillary cell carcinoma, mesothelioma, glioma, and stomach adenocarcinoma. The abundance of fibroblasts was also more representative of the MSC score than the stromal score. Our findings supported the combined use of the TIDE algorithm and neural network to predict the accuracy of MSC-related genes for immunotherapy. Conclusion: We comprehensively characterized the transcriptome, genome, and epigenetics of MSCs in pan-cancer and revealed the crosstalk of MSCs in the tumor microenvironment, especially with cancer-related fibroblasts. It is suggested that this may be one of the key sources of resistance to cancer immunotherapy.

Broadening horizons: the role of ferroptosis in polycystic ovary syndrome.

Polycystic ovarian syndrome (PCOS) is a common heterogeneous reproductive endocrine metabolic disorder in women of reproductive age characterized by clinical and biochemical hyperandrogenemia, ovulation disorders, and polycystic ovarian morphology. Ferroptosis is a novel type of cell death driven by iron accumulation and lipid peroxidation. Ferroptosis plays a role in maintaining redox balance, iron metabolism, lipid metabolism, amino acid metabolism, mitochondrial activity, and many other signaling pathways linked to diseases. Iron overload is closely related to insulin resistance, decreased glucose tolerance, and the occurrence of diabetes mellitus. There is limited research on the role of ferroptosis in PCOS. Patients with PCOS have elevated levels of ferritin and increased reactive oxygen species in ovarian GCs. Studying ferroptosis in PCOS patients is highly important for achieving personalized treatment. This article reviews the progress of research on ferroptosis in PCOS, introduces the potential connections between iron metabolism abnormalities and oxidative stress-mediated PCOS, and provides a theoretical basis for diagnosing and treating PCOS.

Enhancing Rapid Li+/Na+ Storage Performance via Interface Engineering of Reduced Graphene Oxide-Wrapped Bimetallic Sulfide Nanocages.

Transition-metal sulfide is considered to be an admirable transformational electrode material due to low cost, large specific capacity, and good reversibility in lithium-ion batteries (LIBs) and sodium-ion batteries (SIBs). Herein, the reduced graphene oxide-wrapped open bimetallic sulfide (NiS2-Co3S4@rGO) nanocage, derived from nickel-cobalt Prussian blue, was obtained by two-step calcination. There are luxuriant pore structures in the nanocage composite with a specific surface area of 85.28 m2 g-1, which provides plentiful paths for rapid transmission of Li+/Na+ and alleviates the volume stress caused by insertion and extraction of alkali metal ions. The excellent interface combination of bimetallic sulfide wrapped in reduced graphene oxide improves the conductivity and overall performance of the battery. Thanks to the special interface engineering, the open NiS2-Co3S4@rGO nanocage composite displays rapid lithium storage properties with an average diffusion coefficient of 8.5 × 10-13 cm2 s-1. Moreover, after 300 cycles, the reversible capacity of the composite is 1113.2 mAh g-1 at 1 A g-1. In SIBs, the capacity of the open NiS2-Co3S4@rGO composite is 487.9 mAh g-1 when the current density is 5 A g-1. These preeminent performances demonstrate the enormous development prospects of bimetallic sulfide nanocage as anode material in LIBs and SIBs.