transcription initiation

Litchi pericarp is rich in polyphenols, and demonstrates significant biological activity. This study assessed the therapeutic effects of litchi pericarp extract (LPE) on type 2 diabetes mellitus in db/db mice. The results showed that LPE ameliorated symptoms of glucose metabolism disorder, oxidative stress, inflammatory response, and insulin resistance in db/db mice. The mechanistic studies indicated that LPE activates adenosine 5'-monophosphate (AMP)-activated protein kinase (AMPK) and suppresses the protein expression of phosphoenolpyruvate carboxykinase (PEPCK), thereby reducing hepatic gluconeogenesis...

BACKGROUND: Electronic health record (EHR) transitions are known to be highly disruptive, can drastically impact clinician and staff experiences, and may influence patients' experiences using the electronic patient portal. Clinicians and staff can gain insights into patient experiences and be influenced by what they see and hear from patients. Through the lens of an emergency preparedness framework, we examined clinician and staff reactions to and perceptions of their patients' experiences with the portal during an EHR transition at the Department of Veterans Affairs (VA)...

Lysine lactylation (Kla) links metabolism and gene regulation and plays a key role in multiple biological processes. However, the regulatory mechanism and functional consequence of Kla remain to be explored. Here, we report that HBO1 functions as a lysine lactyltransferase to regulate transcription. We show that HBO1 catalyzes the addition of Kla in vitro and intracellularly, and E508 is a key site for the lactyltransferase activity of HBO1. Quantitative proteomic analysis further reveals 95 endogenous Kla sites targeted by HBO1, with the majority located on histones...

The contributions of aberrantly expressed metabolic enzymes to gastric cancer (GC) initiation and progression have been widely appreciated in recent years. Acetyl-CoA acetyltransferase 2 (ACAT2) is one member of the acetyl- CoA thiolase family. Previous studies demonstrated that ACAT2 either promotes or suppresses tumor progression in different conditions. However, the function and mechanisms of ACAT2 in GC remain unknown. We found that the expression of this enzyme was significantly increased in GC tissues compared with normal counterparts, which prompted us to further investigate the roles of this protein in GC biology...

INTRODUCTION: Aboriginal Australians face significant health disparities, with hospitalisation rates 2.3 times greater, and longer hospital length of stay, than non-Indigenous Australians. This additional burden impacts families further through out-of-pocket healthcare expenditure (OOPHE), which includes additional healthcare expenses not covered by universal taxpayer insurance. Aboriginal patients traveling from remote locations are likely to be impacted further by OOPHE. The objective of this study was to examine the impacts and burden of OOPHE for rurally based Aboriginal individuals...

Gene duplication contributes to the evolution of expression and the origin of new genes, but the relative importance of different patterns of duplicate gene expression and mechanisms of retention remains debated and particularly poorly understood in bacteria. Here, we investigated gene expression patterns for two laboratory strains of the cyanobacterium Acaryochloris marina with expanding genomes that contain about ten-fold more gene duplicates compared with most bacteria. Strikingly, we observed a generally stoichiometric pattern of greater combined duplicate transcript dosage with increased gene copy number, in contrast to the prevalence of expression reduction reported for many eukaryotes...

The objective is to evaluate the performance of blood test results, radiomics, and a combination of the two data types on the prediction of the 24-h oxygenation support need for the Coronavirus disease 2019 (COVID-19) patients. In this retrospective cohort study, COVID-19 patients with confirmed real-time reverse transcription-polymerase chain reaction assay (RT-PCR) test results between February 2020 and August 2021 were investigated. Initial blood cell counts, chest radiograph, and the status of oxygenation support used within 24 h were collected (n = 290; mean age, 45 ± 19 years; 125 men)...

The chloroplast thylakoid membrane is composed of membrane lipids and photosynthetic protein complexes, and orchestration of thylakoid lipid biosynthesis and photosynthesis-associated protein accumulation is considered important for thylakoid development. Galactolipids consist of ~80% of the thylakoid lipids and their biosynthesis is fundamental for chloroplast development. We previously reported that the suppression of galactolipid biosynthesis decreased the expression of photosynthesis-associated nuclear- and plastid-encoded genes (PhANGs and PhAPGs)...

As population immunity to SARS-CoV-2 evolves and new variants emerge, the role and accuracy of antigen tests remain active questions. To describe recent test performance, the detection of SARS-CoV-2 by antigen testing was compared with that by reverse transcription-polymerase chain reaction (RT-PCR) and viral culture testing during November 2022-May 2023. Participants who were enrolled in a household transmission study completed daily symptom diaries and collected two nasal swabs (tested for SARS-CoV-2 via RT-PCR, culture, and antigen tests) each day for 10 days after enrollment...

Structural muscle changes, including muscle atrophy and fatty infiltration, follow rotator cuff tendon tear and are associated with a high repair failure rate. Despite extensive research efforts, no pharmacological therapy is available to successfully prevent both muscle atrophy and fatty infiltration after tenotomy of tendomuscular unit without surgical repair. Poly(ADP-ribose) polymerases (PARPs) are identified as a key transcription factors involved in the maintenance of cellular homeostasis. PARP inhibitors have been shown to influence muscle degeneration, including mitochondrial hemostasis, oxidative stress, inflammation and metabolic activity, and reduced degenerative changes in a knockout mouse model...

In 1999, the first biosynthetic gene cluster (BGC), synthesizing the virulence factor DHN melanin, was characterized in Aspergillus fumigatus . Since then, 19 additional BGCs have been linked to specific secondary metabolites (SMs) in this species. Here, we provide a comprehensive timeline of A. fumigatus BGC discovery and find that initial advances centered around the commonly expressed SMs where chemical structure informed rationale identification of the producing BGC (e.g., gliotoxin, fumigaclavine, fumitremorgin, pseurotin A, helvolic acid, fumiquinazoline)...

The necrotrophic pathogen Botrytis cinerea infects a broad range of plant hosts and causes substantial economic losses to many crops. Although resistance to procymidone has been observed in the field, it remains uncertain why procymidone is usually involved in multidrug resistance (MDR) together with other fungicides. Nine mutants derived from the B. cinerea strain B05.10 through procymidone domestication exhibited high resistance factors (RFs) against both procymidone and fludioxonil. However, the fitness of the mutants was reduced compared to their parental strain, showing non-sporulation and moderate virulence...

This qualitative study aimed to understand men's social connectedness in later life in Portugal focusing on their perceptions, obstacles, strategies, and impact on well-being. The sample included 104 older Portuguese men over 65 years of age ( Mage = 70.76 years). The qualitative data were the direct transcriptions of the answers given by participants to the electronic interview using thematic analysis. Findings revealed six overarching themes encompassing 18 subcategories: definitions of social connectedness (social support, community identity, mental health promotion, use of community structures), difficulties/obstacles in maintaining social connectedness (ageism, lack of initiative, physical limitations, psychological traits, resources), strategies/actions or resources to establish social connections (use of technology, use of community groups, leisure and sport activities, church/religion), negative impact of difficulties in establishing relevant social connections (mental health, physical health, relationships), positive actions from being socially connected (positive prescriptions to promote social connectedness), and concerns from being socially disconnected (health risks)...

INTRODUCTION: Defective interleukin-2 (IL-2) production contributes to immune system imbalance in patients with systemic erythematosus lupus (SLE). Recent clinical studies suggested that low-dose IL-2 treatment is beneficial for SLE and the therapeutic effect is associated with regulatory T cell (Treg) expansion. Pharmacological calcineurin inhibition induces a reduction in the number of Tregs because they require stimulation of T cell receptor signaling and IL-2 for optimal proliferation...

Adeno-associated virus (AAV)-mediated gene therapy is widely applied to treat numerous hereditary diseases in animal models and humans. The specific expression of AAV-delivered transgenes driven by cell type-specific promoters should further increase the safety of gene therapy. However, current methods for screening cell type-specific promoters are labor-intensive and time-consuming. Herein, we designed a "multiple vectors in one AAV" strategy for promoter construction in vivo. Through this strategy, we truncated a native promoter for Myo15 expression in hair cells (HCs) in the inner ear, from 1,611 bp down to 1,157 bp, and further down to 956 bp...

BACKGROUND/AIM: Cancer is a complex disease that involves both genetic and epigenetic factors. While emerging evidence clearly suggests that changes in epitranscriptomics play a crucial role in cancer pathogenesis, a comprehensive understanding of the writers, erasers, and readers of epitranscriptomic processes, particularly under apoptotic conditions remains lacking. The aim of this study was to uncover the changes in the expression of m6 A RNA modifiers under apoptotic conditions across various cancer cell lines...

Targeting RNA-binding and modifying proteins via small molecules to modulate post-transcriptional modifications have emerged as a new frontier for chemical biology and therapeutic research. One such RNA-binding protein that regulates the most prevalent eukaryotic RNA modification, N 6 -methyladenosine (m6 A), is the methyltransferase-like protein 16 (METTL16), which plays an oncogenic role in cancers by cofunctioning with other nucleic acid-binding proteins. To date, no potent small-molecule inhibitor of METTL16 or modulator interfering with the METTL16-RNA interaction has been reported and validated, highlighting the unmet need to develop such small molecules to investigate the METTL16-involved regulatory network...

In the 3' untranslated region of the SARS-CoV-2 virus RNA genome, genomic RNA replication is initiated in the highly conserved region called 3'PK, containing three stem structures (P1pk, P2, and P5). According to one proposed mechanism, P1pk and distal P2 stems switch their structure to a pseudoknot through base-pairing, thereby initiating transcription by recruiting RNA-dependent RNA polymerase complexed with nonstructural proteins (nsp)7 and nsp8. However, experimental evidence of pseudoknot formation or structural switching is unavailable...

As one member of the heterogeneous ribonucleoprotein (hnRNP) family, scaffold attachment factor A (SAF-A) or hnRNP U, is an abundant nuclear protein. With RNA and DNA binding activities, SAF-A has multiple functions. The present review focused on the biological structure and different roles of SAF-A and SAF-A-related diseases. It was found that SAF-A maintains the higher-order chromatin organization via RNA and DNA, and regulates transcription at the initiation and elongation stages. In addition to regulating pre-mRNA splicing, mRNA transportation and stabilization, SAF-A participates in double-strand breaks and mitosis repair...

BACKGROUND: Over 80% of lung cancer cases constitute non-small cell lung cancer (NSCLC), making it the most prevalent type of lung cancer globally and the leading cause of cancer-related deaths. The treatment of NSCLC patients with gefitinib has demonstrated promising initial efficacy. However, the underlying mechanism remains unclear. This study aims to investigate how gefitinib affects the mitogen-activated protein kinase kinase (MEK)/extracellular regulated protein kinases (ERK) signaling pathway-mediated growth and death of NSCLC cells...