GPCR-MAPK signaling pathways underpin fitness trade-offs in whitefly.

Trade-offs between evolutionary gain and loss are prevalent in nature, yet their genetic basis is not well resolved. The evolution of insect resistance to insecticide is often associated with strong fitness costs; however, how the fitness trade-offs operates remains poorly understood. Here, we show that the mitogen-activated protein kinase (MAPK) pathway and its upstream and downstream actors underlie the fitness trade-offs associated with insecticide resistance in the whitefly Bemisia tabaci. Specifically, we find a key cytochrome P450 gene CYP6CM1, that confers neonicotinoids resistance to in B. tabaci, is regulated by the MAPKs p38 and ERK through their activation of the transcription factor cAMP-response element binding protein. However, phosphorylation of p38 and ERK also leads to the activation of the transcription repressor Cap "n" collar isoform C (CncC) that negatively regulates exuperantia (Ex), vasa (Va), and benign gonial cell neoplasm (Bg), key genes involved in oogenesis, leading to abnormal ovary growth and a reduction in female fecundity. We further demonstrate that the transmembrane G protein-coupled receptor (GPCR) neuropeptide FF receptor 2 (NPFF2) triggers the p38 and ERK pathways via phosphorylation. Additionally, a positive feedback loop between p38 and NPFF2 leads to the continuous activation of the MAPK pathways, thereby constitutively promoting neonicotinoids resistance but with a significant reproductive cost. Collectively, these findings provide fundamental insights into the role of cis-trans regulatory networks incurred by GPCR-MAPK signaling pathways in evolutionary trade-offs and applied knowledge that can inform the development of strategies for the sustainable pest control.

Dual mutations in the whitefly nicotinic acetylcholine receptor ß1 subunit confer target-site resistance to multiple neonicotinoid insecticides.

Neonicotinoid insecticides, which target insect nicotinic acetylcholine receptors (nAChRs), have been widely and intensively used to control the whitefly, Bemisia tabaci, a highly damaging, globally distributed, crop pest. This has inevitably led to the emergence of populations with resistance to neonicotinoids. However, to date, there have been no reports of target-site resistance involving mutation of B. tabaci nAChR genes. Here we characterize the nAChR subunit gene family of B. tabaci and identify dual mutations (A58T&R79E) in one of these genes (BTß1) that confer resistance to multiple neonicotinoids. Transgenic D. melanogaster, where the native nAChR Dß1 was replaced with BTß1A58T&R79E, were significantly more resistant to neonicotinoids than flies where Dß1 were replaced with the wildtype BTß1 sequence, demonstrating the causal role of the mutations in resistance. The two mutations identified in this study replace two amino acids that are highly conserved in >200 insect species. Three-dimensional modelling suggests a molecular mechanism for this resistance, whereby A58T forms a hydrogen bond with the R79E side chain, which positions its negatively-charged carboxylate group to electrostatically repulse a neonicotinoid at the orthosteric site. Together these findings describe the first case of target-site resistance to neonicotinoids in B. tabaci and provide insight into the molecular determinants of neonicotinoid binding and selectivity.

Global acetylome profiling indicates EPA impedes but OA promotes prostate cancer motility through altered acetylation of PFN1 and FLNA.

Prostate cancer (PCa) is one of the leading causes of cancer morbidity and mortality in men. Metastasis is the main cause of PCa-associated death. Recent evidence indicated a significant reduction in PCa mortality associated with higher ω-3 polyunsaturated fatty acids (PUFAs) consumption. However, the underlying mechanisms remained elusive. In this study, we applied global acetylome profiling to study the effect of fatty acids treatment. Results indicated that oleic acid (OA, monounsaturated fatty acid, MUFA, 100 µM) elevates while EPA (eicosapentaenoic acid, 100 µM) reduces the acetyl-CoA level, which alters the global acetylome. After treatment, two crucial cell motility regulators, PFN1 and FLNA, were found with altered acetylation levels. OA increased the acetylation of PFN1 and FLNA, whereas EPA decreased PFN1 acetylation level. Furthermore, OA promotes while EPA inhibits PCa migration and invasion. Immunofluorescence assay indicated that EPA impedes the formation of lamellipodia or filopodia through reduced localization of PFN1 and FLNA to the leading edge of cells. Therefore, perturbed acetylome may be one critical step in fatty acid-affected cancer cell motility. This study provides some new insights into the response of ω-3 PUFAs treatment and a better understanding of cancer cell migration and invasion modulation.

Structures of the NDP-pyranose mutase belonging to glycosyltransferase family 75 reveal residues important for Mn2+ coordination and substrate binding.

Members of glycosyltransferase family 75 (GT75) not only reversibly catalyze the autoglycosylation of a conserved arginine residue with specific NDP-sugars but also exhibit NDP-pyranose mutase activity that reversibly converts specific NDP-pyranose to NDP-furanose. The latter activity provides valuable NDP-furanosyl donors for glycosyltransferases and requires a divalent cation as a cofactor instead of FAD used by UDP-D-galactopyranose mutase. However, details of the mechanism for NDP-pyranose mutase activity are not clear. Here we report the first crystal structures of GT75 family NDP-pyranose mutases. The novel structures of GT75 member MtdL in complex with Mn2+ and GDP, GDP-D-glucopyranose, GDP-L-fucopyranose, GDP-L-fucofuranose, respectively, combined with site-directed mutagenesis studies, reveal key residues involved in Mn2+ coordination, substrate binding, and catalytic reactions. We also provide a possible catalytic mechanism for this unique type of NDP-pyranose mutase. Taken together, our results highlight key elements of an enzyme family important for furanose biosynthesis.

NOX4-TIM23 interaction regulates NOX4 mitochondrial import and metabolic reprogramming.

Pulmonary fibrosis is a progressive lung disease characterized by macrophage activation. Asbestos-induced expression of nicotinamide adenine dinucleotide phosphate hydrogen oxidase 4 (NOX4) in lung macrophages mediates fibrotic progression by the generation of mitochondrial reactive oxygen species (ROS), modulating mitochondrial biogenesis, and promoting apoptosis resistance; however, the mechanism(s) by which NOX4 localizes to mitochondria during fibrosis is not known. Here, we show that NOX4 localized to the mitochondrial matrix following asbestos exposure in lung macrophages via direct interaction with TIM23. TIM23 and NOX4 interaction was found in lung macrophages from human subjects with asbestosis, while it was absent in mice harboring a conditional deletion of NOX4 in lung macrophages. This interaction was localized to the proximal transmembrane region of NOX4. Mechanistically, TIM23 augmented NOX4-induced mitochondrial ROS and metabolic reprogramming to oxidative phosphorylation. Silencing TIM23 decreased mitochondrial ROS and oxidative phosphorylation. These observations highlight the important role of the mitochondrial translocase TIM23 interaction with NOX4. Moreover, this interaction is required for mitochondrial redox signaling and metabolic reprogramming in lung macrophages.

Developmental pleiotropy of SDP1 from seedling to mature stages in B. napus.

Rapeseed, an important oil crop, relies on robust seedling emergence for optimal yields. Seedling emergence in the field is vulnerable to various factors, among which inadequate self-supply of energy is crucial to limiting seedling growth in early stage. SUGAR-DEPENDENT1 (SDP1) initiates triacylglycerol (TAG) degradation, yet its detailed function has not been determined in B. napus. Here, we focused on the effects of plant growth during whole growth stages and energy mobilization during seedling establishment by mutation in BnSDP1. Protein sequence alignment and haplotypic analysis revealed the conservation of SDP1 among species, with a favorable haplotype enhancing oil content. Investigation of agronomic traits indicated bnsdp1 had a minor impact on vegetative growth and no obvious developmental defects when compared with wild type (WT) across growth stages. The seed oil content was improved by 2.0-2.37% in bnsdp1 lines, with slight reductions in silique length and seed number per silique. Furthermore, bnsdp1 resulted in lower seedling emergence, characterized by a shrunken hypocotyl and poor photosynthetic capacity in the early stages. Additionally, impaired seedling growth, especially in yellow seedlings, was not fully rescued in medium supplemented with exogenous sucrose. The limited lipid turnover in bnsdp1 was accompanied by induced amino acid degradation and PPDK-dependent gluconeogenesis pathway. Analysis of the metabolites in cotyledons revealed active amino acid metabolism and suppressed lipid degradation, consistent with the RNA-seq results. Finally, we proposed strategies for applying BnSDP1 in molecular breeding. Our study provides theoretical guidance for understanding trade-off between oil accumulation and seedling energy mobilization in B. napus.

TRIM21 is critical in regulating hepatocellular carcinoma growth and response to therapy by altering the MST1/YAP pathway.

Liver cancer is the sixth most common cancer and the third leading cause of cancer-related death globally. Despite efforts being made in last two decades in cancer diagnosis and treatment, the 5-year survival rate of liver cancer remains extremely low. TRIM21 participates in cancer metabolism, glycolysis, immunity, chemosensitivity and metastasis by targeting various substrates for ubiquitination. TRIM21 serves as a prognosis marker for human hepatocellular carcinoma (HCC), but the mechanism by which TRIM21 regulates HCC tumorigenesis and progression remains elusive. In this study, we demonstrated that TRIM21 protein levels were elevated in human HCC. Elevated TRIM21 expression was associated with HCC progression and poor survival. Knockdown of TRIM21 in HCC cell lines significantly impaired cell growth and metastasis and enhanced sorafenib-induced toxicity. Mechanistically, we found that knockdown of TRIM21 resulted in cytosolic translocation and inactivation of YAP. At the molecular level, we further identified that TRIM21 interacted and induced ubiquitination of MST1, which resulted in MST1 degradation and YAP activation. Knockdown of MST1 or overexpression of YAP reversed TRIM21 knockdown-induced impairment of HCC growth and chemosensitivity. Taken together, the current study demonstrates a novel mechanism that regulates the Hippo pathway and reveals TRM21 as a critical factor that promotes growth and chemoresistance in human HCC.

A Noncentrosymmetric Metal-Free Borophosphate: Achieving a Large Birefringence and Excellent Stability by Covalent-Linkage.

Organic-inorganic hybrid linear and nonlinear optical (NLO) materials have received increasingly wide spread attention in recent years. Herein, the first hybrid noncentrosymmetric (NCS) borophosphate, (C5H6N)2B2O(HPO4)2 (4PBP), is rationally designed and synthesized by a covalent-linkage strategy. 4-pyridyl-boronic acid (4 PB) is considered as a bifunctional unit, which may effectively improve the optical properties and stability of the resultant material. On the one hand, 4 PB units are covalently linked with PO3(OH) groups via strong B-O-P connections, which significantly enhances the thermal stability of 4PBP (decomposition at 321, vs lower 200 °C of most of hybrid materials). On the other hand, the planar π-conjugated C5H6N units and their uniform layered arrangements represent large structural anisotropy and hyperpolarizability, achieving the largest birefringence (0.156 @ 546 nm) in the reported borophosphates and a second-harmonic generation response (0.7 × KDP). 4PBP also exhibits a wide transparency range (0.27-1.50 µm). This work not only provides a promising birefringent material, but also offers a practical covalent-attachment strategy for the rational design of new high-performance optical materials.

Discrepancy of coordinate system selection in backscattering Mueller matrix polarimetry: exploring photon coordinate system transformation invariants.

In biomedical studies, Mueller matrix polarimetry is gaining increasing attention because it can comprehensively characterize polarization-related vectorial properties of the sample, which are crucial for microstructural identification and evaluation. For backscattering Mueller matrix polarimetry, there are two photon coordinate selection conventions, which can affect the following Mueller matrix parameters calculation and information acquisition quantitatively. In this study, we systematically analyze the influence of photon coordinate system selection on the backscattering Mueller matrix polarimetry. We compare the Mueller matrix elements in the right-handed-nonunitary and non-right-handed-unitary coordinate systems, and specifically deduce the changes of Mueller matrix polar decomposition, Mueller matrix Cloude decomposition and Mueller matrix transformation parameters widely used in backscattering Mueller matrix imaging as the photon coordinate system varied. Based on the theoretical analysis and phantom experiments, we provide a group of photon coordinate system transformation invariants for backscattering Mueller matrix polarimetry. The findings presented in this study give a crucial criterion of parameters selection for backscattering Mueller matrix imaging under different photon coordinate systems.

Polarization feature fusion and calculation of birefringence dynamics in complex anisotropic media.

As a complex anisotropic medium, variation in birefringence within biological tissues is closely associated with numerous physiological behaviors and phenomena. In this Letter, we propose a polarization feature fusion method and corresponding polarimetric parameters, which exhibit excellent performance of capturing the birefringence dynamic variation process in complex anisotropic media. By employing the feature fusion method, we combine and transform polarization basis parameters (PBPs) to derive fused polarization feature parameters (FPPs) with explicit expressions. Subsequently, we conduct Monte Carlo (MC) simulation to demonstrate the effectiveness of the proposed FPPs from two variation dimensions of birefringence direction θ and modulus Δn. Leveraging mathematical modeling and linear transformations, we investigate and abstract their response patterns concerning θ and Δn. Finally, the experiments confirm that the FPPs show superior adaptability and interpretability in characterizing the birefringence dynamic process of turbid media. The findings presented in this study provide new, to the best of our knowledge, methodological insights of information extraction for computational polarimetry in biomedical research.

Polarization enhancement mechanism from tissue staining in multispectral Mueller matrix microscopy.

Mueller matrix microscopy can provide comprehensive polarization-related optical and structural information of biomedical samples label-freely. Thus, it is regarded as an emerging powerful tool for pathological diagnosis. However, the staining dyes have different optical properties and staining mechanisms, which can put influence on Mueller matrix microscopic measurement. In this Letter, we quantitatively analyze the polarization enhancement mechanism from hematoxylin and eosin (H&E) staining in multispectral Mueller matrix microscopy. We examine the influence of hematoxylin and eosin dyes on Mueller matrix-derived polarization characteristics of fibrous tissue structures. Combined with Monte Carlo simulations, we explain how the dyes enhance diattenuation and linear retardance as the illumination wavelength changed. In addition, it is demonstrated that by choosing an appropriate incident wavelength, more visual Mueller matrix polarimetric information can be observed of the H&E stained tissue sample. The findings can lay the foundation for the future Mueller matrix-assisted digital pathology.

Detrimental Role of CXCR3 in α-Naphthylisothiocyanate- and Triptolide-Induced Cholestatic Liver Injury.

The chemokine receptor CXCR3 is functionally pleiotropic, not only recruiting immune cells to the inflamed liver but also mediating the pathological process of cholestatic liver injury (CLI). However, the mechanism of its involvement in the CLI remains unclear. Both alpha-naphthylisothiocyanate (ANIT) and triptolide are hepatotoxicants that induce CLI by bile acid (BA) dysregulation, inflammation, and endoplasmic reticulum (ER)/oxidative stress. Through molecular docking, CXCR3 is a potential target of ANIT and triptolide. Therefore, this study aimed to investigate the role of CXCR3 in ANIT- and triptolide-induced CLI and to explore the underlying mechanisms. Wild-type mice and CXCR3-deficient mice were administered with ANIT or triptolide to compare CLI, BA profile, hepatic recruitment of IFN-γ/IL-4/IL-17+CD4+T cells, IFN-γ/IL-4/IL-17+iNKT cells and IFN-γ/IL-4+NK cells, and the expression of ER/oxidative stress pathway. The results showed that CXCR3 deficiency ameliorated ANIT- and triptolide-induced CLI. CXCR3 deficiency alleviated ANIT-induced dysregulated BA metabolism, which decreased the recruitment of IFN-γ+NK cells and IL-4+NK cells to the liver and inhibited ER stress. After triptolide administration, CXCR3 deficiency ameliorated dysregulation of BA metabolism, which reduced the migration of IL-4+iNKT cells and IL-17+iNKT cells and reduced oxidative stress through inhibition of Egr1 expression and AKT phosphorylation. Our findings suggest a detrimental role of CXCR3 in ANIT- and triptolide-induced CLI, providing a promising therapeutic target and introducing novel mechanisms for understanding cholestatic liver diseases.

Exploring the chemical dynamics of phenanthrene (C14H10) formation via the bimolecular gas-phase reaction of the phenylethynyl radical (C6H5CC) with benzene (C6H6).

The exploration of the fundamental formation mechanisms of polycyclic aromatic hydrocarbons (PAHs) is crucial for the understanding of molecular mass growth processes leading to two- and three-dimensional carbonaceous nanostructures (nanosheets, graphenes, nanotubes, buckyballs) in extraterrestrial environments (circumstellar envelopes, planetary nebulae, molecular clouds) and combustion systems. While key studies have been conducted exploiting traditional, high-temperature mechanisms such as the hydrogen abstraction-acetylene addition (HACA) and phenyl addition-dehydrocyclization (PAC) pathways, the complexity of extreme environments highlights the necessity of investigating chemically diverse mass growth reaction mechanisms leading to PAHs. Employing the crossed molecular beams technique coupled with electronic structure calculations, we report on the gas-phase synthesis of phenanthrene (C14H10)-a three-ring, 14π benzenoid PAH-via a phenylethynyl addition-cyclization-aromatization mechanism, featuring bimolecular reactions of the phenylethynyl radical (C6H5CC, X2A1) with benzene (C6H6) under single collision conditions. The dynamics involve a phenylethynyl radical addition to benzene without entrance barrier leading eventually to phenanthrene via indirect scattering dynamics through C14H11 intermediates. The barrierless nature of reaction allows rapid access to phenanthrene in low-temperature environments such as cold molecular clouds which can reach temperatures as low as 10 K. This mechanism constitutes a unique, low-temperature framework for the formation of PAHs as building blocks in molecular mass growth processes to carbonaceous nanostructures in extraterrestrial environments thus affording critical insight into the low-temperature hydrocarbon chemistry in our universe.

Metal-Binding Protein TaGlo1 Improves Fungal Resistance to Arsenite (AsIII) and Methylarsenite (MAsIII) in Paddy Soil.

Trivalent arsenicals such as arsenite (AsIII) and methylarsenite (MAsIII) are thought to be ubiquitous in flooded paddy soils and have higher toxicity than pentavalent forms. Fungi are widely prevalent in the rice rhizosphere, and the latter is considered a hotspot for As uptake. However, few studies have focused on alleviating As toxicity in paddy soils using fungi. In this study, we investigated the mechanism by which the protein TaGlo1, derived from the As-resistant fungal strain Trichoderma asperellum SM-12F1, mitigates AsIII and MAsIII toxicity in paddy soils. Taglo1 gene expression in Escherichia coli BL21 conferred strong resistance to AsIII and MAsIII, while purified TaGlo1 showed a high affinity for AsIII and MAsIII. Three cysteine residues (Cys13, Cys18, and Cys71) play crucial roles in binding with AsIII, while only two (Cys13 and Cys18) play crucial roles for MAsIII binding. TaGlo1 had a stronger binding strength for MAsIII than AsIII. Importantly, up to 90.2% of the homologous TaGlo1 proteins originate from fungi by GenBank searching. In the rhizospheres of 14 Chinese paddy soils, Taglo1 was widely distributed and its gene abundance increased with porewater As. This study highlights the potential of fungi to mitigate As toxicity and availability in the soil-rice continuum and suggests future microbial strategies for bioremediation.

Unconventional gas-phase synthesis of biphenyl and its atropisomeric methyl-substituted derivatives.

The biphenyl molecule (C12H10) acts as a fundamental molecular backbone in the stereoselective synthesis of organic materials due to its inherent twist angle causing atropisomerism in substituted derivatives and in molecular mass growth processes in circumstellar environments and combustion systems. Here, we reveal an unconventional low-temperature phenylethynyl addition-cyclization-aromatization mechanism for the gas-phase preparation of biphenyl (C12H10) along with ortho-, meta-, and para-substituted methylbiphenyl (C13H12) derivatives through crossed molecular beams and computational studies providing compelling evidence on their formation via bimolecular gas-phase reactions of phenylethynyl radicals (C6H5CC, X2A1) with 1,3-butadiene-d6 (C4D6), isoprene (CH2C(CH3)CHCH2), and 1,3-pentadiene (CH2CHCHCHCH3). The dynamics involve de-facto barrierless phenylethynyl radical additions via submerged barriers followed by facile cyclization and hydrogen shift prior to hydrogen atom emission and aromatization to racemic mixtures (ortho, meta) of biphenyls in overall exoergic reactions. These findings not only challenge our current perception of biphenyls as high temperature markers in combustion systems and astrophysical environments, but also identify biphenyls as fundamental building blocks of complex polycyclic aromatic hydrocarbons (PAHs) such as coronene (C24H12) eventually leading to carbonaceous nanoparticles (soot, grains) in combustion systems and in deep space thus affording critical insight into the low-temperature hydrocarbon chemistry in our universe.

Recent advances in catalyst design, performance, and challenges of metal-heteroatom-co-doped biochar as peroxymonosulfate activator for environmental remediation.

The escalation of global water pollution due to emerging pollutants has gained significant attention. To address this issue, catalytic peroxymonosulfate (PMS) activation technology has emerged as a promising treatment approach for effectively decontaminating a wide range of pollutants. Recently, modified biochar has become an increasingly attractive as PMS activator. Metal-heteroatom-co-doped biochar (MH-BC) has emerged as a promising catalyst that can provide enhanced performance over heteroatom-doped and metal-doped biochar due to the synergism between metal and heteroatom in promoting PMS activation. Therefore, this review aims to discuss the fabrication pathways (i.e., internal vs external doping and pre-vs post-modification) and key parameters (i.e., source of precursors, synthesis methods, and synthesis conditions) affecting the performance of MH-BC as PMS activator. Subsequently, an overview of all the possible PMS activation pathways by MH-BC is provided. Subsequently, Also, the detection, identification, and quantification of several reactive species (such as, •OH, SO4•-, O2•-, 1O2, and high valent oxo species) generated in the catalytic PMS system by MH-BC are also evaluated. Lastly, the underlying challenges associated with poor stability, the lack of understanding regarding the interaction between metal and heteroatom during PMS activation and quantification of radicals in multi-ROS system are also deliberated.

A comparative evaluation of biochar and Paenarthrobacter sp. AT5 for reducing atrazine risks to soybeans and bacterial communities in black soil.

Application of biochar and inoculation with specific microbial strains offer promising approaches for addressing atrazine contamination in agricultural soils. However, determining the optimal method necessitates a comprehensive understanding of their effects under similar conditions. This study aimed to evaluate the effectiveness of biochar and Paenarthrobacter sp. AT5, a bacterial strain known for its ability to degrade atrazine, in reducing atrazine-related risks to soybean crops and influencing bacterial communities. Both biochar and strain AT5 significantly improved atrazine degradation in both planted and unplanted soils, with the most substantial reduction observed in soils treated with strain AT5. Furthermore, bioaugmentation with strain AT5 outperformed biochar in enhancing soybean growth, photosynthetic pigments, and antioxidant defenses. While biochar promoted higher soil bacterial diversity compared to strain AT5, the latter selectively enriched specific bacterial populations. Additionally, soil inoculated with strain AT5 displayed a notable increase in the abundance of key genes associated with atrazine degradation (trzN, atzB, and atzC), surpassing the effects observed with biochar addition, thus highlighting its effectiveness in mitigating atrazine risks in soil.

Evaluating the impact of COVID-19 outbreak on hepatitis B and forecasting the epidemiological trend in mainland China: a causal analysis.

BACKGROUND: It is uncertain how COVID-19 outbreak influences the hepatitis B epidemics. This study aims to evaluate the effects on hepatitis B owing to the COVID-19 outbreak and forecast the hepatitis B epidemiological trend in mainland China to speed up the course of the "End viral hepatitis Strategy". METHODS: We estimated the causal impacts and created a forecast through adopting monthly notifications of hepatitis B each year from 2005 to 2020 in mainland China using the Bayesian structural time series (BSTS) method. RESULTS: The hepatitis B epidemics fluctuates irregularly during the period 2005-2007(APC = 8.7, P = 0.246) and 2015-2020(APC = 1.7, P = 0.290), and there is a downturn (APC=-3.2, 95% CI -5.2 to -1.2, P = 0.006) from 2007 to 2015 in mainland China. The COVID-19 outbreak was found to have a monthly average reduction on the hepatitis B epidemics of 26% (95% CI 18-35%) within the first three months in 2020,17% (95% CI 7.7-26%) within the first six months in 2020, and 10% (95% CI19-22%) all year as a result of the COVID-19 outbreak, (probability of causal effect = 96.591%, P = 0.034) and the forecasts showed an upward trend from 2021 to 2025 (annual percentage change = 4.18, 95% CI 4.0 to 4.3, P < 0.001). CONCLUSION: The COVID-19 has a positive effect on the decline of hepatitis B cases. And the potential of BSTS model to forecast the epidemiological trend of the hepatitis B can be applied in automatic public health policymaking in mainland China.

Role of C/EBP Homologous Protein in Vascular Stenosis After Carotid Artery Injury.

The study aims to explore the fluctuating expression of C/EBP Homologous Protein (CHOP) following rat carotid artery injury and its central role in vascular stenosis. Using in vivo rat carotid artery injury models and in vitro ischemia and hypoxia cell models employing human aortic endothelial cells (HAECs) and vascular smooth muscle cells (T/G HA-VSMCs), a comprehensive investigative framework was established. Histological analysis confirmed intimal hyperplasia in rat models. CHOP expression in vascular tissues was assessed using Western blot and immunohistochemical staining, and its presence in HAECs and T/G HA-VSMCs was determined through RT-PCR and Western blot. The study evaluated HAEC apoptosis, inflammatory cytokine secretion, cell proliferation, and T/G HA-VSMCs migration through Western blot, ELISA, CCK8, and Transwell migration assays. The rat carotid artery injury model revealed substantial fibrous plaque formation and vascular stenosis, resulting in an increased intimal area and plaque-to-lumen area ratio. Notably, CHOP is markedly elevated in vessels of the carotid artery injury model compared to normal vessels. Atorvastatin effectively mitigated vascular stenosis and suppresses CHOP protein expression. In HAECs, ischemia and hypoxia-induced CHOP upregulation, along with heightened TNFα, IL-6, caspase3, and caspase8 levels, while reducing cell proliferation. Atorvastatin demonstrated a dose-dependent suppression of CHOP expression in HAECs. Downregulation of CHOP or atorvastatin treatment led to reduced IL-6 and TNFα secretion, coupled with augmented cell proliferation. Similarly, ischemia and hypoxia conditions increased CHOP expression in T/G HA-VSMCs, which was concentration-dependently inhibited by atorvastatin. Furthermore, significantly increased MMP-9 and MMP-2 concentrations in the cell culture supernatant correlated with enhanced T/G HA-VSMCs migration. However, interventions targeting CHOP downregulation and atorvastatin usage curtailed MMP-9 and MMP-2 secretion and suppressed cell migration. In conclusion, CHOP plays a crucial role in endothelial injury, proliferation, and VSMCs migration during carotid artery injury, serving as a pivotal regulator in post-injury fibrous plaque formation and vascular remodeling. Statins emerge as protectors of endothelial cells, restraining VSMCs migration by modulating CHOP expression.

Lactiplantibacillusplantarum JS19-adjunctly fermented goat milk alleviates D-galactose-induced aging by modulating oxidative stress and intestinal microbiota in mice.

Oxidative stress is a crucial factor in the age-related decline in physiological, genomic, metabolic, and immunological functions. We screened Lactiplantibacillus plantarum JS19 (L. plantarum JS19), which has been shown to possess therapeutic properties in mice with ulcerative colitis. In this study, L. plantarum JS19-adjunctly fermented goat milk (LAF) was employed to alleviate D-galactose-induced aging and regulate intestinal flora in an aging mouse model. The oral administration of LAF effectively improved the health of spleen and kidney in mice, while mitigating the hepatocyte and oxidative damage induced by D-galactose. Additionally, LAF alleviated D-galactose-induced dysbiosis of the intestinal flora by reducing the abundance of harmful bacteria Desulfovibrio and Helicobacter, while greatly promoting the growth of beneficial Rikenellaceae_RC9_gut_group and Eubacterium. Biomarker 5-hydroxyindole-3-acetic acid was found to be positively linked with those harmful bacteria, while bio-active metabolites were strongly correlated with the beneficial genus. These observations suggest that LAF possesses the capability to mitigate the effects of D-galactose-induced aging in a mouse model through the regulation of oxidative stress, the gut microbiota composition, and levels of fecal metabolites. Consequently, these findings shed light on the potential of LAF as a functional food with anti-aging properties.