Lysosomes finely control macrophage inflammatory function via regulating the release of lysosomal Fe through TRPML1 channel.

Lysosomes are best known for their roles in inflammatory responses by engaging in autophagy to remove inflammasomes. Here, we describe an unrecognized role for the lysosome, showing that it finely controls macrophage inflammatory function by manipulating the lysosomal Fe-prolyl hydroxylase domain enzymes (PHDs)-NF-κB-interleukin 1 beta (IL1B) transcription pathway that directly links lysosomes with inflammatory responses. TRPML1, a lysosomal cationic channel, is activated secondarily to ROS elevation upon inflammatory stimuli, which in turn suppresses IL1B transcription, thus limiting the excessive production of IL-1β in macrophages.

Fecal microbiota transplantation: transitioning from chaos and controversial realm to scientific precision era.

With the popularization of modern lifestyles, the spectrum of intestinal diseases has become increasingly diverse, presenting significant challenges in its management. Traditional pharmaceutical interventions have struggled to keep pace with these changes, leaving many patients refractory to conventional pharmaceutical treatments. Fecal microbiota transplantation (FMT) has emerged as a promising therapeutic approach for enterogenic diseases.

Prognosticating WHO/ISUP grade in clear cell renal cell carcinoma: Insights from amide proton transfer-weighted MRI.

Background: Preoperative prediction of clear cell renal cell carcinoma (ccRCC) grade can support optimal selection of surgical resection strategies. Currently, there is no effective preoperative method for accurately assessing the histologic grade of ccRCC. More precise, non-invasive prediction methods are needed.

Comparative proteomic landscapes elucidate human preimplantation development and failure.

Understanding mammalian preimplantation development, particularly in humans, at the proteomic level remains limited. Here, we applied our comprehensive solution of ultrasensitive proteomic technology to measure the proteomic profiles of oocytes and early embryos and identified nearly 8,000 proteins in humans and over 6,300 proteins in mice. We observed distinct proteomic dynamics before and around zygotic genome activation (ZGA) between the two species.

Global, regional and national burden of neuroblastoma and other peripheral nervous system tumors, 1990 to 2021 and predictions to 2035: visualizing epidemiological characteristics based on GBD 2021.

Background: Neuroblastoma (NB) is the most common extracranial malignant solid tumor in children, accounting for >15 % of cancer-related deaths in children. We analyzed the epidemiological statistical indicators of neuroblastoma and other peripheral nervous system tumors patients from 1990 to 2021 in Global Burden of Disease (GBD) 2021 database, aiming to provide valuable insights for public health interventions and clinical practices.

Methods: Based on the GBD 2021 database, this study analyzed the incidence, mortality, prevalence, and Disability-Adjusted Life-Years (DALYs) of neuroblastoma and other peripheral nervous system tumors from 1990 to 2021, stratified by sociodemographic development index (SDI) and geographic regions.

Derivation of induced pluripotent stem cell FDZSi002-A from a 67-year-old Chinese Han Prostate cancer patient.

Prostate cancer (PCa) is the most common malignant tumor of the male reproductive system. In this study, we generated an induced pluripotent stem cell (iPSC) line from the peripheral blood mononuclear cells (PBMCs) of a 67-year-old male patient and diagnosed with PC. The established iPSCs were confirmed by flow cytometry and immunofluorescence.

Chitosan and ibuprofen grafted electrospun polylactic acid/gelatin membrane mitigates inflammatory response.

Electrospun membranes with biomimetic fibrous structures and high specific surfaces benefit cell proliferation and tissue regeneration but are prone to cause chronic inflammation and foreign body response (FBR). To solve these problems, we herein report an approach to functionalize electrospun membranes with antibacterial and anti-inflammatory components to modulate inflammatory responses and improve implantation outcomes. Specifically, electrospun polylactic acid (PLA)/gelatin (Gel) fibers were grafted with chitosan (CS) and ibuprofen (IBU) via carbodiimide chemistry.

One hundred thirty-four germ line PU.1 variants and the agammaglobulinemic patients carrying them.

Leukopoiesis is lethally arrested in mice lacking the master transcriptional regulator PU.1. Depending on the animal model, subtotal PU.

Diverse autoinhibitory mechanisms of FIIND-containing proteins: Insight into regulation of NLRP1 and CARD8 inflammasome.

Function-to-find domain (FIIND)-containing proteins, including NLRP1 and CARD8, are vital components of the inflammasome signaling pathway, critical for the innate immune response. These proteins exist in various forms due to autoproteolysis within the FIIND domain, resulting in full-length (FL), cleaved N-terminal (NT), and cleaved C-terminal (CT) peptides, which form autoinhibitory complexes in the steady state. However, the detailed mechanism remains elusive.

Mutant KRAS and CK2 Cooperatively Stimulate SLC16A3 Activity to Drive Intrahepatic Cholangiocarcinoma Progression.

Intrahepatic cholangiocarcinoma (iCCA) is a lethal malignancy affecting the liver and biliary system. Enhanced understanding of the pathogenic mechanisms underlying iCCA tumorigenesis and the discovery of appropriate therapeutic targets are imperative to improve patient outcomes. Here, we investigated the functions and regulations of solute carrier family 16 member 3 (SLC16A3), which has been reported to be a biomarker of poor prognosis in iCCA.

Deep-Learning Generated Synthetic Material Decomposition Images Based on Single-Energy CT to Differentiate Intracranial Hemorrhage and Contrast Staining Within 24 Hours After Endovascular Thrombectomy.

Aims: To develop a transformer-based generative adversarial network (trans-GAN) that can generate synthetic material decomposition images from single-energy CT (SECT) for real-time detection of intracranial hemorrhage (ICH) after endovascular thrombectomy.

Materials: We retrospectively collected data from two hospitals, consisting of 237 dual-energy CT (DECT) scans, including matched iodine overlay maps, virtual noncontrast, and simulated SECT images. These scans were randomly divided into a training set (n = 190) and an internal validation set (n = 47) in a 4:1 ratio based on the proportion of ICH.

Rationale and Design of the InsightPFA Trial: A Prospective, Multicenter, Randomized Controlled Trial of the Irreversible Electroporation-Based Pulsed Field Ablation Versus Radiofrequency Ablation in Chinese Patients With Symptomatic Paroxysmal Atrial Fibrillation.

Background: Pulsed field ablation (PFA) is gaining recognition as a nonthermal, tissue-specific technique for the treatment of atrial fibrillation (AF). The preclinical evaluation of the investigated novel PFA system from Insight Medtech Co. Ltd has demonstrated feasibility, safety, and 30-day efficacy for pulmonary vein isolation (PVI) in the swine model.

Chain of Risks Evaluation (CORE): A framework for safer large language models in public mental health.

Large language models (LLMs) have gained significant attention for their capabilities in natural language understanding and generation. However, their widespread adoption potentially raises public mental health concerns, including issues related to inequity, stigma, dependence, medical risks, and security threats. This review aims to offer a perspective within the actor-network framework, exploring the technical architectures, linguistic dynamics, and psychological effects underlying human-LLMs interactions.

Targeting p21-Positive Senescent Chondrocytes via IL-6R/JAK2 Inhibition to Alleviate Osteoarthritis.

Osteoarthritis (OA) is an age-related degenerative joint disease, prominently influenced by the pro-inflammatory cytokine interleukin-6 (IL-6). Although elevated IL-6 levels in joint fluid are well-documented, the uneven cartilage degeneration observed in knee OA patients suggests additional underlying mechanisms. This study investigates the role of interleukin-6 receptor (IL-6R) in mediating IL-6 signaling and its contribution to OA progression.

Upregulation of CD19 by low-dose chidamide promotes CAR T cells functionality in B-cell non-Hodgkin lymphoma.

B-cell non-Hodgkin lymphoma (B-NHL) is a highly heterogeneous group of lymphopoietic malignancies that account for 85% to 90% of all non-Hodgkin lymphomas. In recent years, CD19 Chimeric antigen receptor T (CAR T) cell immunotherapy has significantly improved the cure rate of B-NHL patients, but there are still some patients who cannot achieve remission after treatment, or relapse after remission. Therefore, it is of great importance to overcome the drug resistance of CD19 CAR T cells after B-NHL treatment and reduce the recurrence rate of CD19 CAR T cells after B-NHL treatment.

Fertility-sparing treatment outcomes using immune checkpoint inhibitors in endometrial cancer patients with Lynch syndrome.

Objective: To evaluate the efficacy of immune checkpoint inhibitors (ICIs) for fertility-sparing treatment in Lynch syndrome-associated endometrial cancer (LS-EC).

Methods: Four LS-EC cases received programmed cell death protein 1 (PD-1) inhibitors for fertility preservation at the Obstetrics and Gynecology Hospital of Fudan University from 2017 to 2023. The clinical data and long-term outcomes were retrospectively reviewed.

and activity of 1,2,3,4,6-O-pentagalloyl-glucose against .

Invasive fungal infections have become an increasingly serious threat to global human health, underscoring the urgent need for the development of new antifungal drugs. In this study, we found a natural polyphenolic compound 1,2,3,4,6-O-pentagalloyl-glucose (PGG), which is present in various plants and herbs. PGG showed broad-spectrum antifungal activities, enhancing the efficacy of fluconazole.

Osteopenia Metabolomic Biomarkers for Early Warning of Osteoporosis.

: This study aimed to capture the early metabolic changes before osteoporosis occurs and identify metabolomic biomarkers at the osteopenia stage for the early prevention of osteoporosis. : Metabolomic data were generated from normal, osteopenia, and osteoporosis groups with 320 participants recruited from the Nicheng community in Shanghai. We conducted individual edge network analysis (iENA) combined with a random forest to detect metabolomic biomarkers for the early warning of osteoporosis.

High FGF18 expression levels predict poor prognosis in endometrial carcinoma patients and promote tumor growth and metastasis.

Objective: To investigate if fibroblast growth factor 18 (FGF18) expression plays an important role in endometrial carcinoma (EC).

Methods: The clinicopathological associations and prognostic value of FGF18 expression were retrospectively analyzed in 190 patients with EC. FGF18 expression was stably knocked down in EC cell lines.

Development and Validation of a Predictive Model Based on Serum Silent Information Regulator 6 Levels in Chinese Older Adult Patients: Cross-Sectional Descriptive Study.

Background: Serum levels of silent information regulator 6 (SIRT6), a key biomarker of aging, were identified as a predictor of coronary artery disease (CAD), but whether SIRT6 can distinguish severity of coronary artery lesions in older adult patients is unknown.

Objectives: This study developed a nomogram to demonstrate the functionality of SIRT6 in assessing severity of coronary artery atherosclerosis.

Methods: Patients aged 60 years and older with angina pectoris were screened for this single-center clinical study between October 1, 2022, and March 31, 2023.

Extracellular matrix shapes cancer stem cell behavior in breast cancer: a mini review.

Today, cancer has become one of the leading global tragedies. It occurs when a small number of cells in the body mutate, causing some of them to evade the body's immune system and proliferate uncontrollably. Even more irritating is the fact that patients with cancers frequently relapse after conventional chemotherapy and radiotherapy, leading to additional suffering.

Transcription factor specificity protein (SP) family in renal physiology and diseases.

Dysregulated specificity proteins (SPs), members of the C2H2 zinc-finger family, are crucial transcription factors (TFs) with implications for renal physiology and diseases. This comprehensive review focuses on the role of SP family members, particularly SP1 and SP3, in renal physiology and pathology. A detailed analysis of their expression and cellular localization in the healthy human kidney is presented, highlighting their involvement in fatty acid metabolism, electrolyte regulation, and the synthesis of important molecules.