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关键词： AMP-activated Protein Kinase   Forkhead Box O1   Overwintering Starvation Stress   Peroxisome Proliferator-activated Receptor Gamma Coactivator 1-alpha   Pyruvate Dehydrogenase Kinase 4   Skeletal Muscle Gluconeogenesis  

摘要： During the wintering period characterized by feed scarcity, animals activate the sympathetic nervous system (SNS)-beta-adrenergic receptor (beta AR)-AMP-activated protein kinase (AMPK)/peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1 alpha) signaling pathway in their bodies. This activation increases the transcriptional activity of forkhead box O1 (FOXO1) transcription factor and pyruvate dehydrogenase kinase 4 (PDK4), leading to the upregulation of gluconeogenesis-limiting genes phosphoenolpyruvate carboxykinase (PEPCK) and glucose-6-phosphatase (G6Pase). Additionally, it enhances the functions of carnitine palmitoyltransferase 1 (CPT1), uncoupling protein 1 (UCP1), cluster of differentiation 36 (CD36), and fatty acid transport protein (FATP). This promotes promote intermuscular fat oxidation and the production of gluconeogenesis precursor glycerol, thereby enhancing animal skeletal muscle gluconeogenesis to maintain animal energy homeostasis and life activities under low temperature and starvation conditions. This article describes the effects of overwintering starvation stress on the AMPK/ PGC-1 alpha signaling pathway and its molecular mechanism in animal skeletal muscle gluconeogenesis. The aim to provide a theoretical basis for optimizing sustainable breeding strategies and improving animal production performance in alpine regions.

摘要： With rising obesity rates and increasing glucagon-like peptide-1 receptor agonist (GLP-1 RA) use, understanding perinatal prescribing patterns is important. We conducted a retrospective cohort study to examine semaglutide and tirzepatide prescribing among pregnant patients in the United States from 2019 to 2024. We analyzed prescriptions during the year before and after delivery, grouping deliveries into 6-month periods and applying segmented linear regression with data-driven change-point detection to identify prescribing-trend shifts. Prevalence of GLP-1 RA prescribing increased from 0.2 to 6.4 per 1,000 deliveries predelivery and from 0.3 to 14.6 per 1,000 deliveries postdelivery, with significant prescribing change points indicating accelerated prescribing in June 2022 for the predelivery period and in March 2021 for the postdelivery period. These findings suggest rapid adoption of GLP-1 RAs in the perinatal period and underscore the need for evidence-based safety data for these medications.

关键词： 1,2,4-triazole-3-carboxylates   ribavirin full deoxy analogs   antiviral agents   SARS-CoV2   acylamidrazones  

摘要： 5-Substituted analogs of the ribavirin heterocyclic base showed significant antiviral activity against SARS-CoV2 together with reduced toxicity, compared to ribavirin. Using the SARS-CoV2 attachment model, it was found that 5-(pyridin-4-yl)-1,2,4-triazole-3-carboxamide and 5-(tetrahydrofuran-2-yl)-1,2,4-triazole-3-carboxamide, as well as the isosteric derivative of the latter, namely, 5-(tetrahydrofuran-2-yl)-1,2,4-triazole-3-carbothioamide, could act through inhibiting viral attachment to the cell.

关键词： dehydroxylative allylation   benzyl alcohol   allylsilane   Br & oslash   nsted acid   1,1,1,3,3,3-hexafluoro-2-propanol  

摘要： A direct dehydroxylative allylation reaction of benzylic alcohols with allylsilanes catalyzed by Br & oslash;nsted acids in 1,1,1,3,3,3-hexafluoro-2-propanol was developed. A wide variety of secondary and tertiary benzylic alcohols are applicable to the reaction with various allyltrimethylsilanes, to provide the corresponding coupling products in high yields. Using this catalytic transformation, a concise and short-step synthesis of (+/-)-crucudiol was achieved.

摘要： What is the relevant market in private international law? Determining the applicable law in antitrust and unfair competition law is one of the first questions in international damages claims. From a European perspective, the lex fori in private enforcement actions is Art. 6 Rome II Regulation. Here, the connecting factor is the relevant market. There is extensive literature on the market definition in antitrust law. However, there is a long-standing debate on how to approach the relevant market in antitrust and unfair competition law in the context of private international law. The purpose of this paper is to define the relevant market in private international law. It examines whether the market definition from antitrust law can be used to determine the applicable law. Also, it will examine whether the connecting factors in international antitrust and unfair competition law correspond (Art. 6(3)(a) and Art. 6(1) Rome II Regulation). Finally, several approaches to restrict the effects doctrine and the impact principle in antitrust and unfair competition law are discussed. The discussion follows the method of legal interpretation enriched with economic arguments, which have been largely ignored in previous debates.

关键词： Lie group action   Controllability   Control systems   Control sets   Flag manifolds  

摘要： The main purpose of this paper is to provide an explicit description of the invariant control sets for a class of control systems induced on the unit quaternion sphere S-3 by the action of the Lorentz group SO(1,4) and then generalize it to the sphere Sn-1. These control sets are the maximal subsets of approximate controllability for the control systems. Describing them in detail is generally challenging due to the complexity of the geometry and topology of the underlying differentiable manifold and the behavior of the vector fields defining the control system. In this work, the Lie theory and the quaternions play a fundamental role in achieving our main results.

关键词： integrated domains   NLR immune receptors   pathogen effectors   plant immunity   protein engineering  

关键词： paclitaxel/albumin-paclitaxel   platinum   anti-PD-1/L1   non-small cell lung cancer   meta-analysis  

摘要： Platinum-based dual-drug chemotherapy is the standard first-line treatment for non-small cell lung cancer. It inhibits tumor proliferation through cytotoxic effects. However, in clinical practice, 30-40% of patients will experience disease progression due to primary or secondary drug resistance. The present study aimed to analyze the clinical efficacy and adverse reactions of anti-PD-1/L1 + paclitaxel/albumin-paclitaxel + platinum and paclitaxel/albumin-paclitaxel + platinum in the treatment of advanced non-small cell lung cancer. Computer searches were conducted in PubMed, The Cochrane Library, EMbase, China National Knowledge Infrastructure, Wanfang Data, VIPernet and China Biology Medicine databases. Randomized controlled trials on the clinical efficacy of taxel/albumin-paclitaxel + platinum and the combination of taxel/albumin-paclitaxel + platinum immunotherapy drugs in patients with non-small cell lung cancer were collected from the establishment of the database to May 2025. Meta-analysis was conducted using RevMan 5.4 software. A total of five randomized controlled trials were included, involving a total of 3,683 patients. The meta-analysis showed that the median survival rate and the incidence of asymptomatic recurrence in the experimental group (anti-PD-1/L1 + paclitaxel/albumin-paclitaxel + platinum combined immunotherapy drugs) for the treatment of non-small cell lung cancer were higher than those in the control group (paclitaxel/albumin-paclitaxel + platinum). The median progression-free and overall survival time in the experimental group were longer than those in the control group, and the incidence of side effects was higher than that in the control group. The experimental group had advantages in treating non-small cell lung cancer during the asymptomatic remission period and prolonging survival time, but the incidence of adverse reactions decreased.

关键词： early-onset Alzheimer's disease   PSEN1 mutation   parkinsonism   positron emission tomography   multimodal imaging  

摘要： We report the multimodal PET/MR imaging findings in a 31-year-old woman with a novel presenilin 1 (PSEN1) missense mutation (c.699G>A, p.M233I) who developed progressive cognitive decline and parkinsonian features. Multimodal imaging, including glucose metabolism, dopamine transporter function, amyloid-beta pathology, and tau protein PET imaging, combined with structural MRI, revealed widespread abnormalities concordant with her clinical manifestations. Findings included glucose hypometabolism, dopaminergic dysfunction, amyloid and tau deposition, and cerebellar atrophy. This case highlights the diagnostic value of multiprobe PET/MR imaging in characterizing complex neurodegenerative phenotypes and expands the genotypic and phenotypic spectrum of PSEN1-associated early-onset Alzheimer's disease (EOAD) with parkinsonism.