Transcriptome-wide mapping of N3-methylcytidine modification at single-base resolution.

3-Methylcytidine (m3C), a prevalent modification of transfer RNAs (tRNAs), was recently identified in eukaryotic messenger RNAs (mRNAs). However, its precise distribution and formation mechanisms in mRNAs remain elusive. Here, we develop a novel approach, m3C immunoprecipitation and sequencing (m3C-IP-seq), utilizing antibody enrichment to profile the m3C methylome at single-nucleotide resolution.

Severe metabolic accumulation of VV116 in kidney transplant patients with impaired renal function: a case series report.

The treatment of COVID-19 in the post-transplant individuals is challenging, primarily due to the drug-drug interaction between nirmatrelvir/ritonavir and tacrolimus. Deuremidevir hydrobromide tablets (VV116) is an orally small molecule agents target SARS-CoV-2 RdRp and inhibits viral replication. It may have a low likelihood of drug-drug interactions and has a potential to provide new treatment option.

Antiviral Effectiveness, Clinical Outcomes, and Artificial Intelligence Imaging Analysis for Hospitalized COVID-19 Patients Receiving Antivirals.

Introduction: There is still a lack of clinical evidence comprehensively evaluating the effectiveness of antiviral treatments for COVID-19 hospitalized patients.

Methods: A retrospective cohort study was conducted at Beijing You'An Hospital, focusing on patients treated with nirmatrelvir/ritonavir or azvudine. The study employed a tripartite analysis-viral dynamics, survival curve analysis, and AI-based radiological analysis of pulmonary CT images-aiming to assess the severity of pneumonia.

Pharmacological Interventions for Cirrhotic Ascites: From Challenges to Emerging Therapeutic Horizons.

Ascites is the most common complication in patients with decompensated cirrhosis. This condition results in a severely impaired quality of life, excessive healthcare use, recurrent hospitalizations and significant morbidity and mortality. While loop diuretics and mineralocorticoid receptor antagonists are commonly employed for symptom relief, our understanding of their impact on survival remains limited.

SIRT6 Inhibits Anoikis of Colorectal Cancer Cells by Down-Regulating NDRG1.

Anoikis, a form of apoptosis resulting from the loss of cell-extracellular matrix interaction, is a significant barrier to cancer cell metastasis. However, the epigenetic regulation of this process remains to be explored. Here, we demonstrate that the histone deacetylase sirtuin 6 (SIRT6) plays a pivotal role in conferring anoikis resistance to colorectal cancer (CRC) cells.

From germline genome to highly fragmented somatic genome: genome-wide DNA rearrangement during the sexual process in ciliated protists.

Unlabelled: Genomes are incredibly dynamic within diverse eukaryotes and programmed genome rearrangements (PGR) play important roles in generating genomic diversity. However, genomes and chromosomes in metazoans are usually large in size which prevents our understanding of the origin and evolution of PGR. To expand our knowledge of genomic diversity and the evolutionary origin of complex genome rearrangements, we focus on ciliated protists (ciliates).

Application of RNA interference and protein localization to investigate housekeeping and developmentally regulated genes in the emerging model protozoan Paramecium caudatum.

Unicellular eukaryotes represent tremendous evolutionary diversity. However, the molecular mechanisms underlying this diversity remain largely unexplored, partly due to a limitation of genetic tools to only a few model species. Paramecium caudatum is a well-known unicellular eukaryote with an unexpectedly large germline genome, of which only two percent is retained in the somatic genome following sexual processes, revealing extensive DNA elimination.

Activation of METTL3 Promotes White Adipose Tissue Beiging and Combats Obesity.

Unlabelled: The induction of beige adipocytes in white adipose tissue (WAT), also known as WAT beiging, improves glucose and lipid metabolism. However, the regulation of WAT beiging at the posttranscriptional level remains to be studied. Here, we report that METTL3, the methyltransferase of N6-methyladenosine (m6A) mRNA modification, is induced during WAT beiging in mice.

Adipocyte YTH N(6)-methyladenosine RNA-binding protein 1 protects against obesity by promoting white adipose tissue beiging in male mice.

Obesity, one of the most serious public health issues, is caused by the imbalance of energy intake and energy expenditure. N(6)-methyladenosine (mA) RNA modification has been recently identified as a key regulator of obesity, while the detailed mechanism is elusive. Here, we find that YTH RNA binding protein 1 (YTHDF1), an mA reader, acts as an essential regulator of white adipose tissue metabolism.

Comparative analysis of single-cell genome sequencing techniques toward the characterization of germline and somatic genomes in ciliated protists.

Ciliated protists contain both germline micronucleus (MIC) and somatic macronucleus (MAC) in a single cytoplasm. Programmed genome rearrangements occur in ciliates during sexual processes, and the extent of rearrangements varies dramatically among species, which lead to significant differences in genomic architectures. However, genomic sequences remain largely unknown for most ciliates due to the difficulty in culturing and in separating the germline from the somatic genome in a single cell.

ACSL4 promotes microglia-mediated neuroinflammation by regulating lipid metabolism and VGLL4 expression.

Acyl-CoA synthetase long-chain family member 4 (ACSL4) is an important isozyme in polyunsaturated fatty acid (PUFA) metabolism. The role of ACSL4 in the lipopolysaccharide (LPS)-induced inflammation of microglia, and the effects of ACSL4-mediated inflammation on the progression of Parkinson's disease (PD) are unknown. In this study, we found that ACSL4 expression was increased after LPS stimulation.

[Experimental Study of Using Aloe Vera Gel to Treat Diabetic Chronic Cutaneous Ulcers in Bama Miniature Pigs].

Objective: To investigate the efficacy, safety, and mechanism of topical application of aloe vera gel (AVG) to treat diabetic chronic cutaneous ulcers in Bama miniature pigs.

Methods: The Bama miniature pig model of diabetic chronic skin wounds was constructed and the model pigs were randomly assigned to AVG daily administration group (AVG QD), aloe vera gel every-other-day administration group (AVG QOD), and diabetic control group (DC). A non-diabetic chronic skin wounds model pig was set as the non-diabetic control group (NDC).

Small RNA-mediated genome rearrangement pathways in ciliates.

Most eukaryotes employ a combination of transcriptional and post-transcriptional silencing mechanisms to suppress transposons, yet ciliates employ a more extreme approach. They separate germline and somatic functions into distinct nuclei, enabling the elimination of transposons from the active somatic genome through diverse small RNA-mediated genome rearrangement pathways during sexual processes.

Transcranial Direct-Current Stimulation Regulates MCT1-PPA-PTEN-LONP1 Signaling to Confer Neuroprotection After Rat Cerebral Ischemia-Reperfusion Injury.

Propionic acid (PPA) is a critical metabolite involved in microbial fermentation, which functions to reduce fat production, inhibit inflammation, and reduce serum cholesterol levels. The role of PPA in the context of cerebral ischemia-reperfusion (I/R) injury has yet to be clarified. Increasing evidence indicate that transcranial direct-current stimulation (tDCS) is a safe approach that confers neuroprotection in cerebral ischemia injury.

Severe Intermittent Hypoxia Modulates the Macrophage Phenotype and Impairs Wound Healing Through Downregulation of HIF-2α.

Background: Obstructive sleep apnea is prevalent in patients with diabetic foot ulcers, while the effect of intermittent hypoxia on wound healing is unclear. The objective of this study was to investigate the effect of severe intermittent hypoxia on wound healing.

Methods: C57BL/6 mice were exposed to 5 weeks of severe intermittent hypoxia or normoxia.

Global mortality of diabetic foot ulcer: A systematic review and meta-analysis of observational studies.

Aim: To estimate the long-term mortality and risk factors in patients with diabetic foot ulcer (DFU).

Methods: We systematically searched Medline (PubMed), Embase, Scopus, Web of Science, Cochrane Library, China Science and Technology Journal Database (CQVIP), China National Knowledge Infrastructure, the Chinese Biomedical Literature Database (SinoMed) and Wanfang Data from 1 January 2011 to 31 July 2022. All observational studies that reported long-term mortality of patients with DFU were included.

A novel isoform of hydroxyacyl-CoA dehydrogenase inhibits cell proliferation.

Hydroxyacyl-CoA dehydrogenase (HADH) catalyzes the third reaction of mitochondrial β-oxidation cascade, while the regulation of its expression and function remains to be elucidated. Using the quantitative translation initiation sequencing (QTI-seq), we have identified that murine Hadh mRNA has two alternative translation start codons. We demonstrated that translation from upstream start codon encodes the mitochondrial isoform of HADH, while translation from downstream start codon produces a short isoform (HADH-S) with predominant nuclear localization.

Efficacy and Safety of Pentoxifylline for Venous Leg Ulcers: An Updated Meta-Analysis.

The venous leg ulcers are debilitating, painful, and often unresponsive to advanced dressing treatments, so drugs used locally and systematically are essential adjuvant therapy-pentoxifylline (PTX) whose anti-inflammatory effects may offer a promising avenue to treat venous leg ulcers. However, the current results are controversial. To further evaluate the efficacy and safety of PTX, we performed an updated meta-analysis of randomized placebo-controlled trials of PTX in the treatment of venous leg ulcers.

A new approach for investigating the relative contribution of basal glucose and postprandial glucose to HbA1.

To develop an accurate method for evaluating the relative contributions of basal glucose (BG) and postprandial glucose (PPG) to glycated haemoglobin (HbA1c) in subjects with hyperglycaemia using a Continuous Glucose Monitoring System (CGMS®). The subjects were divided into the normal glucose tolerance (NGT), impaired glucose tolerance (IGT), newly-diagnosed type 2 diabetes (NDDM), and drug-treated type 2 diabetes (T2DM) groups. We evaluated the relative contributions of BG and PPG to HbA1c in patients with hyperglycaemia according to three different baseline values.

Extremity Gangrene Caused by HBV-Related Cryoglobulinemia Vasculitis in a Patient with Diabetes - A Case Report.

We presented a case of hepatitis B virus (HBV)-related type III cryoglobulinemia vasculitis (CryoVas) characterized by extremity gangrene in a patient with diabetes. The 60-year-old female had a 10-year history of poorly controlled type 2 diabetes mellitus. She complained of sudden onset pain and swelling of toes which quickly progressed to gangrene, with fingers becoming pain and dark violet.

YTHDF1-regulated expression of TEAD1 contributes to the maintenance of intestinal stem cells.

N6-methyladenosine (mA) mRNA modification has been defined as a crucial regulator in various biological processes. Recent studies indicated an essential role of YTHDF1, an mA reader, in the maintenance of intestinal stem cells (ISCs), while the detailed mechanism remains to be explored. By searching our mA sequencing, RNA sequencing, and ribosome profiling data, we identified the transcriptional enhanced associate domain 1 (TEAD1) as a direct target of YTHDF1.