Search

Background As one of the most common congenital abnormalities in male births, cryptorchidism has been found to have a polygenic aetiology according to previous studies of common variants. However, little is known about genetic predisposition of rare variants for cryptorchidism, since rare variants have larger effective size on diseases than common variants. Methods In this study, a cohort of 115 Chinese probands with cryptorchidism was analysed using whole-genome sequencing, alongside 19 parental controls and 2136 unaffected men. Additionally, CRISPR-Cas9 editing of a conserved variant was performed in a mouse model, with MRI screening used to observe the phenotype. Results In 30 of 115 patients (26.1%), we identified four novel genes (ARSH, DMD, MAGEA4 and SHROOM2) affecting at least five unrelated patients and four known genes (USP9Y, UBA1, BCORL1 and KDM6A) with the candidate rare pathogenic variants affecting at least two cases. Burden tests of rare variants revealed the genome-wide significances for newly identified genes (p<2.5x10-6) under the Bonferroni correction. Surprisingly, novel and known genes were mainly found on X chromosome (seven on X and one on Y) and all rare X-chromosomal segregating variants exhibited a maternal inheritance rather than de novo origin. CRISPR- Cas9 mouse modelling of a splice donor loss variant in DMD (NC_000023.1 1:g.32454661C>G), which resides in a conserved site across vertebrates, replicated bilateral cryptorchidism phenotypes, confirmed by MRI at 4 and 10 weeks. The movement tests further revealed symptoms of Duchenne muscular dystrophy (DMD) in transgenic mice. Conclusion Our results revealed the role of the DMD gene mutation in causing cryptorchidism. The results also suggest that maternal-X inheritance of pathogenic defects could have a predominant role in the development of cryptorchidism. [ABSTRACT FROM AUTHOR]

The progressive decline of the coal industry necessitates the development of effective treatment solutions for acid mine drainage (AMD), which is characterized by high acidity and elevated concentrations of heavy metals. This study proposes an innovative approach leveraging sulfate-reducing bacteria (SRB) acclimated to contaminated anaerobic environments. The research focused on elucidating the physiological characteristics and optimal growth conditions of SRB, particularly in relation to the pH level and temperature. The experimental findings reveal that the SRB exhibited a sulfate removal rate of 88.86% at an optimal temperature of 30 ◦C. Additionally, SRB gel particles were formulated using sodium alginate (SA) and carboxymethyl cellulose (CMC), and their performance was assessed under specific conditions (pH = 6, C/S = 1.5, T = 30 ◦C, CMC = 4.5%, BSNa = 0.4 mol/L, and cross-linking time = 9 h). Under these conditions, the SRB gel particles demonstrated an enhanced sulfate removal efficiency of 91.6%. Thermal analysis via differential scanning calorimetry (DSC) and thermogravimetric analysis (TGA) provided further insights into the stability and properties of the SRB gel spheres. The findings underscore the potential of SRBbased bioremediation as a sustainable and efficient method for AMD treatment, offering a novel and environmentally friendly solution to mitigating the adverse effects of environmental contamination. [ABSTRACT FROM AUTHOR]

Background: Propofol is widely used during anesthesia. However, propofolinduced injection pain (PIP) is considered an unpleasant perioperative outcome. This study aimed to investigate the efficacy of a mixture of esketamine and propofol in preventing propofol injection pain in patients undergoing general anesthesia. Methods: This was a prospective, double-blind, multicenter, and randomized controlled trial. We included 252 adult patients with the American Society of Anesthesiologists physical status I to II who underwent surgery under general anesthesia. Patients were randomly allocated in a 1:1:1:1 ratio to four groups (n = 63 per group). Group NS received a mixture of 1% propofol (20 ml) and 0.9% normal saline (1 ml), group ESK-4 received a mixture of 1% propofol (20 ml) and esketamine 4mg (diluted with 0.9% normal saline, 1 ml), group ESK-12 received a mixture of 1% propofol (20 ml) and esketamine 12 mg (diluted with 0.9% normal saline, 1 ml), and group ESK-20 received a mixture of 1% propofol (20 ml) and esketamine 20 mg (diluted with 0.9% normal saline, 1 ml) as sedative drugs during anesthesia. The primary outcome was the incidence and distribution of different degrees of PIP. The secondary outcomes were vital signs, characteristics of surgery and anesthesia, and adverse events. Results: The incidence of PIP in group ESK-20 (33.3%) was significantly lower than that in groups NS, ESK-4, and ESK-12 (63.3%, 62.2%, and 49.1%, respectively; p < 0.01). The incidence of moderate PIP in group NS (33.3%) and group ESK-4 (22.6%) was higher than that in groups ESK-12 (7.5%) and ESK-20 (6.7%). The incidence of severe PIP in group NS (6.7%) and group ESK-4 (9.4%) was higher than that in groups ESK-12 (1.9%) and ESK-20 (0%). There were no differences in the vital signs, characteristics of surgery and anesthesia, or adverse events between the groups. Conclusion: Our results indicated that the esketamine-propofol admixture reduced the incidence of PIP in patients undergoing general anesthesia without severe side effects. [ABSTRACT FROM AUTHOR]

Cryopreservation of small quantities of human spermatozoa whilst maintaining adequate post- thawing motility has been found an essential challenge for male fertility preservation. Therefore, the study used an effective, and convenient rapid- freezing method to freeze small amounts of human spermatozoa by adding self- prepared cryoprotectant (SPC) without animal component. In the feasibility experiment, no significant differences in progressive motility, normal sperm morphology, vitality or DNA fragmentation index between the conventional slow freezing and rapid freezing were realised. The present study prospectively analysed the effects of sperm freezing and resuscitation in 175 patients with severe oligozoospermia (sperm concentration <1 x 106/ml). We observed the 120 severe oligozoospermia specimens had a mean recovery rate of 60.19% ± 10.43% and a mean cryosurvival rate of 68.0% ± 9.17%. In addition, 55 cryptozoospermia specimens were analysed. The small- volume cryopreservation showed advantages. The total sperm recovery, motility recovery and sperm loss rates were 98.48%, 50.17% and 1.52% respectively. In short, the SPC is safe and effective, and can be used to rapidly freeze severe oligozoospermia specimens. That is useful for successful sperm freezing whilst avoiding the risk of azoospermia in the later stages and promoting comprehensive fertility preservation. [ABSTRACT FROM AUTHOR]

The improvement performance of refrigerating dehumidification system was theoretically discusses based on a dehumidification model. The influence of evaporator inlet wind speed, dry bulb temperature and relative humidity on dehumidification were analysed by the model. The results show that, when inlet air temperature and humidity were kept constant, the dehumidification capacity increased first and then decreased with increase of the wind speed. When the moisture content and the wind speed of the inlet air were kept constant, the dehumidification capacity gradually decreased with increase of the inlet air dry bulb temperature. The inlet air dry bulb temperature was between 21-36 °C and the relative humidity was between 40% and 85%, the difference between the inlet air wet bulb temperature and the evaporation temperature at the optimum COP was about 10 °C. There was a nearly linear relationship between the corresponding evaporation temperature at the optimal COP and the evaporation temperature with the maximum dehumidification capacity, compared with the test value, the error was less than 10%. [ABSTRACT FROM AUTHOR]

NOD-like receptors (NLRs) are traditionally recognized as major inflammasome components. The role of NLRs in germ cell differentiation and reproduction is not known. Here, we identified the gonadspecific Nlrp14 as a pivotal regulator in primordial germ cell-like cell (PGCLC) differentiation in vitro. Physiologically, knock out of Nlrp14 resulted in reproductive failure in both female and male mice. In adult male mice, Nlrp14 knockout (KO) inhibited differentiation of spermatogonial stem cells (SSCs) and meiosis, resulting in trapped SSCs in early stages, severe oligozoospermia, and sperm abnormality. Mechanistically, NLRP14 promoted spermatogenesis by recruiting a chaperone cofactor, BAG2, to bind with HSPA2 and form the NLRP14-HSPA2-BAG2 complex, which strongly inhibited ChIPmediated HSPA2 polyubiquitination and promoted its nuclear translocation. Finally, loss of HSPA2 protection and BAG2 recruitment by NLRP14 was confirmed in a human nonsense germline variant associated with male sterility. Together, our data highlight a unique proteasome-mediated, noncanonical function of NLRP14 in PGCLC differentiation and spermatogenesis, providing mechanistic insights of gonad-specific NLRs in mammalian germline development. [ABSTRACT FROM AUTHOR]

Background Male infertility is a prevalent issue worldwide, mostly due to the impaired sperm motility. Multiple morphological abnormalities of the sperm flagella (MMAF) present aberrant spermatozoa with absent, short, coiled, bent and irregular-calibre flagella resulting in severely decreased motility. Previous studies reported several MMAF-associated genes accounting for approximately half of MMAF cases. Methods and result We conducted genetic analysis using whole-exome sequencing in 88 Han Chinese MMAF probands. CFAP65 homozygous mutations were identified in four unrelated consanguineous families, and CFAP65 compound heterozygous mutations were found in two unrelated cases with MMAF. All these CFAP65 mutations were null, including four frameshift mutations (c.1775delC [p.Pro592Leufs*8], c.3072_3079dup [p.Arg1027Profs*41], c.1946delC [p.Pro649Argfs*5] and c.1580delT [p.Leu527Argfs*31]) and three stop-gain mutations (c.4855C>T [p.Arg1619*], c.5270T>A [p.Leu1757*] and c.5341G>T [p.Glu1781*]). Additionally, two homozygous CFAP65 variants likely affecting splicing were identified in two MMAF-affected men of Tunisian and Iranian ancestries, respectively. These biallelic variants of CFAP65 were verified by Sanger sequencing and were absent or very rare in large data sets aggregating sequence information from various human populations. CFAP65, encoding the cilia and flagella associated protein 65, is highly and preferentially expressed in the testis. Here we also generated a frameshift mutation in mouse orthologue Cfap65 using CRISPR-C as9 technology. Remarkably, the phenotypes of Cfap65-mutated male mice were consistent with human MMAF. [ABSTRACT FROM AUTHOR]

Abstract: We first report the hybrids of TiO2 and graphene (Gr) used as the support of Pd nanoparticles, showing high performance electrocatalysts for formic acid oxidation. The hybrids are prepared with the solvothermal method, and tetrabutyl titanate and graphene-oxide (GO) are used as the precursors. The initial mass ratios of Ti:GO in the precursors are 0.07, 0.15, 0.26, 0.60, respectively. Compared to Pd/graphene, the as-obtained Pd/TiO2-Gr electrocatalysts exhibit higher catalytic activity and stability. Among them, the Pd/TiO2-Gr (Ti : GO = 0.26, initial mass ratio) exhibit the highest activity. Its current density is about 3.1 times of Pd/graphene, and the agglomeration of Pd metal that can be seen in Pd/graphene has been inhibited in the as prepared Pd/TiO2-Gr. Thus the electrocatalytic performance of Pd for formic acid oxidation is greatly improved by the binary TiO2-graphene support. [ABSTRACT FROM AUTHOR]

It is believed that a transition region may exist between the bulk adhesive and the adherend, which would play an important role in the performance of the joint. Epoxy/aluminum joints were studied using a nano-indenter and an atomic force microscope (AFM). Some samples were based on direct bonding of aluminum specimens with the epoxy adhesive and some used aluminum samples pre-coated with a softer epoxy system to simulate a soft interphase. The topography of indented samples was measured using AFM and the image was used to define the indentation positions. Results were interpreted in terms of three types of interactions of the indenter with the sample in the interface region: (a) direct contact of the indenter with both phases during indentation, (b) contact of the indenter with a single phase but for which the indentation response was directly affected by the adjacent phase and (c) contact with a modified resin phase near the interface the: 'interphase'. The importance of sample surface preparation was also studied. Results showed that polishing the surface often resulted in formation of ridges and troughs near the interface which resulted in artifacts, which could be interpreted as indicating the presence of a soft interphase. [ABSTRACT FROM AUTHOR]