Association of novel DNAH11 variants with asthenoteratozoospermia lead to male infertility.

Background: Bi-allelic variants in DNAH11 have been identified as causative factors in Primary Ciliary Dyskinesia, leading to abnormal respiratory cilia. Nonetheless, the specific impact of these variants on human sperm flagellar and their involvement in male infertility remain largely unknown.

Methods: A collaborative effort involving two Chinese reproductive centers conducted a study with 975 unrelated infertile men.

CALR3 defects disrupt sperm-zona pellucida binding in humans: new insights into male factor fertilization failure and relevant clinical therapeutic approaches.

Study Question: Do biallelic deleterious variants of Calreticulin 3 (CALR3) cause fertilization failure (FF), resulting in male infertility in humans?

Summary Answer: Biallelic mutations in CALR3 were identified in two infertile men from unrelated families and were shown to cause FF associated with failed sperm-zona pellucida (ZP) binding.

What Is Known Already: In male mice, the Calr3-knockout has been reported to cause male infertility and FF. However, the mechanism behind this remains unclear in humans.

Adenylate kinase phosphate energy shuttle underlies energetic communication in flagellar axonemes.

The complexities of energy transfer mechanisms in the flagella of mammalian sperm flagella have been intensively investigated and demonstrate significant diversity across species. Enzymatic shuttles, particularly adenylate kinase (AK) and creatine kinase (CK), are pivotal in the efficient transfer of intracellular ATP, showing distinct tissue- and species-specificity. Here, the expression profiles of AK and CK were investigated in mice and found to fall into four subgroups, of which Subgroup III AKs were observed to be unique to the male reproductive system and conserved across chordates.

Differentiation of bone marrow mesenchymal stem cells into Leydig-like cells with testicular extract liquid in vitro.

Differentiation of Leydig cells plays a key role in male reproductive function. Bone marrow mesenchymal stem cells (BMSCs) have emerged as a potential cell source for generating Leydig-like cells due to their multipotent differentiation capacity and accessibility. This study aimed to investigate the morphological and genetic expression changes of BMSCs during differentiation into Leydig-like cells.

LRRC23 deficiency causes male infertility with idiopathic asthenozoospermia by disrupting the assembly of radial spokes.

Asthenozoospermia (AZS) is the primary cause of infertility in males. The radial spoke (RS) is an axonemal structure, connecting the peripheral doublet microtubules with the central pair of microtubules. This T-shaped multiprotein complex functions as a mechanochemical sensor to promote sperm motility.

DNALI1 deficiency causes male infertility with severe asthenozoospermia in humans and mice by disrupting the assembly of the flagellar inner dynein arms and fibrous sheath.

The axonemal dynein arms (outer (ODA) and inner dynein arms (IDAs)) are multiprotein structures organized by light, intermediate, light intermediate (LIC), and heavy chain proteins. They hydrolyze ATP to promote ciliary and flagellar movement. Till now, a variety of dynein protein deficiencies have been linked with asthenospermia (ASZ), highlighting the significance of these structures in human sperm motility.

Novel variants associated with male infertility in two Chinese families.

Introduction: Infertility is a major disease affecting human life and health, among which male factors account for about half. Asthenoteratozoospermia accounts for the majority of male infertility. High-throughput sequencing techniques have identified numerous variants in genes responsible for asthenoteratozoospermia; however, its etiology still needs to be studied.

Bi-allelic human TEKT3 mutations cause male infertility with oligoasthenoteratozoospermia owing to acrosomal hypoplasia and reduced progressive motility.

Oligoasthenoteratozoospermia (OAT) can result in male infertility owing to reduced sperm motility and abnormal spermatozoan morphology. The Tektins are a family of highly conserved filamentous proteins expressed in the axoneme and associated structures in many different metazoan species. Earlier studies on mice identified Tektin3 (Tekt3) as a testis-enriched gene, and knockout of Tekt3 resulted in asthenozoospermia in the mice.

Novel Variants Induce Super-Length Mitochondrial Sheath and Asthenoteratozoospermia in Humans.

Asthenoteratozoospermia is one of the major factors for male infertility, whereas the causes of large numbers of cases are still unknown. We identified compound heterozygous variants of in three unrelated individuals from a cohort of 105 patients with asthenoteratozoospermia by exome sequencing. Deleterious variations caused severe disassembly of the fibrous sheath and axonemal defects.

Development and validation of a deep learning algorithm based on fundus photographs for estimating the CAIDE dementia risk score.

Background: the Cardiovascular Risk Factors, Aging, and Incidence of Dementia (CAIDE) dementia risk score is a recognised tool for dementia risk stratification. However, its application is limited due to the requirements for multidimensional information and fasting blood draw. Consequently, an effective and non-invasive tool for screening individuals with high dementia risk in large population-based settings is urgently needed.

Long-term exposure to genistein inhibits the proliferation of gallbladder cancer by downregulating the MCM complex.

Soy isoflavones are natural tyrosine kinase inhibitors closely associated with decreased morbidity and mortality of various tumors. The activation of tyrosine kinases such as ERBB2 is the mechanism by which cholecystitis transforms into gallbladder cancer (GBC), therefore, it is important to investigate the relationship between long-term exposure to soy isoflavones and the occurrence and progression of GBC. This case-control study (n = 85 pairs) found that the high level of plasma soy isoflavone-genistein (GEN) was associated with a lower risk of gallbladder cancer (≥326.

3D deep learning versus the current methods for predicting tumor invasiveness of lung adenocarcinoma based on high-resolution computed tomography images.

Background: Different pathological subtypes of lung adenocarcinoma lead to different treatment decisions and prognoses, and it is clinically important to distinguish invasive lung adenocarcinoma from preinvasive adenocarcinoma (adenocarcinoma and minimally invasive adenocarcinoma). This study aims to investigate the performance of the deep learning approach based on high-resolution computed tomography (HRCT) images in the classification of tumor invasiveness and compare it with the performances of currently available approaches.

Methods: In this study, we used a deep learning approach based on 3D conventional networks to automatically predict the invasiveness of pulmonary nodules.

Biallelic loss-of-function mutations in SEPTIN4 (C17ORF47), encoding a conserved annulus protein, cause thin midpiece spermatozoa and male infertility in humans.

Asthenoteratozoospermia is the primary cause of infertility in humans. However, the genetic etiology remains largely unknown for those suffering from severe asthenoteratozoospermia caused by thin midpiece defects. In this study, we identified two biallelic loss-of-function variants of SEPTIN4 (previously SEPT4) (Patient 1: c.

A homozygous loss-of-function mutation in FBXO43 causes human non-obstructive azoospermia.

Non-obstructive azoospermia (NOA) represents one of the most serious forms of male infertility caused by spermatogenic failure. Despite multiple genes found to be associated with human NOA, the genetic basis of this idiopathic disease remains largely unknown. FBXO43 is a direct inhibitor of the anaphase-promoting complex/cyclosome (APC/C) E3 ligase and crucially important in mouse spermatogenesis.

FBXO47 regulates telomere-inner nuclear envelope integration by stabilizing TRF2 during meiosis.

During meiosis, telomere attachment to the inner nuclear envelope is required for proper pairing of homologous chromosomes and recombination. Here, we identified F-box protein 47 (FBXO47) as a regulator of the telomeric shelterin complex that is specifically expressed during meiotic prophase I. Knockout of Fbxo47 in mice leads to infertility in males.