A conserved fertilization complex bridges sperm and egg in vertebrates.

Fertilization, the basis for sexual reproduction, culminates in the binding and fusion of sperm and egg. Although several proteins are known to be crucial for this process in vertebrates, the molecular mechanisms remain poorly understood. Using an AlphaFold-Multimer screen, we identified the protein Tmem81 as part of a conserved trimeric sperm complex with the essential fertilization factors Izumo1 and Spaca6.

Orientation Determination of Cryo-EM Projection Images Using Reliable Common Lines and Spherical Embeddings.

Three-dimensional (3D) reconstruction in single-particle cryo-electron microscopy (cryo-EM) is a critical technique for recovering and studying the fine 3D structure of proteins and other biological macromolecules, where the primary issue is to determine the orientations of projection images with high levels of noise. This paper proposes a method to determine the orientations of cryo-EM projection images using reliable common lines and spherical embeddings. First, the reliability of common lines between projection images is evaluated using a weighted voting algorithm based on an iterative improvement technique and binarized weighting.

An Exact Bayesian Model for Meta-Analysis of the Standardized Mean Difference with Its Simultaneous Credible Intervals.

While Bayesian methodology is increasingly favored in behavioral research for its clear probabilistic inference and model structure, its widespread acceptance as a standard meta-analysis approach remains limited. Although some conventional Bayesian hierarchical models are frequently used for analysis, their performance has not been thoroughly examined. This study evaluates two commonly used Bayesian models for meta-analysis of standardized mean difference and identifies significant issues with these models.

Specific Knockout of Notch-1 in Macrophages Modulate the Progression of Hepatic Insulin Resistance in HFD Fed Mice via Regulating IRE1α-XBP1 Signals.

Objective: To develop an intervention based on Notch-1 signalling pathway blockade by investigating the potential application of the neurogenic locus notch homologue protein 1(Notch-1) signalling pathway as a key regulator of chronic inflammation and adipogenesis in the treatment of hepatic insulin resistance (HIR).

Study Design: Experimental study. Place and Duration of the Study: Animal Laboratory of the Fourth Hospital of Hebei Medical University, Shijiazhuang, China, from April 2021 to June 2022.

ZP2 cleavage blocks polyspermy by modulating the architecture of the egg coat.

Following the fertilization of an egg by a single sperm, the egg coat or zona pellucida (ZP) hardens and polyspermy is irreversibly blocked. These events are associated with the cleavage of the N-terminal region (NTR) of glycoprotein ZP2, a major subunit of ZP filaments. ZP2 processing is thought to inactivate sperm binding to the ZP, but its molecular consequences and connection with ZP hardening are unknown.

A kinetic model for solving a combination optimization problem in ab-initio Cryo-EM 3D reconstruction.

Cryo-Electron Microscopy (cryo-EM) is a widely used and effective method for determining the three-dimensional (3D) structure of biological molecules. For ab-initio Cryo-EM 3D reconstruction using single particle analysis (SPA), estimating the projection direction of the projection image is a crucial step. However, the existing SPA methods based on common lines are sensitive to noise.

Macrophage-specific deletion of Notch-1 induced M2 anti-inflammatory effect in atherosclerosis via activation of the PI3K-oxidative stress axis.

Objective: Notch-1 signaling is significantly associated with the occurrence and development of atherosclerosis (AS). However, the molecular mechanisms underlying the specific deletion of Notch-1 in AS-associated macrophages are not fully understood. This study aimed to investigate the effects of Notch-1 in AS.

Specific knockout of notch-1 attenuates non-alcoholic fatty liver disease by promoting SHP2 phosphorylation.

Objective: To investigate the effect of Notch-1 signaling on NAFLD and its molecular mechanism.

Methods: The lipid deposition in liver tissues was detected by oil red O staining. Western blotting was performed to detect the expressions of SREBP1C, SREBP2, LXR, IL-1β, IL-18, NLRP3, Notch-1, NOX2, NOX4, p-PI3K and p-SHP2 in macrophages, and the expressions of ALIX, CD9, IL-1β and SREBP1C in exosomes.

Down-regulation of EZH2 genes targeting RUNX3 affects proliferation, invasion, and metastasis of human colon cancer cells by Wnt/β-catenin signaling pathway.

In order to detect the effect of EZH2 genes on proliferation, migration, invasion, and apoptosis of colon carcinoma cell strains HCT116 and HT29 by the Wnt/β-catenin signaling pathway, qRT-PCR was applied to measure relative expressions of EZH2, RUNX3, CEA, CA199, MMP-9, VEGF, β-catenin, and CyclinD1 in each group; Western-blot was employed with the intention of exploring relative expressions of these proteins and ; monoclonal proliferation experiments and CCK-8 assay was adopted so as to check cell proliferation; the effect on cell migration was investigated via Transwell assay and cell scratch wound assay; flow cytometry was applied with a view to determining the effect on cell apoptosis. Transfected HCT116 cells are injected subcutaneously into nude mice. In colon cell strains HCT-116 and HT29, contrasted to the si-NC group, the RUNX3 expression was prominently up-regulated in the si-EZH2 group.

Assessment of infant gonadal dose irradiated from urine-contaminated diapers during diuretic renal scintigraphy.

Objective: To estimate the gonadal doses irradiated from urine- contaminated diapers during diuretic renal scintigraphy.

Methods: Images of 31 patients (18 males and 13 females) with urine-contaminated diapers during 99m Tc-MAG3 renal scintigraphy were analyzed. The count rate of the diapers was converted into a time-activity curve based on the calibrated factor of the gamma camera system.

Macrophage-derived SHP-2 inhibits the metastasis of colorectal cancer via Tie2-PI3K signals.

This research aimed to explore the influence of Src homology-2 containing protein tyrosine phosphatase (SHP-2) on the functions of tyrosine kinase receptors with immunoglobulin and EGF homology domains 2 (Tie2)-expressing monocyte/macrophages (TEMs) and the influence of the angiopoietin(Ang)/Tie2-phosphatidylinositol-3-kinase (PI3K)/protein kinase B (Akt)/mammalian target of rapamycin (mTOR) (Ang/Tie2-PI3K/Akt/mTOR) signaling pathway on the tumor microvascular remodeling in an immunosuppressive microenvironment. , SHP-2-deficient mice were used to construct colorectal cancer (CRC) liver metastasis models. SHP-2-deficient mice had significantly more metastatic cancer and inhibited nodules on the liver surface than wild-type mice, and the high-level expression of p-Tie2 was found in the liver tissue of the macrophages' specific SHP-2-deficient mice (SHP-2MAC-KO) + planted tumor mice.

An Unsupervised Classification Algorithm for Heterogeneous Cryo-EM Projection Images Based on Autoencoders.

Heterogeneous three-dimensional (3D) reconstruction in single-particle cryo-electron microscopy (cryo-EM) is an important but very challenging technique for recovering the conformational heterogeneity of flexible biological macromolecules such as proteins in different functional states. Heterogeneous projection image classification is a feasible solution to solve the structural heterogeneity problem in single-particle cryo-EM. The majority of heterogeneous projection image classification methods are developed using supervised learning technology or require a large amount of a priori knowledge, such as the orientations or common lines of the projection images, which leads to certain limitations in their practical applications.

On the correction of respiratory motion-induced image reconstruction errors in positron-emission tomography-guided radiation therapy.

Background And Purpose: Free breathing (FB) positron emission tomography (PET) images are routinely used in radiotherapy for lung cancer patients. Respiration-induced artifacts in these images compromise treatment response assessment and obstruct clinical implementation of dose painting and PET-guided radiotherapy. The purpose of this study is to develop a blurry image decomposition (BID) method to correct motion-induced image-reconstruction errors in FB-PETs.

1700029I15Rik orchestrates the biosynthesis of acrosomal membrane proteins required for sperm-egg interaction.

Sperm acrosomal membrane proteins, such as Izumo sperm-egg fusion 1 (IZUMO1) and sperm acrosome-associated 6 (SPACA6), play essential roles in mammalian gamete binding or fusion. How their biosynthesis is regulated during spermiogenesis has largely remained elusive. Here, we show that knockout male mice are severely subfertile and their spermatozoa do not fuse with eggs.

ADAD2 functions in spermiogenesis and piRNA biogenesis in mice.

Background: Adenosine deaminase domain containing 2 (ADAD2) is a testis-specific protein composed of a double-stranded RNA binding domain and a non-catalytic adenosine deaminase domain. A recent study showed that ADAD2 is indispensable for the male reproduction in mice. However, the detailed functions of ADAD2 remain elusive.

Eukaryotic fertilization and gamete fusion at a glance.

In sexually reproducing organisms, the genetic information is transmitted from one generation to the next via the merger of male and female gametes. Gamete fusion is a two-step process involving membrane recognition and apposition through ligand-receptor interactions and lipid mixing mediated by fusion proteins. HAP2 (also known as GCS1) is a bona fide gamete fusogen in flowering plants and protists.

Macrophage-Derived Exosomes in TLR9 Mice Ameliorate Sepsis-Induced Mitochondrial Oxidative Stress and Apoptosis in Cardiomyocytes.

Objective: To explore the mechanisms of TLR9 from macrophages on mitochondrial apoptosis in cardiomyocytes at early stage of sepsis.

Methods: The and sepsis mice were bone marrow transplantation (BMT) with wild type (WT) or (toll-like receptor 9) TLR9 knockout ( or KO) myeloid cells and then constructed by cecum ligation and puncture (CLP) as vivo experiment and cardiomyocytes cocultured with WT or TLR9-deficient macrophages treated with LPS as vitro experiment, respectively. Sepsis model were performed by CLP.

Human sperm TMEM95 binds eggs and facilitates membrane fusion.

encodes a sperm acrosomal membrane protein, whose knockout has a male-specific sterility phenotype in mice. knockout murine sperm can bind to, but do not fuse with, eggs. How TMEM95 plays a role in membrane fusion of sperm and eggs has remained elusive.

Pan-Cancer Study of SHC-Adaptor Protein 1 (SHC1) as a Diagnostic, Prognostic and Immunological Biomarker in Human Cancer.

Recent studies highlight the carcinogenesis role of SHC-adaptor protein 1 (SHC1) in cancer initiation, development, and progression. However, its aberrant expression, diagnostic and prognostic value remain unknown in a variety of tumors. The SHC1 expression profiles were analyzed using GTEx database, TCGA database, Oncomine and CPTAC database.

3D reconstruction from cryo-EM projection images using two spherical embeddings.

Single-particle analysis (SPA) in cryo-electron microscopy has become a powerful tool for determining and studying the macromolecular structure at an atomic level. However, since the SPA problem is a non-convex optimization problem with enormous search space and there is high level of noise in the input images, the existing methods may produce biased or even wrong final models. In this work, to deal with the problem, consistent constraints from the input data are explored in an embedding space, a 3D spherical surface.