Melatonin improves endometrial receptivity and embryo implantation via MT2/PI3K/LIF signaling pathway in sows.

Background: Increased backfat thickness of sows in early gestation is negative to reproductive performance. Endometrial receptivity is an important determinant of reproductive success, but it is unclear whether the effect of sow backfat thickness on litter size is associated with endometrial receptivity and whether melatonin treatment may have benefits. The present study seeks to answer these questions through in vitro and in vivo investigations.

Clinicopathological and prognostic factor analyses of primary fallopian tube carcinoma and high-grade serous ovarian cancer: a single-institution retrospective study.

Objective: This study aimed to evaluate and compare the clinicopathologic features of primary fallopian tubal carcinoma (PFTC) and high-grade serous ovarian cancer (HGSOC) and explore the prognostic factors of these two malignant tumors.

Methods: Fifty-seven patients diagnosed with PFTC from 2006 to 2015 and 60 patients diagnosed with HGSOC from 2014 to 2015 with complete prognostic information were identified at Women's Hospital of Zhejiang University. The clinicopathological and surgical data were collected, and the survival of the patients was followed for 5 years after surgery.

Divergent paths of mammary gland involution: unveiling the cellular dynamics in abruptly and gradually involuted mouse models.

Background: Epidemiological studies associate an increase in breast cancer risk, particularly triple-negative breast cancer (TNBC), with lack of breastfeeding. This is more prevalent in African American women, with significantly lower rate of breastfeeding compared to Caucasian women. Prolonged breastfeeding leads to gradual involution (GI), whereas short-term or lack of breastfeeding leads to abrupt involution (AI) of the breast.

De-escalation of surgical and radiation treatment in elderly luminal breast cancer patients, single institution report and review of the evidence.

Background: De-intensification of anti-cancer therapy without significantly affecting outcomes is an important goal. Omission of axillary surgery or breast radiation is considered a reasonable option in elderly patients with early-stage breast cancer and good prognostic factors. Data on avoidance of both axillary surgery and radiation therapy (RT) is scarce and inconclusive.

SMORE: spatial motifs reveal patterns in cellular architecture of complex tissues.

Deciphering the link between tissue architecture and function requires methods to identify and interpret patterns in spatial arrangement of cells. We present SMORE, an approach to detect patterns in sequential arrangements of cells and examine their associated gene expression specializations. Applied to retina, brain, and embryonic tissue maps, SMORE identifies novel spatial motifs, including one that offers a new mechanism of action for type 1b bipolar cells.

Integrative multiomics reveals common endotypes across PSEN1, PSEN2, and APP mutations in familial Alzheimer's disease.

Background: PSEN1, PSEN2, and APP mutations cause Alzheimer's disease (AD) with an early age at onset (AAO) and progressive cognitive decline. PSEN1 mutations are more common and generally have an earlier AAO; however, certain PSEN1 mutations cause a later AAO, similar to those observed in PSEN2 and APP.

Methods: We examined whether common disease endotypes exist across these mutations with a later AAO (~ 55 years) using hiPSC-derived neurons from familial Alzheimer's disease (FAD) patients harboring mutations in PSEN1, PSEN2, and APP and mechanistically characterized by integrating RNA-seq and ATAC-seq.

Association of female genital schistosomiasis and human papillomavirus and cervical pre-cancer: a systematic review.

Background: S. haematobium is a recognized carcinogen and is associated with squamous cell carcinoma of the bladder. Its association with high-risk(HR) human papillomavirus (HPV) persistence, cervical pre-cancer and cervical cancer incidence has not been fully explored.

KDM6A facilitates Xist upregulation at the onset of X inactivation.

Background: X chromosome inactivation (XCI) is a female-specific process in which one X chromosome is silenced to balance X-linked gene expression between the sexes. XCI is initiated in early development by upregulation of the lncRNA Xist on the future inactive X (Xi). A subset of X-linked genes escape silencing and thus have higher expression in females, suggesting female-specific functions.

A prospective, multicenter analysis of the integrated 31-gene expression profile test for sentinel lymph node biopsy (i31-GEP for SLNB) test demonstrates reduced number of unnecessary SLNBs in patients with cutaneous melanoma.

Background: National Comprehensive Cancer Network guidelines recommend sentinel lymph node biopsy (SLNB) for patients with > 10% risk of positivity, consider SLNB with 5-10% risk, and foregoing with < 5% risk. The integrated 31-gene expression profile (i31-GEP) algorithm combines the 31-GEP with clinicopathologic variables, estimating SLN positivity risk.

Methods: The i31-GEP SLNB risk prediction accuracy was assessed in patients with T1-T2 tumors enrolled in the prospective, multicenter DECIDE study (n = 322).

Mixed method study of feasibility and acceptability of electronic screening for measurement-based symptom monitoring of veterans accessing mental health treatment in VA community care program settings.

Background: 2022 survey data showed 29% of Veterans utilized Veterans Affairs (VA) paid health care at a non-VA facility, 6% higher than in 2021. Despite an increase in the number of Veterans accessing care in the community via the MISSION Act Community Care Program (CCP), there is limited information on the quality of mental health care delivered to Veterans in these settings. Further, Veterans report barriers to quality care, including poor communication between CCP and VA providers, which can result in negative patient outcomes.

Built environment change for injury prevention: insights from public health professionals across public health units in Ontario, Canada.

Background: Road-related injuries and deaths are among the most significant and avoidable public health problems in Canada. Modifications to the built environment (BE) can reduce injury rates for vulnerable road users (VRUs) and other priority populations who experience disproportionate risk. This paper highlights public health professionals' experiences working in injury prevention across Ontario public health units (PHUs) navigating barriers and facilitators to BE change.

Acute administration of NLX-101, a Serotonin 1A receptor agonist, improves auditory temporal processing during development in a mouse model of Fragile X Syndrome.

Background: Fragile X syndrome (FXS) is a leading known genetic cause of intellectual disability and autism spectrum disorders (ASD)-associated behaviors. A consistent and debilitating phenotype of FXS is auditory hypersensitivity that may lead to delayed language and high anxiety. Consistent with findings in FXS human studies, the mouse model of FXS, the Fmr1 knock out (KO) mouse, shows auditory hypersensitivity and temporal processing deficits.

Response of Kapok seedlings were irrigated with water of different qualities and heavy metal contents for foliar application of antioxidants.

Background: The imbalance between Egypt's water requirements and supply necessitates the use of unconventional water sources, such as treated sewage water (TSW) and agricultural drainage water (ADW), to combat water scarcity. This study investigated the effects of foliar glycine betaine (GB) on vegetative growth parameters, physiological characteristics, photosynthetic pigments, leaf element contents, anatomical leaf structures, and antioxidant activity. The experiment was conducted in two successive seasons (2021/2022 and 2022/2023) using Kapok seedlings irrigated with ADW and TSW at different mixing ratios with normal irrigation water (NIW) (25%, 50%, 75%, and 100%), combined with foliar spraying of GB at concentrations of 0.

Migraine in men.

Background: Migraine is a common primary headache disorder, less frequently affecting men than women, and often regarded as predominantly a "women's disease." Despite this, migraine in men presents with unique characteristics in terms of symptoms, treatment responses, comorbidities, and pain perception. Historically, research has focused more on migraine in women, overlooking critical male-specific aspects.

GLiDe: a web-based genome-scale CRISPRi sgRNA design tool for prokaryotes.

Background: CRISPRi screening has become a powerful approach for functional genomic research. However, the off-target effects resulting from the mismatch tolerance between sgRNAs and their intended targets is a primary concern in CRISPRi applications.

Results: We introduce Guide Library Designer (GLiDe), a web-based tool specifically created for the genome-scale design of sgRNA libraries tailored for CRISPRi screening in prokaryotic organisms.

Synthesis of tertiary alkyl amines via photoinduced copper-catalysed nucleophilic substitution.

In view of the high propensity of tertiary alkyl amines to be bioactive, the development of new methods for their synthesis is an important challenge. Transition-metal catalysis has the potential to greatly expand the scope of nucleophilic substitution reactions of alkyl electrophiles; unfortunately, in the case of alkyl amines as nucleophiles, only one success has been described so far: the selective mono-alkylation of primary amines to form secondary amines. Here, using photoinduced copper catalysis, we report the synthesis of tertiary alkyl amines from secondary amines and unactivated alkyl electrophiles, two readily available coupling partners.

Stereoselective amino alcohol synthesis via chemoselective electrocatalytic radical cross-couplings.

Amino alcohols are vital in natural products, pharmaceuticals and agrochemicals, and as key building blocks for various applications. Traditional synthesis methods often rely on polar bond retrosynthetic analysis, requiring extensive protecting group manipulations that complicate direct access. Here we show a streamlined approach using a serine-derived chiral carboxylic acid in stereoselective electrocatalytic decarboxylative transformations, enabling efficient access to enantiopure amino alcohols.

Sex-specific mechanisms in vascular aging: exploring cellular and molecular pathways in the pathogenesis of age-related cardiovascular and cerebrovascular diseases.

Aging remains the foremost risk factor for cardiovascular and cerebrovascular diseases, surpassing traditional factors in epidemiological significance. This review elucidates the cellular and molecular mechanisms underlying vascular aging, with an emphasis on sex differences that influence disease progression and clinical outcomes in older adults. We discuss the convergence of aging processes at the macro- and microvascular levels and their contributions to the pathogenesis of vascular diseases.

Impact of physical activity and exercise training on health-related quality of life in older adults: an umbrella review.

Health-related quality of life (HRQoL) is inversely associated with all-cause mortality in older adults and may be improved with physical activity and exercise training. The objective of this umbrella review was to determine the impact of physical activity and exercise training on HRQoL in younger-old (average age ≤ 75 years) and older-old (average age > 75 years) adults. Our umbrella review (CRD42023481145) included 39 systematic reviews (21/39 with meta-analysis) including 113 unique individual studies of 13391 unique participants.

Effects of LinTT1-peptide conjugation on the properties of poly(ethylene glycol)-block-(ε-caprolactone) nanoparticles prepared by the nanoprecipitation method.

Functionalization of polymer nanoparticles (NPs) with targeting peptides is of interest for drug delivery applications to enhance tumor accumulation and penetration. Herein, we evaluated the feasibility of two different methods for the attachment of a tumor-penetrating peptide LinTT1 (AKRGARSTA) to poly(ethylene glycol)-block-poly(ε-caprolactone) (PCL-PEG) NPs: (1) "post-conjugation" onto pre-formed nanoparticles, and (2) "pre-conjugation", the synthesis and purification of peptide-polymer conjugates and subsequent nanoprecipitation of the conjugates diluted with non-functionalized polymers. Conjugation of the labelled peptide via maleimide-thiol chemistry was verified by gel permeation chromatography (GPC) and fluorescence measurements.

Guruism and Cultic Social Dynamics in Psychedelic Practices and Organisations.

This chapter explores the risks of guruism and cultic social dynamics in organisations that work with psychedelic drugs, which include therapist offices, clinics, research departments, retreat centres, training programmes, NGOs, underground ceremonies and new religious movements. It has been hypothesised, and argued by experienced practitioners, that psychedelics can increase suggestibility, amplify transference and facilitate an intense form of projective mechanisms in the recipients. They may thereby lead to ego-inflation and feelings of grandiosity and omnipotence in those giving the drugs and intensify cultic social dynamics in psychedelic communities - all of which can create conditions that make cases of harm and misconduct more likely to occur and go unreported.

Clinicogenomic landscape of pancreatic adenocarcinoma identifies KRAS mutant dosage as prognostic of overall survival.

Nearly all pancreatic adenocarcinomas (PDAC) are genomically characterized by KRAS exon 2 mutations. Most patients with PDAC present with advanced disease and are treated with cytotoxic therapy. Genomic biomarkers prognostic of disease outcomes have been challenging to identify.

A bipartite bacterial virulence factor targets the complement system and neutrophil activation.

The complement system and neutrophils constitute the two main pillars of the host innate immune defense against infection by bacterial pathogens. Here, we identify T-Mac, a novel virulence factor of the periodontal pathogen Treponema denticola that allows bacteria to evade both defense systems. We show that T-Mac is expressed as a pre-protein that is cleaved into two functional units.

Hypoxia promotes tumor immune evasion by suppressing MHC-I expression and antigen presentation.

Hypoxia is a common feature of solid tumors that has previously been linked to resistance to radiotherapy and chemotherapy, and more recently to immunotherapy. In particular, hypoxic tumors exclude T cells and inhibit their activity, suggesting that tumor cells acquire a mechanism to evade T-cell recognition and killing. Our analysis of hypoxic tumors indicates that hypoxia downregulates the expression of MHC class I and its bound peptides (i.