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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.
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HLA-DPB1*05:01:20 differs from HLA-DPB1*05:01:01:01 by one nucleotide in exon 3.
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Alelos , Pueblo Asiatico , Secuencia de Bases , Exones , Cadenas beta de HLA-DP , Prueba de Histocompatibilidad , Análisis de Secuencia de ADN , Humanos , Cadenas beta de HLA-DP/genética , Pueblo Asiatico/genética , Análisis de Secuencia de ADN/métodos , Donantes de Tejidos , Alineación de Secuencia , Codón , Pueblos del Este de AsiaRESUMEN
HLA-C*03:652 differs from the HLA-C*03:04:01:01 by one nucleotide in exon 3.
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Alelos , Pueblo Asiatico , Secuencia de Bases , Exones , Antígenos HLA-C , Prueba de Histocompatibilidad , Análisis de Secuencia de ADN , Humanos , Antígenos HLA-C/genética , Pueblo Asiatico/genética , Análisis de Secuencia de ADN/métodos , Alineación de Secuencia , Codón , Pueblos del Este de AsiaRESUMEN
HLA-B*38:103N differs from HLA-B*38:02:01:01 by one nucleotide in exon 3.
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Antígenos HLA-B , Nucleótidos , Humanos , Alelos , Análisis de Secuencia de ADN , Antígenos HLA-B/genética , ChinaRESUMEN
HLA-B*46:01:42 differs from HLA-B*46:01:01:01 by one nucleotide in exon 5.
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Genes MHC Clase I , Nucleótidos , Humanos , Alelos , Antígenos HLA-B/genética , China , Análisis de Secuencia de ADNRESUMEN
HLA-C*08:273 differs from HLA-C*08:01:01:01 by one nucleotide in exon 2.
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Genes MHC Clase I , Antígenos HLA-C , Humanos , Antígenos HLA-C/genética , Alelos , Nucleótidos , China , Análisis de Secuencia de ADNRESUMEN
HLA-B*48:01:13 differs from HLA-B*48:01:01:01 by one nucleotide in exon 5.
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Antígenos HLA-B , Nucleótidos , Humanos , Alelos , Análisis de Secuencia de ADN , Antígenos HLA-B/genética , ChinaRESUMEN
HLA-A*11:448 differs from HLA-A*11:01:01:01 by one nucleotide in exon 5.
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Antígenos HLA-A , Nucleótidos , Humanos , Alelos , Análisis de Secuencia de ADN , Antígenos HLA-A/genética , ChinaRESUMEN
HLA-B*27:267 differs from HLA-B*27:04:01 by one nucleotide in exon 2.
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Pueblos del Este de Asia , Antígenos HLA-B , Humanos , Alelos , Análisis de Secuencia de ADN , Antígenos HLA-B/genética , NucleótidosRESUMEN
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.
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Inteligencia Artificial , Infertilidad Masculina , Masculino , Humanos , Microscopía por Crioelectrón , Motilidad Espermática/genética , Semen , Espermatozoides , Microtúbulos/metabolismo , Cola del Espermatozoide/química , Cola del Espermatozoide/metabolismo , Proteínas de Microtúbulos/química , Infertilidad Masculina/genética , Infertilidad Masculina/metabolismoRESUMEN
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.
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Anemia Aplásica , Enfermedades Hematológicas , Humanos , Estudios Retrospectivos , Anemia Aplásica/genética , Pueblos del Este de Asia , Receptores KIR/genética , Genotipo , Enfermedades Hematológicas/genética , Frecuencia de los GenesRESUMEN
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.
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Cilios , Motilidad Espermática , Humanos , Masculino , Ratones , Animales , Semen , Flagelos , Dineínas , Modelos Animales de Enfermedad , MamíferosRESUMEN
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.
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Aflatoxina B1 , Arachis , Aflatoxina B1/metabolismo , Aflatoxina B1/toxicidad , Animales , Arachis/metabolismo , Bovinos , Heces , Inactivación Metabólica , MicrobacteriumRESUMEN
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.
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@#AIM: To evaluate the clinical effects and safety of Loratadine combined with Diclofenac sodium eye drops in the treatment of allergic conjunctivitis by system review.METHODS:Using “Loratadine” “Diclofenac sodium” and “allergic conjunctivitis” as keywords, a randomized controlled trial of Loratadine combined with diclofenac sodium in the treatment of allergic conjunctivitis was searched in Embase, Cochrane library, Pubmed, CNKI, Wanfang database, VIP and SionMed. The retrieval time is from the establishment of the database to July 2021. The risk bias tool provided by the Cochrane cooperation scale was used to assess the risk bias of included studies of RCTs. The publication bias of the included studies was assessed by the Egger's test. Meta-analysis of clinical efficiency, incidence of adverse effects, ocular itch score, and discharge score were using RevMan 5.3. Descriptive analysis were performed on the results with high heterogeneity.RESULTS:A total of 19 articles were included, all of which were Chinese literatures, including 1 931 patients(2 044 eyes). The control group was treated with Loratadine, and the experimental group was treated with Loratadine combined with Diclofenac sodium eye drops. The Meta-analysis showed that the clinical effect of experimental group was better than control group(<i>OR</i>=4.43, 95%<i>CI</i>:3.26-6.03,<i>P</i><0.00001).The incidence of adverse reaction was lower than control group(<i>OR</i>=0.32, 95%<i>CI</i>:0.2-0.52,<i>P</i><0.00001). The Score of ocular itching(<i>MD</i>=-0.36, 95%<i>CI</i>:-0.39 to -0.33,<i>P</i><0.00001)and discharge(<i>MD</i>=-0.24,95%<i>CI</i>: -0.31 to -0.18,<i>P</i><0.00001)in experimental group was lower than control group. All the studies on hyperemia and edema of conjunctiva, conjunctival papilla or follicle proliferation and foreign body sensation in patients with allergic conjunctivitis showed that the experimental group could significantly reduce the above symptoms(all <i>P</i><0.05). Egger's test was performed on the total effective rate, the incidence of adverse reaction. The results showed that there was publication bias in the total effective. Trim and fill method showed that the publication bias did not affect the results.CONCLUSION: On the basis of the oral Loratadine, combined with Diclofenac sodium eye drops has a certain clinical efficacy in the treatment of allergic conjunctivitis, which can improve the clinical symptoms such as ocular itching, foreign body sensation, hyperemia and edema of conjunctiva, and the incidence of adverse reactions is low, which can provide evidence-based basis for the drug treatment of allergic conjunctivitis in the future. However, due to the low intensity of the included research evidence, more multicenter, randomized double-blind clinical trials are needed in the future, so that to improve the evidence intensity.
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@#AIM: To evaluate the clinical effects of subconjunctival injection of vitamin C in the treatment of corneal ulcer by using Meta-analysis.<p>METHODS: Using “vitamin C” and “corneal ulcer” as keywords, the randomized controlled trials(RCT)of subconjunctival injection of vitamin C in Embase, Cochrane library, Pubmed, CNKI and Wanfang database in the treatment of corneal ulcer was searched. Relevant reference published before February 2021. The risk bias tool provided by the Cochrane cooperation scale was used to assess the risk bias of included studies of RCTs. The publication bias of the included studies were assessed by the Egger's test with Stata software. Meta-analysis was performed with RevMan 5.3.<p>RESULTS: A total of 32 eligible articles were included, all of which were Chinese literatures, with a total of 4 514 patients. The control group was treated with routine treatment, and the experimental group was treated with subconjunctival injection of vitamin C combined with routine treatment. The Meta-analysis showed that the experimental group was better than control group(<i>OR</i>=4.61, 95%<i>CI</i>:3.70, 5.74). The recurrence rate was lower than control group(<i>OR</i>=0.24, 95%<i>CI</i>: 0.18, 0.31). The cure time in experimental group was shorter than control group(<i>MD</i>= -6.29, 95%<i>CI</i>: -7.08, -5.51), 32 studies do not adequately report adverse drug reactions(ADR). Egger's test was performed on the total effective rate, recurrence rate and cure time. The results showed that there was publication bias in the total effective rate and cure time. Trim and fill method showed that the publication bias did not affect the results.<p>CONCLUSION: Subconjunctival injection of vitamin C is feasible in the treatment of corneal ulcer. The clinical effect, cure time and recurrence rate were better than routine treatment. However, due to the low intensity of the included research evidence, more multicenter, randomized double-blind clinical trials are needed to improve the evidence intensity of vitamin C in the treatment of corneal ulcer.
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Pneumonia caused by SARS-CoV-2 has seriously threatened human life and health worldwide and caused a large number of deaths. Viral infection and acute inflammation are important causes of death, so it is particularly important to combine antiviral therapy with anti-inflammatory therapy. Glycyrrhizic acid, the main component of the glycyrrhizic root extract, has a wide range of pharmacological effects as well as high efficiency and low toxicity, its preparation has been widely used in the treatment of chronic hepatitis and other diseases. Glycyrrhizic acid can regulate the expression and release of a variety of cytokines and play a significant anti-inflammatory effect. At the same time, glycyrrhizic acid also showed significant inhibition towards a variety types of viruses. Therefore, the potential application of glycyrrhizic acid as COVID-19 treatment should be explored.
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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.
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Decápodos , Palaemonidae , Animales , Cuevas , China , Agua DulceRESUMEN
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.