design and structure of a peptide-centric TCR mimic binding module.

T cell receptor (TCR) mimics offer a promising platform for tumor-specific targeting of peptide-MHC in cancer immunotherapy. Here, we designed a α-helical TCR mimic (TCRm) specific for the NY-ESO-1 peptide presented by HLA-A 02, achieving high on-target specificity with nanomolar affinity (K = 9.5 nM).

Ultrasound-Activated Precise Sono-Immunotherapy for Breast Cancer with Reduced Pulmonary Fibrosis.

Immune checkpoint inhibitors have demonstrated remarkable efficacy across various cancer types. However, immune-related adverse events (irAEs) pose a significant challenge in immunotherapy, particularly the associated pneumonia as the primary adverse reaction, which can lead to irreversible pulmonary fibrosis. Additionally, monotherapy with programmed death ligand (PD-L1) inhibitors has shown limited effectiveness.

Emphysematous pyelonephritis caused by Raoultella ornithinolytica: a case report.

Background: Emphysematous pyelonephritis is a rare and severe urinary tract infection that is potentially life-threatening and easily progresses to septic shock. In this report, we present a unique case of emphysematous pyelonephritis caused by Raoultella ornithinolytica.

Case Presentation: An 86-year-old man presented with severe back pain of 3 days' duration.

Two-factor authentication underpins the precision of the piRNA pathway.

The PIWI-interacting RNA (piRNA) pathway guides the DNA methylation of young, active transposons during germline development in male mice. piRNAs tether the PIWI protein MIWI2 (PIWIL4) to the nascent transposon transcript, resulting in DNA methylation through SPOCD1 (refs. ).

GSB: GNGS and SAG-BiGRU network for malware dynamic detection.

With the rapid development of the Internet, the continuous increase of malware and its variants have brought greatly challenges for cyber security. Due to the imbalance of the data distribution, the research on malware detection focuses on the accuracy of the whole data sample, while ignoring the detection rate of the minority categories' malware. In the dataset sample, the normal data samples account for the majority, while the attacks' malware accounts for the minority.

Targeted isolation, identification, and antioxidant evaluation of aromatic polyketides from a plant-derived fungus Ophiobolus cirsii LZU-1509.

There are >350 species of the Ophiobolus genus, which is not yet very well-known and lacks research reports on secondary metabolites. Three new 3,4-benzofuran polyketides 1-3, a new 3,4-benzofuran polyketide racemate 4, two new pairs of polyketide enantiomers (±)-5 and (±)-7, two new acetophenone derivatives 6 and 8, and three novel 1,4-dioxane aromatic polyketides 9-11, were isolated from a fungus Ophiobolus cirsii LZU-1509 derived from an important medicinal and economic crop Anaphalis lactea. The isolation was guided by LC-MS/MS-based GNPS molecular networking analysis.

Isolation and Identification of Novel Antioxidant Polyketides from an Endophytic Fungus LZU-1509.

Sixteen new polyketides, ophicirsins A-P (), including four novel carbon skeletons (, , , and ), were isolated from the extract of an endophytic fungus LZU-1509. The unique frameworks of ophicirsin N () and O () feature a different cyclic ether connected with an aromatic ring system. Ophicirsin P () is characterized by the unprecedented heterozygote of a polyketide and an alkaloid.

Krüppel-like factor 5 rewires NANOG regulatory network to activate human naive pluripotency specific LTR7Ys and promote naive pluripotency.

Endogenous retroviruses (ERVs) have been reported to participate in pre-implantation development of mammalian embryos. In early human embryogenesis, different ERV sub-families are activated in a highly stage-specific manner. How the specificity of ERV activation is achieved remains largely unknown.

Early versus delayed enteral nutrition for neonatal hypoxic-ischemic encephalopathy undergoing therapeutic hypothermia: a randomized controlled trial.

Background: The practice of therapeutic hypothermia (TH) is widely used for neonatal hypoxic-ischemic encephalopathy (HIE) despite its corresponding feeding strategies are still controversial. This randomized controlled trial (RCT) demonstrated to evaluate the effect of early vs. delayed enteral nutrition on the incidence of feeding intolerance (FI) and other association during TH.

Organizing structural principles of the IL-17 ligand-receptor axis.

The IL-17 family of cytokines and receptors have central roles in host defence against infection and development of inflammatory diseases. The compositions and structures of functional IL-17 family ligand-receptor signalling assemblies remain unclear. IL-17E (also known as IL-25) is a key regulator of type 2 immune responses and driver of inflammatory diseases, such as allergic asthma, and requires both IL-17 receptor A (IL-17RA) and IL-17RB to elicit functional responses.

Homotypic fibrillization of TMEM106B across diverse neurodegenerative diseases.

Misfolding and aggregation of disease-specific proteins, resulting in the formation of filamentous cellular inclusions, is a hallmark of neurodegenerative disease with characteristic filament structures, or conformers, defining each proteinopathy. Here we show that a previously unsolved amyloid fibril composed of a 135 amino acid C-terminal fragment of TMEM106B is a common finding in distinct human neurodegenerative diseases, including cases characterized by abnormal aggregation of TDP-43, tau, or α-synuclein protein. A combination of cryoelectron microscopy and mass spectrometry was used to solve the structures of TMEM106B fibrils at a resolution of 2.

Crystal structure and functional analysis of mycobacterial erythromycin resistance methyltransferase Erm38 reveals its RNA-binding site.

Erythromycin resistance methyltransferases (Erms) confer resistance to macrolide, lincosamide, and streptogramin antibiotics in Gram-positive bacteria and mycobacteria. Although structural information for ErmAM, ErmC, and ErmE exists from Gram-positive bacteria, little is known about the Erms in mycobacteria, as there are limited biochemical data and no structures available. Here, we present crystal structures of Erm38 from Mycobacterium smegmatis in apoprotein and cofactor-bound forms.

Early-Stage Primary Anti-inflammatory Therapy Enhances the Regenerative Efficacy of Platelet-Rich Plasma in a Rabbit Achilles Tendinopathy Model.

Background: Tendinopathy is a pervasive clinical problem that afflicts both athletes and the general public. Although the inflammatory changes in tendinopathy are well characterized, how the therapeutic effects of platelet-rich plasma (PRP) on tendinopathy are being modulated by the inflammatory environment is not well defined.

Purpose/hypothesis: In this study, we aimed to compare the therapeutic effects of PRP alone versus a combination of PRP with a primary glucocorticoid (GC) injection at the early stage of tendinopathy.

All-yarn triboelectric nanogenerator and supercapacitor based self-charging power cloth for wearable applications.

Despite rapid developments, multifunctional wearable electronics are still not significant in practical applications as compared to portable and stretchable power devices. In this paper, we present the flexible and easy large-scale production of single-electrode mode triboelectric nanogenerator (TENG) and supercapacitor yarn-based self-charging power fabric, for simultaneously converting and storing biomechanical energy. Fabricated using traditional knitting technologies, the self-charging power fabric can adapt to complex mechanical deformations owing to its high flexibility and stretchability.

Ursodeoxycholic Acid at 18-22 mg/kg/d Showed a Promising Capacity for Treating Refractory Primary Biliary Cholangitis.

Aim: To compare the response between the current recommended dosage 13-15 mg/kg/d and 20 mg/kg/d dose of ursodeoxycholic acid (UDCA) in primary biliary cholangitis (PBC) patients who do not respond completely to a standard dose of UDCA.

Methods: We included 73 patients with poor response and randomized them into two groups to investigate whether increasing the dosage of UDCA was beneficial to nonresponders. Patients assigned to the 13-15 mg/kg/d group continued with standard therapy, and participants in the 18-22 mg/kg/d group switched to the higher dosage (18-22 mg/kg/d), with a follow-up of 12 months for both groups.

Long-range structural defects by pathogenic mutations in most severe glucose-6-phosphate dehydrogenase deficiency.

Glucose-6-phosphate dehydrogenase (G6PD) deficiency is the most common blood disorder, presenting multiple symptoms, including hemolytic anemia. It affects 400 million people worldwide, with more than 160 single mutations reported in G6PD. The most severe mutations (about 70) are classified as class I, leading to more than 90% loss of activity of the wild-type G6PD.

Brain-Derived Neurotrophic Factor Regulates Ishikawa Cell Proliferation through the TrkB-ERK1/2 Signaling Pathway.

(1) Background: Endometrial regulation is a necessary condition for maintaining normal uterine physiology, which is driven by many growth factors. Growth factors produced in the endometrium are thought to be related to the proliferation of endometrial cells induced by estradiol-17β (E). In this study, we found that E can induce the secretion of brain-derived neurotrophic factor (BDNF) in Ishikawa cells (the cells of an endometrial cell line).

MicroRNAs in autoimmune liver diseases: from diagnosis to potential therapeutic targets.

Autoimmune liver diseases (AILDs) are a group of liver disorders composed of autoimmune hepatitis (AIH), primary biliary cholangitis (PBC), and primary sclerosing cholangitis (PSC) characterized by chronic hepatic and biliary inflammation. Although several genetic factors, such as HLA alleles, TNFA, and CTLA-4, have been reported in the pathogenesis of AILDs, many details remain unknown. In recent years, microRNAs (miRNAs) have emerged as crucial components in the diagnosis and therapeutic applications of various autoimmune diseases, including systemic lupus erythematosus (SLE), glomerulonephritis, and AILDs.