Suppression of melanoma by mice lacking MHC-II: Mechanisms and implications for cancer immunotherapy.

Immune checkpoint inhibitors interfere with T cell exhaustion but often fail to cure or control cancer long-term in patients. Using a genetic screen in C57BL/6J mice, we discovered a mutation in host H2-Aa that caused strong immune-mediated resistance to mouse melanomas. H2-Aa encodes an MHC class II α chain, and its absence in C57BL/6J mice eliminates all MHC-II expression.

Biodegradable Ruthenium-Rhenium Complexes Containing Nanoamplifiers: Triggering ROS-Induced CO Release for Synergistic Cancer Treatment.

The constrained effectiveness of photodynamic therapy (PDT) has impeded its widespread use in clinical practice. Urgent efforts are needed to address the shortcomings faced in photodynamic therapy, such as photosensitizer toxicity, short half-life, and limited action range of reactive oxygen species (ROS). In this study, a biodegradable copolymer nanoamplifier is reported that contains ruthenium complex (Ru-complex) as photosensitizer (PS) and rhenium complex (Re-complex) as carbon monoxide (CO)-release molecule (CORM).

Lrp10 suppresses IL7R limiting CD8 T cell homeostatic expansion and anti-tumor immunity.

Signals emanating from the T-cell receptor (TCR), co-stimulatory receptors, and cytokine receptors each influence CD8 T-cell fate. Understanding how these signals respond to homeostatic and microenvironmental cues can reveal new ways to therapeutically direct T-cell function. Through forward genetic screening in mice, we discover that loss-of-function mutations in LDL receptor-related protein 10 (Lrp10) cause naive and central memory CD8 T cells to accumulate in peripheral lymphoid organs.

Association between predicted fat mass, predicted lean mass, predicted percent fat and type 2 diabetes mellitus in Japanese adults: a retrospective study.

Background: Type 2 diabetes mellitus (T2DM) is known to have obesity as a risk factor. Body mass index cannot distinguish between lean mass and fat mass. We aimed to examine the association between predicted fat mass, predicted lean mass, predicted percent fat and risk of T2DM in Japanese adults.

REDUCED CX43 EXPRESSION INDUCES AUTOPHAGY THROUGH ACTIVATION OF THE AMPK-MTOR-ULK1 SIGNALING PATHWAY IN THE COMMON BILE DUCT LIGATION RAT HEART.

Backgrounds: This study aimed to investigate the relationship between Cx43 expression and autophagy mediated by the AMPK-mTOR-Ulk1 signaling pathway in jaundice heart. Methods: In this study, a jaundice model was established in common bile duct ligation (CBDL) rats. Cardiac injury was assessed using various methods including myocardial injury indicators, echocardiography, transmission electron microscopy, hematoxylin and eosin staining, Masson staining, immunohistochemical analyses, and immunofluorescence staining.

The prophylaxis functions of Lactobacillus fermentum GLF-217 and Lactobacillus plantarum FLP-215 on ulcerative colitis via modulating gut microbiota of mice.

Background: The strong connection between gut microbes and human health has been confirmed by an increasing number of studies. Although probiotics have been found to relieve ulcerative colitis, the mechanism varies by the species involved. In this study, the physiological, immune and pathological factors of mice were measured and shotgun metagenomic sequencing was conducted to investigate the potential mechanisms in preventing ulcerative colitis.

Lrp10 suppresses IL7R limiting CD8 T cell homeostatic expansion and anti-tumor immunity.

Signals emanating from the T cell receptor (TCR), co-stimulatory receptors, and cytokine receptors each influence CD8 T cell fate. Understanding how these signals respond to homeostatic and microenvironmental cues can reveal new ways to therapeutically direct T cell function. Through forward genetic screening in mice, we discovered that loss-of-function mutations in ( ) caused naïve and central memory CD8 T cells to accumulate in peripheral lymphoid organs.

Seizure course of PCDH19 clustering epilepsy in female children: A multicentre cohort study in China.

Aim: To investigate the seizure course of PCDH19 clustering epilepsy (PCDH19-CE) in a cohort of female children in China.

Method: This ambidirectional cohort study examined 113 female patients with PCDH19-CE through multicentre collaboration. Prognostic factors for seizure freedom were evaluated by multivariate Cox regression analysis.

CKCC1858 alleviates hyperlipidemia in golden hamsters on a high-fat diet modulating gut microbiota.

To investigate the effect of probiotic CKCC1858, LF on the prevention of hyperlipidemia and its correlation with gut microbiota, golden hamsters were fed a high-fat diet alone or in combination with the probiotic for 6 weeks. The results showed that the LF intervention alleviated HFD-induced hyperlipidemia and liver damage, as evidenced by the reduced serum lipid profile levels and liver function markers. More importantly, the LF intervention attenuated HFD-induced microbiota dysbiosis by enhancing the abundance of SCFA-producing bacteria and reshaping the metabolic functions of the gut microbiota, likely contributing to its pronounced preventive effects on hyperlipidemia.

Virus-like particles nanoreactors: from catalysis towards bio-applications.

Virus-like particles (VLPs) are self-assembled supramolecular structures found in nature, often used for compartmentalization. Exploiting their inherent properties, including precise nanoscale structures, monodispersity, and high stability, these architectures have been widely used as nanocarriers to protect or enrich catalysts, facilitating catalytic reactions and avoiding interference from the bulk solutions. In this review, we summarize the current progress of virus-like particles (VLPs)-based nanoreactors.

CKCC1913 mediated modulation of the gut-liver axis alleviated insulin resistance and liver damage induced by type 2 diabetes.

Type 2 diabetes mellitus (T2DM) is a chronic metabolic disorder characterized by dysregulation of lipid metabolism, insulin resistance, and gut microbiota disorder. Compared to drug interventions, probiotic interventions may have a more enduring effect without producing any side effects. Thus, the potential of probiotics as a therapeutic approach for diabetes and other metabolic disorders has gained increasing attention in recent years.

Transformable nanodrugs for overcoming the biological barriers in the tumor environment during drug delivery.

Drug delivery systems have been studied massively with explosive growth in the last few decades. However, challenges such as biological barriers are still obstructing the delivery efficiency of nanomedicines. Reports have shown that the physicochemical properties, such as the morphologies of nanodrugs, could highly affect their biodistribution and bioavailability.

Excited-state and charge-carrier dynamics in binary conjugated polymer dots towards efficient photocatalytic hydrogen evolution.

Aqueous dispersed conjugated polymer dots (Pdots) have shown promising application in photocatalytic hydrogen evolution. To efficiently extract photogenerated charges from type-II heterojunction Pdots for hydrogen evolution, the mechanistic study of photophysical processes is essential for Pdot optimization. Within this work, we use a PFODTBT donor (D) polymer and an ITIC small molecule acceptor (A) as a donor/acceptor (D/A) model system to study their excited states and charge/energy transfer dynamics steady-state and time-resolved photoluminescence spectroscopy, respectively.

Photosynthetic Polymer Dots-Bacteria Biohybrid System Based on Transmembrane Electron Transport for Fixing CO into Poly-3-hydroxybutyrate.

Organic semiconductor-microbial photosynthetic biohybrid systems show great potential in light-driven biosynthesis. In such a system, an organic semiconductor is used to harvest solar energy and generate electrons, which can be further transported to microorganisms with a wide range of metabolic pathways for final biosynthesis. However, the lack of direct electron transport proteins in existing microorganisms hinders the hybrid system of photosynthesis.

Detecting genomic mosaicism in "de novo" genetic epilepsy by amplicon-based deep sequencing.

Aim: To investigate the occurrence of mosaicism in epilepsy probands and their parents using amplicon-based deep sequencing (ADS).

Methods: Patients were recruited from the outpatient of Peking University First Hospital. Two hundred and sixty-four probands with pathogenic variants tested by next-generation sequencing (NGS) were enrolled.

IL6 supports long-term expansion of hepatocytes in vitro.

Hepatocytes are very difficult to expand in vitro. A few studies have demonstrated that chemical cocktails with growth factors or Wnt ligands can support long-term expansion of hepatocytes via dedifferentiation. However, the culture conditions are complex, and clonal expansion of hepatic progenitors with full differentiation capacity are rarely reported.

-related epilepsy in mosaic males: The phenotypic implication of genotype and variant allele frequency.

Objective: To analyze the genotypes and phenotypes of mosaic male patients with -related epilepsy (-RE) and explore the correlation between genotype, variant allele frequency (VAF), and phenotypic severity.

Methods: Clinical data and peripheral blood samples of 11 male mosaic patients were collected and analyzed in our study. The VAF of the gene from peripheral blood was quantified using amplicon-based deep sequencing.

Preparation, characterization, evaluation and mechanistic study of organic polymer nano-photocatalysts for solar fuel production.

Production of renewable fuels from solar energy and abundant resourses, such as water and carbon dioxide, photocatalytic reactions is seen as a promising strategy to adequately address the climate challenge. Photocatalytic systems based on organic polymer nanoparticles (PNPs) are seen as one avenue to transform solar energy into hydrogen and other solar fuels. Semiconducting PNPs are light-harvesting materials with exceptional optical properties, photostability, low cost and low cytotoxity, whose performance surpasses conventional organic dyes and inorganic semiconductors.

Polymer Dots as Photoactive Membrane Vesicles for [FeFe]-Hydrogenase Self-Assembly and Solar-Driven Hydrogen Evolution.

A semiartificial photosynthesis approach that utilizes enzymes for solar fuel production relies on efficient photosensitizers that should match the enzyme activity and enable long-term stability. Polymer dots (Pdots) are biocompatible photosensitizers that are stable at pH 7 and have a readily modifiable surface morphology. Therefore, Pdots can be considered potential photosensitizers to drive such enzyme-based systems for solar fuel formation.

RNPS1 inhibits excessive tumor necrosis factor/tumor necrosis factor receptor signaling to support hematopoiesis in mice.

Null mutations of spliceosome components or cofactors are homozygous lethal in eukaryotes, but viable hypomorphic mutations provide an opportunity to understand the physiological impact of individual splicing proteins. We describe a viable missense allele (F181I) of Rnps1 encoding an essential regulator of splicing and nonsense-mediated decay (NMD), identified in a mouse genetic screen for altered immune cell development. Homozygous mice displayed a stem cell–intrinsic defect in hematopoiesis of all lineages due to excessive apoptosis induced by tumor necrosis factor (TNF)–dependent death signaling.

[Hyperbilirubinemia induced oxidative stress resulting in glomerular injury in rats].

Objective: To observe the effect of hyperbilirubinemia on glomerulus of rats, and to explore its dose-response and mechanism.

Methods: Twenty-four adult male Sprague-Dawley (SD) rats were divided into four groups according to the random number table method, with 6 rats in each group. Hyperbilirubinemia rat model was reproduced by intraperitoneal injection of bilirubin once every 12 hours for 4 times, at doses of 50, 100, and 200 mg/kg in low, medium, and high dose bilirubin group (LB group, MB group, HB group), respectively.

Muscle magnetic resonance imaging in patients with LAMA2-related muscular dystrophy.

LAMA2-related muscular dystrophy (LAMA2-MD) is classified into congenital muscular dystrophy type 1A (MDC1A) and autosomal recessive limb-girdle muscular dystrophy-23 (LGMDR23). The purpose of this study was to identify the involvement pattern of thigh muscles of LAMA2-MD patients on magnetic resonance imaging. Fourteen MDC1A and 3 LGMDR23 patients were included, with 21 known and 8 novel LAMA2 disease-causing variants.