Microplastics and Nanoplastics Effects on Plant-Pollinator Interaction and Pollination Biology.

Microplastics and nanoplastics (MNPs) contamination is an emerging environmental and public health concern, and these particles have been reported both in aquatic and terrestrial ecosystems. Recent studies have expanded our understanding of the adverse effects of MNPs pollution on human, terrestrial, and aquatic animals, insects, and plants. In this perspective, we describe the adverse effects of MNPs particles on pollinator and plant health and discuss the mechanisms by which MNPs disrupt the pollination process. We discuss the evidence and integrate transcriptome studies to investigate the negative effects of MNPs on the molecular biology of pollination, which may cause delay or inhibit the pollination services. We conclude by addressing challenges to plant-pollinator health from MNPs pollution and argue that such harmful effects disrupt the communication between plant and pollinator for a successful pollination process.

Danggui Buxue Tang: A Review of its Major Components.

Context: Danggui Buxue Tang (DBT) is a classical Chinese medicine that practitioners have used for thousands of years. Historically, those practitioners have used 16 prescriptions of DBT but currently are using only three prescriptions. Objective: The review intended to summarize pharmacological profiles of DBT and also clarify the major active chemicals found within it to provide a better understanding of the significance of DBT clinically. Design: The research team performed a narrative review by searching Pubmed databases. The search used the keywords Danggui Buxue Tang, bioactive chemcials, pharmacological functions. Setting: The databases setting were done by Gong Guowei and Zhou Xuan in the Zunyi Medical University, Zhuhai campus. Results: There are multiple results related to the crude fractions isolated from Danggui Buxue Tang, and also included the clinical trails. Conclusions: Thousands of years of clinical experience have ensured the efficacy of TCM treatments, which can determine the direction of basic research. That research can modify formulas at the molecular level to improve targeting and specificity in the treatment of specific diseases. As a result, the discovery and identification of new compounds within the herbal complex can provide useful research ideas and ensure the viability of new drug development.

Silencing the triacylglycerol lipase (TGL) gene decreases the number of apyrene sperm and inhibits oviposition in Sitotroga cerealella.

Triacylglycerol lipase (TGL) is an essential lipid metabolism enzyme that also plays a critical role in energy metabolism; however, how it regulates other life processes is unknown. To investigate the functional role of TGL in moth reproduction, males Sitotroga cerealella were used as a model. The TGL gene was cloned and analysed. The results showed that the open reading frame of TGL was 1968 bp long and contained three conserved regions. TGL gene expression was higher in the larval and early adult stages than in the pupal stage, with the highest levels observed in the fat body, testis and accessory glands during the early adult stage. Moreover, after TGL in male adults was silenced through RNAi, the protein content in male accessory glands remained unchanged, and the spermatophore transferred into females mated with TGL-silenced males became small and empty; meanwhile, the number of apyrene sperm in the spermatophore was significantly reduced due to the reduction of apyrene sperm in males, which eventually led to the significant reduction of egg-laying amount. All of the findings suggest that TGL regulates the amount of sperm in male moths as well as the morphology and quality of spermatophores transferred to females after mating with treated males, implying that TGL is critical for Sitotroga cerealella's reproductive process.

Diallyl trisulfide reduced the reproductive capacity of male Sitotroga cerealella via the regulation of juvenile and ecdysone hormones.

Environmental pollution and resistance in animals are major concerns for the application of synthetic pesticides. Diallyl trisulfide (DAT), an active compound in garlic essential oil, is a novel tool for active and safe control of agricultural insect pests. In this study, we analysed the effects of DAT (0.01 µL/L) on the protein content in male reproductive tissues (accessory glands, ejaculatory ducts, and testis), and juvenile hormone (JH) and ecdysone titres in a highly detrimental pest of stored products, Sitotroga cerealella. Evaluation of the expression profile of JH and ecdysone pathway-related genes in various tissues indicated that the accessory gland protein and ecdysone titres were markedly decreased after DAT fumigation, whereas the testis protein content and JH titre were increased. However, the protein content of the ejaculatory ducts remained unchanged between the treated and control groups. Further investigation revealed that DAT disrupted the mRNA expression of key enzymes involved in JH and ecdysone pathways. While increased mRNA levels of juvenile hormone acid O-methyltransferase (JHMAT) and Kruppel homologue 1 (Kr-h1) were observed after 4 and 7 h of DAT fumigation, the levels of juvenile hormone epoxide hydrolase (JHEH) were substantially reduced 3 h post-fumigation. mRNA levels of the ecdysone-responsive gene, FTZF1, and cytochrome P450 enzyme, CYP315A1, were notably decreased at 7 h and 4 h, respectively, post-fumigation, whereas CYP314A1 and CYP302A1 mRNA levels decreased after 3 h and 4 h, respectively. While DAT fumigation disrupted sperm number in the testis, ejaculatory ducts, and seminal vesicles, topical application of the 20-hydroxyecdysone (20E) analogue also lowered sperm number in the ejaculatory ducts. Topical application of methoprene, a JH analogue, increased the protein content in the testes, but not in the accessory glands or ejaculatory ducts. However, the survival rate was not affected by the topical application of methoprene or 20E. These data suggest that DAT regulates JH and ecdysone via its molecular pathway genes and modulates endocrine secretion during the male reproductive process.

Novel compound heterozygous variants of DNAH17 in a Chinese infertile man with multiple morphological abnormalities of sperm flagella.

Multiple morphological abnormalities of the sperm flagellum (MMAF) have been reported to be an important cause of male infertility and reflect a heterogeneous genetic disorder. Previous studies have identified dozens of candidate pathogenic genes for MMAF, but the aetiology in approximately 50% of cases remains unexplained. The present study aimed to identify novel potentially pathogenic gene variants of MMAF. A Chinese family with a 32-year-old infertile proband presenting with MMAF was recruited, and sperm morphology of the patient was examined by Papanicolaou staining. Whole exome sequencing was performed on the proband and Sanger sequencing was used to identify genetic variants in the family. The frequencies of variants were assessed using public databases and the effects on protein structure and function were predicted by online bioinformatics tools. The patient exhibited asthenozoospermia and a MMAF phenotype. Novel compound heterozygous variants (c.5368C > T, p.R1790C and c.13183C > T, p.R4395W) of the DNAH17 gene were identified in the patient, and showed autosomal recessive inheritance in this family. These variants were very rare in the GnomAD database. The two mutated amino acids were located in a highly conserved region of the DNAH17 protein. In silico analysis revealed that the compound heterozygous variants may compromise the function of DNAH17. Our findings expand upon the spectrum of pathogenic DNAH17 variants that are responsible for MMAF, and provide new knowledge for genetic counselling of male infertility due to MMAF.

LncRNA HOTAIR regulates the expression of E-cadherin to affect nasopharyngeal carcinoma progression by recruiting histone methylase EZH2 to mediate H3K27 trimethylation.

BACKGROUND/AIM: There has been increasing evidence for the function of long non-coding RNA (lncRNA) in nasopharyngeal carcinoma (NPC). We aim to delve into the position of lncRNA HOX antisense intergenic RNA (HOTAIR), together with enhancer of zeste homolog 2 (EZH2), E-cadherin and trimethylation of lysine 27 on histone H3 (H3K27me3) in NPC. METHODS: HOTAIR, EZH2, and E-cadherin expression in NPC tissues and cells were tested. NPC cell biological functions were examined through gain-of and loss-of function assays. The mechanism of lncRNA HOTAIR/E-cadherin/EZH2/H3K27 axis in NPC was decoded. RESULTS: LncRNA HOTAIR and EZH2 were highly expressed in NPC, and E-cadherin was lowly expressed. Down-regulation of HOTAIR or EZH2 inhibited NPC cell progression and tumor growth. HOTAIR recruited histone methylase EZH2 to mediate trimethylation of H3K27 and regulated E-cadherin expression. CONCLUSION: HOTAIR inhibits E-cadherin by stimulating the trimethylation of H3K27 to promote NPC cell progression through recruiting histone methylase EZH2.

FASCIN regulates actin assembly for spindle movement and polar body extrusion in mouse oocyte meiosis.

During mouse oocyte meiotic maturation, actin filaments play multiple roles in meiosis such as spindle migration and cytokinesis. FASCIN is shown to be an actin-binding and bundling protein, making actin filaments tightly packed and parallel-aligned, and FASCIN is involved in several cellular processes like adhesion and migration. FASCIN is also a potential prognostic biomarker and therapeutic target for the treatment of metastatic disease. However, little is known about the functions of FASCIN in oocyte meiosis. In the present study, we knocked down the expression of FASCIN, and our results showed that FASCIN was essential for oocyte maturation. FASCIN was all expressed in the different stages of oocyte meiosis, and it mainly localized at the cortex of oocytes from the GV stage to the MII stage and showed a similar localization pattern with actin and DAAM1. Depletion of FASCIN affected the extrusion of the first polar body, and we also observed that some oocytes extruded from the large polar bodies. This might have resulted from the defects of actin assembly, which further affected the meiotic spindle positioning. In addition, we showed that inhibition of PKC activity decreased FASCIN expression, indicating that FASCIN might be regulated by PKC. Taken together, our results provided evidence for the important role of FASCIN on actin filaments for spindle migration and polar body extrusion in mouse oocyte meiosis.

Effects of diallyl trisulfide, an active substance from garlic essential oil, on structural chemistry of chitin in Sitotroga cerealella (Lepidoptera: Gelechiidae).

The environmental pollution, evolution of resistance, and risks to human and aquatic animal health associated with pesticide application have attracted much attention globally. Herein, we tested the capacity of diallyl trisulfide (DAT) from garlic essential oil to control the destructive stored-product pest, Sitotroga cerealella. The effects of DAT on the total content of cuticular chitin and structure of adults S. cerealella were evaluated. This study was the first to investigate changes in chitin structure in adults due to exposure to DAT through Fourier-transform infrared spectroscopy, thermogravimetric analysis, X-ray diffraction, and differential scanning calorimetry. The results of these analyses revealed that the cuticular chitin content of pests decreased after DAT treatment. DAT treatment also reduced thermal stability and crystallinity of chitin. These findings indicate that DAT is a potent biopesticide that is active against the moth, and establishes the basis for its use as an IPM and alternative to chitin synthesis inhibitors.

[Correlation of single nucleotide polymorphisms of the osteopontin gene with astheozoospermia].

OBJECTIVE: To investigate the correlation of the single nucleotide polymorphisms (SNP) rs1126772, rs117291487, rs11730582, rs142608941 and rs6813526 of the osteopontin (OPN) gene with the risk of asthenozoospermia (AZS). METHODS: We included 135 AZS patients in the AZS group and another 239 fertile men as normal controls. Using the SNaPshot technique, we genotyped the rs1126772, rs117291487, rs11730582, rs142608941 and rs6813526 polymorphisms of the OPN gene in all the subjects and analyzed the correlation of the five SNPs with AZS. RESULTS: The GA genotype and A allele of the OPN gene rs1126772 were found to be correlated with the risk of AZS (GA vs AA: OR = 0.55, 95% CI: 0.35－0.86, P = 0.009; A vs G: OR = 0.64, 95% CI: 0.46－0.89, P = 0.007), and so was the CT genotype and T allele at the RS11730582 locus (CT vs TT: OR = 0.526, 95% CI: 0.34－0.82, P = 0.009; T vs C: OR = 0.60, 95% CI: 0.44－0.83, P = 0.002). Haplotype analysis showed that the AATCT haplotype decreased the risk of AZS (AATCT: OR = 0.61, 95% CI: 0.42－0.88, P = 0.008) . CONCLUSIONS: The polymorphisms of the OPN gene RS1126772 and RS11730582 may reduce the risk of AZS.

Alteration in the sensitivity to crizotinib by Na+/H+ exchanger regulatory factor 1 is dependent to its subcellular localization in ALK-positive lung cancers.

BACKGROUND: Na+/H+ exchanger regulatory factor 1 (NHERF1) is an important scaffold protein participates in the modulation of a variety of intracellular signal pathways. NHERF1 was able to enhance the effects of chemo-drugs in breast and cervical cancer cells. Anaplastic lymphoma kinase (ALK) fusion mutations are validated molecules targeted therapy in lung cancers, where crizotinib can be used as the specific inhibitor to suppress tumor progression. However, due to the less frequent occurrence of ALK mutations and the complexity for factors to determine drug responses, the genes that could alter crizotinib sensitivity are unclear. METHODS: Both ALK-translocated and ALK-negative lung adenocarcinoma specimens in tissue sections were collected for immunohistochemistry. The possible mechanisms of NHERF1 and its role in the cell sensitivity to crizotinib were investigated using an ALK-positive and crizotinib-sensitive lung adenocarcinoma cell line H3122. Either a NHERF1 overexpression vector or agents for NHERF1 knockdown was used for crizotinib sensitivity measures, in association with cell viability and apoptosis assays. RESULTS: The expression level of NHERF1 in ALK-translocated NSCLC was significantly higher than that in other lung cancer tissues. NHERF1 expression in ALK positive lung cancer cells was regulated by ALK activities, and was in return able to alter the sensitivity to crizotinib. The function of NHERF1 to influence crizotinib sensitivity was depending on its subcellular distribution in cytosol instead of its nucleus localized form. CONCLUSION: Ectopically overexpressed NHERF1 could be a functional protein for consideration to suppress lung cancers. The determination of NHERF1 levels in ALK positive NSCLC tissues might be useful to predict crizotinib resistance, especially by distinguishing cytosolic or nuclear localized NHERF1 for the overexpressed molecules.

Treatment delay in childhood pleural tuberculosis and associated factors.

BACKGROUND: Delay in diagnosis and treatment worsens the disease and clinical outcomes, which further enhances the transmission of tuberculosis (TB) in the community. Therefore, this study aims to assess treatment delay and its associated factors among childhood pleural TB patients in China. METHODS: Between January 2006 and December 2019, consecutive patients aged ≤15 years with definite or possible pleural TB were included for analysis. Treatment delay duration was defined as the time interval from the onset of symptoms to treatment initiation and was stratified into two categories: < 30 days, ≥30 days (median delay day is 30 days). The electronic medical records of children were reviewed to obtain demographic characteristics, clinical characteristics, laboratory examinations, and radiographic findings. Univariate and multivariate logistic regressions were used to explore the factors associated with treatment delay in patients. RESULTS: A total of 154 children with pleural TB were included, with a mean age of 12.4 ± 3.3 years. The median treatment delay was 30 days (interquartile range, 10-60 days) and 51.3% (n = 79) of patients underwent a treatment delay. Multivariate analysis revealed that heart rate (≤92 beats/min, age-adjusted OR = 2.503, 95% CI: 1.215, 5.155) and coefficient of variation of red cell distribution width (RDW-CV, ≥12.9%, age-adjusted OR = 4.705, 95% CI: 2.048, 10.811) were significant risk factors for treatment delays in childhood pleural TB. CONCLUSION: Our findings suggested that a significant treatment delay occurs among children with pleural TB in China. Patients with a low heart rate or a high RDW-CV experienced delays in the initiation of anti-TB therapy. Therefore, well awareness of the associations between clinical characteristics and treatment delay may improve the management of children with pleural TB and enable us to develop preventive strategies to reduce the treatment delay.

Genetic polymorphisms in interleukin 13 gene with the susceptibility to nasopharyngeal carcinoma in a Chinese population.

Although inflammation is emerging as a candidate risk factor in tumorigenesis of nasopharyngeal carcinoma (NPC). In particular, Interleukin (IL) 13 involved inflammatory diseases and cancers. Single nucleotide polymorphisms in IL-13 have been associated with multiple cancers. The study analyzed genetic polymorphisms in IL-13 aiming to investigate its' potential susceptibility with the NPC. The genotyping of polymorphisms (rs20541, rs1295687 and rs2069744) was examined by Snapshot SNP and DNA sequencing. All SNPs were within Hardy-Weinberg equilibrium and each appeared in three genotypes in NPC and controls. Adjusted logistic regression showed that the TT genotype of rs20541 increased the risk of lymph node metastasis (TT vs. CC: OR = 2.87, 95%CI, 1.33-6.18, P = 0.007). CT/CC genotypes were associated with the decreased the risk of lymph node metastasis in NPC (CT/CC vs. TT: OR = 0.32, 95%CI, 0.16-0.65, P = 0.002). The concentration of IL-13 was significantly elevated in NPC patients compared with controls (P = 0.012). Moreover, significant differences were detected in the T-C-T haplotype distribution between NPC patients and controls (OR = 2.47, 95%CI, 1.06-5.78, P = 0.031). Our results, the first report, provide evidence that rs20541 polymorphisms may affect the lymph node metastasis of NPC patients in Chinese population.

Exosomal lncRNA HNF1A-AS1 affects cisplatin resistance in cervical cancer cells through regulating microRNA-34b/TUFT1 axis.

BACKGROUND: There is growing evidence of the role of long non-coding RNAs (lncRNAs) in cervical cancer (CC). The objective was to discuss whether exosomal lncRNA HNF1A-AS1 impacted drug resistance in CC via binding to microRNA-34b (miR-34b) and regulating TUFT1 expression. METHODS: The expression of HNF1A-AS1 in normal cervical epithelial cells, cisplatin (DDP)-sensitive cell line (HeLa/S) and DDP-resistant cell line (HeLa/DDP) cells were detected. HeLa/S and HeLa/DDP cells were interfered with HNF1A-AS1 to determine IC50, proliferation, colony formation and apoptosis of CC cells. The exosomes were isolated and identified. Subcellular localization of HNF1A-AS1, expression of miR-34b and TUFT1 in receptor cells were also verified. The binding site between HNF1A-AS1 and miR-34b, together with miR-34b and TUFT1 were confirmed. Tumorigenic ability of cells in nude mice was also detected. RESULTS: HNF1A-AS1 was upregulated in DDP-resistant cell line HeLa/DDP. Silencing HNF1A-AS1 suppressed CC cell proliferation and promoted its apoptosis. HNF1A-AS1 was found to act as a competing endogenous RNA (ceRNA) of miR-34b to promote the expression of TUFT1. Exosomes shuttled HNF1A-AS1 promoted the proliferation and drug resistance of CC cells and inhibited their apoptosis by upregulating the expression of TUFT1 and downregulating miR-34b. Furthermore, suppressed exosomal HNF1A-AS1 in combination with DDP inhibited tumor growth in nude mice. CONCLUSION: Our study provides evidence that CC-secreted exosomes carrying HNF1A-AS1 as a ceRNA of miR-34b to promote the expression of TUFT1, thereby promoting the DDP resistance in CC cells.

Association of GRP78 promoter polymorphisms and serum GRP78 level with risk of asthenozoospermia.

PURPOSE: The aim of this study was undertaken to investigate the association of 78-kDa glucose-regulated protein (GRP78) gene promoter polymorphisms with risk of asthenozoospermia (AZS) men. In addition, we performed association analysis between GRP78 promoter mutations and serum GRP78 level in asthenozoospermia. METHODS: The study population comprised 400 subjects with AZS patients and 400 healthy controls. We assessed GRP78 rs3216733, rs17840761, and rs17840762 polymorphisms by using Snapshot SNP genotyping assays; serum GRP78 level was measured by enzyme-linked immunosorbent assay (ELISA). Semen quality was assessed by computer-assisted semen analysis. RESULTS: We found that rs3216733 was associated with increased risk of AZS (Gd vs. dd: adjusted OR = 1.42, 95% CI, 1.06-1.93, P = 0.020; Gd/GG vs. dd: adjusted OR = 1.43, 95% CI, 1.08-1.91, P = 0.013; G vs. d adjusted OR = 1.26, 95% CI, 1.03-1.56, P = 0.027). The haplotype analyses showed the frequency of G-C-C haplotype was significantly higher in AZS (P = 0.026). The percentage of progressive motility sperm was lower in the asthenozoospermic men with Gd and Gd/GG genotypes than dd genotype (P = 0.003). Moreover, the serum GRP78 levels were significantly lower in rs3216733 Gd/GG genotypes compared with the dd genotype (P < 0.001). CONCLUSION: Our findings suggest that rs3216733 Gd/GG genotypes contribute to poor sperm motility, probably by decreasing the level of GRP78.

Efficacy of Metarhizium anisopliae isolate MAX-2 from Shangri-la, China under desiccation stress.

BACKGROUND: Metarhizium anisopliae, a soil-borne entomopathogen found worldwide, is an interesting fungus for biological control. However, its efficacy in the fields is significantly affected by environmental conditions, particularly moisture. To overcome the weakness of Metarhizium and determine its isolates with antistress capacity, the efficacies of four M. anisopliae isolates, which were collected from arid regions of Yunnan Province in China during the dry season, were determined at different moisture levels, and the efficacy of the isolate MAX-2 from Shangri-la under desiccation stress was evaluated at low moisture level. RESULTS: M. anisopliae isolates MAX-2, MAC-6, MAL-1, and MAQ-28 showed gradient descent efficacies against sterile Tenebrio molitor larvae, and gradient descent capacities against desiccation with the decrease in moisture levels. The efficacy of MAX-2 showed no significant differences at 35% moisture level than those of the other isolates. However, significant differences were found at 8% to 30% moisture levels. The efficacies of all isolates decreased with the decrease in moisture levels. MAX-2 was relatively less affected by desiccation stress. Its efficacy was almost unaffected by the decrease at moisture levels > 25%, but slowly decreased at moisture levels < 25%. By contrast, the efficacies of other isolates rapidly decreased with the decrease in moisture levels. MAX-2 caused different infection characteristics on T. molitor larvae under desiccation stress and in wet microhabitat. Local black patches were found on the cuticles of the insects, and the cadavers dried without fungal growth under desiccation stress. However, dark black internodes and fungal growth were found after death of the insects in the wet microhabitat. CONCLUSIONS: MAX-2 showed significantly higher efficacy and superior antistress capacity than the other isolates under desiccation stress. The infection of sterile T. molitor larvae at low moisture level constituted a valid laboratory bioassay system in evaluating M. anisopliae efficacy under desiccation stress.

Discussion: Harnessing microbiome-mediated adaptations in insect pollinators to mitigate climate change impact on crop pollination.

Insect pollinators, vital for agriculture and biodiversity, face escalating threats from climate change. We argue and explore the pivotal role of the microbiomes in shaping adaptations of insect pollinator resilience amid climate-induced challenges (climate change and habitat alteration). Examining diverse taxonomic groups, we unravel the interplay between insect physiology, microbiomes, and adaptive mechanisms. Climate-driven alterations in microbiomes impact insect health, behavior, and plant interactions, posing significant effects on agricultural ecosystems. We propose harnessing microbiome-mediated adaptations as a strategic approach to mitigate climate change impacts on crop pollination. Insights into insect-pollinator microbiomes offer transformative avenues for sustainable agriculture, including probiotic interventions (use of EM PROBIOTIC) and microbiome engineering (such as engineering gut bacteria) to induce immune responses and enhanced pollination services. Integrating microbiome insights into conservation practices elucidates strategies for preserving pollinator habitats, optimizing agricultural landscapes, and developing policies to safeguard pollinator health in the face of environmental changes. Finally, we stress interdisciplinary collaboration and the urgency of understanding pollinator microbiome dynamics under climate change in future research.

Embryonic exposure to aluminum chloride blocks the onset of spermatogenesis through disturbing the dynamics of testicular tight junctions via upregulating Slc25a5 in offspring.

Studies have revealed neurotoxicity, hepatotoxicity, and developmental and reproductive toxicity in mice exposed to aluminum. However, relatively few studies have been conducted to clarify the mechanism underlying the impact of embryonic exposure to aluminum on the development of the male reproductive system in offspring. Pregnant mice were administered aluminum chloride (AlCl3) by gavage from day 12.5 of gestation until birth. Our findings demonstrated that embryonic exposure to AlCl3 disrupted testicular development and spermatogenesis by impairing testicular architecture, reducing sperm count, and upregulating the expression of tight junction (TJ) protein between Sertoli cells (SCs). Further in vitro studies revealed that treatment with AlCl3 stabilized TJ proteins Occludin and ZO-1 expression by inhibiting ERK signaling pathway activation, thereby upregulating Slc25a5 expression which induced ATP production leading to disruption of cytoskeletal protein homeostasis. Therefore, the study provided a new mechanistic insight into how AlCl3 exposure interfered with testicular development and spermatogenesis while suggesting that Slc25a5 might be a target affected by AlCl3 influencing cell metabolism.

Identification of a Homozygous Mutation of CCDC40 in a Chinese Infertile Man with MMAF and PCD-like Phenotypes.

Aims: Asthenozoospermia is the most common factor of male infertility, mainly caused by multiple morphological abnormalities of the sperm flagella (MMAF) and primary ciliary dyskinesia (PCD). Previous studies have shown that genetic factors may contribute to MMAF and PCD. The study aimed to identify novel potentially pathogenic gene mutations in a Chinese infertile man with MMAF and PCD-like phenotypes. Methods: A Chinese infertile man with MMAF and PCD was enrolled in this study. Whole exome sequencing and Sanger sequencing were performed to identify potential causative genes and mutations. Results: A novel homozygous missense mutation (c.1450G>A; p.E484K) of CCDC40 was finally identified and Sanger sequencing confirmed that the patient carried the homozygous mutation, which was inherited from his parents. We reported the first homozygous missense CCDC40 mutation in infertile men with MMAF but had other milder PCD symptoms. Conclusion: Our findings not only broaden the disease-causing mutation spectrum of CCDC40 but also provide new insight into the correlation between CCDC40 mutations and MMAF.