Time-Lapse Acquisition of Both Freely Secreted Proteome and Exosome Encapsulated Proteome in Live Organoids' Microenvironment.

Proteomic communications in neighboring microenvironments during early organ development is a dynamic process that continuously reshapes human embryonic stem cells (hESCs) developmental fate. Such dynamic proteomic alteration in the microenvironment consists of both freely secreted proteome and exosome-encapsulated proteome. Simultaneous monitoring of the time-lapse shift of both proteomes with live organoids remains technically challenging.

Improving regulatory T cell-based therapy: insights into post-translational modification regulation.

Regulatory T (Treg) cells are pivotal for maintaining immune homeostasis and play essential roles in various diseases, such as autoimmune diseases, graft-versus-host disease (GVHD), tumors, and infectious diseases. Treg cells exert suppressive function via distinct mechanisms, including inhibitory cytokines, granzyme or perforin-mediated cytolysis, metabolic disruption, and suppression of dendritic cells. Forkhead Box P3 (FOXP3), the characteristic transcription factor, is essential for Treg cell function and plasticity.

Nonlinear relationship of red blood cell indices (MCH, MCHC, and MCV) with all-cause and cardiovascular mortality: A cohort study in U.S. adults.

Background: In recent years, increasing attention has been focused on the impact of red blood cell indices (RCIs) on disease prognosis. We aimed to investigate the association of mean corpuscular hemoglobin (MCH), mean corpuscular hemoglobin concentration (MCHC), and mean corpuscular volume (MCV) with mortality.

Methods: The study used cohort data from U.

Attention mechanism-enhanced graph convolutional neural network for unbalanced lithology identification.

In this study, we propose a novel method for identifying lithology using an attention mechanism-enhanced graph convolutional neural network (AGCN). The aim of this method is to address the limitations of traditional approaches that evaluate unbalanced lithology by improving the identification of thin layers and small samples, while providing reliable data support for reservoir evaluation. To achieve this goal, we begin by using Principal Component Analysis (PCA) with maximum and minimum distance clustering (Max-min-distance) to correct the logging curves, which compensates for the low resolution of thin layers and enhances the accuracy of stratigraphic representation.

The mouse multi-organ proteome from infancy to adulthood.

The early-life organ development and maturation shape the fundamental blueprint for later-life phenotype. However, a multi-organ proteome atlas from infancy to adulthood is currently not available. Herein, we present a comprehensive proteomic analysis of ten mouse organs (brain, heart, lung, liver, kidney, spleen, stomach, intestine, muscle and skin) at three crucial developmental stages (1-, 4- and 8-weeks after birth) acquired using data-independent acquisition mass spectrometry.

Puerarin alleviates acrolein-induced atherosclerosis by activating the MYH9-mediated SIRT1/Nrf2 cascade to inhibit the activation of inflammasome.

Puerarin (Pue) has significant antioxidant and anti-inflammatory properties. This work was designed to clarify and investigate the potential mechanisms of Pue in atherosclerosis (AS) progression. In vivo, acrolein (Acr) was inhaled through drinking water to construct AS model.

Uncovering the key pharmacodynamic material basis and possible molecular mechanism of Xiaoke formulation improve insulin resistant through a comprehensive investigation.

Ethnopharmacological Relevance: Xiaoke formulation (XKF) has been utilized in clinical practice for decades in China as a treatment option for mild to moderate type 2 diabetes. However, there is still a need for systematic research to uncover the key pharmacodynamic material basis and mechanism of XKF.

Aim Of The Study: Aim of to investigate the distribution and metabolism of XKF in normal and insulin resistant (IR) mice were different, and elucidate its key pharmacodynamic material basis and mechanism of action.

Baicalin circumvents anti-PD-1 resistance by regulating the gut microbiota metabolite short-chain fatty acids.

Baicalin is a small molecule medication used to treat hepatitis. Our research group discovered that administering baicalin orally to mice following fecal microbiota transplantation from patients resistant to ICIs supported anti-PD-1 activity. However, the precise mechanisms behind this effect are presently unknown.

β-Elemene in zedoary turmeric oil injection induces dyspnea by binding to hemoglobin and upregulating HIF-1α.

Ethnopharmacological Relevance: Zedoary turmeric oil injection (ZTOI) extracted from the rhizome extract of Curcuma phaeocaulis Valeton, Curcuma wenyujin Y. H. Chen et C.

SETD2 deficiency accelerates sphingomyelin accumulation and promotes the development of renal cancer.

Patients with polycystic kidney disease (PKD) encounter a high risk of clear cell renal cell carcinoma (ccRCC), a malignant tumor with dysregulated lipid metabolism. SET domain-containing 2 (SETD2) has been identified as an important tumor suppressor and an immunosuppressor in ccRCC. However, the role of SETD2 in ccRCC generation in PKD remains largely unexplored.

USP47 inhibits m6A-dependent c-Myc translation to maintain regulatory T cell metabolic and functional homeostasis.

The functional integrity of Tregs is interwoven with cellular metabolism; however, the mechanisms governing Treg metabolic programs remain elusive. Here, we identified that the deubiquitinase USP47 inhibited c-Myc translation mediated by the RNA N6-methyladenosine (m6A) reader YTHDF1 to maintain Treg metabolic and functional homeostasis. USP47 positively correlated with the tumor-infiltrating Treg signature in samples from patients with colorectal cancer and gastric cancer.

Platinum-Chimeric Carrier Cells for Ultratrace Cell Analysis in Mass Cytometry.

Mass cytometry by time-of-flight (CyTOF), a high-dimensional single-cell analysis platform, detects up to 50 biomarkers at single-cell resolution. However, CyTOF analysis of biological samples with a minimal number of available cells or rare cell subsets remains a major technical challenge due to the extensive loss of cells during cell recovery, staining, and acquisition. Here, we introduce a platinum-chimeric carrier cell strategy for mass cytometry profiling of ultratrace cell samples.

Superparamagnetic Composite Nanobeads Anchored with Molecular Glues for Ultrasensitive Label-free Proteomics.

Mass spectrometry has emerged as a mainstream technique for label-free proteomics. However, proteomic coverage for trace samples is constrained by adsorption loss during repeated elution at sample pretreatment. Here, we demonstrated superparamagnetic composite nanoparticles functionalized with molecular glues (MGs) to enrich proteins in trace human biofluid.

Lactoferrin attenuates cardiac fibrosis and cardiac remodeling after myocardial infarction via inhibiting mTORC1/S6K signaling pathway.

Myocardial infarction (MI) causes a severe injury response that eventually leads to adverse cardiac remodeling and heart failure. Lactoferrin (Ltf), as a secreted protein, bears multi-pharmacological properties. Present study aims to establish the cardioprotective function and corresponding mechanism of Ltf in MI process.

[Rationality evaluation of Shuanghuanglian Injection combined with Ampicillin Sodium for Injection based on sequential analysis].

The lack of rationality evaluation method for drug combination has long restricted its clinical application. In view of this, this study took Shuanghuanglian Injection as model drug and established a "physical-chemical-biological" sequential analysis method, which is expected to provide clues for improving the safety and effectiveness of clinical drug combination. With the methods of insoluble particle testing, isothermal titration calorimetry(ITC), and real time cellular analysis(RTCA), the rationality of Shuanghuanglian Injection combined with Ampicillin Sodium for Injection was assessed.

Polystyrene microplastic exposure induces insulin resistance in mice via dysbacteriosis and pro-inflammation.

Microplastics (MPs) as emerging contaminants have become a global environmental problem. However, studies on the effects of MPs on metabolic diseases remain limited. Here, we evaluated the effects of polystyrene (PS), one of the most prominent types of MPs, on insulin sensitivity in mice fed with normal chow diet (NCD) or high-fat diet (HFD), and explained the underlying mechanisms.

Sickle-like Inertial Microfluidic System for Online Rare Cell Separation and Tandem Label-Free Quantitative Proteomics (Orcs-Proteomics).

Label-free proteomics with trace clinical samples provides a wealth of actionable insights for personalized medicine. Clinically acquired primary cells, such as circulating tumor cells (CTCs), are usually with low abundance that is prohibitive for conventional label-free proteomics analysis. Here, we present a sickle-like inertial microfluidic system for online rare cell separation and tandem label-free proteomics (namely, Orcs-proteomics).

Poly (N-vinylpyrrolidone) modification mitigates plasma protein corona formation on phosphomolybdate-based nanoparticles.

Phosphomolybdate-based nanoparticles (PMo-based NPs) have been commonly applied in nanomedicine. However, upon contact with biofluids, proteins are quickly adsorbed onto the NPs surface to form a protein corona, which induces the opsonization and facilitates the rapid clearance of the NPs by macrophage uptake. Herein, we introduce a family of structurally homologous PMo-based NPs (CDS-PMo@PVP(x = 0 ~ 1) NPs) capping diverse content of zwitterionic polymer poly (N-vinylpyrrolidone) (PVP) to regulate the protein corona formation on PMo-based NPs.

ZFP91 disturbs metabolic fitness and antitumor activity of tumor-infiltrating T cells.

Proper metabolic activities facilitate T cell expansion and antitumor function; however, the mechanisms underlying disruption of the T cell metabolic program and function in the tumor microenvironment (TME) remain elusive. Here, we show a zinc finger protein 91-governed (ZFP91-governed) mechanism that disrupts the metabolic pathway and antitumor activity of tumor-infiltrating T cells. Single-cell RNA-Seq revealed that impairments in T cell proliferation and activation correlated with ZFP91 in tissue samples from patients with colorectal cancer.

Lipophagy: A New Perspective of Natural Products in Type 2 Diabetes Mellitus Treatment.

Autophagy has been reported to involve in the pathogenesis of type 2 diabetes mellitus (T2DM), which protects the insulin target tissues and pancreatic β-cells. However, autophagy is inhibited when the cells are lipid overload. That, in turn, increases the accumulation of fat.

[Exploration on rationality evaluation approach of drug combination medication based on sequential analysis and machine learning].

Drug combination is a common clinical phenomenon. However, the scientific implementation of drug combination is li-mited by the weak rational evaluation that reflects its clinical characteristics. In order to break through the limitations of existing evaluation tools, examining drug-to-drug and drug-to-target action characteristics is proposed from the physical, chemical and biological perspectives, combining clinical multicenter case resources, domestic and international drug interaction public facilities with the aim of discovering the common rules of drug combination.

ZFP91 is required for the maintenance of regulatory T cell homeostasis and function.

Autophagy programs the metabolic and functional fitness of regulatory T (T reg) cells to establish immune tolerance, yet the mechanisms governing autophagy initiation in T reg cells remain unclear. Here, we show that the E3 ubiquitin ligase ZFP91 facilitates autophagy activation to sustain T reg cell metabolic programming and functional integrity. T reg cell-specific deletion of Zfp91 caused T reg cell dysfunction and exacerbated colonic inflammation and inflammation-driven colon carcinogenesis.

Methylation-Induced Silencing of ALDH2 Facilitates Lung Adenocarcinoma Bone Metastasis by Activating the MAPK Pathway.

Bone metastasis (BM) dramatically reduces the quality of life and life expectancy in lung adenocarcinoma (LUAD) patients. There is an urgent need to identify potential biomarkers for application in the treatment of this deadly disease. We compared patient BM, LUAD, and para-LUAD tissues using proteomic analysis and identified aldehyde dehydrogenase 2 (ALDH2), which can detoxify acetaldehyde to acetic acid, as one of the key regulators in lung tumor metastasis.

Mouse Double Minute 2 Homolog-Mediated Ubiquitination Facilitates Forkhead Box P3 Stability and Positively Modulates Human Regulatory T Cell Function.

Regulatory T cells (Treg cells) are essential for maintaining immune tolerance, and the dysfunction of Treg cells may cause autoimmune diseases and tumors. Forkhead box P3 (FOXP3) is the key transcription factor controlling Treg cell development and suppressive function. Mouse double minute 2 homolog (MDM2), an E3 ubiquitin ligase, has been identified as an oncoprotein that mediates the ubiquitination and degradation of tumor suppressor p53; however, whether it has functions in Treg cells remains unknown.

MgAl monolayer hydrotalcite increases the hypoglycemic effect of berberine by enhancing its oral bioavailability.

Berberine (BBR) is a potential novel agent to treat diabetes, but its oral bioavailability is restricted by the poor solubility, which greatly limits its clinical application. Here, a new drug delivery system of BBR-MgAl monolayer hydrotalcite (BBR/MLDH) was prepared to increase the solubility and bioavailability of BBR. The results showed that BBR/MLDH presented as a uniform hexagonal plate-like particle with a loading capacity of 28.