Pyruvate Abundance Confounds Aminoglycoside Killing of Multidrug-Resistant Bacteria via Glutathione Metabolism.

To explore whether the metabolic state reprogramming approach may be used to explore previously unknown metabolic pathways that contribute to antibiotic resistance, especially those that have been neglected in previous studies, pyruvate reprogramming was performed to reverse the resistance of multidrug-resistant . Surprisingly, we identified a pyruvate-regulated glutathione system that occurs by boosting glycine, serine, and threonine metabolism. Moreover, cysteine and methionine metabolism played a key role in this reversal.

Authors' reply to comments on "Improved photostability, solubility, hygroscopic stability and antimicrobial activity of fleroxacin by synthesis of fleroxacin-D-tartaric acid pharmaceutical salt".

This article responds to Dr. Shayanfar's comment "Improvement of photostability, solubility, hygroscopic stability and antimicrobial activity of fleroxacin by synthesizing fleroxacin-D-tartaric acid pharmaceutical salt". We rationalized and explained the solubility study portion of the published novel pharmaceutical salt (fleroxacin-D-tartaric acid, FL-D-TT).

Eukaryotic translation initiation factor 6-mediated ribosome biogenesis promotes synovial aggression and inflammation by increasing the translation of SP1 in rheumatoid arthritis.

Introduction: Fibroblast-like synoviocytes (FLSs) play critical roles in synovial inflammation and aggression in rheumatoid arthritis (RA). Here, we explored the role of eukaryotic translation initiation factor 6 (eIF6) in regulating the biological behaviors of FLSs from patients with RA.

Methods: FLSs were isolated from the synovial tissues of RA patients.

Label-free quantitative proteomic analysis of functional changes of goat milk whey proteins subject to heat treatments of ultra-high-temperature and the common low-temperature.

This work investigated the functional changes in whey proteins obtained from goat milk subject to various temperature treatments. Ultra-high temperature instantaneous sterilization (UHTIS) caused less damage than the common low-temperature, whereas spray-drying treatment had the opposite effect. A total of 426 proteins were identified in UHTIS and control treatment groups, including 386 common proteins and 16 and 14 unique proteins.

Lipid Hydrolysis, Oxidation, and Fatty Acid Formation Pathway Mapping of Synergistically Fermented Sausage and Characterization of Lipid Mediating Genes.

Starter cultures play a significant role in lipid hydrolysis, prevention of lipid oxidation, and synthesis of fatty acid in fermented sausage, enhancing product quality. In this study, five synergistic bacterial strains were used, including (B-3), DLS-24 (D-24), DLS-29 (D-29), (B-1), and (B-2). Sausage B1B3D24 gave the highest free fatty acid with 39.

Using four-point subcutaneous injection of lymphatic contrast-enhanced ultrasound to diagnose lymphedema of lower extremity.

Background: The diagnosis of lymphedema primarily relies on the clinical symptoms, signs, medical history and imaging. Objective lymphatic imaging helps improving the diagnosis of lymphedema. This study aimed to develop an effective imaging tool to diagnose lymphedema.

Indoxyl sulfate exacerbates alveolar bone loss in chronic kidney disease through ferroptosis.

Objectives: The purpose of this study was to determine whether indoxyl sulfate (IS) is involved in alveolar bone deterioration and to elucidate the mechanism underlying alveolar bone loss in chronic kidney disease (CKD) patients.

Materials And Methods: Mice were divided into the control group, CP group (ligature-induced periodontitis), CKD group (5/6 nephrectomy), and CKD + CP group. The concentration of IS in the gingival crevicular fluid (GCF) was determined by HPLC.

C2H2 zinc finger protein PagIDD15A regulates secondary wall thickening and lignin biosynthesis in poplar.

Wood production is largely determined by the activity of cambial cell proliferation, and the secondary cell wall (SCW) thickening of xylem cells determines the wood property. In this study, we identified an INDETERMINATE DOMAIN (IDD) type C2H2 zinc finger transcription factor PagIDD15A as a regulator of wood formation in Populus alba × Populus glandulosa. Downregulation of PagIDD15A expression by RNA interference (RNAi) inhibited xylem development and xylem cell secondary wall thickening.

PagJAZ5 regulates cambium activity through coordinately modulating cytokinin concentration and signaling in poplar.

Wood is resulted from the radial growth paced by the division and differentiation of vascular cambium cells in woody plants, and phytohormones play important roles in cambium activity. Here, we identified that PagJAZ5, a key negative regulator of jasmonate (JA) signaling, plays important roles in enhancing cambium cell division and differentiation by mediating cytokinin signaling in poplar 84K (Populus alba × Populus glandulosa). PagJAZ5 is preferentially expressed in developing phloem and cambium, weakly in developing xylem cells.

SCG5 and MITF may be novel markers of copper metabolism immunorelevance in Alzheimer's disease.

The slow-developing neurological disorder Alzheimer's disease (AD) has no recognized etiology. A bioinformatics investigation verified copper metabolism indicators for AD development. GEO contributed AD-related datasets GSE1297 and GSE5281.

Attenuates Virulence upon Oxytetracycline Resistance.

The relationship between antibiotic resistance and bacterial virulence has not yet been fully explored. Here, we use as the research model to investigate the proteomic change upon oxytetracycline resistance (LTB4-R). Compared to oxytetracycline-sensitive (LTB4-S), LTB4-R has 234 differentially expressed proteins, of which the abundance of 84 proteins is downregulated and 15 proteins are enriched to the Type III secretion system, Type VI secretion system, and flagellum pathways.

α-Ketoglutarate downregulates thiosulphate metabolism to enhance antibiotic killing.

Potentiation of the effects of currently available antibiotics is urgently required to tackle the rising antibiotics resistance. The pyruvate (P) cycle has been shown to play a critical role in mediating aminoglycoside antibiotic killing, but the mechanism remains unexplored. In this study, we investigated the effects of intermediate metabolites of the P cycle regarding the potentiation of gentamicin.

PagMYB180 regulates adventitious rooting via a ROS/PCD-dependent pathway in poplar.

The formation of adventitious roots (AR) is an essential step in the vegetative propagation of economically woody species. Reactive oxygen species (ROS) function as signaling molecules in regulating root growth and development. Here, we identified an R2R3-MYB transcription factor PagMYB180 as a regulator of AR formation in hybrid poplar (Populus alba × Populus glandulosa).

Acod1/itaconate activates Nrf2 in pulmonary microvascular endothelial cells to protect against the obesity-induced pulmonary microvascular endotheliopathy.

Background: Obesity is the main risk factor leading to the development of various respiratory diseases, such as asthma and pulmonary hypertension. Pulmonary microvascular endothelial cells (PMVECs) play a significant role in the development of lung diseases. Aconitate decarboxylase 1 (Acod1) mediates the production of itaconate, and Acod1/itaconate axis has been reported to play a protective role in multiple diseases.

NAT10 promotes synovial aggression by increasing the stability and translation of N4-acetylated PTX3 mRNA in rheumatoid arthritis.

Objective: Recent studies indicate that N-acetyltransferase 10 (NAT10)-mediated ac4C modification plays unique roles in tumour metastasis and immune infiltration. This study aimed to uncover the role of NAT10-mediated ac4C in fibroblast-like synoviocytes (FLSs) functions and synovial immune cell infiltration in rheumatoid arthritis (RA).

Methods: FLSs were obtained from active established patients with RA.

Coptisine inhibits aggressive and proliferative actions of fibroblast like synoviocytes and exerts a therapeutic potential for rheumatoid arthritis.

Objective: Coptisine, a natural bioactive small molecular compound extracted from traditional Chinese herb Coptis chinensis, has been shown to exhibit anti-tumor effect. However, its contribution to autoimmune diseases such as rheumatoid arthritis (RA) is unknown. Here, we evaluate the effect of coptisine in controlling fibroblast-like synoviocytes (FLS)-mediated synovial proliferation and aggression in RA and further explore its underlying mechanism(s).

Engineered exosomes mediated targeted delivery of neuroprotective peptide NR2B9c for the treatment of traumatic brain injury.

Neuroprotection is one of the core treatment strategies for brain injuries including traumatic brain injury (TBI). NR2B9c is a promising neuroprotective peptide but its clinical translation is limited because of poor brain penetrability. Exosomes are naturally occurring nanovesicles having therapeutic potential for TBI as well as an efficient drug delivery carrier to the brain.

A role of TRIM59 in pulmonary hypertension: modulating the protein ubiquitylation modification.

Background: Pulmonary hypertension (PH), an infrequent disease, is characterized by excessive pulmonary vascular remodeling and proliferation of pulmonary artery smooth muscle cells (PASMCs). However, its underlying molecular mechanisms remain unclear. Uncovering its molecular mechanisms will be beneficial to the treatment of PH.

CXCL10 May Be Responsible for Susceptibility to Pulmonary Embolism in COVID-19 Patients.

Background: Although the potential of coronavirus disease 2019 (COVID-19) patients to develop pulmonary embolism (PE) is widely recognized, the underlying mechanism has not been completely elucidated. This study aimed to identify genes common to COVID-19 and PE to reveal the underlying pathogenesis of susceptibility to PE in COVID-19 patients.

Methods: COVID-19 genes were obtained from the GEO database and the OMIM, CTD, GeneCards, and DisGeNET databases; PE genes were obtained from the OMIM, CTD, GeneCards, and DisGeNET databases.

Untargeted metabolite profiling of serum in rats exposed to pyrraline.

Unlabelled: Pyrraline, one of advanced glycation end-products, is formed in advanced Maillard reactions. It was reported that the presence of pyrraline was tested to be associated with nephropathy and diabetes. Pyrraline might result in potential health risks because many modern diets are heat processed.

ALKBH5-Mediated RNA m A Methylation Regulates the Migration, Invasion, and Proliferation of Rheumatoid Fibroblast-Like Synoviocytes.

Objective: Fibroblast-like synoviocytes (FLSs) are critical for promoting joint damage in rheumatoid arthritis (RA). N -methyladenosine (m A) modification plays key roles in various diseases, but its role in the pathogenesis of RA is largely unknown. Here, we investigate increased demethylase ALKBH5 promotion of proliferation, migration, and invasion of RA FLSs via regulating JARID2 expression.

Schisandrin treatment suppresses the proliferation, migration, invasion, and inflammatory responses of fibroblast-like synoviocytes from rheumatoid arthritis patients and attenuates synovial inflammation and joint destruction in CIA mice.

Background: Rheumatoid arthritis (RA) is a systemic autoimmune disease causing joint dysfunction. As disease-modifying anti-rheumatic drugs (DMARDs) have poor efficacy in 20% to 25% of RA patients, additional novel RA medications are urgently needed. Schisandrin (SCH) has multiple therapeutic effects.