Endogenous Protein-Modified Gold Nanorods as Immune-Inert Biomodulators for Tumor-Specific Imaging and Therapy.

Engineered modifications of nanomaterials inspired by nature hold great promise for disease-specific imaging and therapies. However, conventional polyethylene glycol modification is limited by immune system rejection. The manipulation of gold nanorods (Au NRs) modified by endogenous proteins (eP@Au) is reported as an engineered biomodulator for enhanced breast tumor therapy.

The Disturbed Microbial Niches of Itchy Scalp.

Background: Scalp itch without evident cause is an uncomfortable symptom that annoys many people in life but lacks adequate attention in academic.

Aims: To investigate the relationship between scalp itching and microorganisms, and identify the key microbes and predicted functions associated with scalp itching, furtherly to provide useful targets for scalp itch solution.

Methods: We performed microbial comparison between 44 normal subjects and 89 subjects having scalp itching problem with un-identified origin based on 16S rRNA gene sequencing and ddPCR (digital droplet PCR), and identified itch relevant microbes and predicted functions.

Targeting intracellular cancer proteins with tumor-microenvironment-responsive bispecific nanobody-PROTACs for enhanced therapeutic efficacy.

Proteolysis targeting chimeras (PROTACs) are pivotal in cancer therapy for their ability to degrade specific proteins. However, their non-specificity can lead to systemic toxicity due to protein degradation in normal cells. To address this, we have integrated a nanobody into the PROTACs framework and leveraged the tumor microenvironment to enhance drug specificity.

Exercise and exerkines: Mechanisms and roles in anti-aging and disease prevention.

Aging is a complex biological process characterized by increased inflammation and susceptibility to various age-related diseases, including cognitive decline, osteoporosis, and type 2 diabetes. Exercise has been shown to modulate mitochondrial function, immune responses, and inflammatory pathways, thereby attenuating aging through the regulation of exerkines secreted by diverse tissues and organs. These bioactive molecules, which include hepatokines, myokines, adipokines, osteokines, and neurokines, act both locally and systemically to exert protective effects against the detrimental aspects of aging.

Serum O-glycosylated HBsAg levels correlate with HBV RNA in HBeAg positive CHB patients during antiviral therapy.

Background: Recent evidence has indicated that the O-glycosylated PreS2 domain of the middle HBsAg is a distinguishing characteristic that allows the identification of HBsAg of HBV Dane particles and SVPs. This study's objective was to assess the changes in serum O-glycosylated HBsAg levels in CHB patients undergoing ETV or Peg-IFNα treatment.

Methods: Our retrospective study enrolled 86 patients with genotype C CHB.

High hydrostatic pressure promotes gene transcription via a cystathionine-β-synthase domain-containing protein in the hyperthermophilic archaeon Pyrococcus yayanosii.

Cystathionine-β-synthase (CBS) domains are ubiquitously prevalent in all kingdoms of life. Remarkably, in archaea, proteins consisting of solely CBS domains are widespread. However, the biological functions of CBS proteins in archaea are still unknown.

Gene Doping Detection From the Perspective of 3D Genome.

Since the early 20th century, the concept of doping was first introduced. To achieve better athletic performance, chemical substances were used. By the mid-20th century, it became gradually recognized that the illegal use of doping substances can seriously endangered athletes' health and compromised the fairness of sports competitions.

The transcriptional repressor HEY2 regulates mitochondrial oxidative respiration to maintain cardiac homeostasis.

Energy deprivation and metabolic rewiring of cardiomyocytes are widely recognized hallmarks of heart failure. Here, we report that HEY2 (a Hairy/Enhancer-of-split-related transcriptional repressor) is upregulated in hearts of patients with dilated cardiomyopathy. Induced Hey2 expression in zebrafish hearts or mammalian cardiomyocytes impairs mitochondrial respiration, accompanied by elevated ROS, resulting in cardiomyocyte apoptosis and heart failure.

Mms22-Rtt107 axis attenuates the DNA damage checkpoint and the stability of the Rad9 checkpoint mediator.

The DNA damage checkpoint is a highly conserved signaling pathway induced by genotoxin exposure or endogenous genome stress. It alters many cellular processes such as arresting the cell cycle progression and increasing DNA repair capacities. However, cells can downregulate the checkpoint after prolonged stress exposure to allow continued growth and alternative repair.

Histone lactylation-driven YTHDC1 promotes hepatocellular carcinoma progression via lipid metabolism remodeling.

Lipid metabolism reprogramming is critical for the initiation and progression of hepatocellular carcinoma (HCC). However, how the dysregulation of lipid metabolism contributes to HCC development remains largely unknown. Here, we report that the mA reader YTHDC1-mediated epigenetic regulation of the long noncoding RNA NEAT1 activates stearoyl-CoA desaturase (SCD)-associated lipid metabolic processes during HCC progression.

Functional anti-inflammatory mesoporous silica nanoplatform for Synergistic and Targeted abdominal aortic aneurysm treatment.

Abdominal aortic aneurysm (AAA) is a chronic inflammation-driven disease characterized by aortic wall destruction and expansion, leading to high morbidity and mortality. However, previous drug treatments for its common risk factors have not achieved favorable results, and the early prevention and treatment is still the main clinical dilemma. Anti-inflammation therapy is a promising therapeutical method targeting its pathogenesis mechanism, but it has not been explored in depth.

Metal-organic framework-based nanoplatforms for synergistic anti-atherosclerosis therapy by regulating the PI3K/AKT/MSR1 pathway in macrophages.

Atherosclerosis is the main pathogenic factor of various cardiovascular diseases. During the pathogenesis of atherosclerosis, macrophages play a major role, mainly by secreting pro-inflammatory cytokines and taking in lipids to form foam cells. Thiamine pyrophosphate (TPP) is an antagonist of the P2Y6 receptor, which is overexpressed on macrophages during atherosclerosis and facilitates the lipid phagocytosis of macrophages.

Characterization of a tomato chlh mis-sense mutant reveals a new function of ChlH in fruit ripening.

Tomato fruit ripening is a complex developmental process that is important for fruit quality and shelf life. Many factors, including ethylene and several key transcription factors, have been shown to play important roles in the regulation of tomato fruit ripening. However, our understanding of the regulation of tomato fruit ripening is still limited.

Zhishi Xiebai Guizhi Decoction modulates hypoxia and lipid toxicity to alleviate pulmonary vascular remodeling of pulmonary hypertension in rats.

Background: Pulmonary hypertension (PH) is a severe cardio-pulmonary vascular disease, involves complex molecular mechanism especially during the pathological process of pulmonary vascular remodeling, brings a significant challenge to clinical treatment and thus resulting in high mortality rates. Classic Traditional Chinese medicine formula, Zhishi Xiebai Guizhi Decoction (ZXGD), holds therapeutic potential for PH. In present study, we sought to explore therapeutic potential of ZXGD against PH in rats.

Structure-Based Screening and Optimization of PafA Inhibitors with Potent Anti-Tuberculosis Activity.

Tuberculosis (TB), caused by (), remains a major global health challenge, primarily due to the increasing prevalence of drug resistance. Consequently, the development of drugs with novel modes of action (MOAs) is urgently required. In this study, we discovered and characterized two potent inhibitors, Pi-1-58 and Pi-2-26, targeting the prokaryotic ubiquitin-like protein (Pup) ligase PafA of .

Ablation of CCL17-positive hippocampal neurons induces inflammation-dependent epilepsy.

Objective: Neuronal cell death and neuroinflammation are characteristic features of epilepsy, but it remains unclear whether neuronal cell death as such is causative for the development of epileptic seizures. To test this hypothesis, we established a novel mouse line permitting inducible ablation of pyramidal neurons by inserting simian diphtheria toxin (DT) receptor (DTR) cDNA into the Ccl17 locus. The chemokine CCL17 is expressed in pyramidal CA1 neurons in adult mice controlling microglial quiescence.

Design and synthesis of fluorescence-labeled nucleotide with a cleavable aryl-triazene linker for DNA sequencing by synthesis.

A novel acid-cleavable triazene linker was synthesized and then reacted with modified 2'-deoxyuridine triphosphate (dUTP), followed by Cy3 NHS ester, the final product serves as an excellent reversible terminator for DNA sequencing by synthesis (DNA SBS). The synthesized dye-labeled terminator incorporated into DNA strand faithfully in a DNA-elongation, and the fluorophore incorporated into DNA strands was cleaved completely under weak acidic conditions within short time. Further the first cleaved product can be incorporated with 100% efficiency for the second time.

A prospective multi-cohort study identifies and validates a 5-gene peripheral blood signature predictive of immunotherapy response in non-small cell lung cancer.

Background: Immune checkpoint inhibitors (ICIs) have revolutionized the treatment landscape for non-small cell lung cancer (NSCLC). The variability in patient responses necessitates a blood-based, multi-cohort gene signature to predict ICI response in NSCLC.

Methods: We performed transcriptomic profiling of peripheral blood mononuclear cell (PBMC) and buffy coat (BC) samples from three independent cohorts of NSCLC patients treated with ICIs: a retrospective cohort (PMBCR, n = 59), a retrospective validation cohort (BC, n = 44), and a prospective validation cohort (PBMCP, n = 42).

Netrin1-Enriched Exosomes From Genetically Modified ADSCs as a Novel Treatment for Diabetic Limb Ischemia.

Diabetic limb ischemia (DLI) is a frequent complication of diabetes and the leading cause of non-traumatic amputation. Traditional treatments like stent placement and bypass surgery may not suit all patients. Exosome transplantation has emerged as a promising therapy.

Investigating TCR-pMHC interactions for TCRs without identified epitopes by constructing a computational pipeline.

The molecular mechanisms underlying epitope recognition by T cell receptors (TCRs) are critical for activating T cell immune responses and rationally designing TCR-based therapeutics. Single-cell sequencing techniques vastly boost the accumulation of TCR sequences, while the limitation of available TCR-pMHC structures hampers further investigations. In this study, we proposed a computational pipeline that incorporates structural information and single-cell sequencing data to investigate the epitope-recognition mechanisms for TCRs without identified epitopes.