Unveiling distinct clinical manifestations of primary familial brain calcifications in Asian and European patients: A study based on 10-year individual-level data.

Background: Primary Familial Brain Calcification (PFBC) can manifest clinically with a complex and heterogeneous array of symptoms, including parkinsonism, dysarthria, and cognitive impairment. However, the distinct presentations of PFBC in Asian and European populations remain unclear.

Methods: We conducted a systematic search of PubMed for studies involving genetically confirmed PFBC patients.

Tryptophan Ameliorates Metabolic Syndrome by Inhibiting Intestinal Farnesoid X Receptor Signaling: The Role of Gut Microbiota-Bile Acid Crosstalk.

Metabolic syndrome (MS) is a progressive metabolic disease characterized by obesity and multiple metabolic disorders. Tryptophan (Trp) is an essential amino acid, and its metabolism is linked to numerous physiological functions and diseases. However, the mechanisms by which Trp affects MS are not fully understood.

Novel antibody-antibiotic conjugate using KRM-1657 as payload eliminates intracellular MRSA in vitro and in vivo.

Staphylococcus aureus is considered to be an extracellular pathogen. However, survival of S.aureus within host cells may cause long-term colonization and clinical failure.

Leucine Supplementation Modulates Lipid Metabolism and Inflammation in Early Weaning Piglets.

Early weaning can induce the programmed dysregulation of glycolipid metabolism and inflammation in adult animals. The primary objective of this study was to evaluate the efficacy of leucine supplementation administered promptly after early weaning in mitigating these adverse effects in piglets. At day 21, 24 piglets were randomly selected and divided into 3 groups: EW group where the piglets were weaned at day 21 and fed basal diet, EWL group where the piglets were weaned at day 21 and fed the basal diet with supplementation of 1% leucine, and C group where the piglets were fed basal diet and weaned at 28 days.

Sex differences in the correlation between white matter hyperintensity and 3-month outcome in acute stroke patients.

Background: The severity of white matter hyperintensities (WMH) has been shown to be an independent predictor of poor stroke outcome, but the effect of sex on this correlation has not been investigated further. Therefore, the purpose of our study was to assess whether there was a sex difference between the severity of WMH and poor stroke outcome.

Methods: This retrospective study included 449 patients with acute ischemic stroke (AIS) who received intravenous thrombolysis.

Scheduling optimization of electric energy meter distribution vehicles for intelligent batch rotation.

As industrial technology continues to advance through integration, society's demand for electricity is rapidly increasing. To meet the requirements of refined grid management and address the elevated challenges arising from the increased electrical load, this paper delves into the investigation of distribution vehicle scheduling for the practical scenario of batch rotation of smart meters. Initially, based on the practical distribution task requirements of a provincial metrology verification center, a multi-level optimization model is constructed for the batch rotation and distribution vehicle scheduling of smart meters.

Branched-chain amino acid modulation of lipid metabolism, gluconeogenesis, and inflammation in a finishing pig model: targeting leucine and valine.

Branched-chain amino acids (BCAAs) play a regulatory role in adipogenesis and energy balance. Therefore, this study aimed to investigate the impact of BCAA supplements, especially leucine (Leu) and valine (Val) supplementation, on lipid metabolism and related disorders in a finishing pig model. The results demonstrated that Leu (1%) and Val decreased serum as well as hepatic lipid accumulation.

Glutamine Ameliorates Liver Steatosis via Regulation of Glycolipid Metabolism and Gut Microbiota in High-Fat Diet-Induced Obese Mice.

Obesity and its associated conditions, such as nonalcoholic fatty liver disease (NAFLD), are risk factors for health. The aim of this study was to explore the effects of glutamine (Gln) on liver steatosis induced by a high-fat diet (HFD) and HEPG2 cells induced by oleic acid. Gln demonstrated a positive influence on hepatic homeostasis by suppressing acetyl CoA carboxylase (ACC) and fatty acid synthase (FAS) and promoting sirtuin 1 (SIRT1) expression while improving glucose metabolism by regulating serine/threonine protein kinase (AKT)/factor forkhead box O1 (FOXO1) signals in vivo and in vitro.

USP2 promotes tumor immune evasion via deubiquitination and stabilization of PD-L1.

The abnormal upregulation of programmed death ligand-1 (PD-L1) on tumor cells impedes T-cell mediated cytotoxicity through PD-1 engagement, and further exploring the mechanisms regulation of PD-L1 in cancers may enhance the clinical efficacy of PD-L1 blockade. Here, using single-guide RNAs (sgRNAs) screening system, we identify ubiquitin-specific processing protease 2 (USP2) as a novel regulator of PD-L1 stabilization for tumor immune evasion. USP2 directly interacts with and increases PD-L1 abundance in colorectal and prostate cancer cells.

Application of a New Approach for Laparoscopic Resection of Bismuth IIIa Hilar Cholangiocarcinoma.

Hilar cholangiocarcinoma (HCCA) has a high degree of malignancy and poor prognosis, and the best long-term prognosis can only be achieved by radical resection. However, the surgical steps are complicated, and the operating space is limited, making it hard to complete laparoscopically. So our team proposes a new surgical approach for laparoscopic left-liver-first anterior radical modular orthotopic right hemihepatectomy (Lap-Larmorh).

How to implement minimally invasive duodenum-preserving total pancreatic head resection for patients with pancreatic head lesions: A retrospective study.

Laparoscopic duodenum-preserving pancreatic head resection (LDPPHR) has been widely reported. However, due to the challenges involved in performing total pancreatic head resection during operation, there are few studies reporting it. Between November 2016 and October 2022, we performed laparoscopic duodenum-preserving total pancreatic head resection (LDPPHRt) on 64 patients in the Department of Hepatobiliary Surgery, the Second Hospital of Hebei Medical University.

Guanidine-modified albumin-MMAE conjugates with enhanced endocytosis ability.

Aiming to address the insufficient endocytosis ability of traditional albumin drug conjugates, this paper reports elegant guanidine modification to improve efficacy for the first time. A series of modified albumin drug conjugates were designed and synthesized with different structures, including guanidine (GA), biguanides (BGA) and phenyl (BA), and different quantities of modifications. Then, the endocytosis ability and / potency of albumin drug conjugates were systematically studied.

Raddeanin A Enhances Mitochondrial DNA-cGAS/STING Axis-Mediated Antitumor Immunity by Targeting Transactive Responsive DNA-Binding Protein 43.

Immune checkpoint therapies (ICT) have achieved unprecedented efficacy in multiple cancer treatments, but are still limited by low clinical response rates. Identification of immunogenic cell death (ICD)-inducing drugs that can induce tumor cell immunogenicity and reprogram the tumor microenvironment is an attractive approach to enhance antitumor immunity. In the present study, Raddeanin A (RA), an oleanane class triterpenoid saponin isolated from Anemone raddeana Regel, is uncovered as a potent ICD inducer through an ICD reporter assay combined with a T cell activation assay.

Development of a nitroreductase-dependent theranostic payload for antibody-drug conjugate.

Antibody-drug conjugates are gradually revolutionizing anticancer therapy. Payload is one of the most crucial components of ADC for high antitumor activity. However, there is no direct and real-time monitoring method for the intracellular release mechanism of the payload.

Clinical Value Analysis of Hepatectomy Based on Minimally Invasive Surgical Imaging for Hepatolithiasis.

Objective: To investigate the clinical value of hepatectomy based on minimally invasive surgical images in the treatment of hepatolithiasis.

Methods: The clinical data of 87 patients with hepatolithiasis who received treatment in the Department of General Surgery of our hospital from February 2020 to September 2021 were retrospectively analyzed. According to different surgical methods, the patients were divided into minimally invasive group ( = 43) and laparotomy group ( = 44).

Portal vein thrombosis in a noncirrhotic patient after hemihepatectomy: A case report and review of literature.

Background: Portal vein thrombosis (PVT) is a condition caused by hemodynamic disorders. It may be noted in the portal vein system when there is an inflammatory stimulus in the abdominal cavity. However, PVT is rarely reported after hepatectomy.

oligosaccharides increase serotonin in the brain and ameliorate depression promoting 5-hydroxytryptophan production in the gut microbiota.

oligosaccharides (MOO) are an oral drug approved in China for the treatment of depression in China. However, MOO is hardly absorbed so that their anti-depressant mechanism has not been elucidated. Here, we show that oral MOO acted on tryptophan → 5-hydroxytryptophan (5-HTP) → serotonin (5-HT) metabolic pathway in the gut microbiota.

Threonine supplementation prevents the development of fat deposition in mice fed a high-fat diet.

Obesity is the main factor involved in the onset of many diseases. Threonine supplementation has been demonstrated to reduce fat mass and serum triglycerides in already obese mice. However, it is unclear whether threonine could inhibit the development of obesity in mice without previous high-fat diet induction.

LDL receptor-related protein 1 (LRP1), a novel target for opening the blood-labyrinth barrier (BLB).

Inner ear disorders are a cluster of diseases that cause hearing loss in more than 1.5 billion people worldwide. However, the presence of the blood-labyrinth barrier (BLB) on the surface of the inner ear capillaries greatly hinders the effectiveness of systemic drugs for prevention and intervention due to the low permeability, which restricts the entry of most drug compounds from the bloodstream into the inner ear tissue.

A Functional Screening Identifies a New Organic Selenium Compound Targeting Cancer Stem Cells: Role of c-Myc Transcription Activity Inhibition in Liver Cancer.

Cancer stem cells (CSCs) are reported to play essential roles in chemoresistance and metastasis. Pathways regulating CSC self-renewal and proliferation, such as Hedgehog, Notch, Wnt/β-catenin, TGF-β, and Myc, may be potential therapeutic targets. Here, a functional screening from the focused library with 365 compounds is performed by a step-by-step strategy.

Design, synthesis and biological activity evaluation of a series of bardoxolone methyl prodrugs.

Bardoxolone methyl (CDDO-Me) has exhibited positive therapeutic effects in clinical trials for diabetic nephropathy (DN), but serious safety risks in the heart exist because of the potential off-target response resulting from the highly active part of CDDO-Me. Herein, we reported a novel strategy to prepare Cathepsin B (CTSB) cleavable and improved water-soluble prodrugs of CDDO-Me. CTSB linkers connection to the highly active α-cyano-α, β-unsaturated ketone (CUK) part of CDDO-Me with the incorporation of polyethylene glycol (PEG) moieties, provided a series of prodrugs of CDDO-Me without CUK part exposure.

Development of applicable thiol-linked antibody-drug conjugates with improved stability and therapeutic index.

Maleimides are typically applicable for coupling with reactive thiol moieties of antibodies in antibody-drug conjugates (ADCs) via the thiol-Michael click chemistry. Even so, the thiosuccinimide group produced in ADCs is unstable under physiological conditions, which is a unresolved issue in the ADC industry that can cause serious off-target toxicity. Committed to solving the stability defects of traditional thiosuccinimide-containing ADCs, we explored a series of linkers based on the ring-opening hydrolysates of thiosuccinimide.