Therapeutic gene correction of HBB frameshift CD41-42 (-TCTT) deletion in human hematopoietic stem cells.

Β-thalassemia is one of the global health burdens. The CD41-42 (-TCTT) mutation at HBB is the most prevalent pathogenic mutation of β-thalassemia in both China and Southeast Asia. Previous studies focused on repairing the HBB CD41-42 (-TCTT) mutation in β-thalassemia patient-specific induced pluripotent stem cells, which were subsequently differentiated into hematopoietic stem and progenitor cells (HSPCs) for transplantation.

Computational Elucidation of Hub Genes and Pathways Correlated with the Development of 5-Fluorouracil Resistance in HCT 116 Colorectal Carcinoma Cell Line.

Colorectal cancer (CRC) is the third most deadly cancer diagnosed in both men and women. 5-Fluorouracil (5-FU) treatment frequently causes the CRC cells to become chemoresistance, which has a negative impact on prognosis. Using bioinformatic techniques, this work describes important genes and biological pathways linked to 5-FU resistance in CRC cells.

Growth hormone-releasing hormone signaling and manifestations within the cardiovascular system.

Growth hormone (GH)-releasing hormone (GHRH), a hypothalamic peptide initially characterized for its role in GH regulation, has gained increasing attention due to its GH-independent action on peripheral physiology, including that of the cardiovascular system. While its effects on the peripheral vasculature are still under investigation, GHRH and synthetic agonists have exhibited remarkable receptor-mediated cardioprotective properties in preclinical models. GHRH and its analogs enhance myocardial function by improving contractility, reducing oxidative stress, inflammation, and offsetting pathological remodeling.

Adenine base editor corrected ADPKD point mutations in hiPSCs and kidney organoids.

Autosomal dominant polycystic kidney disease (ADPKD) is a dominant genetic disorder caused primarily by mutations in the PKD1 gene, resulting in the formation of numerous cysts and eventually kidney failure. However, there are currently no gene therapy studies aimed at correcting PKD1 gene mutations. In this study, we identified two mutation sites associated with ADPKD, c.

Increasing the robustness of Escherichia coli for aromatic chemicals production through transcription factor engineering.

Engineering microbial cell factories has been widely used to produce a variety of chemicals, including natural products, biofuels, and bulk chemicals. However, poor robustness limits microbial production on an industrial scale. Microbial robustness is essential to ensure reliable and sustainable production of targeted chemicals.

Evolution of Human Pair Bonds as a Consequence of Male-Biased Mating Sex Ratios?

Compared to our closest primate relatives, human life history involves greater longevity, which includes a distinctive postmenopausal life stage. Given mammalian reproductive physiology in which females build a finite stock of cells that can become oocytes early in life, which then continuously deplete mostly through cell death while males produce new sperm throughout adulthood, the postmenopausal stage makes the sex ratio in the fertile pool, called the adult sex ratio (ASR), male biased. Additionally, this affects a more fine-grained ratio, the operational sex ratio (OSR), defined as the ratio of males to females currently able to conceive.

Targeting oncogene-induced cellular plasticity for tumor therapy.

Cellular plasticity, the remarkable adaptability of cancer cells to survive under various stress conditions, is a fundamental hallmark that significantly contributes to treatment resistance, tumor metastasis, and disease recurrence. Oncogenes, the driver genes that promote uncontrolled cell proliferation, have long been recognized as key drivers of cellular transformation and tumorigenesis. Paradoxically, accumulating evidence demonstrates that targeting certain oncogenes to inhibit tumor cell proliferation can unexpectedly induce processes like epithelial-to-mesenchymal transition (EMT), conferring enhanced invasive and metastatic capabilities.

Targeted inhibition of PqsR in Pseudomonas aeruginosa PAO1 quorum-sensing network by chalcones as promising antibacterial compounds.

Background: Pseudomonas aeruginosa's inherent and adapted resistance makes this pathogen a serious problem for antimicrobial treatments. Furthermore, its biofilm formation ability is the most critical armor against antimicrobial therapy, and the virulence factors, on the other hand, contribute to fatal infection and other recalcitrant phenotypic characteristics. These capabilities are harmonized through cell-cell communication called Quorum Sensing (QS), which results in gene expression regulation via three major interconnected circuits: las, rhl, and pqs system.

Low skeletal muscle mass contributes to the prognosis of patients with superficial esophageal cancer treated with definitive chemoradiotherapy.

Background: Herein, we aimed to examine the relationship between sarcopenia, neutrophil-lymphocyte ratio (NLR), Charlson comorbidity index (CCI), and prognostic nutritional index (PNI) in patients with superficial esophageal carcinoma who underwent definitive chemoradiotherapy (CRT).

Methods: We retrospectively analyzed 100 patients (87 males) diagnosed with cT1N0M0 esophageal squamous cell carcinoma. The included patients underwent CRT as an initial treatment.

Uncovering the intricacies of IGF-1 in Alzheimer's disease: new insights from regulation to therapeutic targeting.

Alzheimer's disease (AD) is a progressive neurodegenerative disorder characterized by the accumulation of amyloid-β plaques and tau tangles, leading to cognitive decline and dementia. Insulin-like Growth Factor-1 (IGF-1) is similar in structure to insulin and is crucial for cell growth, differentiation, and regulating oxidative stress, synaptic plasticity, and mitochondrial function. IGF-1 exerts its physiological effects by binding to the IGF-1 receptor (IGF-1R) and activating PI3K/Akt pathway.

Variation in cancer risk between organs can not be explained by the degree of somatic clonal expansion.

Somatic clonal expansion refers to the proliferation and expansion of a cell clone within a multicellular organism. Since cancer also results from the uncontrolled proliferation of few cell clones, it is generally believed that aging-associated somatic clonal expansion observed in normal tissues represents a precancerous condition. For instance, hematological malignancy is often preceded by clonal hematopoiesis.

Chemical composition, antibacterial and antioxidant activities of Piper betle and Anethum graveolens essential oils against Methicillin-resistant Staphylococcus aureus clinical isolates.

Methicillin-resistant Staphylococcus aureus (MRSA) is one of the leading causes of infection worldwide due to its antimicrobial resistance. Plant-derived essential oils (EOs) have undergone extensive observational and clinical research to explore their antimicrobial properties. The present study aimed to check mec A positive MRSA isolates using sequencing analysis, determination of chemical composition using gas chromatography-mass spectroscopy (GC-MS), antioxidant, and antimicrobial activity of Anethum graveolens and Piper betle EOs against the infectious agent MRSA.

Multi-omics sequencing of gastroesophageal junction adenocarcinoma reveals prognosis-relevant key factors and a novel immunogenomic classification.

Background: Gastroesophageal junction adenocarcinoma (GEJAC) exhibits distinct molecular characteristics due to its unique anatomical location. We sought to investigate effective and reliable molecular classification of GEJAC to guide personalized treatment.

Methods: We analyzed the whole genomic, transcriptomic, T-cell receptor repertoires, and immunohistochemical data in 92 GEJAC patients and delineated the landscape of genetic and immune alterations.

Anti-melanoma differentiation-associated gene 5 antibody-positive interstitial lung disease masquerading as rheumatoid arthritis-associated interstitial lung disease or overlapping with the same: a phenomenon driven by a probable genetic predisposition.

Rheumatoid arthritis (RA) is a systemic, progressive illness marked by persistent synovitis that causes substantial functional disability. Treatment delays frequently affect health-related quality of life. Extra-articular features are prevalent findings in RA, which leads to significant morbidity and mortality.

Ovarian function after COVID-19: long-term effects and vaccine safety in ART patients.

Purpose: This study aimed to evaluate the long-term impact of mild COVID-19 infection and COVID-19 vaccination on ovarian function in patients undergoing assisted reproductive technology (ART). Specifically, we assessed ovarian outcomes between 9 and 18 months post-infection and investigated the effects of COVID-19 vaccines (inactivated virus and adenovirus) on reproductive parameters.

Methods: The study included two objectives: (a) examining ovarian function in post-COVID-19 patients (9-18 months post-infection) compared to a control group and (b) comparing reproductive outcomes in vaccinated versus unvaccinated patients.

A simple and effective method to remove pigments from heterologous secretory proteins expressed in Pichia pastoris.

Pichia pastoris is a popular yeast host for high-level heterologous expression of proteins on an industrial scale owing to its reliable expression, robust growth, high fermentation density, and easy genetic manipulation and cultivation at a relatively low cost. Of particular interest is its high secretion efficiency for small proteins including insulin, human serum albumin, vaccines, enzymes, and llama-derived heavy-chain only antibodies (nanobodies) for pharmaceutical and research applications. However, a recurring challenge in using P.

Hydrogen Sulfide (HS) Generated in the Colon Induces Neuropathic Pain by Activating Spinal NMDA Receptors in a Rodent Model of Chronic Constriction Injury.

Neuropathic pain (NP) imposes a significant burden on individuals, manifesting as nociceptive anaphylaxis, hypersensitivity, and spontaneous pain. Previous studies have shown that traumatic stress in the nervous system can lead to excessive production of hydrogen sulfide (HS) in the gut. As a toxic gas, it can damage the nervous system through the gut-brain axis.

Transcriptomic insight into zinc dependency of vindoline accumulation in Catharanthus roseus leaves: relevance and potential role of a CrZIP.

Foliar-applied Zn on Catharanthus roseus enhanced production of vindoline, the main impediment precursor for costly anticancer bisindoles. A leaf-abundant CrZIP was characterized for likely role in modulating vindoline metabolism. The leaf-localized Catharanthus roseus alkaloid, vindoline, is the major impediment precursor in the production of scanty and expensive anticancer bisindoles, vinblastine and vincristine.

Technologies for studying phase-separated biomolecular condensates.

Biomolecular condensates, also referred to as membrane-less organelles, function as fundamental organizational units within cells. These structures primarily form through liquid-liquid phase separation, a process in which proteins and nucleic acids segregate from the surrounding milieu to assemble into micron-scale structures. By concentrating functionally related proteins and nucleic acids, these biomolecular condensates regulate a myriad of essential cellular processes.

The ability of CD4CD8 T cells to distinguish between Epstein-Barr virus-associated hemophagocytic lymphohistiocytosis and pediatric infectious mononucleosis.

Epstein-Barr virus (EBV)-related hemophagocytic lymphohistiocytosis (EBV-HLH) and infectious mononucleosis (IM) are characterized by fever, hepatomegaly, and splenomegaly, but HLH has a 50% lethality rate. Therefore, this study aimed to compare the laboratory findings in differentiating EBV-HLH children from IM children who have fever, hepatomegaly, or splenomegaly. A total of 131 IM patients and 29 EBV-HLH pediatric patients with fever, hepatomegaly, or splenomegaly were enrolled in our study.

Lipid Levels and Lung Cancer Risk: Findings from the Taiwan National Data Systems from 2012 to 2018.

Background: Lipids are known to be involved in carcinogenesis, but the associations between lipid profiles and different lung cancer histological classifications remain unknown.

Methods: Individuals who participated in national adult health surveillance from 2012 to 2018 were included. For patients who developed lung cancer during follow-up, a 1:2 control group of nonlung cancer participants was selected after matching.

RNA structure: implications in viral infections and neurodegenerative diseases.

RNA is an intermediary between DNA and protein, a catalyzer of biochemical reactions, and a regulator of genes and transcripts. RNA structures are essential for complicated functions. Recent years have witnessed rapid advancements in RNA secondary structure probing techniques.

Metabolic engineering for single-cell protein production from renewable feedstocks and its applications.

Proteins are indispensable for maintaining a healthy diet and performing crucial functions in a multitude of physiological processes. The growth of the global population and the emergence of environmental concerns have significantly increased the demand for protein-rich foods such as meat and dairy products, exerting considerable pressure on global food supplies. Single-cell proteins (SCP) have emerged as a promising alternative source, characterized by their high protein content and essential amino acids, lipids, carbohydrates, nucleic acids, inorganic salts, vitamins, and trace elements.

Dental Pulp Stem Cells Attenuate Early Brain Injury After Subarachnoid Hemorrhage via miR-26a-5p/PTEN/AKT Pathway.

Subarachnoid hemorrhage (SAH) is a type of hemorrhagic stroke with high morbidity, mortality and disability, and early brain injury (EBI) after SAH is crucial for prognosis. Recently, stem cell therapy has garnered significant attention in the treatment of neurological diseases. Compared to other stem cells, dental pulp stem cells (DPSCs) possess several advantages, including abundant sources, absence of ethical concerns, non-invasive procurement, non-tumorigenic history and neuroprotective potential.

Differential Neuronal Activation of Nociceptive Pathways in Neuropathic Pain After Spinal Cord Injury.

Neuropathic pain, a prevalent complication following spinal cord injury (SCI), severely impairs the life quality of patients. No ideal treatment exists due to incomplete knowledge on underlying neural processes. To explore the SCI-induced effect on nociceptive circuits, the protein expression of c-Fos was analyzed as an indicator of neuronal activation in a rat contusion model exhibiting below-level pain.