Arabidopsis Sar1b is critical for pollen tube growth.

Pollen tube growth is an essential step leading to reproductive success in flowering plants, in which vesicular trafficking plays a key role. Vesicular trafficking from endoplasmic reticulum to the Golgi apparatus is mediated by the coat protein complex II (COPII). A key component of COPII is small GTPase Sar1. Five Sar1 isoforms are encoded in the Arabidopsis genome and they show distinct while redundant roles in various cellular and developmental processes, especially in reproduction. Arabidopsis Sar1b is essential for sporophytic control of pollen development while Sar1b and Sar1c are critical for gametophytic control of pollen development. Because functional loss of Sar1b and Sar1c resulted in pollen abortion, whether they influence pollen tube growth was unclear. Here we demonstrate that Sar1b mediates pollen tube growth, in addition to its role in pollen development. Although functional loss of Sar1b does not affect pollen germination, it causes a significant reduction in male transmission and of pollen tube penetration of style. We further show that membrane dynamics at the apex of pollen tubes are compromised by Sar1b loss-of-function. Results presented provide further support of functional complexity of the Sar1 isoforms.

Global richness patterns of alpine genus Gentiana depend on multiple factors.

Environmental factors impact species richness differently across taxonomic groups, and understanding the geographic patterns and drivers influencing alpine plant richness remains limited. This study compiled global distribution data of 404 species of Gentiana, an alpine genus, and analyzed the relative effects of different environmental factors and several previously proposed models on the variation of Gentiana richness. By evaluating the effects of range size and regions on the relationships between Gentiana richness and environmental factors, we found that all tested environmental factors had weak effects on richness variation for all species and wide-ranging species, while habitat heterogeneity was the best predictor for narrow-ranging species. Habitat heterogeneity was the main driver of richness variation in Europe and Asia, but not in North America. The multiple regression model that included variables for energy, water, seasonality, habitat heterogeneity and past climate change had the highest explanatory power, but it still explained less than 50% of the variation in species richness for all Gentiana species at both global and regional scale, except for Europe. The limited explanatory power of environmental factors in explaining species richness patterns for all species, along with the variations observed among regions, suggest that other factors, such as evolutionary processes and biogeographic history may have also influenced the geographic patterns of Gentiana species richness. In conclusion, our results indicate a limited influence of climate factors on alpine species richness, while habitat heterogeneity, along with its impacts on speciation and dispersal, likely play significant roles in shaping the richness of alpine Gentiana species.

Bioengineered Artificial Extracellular Vesicles Presenting PD-L1 and Gal-9 Ameliorate New-onset Type 1 Diabetes.

An important factor in the development of Type 1 diabetes (T1D) is the deficiency of inhibitory immune checkpoint ligands, specifically programmed cell death ligand 1 (PD-L1) and Galectin-9 (Gal-9), in ß-cells. Hence, modulation of the pancreas infiltrated T lymphocytes by exogenous PD-L1 or Gal-9 is an ideal approach for treating the new-onset T1D. Herein, we genetic engineered the macrophage cells to generate artificial extracellular vesicles (aEVs) overexpressing PD-L1 and Gal-9, which could restrict the islets autoreactive T lymphocytes and protect ß-cells from destruction. Intriguingly, overexpressing Gal-9 spurred macrophage polarization to M2 phenotype with immune suppressive attribute. Alternatively, both of PD-L1 and Gal-9 presenting aEVs (PD-L1-Gal-9 aEVs) favorably adhere to T cells via the interaction of programmed cell death protein 1 (PD-1)/PD-L1 or T cell immunoglobulin mucin 3 (TIM-3)/Gal-9. Moreover, PD-L1-Gal-9 aEVs prominently promoted effector T cell apoptosis and splenic regulatory T cells (Treg) cells differentiation in vitro. Virtually, PD-L1-Gal-9 aEVs efficaciously reversed the new-onset hyperglycemia in the NOD mice, prevented T1D progress, and declined the proportion and activation of CD4+ and CD8+ T cells infiltrating the pancreas notably, which together contributed to preserving the residual ß-cells survival and mitigating the hyperglycemia.

Effect of smoking cessation medications on intracranial aneurysm risk: A Mendelian randomization study.

INTRODUCTION: We aim to assess the association between smoking behavior and intracranial aneurysms (IAs) and the effect of smoking cessation medications on IAs at the genetic level. METHODS: Causal effects of four phenotypes: 1) age at initiation of regular smoking, 2) cigarettes smoked per day, 3) smoking cessation, and 4) smoking initiation on IAs, were analyzed using two-sample inverse-variance weighted Mendelian randomization analyses. The effects of genes interacting with the smoking cessation medications were analyzed using cis-expression quantitative trait loci genetic instruments on IAs using summary statistics-based Mendelian randomization analyses. Colocalization analyses were then used to test whether the genes shared causal variants with IAs. The role of confounding phenotypes as potential causative mechanisms of IAs at these gene loci was tested. RESULTS: Cigarettes smoked per day (OR=2.89; 95% CI:1.85-4.51) and smoking initiation on IAs (OR=4.64; 95% CI: 2.64-8.15) were significantly associated with IA risk. However, age at initiation of regular smoking (OR=0.54; 95% CI: 0.10-2.8) and smoking cessation (OR=6.80; 95% CI: 0.01-4812) had no overall effect on IAs. Of 88 genes that interacted with smoking cessation medications, two had a causal effect on IA risk. Genetic variants affecting HYKK levels showed strong evidence of colocalization with IA risk. Higher HYKK levels in the blood were associated with a lower IA risk. Gene target analyses revealed that cigarettes/day could be a main mediator of HYKK's effect on IA risk. CONCLUSIONS: This study provides evidence supporting that smoking initiation on IAs and cigarettes/day may increase IA risk. Increased HYKK gene expression may reduce IA risk. This can be explained by the increased number of cigarettes consumed daily. HYKK could also reduce IA risk due to the positive effect of continuous abstinence and varenicline therapy on smoking cessation.

Dulaglutide restores endothelial progenitor cell levels in diabetic mice and mitigates high glucose-induced endothelial injury through SIRT1-mediated mitochondrial fission.

Type 2 diabetes mellitus (T2DM) significantly impairs the functionality and number of endothelial progenitor cells (EPCs) and resident endothelial cells, critical for vascular repair and regeneration, exacerbating the risk of vascular complications. GLP-1 receptor agonists, like dulaglutide, have emerged as promising therapeutic agents due to their multifaceted effects, including the enhancement of EPC activity and protection of endothelial cells. This study investigates dulaglutide's effects on peripheral blood levels of CD34+ and CD133+ cells in a mouse model of lower limb ischemia and its protective mechanisms against high-glucose-induced damage in endothelial cells. Results demonstrated that dulaglutide significantly improves blood flow, reduces tissue damage and inflammation in ischemic limbs, and enhances glycemic control. Furthermore, dulaglutide alleviated high-glucose-induced endothelial cell damage, evident from improved tube formation, reduced reactive oxygen species accumulation, and restored endothelial junction integrity. Mechanistically, dulaglutide mitigated mitochondrial fission in endothelial cells under high-glucose conditions, partly through maintaining SIRT1 expression, which is crucial for mitochondrial dynamics. This study reveals the potential of dulaglutide as a therapeutic option for vascular complications in T2DM patients, highlighting its role in improving endothelial function and mitochondrial integrity.

Optimal Glycated Hemoglobin Cutoff for Diagnosis of Diabetes and Prediabetes in Chinese Breast Cancer Women.

Purpose: Glycated hemoglobin (HbA1c) is widely used in diabetes management and now recommended for diagnosis and risk assessment. Our research focused on investigating the optimal cutoff points of HbA1c for diagnosis of diabetes and prediabetes in Chinese breast cancer women, aiming to enhance early detection and tailor treatment strategies. Patients and Methods: This study involved 309 breast cancer women without diabetes history in China. Patients were categorized into groups of newly diagnosed diabetes, prediabetes, and normal glucose tolerance using oral glucose tolerance test (OGTT) according to the 2010 ADA criteria. HbA1c data were collected from all patients. Receiver operating characteristic (ROC) curve analysis was used to assess the effectiveness of the HbA1c screening. Results: Among the 309 breast cancer women without diabetes history, 96 (31.0%) were identified with diabetes and 130 (42.1%) had prediabetes according to OGTT, and the incidence of normal glucose tolerance was only 26.9% (83). ROC curve analysis, using OGTT as a reference, revealed that the area under the curve of 0.903 (P<0.001, 95% CI, 0.867-0.938) for HbA1c alone, indicating high accuracy. The optimal HbA1c cutoff for identifying diabetes was determined to be 6.0%, with a sensitivity of 78.1% and specificity of 86.4%. For prediabetes, the ROC curve for HbA1c alone showed that the area under the ROC curve of 0.703 (P<0.001, 95% CI, 0.632-0.774), with an optimal cutoff of 5.5% (sensitivity of 76.9% and specificity of 51.8%). Conclusion: The prevalence of undiagnosed diabetes is very high in breast cancer women without diabetes history in China. The optimal cutoff points of HbA1c for identifying diabetes and prediabetes are 6.0% and 5.5% in Chinese breast cancer women, respectively.

Identification of methylation driver genes for predicting the prognosis of pancreatic cancer patients based on whole-genome DNA methylation sequencing technology.

This study was based on the use of whole-genome DNA methylation sequencing technology to identify DNA methylation biomarkers in tumor tissue that can predict the prognosis of patients with pancreatic cancer (PCa). TCGA database was used to download PCa-related DNA methylation and transcriptome atlas data. Methylation driver genes (MDGs) were obtained using the MethylMix package. Candidate genes in the MDGs were screened for prognostic relevance to PCa patients by univariate Cox analysis, and a prognostic risk score model was constructed based on the key MDGs. ROC curve analysis was performed to assess the accuracy of the prognostic risk score model. The effects of PIK3C2B knockdown on malignant phenotypes of PCa cells were investigated in vitro. A total of 2737 differentially expressed genes were identified, with 649 upregulated and 2088 downregulated, using 178 PCa samples and 171 normal samples. MethylMix was employed to identify 71 methylation-driven genes (47 hypermethylated and 24 hypomethylated) from 185 TCGA PCa samples. Cox regression analyses identified eight key MDGs (LEF1, ZIC3, VAV3, TBC1D4, FABP4, MAP3K5, PIK3C2B, IGF1R) associated with prognosis in PCa. Seven of them were hypermethylated, while PIK3C2B was hypomethylated. A prognostic risk prediction model was constructed based on the eight key MDGs, which was found to accurately predict the prognosis of PCa patients. In addition, the malignant phenotypes of PANC-1 cells were decreased after the knockdown of PIK3C2B. Therefore, the prognostic risk prediction model based on the eight key MDGs could accurately predict the prognosis of PCa patients.

Braden score can independently predict 90-day mortality in critically ill patients with dementia.

BACKGROUND: Dementia is a significant cause of death in the older population and is becoming an important public health issue as the population ages and the prevalence of dementia increases. The Braden score is one of the most commonly used clinical tools to assess the risk of skin pressure injury in patients, and some studies have reported that it may reflect the state of frailty of patients. The present study attempted to explore the association between Braden score and 90-day mortality, pressure injury, and aspiration pneumonia in older patients with dementia in the intensive care unit (ICU). METHODS: The study involved extracting crucial data from the Medical Information Market for Intensive Care IV (MIMIC-IV) database using Structured Query Language, with a license certificate obtained after completing the necessary training and examination available on the MIMIC-IV website. A retrospective analysis was performed on older patients with dementia, aged 65 or older, who were first admitted to the ICU. Ninth and tenth revision International Classification of Diseases codes were used to identify patients with dementia. The primary outcome was 90-day mortality. Cox proportional hazards models were used to determine the association between Braden score and death, and hazard ratios (HR) and 95% confidence intervals (CI) were calculated. Propensity score matching and E-value assessments were employed for sensitivity analysis. RESULTS: A total of 2892 patients with a median age of approximately 85 years (interquartile range 78.74-89.59) were included, of whom 1625 were female (56.2%). Patients had a median Braden score of 14 (interquartile range 12-15) at ICU admission. Braden score at ICU admission was inversely associated with 90-day mortality risk after adjustment for demographics, severity of illness, treatment and medications, delirium, and sepsis (adjusted HR: 0.92, 95% CI: 0.87-0.98, p = 0.006). Patients were divided into two groups with a cut-off value of 15: high-risk group and low-risk group. Compared to the low-risk group (Braden score >15), the risk of 90-day mortality was significantly increased in the high-risk group (Braden score ≤15) (adjusted HR: 1.52, 95% CI: 1.10-2.09, p = 0.011, E-value: 2.01), the risk of pressure injury (adjusted OR: 2.62, 95% CI: 2.02-3.43, E-value: 2.62) and aspiration pneumonia (adjusted OR: 2.55, 95% CI: 1.84-3.61, E-value: 2.57) was also significantly higher. CONCLUSIONS: The Braden score may be a quick and simple screening tool to identify the risk of adverse outcomes in critically ill older adults with dementia.

CLK2 mediates IκBα-independent early termination of NF-κB activation by inducing cytoplasmic redistribution and degradation.

Activation of the NF-κB pathway is strictly regulated to prevent excessive inflammatory and immune responses. In a well-known negative feedback model, IκBα-dependent NF-κB termination is a delayed response pattern in the later stage of activation, and the mechanisms mediating the rapid termination of active NF-κB remain unclear. Here, we showed IκBα-independent rapid termination of nuclear NF-κB mediated by CLK2, which negatively regulated active NF-κB by phosphorylating the RelA/p65 subunit of NF-κB at Ser180 in the nucleus to limit its transcriptional activation through degradation and nuclear export. Depletion of CLK2 increased the production of inflammatory cytokines, reduced viral replication and increased the survival of the mice. Mechanistically, CLK2 phosphorylated RelA/p65 at Ser180 in the nucleus, leading to ubiquitin‒proteasome-mediated degradation and cytoplasmic redistribution. Importantly, a CLK2 inhibitor promoted cytokine production, reduced viral replication, and accelerated murine psoriasis. This study revealed an IκBα-independent mechanism of early-stage termination of NF-κB in which phosphorylated Ser180 RelA/p65 turned off posttranslational modifications associated with transcriptional activation, ultimately resulting in the degradation and nuclear export of RelA/p65 to inhibit excessive inflammatory activation. Our findings showed that the phosphorylation of RelA/p65 at Ser180 in the nucleus inhibits early-stage NF-κB activation, thereby mediating the negative regulation of NF-κB.

Specific convulsions and brain damage in children hospitalized for Omicron BA.5 infection: an observational study using two cohorts.

BACKGROUND: SARS-CoV-2 continues to mutate over time, and reports on children infected with Omicron BA.5 are limited. We aimed to analyze the specific symptoms of Omicron-infected children and to improve patient care. METHODS: We selected 315 consecutively hospitalized children with Omicron BA.5 and 16,744 non-Omicron-infected febrile children visiting the fever clinic at our hospital between December 8 and 30, 2022. Specific convulsions and body temperatures were compared between the two cohorts. We analyzed potential associations between convulsions and vaccination, and additionally evaluated the brain damage among severe Omicron-infected children. RESULTS: Convulsion rates (97.5% vs. 4.3%, P < 0.001) and frequencies (median: 2.0 vs. 1.6, P < 0.001) significantly differed between Omicron-infected and non-Omicron-infected febrile children. The body temperatures of Omicron-infected children were significantly higher during convulsions than when they were not convulsing and those of non-Omicron-infected febrile children during convulsions (median: 39.5 vs. 38.2 and 38.6 °C, both P < 0.001). In the three Omicron-subgroups, the temperature during convulsions was proportional to the percentage of patients and significantly differed ( P < 0.001), while not in the three non-Omicron-subgroups ( P = 0.244). The convulsion frequency was lower in the 55 vaccinated children compared to the 260 non-vaccinated children (average: 1.8 vs. 2.1, P < 0.001). The vaccination dose and convulsion frequency in Omicron-infected children were significantly correlated ( P < 0.001). Fifteen of the 112 severe Omicron cases had brain damage. CONCLUSIONS: Omicron-infected children experience higher body temperatures and frequencies during convulsions than those of non-Omicron-infected febrile children. We additionally found evidence of brain damage caused by infection with omicron BA.5. Vaccination and prompt fever reduction may relieve symptoms.

Gas-Responsive and Gas-Releasing Polymer Assemblies.

In order to explore the unique physiological roles of gas signaling molecules and gasotransmitters in vivo, chemists have engineered a variety of gas-responsive polymers that can monitor their changes in cellular milieu, and gas-releasing polymers that can orchestrate the release of gases. These have advanced their potential applications in the field of bio-imaging, nanodelivery, and theranostics. Since these polymers are of different chain structures and properties, the morphology of their assemblies will manifest distinct transitions after responding to gas or releasing gas. In this review, we summarize the fundamental design rationale of gas-responsive and gas-releasing polymers in structure and their controlled transition in self-assembled morphology and function, as well as present some perspectives in this prosperous field. Emerging challenges faced for the future research are also discussed.

Identification of ACAA1 and HADHB as potential prognostic biomarkers based on a novel fatty acid oxidation-related gene model in head and neck squamous cell carcinoma: A retrospective study.

OBJECTIVES: To investigate the importance of fatty acid oxidation (FAO)-related genes in predicting the progression and prognosis of head and neck squamous cell carcinoma (HNSCC). METHODS: The FAO-related gene prognostic model was established employing Cox regression analyses, during which accuracy and sensitivity of the gene model were evaluated in The Cancer Genome Atlas (TCGA) internal testing and Gene Expression Omnibus (GEO) external validation cohorts. Ultimately, hub genes were identified among 13 model genes using STRING and Cytoscape, with preliminary validation carried out through immunohistochemistry. RESULTS: The model, which comprised 13 genes (ABCD2, ACAA1, ACACB, AKT1, CNR1, CPT1C, CROT, ECHDC2, ETFA, HADHB, IRS2, LONP2, and SLC25A17), was established. On the basis of the median risk score, the two cohorts were grouped into low-and high-risk groups in the subsequent test and validation, and the former exhibited significantly higher survival rates than the latter. Nomograms were established based on prognostic factors, including stage and risk score, and individualized for the prediction of HNSCC patients. Ultimately, immunohistochemical staining showed that ACAA1 and HADHB were significantly under-expressed in HNSCC, with a favorable prognosis associated with low HADHB and high ACAA1. CONCLUSIONS: The gene prognostic model has illustrated promising capability in predicting the prognosis, and ACAA1 and HADHB might serve as potential therapeutic biomarkers for HNSCC patients.

5.1 µm Ion-Regulated Rigid Quasi-Solid Electrolyte Constructed by Bridging Fast Li-Ion Transfer Channels for Lithium Metal Batteries.

An ultra-thin quasi-solid electrolyte (QSE) with dendrite-inhibiting properties is a requirement for achieving high energy density quasi-solid lithium metal batteries (LMBs). Here, a 5.1 µm rigid QSE layer is directly designed on the cathode, in which Kevlar (poly(p-phenylene terephthalate)) nanofibers (KANFs) with negatively charged groups bridging metal-organic framework (MOF) particles are served as a rigid skeleton, and non-flammable deep eutectic solvent is selected to be encapsulated into the MOF channels, combined with in situ polymerization to complete safe electrolyte system with high rigidness and stability. The QSE with constructed topological network demonstrates high rigidity (5.4 GPa), high ionic conductivity (0.73 mS cm-1 at room temperature), good ion-regulated properties, and improved structural stability, contributing to homogenized Li-ion flux, excellent dendrite suppression, and prolonged cyclic performance for LMB. Additionally, ion regulation influences the Li deposition behavior, exhibiting a uniform morphology on the Li-metal surface after cycling. According to density-functional theory, KANFs bridging MOFs as hosts play a vital function in the free-state and fast diffusion dynamics of Li-ions. This work provides an effective strategy for constructing ultrathin robust electrolytes with a novel ionic conduction mode.

Prevalence and risk factors of thyroid nodules in breast cancer women with different clinicopathological characteristics: a cross-sectional study.

BACKGROUND: Association between breast cancer (BC) and thyroid nodules (TNs) is still unclear. This research was to estimate the prevalence and risk factors of TN in Chinese BC women at initial diagnosis. METHODS: 1731 Chinese early-stage BC women at initial diagnosis underwent thyroid ultrasound and 1:1 age-matched Chinese healthy women underwent health examination in corresponding period were enrolled for analysis. RESULTS: Prevalence of TN and TI-RADS ≥ 4 TN in BC patients (56.27% and 9.76%) were higher than healthy people (46.04% and 5.49%), respectively, P < 0.001. Among BC patients, prevalence of TN and TI-RADS ≥ 4 TN in hormone receptor (HR)-positive patients (59.57% and 11.81%) were higher than HR-negative patients (48.77% and 5.10%), respectively, P < 0.001, while without difference between HR-negative patients and healthy people. After adjusting for age and BMI, HR-positive patients had higher risk of TN (OR = 1.546, 95%CI 1.251-1.910, P < 0.001) and TI-RADS ≥ 4 TN (OR = 3.024, 95%CI 1.943-4.708, P < 0.001) than HR-negative patients. Furthermore, the risk of TI-RADS ≥ 4 TN was higher in patients with estrogen receptor (ER) positive (OR = 2.933, 95%CI 1.902-4.524), progesterone receptor (PR) positive (OR = 1.973, 95%CI 1.378-2.826), Ki-67 < 20% (OR = 1.797, 95%CI 1.280-2.522), and tumor size < 2 cm (OR = 1.804, 95%CI 1.276-2.552), respectively, P < 0.001. CONCLUSIONS: Prevalence of TN, especially TI-RADS ≥ 4 TN, in Chinese early-stage BC women was higher than healthy people. HR-positive patients had higher prevalence and risk of TN, while without difference between HR-negative patients and healthy people. The increased risk of TN was correlated with ER-positive, PR-positive, lower Ki-67 expression, and smaller tumor size.

Arabidopsis class A S-acyl transferases modify the pollen receptors LIP1 and PRK1 to regulate pollen tube guidance.

Protein S-acylation catalyzed by protein S-acyl transferases (PATs) is a reversible lipid modification regulating protein targeting, stability, and interaction profiles. PATs are encoded by large gene families in plants, and many proteins including receptor-like cytoplasmic kinases (RLCKs) and receptor-like kinases (RLKs) are subject to S-acylation. However, few PATs have been assigned substrates, and few S-acylated proteins have known upstream enzymes. We report that Arabidopsis (Arabidopsis thaliana) class A PATs redundantly mediate pollen tube guidance and participate in the S-acylation of POLLEN RECEPTOR KINASE1 (PRK1) and LOST IN POLLEN TUBE GUIDANCE1 (LIP1), a critical RLK or RLCK for pollen tube guidance, respectively. PAT1, PAT2, PAT3, PAT4, and PAT8, collectively named PENTAPAT for simplicity, are enriched in pollen and show similar subcellular distribution. Functional loss of PENTAPAT reduces seed set due to male gametophytic defects. Specifically, pentapat pollen tubes are compromised in directional growth. We determine that PRK1 and LIP1 interact with PENTAPAT, and their S-acylation is reduced in pentapat pollen. The plasma membrane (PM) association of LIP1 is reduced in pentapat pollen, whereas point mutations reducing PRK1 S-acylation affect its affinity with its interacting proteins. Our results suggest a key role of S-acylation in pollen tube guidance through modulating PM receptor complexes.

[Resources and utilization of medicinal plants in countries and regions involved in "the Belt and Road" Initiative].

The protection, development, and utilization of medicinal plant resources are important cornerstones of maintaining human health. However, due to factors such as the reduction of high-quality land resources, deterioration of ecological environments, and excessive and disorderly resource development, medicinal plant resources are becoming scarce, and some of them are insufficiently supplied. With the proposal of "the Belt and Road" Initiative, the cooperation between China and "the Belt and Road" partners(the countries and regions involved in "the Belt and Road" Initiative)is increasingly close, which provides a new opportunity for carrying out trade of medicinal plant resources and alleviating the problem of imbalance and relative inadequacy of medicinal plant resources in countries. This study first determined the distribution and species information of plant resources in countries and regions involved in "the Belt and Road" Initiative by investigating the database of plant distribution and that of medicinal plant resources. Then, according to the published data from the International Union for Conservation of Nature(IUCN) and the Convention on International Trade in Endangered Species of Wild Fauna and Flora(CITES), this study identified the rare and endangered medicinal plants and the medicinal plants under trade control in countries and regions involved in "the Belt and Road" Initiative and finally sorted out the list of potential medicinal plant resources in countries and regions involved in "the Belt and Road" Initiative that can be used by China. This data resource can not only be used for the overall protection of important endangered species but also scientifically guide the development and utilization of medicinal resources, providing guidance and a theoretical basis for the sustainable development of medicinal plant resources in countries and regions involved in "the Belt and Road" Initiative.

Ripretinib inhibits HIV-1 transcription through modulation of PI3K-AKT-mTOR.

Despite the effectiveness of antiretroviral therapy (ART) in prolonging the lifespan of individuals infected with HIV-1, it does not offer a cure for acquired immunodeficiency syndrome (AIDS). The "block and lock" approach aims to maintain the provirus in a state of extended transcriptional arrest. By employing the "block and lock" strategy, researchers endeavor to impede disease progression by preventing viral rebound for an extended duration following patient stops receiving ART. The crux of this strategy lies in the utilization of latency-promoting agents (LPAs) that are suitable for impeding HIV-1 provirus transcription. However, previously documented LPAs exhibited limited efficacy in primary cells or samples obtained from patients, underscoring the significance of identifying novel LPAs that yield substantial outcomes. In this study, we performed high-throughput screening of FDA-approved compound library in the J-Lat A2 cell line to discover more efficacious LPAs. We discovered ripretinib being an LPA candidate, which was validated and observed to hinder proviral activation in cell models harboring latent infections, as well as CD4+ T cells derived from infected patients. We demonstrated that ripretinib effectively impeded proviral activation through inhibition of the PI3K-AKT-mTOR signaling pathway in the HIV-1 latent cells, thereby suppressing the opening states of cellular chromatin. The results of this research offer a promising drug candidate for the implementation of the "block and lock" strategy in the pursuit of an HIV-1 cure.

Intelligent Rapid Detection Techniques for Low-Content Components in Fruits and Vegetables: A Comprehensive Review.

Fruits and vegetables are an important part of our daily diet and contain low-content components that are crucial for our health. Detecting these components accurately is of paramount significance. However, traditional detection methods face challenges such as complex sample processing, slow detection speed, and the need for highly skilled operators. These limitations fail to meet the growing demand for intelligent and rapid detection of low-content components in fruits and vegetables. In recent years, significant progress has been made in intelligent rapid detection technology, particularly in detecting high-content components in fruits and vegetables. However, the accurate detection of low-content components remains a challenge and has gained considerable attention in current research. This review paper aims to explore and analyze several intelligent rapid detection techniques that have been extensively studied for this purpose. These techniques include near-infrared spectroscopy, Raman spectroscopy, laser-induced breakdown spectroscopy, and terahertz spectroscopy, among others. This paper provides detailed reports and analyses of the application of these methods in detecting low-content components. Furthermore, it offers a prospective exploration of their future development in this field. The goal is to contribute to the enhancement and widespread adoption of technology for detecting low-content components in fruits and vegetables. It is expected that this review will serve as a valuable reference for researchers and practitioners in this area.

Running exercise improves astrocyte loss, morphological complexity and astrocyte-contacted synapses in the hippocampus of CUS-induced depression model mice.

Although the antidepressant effects of running exercise have been widely reported, further research is still needed to determine the structural bases for these effects. Astrocyte processes physically contact many synapses and directly regulate the numbers of synapses, but it remains unclear whether running exercise can modulate astrocyte morphological complexity and astrocyte-contacted synapses in the hippocampus of the mice with depressive-like behavior. Male C57BL/6 J mice underwent four weeks of running exercise after four weeks of chronic unpredictable stress (CUS). The sucrose preference test (SPT), tail suspension test (TST) and forced swim test (FST) were used to assess anhedonia in mice. Western blotting was used to measure the expression of astrocyte- and synapse-related proteins. Immunofluorescence and 3D reconstruction were used to quantify the density and morphology of astrocytes, and astrocyte-contacted synapses in each hippocampal subregion. Four weeks of running exercise alleviated depressive-like symptoms in mice. The expression of astrocyte- and synapse-related proteins in the hippocampus; astrocyte process lengths, process numbers, and dendritic arborization; and the number of astrocyte-contacted PSD95 positive synapses in the CA2-3 and DG regions were significantly decreased in the mice with depressive-like behavior, and running exercise successfully reserved these changes. Running exercise improved the decreases in astrocyte morphological complexity and astrocyte-contacted PSD95 positive synapses in the CA2-3 and DG regions of the mice with depressive-like behavior, suggesting that the physical interactions between astrocytes and synapses can be increased by running exercise, which might be an important structural basis for the antidepressant effects of running exercise.