Tacrolimus regulates extracellular vesicle secretion from T cells via autophagy-lysosomal pathway.

Extracellular vesicles (EVs) derived from T cells have been proposed to mediate intercellular communication and orchestrate immune responses. The immunosuppressive drug, tacrolimus (TAC), suppresses T cell activity; however, the impact of TAC on T cell-derived EVs remains primarily unexplored. In this study, human primary T cells purified from healthy donors were used to investigate TAC-mediated regulation of EV secretion by T cells.

Investigation of pH-dependent H NMR urine metabolite profiles for diagnosis of obesity-related disordering.

Background: Human urine is highly favorable for H NMR metabolomics analyses of obesity-related diseases, such as non-alcoholic fatty liver, type 2 diabetes, and hyperlipidemia (HL), due to its non-invasiveness and ease of large-scale collection. However, the wide range of intrinsic urine pH (5.5-8.

Digital boundaries: A study on WeChat parent-child relationships among Chinese college students and their association with family factors.

Objective: This study aims to investigate the current state of WeChat parent-child relationships among college students and their association with family factors.

Methods: Using convenient sampling, 6159 students,age from 18 to 25,the participants were selected from colleges of Chengdu to complete a questionnaire survey on response and attitudes towards parents' WeChat friend requests, Family APGAR Index,Parental Management Scale,Family Conflict Scale,were used as measurement tools.

Results: Responses to parental WeChat friend requests showed significant positive correlations with higher levels of family function satisfaction (r = 0.

SEMA7A-mediated juxtacrine stimulation of IGFBP-3 upregulates IL-17RB at pancreatic cancer invasive front.

Tumor invasion is the hallmark of tumor malignancy. The invasive infiltration pattern of tumor cells located at the leading edge is highly correlated with metastasis and unfavorable patient outcomes. However, the regulatory mechanisms governing tumor malignancy at the invasive margin remain unclear.

Carbene and photocatalyst-catalyzed 3-acylation of indoles for facile access to indole-3-yl aryl ketones.

3-Acyl indoles play important roles in both organic synthesis and diverse types of functional molecules. Herein, a facile nitrogen heterocyclic carbene (NHC) and photocatalyst cooperatively-catalyzed 3-acylation of indoles was disclosed. The reaction proceeded radical cross-coupling of indole-based aryl radical cations with NHC-bound ketyl radical species, which are less explored in radical NHC catalysis.

Exosomal miRNA 16-5p/29a-3p from pancreatic cancer induce adipose atrophy by inhibiting adipogenesis and promoting lipolysis.

Over 80% of the patients with pancreatic ductal adenocarcinoma (PDAC) have cachexia/wasting syndrome. Cachexia is associated with reduced survival, decreased quality of life, and higher metastasis rates. Here, we demonstrate that fat loss is the earliest feature of PDAC-exosome-induced cachexia.

Glutathione determines chronic myeloid leukemia vulnerability to an inhibitor of CMPK and TMPK.

Bcr-Abl transformation leads to chronic myeloid leukemia (CML). The acquirement of T315I mutation causes tyrosine kinase inhibitors (TKI) resistance. This study develops a compound, JMF4073, inhibiting thymidylate (TMP) and cytidylate (CMP) kinases, aiming for a new therapy against TKI-resistant CML.

Comprehending the inhibition mechanism of indole-based bis-acylhydrazone compounds on α-glucosidase: Spectral and theoretical approaches.

Indole-based bis-acylhydrazone compounds can inhibit the activity of α-glucosidase and control the concentration of blood glucose. In this paper, the characteristics of three indole-based bis-acylhydrazone compounds with different inhibitory activities of α-glucosidase as well as the interaction with α-glucosidase were studied by experiments and computational simulation techniques. Enzyme kinetic and spectral experiments showed that the indole-based bis-acylhydrazone compounds were able to inhibit enzyme activity through mixed inhibition dominated by competitive inhibition, and during the binding reaction, indole-based bis-acylhydrazone compounds can quench the intrinsic fluorescence of α-glucosidase through static quenching and an aggregation of the indole-based bis-acylhydrazone with α-glucosidase produces a stable complex with a molar ratio of 1:1, and the combination of indole-based bis-acylhydrazone compounds could lead to slight change in the conformation of α-glucosidase.

Engineered endolysin of phage is a potent and broad-spectrum bactericidal agent against "ESKAPEE" pathogens.

The rise of antimicrobial resistance in ESKAPEE pathogens poses significant clinical challenges, especially in polymicrobial infections. Bacteriophage-derived endolysins offer promise in combating this crisis, but face practical hurdles. Our study focuses on engineering endolysins from a phage, fusing them with ApoE23 and COG133 peptides.

The potential association between metabolic disorders and pulmonary tuberculosis: a Mendelian randomization study.

Background: Metabolic disorders (MetDs) have been demonstrated to be closely linked to numerous diseases. However, the precise association between MetDs and pulmonary tuberculosis (PTB) remains poorly understood.

Method: Summary statistics for exposure and outcomes from genome-wide association studies (GWASs) for exposures and outcomes were obtained from the BioBank Japan Project (BBJ) Gene-exposure dataset.

ApoE Mimetic Peptide COG1410 Kills via Directly Interfering ClpC's ATPase Activity.

Antimicrobial peptides (AMPs) hold promise as alternatives to combat bacterial infections, addressing the urgent global threat of antibiotic resistance. COG1410, a synthetic peptide derived from apolipoprotein E, has exhibited potent antimicrobial properties against various bacterial strains, including . However, our study reveals a previously unknown resistance mechanism developed by against COG1410 involving ClpC.

Unraveling the impact of cancer-associated fibroblasts on hypovascular pancreatic neuroendocrine tumors.

Background: Pancreatic neuroendocrine tumors (PNETs) with low microvessel density and fibrosis often exhibit clinical aggressiveness. Given the contribution of cancer-associated fibroblasts (CAFs) to the hypovascular fibrotic stroma in pancreatic ductal adenocarcinoma, investigating whether CAFs play a similar role in PNETs becomes imperative. In this study, we investigated the involvement of CAFs in PNETs and their effects on clinical outcomes.

Oncogenic KRAS, Mucin 4, and Activin A-Mediated Fibroblast Activation Cooperate for PanIN Initiation.

Over 90% of patients with pancreatic ductal adenocarcinoma (PDAC) have oncogenic KRAS mutations. Nevertheless, mutated KRAS alone is insufficient to initiate pancreatic intraepithelial neoplasia (PanIN), the precursor of PDAC. The identities of the other factors/events required to drive PanIN formation remain elusive.

Nutritional status in patients with active pulmonary tuberculosis and new nutritional risk screening model for active tuberculosis: a national, multicenter, cross-sectional study in China.

Background: Tuberculosis (TB) remains a significant challenge for public health and is closely associated with malnutrition; however, few studies have attempted to screen malnutrition among TB patients. The study aimed to evaluate the nutrition status and build a new nutritional screening model for active TB.

Methods: A retrospective, multicenter, large cross-sectional study was conducted in China from 1 January 2020 to 31 December 2021.

Bicyclic Amidine-Triggered Cyclization of -Alkynylisocyanobenzenes: Synthesis of Lactam-Derived Quinolines.

Efficient access to the synthesis of lactam-derived quinoline through a bicyclic amidine-triggered cyclization reaction from readily prepared -alkynylisocyanobenzenes has been developed. The reaction was initiated by nucleophilic attack of the bicyclic amidines to -alkynylisocyanobenzenes, subsequently with intramolecular cyclization to produce a DBU-quinoline-based amidinium salt, followed by hydrolysis to afford the lactam-derived quinoline in moderate to good yields.

Photosensitive small extracellular vesicles regulate the immune microenvironment of triple negative breast cancer.

Currently, the treatment of triple-negative breast cancer (TNBC) is limited by the special pathological characteristics of this disease. In recent years, photodynamic therapy (PDT) has created new hope for the treatment of TNBC. Moreover, PDT can induce immunogenic cell death (ICD) and improve tumor immunogenicity.

Resolution of an insidious and migratory Mycobacterium tuberculosis-associated secondary organizing pneumonia: a case report and literature review.

Background: Organizing pneumonia (OP) is a rare interstitial lung disease. Secondary organizing pneumonia (SOP) caused by Mycobacterium tuberculosis (MTB) is extremely rare. Migratory MTB-associated SOP is more deceptive and dangerous.

Pancreatic cancer-derived small extracellular vesical ezrin activates fibroblasts to exacerbate cancer metastasis through STAT3 and YAP-1 signaling pathways.

Cancer-associated fibroblasts (CAFs), a major component of the tumor microenvironment (TME) in pancreatic ductal adenocarcinoma (PDAC), play an important role in tumorigenesis, metastasis, and chemoresistance. Tumor-derived small extracellular vesicles (sEVs), which mediate cell-to-cell communication between cancer cells and fibroblasts, are also critical for cancer progression and metastasis. However, it remains unclear how PDAC cell-derived sEVs activate fibroblasts, which contributes to tumor progression.

ApoE Mimetic Peptide COG1410 Exhibits Strong Additive Interaction with Antibiotics Against .

Background: Drug-resistant tuberculosis (TB) is an emerging threat to public health worldwide. Antimicrobial peptide (AMP) is a promising solution to solve the antimicrobial resistance crisis. The apolipoprotein E mimetic peptide COG1410 has been confirmed to simultaneously have neuroprotective, anti-inflammatory, and antibacterial activity.

Podocalyxin-Like Protein 1 Regulates Pluripotency through the Cholesterol Biosynthesis Pathway.

Deciphering signaling mechanisms critical for the extended pluripotent stem cell (EPSC) state and primed pluripotency is necessary for understanding embryonic development. Here, a membrane protein, podocalyxin-like protein 1 (PODXL) as being essential for extended and primed pluripotency, is identified. Alteration of PODXL expression levels affects self-renewal, protein expression of c-MYC and telomerase, and induced pluripotent stem cell (iPSC) and EPSC colony formation.

Structural basis of interleukin-17B receptor in complex with a neutralizing antibody for guiding humanization and affinity maturation.

Upregulation of interleukin-17 receptor B (IL-17RB) is known to be oncogenic, while other IL-17 receptors and ligands are generally involved in pro-inflammatory pathways. We identify a mouse neutralizing monoclonal antibody (mAb) D9, which blocks the IL-17RB/IL-17B pathway and inhibits pancreatic tumorigenesis in an orthotopic mouse model. The X-ray crystal structure of the IL-17RB ectodomain in complex with its neutralizing antibody D9 shows that D9 binds to a predicted ligand binding interface and engages with the A'-A loop of IL-17RB fibronectin III domain 1 in a unique conformational state.

Multiomic characterization and drug testing establish circulating tumor cells as an tool for personalized medicine.

Matching the treatment to an individual patient's tumor state can increase therapeutic efficacy and reduce tumor recurrence. Circulating tumor cells (CTCs) derived from solid tumors are promising subjects for theragnostic analysis. To analyze how CTCs represent tumor states, we established cell lines from CTCs, primary and metastatic tumors from a mouse model and provided phenotypic and multiomic analyses of these cells.

Interplays of glucose metabolism and KRAS mutation in pancreatic ductal adenocarcinoma.

Pancreatic ductal adenocarcinoma (PDAC) is one of the most aggressive and deadliest cancer worldwide. The primary reasons for this are the lack of early detection methods and targeted therapy. Emerging evidence highlights the metabolic addiction of cancer cells as a potential target to combat PDAC.