Case Report: spontaneous mutation in a familial hemophagocytic lymphohistiocytosis patient with a complex heterozygous mutation in .

Familial hemophagocytic lymphohistiocytosis type 2 (FHL2), caused by perforin 1 (PRF 1), is a rare and fatal autosomal recessive disorder characterized by a hyperinflammatory syndrome and the accumulation of activated T lymphocytes and histiocytes in the reticuloendothelial system. Autoimmune lymphoproliferative syndrome (ALPS) is an autoimmune disease that typically presents in children with lymphadenopathy, splenomegaly, and cytopenias or lymphomas. We report a case of a 9-year-old boy who was newly diagnosed with FHL, carrying a new type of compound heterozygous mutations (c.

Exploring the role of ferroptosis in esophageal cancer: mechanisms and therapeutic implications.

With the development of medical and health care, esophageal cancer (EC) has become a disease of concern to the scientific research community. At present, among all treatment regimens for EC, surgical resection is conducive to the prognosis of early patients neoadjuvant therapies are recommended for advanced patients. However, treatments now are not satisfactory in suppressing the progression of EC.

Bile acids and polyphenols inhibit succinic anhydride-induced protein succinylation and amyloid aggregation: Mechanistic insights.

Lysine succinylation is a major post-translational modification affecting diverse proteins, and its excessive occurrence can lead to protein misfolding and aggregation-hallmarks of various proteinopathies, such as amyloid-β and Tau tangle formation in Alzheimer's disease and islet amyloid polypeptide aggregation in type 2 diabetes. Here, we investigated the inhibitory effects of bile acid metabolites (deoxycholic acid, glycocholic acid, and taurocholic acid sodium) and natural polyphenols (anthocyanin and salidroside) on succinylation and succinylation-induced amyloid aggregation. Succinylation levels were evaluated using the ninhydrin assay before and after treatment, and aggregation behavior and structural alterations were characterized by SDS-PAGE, inverted fluorescence microscopy, and intrinsic fluorescence spectroscopy.

Epigenetic clocks and longitudinal plasma biomarkers of Alzheimer's disease.

Introduction: Chronological age is the strongest risk factor for Alzheimer's disease and related dementias (ADRD). However, the association of accelerated biological aging relative to chronological age with ADRD pathology is unclear.

Methods: In a cohort of 2,366 cognitively unimpaired older women from the Women's Health Initiative Memory Study, we examined associations of five baseline measures of epigenetic age acceleration (EAA) with 15-year changes in plasma ADRD biomarkers.

Integration of mRNA and miRNA Analysis Reveals the Regulation of Salt Stress Response in Rapeseed ( L.).

Soil salinization is a major constraint to global crop productivity, highlighting the need to identify salt tolerance genes and their molecular mechanisms. Here, we integrated mRNA and miRNA profile analyses to investigate the molecular basis of salt tolerance of an elite cultivar S268. Time-course RNA-seq analysis revealed dynamic transcriptional reprogramming under 215 mM NaCl stress, with 212 core genes significantly enriched in organic acid degradation and glyoxylate/dicarboxylate metabolism pathways.

Identifying low-risk breast cancer patients for axillary biopsy exemption: a multimodal preoperative predictive model.

Background: As the most prevalent female malignancy worldwide, breast cancer frequently involves axillary lymph node metastasis (ALNM), which critically affects therapeutic algorithms. Current guidelines mandate preoperative ultrasound-guided axillary biopsy for suspicious lymph nodes, potentially exposing some low-risk patients with negative results to invasive risks. To optimize the utilization of biopsy, this study established a multimodal predictive framework that preoperatively assesses axillary lymph node (ALN) status, thereby triaging candidates for ultrasound-guided axillary biopsy.

PPARγ acetylation governs mammary adenocarcinoma tumor growth via acetylated residues that determine DNA sequence-specific binding.

Peroxisome proliferator-activated receptor γ (PPARγ), which is expressed in a variety of malignancies, governs biological functions through transcriptional programs. Defining the molecular mechanisms governing the selection of canonical versus non-canonical PPARγ binding sequences may provide the opportunity to design regulators with distinct functions and side effects. Acetylation at K268/293 in mouse Pparγ2 participates in the regulation of adipose tissue differentiation, and the conserved lysine residues (K154/155) in mouse Pparγ1 governs lipogenesis in breast cancer cells.

Ga/Tb-CP2 as a Paired Radiopharmaceutical Targeting KDM4A and the Preliminary Verification in NCI-H2228 Xenografts Model.

To address the unmet clinical need for Lysine (K)-specific demethylase 4A (KDM4A)-targeted therapies in nonsmall cell lung cancer (NSCLC), we developed a novel theranostic pair, Ga/Tb-CP2, leveraging the epigenetic regulator KDM4A and terbium-161's high linear energy transfer (LET) Auger electrons for precision therapy. The radiopharmaceutical was synthesized via a one-step chelation protocol. Radiochemical purity and stability were validated by radio-HPLC and radio-TLC.

Analysis of factors influencing endometrial polyp recurrence after hysteroscopic polypectomy.

Objective: To analyze the factors influencing the recurrence of endometrial polyps after hysteroscopic polypectomy.

Methods: A retrospective analysis was conducted on the clinical data of 925 patients who underwent hysteroscopic polypectomy for endometrial polyps at the Affiliated Hospital of Shaanxi University of Chinese Medicine from January 2017 to December 2023. All patients were followed up for 6 months, and the factors influencing the recurrence of endometrial polyps after hysteroscopic polypectomy were analyzed.

NAD-dependent dehydrogenases enable efficient growth of Paracoccus denitrificans on the PET monomer ethylene glycol.

Ethylene glycol is a monomer of the plastic polyethylene terephthalate (PET) and an environmental pollutant of increasing concern. Although it is generally accepted that bacteria use ethylene glycol as growth substrate, not all involved enzymes are well understood. Here, we show that Paracoccus denitrificans assimilates ethylene glycol solely via NAD-dependent alcohol and aldehyde dehydrogenases.

The DCIS-IBC guide board on predicting postoperative upgrading in breast ductal carcinoma in situ: clinical insights from a multicenter study.

Background: Ductal carcinoma in situ (DCIS) carries a significant risk of postoperative upgrading to invasive breast cancer (IBC), yet existing prediction models lack validation in Asian populations. This study aimed to develop and validate a population-specific nomogram to preoperatively predict DCIS-to-IBC upgrading in Asian patients.

Methods: A multicenter retrospective cohort of 465 Asian women diagnosed with DCIS by core needle biopsy (2015-2021) was analyzed.

Intestinal NF-κB pathway-mediated pyroptosis contributes to endotoxemia-induced intestinal injury.

Pyroptosis contributes to activation of the innate immunity system and defense against infection by pathogens. Endotoxemia is the host inflammatory storm occurring in response to severe and life-threatening infections caused by endotoxin from gram-negative bacilli. However, whether pyroptosis is involved in intestinal epithelial cell (IEC) or intestinal stem cell (ISC) injury induced by endotoxemia remains unclear.

Biomimetic Chitosan Nanogels Codeliver Drug/Small Activating RNA for Metastasis-Inhibited Necroptosis Therapy of Ovarian Cancer.

Ovarian cancer remains the leading cause of gynecologic malignancy-related deaths. Developing novel nanoplatforms to overcome the low efficacy of chemotherapy and advanced metastasis in ovarian cancer is crucial. Here, we report biomimetic chitosan nanogels (CH NGs) designed to codeliver gambogic acid (GA) and MAS1 small activating RNA (saMAS1).

Physical model and analysis of spectral beam combining system with dual-grating external cavity.

Spectral beam combining (SBC) has the potential to further increase the power irrespective of the limited power of single laser, and to maintain the near-diffraction-limited beam quality. However, the total power, the beam quality, and the spectra of SBC are significantly affected by the crosstalk effect attributed to the "smile" effect. Although crosstalk mitigation methods have been proposed, with the increasing laser number in dense spectral beam combining, the crosstalk caused by the spectral dispersion of single laser may hinder the further improvement of SBC.

Molecular biomarkers for the prognosis of breast cancer: role of amino acid metabolism genes.

The development of precise molecular biomarkers for breast cancer prognosis holds immense potential to improve treatment outcomes. This study aimed to investigate the role of amino acid metabolism genes as predictive markers for breast cancer prognosis and their association with the immune-tumour microenvironment. By employing advanced machine learning algorithms and bioinformatics analysis techniques, the impact of amino acid metabolism-related genes (AAMRGs) on the immune status and overall survival of patients with breast cancer was examined.

Tea polyphenols attenuate glufosinate-induced breast injury by reducing endoplasmic reticulum stress and autophagy.

Owing to the excessive use of glyphosate-based herbicides (GBHs), the amount of drug residues in corn and alfalfa silage exceeds the standard, which may affect the mammary health of dairy animals. The role of glufosinate-ammonium (GLA) in mammary development is not fully understood. Therefore, the aim of this study was to investigate mammary lesions caused by exposure to GLA in vitro and in vivo.

The effect of macromolecular crowding on protein misfolding as well as oxidative aggregation and its corresponding mechanisms under carbamylation conditions.

Protein carbamylation is a non-enzymatic post-translational modification, potentially increasing the risk of misfolding diseases. However, studies on carbamylation in recent years have focused only on amyloid aggregation, ignoring its effect on more toxic oligomers. Additionally, the behavior of proteins in dilute solutions does not fully reflect how these molecules function in their physiological environment.

A novel approach based on PEM electrolysis technology for iron recovery from acid mine drainage: performance and mechanism.

Acid mine drainage (AMD) resulting from mining activities poses a significant global environmental challenge. Iron is the most concentrated pollutant in AMD, which impedes the treatment process of lime neutralization and generates substantial sludge. To achieve efficient removal and resource recovery of iron, a proton exchange membrane (PEM) electrolysis system was developed.

Turning Waste into Treasure: Radiation Byproduct-Induced Fe(III)/Fe(II) Conversion for Efficient Ferroptosis to Improve Iodine-131-Based Transarterial Radioembolization for Liver Tumors.

Transarterial radioembolization (TARE) is a primary palliative treatment for advanced liver cancer. Nonetheless, its therapeutic efficacy is frequently hindered by resistance to tumor cell apoptosis induced by inter-radiotherapy. Induction of multiple cell death modalities provides a potential solution to this challenge.

α-Synuclein condensation in synaptic vesicle function and synucleinopathies.

Research into the crosstalk between α-synuclein (α-syn) and synaptic vesicles (SVs) has gained considerable attention. Notably, the recently discovered liquid-liquid phase separation of α-syn involving SVs is crucial for performing their physiological functions and mediating the transition to pathological aggregates. This review first examines the functional interactions between α-syn and SVs in the context of α-syn's condensation state.

T-betCD8 T cells govern anti-PD-1 responses in microsatellite-stable gastric cancers.

More than 90% of advanced gastric cancers (GC) are microsatellite-stable (MSS). Compared to the high response rate of immune checkpoint inhibitors (ICI) in microsatellite-instability-high (MSI-H) GCs, only 10% of unstratified MSS GCs respond to ICIs. In this study, we apply semi-supervised learning to stratify potential ICI responders in MSS GCs, achieving high accuracy, quantified by an area under the curve of 0.

Electrostatic Regulation of Bola-Amphiphilic Peptide Self-Assembly and Nanotube Formation Induced by Salt Ions.

Peptide self-assembly into nanostructures offers substantial potential for applications in catalysis, drug delivery, and nanodevice fabrication. However, controlling the morphology of these assemblies remains a challenge. In this study, we investigate the role of salt ions in regulating the self-assembly of the bola-amphiphilic peptide KFFFFK, facilitating a transition from twisted fibrils to nanotubes.