Perspective: Pathological transdifferentiation-a novel therapeutic target for cardiovascular diseases and chronic inflammation.

Pathological transdifferentiation, where differentiated cells aberrantly transform into other cell types that exacerbate disease rather than promote healing, represents a novel and significant concept. This perspective discusses its role and potential targeting in cardiovascular diseases and chronic inflammation. Current therapies mainly focus on mitigating early inflammatory response through proinflammatory cytokines and pathways targeting, including corticosteroids, TNF-α inhibitors, IL-1β monoclonal antibodies and blockers, IL-6 blockers, and nonsteroidal anti-inflammatory drugs (NSAIDs), along with modulating innate immune memory (trained immunity).

Sequential Transfer of Blastocysts on Day 5 and Day 6 in Patients with Repeated Implantation Failure in Frozen Embryo Transfer Cycle.

The aim of this study was to evaluate which frozen embryo transfer (FET) strategy benefits the recurrent implantation failure (RIF) population. A retrospective study of 336 women with RIF was performed from July 2020 to October 2023. The patients were divided into three groups according to the FET protocol.

Associations of Ureaplasma urealyticum infection with male infertility and intrauterine insemination outcomes.

Ureaplasma urealyticum (UU) is one of the most commonly occurring pathogens associated with genital tract infections in infertile males, but the impact of seminal UU infection in semen on intrauterine insemination (IUI) outcomes is poorly understood. We collected data from 245 infertile couples who underwent IUI at The First Affiliated Hospital of USTC (Hefei, China) between January 2021 and January 2023. The subjects were classified into two groups according to their UU infection status: the UU-positive group and the UU-negative group.

pH responsive and zwitterionic micelle for enhanced cellular uptake and antitumor performance.

The side effects of small molecule chemotherapeutic drugs (SMCD) have brought great pain to the cancer patients. Many nanodrug carriers can relieve the shortcomings of SMCD, but they have complex synthesis processes and lack biodegradability. To overcome both problems, we synthesized a pH responsive biodegradable zwitterionic molecules (EK-D) by linking zwitterionic polypeptide (EK7) and dodecyl acrylate through a simple click reaction.

A homozygous nonsense variant in HENMT1 causes male infertility in humans and mice.

Background: HENMT1 encodes a small RNA methyltransferase that plays a crucial role in mouse spermatogenesis through the methylation of the 3' end of PIWI-interacting RNAs.

Objectives: Our study aims to elucidate the relationship between HENMT1 and male infertility in humans.

Materials And Methods: A consanguineous family, having a single non-obstructive azoospermia patient was recruited for pathogenic variants screening.

CCDC181 is required for sperm flagellum biogenesis and male fertility in mice.

The structural integrity of the sperm flagellum is essential for proper sperm function. Flagellar defects can result in male infertility, yet the precise mechanisms underlying this relationship are not fully understood. CCDC181, a coiled-coil domain-containing protein, is known to localize on sperm flagella and at the basal regions of motile cilia.

A new paradigm in intracellular immunology: Mitochondria emerging as leading immune organelles.

Mitochondria, traditionally recognized as cellular 'powerhouses' due to their pivotal role in energy production, have emerged as multifunctional organelles at the intersection of bioenergetics, metabolic signaling, and immunity. However, the understanding of their exact contributions to immunity and inflammation is still developing. This review first introduces the innovative concept of intracellular immunity, emphasizing how mitochondria serve as critical immune signaling hubs.

Antagonist anti-LIF antibody derived from naive human scFv phage library inhibited tumor growth in mice.

Background: Leukemia inhibitory factor (LIF) is a multifunctional member of the IL-6 cytokine family that activates downstream signaling pathways by binding to the heterodimer consisting of LIFR and gp130 on the cell surface. Previous research has shown that LIF is highly expressed in various tumor tissues (e.g.

Association of redundant foreskin with sexual dysfunction: a cross-sectional study from 5700 participants.

A previous study showed that the length of the foreskin plays a role in the risk of sexually transmitted infections and chronic prostatitis, which can lead to poor quality of sexual life. Here, the association between foreskin length and sexual dysfunction was evaluated. A total of 5700 participants were recruited from the andrology clinic at The First Affiliated Hospital of University of Science and Technology of China (Hefei, China).

Histone demethylase KDM2A recruits HCFC1 and E2F1 to orchestrate male germ cell meiotic entry and progression.

In mammals, the transition from mitosis to meiosis facilitates the successful production of gametes. However, the regulatory mechanisms that control meiotic initiation remain unclear, particularly in the context of complex histone modifications. Herein, we show that KDM2A, acting as a lysine demethylase targeting H3K36me3 in male germ cells, plays an essential role in modulating meiotic entry and progression.

Strengthening an Intramolecular Non-Classical Hydrogen Bond to Get in Shape for Binding.

In this research article, we report on the strengthening of a non-classical hydrogen bond (C-H⋅⋅⋅O) by introducing electron withdrawing groups at the carbon atom. The approach is demonstrated on the example of derivatives of the physiological E-selectin ligand sialyl Lewis (1, sLe). Its affinity is mainly due to a beneficial entropy term, which is predominantly caused by the pre-organization of sLe in its binding conformation.

SARS-CoV-2 Vaccination Improves Semen Quality in Men Recovered From COVID-19: A Retrospective Cohort Study.

Coronavirus disease 2019 (COVID-19) has been reported to decrease semen quality in reproductive-age men. Semen quality in vaccinated men after SARS-CoV-2 infection remains unclear. We recruited reproductive-age Chinese men scheduled for COVID-19 vaccination from December 2022 to March 2023.

Caspase-4/11 promotes hyperlipidemia and chronic kidney disease-accelerated vascular inflammation by enhancing trained immunity.

To determine whether hyperlipidemia and chronic kidney disease (CKD) have a synergy in accelerating vascular inflammation via trained immunity (TI), we performed aortic pathological analysis and RNA-Seq of high-fat diet-fed (HFD-fed) 5/6 nephrectomy CKD (HFD+CKD) mice. We made the following findings: (a) HFD+CKD increased aortic cytosolic LPS levels, caspase-11 (CASP11) activation, and 998 gene expressions of TI pathways in the aorta (first-tier TI mechanism); (b) CASP11-/- decreased aortic neointima hyperplasia, aortic recruitment of macrophages, and casp11-gasdermin D-mediated cytokine secretion; (c) CASP11-/- decreased N-terminal gasdermin D (N-GSDMD) membrane expression on aortic endothelial cells and aortic IL-1B levels; (d) LPS transfection into human aortic endothelial cells resulted in CASP4 (human)/CASP11 (mouse) activation and increased N-GSDMD membrane expression; and (e) IL-1B served as the second-tier mechanism underlying HFD+CKD-promoted TI. Taken together, hyperlipidemia and CKD accelerated vascular inflammation by promoting 2-tier trained immunity.

A novel homozygous missense TTC12 variant identified in an infertile Pakistani man with severe oligoasthenoteratozoospermia and primary ciliary dyskinesia.

TTC12 is a cytoplasmic and centromere-localized protein that plays a role in the proper assembly of dynein arm complexes in motile cilia in both respiratory cells and sperm flagella. This finding underscores its significance in cellular motility and function. However, the wide role of TTC12 in human spermatogenesis-associated primary ciliary dyskinesia (PCD) still needs to be elucidated.