Bilayer Microneedles Loading Nanozymes and Quantum Dots with Gradient Photothermal Antibacterial, Exudate Control, Antioxidation, and pH Monitoring for Enhanced Diabetic Wound Healing.

Chronic diabetic wounds are characterized by excessive oxidative stress, persistent infection, immune dysregulation, and excessive exudate, all of which hinder effective healing. However, most current microneedle (MN) platforms overlook exudate management and real-time wound monitoring. Herein, we present a multifunctional hydrogel MN patch composed of gelatin methacryloyl (GM), polydopamine-coated cerium oxide nanozymes (P@C NPs), and nitrogen-doped carbon quantum dots (N-CDs).

[Clinical efficacy of Wenshen Chushi Decoction combined with LIPUS on erectile dysfunction with renal deficiency and phlegm-dampness syndrome].

Objective: To explore the clinical efficacy of Wenshen Chushi Decoction combined with low intensity pulsed ultrasound (LIPUS) on erectile dysfunction (ED) caused by renal deficiency and phlegm-dampness syndrome.

Methods: One hundred and twenty ED patients were included from the Department of Andrology in the First Hospital of Hunan University of Traditional Chinese Medicine. The patients in control group were treated with Wenshen Chushi Decoction.

tRNA modification profiling reveals epitranscriptome regulatory networks in Pseudomonas aeruginosa.

Transfer RNA (tRNA) modifications have emerged as critical post-transcriptional regulators of gene expression affecting diverse biological and disease processes. While there is extensive knowledge about the enzymes installing the dozens of post-transcriptional tRNA modifications-the tRNA epitranscriptome-very little is known about how metabolic, signaling, and other networks integrate to regulate tRNA modification levels. Here, we took a comprehensive first step at understanding epitranscriptome regulatory networks by developing a high-throughput tRNA isolation and mass spectrometry-based modification profiling platform and applying it to a Pseudomonas aeruginosa transposon insertion mutant library comprising 5746 strains.

Limitations of Current Machine-Learning Models in Predicting Enzymatic Functions for Uncharacterized Proteins.

Thirty to seventy percent of proteins in any given genome have no assigned function and have been labeled as the protein "unknome". This large knowledge shortfall is one of the final frontiers of biology. Machine-Learning (ML) approaches are enticing, with early successes demonstrating the ability to propagate functional knowledge from experimentally characterized proteins.

In vitro assessment of the osteogenic and antibacterial capabilities of Mg-MOF particles with encapsulated Levofloxacin within polydopamine.

Infectious bone defect is a condition where infection and bone defect occur simultaneously. The simultaneous achievement of effective antimicrobial management and enhanced bone regeneration continues to present a major hurdle in musculoskeletal therapeutics. To address these limitations, we have developed a novel osteoconductive material, this material (PDA@Mg-MOF-LEV) consists of Magnesium-based metal-organic frameworks (Mg-MOF) particles loaded with the antibiotic levofloxacin (LEV) and coated with polydopamine (PDA), which integrates photothermal therapy with antibiotic delivery to combat bacterial drug resistance and facilitate bone tissue regeneration.

Efficacy and safety of vertebroplasty versus posterior pedicle screw in treating stage III Kummell's disease without neurological deficits: A systematic review and meta-analysis.

ObjectiveThis study aimed to evaluate the efficacy and safety of vertebroplasty versus posterior pedicle screw fixation combined with vertebroplasty in treating stage III Kummell's disease without neurological deficits.MethodA systematic literature search was conducted across six databases. A meta-analysis of prospective and retrospective studies meeting the inclusion criteria was conducted using Review Manager 5.

The oncogene SLC35F2 is a high-specificity transporter for the micronutrients queuine and queuosine.

The nucleobase queuine (q) and its nucleoside queuosine (Q) are micronutrients derived from bacteria that are acquired from the gut microbiome and/or diet in humans. Following cellular uptake, Q is incorporated at the wobble base (position 34) of tRNAs that decode histidine, tyrosine, aspartate, and asparagine codons, which is important for efficient translation. Early studies suggested that cytosolic uptake of queuine is mediated by a selective transporter that is regulated by mitogenic signals, but the identity of this transporter has remained elusive.

Are Bacterial Processes Dependent on Global Ribosome Pausing Affected by tRNA Modification Defects?

By integrating a literature review with transcriptomic, proteomic, and phenotypic data from two model bacteria, Escherichia coli and Vibrio cholerae, we put forward the hypothesis that defects in tRNA modification broadly impact processes that are evolutionarily tuned to be sensitive to translation speed. These include the translation of regulatory proteins associated with motility, iron homeostasis, and leader peptide-driven attenuation mechanisms. Some of these translation speed-dependent processes are influenced by the absence of a single modification, while others are affected by the absence of multiple modifications.

A thiouracil desulfurase protects Clostridioides difficile RNA from 4-thiouracil incorporation, providing a competitive advantage in the gut.

Nucleotides are essential building blocks for major cellular macromolecules and are critical for life. Consequently, bacterial pathogens must acquire or synthesize nucleotides during infection. Clostridioides difficile is the most common hospital-acquired gastrointestinal infection, and nutrient acquisition is critical for pathogenesis.

Temporal dynamics and metagenomics of phosphorothioate epigenomes in the human gut microbiome.

Background: Epigenetic regulation of gene expression and host defense is well established in microbial communities, with dozens of DNA modifications comprising the epigenomes of prokaryotes and bacteriophage. Phosphorothioation (PT) of DNA, in which a chemically reactive sulfur atom replaces a non-bridging oxygen in the sugar-phosphate backbone, is catalyzed by dnd and ssp gene families widespread in bacteria and archaea. However, little is known about the role of PTs or other microbial epigenetic modifications in the human microbiome.

Network Pharmacology and Experiments to Verify the Effect and Potential Mechanism of Baicalein on Osteoporosis.

Background: Baicalein (BN), a potent flavonoid derived from scutellaria scutellaria, exhibits an array of noteworthy attributes, such as anti-inflammatory, antibacterial, and antipyretic properties. Furthermore, its potential in treating osteoporosis has been highlighted. Nonetheless, the exact modes of action responsible for its therapeutic effects remain obscure.

Efficacy and safety of Epimedium total flavonoids for primary osteoporosis: a systematic review and meta-analysis.

Background: Epimedium total flavonoids (EF) have been recommended to be one of the effective components in Traditional Chinese Medicine (TCM) for the treatment of primary osteoporosis (POP) in China. Due to the lack of evidence-based medical evidence on the efficacy and safety of EF for the treatment of POP, the current systematic review and meta-analysis was carried out aimed at evaluating the curative effects and safety profile of EF treatment for POP in order to provide decision making references for clinical research.

Methods: The PubMed, Cochrane Library, EMBASE, Web of Science, CNKI, Wanfang, and VIP databases were searched from the date of inception to 11 August 2024.

Queuosine salvage in Houston 1: a unique evolutionary path.

Queuosine (Q) stands out as the sole tRNA modification that can be synthesized via salvage pathways. Comparative genomic analyses identified specific bacteria that showed a discrepancy between the projected Q salvage route and the predicted substrate specificities of the two identified salvage proteins: (1) the distinctive enzyme tRNA guanine-34 transglycosylase (bacterial TGT, or bTGT), responsible for inserting precursor bases into target tRNAs; and (2) queuosine precursor transporter (QPTR), a transporter protein that imports Q precursors. Organisms such as the facultative intracellular pathogen , which possess only bTGT and QPTR but lack predicted enzymes for converting preQ to Q, would be expected to salvage the queuine (q) base, mirroring the scenario for the obligate intracellular pathogen .

HTF4 modulates the transcription of GID2 to promote the malignant biological behavior of pancreatic cancer.

Background: Helix-loop-helix transcription factor 4 (HTF4) as an anti-cancer target has been reported in many human cancers, but limited data exists regarding the effect of HTF4 in pancreatic cancer. In this study, we aimed to investigate the role of HTF4 in pancreatic cancer.

Methods: The expression levels of HTF4 in clinical pancreatic cancer samples were measured.

Exploring a unique class of flavoenzymes: Identification and biochemical characterization of ribosomal RNA dihydrouridine synthase.

Dihydrouridine (D), a prevalent and evolutionarily conserved base in the transcriptome, primarily resides in tRNAs and, to a lesser extent, in mRNAs. Notably, this modification is found at position 2449 in the 23S rRNA, strategically positioned near the ribosome's peptidyl transferase site. Despite the prior identification, in genome, of three dihydrouridine synthases (DUS), a set of NADPH and FMN-dependent enzymes known for introducing D in tRNAs and mRNAs, characterization of the enzyme responsible for D2449 deposition has remained elusive.

tRNA modification profiling reveals epitranscriptome regulatory networks in .

Transfer RNA (tRNA) modifications have emerged as critical posttranscriptional regulators of gene expression affecting diverse biological and disease processes. While there is extensive knowledge about the enzymes installing the dozens of post-transcriptional tRNA modifications - the tRNA epitranscriptome - very little is known about how metabolic, signaling, and other networks integrate to regulate tRNA modification levels. Here we took a comprehensive first step at understanding epitranscriptome regulatory networks by developing a high-throughput tRNA isolation and mass spectrometry-based modification profiling platform and applying it to a transposon insertion mutant library comprising 5,746 strains.

Limitations of Current Machine-Learning Models in Predicting Enzymatic Functions for Uncharacterized Proteins.

Unlabelled: Thirty to seventy percent of proteins in any given genome have no assigned function and have been labeled as the protein "unknome". This large knowledge shortfall is one of the final frontiers of biology. Machine-Learning (ML) approaches are enticing, with early successes demonstrating the ability to propagate functional knowledge from experimentally characterized proteins.

New-QiangGuYin-Containing Serum Inhibits Osteoclast-Derived Exosome Secretion and Down-Regulates Notum to Promote Osteoblast Differentiation.

New-QiangGuYin (N-QGY), the addition of sea buckthorn on the basis of QGY formula, is herbal formula widely used clinically in China for the treatment of osteoporosis (OP), but its mechanism warrants further exploration. The mechanisms of QGY and N-QGY in the treatment of OP are probed from the perspective of osteoclast-osteoblast balance. Thirty Sprague-Dawley rats are randomly divided into N-QGY group, QGY group, and Control group.

Phosphorothioate DNA modification by BREX Type 4 systems in the human gut microbiome.

Among dozens of microbial DNA modifications regulating gene expression and host defense, phosphorothioation (PT) is the only known backbone modification, with sulfur inserted at a non-bridging oxygen by and gene families. Here we explored the distribution of PT genes in 13,663 human gut microbiome genomes, finding that 6.3% possessed or genes predominantly in Bacillota, Bacteroidota, and Pseudomonadota.

PT-seq: A method for metagenomic analysis of phosphorothioate epigenetics in complex microbial communities.

Among dozens of known epigenetic marks, naturally occurring phosphorothioate (PT) DNA modifications are unique in replacing a non-bridging phosphate oxygen with redox-active sulfur and function in prokaryotic restriction-modification and transcriptional regulation. Interest in PTs has grown due to the widespread distribution of the , and genes among bacteria and archaea, as well as the discovery of PTs in 5-10% of gut microbes. Efforts to map PTs in complex microbiomes using existing next-generation and direct sequencing technologies have failed due to poor sensitivity.

Temporal dynamics and metagenomics of phosphorothioate epigenomes in the human gut microbiome.

Background: Epigenetic regulation of gene expression and host defense is well established in microbial communities, with dozens of DNA modifications comprising the epigenomes of prokaryotes and bacteriophage. Phosphorothioation (PT) of DNA, in which a chemically-reactive sulfur atom replaces a non-bridging oxygen in the sugar-phosphate backbone, is catalyzed by and gene families widespread in bacteria and archaea. However, little is known about the role of PTs or other microbial epigenetic modifications in the human microbiome.

Deciphering the Diversity in Bacterial Transporters That Salvage Queuosine Precursors.

Queuosine (Q) is a modification of the wobble base of tRNA harboring GUN anticodons with roles in decoding accuracy and efficiency. Its synthesis is complex with multiple enzymatic steps, and several pathway intermediates can be salvaged. The only two transporter families known to salvage Q precursors are QPTR/COG1738 and QrtT/QueT.

Biosynthesis and function of 7-deazaguanine derivatives in bacteria and phages.

SUMMARYDeazaguanine modifications play multifaceted roles in the molecular biology of DNA and tRNA, shaping diverse yet essential biological processes, including the nuanced fine-tuning of translation efficiency and the intricate modulation of codon-anticodon interactions. Beyond their roles in translation, deazaguanine modifications contribute to cellular stress resistance, self-nonself discrimination mechanisms, and host evasion defenses, directly modulating the adaptability of living organisms. Deazaguanine moieties extend beyond nucleic acid modifications, manifesting in the structural diversity of biologically active natural products.