Unraveling the genetic and pathophysiological mechanisms underlying disorders of sex development.

Disorders of sex development (DSDs) encompass a spectrum of congenital conditions characterized by discordance among chromosomal, gonadal, and anatomical sex. Advances in genetic and molecular technologies have elucidated a complex landscape of underlying etiologies, including mutations in genes regulating sex determination and differentiation, copy number variations, and epigenetic alterations. These discoveries have not only enhanced diagnostic accuracy but also deepened our understanding of the molecular mechanisms driving DSDs.

Simultaneous Modulation of Mesoporosity and Al Siting for Superior Performance Zeolite Catalyst in Ethylene Dehydroaromatization to Aromatics.

Porosity and Al siting are key levers for optimizing zeolite catalysts, yet they are often addressed independently due to the lack of effective integrated tuning strategies. Herein, we report an integrative methodology for preparing hierarchical zeolite (Z) with interconnected mesostructures and tunable Al siting, achieved via regioselective dissolution of Al-rich domains by presetting accessible and inaccessible zones within parent zeolite (Z). Remarkably, ∼60% of the framework channels' Al atoms were selectively removed without impairing the channel intersections' Al atoms.

Facile Synthesis of Zeolite Beta with Hierarchical Micromesoporosity Promoted by Citric Acid: Strategy and Working Mechanism.

The introduction of mesoporosity is of great importance because mass-transportation limitations within microporous systems hinder their catalytic performance. The direct formation of mesoporosity in zeolite is generally achieved through the use of an additional and expensive organic template, which limits its industrial applications. In this investigation, we reported a facile procedure for synthesizing zeolite Beta with micromesoporosity, in which tetraethylammonium hydroxide (TEAOH)/crystal seeds (CS) worked as the micropore-directing agents, assisted by simple citric acid (CA) containing hydroxyl carboxylic groups.

Polyphosphate coacervate gels for manufacturing of manganese loaded glass powders and fibres: structural, cytocompatibility and surface bioactivity study.

Phosphate-based glasses (PGs) are promising bioresorbable materials for controlled delivery of therapeutic species and tissue regeneration. The traditional method of synthesis of PGs involves the use of high temperatures, which limits their biomedical applications. The main goal of this work was to manufacture Mn loaded PGs for bone regeneration using an alternative, versatile and sustainable manufacturing technique.

The RNA demethylase FTO promotes glutamine metabolism in clear cell renal cell carcinoma through the regulation of SLC1A5.

Glutamine reprogramming plays a crucial role in the growth and survival of clear cell renal cell carcinoma (ccRCC), although the mechanisms governing its regulation are still not fully understood. We demonstrate that the RNA demethylase fat mass and obesity-associated gene (FTO) drives glutamine reprogramming to support ccRCC growth and survival. Genetic and pharmacologic inhibition of FTO in ccRCC cells impaired glutamine-derived reductive carboxylation, depleted pyrimidines, and increased reactive oxygen species.

Hydrogeochemical analysis and tracing of heavy metal contamination in groundwater using self-organizing mapping.

In recent years, heavy metal pollution in mines has garnered significant attention. However, systematic research on the hydrogeochemical characteristics and heavy metal migration patterns in groundwater at abandoned mine sites remains limited. Therefore we analyzed the hydrogeochemical characteristics and heavy metal migration patterns of groundwater at an abandoned iron ore mine in Jiangxi Province, China.

Identification of Molecular Subtypes of Clear-Cell Renal Cell Carcinoma in Patient-Derived Xenografts Using Multi-Omics.

: Clear-cell renal cell carcinoma (ccRCC) is a heterogenous disease that can be classified into multiple molecular subtypes with differential prognosis and sensitivities to treatments based on their genomic, transcriptomic, proteomic, and metabolic profiles. Patient-derived xenografts (PDXs) are high-fidelity cancer models because they maintain similar genotypes and immunohistologic phenotypes to the parental tumors and respond to standard-of-care therapies as expected. However, whether the molecular subtypes identified in ccRCC patient samples are preserved in PDX models is not clear.

The olfactory receptor OR51E2 regulates prostate cancer aggressiveness and modulates STAT3 in prostate cancer cells and in xenograft tumors.

Background: Despite advancements in the detection and treatment of prostate cancer, the molecular mechanisms underlying its progression remain unclear. This study aimed to investigate the role of the receptor OR51E2, which is commonly upregulated in prostate cancer, in the progression of this disease.

Methods: We investigated the physiological effects of OR51E2 through CRISPR-Cas9-induced monoclonal OR51E2 knockout.

A lipid starvation strategy-synergized neutrophil activation for postoperative melanoma immunotherapy.

Abnormal metabolism of melanoma cells on lipids reveals that breaking their lipid addiction provides a starvation strategy to enhance immunotherapy effects and reduce resistance. Herein, we propose an extracellular matrix-inspired scaffold fabricated by multiple cross-linking of collagen and elastin encapsulated with fatty acid transporter proteins (FATP) inhibitor lipofermata (Lipo) to close the "valve" of lipid transported into both melanoma cells and pro-tumor neutrophils. Meanwhile, model TGF-β inhibitor loaded in scaffold synergized with Lipo to polarize postoperative locally enriched neutrophils towards cytotoxic N1 phenotypes after blocking their energy supply and modulate postsurgical immunosuppressive tumor microenvironment.

Targeting AXL Inhibits the Growth and Metastasis of Prostate Cancer in Bone.

Purpose: After failing primary and secondary hormonal therapy, castration-resistant and neuroendocrine prostate cancer metastatic to the bone is invariably lethal, although treatment with docetaxel and carboplatin can modestly improve survival. Therefore, agents targeting biologically relevant pathways in prostate cancer and potentially synergizing with docetaxel and carboplatin in inhibiting bone metastasis growth are urgently needed.

Experimental Design: Phosphorylated (activated) AXL expression in human prostate cancer bone metastases was assessed by IHC staining.

Colon-specific controlled release of oral liposomes for enhanced chemo-immunotherapy against colorectal cancer.

A colon-specific drug delivery system has great potential for the oral administration of colorectal cancer. However, the uncontrollable fate of liposomes makes their effectiveness for colonic location, and intratumoral accumulation remains unsatisfactory. Here, an oral colon-specific drug delivery system (CBS-CS@Lipo/Oxp/MTZ) was constructed by covalently conjugating spores (CBS) with drugs loaded chitosan (CS)-coated liposomes, where the model chemotherapy drug oxaliplatin (Oxp) and anti-anaerobic bacteria agent metronidazole (MTZ) were loaded.

Sialylated glycoproteins suppress immune cell killing by binding to Siglec-7 and Siglec-9 in prostate cancer.

Prostate cancer is the second leading cause of male cancer death in the U.S. Current immune checkpoint inhibitor-based immunotherapies have improved survival for many malignancies; however, they have failed to prolong survival for prostate cancer.

Establishing and Characterizing the Molecular Profiles, Cellular Features, and Clinical Utility of a Patient-Derived Xenograft Model Using Benign Prostatic Tissues.

Benign prostatic hyperplasia (BPH) is a common condition marked by the enlargement of the prostate gland, which often leads to significant urinary symptoms and a decreased quality of life. The development of clinically relevant animal models is crucial for understanding the pathophysiology of BPH and improving treatment options. This study aims to establish a patient-derived xenograft (PDX) model using benign prostatic tissues to explore the molecular and cellular mechanisms of BPH.

A biomimetic spore nanoplatform for boosting chemodynamic therapy and bacteria-mediated antitumor immunity for synergistic cancer treatment.

Bacterial-based antitumor immunity has become a promising strategy to activate the immune system for fighting cancer. However, the potential application of bacterial therapy is hindered by the presence of instability and susceptibility to infections within bacterial populations. Furthermore, monotherapy is ineffective in completely eliminating complex cancer with multiple contributing factors.

AZGP1 deficiency promotes angiogenesis in prostate cancer.

Background: Loss of AZGP1 expression is a biomarker associated with progression to castration resistance, development of metastasis, and poor disease-specific survival in prostate cancer. However, high expression of AZGP1 cells in prostate cancer has been reported to increase proliferation and invasion. The exact role of AZGP1 in prostate cancer progression remains elusive.

Identification and characterization of intact glycopeptides in human urine.

Glycoproteins in urine have the potential to provide a rich class of informative molecules for studying human health and disease. Despite this promise, the urine glycoproteome has been largely uncharacterized. Here, we present the analysis of glycoproteins in human urine using LC-MS/MS-based intact glycopeptide analysis, providing both the identification of protein glycosites and characterization of the glycan composition at specific glycosites.

Construction and Application of Fluorescent Probes with Imine Protective Groups for Hypochlorite Detection.

Several fluorescent probes have been designed to detect ClO in biological systems based on the isomerization mechanism of C = N bonds. Particularly, fluorescein has emerged as an important fluorophore for detecting ClO because of its unique properties. Previously, we introduced the fluorescein analog F-1 with an active aldehyde group.

Dynamic regulation of drug biodistribution by turning tumors into decoys for biomimetic nanoplatform to enhance the chemotherapeutic efficacy of breast cancer with bone metastasis.

Breast cancer with bone metastasis accounts for serious cancer-associated pain which significantly reduces the quality of life of affected patients and promotes cancer progression. However, effective treatment using nanomedicine remains a formidable challenge owing to poor drug delivery efficiency to multiple cancer lesions and inappropriate management of cancer-associated pain. In this study, using engineered macrophage membrane (EMM) and drugs loaded nanoparticle, we constructed a biomimetic nanoplatform (EMM@DJHAD) for the concurrent therapy of bone metastatic breast cancer and associated pain.

Orchestrating antigen delivery and presentation efficiency in lymph node by nanoparticle shape for immune response.

Activating humoral and cellular immunity in lymph nodes (LNs) of nanoparticle-based vaccines is critical to controlling tumors. However, how the physical properties of nanovaccine carriers orchestrate antigen capture, lymphatic delivery, antigen presentation and immune response in LNs is largely unclear. Here, we manufactured gold nanoparticles (AuNPs) with the same size but different shapes (cages, rods, and stars), and loaded tumor antigen as nanovaccines to explore their disparate characters on above four areas.

Diagnosis, treatment, and research status of rare diseases related to birth defects.

Rare diseases are diseases that occur at low prevalence, and most of them are chronic and serious diseases that are often life-threatening. Currently, there is no unified definition for rare diseases. The diagnosis, treatment, and research of rare diseases have become the focus of medicine and biopharmacology, as well as the breakthrough point of clinical and basic research.

Distinguishing Renal Cell Carcinoma From Normal Kidney Tissue Using Mass Spectrometry Imaging Combined With Machine Learning.

Purpose: Accurately distinguishing renal cell carcinoma (RCC) from normal kidney tissue is critical for identifying positive surgical margins (PSMs) during partial and radical nephrectomy, which remains the primary intervention for localized RCC. Techniques that detect PSM with higher accuracy and faster turnaround time than intraoperative frozen section (IFS) analysis can help decrease reoperation rates, relieve patient anxiety and costs, and potentially improve patient outcomes.

Materials And Methods: Here, we extended our combined desorption electrospray ionization mass spectrometry imaging (DESI-MSI) and machine learning methodology to identify metabolite and lipid species from tissue surfaces that can distinguish normal tissues from clear cell RCC (ccRCC), papillary RCC (pRCC), and chromophobe RCC (chRCC) tissues.