Pharmacokinetic-pharmacodynamic and tissue distribution studies in physiological and cerebral ischemia-reperfusion injury rats after oral administration of anisodine hydrobromide tablets.

Aim: We aim to establish a rapid and sensitive UPLC-MS/MS method to analyze the pharmacokinetics of oral anisodine hydrobromide (AH) tablets.

Methods: Comparison of pharmacokinetic differences between AH (present in vivo as anisodine) and its metabolite NOAT3 in two groups of rats after administration of AH at doses of 5, 10, and 20 mg/kg. In addition, plasma concentrations of AH were used as a pharmacokinetic parameter, and interleukin-1β (IL-1β) and lactic dehydrogenase (LDH) were selected as pharmacodynamic indicators to establish a pharmacokinetics-pharmacodynamics (PK-PD) combined model in physiological and CIRI model rats, to analyze the protective effect of AH against CIRI.

ClpP-based MtPTAC technology enables targeted degradation of inner mitochondrial membrane proteins.

Mitochondrial proteostasis is essential for tumorigenesis, and mitochondrial inner membrane proteins have emerged as meaningful targets due to their crucial functions in regulating apoptosis, maintaining oxidative phosphorylation, and influencing tumor initiation and progression. Targeted protein degradation (TPD) has garnered significant attention as a promising therapeutic approach. However, conventional TPD platforms relying on the ubiquitin-proteasome system or lysosomal pathways encounter inherent obstacles in targeting proteins sequestered within the mitochondrial compartment and cannot degrade mitochondrial inner membrane proteins.

Time from waking to first cigarette, accelerated biological aging, and risk of premature mortality.

Background: The relationship between the time from waking to first cigarette (TWFC) and premature mortality remains unclear. This study aims to assess the association between TWFC and the risk of premature mortality, and to explore the role of accelerated biological aging in this relationship.

Methods: A total of 309,308 participants from the UK Biobank were included in this study.

SPARE: Symmetrized Point-to-Plane Distance for Robust Non-Rigid 3D Registration.

Existing optimization-based methods for non-rigid registration typically minimize an alignment error metric based on the point-to-point or point-to-plane distance between corresponding point pairs on the source surface and target surface. However, these metrics can result in slow convergence or a loss of detail. In this paper, we propose SPARE, a novel formulation that utilizes a symmetrized point-to-plane distance for robust non-rigid registration.

Iceberg-like pyramids in industrially textured silicon enabled 33% efficient perovskite-silicon tandem solar cells.

The pursuit of higher-efficiency solar cells has spurred the integration of perovskite materials with silicon-based technologies, yet achieving an efficient tandem architecture that leverages industrially textured silicon (ITS) with pyramid sizes larger than 2 μm remains a significant challenge. Such textured surfaces complicate the uniform coverage of the subsequent hole-selective layer deposition and the high-quality deposition of perovskites, ultimately causing significant contact losses in tandem devices. This study presents a tandem solar cell architecture that employs localized submicron contacts, enabled by silica (SiO) nanospheres, to effectively regulate silicon substrate surfaces that exhibit iceberg-like pyramids.

Isolation, characterization and application of probiotic Lactobacillus sakei from Larimichthys crocea intestine.

Currently, disease management is a major challenge for high-density aquaculture in China and a major factor limiting the healthy and sustainable development of our aquaculture industry. Research on fish-derived probiotics as safe feed additives is still relatively limited. In this study, we screened Larimichthys crocea for intestinal lactobacilli, obtained high adhesion strain Lactobacillus sakei YLD10, and further investigated its probiotic function and mechanism of resistance to Pseudomonas plecoglossicida infection.

Omega‑3 Modify the Adverse Effects of Long-Term Exposure to Ambient Air Pollution on the Incidence of Chronic Obstructive Pulmonary Disease: Evidence from a Nationwide Prospective Cohort Study.

We aim to assess the modification effects of omega-3 polyunsaturated fatty acid (PUFA) levels on relationships between long-term air pollutants exposure and chronic obstructive pulmonary disease (COPD) risk. A total of 82,706 nonsmokers were finally included in the UK Biobank. The concentrations of circulating omega-3 PUFA (including total omega-3 and docosahexaenoic acid [DHA]) were measured by using a targeted high-throughput nuclear magnetic resonance metabolomics platform.

Associations of Long-Term Night Shift Work With Incident Irritable Bowel Syndrome: A Population-Based Cohort Study.

Background And Aim: To explore the impact of long-term night shift work on the incidence of irritable bowel syndrome (IBS) and the underlying mechanism.

Methods: This cohort study included 239 760 participants who were in paid employment or self-employed from the UK Biobank. The start date refers to the date when a participant joined the cohort between 2006 and 2010, whereas the end of follow-up was December 31, 2021.

Silica-induced innate immune activation drives macrophage pyroptosis and lung inflammation through glycolytic reprogramming.

Prolonged inhalation of silica causes silicosis, characterized by persistent lung inflammation and irreversible fibrosis, but the mechanism has not been fully illuminated. In the present study, silicosis cases and healthy controls were employed to access the associations between Toll-like receptor 4 (TLR4) and silicosis risk. Silicosis mouse models and macrophage models were established to investigate whether the TLR4/NF-κB pathway drives pyroptosis through glycolytic reprogramming.

Calcium Supplementation, Genetic Susceptibility, and Idiopathic Pulmonary Fibrosis Risk: A Prospective Study.

Background: The association between calcium supplementation and the risk of incident idiopathic pulmonary fibrosis (IPF) is largely unknown.

Objectives: This study aimed to investigate the association of calcium supplementation with IPF incidence and further explore the modifying effect of genetic susceptibility.

Methods: This study analyzed 472,468 participants from the UK Biobank.

New mechanistic understanding of FXR agonist Vonafexor: inducing sublethal damage of HBV-positive liver cancer cells via promoting anti-tumor immunity.

Background: In hepatitis B virus (HBV)-infected patients, there's an increase in exhausted T and NK cells, as well as myeloid-derived suppressor cells (MDSCs) in liver, suggesting that boosting immune responses is beneficial. While Vonafexor inhibits HBV transcriptional activity, its effects on the immune microenvironment of HBV-positive hepatocellular carcinoma (HCC) and the mechanisms of immune clearance of these infected cells are not well understood.

Methods: In this study, tumor tissues from HBV-positive HCC patients were orthotopically transplanted into the livers of Hu-SRC mice to replicate the tumor microenvironment of the patients.

They look virtually the same: Extraretinal representation of symmetry in virtual reality.

The brain must identify objects from different viewpoints that change the retinal image. This study examined the conditions under which the brain spends computational resources to construct view-invariant, extraretinal representations in a 3D virtual environment. We focused on extraretinal representation of visual symmetry.

N-glycosylated LTβR increases the Th17/Treg cell ratio in liver cancer by blocking RORC ubiquitination and FOXP3 transcription.

LTβR-overexpressing CAR-T cells have demonstrated surprising effectiveness against solid tumors, exhibiting strong anti-exhaustion and proliferation capabilities. However, the role of LTβR in CD4 T cell differentiation and anti-tumor activity remains unclear. In this study, we employed primary or subcutaneous mouse hepatocellular carcinoma (HCC) models and flow cytometry to study the impact of conditional knock-in of Ltbr on CD4 T cell differentiation and response, particularly the Th17/Treg cell ratio, and its influence on HCC progression.

Intratumoral Brevibacillus parabrevis enhances antitumor immunity by inhibiting NK cell ferroptosis in hepatocellular carcinoma.

It is known that intestinal flora affects the number and function of NK cells through metabolites, thereby regulating the response of tumors to chemotherapy or immunotherapy. However, little is known about whether intratumoral bacteria are involved in NK cell-mediated antitumor immunity. In this study, 2bRAD-M analysis was performed on patient hepatocellular carcinoma and paired tissues to determine the composition of the intratumoral microbiota.

Short-term starvation inhibits CD36 N-glycosylation and downregulates USP7 UFMylation to alleviate RBPJ-maintained T cell exhaustion in liver cancer.

Short-term starvation (STS) has been shown to enhance the sensitivity of tumors to chemotherapy while concurrently safeguarding normal cells from its detrimental side effects. Nonetheless, the extent to which STS relies on the anti-tumor immune response to impede the progression of hepatocellular carcinoma (HCC) remains uncertain. In this study, we employed mass cytometry, flow cytometry, immunoprecipitation, immunoblotting, CUT&Tag, RT-qPCR, and DNA pull-down assays to evaluate the relationship between STS and T-cell antitumor immunity in HCC.

Neurogranin facilitates maintaining the immunosuppressive state of hepatocellular carcinoma by promoting TGF-β1 secretion.

Immunotherapy has revolutionized cancer treatment, but its effectiveness is limited due to the complexity of the tumor immune microenvironment. Identifying reliable biomarkers that can predict immunotherapy response is essential for enhancing treatment strategies. This study evaluated the potential of Neurogranin (NRGN) as a biomarker for prognosis and immunotherapy response across multiple cancers.

Ethylene modulates the phenylpropanoid pathway by enhancing expression via the ERF5-melatonin-ERF104 pathway in grape seeds.

The interaction between ethylene and melatonin in the regulation of polyphenol metabolism and the underlying mechanism remain largely unclear. This work demonstrated that ethylene treatment increased melatonin biosynthesis by inducing the expression in grape seeds. Ethylene-induced VvERF5 transactivated via binding to the ethylene response element in its promoter.

The interaction between a leflunomide-response methylation site (cg17330251) and variant (rs705379) on response to leflunomide in patients with rheumatoid arthritis.

Objectives: This research aims to reveal the mechanisms of the effect of the Paraoxonase 1 () gene on response to leflunomide (LEF) in rheumatoid arthritis (RA) patients, in terms of single nucleotide polymorphism (SNP), DNA methylation levels.

Methods: A total of 240 RA patients enrolled were categorized into the good response group and the non-response group according to the difference in DAS28 scores between baseline and 6 months after LEF administration. The identified LEF-response cytosine-phosphate-guanines (CpGs) island (cg17330251) and its internal SNPs (rs705379, etc.

Chlorogenic Acid Ameliorates Acetaminophen-Induced Liver Injury Through AMPK/mTOR/ULK1-Mediated Autophagy Activation.

Acetaminophen (APAP)-induced liver injury (AILI) is a universal liver disease and the predominant cause of acute liver failure in clinical practice. Autophagy is a highly conserved intracellular degradation pathway, with accumulating evidence indicating its involvement in APAP hepatotoxicity. Notably, the serine/threonine AMP-activated protein kinase (AMPK)/mammalian target of rapamycin (mTOR)/unc-51-like kinase 1 (ULK1) pathway serves as the most classical autophagy pathway and engages in autophagy activation.

Borrow Strength to Exert: Low-Crystallinity Prussian Blue for Reduction Overload Enhanced Photothermal Therapy.

The strategy "Borrow strength to exert" in Sun Tzu's Art of War refers to borrowing external forces to withstand the enemy. Inspired by this, applying this thought to cancer treatment can achieve a more efficient therapeutic effect. Therefore, a fulcrum to borrow the force is vital and significant.

Assessing the relationships of 1,400 blood metabolites with abdominal aortic aneurysm: a Mendelian randomization study.

Background: Abdominal aortic aneurysm (AAA) is one of the most dangerous types of vascular diseases worldwide. Metabolic disturbance affects disease risk and provide underlying therapeutic targets. Previous studies have reported an association between metabolic disorders and AAA.

PPARα suppresses growth of hepatocellular carcinoma in a high-fat diet context by reducing neutrophil extracellular trap release.

Background & Aims: The role of infiltrating neutrophils in hepatocellular carcinoma (HCC) is modulated by cellular metabolism, specifically lipid homeostasis. Throughout the progression of HCC, alterations in lipid metabolism are intricately linked with regulation of neutrophil function and the release of neutrophil extracellular traps (NETs). However, how much the protumor effect of a high-fat diet (HFD) depends on NETs and the potential interplay between NETs and other leukocytes in HCC remains uncertain.

Ethylene increases the NaHCO stress tolerance of grapevines partially via the VvERF1B-VvMYC2-VvPMA10 pathway.

Here, we evaluated the role of ethylene in regulating the NaHCO stress tolerance of grapevines and clarified the mechanism by which VvERF1B regulates the response to NaHCO stress. The exogenous application of ACC and VvACS3 overexpression in grapevines and grape calli revealed that ethylene increased NaHCO stress tolerance, and this was accompanied by increased plasma membrane H-ATPase (PMA) activity. The expression of VvERF1B was strongly induced by ACC, and overexpression of this gene in grapevines conferred increased NaHCO stress tolerance and enhanced PMA activity and H and oxalate secretion.

Intravenous injection of PCSK9 gain-of-function mutation in C57BL/6J background mice on Angiotensin II-induced AAA.

Objective: This study was performed to compare the incidence of Angiotensin II (Ang II)-induced abdominal aortic aneurysms (AAA) between intravenous and intraperitoneal injection of AAV8.mPCSK9 in wild-type (WT) mice with C57BL/6J background and the pathological differences of above model in WT and ApoE mice.

Design: Male WT mice were injected intraperitoneally or intravenously with either a AAV8.

Oriented wide-bandgap perovskites for monolithic silicon-based tandems with over 1000 hours operational stability.

The instability of hybrid wide-bandgap (WBG) perovskite materials (with bandgap larger than 1.68 eV) still stands out as a major constraint for the commercialization of perovskite/silicon tandem photovoltaics, yet its correlation with the facet properties of WBG perovskites has not been revealed. Herein, we combine experiments and theoretical calculations to comprehensively understand the facet-dependent instability of WBG perovskites.