NAE1-mediated neddylation coordinates ubiquitination regulation of meiotic recombination during spermatogenesis.

Meiotic homologous recombination is a critical event in gametogenesis, which is tightly regulated to ensure the generation of crossovers on homologous chromosomes. This process is crucial for ensuring the accurate segregation of genetic material and maintaining genetic diversity within species, ultimately contributing to reproductive success. Nevertheless, comprehensive mechanisms of post-translational modification (PTM) regulating homologous recombination during meiosis require further investigation.

Precise amplification-free detection of highly structured RNA with an enhanced SCas12a assay.

The CRISPR/Cas12a system has revolutionized molecular diagnostics, yet the direct detection of RNA, particularly those with complex structures, remains a significant challenge. Here, we present an updated SCas12a system, termed SCas12aV2, which enables precise, amplification-free detection of highly structured RNA molecules. By optimizing the length of scaffold RNA, targeting asymmetric structures, and utilizing dsDNA-ssDNA hybrid activators, we have significantly reduced steric hindrance in the detection system, thereby markedly enhancing both sensitivity and kinetics compared to traditional DNA activators.

NAT10-mediated mRNA -acetylation is essential for the translational regulation during oocyte meiotic maturation in mice.

The precise translational regulation of maternal messenger RNAs (mRNAs) drives mammalian oocyte maturation. However, the function and mechanism of posttranscriptional chemical modifications, especially the newly identified -acetylcytidine (acC) modification catalyzed by -acetyltransferase 10 (NAT10), are unknown. In this study, we developed a low-input acC sequencing technology, acC LACE-seq, and mapped 8241 acC peaks at the whole-transcriptome level using 50 mouse oocytes at the germinal vesicle stage.

Thermally adaptive iohexol-loaded microcages for local computerized tomography.

As one of the most used non-invasive imaging modalities, X-ray computed tomography (CT) has many outstanding advantages, but its wide application is still limited owing to various defects of its contrast agents, such as their short retention time, non-specific distribution, and potential nephrotoxicity. Herein, a non-ionic poly(acrylamide--acrylonitrile) copolymer with an upper critical solution temperature (UCST) was utilized to construct novel thermo-responsive microcages (MCs) with a hydrodynamic size of 5-10 μm, which is slightly less than the diameter of a blood vessel, for targeted CT imaging. These MCs exhibited excellent thermo-responsive capability, featuring the appropriate UCST value between 35-40 °C.

The numbers of biopsied cells in routine clinical process of preimplantation genetic testing (PGT) do not affect the pregnancy outcomes of embryos.

Study Question: Does the number of biopsied trophectoderm cells sampled for preimplantation genetic testing for monogenic disease (PGT-M) affect subsequent clinical outcomes for those selected embryos?

Summary Answer: The number of biopsied cells does not affect the pregnancy outcome of preimplantation genetically tested embryos.

What Is Known Already: The successful execution of PGT relies on the availability of a certain number of high-quality biopsied cells. Evidence in the literature has reported that blastocyst biopsies may have a negative impact on clinical outcomes.

A new phase of China-ASEAN health cooperation: the China-ASEAN Beijing Declaration on Cooperation in Innovation of Health Products and Technologies.

Utilizing innovative methods to advance the research and development (R&D) of health products and enhance their accessibility has become crucial to achieving universal health coverage, addressing public health emergencies, and promoting population health and wellbeing. However, structural contradictions do exist in the supply and demand of health products in the Association of Southeast Asian Nations (ASEAN). With the joint support of the Ministry of Science and Technology of China, the Ministry of Education, and the China-ASEAN Center, Peking University established the China-ASEAN Science and Technology Cooperation Center for Public Health in April 2023.

Allelic transcriptomic profiling identifies the role of PRD-like homeobox genes in human embryonic-cleavage-stage arrest.

Cleavage-stage arrest in human embryos substantially limits the success rate of infertility treatment, with maternal-to-zygotic transition (MZT) abnormalities being a potential contributor. However, the underlying mechanisms and regulators remain unclear. Here, by performing allelic transcriptome analysis on human preimplantation embryos, we accurately quantified MZT progression by allelic ratio and identified a fraction of 8-cell embryos, at the appropriate developmental time point and exhibiting normal morphology, were in transcriptionally arrested status.

The intestinal fungus Aspergillus tubingensis promotes polycystic ovary syndrome through a secondary metabolite.

Polycystic ovary syndrome (PCOS) affects 6%-10% of women of reproductive age and is known to be associated with disruptions in the gut bacteria. However, the role of the gut mycobiota in PCOS pathology remains unclear. Using culture-dependent and internal transcribed spacer 2 (ITS2)-sequencing methods, we discovered an enrichment of the gut-colonizable fungus Aspergillus tubingensis in 226 individuals, with or without PCOS, from 3 different geographical areas within China.

Artificial Intelligence-Powered Training Database for Clinical Thinking: App Development Study.

Background: With the development of artificial intelligence (AI), medicine has entered the era of intelligent medicine, and various aspects, such as medical education and talent cultivation, are also being redefined. The cultivation of clinical thinking abilities poses a formidable challenge even for seasoned clinical educators, as offline training modalities often fall short in bridging the divide between current practice and the desired ideal. Consequently, there arises an imperative need for the expeditious development of a web-based database, tailored to empower physicians in their quest to learn and hone their clinical reasoning skills.

On the probability of necessity and sufficiency of explaining Graph Neural Networks: A lower bound optimization approach.

The explainability of Graph Neural Networks (GNNs) is critical to various GNN applications, yet it remains a significant challenge. A convincing explanation should be both necessary and sufficient simultaneously. However, existing GNN explaining approaches focus on only one of the two aspects, necessity or sufficiency, or a heuristic trade-off between the two.

Recent advances in spatiotemporal control of the CRISPR/Cas9 system.

The CRISPR/Cas9 gene-editing technology, derived from the adaptive immune mechanisms of bacteria, has demonstrated remarkable advantages in fields such as gene function research and the treatment of genetic diseases due to its simplicity in design, precise targeting, and ease of use. Despite challenges such as off-target effects and cytotoxicity, effective spatiotemporal control strategies have been achieved for the CRISPR/Cas9 system through precise regulation of Cas9 protein activity as well as engineering of guide RNAs (gRNAs). This review provides a comprehensive analysis of the core components and functional mechanisms underlying the CRISPR/Cas9 system, highlights recent advancements in spatiotemporal control strategies, and discusses future directions for development.

Magnetic Nanocarriers for pH/GSH/NIR Triple-Responsive Drug Release and Synergistic Therapy in Tumor Cells.

In this study, the mesoporous FeO nanodrug carriers containing disulfide bonds (CHO-SMNPs) were successfully synthesized and characterized. Doxorubicin (DOX) was loaded onto the CHO-SMNPs as a model drug and gatekeeper through the formation of imine bonds with the aldehyde groups on the surface of the mesoporous materials. This drug carrier demonstrates effective drug release triggered by pH, glutathione (GSH), and near-infrared (NIR) light, along with satisfactory photothermal conversion efficiency under NIR irradiation at 808 nm.

Bile acids in follicular fluid: potential new therapeutic targets and predictive markers for women with diminished ovarian reserve.

Objective: To investigate the changes in bile acid (BA) metabolites within the follicular fluid (FF) of patients with diminished ovarian reserve (DOR) and to identify novel diagnostic markers that could facilitate early detection and intervention in DOR patients.

Design: A total of 182 patients undergoing assisted reproductive technology (ART) were enrolled and categorized into the normal ovarian reserve (NOR) group (n = 91) or the DOR group (n = 91) to measure BA levels in FF. To identify the changes in granulosa cells (GCs), we collected GCs from an additional 7 groups of patients for transcriptome sequencing.

Epidemiological investigation of adult emergency infusion adverse drug reactions (EIADR) in Nanjing, China: a prospective cross-sectional study (EIADR II).

Objective: To analyze the clinical characteristics of adverse drug reactions (ADRs) in adults receiving emergency infusions at a tertiary hospital.

Methods: We conducted a prospective observational cohort study involving 585 adult patients who experienced adverse drug reactions (ADRs) between 20 November 2019, and 20 November 2023, during intravenous infusions in the emergency infusion room of a tertiary hospital. The analysis included patients' gender, age, type of drugs involved, organ-system involvement, clinical manifestations of ADRs, severity grading of ADRs, and preventability of ADRs.

π-HuB: the proteomic navigator of the human body.

The human body contains trillions of cells, classified into specific cell types, with diverse morphologies and functions. In addition, cells of the same type can assume different states within an individual's body during their lifetime. Understanding the complexities of the proteome in the context of a human organism and its many potential states is a necessary requirement to understanding human biology, but these complexities can neither be predicted from the genome, nor have they been systematically measurable with available technologies.

Fine particulate matter and ovarian health: A review of emerging risks.

Fine particulate matter (PM) pollution has raised significant public concerns, especially for vulnerable populations. Studies have indicated the association between PM and ovarian disorders, although the mechanisms underlying the effects have not yet been fully elucidated. In this review, we elucidated three main conditions pertaining to ovarian function that may result from exposure to PM diminished ovarian reserve, polycystic ovary syndrome, and infertility.

Clinical spectrum and molecular basis in 19 Chinese patients with 46, XY disorder of sexual development caused by NR5A1 mutations.

Background: Nuclear receptor subfamily 5 group A member 1 (NR5A1) plays pivotal roles in steroidogenesis and gonadal development. 46, XY disorder of sexual development (DSD) caused by NR5A1 mutations is a rare genetic condition. This study aimed to provide a comprehensive analysis of the clinical characteristics and molecular defects observed in 19 Chinese patients with NR5A1 variants, including assessing the deleterious effects of novel variants in vitro and evaluating their functional impact on the gonad and adrenal glands in vivo.

Outcomes of subsequent IVF cycles among women with PCOS after the first unstimulated IVM treatment: a single-center matched retrospective case-control study.

Objective: maturation (IVM) is an advanced technique and an alternative to conventional fertilization (IVF). It is safe, effective, and cost-effective in patients with polycystic ovary syndrome (PCOS). However, no clinical guidelines state that IVM could work without compromised pregnancy outcomes in patients with PCOS.

Analytical prediction of electromagnetic performance for surface-embedded permanent magnet in-wheel machines considering iron's nonlinearity.

Accurate magnetic field calculation is the premise of electromagnetic performance prediction. Conventional subdomain (SD) techniques assume that the iron's relative permeability is infinite, leading to falsely overestimated flux density. We propose an accurate magnetic field analytical model for permanent magnet (PM) in-wheel machines considering iron's magnetization nonlinearity and saturation.

One fresh cleavage-stage single embryo transfer (SET) plus one frozen-thawed blastocyst-stage SET or one fresh cleavage-stage double embryo transfer? A retrospective matched cohort study.

Study Question: Are there significant differences in fertility outcomes between transferring two cleavage-stage embryos in a single fresh cycle and transferring one cleavage-stage embryo in a fresh cycle and one blastocyst-stage embryo in the subsequent frozen-thawed cycle?

Summary Answer: In women aged <38 years with two embryos available, transferring one cleavage-stage embryo in a fresh cycle and one blastocyst-stage embryo in the subsequent frozen-thawed cycle increased live birth rates and decreased multiple live birth rates compared to transferring two cleavage-stage embryos in a single fresh cycle.

What Is Known Already: The strategy of repeated single embryo transfer (SET) has emerged as a solution to address the reduced live birth rates associated with SET per cycle. There is substantial evidence indicating that the cumulative live birth rate after repeated SET is comparable to that of double embryo transfer (DET), while significantly reducing the incidence of multiple pregnancies.

The NAD precursor nicotinamide riboside protects against postovulatory aging in vitro.

Purpose: Postovulatory aging (POA) of oocytes is clinically significant as it mirrors the degeneration observed in maternally aged oocytes, leading to substantial impairments in oocyte quality and the success rates of artificial reproductive technology (ART). The molecular alterations associated with POA, such as the degeneration of the first polar body, an increase in perivitelline space, reactive oxygen species (ROS) accumulation, energy depletion, and chromosomal and DNA damage, underscore the urgency of finding interventions to mitigate these effects. This study aims to identify whether nicotinamide riboside (NR) can prevent POA during the process of in vitro culture and raise the success rates of ART.