Microbiota-derived 3-Methyl-L-histidine mediates the proatherogenic effect of high chicken protein diet.

Diet rich in chicken protein has gained a widespread popularity for its profound effect on weight loss and glycemic control; however, its long-term effect on cardiovascular health and the underlying mechanisms remains obscure. Here, we demonstrated that higher intake of chicken protein was an independent risk factor for sub-clinical atherosclerosis. Adherence to high chicken protein diet (HCD) alleviated excessive weight gain and glycemic control regardless of the presence of gut microbiota in apolipoprotein E-deficient mice.

U2AF1 mutation causes an oxidative stress and DNA repair defect in hematopoietic and leukemic cells.

U2AF1 is a core component of spliceosome and controls cell-fate specific alternative splicing. U2AF1 mutations have been frequently identified in myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML) patients, and mutations in U2AF1 are associated with poor prognosis in hematopoietic malignant diseases. Here, by forced expression of mutant U2AF1 (U2AF1 S34F) in hematopoietic and leukemic cell lines, we find that U2AF1 S34F causes increased reactive oxygen species (ROS) production.

Loop33 × 123 CAR-T targeting CD33 and CD123 against immune escape in acute myeloid leukemia.

Background: Immunotherapy, such as chimeric antigen receptor T (CAR-T) cells targeting CD33 or CD123, has been well developed over the past decade for the treatment of acute myeloid leukemia (AML). However, the inability to sustain tumor-free survival and the possibility of relapse due to antigen loss have raised concerns. A dual targeting of CD33 and CD123 is needed for better outcomes.

A dual-targeting approach with anti-IL10R CAR-T cells engineered to release anti-CD33 bispecific antibody in enhancing killing effect on acute myeloid leukemia cells.

Background: Immunotherapies, including chimeric antigen receptor (CAR) T cells and bispecific antibodies (BsAbs), encounter several challenges in the management of acute myeloid leukemia (AML), including limited persistence of these treatments, antigen loss and resistance of leukemia stem cells (LSCs) to therapy.

Methods: Here, we proposed a novel dual-targeting approach utilizing engineered anti-IL10R CAR-T cells to secrete bispecific antibodies targeting CD33. This innovative strategy, rooted in our previous research which established a connection between IL-10 and the stemness of AML cells, designed to improve targeting efficiency and eradicate both LSCs and AML blasts.

Engineering cell-derived extracellular matrix for peripheral nerve regeneration.

Extracellular matrices (ECMs) play a key role in nerve repair and are recognized as the natural source of biomaterials. In parallel to extensively studied tissue-derived ECMs (ts-ECMs), cell-derived ECMs (cd-ECMs) also have the capability to partially recapitulate the complicated regenerative microenvironment of native nerve tissues. Notably, cd-ECMs can avoid the shortcomings of ts-ECMs.

Slow-replicating leukemia cells represent a leukemia stem cell population with high cell-surface CD74 expression.

Persistence of quiescent leukemia stem cells (LSCs) after treatment most likely contributes to chemotherapy resistance and poor prognosis of leukemia patients. Identification of this quiescent cell population would facilitate eradicating LSCs. Here, using a cell-tracing PKH26 (PKH) dye that can be equally distributed to daughter cells following cell division in vivo, we identify a label-retaining slow-cycling leukemia cell population from AML1-ETO9a (AE9a) leukemic mice.

Gut microbial metabolism is linked to variations in circulating non-high density lipoprotein cholesterol.

Background: Non-high-density lipoprotein cholesterol (non-HDL-c) was a strong risk factor for incident cardiovascular diseases and proved to be a better target of lipid-lowering therapies. Recently, gut microbiota has been implicated in the regulation of host metabolism. However, its causal role in the variation of non-HDL-c remains unclear.

Activating innate immune responses repolarizes hPSC-derived CAR macrophages to improve anti-tumor activity.

Generation of chimeric antigen receptor macrophages (CAR-Ms) from human pluripotent stem cells (hPSCs) offers new prospects for cancer immunotherapy but is currently challenged by low differentiation efficiency and limited function. Here, we develop a highly efficient monolayer-based system that can produce around 6,000 macrophages from a single hPSC within 3 weeks. Based on CAR structure screening, we generate hPSC-CAR-Ms with stable CAR expression and potent tumoricidal activity in vitro.

Metabolic interplay: tumor macrophages and regulatory T cells.

The tumor microenvironment (TME) contains a complex cellular ecosystem where cancer, stromal, vascular, and immune cells interact. Macrophages and regulatory T cells (Tregs) are critical not only for maintaining immunological homeostasis and tumor growth but also for monitoring the functional states of other immune cells. Emerging evidence reveals that metabolic changes in macrophages and Tregs significantly influence their pro-/antitumor functions through the regulation of signaling cascades and epigenetic reprogramming.

High Plant Protein Diet Ameliorated Hepatic Lipid Accumulation Through the Modulation of Gut Microbiota.

Scope: Substituting plant protein for animal protein has emerged as a promising strategy for managing atherogenic lipids. However, the impact of long-term intake of a high plant protein diet (HPD) on hepatic lipid disorder remains unclear.

Methods And Results: Eight-week-old apolipoprotein E deficient (apoE ) mice are fed with either a normal protein diet (NCD) or HPD for 12 weeks.

Universal Anti-CD7 CAR-T Cells Targeting T-ALL and Functional Analysis of CD7 Antigen on T/CAR-T Cells.

Chimeric antigen receptor T (CAR-T) cell therapy initiates new methods and turns the scale of clinical treatment on relapsed/refractory acute T lymphoblastic leukemia (T-ALL). In this study, we generated the second-generation CD7-targeting CAR-T cells with a new antigen-binding single-chain variable fragment sequence and made it universal via CRISPR-based knockout of and genes (termed UCAR-T). The CD7 UCAR-T cells can efficiently proliferate and lyse T-ALL tumor cell , along with prominent proinflammatory cytokines secretion.

Mitochondria Dictate Function and Fate of HSCs and T Cells.

Hematopoietic stem cells (HSC) and T cells are intimately related, lineage-dependent cell populations that are extensively used as therapeutic products for the treatment of hematologic malignancies and certain types of solid tumors. These cellular therapies can be life-saving treatments; however, their efficacies are often limited by factors influencing their activity and cellular properties. Among these factors is mitochondrial metabolism, which influences the function and fate commitment of both HSCs and T cells.

Regulatory circuits of mitophagy restrict distinct modes of cell death during memory CD8 T cell formation.

Mitophagy, a central process guarding mitochondrial quality, is commonly impaired in human diseases such as Parkinson's disease, but its impact in adaptive immunity remains unclear. The differentiation and survival of memory CD8 T cells rely on oxidative metabolism, a process that requires robust mitochondrial quality control. Here, we found that Parkinson's disease patients have a reduced frequency of CD8 memory T cells compared with healthy donors and failed to form memory T cells upon vaccination against COVID-19, highlighting the importance of mitochondrial quality control for memory CD8 T cell formation.

2B4 inhibits the apoptosis of natural killer cells through phosphorylated extracellular signal-related kinase/B-cell lymphoma 2 signal pathway.

Background Aims: Decades after the identification of natural killer (NK) cells as potential effector cells against malignantly transformed cells, an increasing amount of research suggests that NK cells are a prospective choice of immunocytes for cancer immunotherapy in addition to T lymphocytes for cancer immunotherapy. Recent studies have led to a breakthrough in the combination of hematopoietic stem-cell transplantation with allogeneic NK cells infusion for the treatment of malignant tumors. However, the short lifespan of NK cells in patients is the major impediment, limiting their efficacy.

Cardiometabolic benefits of Lacticaseibacillus paracasei 8700:2: A randomized double-blind placebo-controlled trial.

Background & Aims: Modulating microbial metabolism via probiotic supplementation has been proposed as an attractive strategy for the prevention of cardiometabolic diseases. Recently, Lacticaseibacillus paracasei (L. paracasei) was reported to alleviate metabolic disorders in murine models, however, its beneficial effects in humans remain to be determined.

Construction of CD19 targeted dual- and enhanced dual-antibodies and their efficiency in the treatment of B cell malignancy.

Background: T cell-redirecting bispecific antibodies establish a connection between endogenous T cells and tumor cells, activating T cells function to eliminate tumor cells without ex vivo genetic alteration or manipulation. Here, we developed a novel dual-specific antibody (DuAb) and an enhanced DuAb (EDuAb) with different stimulation signal to activate T cells, and evaluated their impact on the treatment of acute lymphoblastic leukemia (ALL).

Methods: The expression plasmids of the DuAb and EDuAb containing CD80 molecule were constructed by cloning heavy chain and light chain variable fragments from anti-human CD19 (HI19a) and CD3 (HIT3a) monoclonal antibody hybridomas, respectively.

Preparation and assessment of an optimized multichannel acellular nerve allograft for peripheral nerve regeneration.

Peripheral nerve regeneration after injury is still a clinical problem. The application of autologous nerve grafting, the gold standard treatment, is greatly restricted. Acellular nerve allografts (ANAs) are considered promising alternatives, but they are difficult to achieve satisfactory therapeutic outcomes, which may be attributed to their compact inherent ultrastructure and substantial loss of extracellular matrix (ECM) components.

Implications from proteomic studies investigating circadian rhythm disorder-regulated neurodegenerative disease pathology.

Neurodegenerative diseases (NDs) affect 15% of the world's population and are becoming an increasingly common cause of morbidity and mortality worldwide. Circadian rhythm disorders (CRDs) have been reported to be involved in the pathogenic regulation of various neurologic diseases, including Alzheimer's disease, Parkinson's disease, Huntington's disease, multiple sclerosis and amyotrophic lateral sclerosis. Proteomic technology is helpful to explore treatment targets for CRDs in patients with NDs.

Gestational and Postpartum Complications in Patients with First Trimester Thyrotoxicosis: A Prospective Multicenter Cohort Study from Northeast China.

Gestational transient thyrotoxicosis (GTT) and Graves' disease (GD) are the most common causes of hyperthyroidism during pregnancy. However, few studies have compared pregnancy outcomes of patients who had GTT with those who had GD in the first trimester of pregnancy. We conducted a prospective multicenter cohort study in China.

The inhibitory effect of vitamin D on myocardial homocysteine levels involves activation of Nrf2-mediated methionine synthase.

Background: Homocysteine (Hcy) is a synthetic amino acid containing sulfhydryl group, which is an intermediate product of the deep metabolic pathway of methionine and cysteine. The abnormal increase in fasting plasma total Hcy concentration caused by various factors is called hyperhomocysteine (HHcy). HHcy is closely relevant to the occurrence and progression of diverse cardiovascular and cerebrovascular diseases, such as coronary heart disease, hypertension and diabetes, etc.