Pathogenic Detection by Metagenomic Next-generation Sequencing in Skin and Soft Tissue Infection.

Background/aim: Skin and soft tissue infections (SSTIs) can be life-threatening, but the conventional bacterial cultures have low sensitivity and are time-consuming. Metagenomic next-generation sequencing (mNGS) is widely used as a diagnostic tool for detecting pathogens from infection sites. However, the use of mNGS for pathogen detection in SSTIs and related research is still relatively limited.

Exposure of antral follicles to medroxyprogesterone acetate during stimulation does not cause molecular perturbations in gonadotropin-responsiveness and steroidogenic function of granulosa cells in progestin-primed cycles.

Study Question: Does medroxyprogesterone acetate (MPA) exposure in progestin-primed ovarian stimulation (PPOS) cycles cause molecular perturbations in the steroidogenic function and gonadotropin responsiveness of the granulosa cells?

Summary Answer: PPOS cycles are identical to traditional GnRH antagonist cycles not only for clinical IVF characteristics but also for gonadotropin receptor expression, response to gonadotropins, and steroidogenic function at the molecular level.

What Is Known Already: PPOS is increasingly used as an alternative to GnRH antagonists due to the inhibitory effect of progesterone on LH release by reducing GnRH pulsatility at the hypothalamic level. Although a growing body of evidence from clinical studies did not indicate significant differences between PPOS and antagonist protocols for IVF cycle characteristics and obstetrical outcomes, it is still unknown whether exposure of the antral follicle cohort to progesterone or its synthetic derivatives during ovarian stimulation causes any subtle molecular aberrations in terms of steroidogenesis and gonadotropin responsiveness.

Prostate cancer stem cells and their targeted therapies.

Prostate cancer (PCa) is the most common malignancy among men worldwide. Through androgen receptor signaling inhibitor (ARSI) treatment, patients eventually succumb to castration-resistant prostate cancer (CRPC). For this, the prostate cancer stem cells (PCSCs), as a minor population of tumor cells that can promote tumor relapse, ARSI resistance, and disease progression, are gaining attention.

Targeted agents plus CHOP compared with CHOP as the first-line treatment for newly diagnosed patients with peripheral T-cell lymphoma (GUIDANCE-03): an open-label, multicentre phase 2 clinical trial.

Background: Peripheral T-cell lymphoma (PTCL) is a heterogeneous disease with dismal outcomes. We conducted an open-label, phase 2 nonrandomised, externally controlled study to evaluate the efficacy and safety of targeted agents plus CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisolone) (CHOPX) for PTCL in the front-line setting.

Methods: Eligible patients were ≥18 years of age and newly diagnosed PTCL.

Rationally reprogramming single-cell aging trajectories and lifespan through dynamic modulation of environmental inputs.

How do variations in nutrient levels influence cellular lifespan? A dynamical systems model of a core circuit involved in yeast aging suggests principles underlying lifespan extension observed at static and alternating glucose levels that are reminiscent of intermittent fasting regimens.

Unveiling hidden connections in omics data via pyPARAGON: an integrative hybrid approach for disease network construction.

Network inference or reconstruction algorithms play an integral role in successfully analyzing and identifying causal relationships between omics hits for detecting dysregulated and altered signaling components in various contexts, encompassing disease states and drug perturbations. However, accurate representation of signaling networks and identification of context-specific interactions within sparse omics datasets in complex interactomes pose significant challenges in integrative approaches. To address these challenges, we present pyPARAGON (PAgeRAnk-flux on Graphlet-guided network for multi-Omic data integratioN), a novel tool that combines network propagation with graphlets.

NanoLuciferase technology-based detection of TMPRSS2 as attempt to develop anti-coronavirus agents.

•Utilized NanoBiT technology for high-throughput screening.•Identified compounds reducing TMPRSS2 expression, a crucial step for SARS-CoV-2 entry.•Explored a broad range of compound libraries.

variants cause a phenotypic spectrum from early-onset Parkinson's disease to perinatal lethality by disrupting mitochondrial pathways.

Dissecting biological pathways highlighted by Mendelian gene discovery has provided critical insights into the pathogenesis of Parkinson's disease (PD) and neurodegeneration. This approach ultimately catalyzes the identification of potential biomarkers and therapeutic targets. Here, we identify as a new gene implicated in PD and childhood neurodegeneration.

Active Magnesium Boride/Alginate Hydrogels Rejuvenate Senescent Cells.

The clearance of senescent cells may be detrimental to low cell density diseases, such as intervertebral disc degeneration (IVDD), and rejuvenating these cells presents a formidable obstacle. In this study, we investigate a mild-alkalization strategy employing magnesium boride-alginate (MB-ALG) hydrogels to rejuvenate senescent cells associated with age-related diseases. MB-ALG hydrogels proficiently ensnare senescent cells owing to their surface roughness.

Synergistic delivery of hADSC-Exos and antioxidants has inhibitory effects on UVB-induced skin photoaging.

Ultraviolet B (UVB) light exposure accelerates skin photoaging. Human adipose-derived stem cell exosomes (hADSC-Exos) and some antioxidants may have anti-photoaging effects. However, it is unknown whether the combination of hADSC-Exos and antioxidants plays a synergistic role in anti-photoaging.

Repeat administration of human umbilical cord mesenchymal stem cells improves left ventricular diastolic function in mice with heart failure with preserved ejection fraction.

Currently, no therapy is proven to effectively improve heart failure with preserved ejection fraction (HFpEF). Although stem cell therapy has demonstrated promising results in treating ischemic heart disease, the effectiveness of treating HFpEF with human umbilical cord mesenchymal stem cells (hucMSCs) remains unclear. To answer this question, we administered hucMSCs intravenously (i.

Evidence of Mitophagy in Lens Capsule Epithelial Cells of Patients with Pseudoexfoliation Syndrome.

Prcis: Alterations in the PINK-mediated mitophagy pathway play an important role in PEX disease.

Purpose: Pseudoexfoliation Syndrome (PEX) is a condition in which aberrant fibrillary protein builds up in various components of the eye and other extraocular tissues. In this study, we aim to investigate the functionality of intracellular auto-degradative machinery -especially mitophagy- and related genes and proteins in PEX.

Effect of nocturia in patients with different severity of obstructive sleep apnea on polysomnography: A retrospective observational study.

Objective: Obstructive sleep apnea (OSA) is one of the etiologies of nocturia. We analyzed polysomnography (PSG) results to determine correlated factors related to nocturia in OSA patients with different severity.

Methods: Patients with suspected OSA were examined using PSG.

Effect of Parental Severe Mental Disorders on the Timing of Autism Diagnosis: A Family Linkage Study.

The mean diagnosis age of autism was about 5 years in Taiwan. Whether the delayed diagnosis of autism (≥ 6 years) was associated with parental severe mental disorders remained unknown. The parents of 22,859 autistic individuals and 228,590 age- and sex-matched nonautistic individuals were assessed for the presence of severe mental disorders (schizophrenia, bipolar disorder, major depressive disorder, alcohol use disorder, and substance use disorder).

Phase separation of PML/RARα and BRD4 coassembled microspeckles governs transcriptional dysregulation in acute promyelocytic leukemia.

In acute promyelocytic leukemia (APL), the promyelocytic leukemia-retinoic acid receptor alpha (PML/RARα) fusion protein destroys PML nuclear bodies (NBs), leading to the formation of microspeckles. However, our understanding, largely learned from morphological observations, lacks insight into the mechanisms behind PML/RARα-mediated microspeckle formation and its role in APL leukemogenesis. This study presents evidence uncovering liquid-liquid phase separation (LLPS) as a key mechanism in the formation of PML/RARα-mediated microspeckles.

Arsenic trioxide and p97 inhibitor synergize against acute myeloid leukemia by targeting nascent polypeptides and activating the ZAKα-JNK pathway.

Arsenic trioxide (ATO) has exhibited remarkable efficacy in treating acute promyelocytic leukemia (APL), primarily through promoting the degradation of the PML-RARα fusion protein. However, ATO alone fails to confer any survival benefit to non-APL acute myeloid leukemia (AML) patients and exhibits limited efficacy when used in combination with other agents. Here, we explored the general toxicity mechanisms of ATO in APL and potential drugs that could be combined with ATO to exhibit synergistic lethal effects on other AML.

Osteoporosis in Relation to a Bone-Related Aging Biomarker Derived from the Urinary Proteomic Profile: A Population Study.

Screening for and prevention of osteoporosis and osteoporotic fractures is imperative, given the high burden on individuals and society. This study constructed and validated an aging-related biomarker derived from the urinary proteomic profile (UPP) indicative of osteoporosis (UPPost-age). In a prospective population study done in northern Belgium (1985-2019), participants were invited for a follow-up examination in 2005-2010 and participants in the 2005-2010 examination again invited in 2009-2013.