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Emerging evidence suggests that the APOBEC family is implicated in multiple cancers and might be utilized as a new target for cancer detection and treatment. However, the dysregulation and clinical implication of the APOBEC family in clear cell renal cell cancer (ccRCC) remain elusive. TCGA multiomics data facilitated a comprehensive exploration of the APOBEC family across cancers, including ccRCC. Remodeling analysis classified ccRCC patients into two distinct subgroups: APOBEC family pattern cancer subtype 1 (APCS1) and subtype 2 (APCS2). The study investigated differences in clinical parameters, tumor immune microenvironment, therapeutic responsiveness, and genomic mutation landscapes between these subtypes. An APOBEC family-related risk model was developed and validated for predicting ccRCC patient prognosis, demonstrating good sensitivity and specificity. Finally, the overview of APOBEC3B function was investigated in multiple cancers and verified in clinical samples. APCS1 and APCS2 demonstrated considerably distinct clinical features and biological processes in ccRCC. APCS1, an aggressive subtype, has advanced clinical stage and a poor prognosis. APCS1 exhibited an oncogenic and metabolically active phenotype. APCS1 also exhibited a greater tumor mutation load and immunocompromised condition, resulting in immunological dysfunction and immune checkpoint treatment resistance. The genomic copy number variation of APCS1, including arm gain and loss, was much more than that of APCS2, which may help explain the tired immune system. Furthermore, the two subtypes have distinct drug sensitivity patterns in clinical specimens and matching cell lines. Finally, we developed a predictive risk model based on subtype biomarkers that performed well for ccRCC patients and validated the clinical impact of APOBEC3B. Aberrant APOBEC family expression patterns might modify the tumor immune microenvironment by increasing the genome mutation frequency, thus inducing an immune-exhausted phenotype. APOBEC family-based molecular subtypes could strengthen the understanding of ccRCC characterization and guide clinical treatment. Targeting APOBEC3B may be regarded as a new therapeutic target for ccRCC.

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Many annotated long noncoding RNAs (lncRNAs) contain small open reading frames (sORFs), some of which have been demonstrated to encode small proteins or micropeptides with fundamental biological importance. However, functions of lncRNAs-encoded small proteins or micropeptides in viral pathogenesis remain largely unexplored. Here, we identified a 110-amino acid small protein as a key regulator of influenza A virus (IAV) replication. This small protein that we call PESP was encoded by the putative lncRNA PCBP1-AS1. It was observed that both PCBP1-AS1 and PESP were significantly upregulated by IAV infection. Furthermore, they were markedly induced by treatment with either type I or type III interferon. Overexpression of either PCBP1-AS1 or PESP alone significantly enhanced IAV replication. In contrast, shRNA-mediated knockdown of PCBP1-AS1 or CRISPR/Cas9-mediated knockout of PESP markedly inhibited the viral production. Moreover, the targeted deletion or mutation of the sORF within the PCBP1-AS1 transcript, which resulted in the disruption of PESP expression, significantly diminished the capacity of PCBP1-AS1 to enhance IAV replication, underscoring the indispensable role of PESP in the facilitation of IAV replication by PCBP1-AS1. Interestingly, overexpression of PESP enhanced the IAV-induced autophagy by increasing the expression of ATG7, an essential autophagy effector enzyme. We also found that the 7-22 amino acids at the N-terminus of PESP were crucial for its functionality in modulating ATG7 expression and action as an enhancer of IAV replication. Additionally, HSP90AA1, a protein identified previously as a facilitator of autophagy, was found to interact with PESP, resulting in the stabilization of PESP and consequently an increase in the production of IAV. These data reveal a critical lncRNA-encoded small protein that is induced and exploited by IAV during its infection, and provide a significant insight into IAV-host interaction network.

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Source separation and decentralized domestic wastewater treatment represent effective strategies to enhance sewage treatment performance and facilitate water reuse economically. The Living Machine (LM) system has gained widespread adoption for decentralized sewage treatment. While underwater light source has been demonstrated to enhance the treatment performance of open aerobic reactors in LM systems, its influence on the treatment efficiency of a fully multistage LM system remains underreported. In this study, an underwater lamp-added LM system (ULLM) with eight reactors was constructed and investigated. The introduction of underwater light source obviously improved the removal capacity of chemical oxygen demand (COD) and NH4+-N, which was 96.1% and 61.6%, respectively. The diversity of algae, zooplankton, and aquatic animals was notably higher in the light-treated reactors than in the control group (CK) without underwater light source, and substantial alteration in the microbial community of the light-treated reactors was observed compared with CK reactors. At the phylum level, Proteobacteria and Nitrospirae enriched in the underwater light-treated reactors, while Bacteroidetes and Actinobacteria exhibited a decrease after light exposure. At the genus level, Nitrospira and Rhodanobacter were enriched in the ULLM system. Importantly, the prevalence of these two dominant genera was sustained until the final operational stage, indicating their potential key roles in enhancing wastewater treatment performance. The addition of underwater light source proves to be an effective strategy for augmenting the treatment efficiency of the multistage living machine systems, resulting in substantial improvements in pollutant removal. These findings contribute valuable insights into optimizing LM systems for decentralized wastewater treatment.

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To expand the application of nobiletin (NOB) in semi-solid functional foods, bovine serum albumin (BSA)/carboxymethyl inulin (CMI) complexes-stabilized Pickering emulsion (BCPE) (φoil = 60%, v/v) was fabricated, and the swallowing index and bioavailability of the NOB-loaded Pickering emulsion was evaluated. Confocal laser scanning microscope (CLSM) and cryo-scanning electron microscopy (cryo-SEM) images revealed that BSA/CMI complexes attached to the oil-water interface. NOB-loaded BCPE exhibited a viscoelastic and shear-thinning behavior. Fork drip test results suggested that the textural value of unloaded and NOB-loaded emulsions was International Dysphagia Diet Standardisation Initiative Level 4, which could be swallowed directly without chewing. The in vitro lipolysis model suggested that NOB had a faster digestive profile and a higher bioaccessibility in the BCPE than in the oil suspension. The in vivo rat model revealed that the oral bioavailability of NOB was increased by 2.07 folds in BCPE compared to its bioavailability in unformulated oil. Moreover, BCPE led to a higher plasma concentration of the major demethylated metabolite of NOB (4'-demethylnobiletin) than the unformulated oil. Accordingly, BCPE enhanced the oral bioavailability of NOB by improving bioaccessibility, absorption, and biotransformation.

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Objective: The administration of progesterone before transfer in hormone replacement treatment (HRT) is crucial for the clinical outcomes of frozen-thawed embryo transfer (FET), but the optimal duration of progesterone remains controversial. This study aimed to investigate the effect of the duration of progesterone administration on the clinical outcomes of FET cycles. Methods: This prospective cohort study included 353 artificial FET cycles conducted at a reproductive medicine center between April and October 2021. The FET cycles were stratified into four groups based on the duration of progesterone supplementation before the procedure and the embryonic development stage: group P3 (73 patients) received intramuscular progesterone for 3 days and group P4 (87 patients) for 4 days before Day 3 frozen embryo transfer, group P5 (70 patients) for 5 days and group P6 (123 patients) for 6 days before frozen blastocyst transfer. This trial was performed using one or two vitrified embryo(s) when the endometrial thickness reached 7 mm after estrogen supplementation in an artificial cycle. The primary outcome was clinical pregnancy, and secondary outcomes included biochemical pregnancy, implantation, early pregnancy loss, and live births. Results: There were no significant differences in the demographic and clinical characteristics between the groups. No significant difference was observed in the clinical pregnancy rates between groups: 23/73 (31.5%) in group P3 vs 28/87 (32.2%) in group P4 (P = 0.927). Compared to group P5 (41/70, 58.6%), the clinical pregnancy rate was not significantly different in group P6 (77/123, 62.6%, P = 0.753). There was no significant difference in the implantation rates between groups: 33/136 (24.3%) in group P3 vs 34/166 (20.5%) in group P4 (P = 0.431), and 62/133 (46.6%) in group P5 vs 107/231 (46.3%) in group P6 (P = 0.956). The duration of progesterone supplementation (mean: 3.5 ± 0.5 days; range:3-4 days) before Day 3 frozen embryo transfer did not impact clinical pregnancy (odds ratio [OR] 1.048; 95% confidence interval [CI], 0.518-2.119). The duration of progesterone administration (mean: 5.6 ± 0.5 days; range:5-6 days) before frozen blastocyst transfer may not affect clinical pregnancy (OR 1.339; 95% CI, 0.717-2.497). Conclusion: There may be no significant correlation between the duration of progesterone supplementation and pregnancy outcomes in artificial FET cycles, although the clinical pregnancy rate was higher when progesterone supplementation was extended for one day before FET.

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This study aimed to investigate the synergistic effect of γ-glutamyl peptides (γEL, γEV, and γEγEV) and l-glutamate (MSG) on the activation of the umami receptor (T1R1/T1R3) in relation to enhanced umami taste and promoted cholecystokinin (CCK) secretion. The synergy of γ-glutamyl peptides and MSG (1-15 mM, 1:1) caused a significant increase in both the umami taste score by 0.218 ± 0.015-1.216 ± 0.031 times and the CCK secretion by 41.41 ± 6.46-201.16 ± 12.91% when compared to the group treated with individual MSG. The increase in CCK secretion promoted by γ-glutamyl peptides was only reduced by 11.54 ± 0.01-45.65 ± 3.58% after adding yjr CaSR inhibitor (NPS 2143), implying that there were other receptors besides CaSR involved in the stimulation of CCK secretion. The mixture of γEγEV and MSG synergistically increased the intracellular calcium release by 111.26 ± 11.94-135.28 ± 16.60% in STC-1 and 108.47 ± 7.89-152.33 ± 26.26% in HEK 293 compared to MSG. The protein expression for T1R1/T1R3 was increased, indicating that the mixture can activate T1R1/T1R3. The amino acids V277, S147, and D190 of T1R3 can be critical for the binding of γEγEV to T1R3. This is the first report on the synergistic effect of taste-active substances on taste sensation and hormone release via taste receptor activation.

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Background: The recurrence of polyps after endoscopic treatment is a difficult problem and there may be an association between blood lipid levels and colorectal polyps, but this is controversial and the aim of this study is to explore the risk factors for colorectal polyp recurrence. Methods: A total of 357 patients who underwent intestinal polypectomy from January 1, 2019 to June 1, 2020 in Sichuan Provincial People's Hospital were included in this retrospective study to analyze the potential association between blood indices and recurrence risk. Polyp recurrence was defined as the detection of 1 or more polyps at any time after polypectomy, regardless of site. Follow-up was performed through the electronic medical record system. Patients' age, gender, tobacco and alcohol liking, duration of follow-up, body mass index (BMI), polyp size, number, type of pathology, and lipid profiles (triglycerides, cholesterol, apolipoprotein B, and apolipoprotein A) were collected. Results: Triglycerides (1.54±0.95 vs. 1.25±1.01, P=0.036) and apolipoprotein B (0.87±0.26 vs. 0.79±0.16 mL, P=0.001) were significantly different in both the recurrence and non-recurrence groups. Binary logistic regression identified 3 independent risk factors for recurrence: triglycerides [odds ratio (OR): 1.763, 95% confidence interval (CI): 1.003 to 3.098, P=0.049], apolipoprotein B (OR: 5.438, 95% CI: 1.411 to 20.961, P=0.014), and the number of polyps (OR: 2.540, 95% CI: 1.649 to 3.911, P<0.001). Conclusions: High levels of triglycerides, apolipoprotein B, and the number of colorectal polyps are risk factors for colorectal polyp recurrence after endoscopic resection. Therefore, for patients at high risk of polyp recurrence, we recommend aggressive control of triglyceride and apolipoprotein B levels.

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This paper aims to investigate the physical and 3D printing properties of arrowroot starch (AS), a natural biopolymer with many potential health benefits. Scanning electron microscopy images showed that AS granules had mixed spherical and elongated geometries, with average sizes of 10.5 ± 2.5 µm. The molecular weight of AS measured by gel permeation chromatography (GPC) was 3.24 × 107 g/mol, and the amylose/amylopectin ratio of AS was approximately 4:11. AS has an A-type crystal structure, with a gelatinization temperature of 71.8 ± 0.2 °C. The overlap concentration (C*) of AS in aqueous solutions was 0.42% (w/v). Temperature-dependent dynamic rheological analyses of 10% to 30% (w/v) AS fluids showed that the storage modulus (G') reached the maximum values around the gelatinization temperatures, while the yield stress (τy) and flow stress (τf) values all increased with the increase in AS concentration. The printing accuracy of AS gels was found to be associated with the interplay between the G' values and the restorability after extrusion, determined by the three-interval thixotropy tests (3ITT). The optimum 3D printing condition occurred at 20% (w/v) AS, the nozzle diameter of 0.60 mm, the printing speed of 100 mm/s and the extrusion speed of 100 mm/s. Our research provides a promising biopolymer to be used in the design of novel personalized functional foods.

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The significance of conjoined oocytes in the clinical in vitro fertilization (IVF) laboratory setting has been questionable due to the extremely limited data available. This issue is discussed by presenting one case for conjoined oocyte observed in the program of the assisted reproduction and by including a review of corresponding literature. This report describes a successful clinical pregnancy with subsequent live birth from a conjoined oocyte. To our knowledge, there are only three reported cases of successful live birth from conjoined oocytes, but this is the first case of live birth from a blastocyst derived from a conjoined oocyte fertilized using intracytoplasmic sperm injection (ICSI) in a frozen embryo transfer cycle. Moreover, this study reports the first time that live birth of a conjoined oocyte is achieved without removing the degenerated immature oocyte prior to transfer. It demonstrates that the degenerated immature oocyte has no adverse effect on subsequent embryo development and pregnancy outcome. In addition, we reviewed the literature to evaluate the origin, incidence, safety, and significance of conjoined oocytes in reproductive health. We further confirm previous reports that demonstrate that a mature oocyte from conjoined-oocyte complexes can be fertilized by standard IVF or ICSI and lead to the development of a blastocyst, subsequent pregnancy, and live birth.

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Bladder cancer is one of the most common urogenital malignancies in the world, and there are no adequate prognostic indicators. CNTD2 is one of the atypical cyclins, which may be related to the cell cycle and even the development of cancers. Early studies have shown that CNTD2 is closely related to the occurrence and development of many malignant tumors. However, the mechanism of CNTD2 in bladder cancer has not been reported. In our research, we explored the different expressions of CNTD2 between 411 bladder cancers and 19 normal bladder tissues based on the TCGA dataset. CNTD2-related signaling pathways were identified through the GSEA. We analyzed the associations of CNTD2 expression and bladder cancer progression and survival using GSE13507. Compared with 19 cases of normal bladder tissue, CNTD2 gene expression was increased in 411 cases of bladder cancer. The high expression of CNTD2 strongly correlated with grade (P < 0.0001), T classification (P = 0.0001), N classification (P = 0.00011), M classification (P = 0.044), age (P = 0.027), and gender (P = 0.0012). Bladder cancer patients with high CNTD2 expression had shorter overall survival (P < 0.001). In the meantime, univariate and multivariate analyses showed that the increased expression of CNTD2 was an independent factor for poor prognosis in bladder cancer patients (P < 0.001 and P < 0.001, respectively). CNTD2 expression is closely related to bladder cancer progression, and the high expression of CNTD2 may be an adverse biomarker in bladder cancer patients.

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Glutaminase of Bacillus amyloliquefaciens has been used to synthesize the immunomodulatory γ-D-glutamyl-L-tryptophan (γ-D-Glu-L-Trp) and the kokumi-active γ-D-glutamyl peptides. The optimum yield of γ-D-Glu-L-Trp was 55.76 mM in corresponding to a minimum yield of by-product (γ-D-Glu-γ-D-Glu-L-Trp) in the presence of 75 mM D-Gln and 100 mM L-Trp. The glutaminase has a low Km values for the donors (D-Gln and L-Gln:5.53 and 0.98 mM), but high ones for the acceptors (L-Trp, L-Phe, L-Met, L-Val and γ-[D-Glu]( n =1,2,3)-L-Val/L-Phe/L-Met, ranging from 32.51 to 193.05 mM). The highest Km value appearing when n = 2 (γ-[D-Glu]( n =0,1,2)-L-Val/L-Phe/L-Met) suggested the rising difficulty for synthesis when the number of donor increases in the reaction mixtures. The γ-[D-Glu]( n =1,2,3)-L-Val/L-Phe/L-Met at 5 mM can impart the blank chicken broth an enhancing monthfulness, thickness, and umaminess taste.

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Nobiletin has received much attention for its promising biological activities. Owing to its limited solubility, various encapsulation strategies have been developed to enhance nobiletin bioavailability. However, the understanding of the bioavailability and biotransformation of nobiletin in vivo and the correlation between in vitro and in vivo data remains limited. This study developed a high-loading nobiletin (1%) emulsion. The in vitro models, which combined pH-stat lipolysis with a Franz cell, showed very good correlation with in vivo data for the relative bioavailability. Rat studies showed that nobiletin had a high absolute bioavailability (≈20% for oil suspension). Besides, the emulsification improved the amount of bioavailable nobiletin and its major metabolite in the blood by about two times, as compared to an oil suspension. This work provides scientific insights into a rapid screening method for delivery systems and a better understanding of the biological fate of nobiletin in vivo.

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As a functional polysaccharide, inulin was carboxymethylated and it formed nanocomplexes with bovine serum albumin (BSA). The success of obtaining carboxymethyl inulin (CMI) was confirmed by a combination of Fourier transform Infrared (FT-IR), Raman spectroscopy, gel permeation chromatography (GPC), and titration. The effects of pH and ionic strength on the formation of CMI/BSA nanocomplexes were investigated. Our results showed that the formation of complex coacervate (pHφ1) and dissolution of CMI/BSA insoluble complexes (pHφ2) appeared in pH near 4.85 and 2.00 respectively. FT-IR and Raman data confirmed the existence of electrostatic interaction and hydrogen bonding between CMI and BSA. The isothermal titration calorimetry (ITC) results suggested that the process of complex formation was spontaneous and exothermic. The complexation was dominated by enthalpy changes (∆Η < 0, ∆S < 0) at pH 4.00, while it was contributed by enthalpic and entropic changes (∆Η < 0, ∆S > 0) at pH 2.60. Irregularly shaped insoluble complexes and globular soluble nanocomplexes (about 150 nm) were observed in CMI/BSA complexes at pH 4.00 and 2.60 while using optical microscopy and atomic force microscopy, respectively. The sodium chloride suppression effect on CMI/BSA complexes was confirmed by the decrease of incipient pH for soluble complex formation (or pHc) and pHφ1 under different sodium chloride concentrations. This research presents a new functional system with the potential for delivering bioactive food ingredients.

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BACKGROUND: Fusidic acid (FA) (WU-FA-00) is the only commercially available antimicrobial from the fusidane family that has a narrow spectrum of activity against Gram-positive bacteria. METHODS: Herein, the hydrogenation derivative (WU-FA-01) of FA was prepared and both compounds were examined against a panel of six bacterial strains. In addition, their anti-inflammatory properties were evaluated using a 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced mouse ear edema model. RESULTS: The results of the antimicrobial assay revealed that both WU-FA-00 and WU-FA-01 displayed a high level of antimicrobial activity against Gram-positive strains. Moreover, killing kinetic studies were performed and the results were in accordance with the minimum inhibitory concentration and minimum bactericidal concentration results. We also demonstrated that the topical application of WU-FA-00 and WU-FA-01 effectively decreased TPA-induced ear edema in a dose-dependent manner. This inhibitory effect was associated with the inhibition of TPA-induced upregulation of proinflammatory cytokines IL-1ß, TNF-α, and COX-2. WU-FA-01 significantly suppressed the expression levels of p65, IκB-α, and p-IκB-α in the TPA-induced mouse ear model. CONCLUSION: Overall, our results showed that WU-FA-00 and WU-FA-01 not only had effective antimicrobial activities in vitro, especially to the Gram-positive bacteria, but also possessed strong anti-inflammatory effects in vivo. These results provide a scientific basis for developing FA derivatives as antimicrobial and anti-inflammatory agents.

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The wide spread of Klebsiella pneumoniae carbapenemase (KPC)-producing Enterobacteriaceae is great threat to public health in China. Plasmids are among the major factors mediating blaKPC gene dissemination. A total of 156 carbapenem-resistant Enterobacteriaceae (CRE) isolates were identified in a tertiary hospital in China. Six KPC-producing isolates, namely, E. coli (n = 2), E. asburiae (n = 1), C. freundii (n = 1), C. portucalensis (n = 1), and C. koseri (n = 1), tested positive for the pCKPC18-1-like untypeable plasmid, which was described recently in C. freundii. All 6 plasmids could be easily transferred into E. coli by chemical transformation or conjugation and were confirmed by sequencing to harbor blaKPC-2. Multilocus PCRs and EcoRI-RFLP revealed that the 6 untypeable plasmids belonged to 2 isoforms. High-throughput sequencing of representative plasmids (pCP40 and pEC86) led to the identification of 2 plasmids that shared the common backbone genes repA, DnaJ, StpA, and yafB, which were characteristic of the untypeable plasmid, and had similar blaKPC-2 genetic contexts of the Tn3-Tn4401 chimera. Nucleotide comparison revealed high sequence identity of the 2 plasmids with previously reported blaKPC-2-carrying untypeable plasmids. In particular, the pCP40 plasmid from C. portucalensis and the pHS062105-3 plasmid from K. pneumoniae differed by only 20 single-nucleotide polymorphisms (SNPs). To the best of our knowledge, this is the first report of a blaKPC-harboring untypeable plasmid spread into E. coli, E. asburiae, and C. koseri strains in China.

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BACKGROUND: The aim of the present study was to analyze the relationship between the outcomes of hormone replacement therapy frozen embryo transfer (HRT-FET) and serum estradiol and progesterone levels on the day of endometrial transformation and before transplantation. METHODS: Clinical data of patients who underwent 426 cycles of HRT-FET were retrospectively analyzed and were divided into group according to estradiol and progesterone levels. Differences in embryo implantation rate and clinical pregnancy rate were compared, and relationship between estradiol levels and outcome of transplantation was analyzed. RESULTS: During the 426 cycles, clinical pregnancy rate was 49.77% and embryo implantation rate was 27.20%. Differences in estradiol and progesterone levels on the day of endometrial transformation and before transplantation between pregnant and non-pregnant groups were not statistically significant. Furthermore, embryo implantation rate and clinical pregnancy rate among different levels of estradiol patients was not statistical different. On the day before transplantation, serum estradiol level decreased in 98.36% of patients. Differences in implantation rate and clinical pregnancy rate among patients with different extents of decrease in estradiol and different progesterone levels the day before transplantation were statistically significant (P<0.05). CONCLUSIONS: The extent of decrease in serum estradiol and progesterone levels on the day before transplantation may be associated with outcome of HRT-FET.

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OBJECTIVE: To evaluate the efficacy and safety of tamsulosin and solifenacin combination therapy compared with tamsulosin monotherapy for male lower urinary tract symptoms (LUTS). METHODS: We identified all eligible studies that compared tamsulosin and solifenacin combination therapy with tamsulosin monotherapy for male LUTS (up to January 2015). The fixed- or random-effects model was selected depending on the proportion of heterogeneity. RESULTS: Seven articles were identified as eligible for this meta-analysis, with a total of 3063 participants. Synthetic data showed combination therapy had significant improvements in Storage International Prostate Symptom Score (WMD = -0.60; 95% CI: -0.81 to -0.38, P < 0.0001), quality of life (WMD = -0.23; 95% CI: -0.34 to -0.11, P < 0.0001), micturitions per 24 hours (WMD = -0.70; 95% CI: -0.86 to -0.55, P < 0.0001) and urgency episodes per 24 hours (WMD = -0.26; 95% CI: -0.48 to -0.05, P = 0.018). The incidence of adverse effects in the tamsulosin and solifenacin combined therapy group (30.82%) was similar to the tamsulosin monotherapy group (25.75%). Acute urinary retention was seldom reported in the studies and no clinically significant changes regarding Qmax were showed in our meta-analysis. CONCLUSIONS: Tamsulosin and solifenacin combination therapy may be a reasonable option for male LUTS patients, especially for those who have significant storage symptoms. However, PVR should be measured during treatment to assess the increase in PVR or the incidence of AUR.

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BACKGROUND AND OBJECTIVES: Methylenetetrahydrofolate reductase (MTHFR) polymorphism may be a risk factor for male infertility. However, the epidemiologic studies showed inconsistent results regarding MTHFR polymorphism and the risk of male infertility. Therefore, we performed a meta-analysis of published case-control studies to re-examine the controversy. METHODS: Electronic searches of PubMed, EMBASE, Google Scholar and China National Knowledge Infrastructure (CNKI) were conducted to select eligible literatures for this meta-analysis (updated to June 19, 2014). According to our inclusion criteria and the Newcastle-Ottawa Scale (NOS), only high quality studies that observed the association between MTHFR polymorphism and male infertility risk were included. Crude odds ratio (OR) with 95% confidence interval (CI) was used to assess the strength of association between the MTHFR polymorphism and male infertility risk. RESULTS: Twenty-six studies involving 5,575 cases and 5,447 controls were recruited. Overall, MTHFR 677C>T polymorphism showed significant associations with male infertility risk in both fixed effects (CT+TT vs. CC: OR = 1.34, 95% CI: 1.23-1.46) and random effects models (CT+TT vs. CC: OR = 1.39, 95% CI: 1.19-1.62). Further, when stratified by ethnicity, sperm concentration and control sources, the similar results were observed in Asians, Caucasians, Azoo or OAT subgroup and both in population-based and hospital-based controls. Nevertheless, no significant association was only observed in oligo subgroup. CONCLUSIONS: Our results indicated that the MTHFR polymorphism is associated with an increased risk of male infertility. Further well-designed analytical studies are necessary to confirm our conclusions and evaluate gene-environment interactions with male infertility risk.

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OBJECTIVE: To investigate the location and characteristics of microdeletions of Y chromosome azoospermia factor (AZF) genes in infertile males with azoospermia and severe oligozoospermia in southern Sichuan. METHODS: Multiplex PCR was used to detect 18 sequence tagged sites (STS) involved in Y chromosome AZF microdeletions among 224 infertile males (including 134 azoospermia cases and 90 severe oligozoospermia cases) and 70 healthy males. RESULTS: Among the 224 infertile males, the overall frequency of microdeletions was 12.1% (27/224), and were 13.4% (18/134) in those with azoospermia and 10.0% (9/90) in those with severe oligozoospermia. The most frequent microdeletions have occurred in the AZFc region (51.9%). Compared with the 6 STS loci recommended by European Academy of Andrology and European Molecular Genetics Quality Network, 22.7% more deletions were detected based on the 18 STS loci selected from the AZF region. CONCLUSION: Identification of Y chromosome microdeletions has a significant implication on the diagnosis of male infertility. The most frequent microdeletions have occurred in the AZFc region in southern Sichuan. To use more sequence tagged sites for the screening can improve the reliability and detection rate of Y chromosome microdeletions.

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