Novel mutations in LRRC23 cause asthenozoospermia in a nonconsanguineous family.

ABSTRACT: The cause of asthenozoospermia (AZS) is not well understood because of its complexity and heterogeneity. Although some gene mutations have been identified as contributing factors, they are only responsible for a small number of cases. Radial spokes (RSs) are critical for adenosine triphosphate-driven flagellar beating and axoneme stability, which is essential for flagellum motility. In this study, we found novel compound heterozygous mutations in leucine-rich repeat-containing protein 23 ( LRRC23 ; c.1018C>T: p.Q340X and c.881_897 Del: p.R295Gfs*32) in a proband from a nonconsanguineous family with AZS and male infertility. Diff-Quik staining and scanning electron microscopy revealed no abnormal sperm morphology. Western blotting and immunofluorescence staining showed that these mutations suppressed LRRC23 expression in sperm flagella. Additionally, transmission electron microscopy showed the absence of RS3 in sperm flagella, which disrupts stability of the radial spoke complex and impairs motility. Following in vitro fertilization and embryo transfer, the proband's spouse achieved successful pregnancy and delivered a healthy baby. In conclusion, our study indicates that two novel mutations in LRRC23 are associated with AZS, but successful fertility outcomes can be achieved by in vitro fertilization-embryo transfer techniques.

The novel HLA-DPB1*05:01:20 allele, identified by Sanger dideoxy nucleotide sequencing in a Chinese individual.

HLA-DPB1*05:01:20 differs from HLA-DPB1*05:01:01:01 by one nucleotide in exon 3.

The novel HLA-C*03:652 allele, identified by Sanger dideoxy nucleotide sequencing in a Chinese individual.

HLA-C*03:652 differs from the HLA-C*03:04:01:01 by one nucleotide in exon 3.

The novel HLA-B*38:103N allele, identified by Sanger dideoxy nucleotide sequencing in a Chinese individual.

HLA-B*38:103N differs from HLA-B*38:02:01:01 by one nucleotide in exon 3.

The novel HLA-C*08:273 allele, identified by Sanger dideoxy nucleotide sequencing in a Chinese individual.

HLA-C*08:273 differs from HLA-C*08:01:01:01 by one nucleotide in exon 2.

The novel HLA-B*46:01:42 allele, identified by Sanger dideoxy nucleotide sequencing in a Chinese individual.

HLA-B*46:01:42 differs from HLA-B*46:01:01:01 by one nucleotide in exon 5.

The novel HLA-B*48:01:13 allele, identified by Sanger dideoxy nucleotide sequencing in a Chinese individual.

HLA-B*48:01:13 differs from HLA-B*48:01:01:01 by one nucleotide in exon 5.

The novel HLA-A*11:448 allele, identified by Sanger dideoxy nucleotide sequencing in a Chinese individual.

HLA-A*11:448 differs from HLA-A*11:01:01:01 by one nucleotide in exon 5.

The novel HLA-B*27:267 allele, identified by Sanger dideoxy nucleotide sequencing in a Chinese individual.

HLA-B*27:267 differs from HLA-B*27:04:01 by one nucleotide in exon 2.

Exploration of KIR genes and hematological-related diseases in Chinese Han population.

The function of natural killer (NK) cells has previously been implicated in hematopoietic-related diseases. Killer immunoglobulin-like receptors (KIR) play an important role in NK cells after hematopoietic stem cell transplantation. To explore the immunogenetic predisposition of hematological-related diseases, herein, a multi-center retrospective study in China was conducted, analyzing and comparing 2519 patients with hematopathy (mainly, acute lymphoblastic leukemia, acute myeloid leukemia, aplastic anemia, and myelodysplastic syndrome) to 18,108 individuals without known pathology. Genotyping was performed by polymerase chain reaction with specific sequence primers (PCR-SSP). As a result, we discovered four genes including KIR2DL5 (OR: 0.74, 95% CI 0.59-0.93; Pc = 0.0405), 2DS1 (OR: 0.74, 95% CI 0.59-0.93; Pc = 0.0405), 2DS3 (OR: 0.58, 95% CI 0.41-0.81; Pc = 0.0180), and 3DS1 (OR: 0.74, 95% CI 0.58-0.94; Pc = 0.0405) to be protective factors that significantly reduce the risk of aplastic anemia. Our findings offer new approaches to immunotherapy for hematological-related diseases. As these therapies mature, they are promising to be used alone or in combination with current treatments to help to make blood disorders a manageable disease.

Structures of sperm flagellar doublet microtubules expand the genetic spectrum of male infertility.

Sperm motility is crucial for successful fertilization. Highly decorated doublet microtubules (DMTs) form the sperm tail skeleton, which propels the movement of spermatozoa. Using cryo-electron microscopy (cryo-EM) and artificial intelligence (AI)-based modeling, we determined the structures of mouse and human sperm DMTs and built an atomic model of the 48-nm repeat of the mouse sperm DMT. Our analysis revealed 47 DMT-associated proteins, including 45 microtubule inner proteins (MIPs). We identified 10 sperm-specific MIPs, including seven classes of Tektin5 in the lumen of the A tubule and FAM166 family members that bind the intra-tubulin interfaces. Interestingly, the human sperm DMT lacks some MIPs compared with the mouse sperm DMT. We also discovered variants in 10 distinct MIPs associated with a subtype of asthenozoospermia characterized by impaired sperm motility without evident morphological abnormalities. Our study highlights the conservation and tissue/species specificity of DMTs and expands the genetic spectrum of male infertility.

Differential requirements of IQUB for the assembly of radial spoke 1 and the motility of mouse cilia and flagella.

The T-shaped radial spoke (RS) is a protein complex attached to the A microtubule of the outer doublet microtubules, and it extends toward the central pair (CP). It modulates the beat frequency, amplitude, and waveform of the flagella and cilia by serving as a mechanochemical signal transducer between the CP and dyneins. In humans, RS defects cause primary ciliary dyskinesia, but the structural components of triple RSs (RS1, RS2, and RS3) in mammals remain to be elucidated in detail. Here, we introduce a mouse model that lacked the entire RS1 in sperm flagella, due to the deletion of Iqub, while the tracheal cilia possessed intact triple RSs. Furthermore, the absence of IQUB only resulted in male infertility, owing to the sperm motility defect. Based on the mouse model, the RS1 compositions are identified in sperm flagella. In summary, this study elucidates the RS1 components and function in mammalian flagella.

Isolation and Aflatoxin B1-Degradation Characteristics of a Microbacterium proteolyticum B204 Strain from Bovine Faeces.

Aflatoxin B1 (AFB1) is one of the most harmful mycotoxins, raising serious global health and economic problems. Searching for biological approaches for effective and safe AFB1 degradation is imminent. In our study, Microbacterium proteolyticum B204 isolated from bovine faeces degraded 77% of AFB1 after 24 h, becoming the first reported bacteria from the Microbacterium family to possess AFB1 degradation characteristics. Temperature variation showed little effect on its degradation ratio, demonstrating high thermostability of 75% and 79% after boiling and sterilization, respectively. We suppose that the components playing a key role during this process were proteins, considering the decreased degradation rate caused by Proteinase K. Cell viability detection on HepG2 cells indicated that the degradation products were much less toxic than pure AFB1. Furthermore, B204 cell-free culture supernatant also degraded AFB1-contaminated food, such as peanuts, corn and cheese. These results suggested that this strain with AFB1 degradation properties could be a prospective candidate for application in the food and feed industries.

Influence of Social Support Network and Perceived Social Support on the Subjective Wellbeing of Mothers of Children With Autism Spectrum Disorder.

This study explored the relations between the social support network of mothers of children with autism spectrum disorder (ASD), perceived social support, and their subjective wellbeing. The participants were mothers of children with ASD in Shanghai. Their social support network structure was explored via the nomination method. Perceived social support was measured using the Revised Social Provisions Scale for Autism (R-SPS-A), and the mothers' subjective wellbeing was assessed using the Index of Wellbeing, Index of General Affect. A significant correlation was observed between the subjective wellbeing of mothers of children with ASD and perceived social support. Meanwhile, perceived social support was significantly correlated with the effectiveness of overall social support. Finally, perceived social support was also significantly correlated with the network size of social support. Moreover, the effectiveness of social support was significantly associated with the network size of social support and was highly significantly associated with the degree of intimacy of social support. Furthermore, the network size of instrumental support has a significant influence on all perceived social support subdimensions. Overall, social support effectiveness plays an important role in the social support network mechanism on perceived social support and subjective wellbeing in China.

Macrobrachium tenuipes, a new stygophile freshwater prawn specie (Crustacea: Caridea: Palaemonidae) from a karst cave of Guangxi, southwestern China.

Based on morphological, molecular, and ecological evidences, a fourth species of cave-dwelling shrimp Macrobrachium tenuipes sp. nov. is described from Guangxi Zhuang Autonomous Region, southwestern China. This new species with smooth carapace and the extremely slender pereiopods, can be separated from other congeners by the shape of rostrum; the segmental ratios, the arrangement of teeth on the cutting edge of the fingers of second pereiopod; the longer and narrower scaphocerite; and the longer uropodal diaeresis spine. The new taxon is genetically distinct from 18 other species of Macrobrachium for which COI and 18S rRNA sequences are available. The data observed on the habitat and ecology will contribute to the conservation for M. tenuipes sp. nov.

A nanostructured anti-biofilm surface widens the efficacy against spindle-shaped and chain-forming rod-like bacteria.

Current control of pathogenic bacteria at all biomaterial interfaces is poorly attuned to a broad range of disease-causing pathogens. Leading antimicrobial surface functionalization strategies with antimicrobial peptides (AMPs), defensins, have not shown their promised efficacy. One of the main problems is the lack of stability and swift clearance from the surface. Surface nanotopography bearing sharp protrusions is a non-chemical solution that is intrinsically stable and long-lasting. Previously, the geometrically ordered arrays of nanotipped spines repelled or rapidly ruptured bacteria that come into contact. The killing properties so far work on cocci and rod-like bacteria, but there is no validation of the efficacy of protrusional surfaces on pathogenic bacteria with different sizes and morphologies, thus broadening the utility of such surfaces to cover increasingly more disease entities. Here, we report a synthetic analogue of nanotipped spines with a pyramidal shape that show great effectiveness on species of bacteria with strongly contrasting shapes and sizes. To highlight this phenomenon in the field of dental applications where selective bacterial control is vital to the clinical success of biomaterial functions, we modified the poly(methyl)-methacrylate (PMMA) texture and tested it against Streptococcus mutans, Enterococcus faecalis, Porphyromonas gingivalis, and Fusobacterium nucleatum. These nanopyramids performed effectively at levels well above those of normal and roughened PMMA biomaterials for dentistry and a model material for general use in medicine and disease transmission in hospital environments.

Two freshwater shrimp species of the genus Caridina (Decapoda, Caridea, Atyidae) from Dawanshan Island, Guangdong, China, with the description of a new species.

A faunistic and ecological survey was conducted to document the diversity of freshwater atyid shrimps of Dawanshan Island. Two species of Caridina that occur on this island were documented and discussed. One of these, Caridina tetrazona sp. nov. is described and illustrated as new to science. It can be easily distinguished from its congeners based on a combination of characters, which includes a short rostrum, the shape of the endopod of the male first pleopod, the segmental ratios of antennular peduncle and third maxilliped, the slender scaphocerite, and the absence of a median projection on the posterior margin. Live individuals of the new species display a unique coloration pattern with four dark blue transverse bands on the body, and can be easily recognized in the field. So far, despite considerable surveying efforts made on neighboring islands, this species has only been found from a small stream on Dawanshan Island, which suggests that it may have a very limited range, probably endemic to Dawanshan Island. Molecular characteristics of the mitochondrial cytochrome c oxidase subunit I (COI) demonstrate that this species shows sufficient interspecific divergence from its congeners, including C. serrata Stimpson, 1860, which was found in four streams on Dawanshan Island, and has been previously reported on the neighboring islands of Hong Kong, Dong'ao, Wailingding, and Guishan.

Overexpressed DAAM1 correlates with metastasis and predicts poor prognosis in breast cancer.

Recent studies have reported that dishevelled-associated activator of morphogenesis 1 (DAAM1) is remarkably essential for mediating cell migration and invasion in breast cancer (BrCa). Nonetheless, the definite expression profile of DAAM1 in BrCa patients and the impact on metastasis of BrCa in vivo have not been explored up to now. The differential expression of DAAM1 in BrCa and adjacent tissues was assessed via immunohistochemistry (IHC) staining. The metastatic capacities of BrCa SUM-1315 cells were examined in BALB/c nude mice. Besides, the prognostic values of DAAM1 mRNA in BrCa were explored based on Kaplan-Meier (KM) plotter. The expression of DAAM1 protein was notably overexpressed in BrCa tissues compared with that in paired normal breast tissues. The high expression of DAAM1 in BrCa tissues was significantly associated with lymph-node metastasis. Furthermore, DAAM1 overexpression promoted the invasive capacity of BrCa cells and stimulated lung metastatic extent in vivo. We also found that overexpressed DAAM1 mRNA was significantly associated with poor relapse-free survival (RFS), overall survival (OS), distance-metastasis-free survival (DMFS), and post-progression survival (PPS). Our findings reveal that DAAM1 might be a novel therapeutic target to manage the deteriorated metastasis of BrCa and identified DAAM1 as a promising biomarker for unfavorable prognosis in BrCa patients.

Caridina sinanensis, a new species of stygobiotic atyid shrimp (Decapoda, Caridea, Atyidae) from a karst cave in the Guizhou Province, southwestern China.

From a biodiversity survey of a subterranean habitat near Sinan County, Guizhou Province, southwestern China, a new atyid shrimp of the genus Caridina H. Milne Edwards, 1837, C. sinanensis sp. nov. was discovered. The new species can be separated from other congeners based on a combination of characters including depigmentation in body and reduction of eyes, small pigment spot at the centre of the cornea, the shape of rostrum and the endopod of the 1st male pleopod, and the relatively longer appendix interna on the appendix masculina of the 2nd pleopod. Mitochondrial COI and 16S rRNA gene sequences also support the establishment of the new species. Information on the habitat, and the levels of threat are discussed to guide the conservation of C. sinanensis sp. nov.