[Mechanism of Dabugan Decoction in treatment of generalized anxiety disorder based on network pharmacology and experimental verification].

This study aims to explore the mechanism of Dabugan Decoction in the treatment of generalized anxiety disorder(GAD) based on network pharmacology, molecular docking, and animal experiments. Network pharmacology and molecular docking technology were used to obtain the possible targets and related signaling pathways of Dabugan Decoction in the treatment of GAD. The GAD rat model was established, and the corresponding drugs were given by gavage after randomization. After 28 days of continuous intervention, the anxiety state of rats was detected, and the pathological changes of the hippocampus were detected in each group. ELISA and Western blot were used to detect the protein expression levels of related molecules. A total of 65 drug compounds in Dabugan Decoction were obtained, involving 403 targets of action, 7 398 disease targets of GAD, and 279 common targets of "drug-disease". The key nodes in the protein-protein interaction(PPI) network were Akt1, TNF, IL-6, TP53, IL-1ß, etc. Function analysis of Gene Ontology(GO) and enrichment analysis of Kyoto Encyclopedia of Genes and Genomes(KEGG) showed that the PI3K-Akt signaling pathway was the most important pathway. The results of molecular docking showed that the core components of the drug had good binding activity with the corresponding key targets. Animal experiments showed that Dabugan Decoction could effectively improve the anxiety behavior of rats and increase the open arm end movement distance and total distance of rats in the elevated cross labyrinth, the number and stay time of entering the open box, and the time(%) and the number of entering the center of the open field. At the same time, HE staining and Nicil staining showed that the number of hippocampal nerve cells in rats increased, and they were closely arranged. The damage to the cell body was improved, and there was an increase in Nissl substances in the cells. The expression of TNF-α, IL-6, and IL-1ß in rat hippocampus decreased, and the expression of TP53, p-Akt1, and p-PI3K increased. The mechanism may be related to the activation of the PI3K-Akt signaling pathway and the inhibition of inflammatory response. Dabugan Decoction can play a good therapeutic and regulatory role in GAD, reflecting the overall effect of traditional Chinese medicine(TCM) compound and the characteristics of multiple targets and multiple pathways. At the same time, it is preliminarily discussed that the state of GAD may be improved by Dabugan Decoction via-activating PI3K-Akt signaling pathway and inhibiting inflammatory response and anti-apoptosis, thus providing experimental data support for the clinical application of Dabugan Decoction.

Ferroelectric polarization and magnetic structure at domain walls in a multiferroic film.

Domain walls affect significantly ferroelectric and magnetic properties of magnetoelectric multiferroics. The stereotype is that the ferroelectric polarization will reduce at the domain walls due to the incomplete shielding of depolarization field or the effects of gradient energy. By combining transmission electron microscopy and first-principles calculations, we demonstrate that the ferroelectric polarization of tail-to-tail 180° domain walls in ε-Fe2O3 is regulated by the bound charge density. A huge enhancement (43%) of ferroelectric polarization is observed in the type I domain wall with a low bound charge density, while the ferroelectric polarization is reduced to almost zero at the type II domain wall with a high bound charge density. The magnetic coupling across the type I and type II ferroelectric domain walls are antiferromagnetic and ferromagnetic, respectively. Revealing mechanisms for enhancing ferroelectric polarization and magnetic behaviors at ferroelectric domain walls may promote the fundamental research and potential applications of magnetoelectric multiferroics.

Polar Bloch points in strained ferroelectric films.

Topological domain structures have drawn great attention as they have potential applications in future electronic devices. As an important concept linking the quantum and classical magnetism, a magnetic Bloch point, predicted in 1960s but not observed directly so far, is a singular point around which magnetization vectors orient to nearly all directions. Here we show polar Bloch points in tensile-strained ultrathin ferroelectric PbTiO3 films, which are alternatively visualized by phase-field simulations and aberration-corrected scanning transmission electron microscopic imaging. The phase-field simulations indicate local steady-state negative capacitance around the Bloch points. The observation of polar Bloch points and their emergent properties consequently implies novel applications in future integrated circuits and low power electronic devices.

Vaporization of perfluorocarbon attenuates sea-water-drowning-induced acute lung injury by deactivating the NLRP3 inflammasomes in canines.

Seawater-drowning-induced acute lung injury (SD-ALI) is a life-threatening disorder characterized by increased alveolar-capillary permeability, an excessive inflammatory response, and refractory hypoxemia. Perfluorocarbons (PFCs) are biocompatible compounds that are chemically and biologically inert and lack toxicity as oxygen carriers, which could reduce lung injury in vitro and in vivo. The aim of our study was to explore whether the vaporization of PFCs could reduce the severity of SD-ALI in canines and investigate the underlying mechanisms. Eighteen beagle dogs were randomly divided into three groups: the seawater drowning (SW), perfluorocarbon (PFC), and control groups. The dogs in the SW group were intratracheally administered seawater to establish the animal model. The dogs in the PFC group were treated with vaporized PFCs. Probe-based confocal laser endomicroscopy (pCLE) was performed at 3 h. The blood gas, volume air index (VAI), pathological changes, and wet-to-dry (W/D) lung tissue ratios were assessed. The expression of heme oxygenase-1 (HO-1), nuclear respiratory factor-1 (NRF1), and NOD-like receptor family pyrin domain containing-3 (NLRP3) inflammasomes was determined by means of quantitative real-time polymerase chain reaction (qRT-PCR) and immunological histological chemistry. The SW group showed higher lung injury scores and W/D ratios, and lower VAI compared to the control group, and treatment with PFCs could reverse the change of lung injury score, W/D ratio and VAI. PFCs deactivated NLRP3 inflammasomes and reduced the release of caspase-1, interleukin-1ß (IL-1ß), and interleukin-18 (IL-18) by enhancing the expression of HO-1 and NRF1. Our results suggest that the vaporization of PFCs could attenuate SD-ALI by deactivating NLRP3 inflammasomes via the HO-1/NRF1 pathway.

H2O-Mg2+ Waltz-Like Shuttle Enables High-Capacity and Ultralong-Life Magnesium-Ion Batteries.

Mg-ion batteries (MIBs) are promising next-generation secondary batteries, but suffer from sluggish Mg2+ migration kinetics and structural collapse of the cathode materials. Here, an H2O-Mg2+ waltz-like shuttle mechanism in the lamellar cathode, which is realized by the coordination, adaptive rotation and flipping, and co-migration of lattice H2O molecules with inserted Mg2+, leading to the fast Mg2+ migration kinetics, is reported; after Mg2+ extraction, the lattice H2O molecules rearrange to stabilize the lamellar structure, eliminating structural collapse of the cathode. Consequently, the demo cathode of Mg0.75V10O24·nH2O (MVOH) exhibits a high capacity of 350 mAh g-1 at a current density of 50 mA g-1 and maintains a capacity of 70 mAh g-1 at 4 A g-1. The full aqueous MIB based on MVOH delivers an ultralong lifespan of 5000 cycles The reported waltz-like shuttle mechanism of lattice H2O provides a novel strategy to develop high-performance cathodes for MIBs as well as other multivalent-ion batteries.

Dual-Defect Engineering Strategy Enables High-Durability Rechargeable Magnesium-Metal Batteries.

Rechargeable magnesium-metal batteries (RMMBs) are promising next-generation secondary batteries; however, their development is inhibited by the low capacity and short cycle lifespan of cathodes. Although various strategies have been devised to enhance the Mg2+ migration kinetics and structural stability of cathodes, they fail to improve electronic conductivity, rendering the cathodes incompatible with magnesium-metal anodes. Herein, we propose a dual-defect engineering strategy, namely, the incorporation of Mg2+ pre-intercalation defect (P-Mgd) and oxygen defect (Od), to simultaneously improve the Mg2+ migration kinetics, structural stability, and electronic conductivity of the cathodes of RMMBs. Using lamellar V2O5·nH2O as a demo cathode material, we prepare a cathode comprising Mg0.07V2O5·1.4H2O nanobelts composited with reduced graphene oxide (MVOH/rGO) with P-Mgd and Od. The Od enlarges interlayer spacing, accelerates Mg2+ migration kinetics, and prevents structural collapse, while the P-Mgd stabilizes the lamellar structure and increases electronic conductivity. Consequently, the MVOH/rGO cathode exhibits a high capacity of 197 mAh g-1, and the developed Mg foil//MVOH/rGO full cell demonstrates an incredible lifespan of 850 cycles at 0.1 A g-1, capable of powering a light-emitting diode. The proposed dual-defect engineering strategy provides new insights into developing high-durability, high-capacity cathodes, advancing the practical application of RMMBs, and other new secondary batteries.

Role of Platelet/Lymphocyte, Neutrophil/Lymphocyte, and Interleukin-37/Interleukin-17 Ratios in the Occurrence and Treatment of Rheumatoid Arthritis.

This study was designed to investigate the correlation of neutrophil/lymphocyte ratio (NLR), platelet/lymphocyte ratio (PLR), and interleukin (IL)-37/IL-17 ratio with the incidence/treatment of rheumatoid arthritis (RA). Firstly, fifty-eight patients with RA treated at the first affiliated hospital of Xinjiang Medical University from January 2018 to January 2019 were selected as the RA group; forty-nine healthy volunteers were enrolled in the control group. RA patients were treated with disease-modifying anti-rheumatic drugs (DMARDs). Next, the NLR, PLR, IL-37, IL-17 and 28-joint disease activity score using erythrocyte sedimentation rate (DAS28-ESR) were deleted in two groups. Subsequently, Spearman correlation analysis was adopted for the correlations of various indicators before and after treatment in two groups. According to the analysis results, the levels of NLR, PLR, IL-37, and IL-17 before treatment in the RA group were higher than those in the control group (P < .05), but the difference in the IL-37/IL-17 level between the two groups was not significant (P > .05). After treatment, NLR, PLR, and IL-37/IL-17 levels were significantly reduced in RA patients (P < .05). NLR and PLR were significantly positively correlated with DAS28-ESR, ESR and C-reactive protein (CRP), of which represented the disease activity of RA. NLP was strongly correlated with IL-37/IL-17. Collectively, NLR, PLR, IL-37, and IL-17 are closely related to the occurrence of RA. In addition, NLR and IL-37/IL-17 are more suitable than PLR in reflecting the therapeutic effect. Therefore, IL-37/IL-17 can be considered as a new indicator for reflecting the treatment effectiveness of RA.

MCT4-dependent lactate transport: a novel mechanism for cardiac energy metabolism injury and inflammation in type 2 diabetes mellitus.

Diabetic cardiomyopathy (DCM) is a major contributor to mortality in diabetic patients, characterized by a multifaceted pathogenesis and limited therapeutic options. While lactate, a byproduct of glycolysis, is known to be significantly elevated in type 2 diabetes, its specific role in DCM remains uncertain. This study reveals an abnormal upregulation of monocarboxylate transporter 4 (MCT4) on the plasma membrane of cardiomyocytes in type 2 diabetes, leading to excessive lactate efflux from these cells. The disruption in lactate transport homeostasis perturbs the intracellular lactate-pyruvate balance in cardiomyocytes, resulting in oxidative stress and inflammatory responses that exacerbate myocardial damage. Additionally, our findings suggest increased lactate efflux augments histone H4K12 lactylation in macrophages, facilitating inflammatory infiltration within the microenvironment. In vivo experiments have demonstrated that inhibiting MCT4 effectively alleviates myocardial oxidative stress and pathological damage, reduces inflammatory macrophage infiltration, and enhances cardiac function in type 2 diabetic mice. Furthermore, a clinical prediction model has been established, demonstrating a notable association between peripheral blood lactate levels and diastolic dysfunction in individuals with type 2 diabetes. This underscores the potential of lactate as a prognostic biomarker for DCM. Ultimately, our findings highlight the pivotal involvement of MCT4 in the dysregulation of cardiac energy metabolism and macrophage-mediated inflammation in type 2 diabetes. These insights offer novel perspectives on the pathogenesis of DCM and pave the way for the development of targeted therapeutic strategies against this debilitating condition.

Dose-response relationship between sleep duration and cardiovascular metabolic multimorbidity among older adults in China: A nationwide survey.

AIMS AND OBJECTIVES: The purpose of this study was to explore the relationship between the duration of sleep per day and cardiovascular metabolic multimorbidity (CMM) in older adults and to identify how many hours of sleep per day can lead to a lower risk of CMM in older adults. BACKGROUND: CMM are a common syndrome in the older adults. There may be an association between sleep duration and CMM in older adults, with both insomnia and sleep deprivation having an impact on the health of older adults. Therefore, it is important to explore the possibility that older adults who sleep for a few hours per day may have a lower prevalence of CMM. METHODS: The study included 9710 older adults. The sleep duration in this study was assessed by the question "How many hours of sleep do you currently get in a day? ". Older adults were defined as having CMM when they had two or more of the five categories of hypertension, diabetes, heart disease, stroke or cardiovascular disease, dyslipidemia. We used multivariate logistic regression analysis to explore the association among sleep duration and CMM. Restrictive cubic splines were used to examine the shape of the association among sleep duration and the CMM. The STROBE checklist was used for this cross-sectional study. RESULTS: The mean age was 84.78 ± 11.73 years, with 55.5 % being female. Of the total sample, 21.3 % were CMM. When all covariates were adjusted, there was dose-response relationship between sleep duration and CMM. The dose-response relationship between CMM and sleep duration showed that older adults had a lower risk of cardiovascular and metabolic multimorbidity when they slept 9 h and 10 h per day. CONCLUSION: With the increasing population of older adults, the number of older adults suffering from CMM continues to rise, and adequate sleep time can effectively prevent the occurrence of CMM. We should pay attention to the sleep problem of the older adults. RELEVANCE TO CLINICAL PRACTICE: This study provided information for healthcare providers to identify circumstances that increase cardiovascular metabolic multimorbidity and suggest the appropriate sleep duration per day to reduce the risk of disease in older adults. PATIENT OR PUBLIC CONTRIBUTION: Because of the public database data used in this study, all data were collected by survey agency personnel, so this section is not applicable to this study.

Large Polarization Near 50 µC/cm2 in a Single Unit Cell Layer SrTiO3.

The generally nonpolar SrTiO3 has attracted more attention recently because of its possibly induced novel polar states and related paraelectric-ferroelectric phase transitions. By using controlled pulsed laser deposition, high-quality, ultrathin, and strained SrTiO3 layers were obtained. Here, transmission electron microscopy and theoretical simulations have unveiled highly polar states in SrTiO3 films even down to one unit cell at room temperature, which were stabilized in the PbTiO3/SrTiO3/PbTiO3 sandwich structures by in-plane tensile strain and interfacial coupling, as evidenced by large tetragonality (∼1.05), notable polar ion displacement (0.019 nm), and thus ultrahigh spontaneous polarization (up to ∼50 µC/cm2). These values are nearly comparable to those of the strong ferroelectrics as the PbZrxTi1-xO3 family. Our findings provide an effective and practical approach for integrating large strain states into oxide films and inducing polarization in nonpolar materials, which may broaden the functionality of nonpolar oxides and pave the way for the discovery of new electronic materials.

Antifungal activity of ruthenium (II) complex combined with fluconazole against drug-resistant Candida albicans in vitro and its anti-invasive infection in vivo.

With the abuse of antibiotics and azoles, drug-resistant Candida albicans infections have increased sharply and are spreading rapidly, thereby significantly reducing the antifungal efficacy of existing therapeutics. Several patients die of fungal infections every year. Therefore, there is an urgent requirement to develop new drugs. Accordingly, we synthesized a series of polypyridyl ruthenium (II) complexes having the formula [Ru (NN)2 (bpm)] (PF6)2 (N-N = 2,2'-bipyridine) (bpy, in Ru1), 1,10-phenanthroline (phen, in Ru2), 4,7-diphenyl-1,10-phenanthroline (DIP, in Ru3) (bpm = 2,2'-bipyrimidine) and studied their antifungal activities. Ru3 alone had no effect on the drug-resistant strains, but Ru3 combined with fluconazole (FLC) exhibited significant antifungal activity on drug-resistant strains. A high-dose combination of Ru3 and FLC exhibited direct fungicidal activity by promoting the accumulation of reactive oxygen species and damaging the cellular structure of C. albicans. Additionally, the combination of Ru3 and FLC demonstrated potent antifungal efficacy in vivo in a mouse model of invasive candidiasis. Moreover, the combination significantly improved the survival state of mice, restored their immune systems, and reduced renal injury. These findings could provide ideas for the development of ruthenium (II) complexes as novel antifungal agents for drug-resistant microbial stains.

Effect of proanthocyanidins on blood lipids: A systematic review and meta-analysis.

Proanthocyanidins (PCs) are natural antioxidant polyphenols and their effect on the regulation of blood lipids is still controversial. This study was conducted to evaluate the effect of PCs on lipid metabolism. We searched PubMed, Embase, Web of Science, Chinese biomedical literature service system, China National Knowledge Internet, and Wanfang Data with no time restriction until March 18, 2022, using various forms of "proanthocyanidins" and "blood lipid" search terms. Randomized controlled trials investigating the relationship between PCs and lipid metabolism were included. The standard system of Cochrane Collaboration was used to assess the quality of studies. We standardized mean differences (SMDs) with 95% confidence interval (CI) using the random-effects model, Cohen approach. Seventeen studies (17 trials, N = 1138) fulfilled the eligibility criteria. PCs significantly reduced triglyceride, and increased recombinant apolipoprotein A1. Subgroup analysis showed a significant reduction in triglycerides in older adults (≥60 years) and total cholesterol for participants who were not overweight or obese (body mass index <24). An intervention duration of greater than 8 weeks reduced triglyceride and low-density lipoprotein cholesterol levels but increased high-density lipoprotein cholesterol. Different doses of PCs could regulate triglycerides, high-density lipoprotein cholesterol and total cholesterol. PCs have beneficial effects on circulating lipids and may represent a new approach for treating or preventing lipid metabolism disorders. However, more high-quality studies are needed to confirm these results.

[Buyang Huanwu Decoction promotes arteriogenesis after hindlimb ischemia in mice by activating PDGF signaling pathway].

This study aims to investigate the effect of Buyang Huanwu Decoction on blood flow recovery and arteriogenesis after hindlimb ischemia in mice via the platelet-derived growth factor(PDGF) signaling pathway. Forty C57BL/6 mice were randomized into model(clean water, 10 mL·kg~(-1)·d~(-1)), beraprost sodium(positive control, 18 µg·kg~(-1)·d~(-1)), and low-, medium-, and high-dose(10, 20, and 40 g·kg~(-1)·d~(-1), respectively) Buyang Huanwu Decoction groups(n=8). The hindlimb ischemia model was established by femoral artery ligation. The mice were administrated with corresponding agents by gavage daily for 14 days after ligation. For laser Doppler perfusion imaging, the mice were anesthetized and measured under a Periscan PSI imager. The density of capillary and arterio-le in the ischemic gastrocnemius was measured using immunofluorescence staining of the frozen tissue sections. Western blot was employed to determine the expression of PDGF subunit B(PDGFB), phosphorylated mitogen extracellular kinase(p-MEK), MEK, phosphorylated extracellular signal-regulated kinase(p-ERK), and ERK. Real-time PCR was employed to determine the mRNA level of PDGFB. The Buyang Huanwu Decoction-containing serum was used to treat the vascular smooth muscle cells(VSMCs) in hypoxia at doses of 10% and 20%. The proliferation and migration of VSMCs was assessed in vitro. The results showed that compared with the model group, beraprost sodium and Buyang Huanwu Decoction enhanced the blood flow recovery, increased the capillary and arteriole density, and up-regulated the protein levels of PDGFB, p-MEK, p-ERK, and mRNA levels of PDGFB, with the medium-dose Buyang Huanwu Decoction demonstrating the most significant effect. The 10% Buyang Huanwu Decoction-containing serum enhanced the proliferation and migration of VSMCs. Our findings demonstrate that Buyang Huanwu Decoction up-regulates PDGFB transcription and activates PDGF signaling pathway to promote arteriogenesis and blood flow recovery in ischemic gastrocnemius.

ERCP-Net: a channel extension residual structure and adaptive channel attention mechanism for plant leaf disease classification network.

Plant leaf diseases are a major cause of plant mortality, especially in crops. Timely and accurately identifying disease types and implementing proper treatment measures in the early stages of leaf diseases are crucial for healthy plant growth. Traditional plant disease identification methods rely heavily on visual inspection by experts in plant pathology, which is time-consuming and requires a high level of expertise. So, this approach fails to gain widespread adoption. To overcome these challenges, we propose a channel extension residual structure and adaptive channel attention mechanism for plant leaf disease classification network (ERCP-Net). It consists of channel extension residual block (CER-Block), adaptive channel attention block (ACA-Block), and bidirectional information fusion block (BIF-Block). Meanwhile, an application for the real-time detection of plant leaf diseases is being created to assist precision agriculture in practical situations. Finally, experiments were conducted to compare our model with other state-of-the-art deep learning methods on the PlantVillage and AI Challenger 2018 datasets. Experimental results show that our model achieved an accuracy of 99.82% and 86.21%, respectively. Also, it demonstrates excellent robustness and scalability, highlighting its potential for practical implementation.

Magnetic covalent organic frameworks for extraction and determination of endocrine-disrupting chemicals in beverage and water samples.

BACKGROUND: Phenolic endocrine-disrupting chemicals (EDCs) are widespread and easily ingested through the food chain. They pose a serious threat to human health. Magnetic solid-phase extraction (MSPE) is an effective sample pre-treatment technology to determine traces of phenolic EDCs. RESULTS: Magnetic covalent organic framework (COF) (Fe3 O4 @COF) nanospheres were prepared and characterized. The efficient and selective extraction of phenolic EDCs relies on a large specific surface and the inherent porosity of COFs and hydrogen bonding, π-π, and hydrophobic interactions between COF shells and phenolic EDCs. Under optimal conditions, the proposed magnetic solid-phase extraction-high-performance liquid chromatography-ultra violet (MSPE-HPLC-UV) based on the metallic covalent organic framework method for phenolic EDCs shows good linearities (0.002-6 µg mL-1 ), with R2 of 0.995 or higher, and low limits of detection (6-1.200 ng mL-1 ). CONCLUSION: Magnetic covalent organic frameworks (Fe3 O4 @COFs) with good MSPE performance for phenolic EDCs were synthesized by the solvothermal method. The magnetic covalent organic framework-based MSPE-HPLC-UV method was applied successfully to determine phenolic EDCs in beverage and water samples with satisfactory recoveries (90.200%-123%) and relative standard deviations (2.100%-12.100%). © 2023 Society of Chemical Industry.

Hyperglycemia-induced STING signaling activation leads to aortic endothelial injury in diabetes.

Hyperglycaemia-induced endothelial dysfunction is a key factor in the pathogenesis of diabetic microangiopathy and macroangiopathy. STING, which is a newly discovered regulator of innate immunity, has also been reported to play an important role in various metabolic diseases. However, the role of STING in diabetes-induced endothelial cell dysfunction is unknown. In this study, we established a diabetic macroangiopathy mouse model by streptozotocin (STZ) injection combined with high-fat diet (HFD) feeding and a glucotoxicity cell model in high glucose (HG)-treated rat aortic endothelial cells (RAECs). We found that STING expression was specifically increased in the endothelial cells of diabetic arteries, as well as in HG-treated RAECs. Moreover, genetic deletion of STING significantly ameliorated diabetes-induced endothelial cell dysfunction and apoptosis in vivo. Likewise, STING inhibition by C-176 reversed HG-induced migration dysfunction and apoptosis in RAECs, whereas STING activation by DMXAA resulted in migration dysfunction and apoptosis. Mechanistically, hyperglycaemia-induced oxidative stress promoted endothelial mitochondrial dysfunction and mtDNA release, which subsequently activated the cGAS-STING system and the cGAS-STING-dependent IRF3/NF-kB pathway, ultimately resulting in inflammation and apoptosis. In conclusion, our study identified a novel role of STING in diabetes-induced aortic endothelial cell injury and suggested that STING inhibition was a potential new therapeutic strategy for the treatment of diabetic macroangiopathy. Video Abstract.

Phase II multicenter trial: first-line immunochemotherapy with or without radiotherapy in metastatic esophageal squamous cell cancer (SCR-ESCC-01).

This randomized phase II trial (NCT05978193) combines low-dose radiotherapy (LDRT) and conventionally fractionated radiotherapy (CFRT) with immunochemotherapy for metastatic esophageal squamous cell carcinoma, aiming to assess the potential enhanced effect of radiotherapy on immunotherapy. Patients are administered a PD-1 inhibitor along with paclitaxel and platinum-based chemotherapy (arm B), or combined with LDRT and CFRT (arm A). Immunotherapy is given every 3 weeks with chemotherapy for 4 cycles, followed by immunotherapy maintenance therapy for up to 24 months. In arm A, LDRT (2 Gy, 2 fractions; delivered to the primary and all metastatic tumors) precedes each immunochemotherapy cycle for 4 cycles, followed by CFRT (40-50 Gy, 20-25 fractions; delivered to the primary tumor) starting from the fifth immunotherapy cycle. The primary end point is median progression-free survival. Clinical Trial Registration: NCT05978193 (clinicaltrials.gov).

Geological timescales' aging effects of lunar glasses.

Physical aging is a long-lasting research hot spot in the glass community, yet its long-term effects remain unclear because of the limited experimental time. In this study, we discover the extraordinary aging effects in five typical lunar glassy particles with diameters ranging from about 20 to 53 micrometers selected from Chang'e-5 lunar regolith. It is found that geological time scales' aging can lead to unusually huge modulus enhancements larger than 73.5% while much weaker effects on hardness (i.e., varies decoupling evolutions of Young's modulus and hardness during aging) in these lunar glassy samples. Such extraordinary aging effects are primarily attributed to the natural selected complex glassy compositions and structures, consistent with high entropy and minor element doping criteria, prevailing under the special lunar conditions and the extensive aging time for the lunar glasses. This study offers valuable insights for developing high-performance and stable glassy materials for radiation protection and advanced space explorations.

The role of oxidative stress in diabetes mellitus-induced vascular endothelial dysfunction.

Diabetes mellitus is a metabolic disease characterized by long-term hyperglycaemia, which leads to microangiopathy and macroangiopathy and ultimately increases the mortality of diabetic patients. Endothelial dysfunction, which has been recognized as a key factor in the pathogenesis of diabetic microangiopathy and macroangiopathy, is characterized by a reduction in NO bioavailability. Oxidative stress, which is the main pathogenic factor in diabetes, is one of the major triggers of endothelial dysfunction through the reduction in NO. In this review, we summarize the four sources of ROS in the diabetic vasculature and the underlying molecular mechanisms by which the pathogenic factors hyperglycaemia, hyperlipidaemia, adipokines and insulin resistance induce oxidative stress in endothelial cells in the context of diabetes. In addition, we discuss oxidative stress-targeted interventions, including hypoglycaemic drugs, antioxidants and lifestyle interventions, and their effects on diabetes-induced endothelial dysfunction. In summary, our review provides comprehensive insight into the roles of oxidative stress in diabetes-induced endothelial dysfunction.

Impacts of reclamation marsh restoration on greenhouse gas emission in the Sanjiang Plain, China.

To understand the variations in greenhouse gas fluxes during the process of returning cropland to wetland in the Sanjiang Plain, we selected naturally restored wetlands of 4, 7, 11, 16 and 20 years as research objects to compare with a cultivated site (soybean plantation for 13 years) and an uncultivated marsh dominated by Deyeuxia purpurea and Carex schmidtii. We measured carbon dioxide (CO2) and methane (CH4) fluxes using a static chamber-gas chromatography and explored the main influencing factors. The results showed that there were seasonal variations in growing-season CO2 and CH4 fluxes of the restored wetlands, with the seasonal trends in greenhouse gases becoming gradually similar to that of natural marsh with increasing restoration time. The mean growing-season CO2 fluxes increased during the early stage of restoration, but then decreased during the late stage, which decreased from 893.4 mg·m-2·h-1 to 494.0 mg·m-2·h-1 in the 4-year and 20-year sites, respectively. Mean CH4 fluxes increased with restoration time, ranging from a weak CH4 sink (soybean fields, -0.6 mg·m-2·h-1) to a CH4 source of 87.8 mg·m-2·h-1(20-year restored site). The CH4 fluxes of experimental plots were consistently lower than that of natural marsh (96.4 mg·m-2·h-1). Increases in water level and soil conductivity resulting from restoration were the main driving factors for the decrease in CO2 fluxes. The increases in water level and soil dissolved organic carbon resulting from restoration were the primary drivers for the increase of CH4 fluxes in the restored wetlands. The global warming potentials increased with restoration time, ranging from 27.8 t·CO2-eq·hm-2(soybean fields) to 130.8 t·CO2-eq·hm-2(plot of 20-year restoration), which gradually approached that of natural marsh (156.3 t·CO2-eq·hm-2). The emission of GHGs from restored wetlands in the Sanjiang Plain gradually approached those of natural marsh. Further monitoring is required to identify the maturity of restored wetlands for achieving greenhouse gas emissions equivalent to that of natural marshland.