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Background and Objective: Anxiety and depression are experienced following addicted patients durg withdrawal. This study was done to determine the effect of methadone and valproate combination on morphine withdrawal-induced anxiety and depression in male mice. Methods: In this experimental study, ninety-eight male mice were allocated into acute and chronic categories. Animals in acute chronic categories allocated into seven groups including: saline, morphine, methadone (10 mg/kg/bw), valproate (150 mg/kg/bw), three groups of valproate+methadone, in of ratio 1:1, 2:1 and 1:2. Animals were received escalating dose of morphine for 8 consecutive days except saline group. In chronic group, drugs were injected for 30 minutes before morphine administration, while in acute group the drugs were used only at day 8. Anxiety and depression due to naloxone injection (5 mg/kg/bw) was investigated by elevated plus-maze, tail-suspension and open field tests. Results: In the chronic group, valproate + methadone (2:1) combination therapy showed a significant increase in the percentage of open arm entries (53.86±1.9) and percentage of time spent in the open arm (58.58±4.15) compared to the morphine group, with a percentage of entering (28.12±2.03) and percentage of time (17.88±1.77) (P

A test system was designed to evaluate the failure behavior of a thin-wall small-diameter polyethylene tube under internal pressure. The test setup was capable of delivering constant (static) and cyclic (dynamic) pressure patterns as well as maintaining an elevated testing temperature to accelerate the failure. Desired pressure patterns were obtained by controlling the opening/closing duration of the solenoid valves accordingly. A water-sensing system was used to detect the failure time, particularly for small brittle failure. A data acquisition system based on LabView[TM] was used to control and record the applied pressures and the failure times. The constant pressure tests were performed at 65 and 75[degrees]C and the cyclic pressure tests were performed at 75[degrees]C. The test data obtained from the constant pressure tests exhibited two distinguishable linear regions in a log-log plot of hoop stress versus failure time. Slope values of -0.034 and -0.113 were obtained for ductile and brittle regions, respectively. A brittle failure curve with slope of -0.039 was obtained under the cyclic pressure testing condition. The slow crack growth (SCG) failure was considerably accelerated by the cyclic loading., Editor's Note: We present, in its entirety and with minimal editing, the following paper, chosen by the Plastic Pipes and Fittings Special Interest Group as the best paper at ANTEC [...]

Ovulation rate and litter size are traits of fecundity and have a very remarkable economic value that leads to an increase in the production of meat, wool and milk. Therefore, exploring on the candidate and functional genes for these traits is very important. Growth differentiation factor 9 (GDF9), bone morphogenetic protein 15 (BMP15) and bone morphogenetic protein receptor-1B (BMPR1B) are the most important of these genes containing single nucleotide polymorphisms (SNPs) markers that are associated with high fertility in sheeps. The aim of this study was to determine the allelic and genotypic frequencies of seven of these SNPs including; G1, G4, G7 and G8 in GDF9 gene, B2 and B4 in BMP15 gene and FecB in BMPR1B gene among 532 sheeps from eleven of Iranian native breeds using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. For each mutation region, polymerase chain reactions and digestion reactions with specific endonuclease enzymes, were performed. The results showed that G1 mutation presents among ten breeds except Zandi, G4 mutation in all breeds, and the FecB mutation in two breeds; Kalakuei and Zandi. The G7, G8, B2 and B4 mutations were not observed in any of breeds, and all sheeps were homozygote wild type for these four positions. [ABSTRACT FROM AUTHOR]

Utilization of fecundity genes such as GDF9 and BMP15 can help improve reproductive traits in sheep breeding programme. To evaluate effects of missense mutations on protein function, the polymorphisms of GDF9 and BMP15 genes were screened in twelve mehraban sheep using DNA sequencing, followed by protein structure modeling. Six single nucleotide polymorphism (SNPs) known as FecG mutations (G1-G6), were detected in exons 1 and 2 of GDF9 gene. Mutations of G1 (GDF9 exon 1 g.2118 G>A), G4 (GDF9 exon 2 g.3451 T>C) and G6 (GDF9 exon 2 g.3974 G>A) have shown amino acid substitution. None polymorphism was detected in exon 1 and exon 2 of BMP15 gene. Based on identified polymorphisms, individuals were classified into three haplotypes of wild haplotype (without mutation), haplotype A (simultaneous mutations of G1, G2, G3 and G4) and haplotype B (simultaneous mutations of G5 and G6). The 3D-structure of GDF9 protein in A and B haplotypes was rotated 90° and 45° than wild haplotype, respectively. The missenses G1/p.Arg87His, G4/p.Glu241Lys and G6/p.Val332Ile variants were benign. However both the missenses of G7/p.Val371Met and G8/p.Ser315Phe were probably damaging. Phylogenetic tree of GDF9 gene revealed that individuals with A and B haplotypes were distinct from wild haplotypes with bootstrapping values of 63 and 76, respectively. In conclusion, GDF9 protein in A and B haplotypes showed a higher performance than wild haplotype due to synergism effects of simultaneous mutations. These types of mutations with effect on turn and helix of GDF9 conservative regions showed physical and functional interaction with TGFβ proteins. [ABSTRACT FROM AUTHOR]

Despite much attention, history of sheep (Ovis aries) evolution, including its dating, demographic trajectory and geographic spread, remains controversial. To address these questions, we generated 45 complete and 875 partial mitogenomic sequences, and performed a meta-analysis of these and published ovine mitochondrial DNA sequences (n = 3,229) across Eurasia. We inferred that O. orientalis and O. musimon share the most recent female ancestor with O. aries at approximately 0.790 Ma (95% CI: 0.637-0.934 Ma) during the Middle Pleistocene, substantially predating the domestication event (~8-11 ka). By reconstructing historical variations in effective population size, we found evidence of a rapid population increase approximately 20-60 ka, immediately before the Last Glacial Maximum. Analyses of lineage expansions showed two sheep migratory waves at approximately 4.5-6.8 ka (lineages A and B: ~6.4-6.8 ka; C: ~4.5 ka) across eastern Eurasia, which could have been influenced by prehistoric West-East commercial trade and deliberate mating of domestic and wild sheep, respectively. A continent- scale examination of lineage diversity and approximate Bayesian computation analyses indicated that the Mongolian Plateau region was a secondary center of dispersal, acting as a "transportation hub" in eastern Eurasia: Sheep from the Middle Eastern domestication center were inferred to have migrated through the Caucasus and Central Asia, and arrived in North and Southwest China (lineages A, B, and C) and the Indian subcontinent (lineages B and C) through this region. Our results provide new insights into sheep domestication, particularly with respect to origins and migrations to and from eastern Eurasia. [ABSTRACT FROM AUTHOR]

Introduction: Infertility is a common problem around the world followed by psycho-social conesquences. Determining the prevalence of infertility in society can assist health system decision-makers to plan the provision of health and medical services more precisely. This study was conducted in response to the question of the Iranian Scientific Association of Fertility-Infertility with the aim of determining the prevalence of life-time primary and current primary infertilities in the Islamic Republic of Iran. Methods: This study was conducted by using a cross-sectional method on 12000 Iranian women aged 19-49 as the couples. representatives in 28 provinces of the country in 2004-2005. The sampling method was based on the systematic random selection of 400 thirty-household clusters with a proportionate probability to the size of the population of urban and rural areas of each province. The lifetime primary infertility was defined based on one of the two scenarios that follow: The first scenario: 1) A safe contraceptive method has been used after marriage, 2) but the use of contraceptive has been discontinued after a while, 3) 12 months or more past the first discontinuation of the contraceptive method at the time of the study and 4) The case has not become pregnant within 12 months after discontinuation of the contraception method. The second scenario: 1) A safe contraception methods has not been used after marriage, 2) No conception was achieved within 12 months after marriage. The term current primary infertility was applied to a woman who had never been conceived up to the study, as well as being defined by one of the above definitions. Data analysis was conducted by using STATA 8.0 software while considering the concepts of descriptive statistics and computing the 95% confidence intervals. Lowest smoothing method was also used to smooth the scatter plot of the relationship between infertility and age at the time of the first marriage. Results: In this study, 7350 urban and 4650 rural Iranian women, aged 19-49 in 28 provinces were interviewed. Among the 12000 interviewed subjects 630, (5.3%), cases were not eligible for the study and were left out of the study and the denominator of the primary infertility computation fraction. A history of life-time primary infertility was observed in 24.9% of the couples, (95% CI: 23.6-26.2%), as was the prevalence of current primary infertility in 3.4% of them, (95% CI: 3.0-3.8%). The trend of lifetime primary infertility showed that the highest estimate was related to the lowest marriage age and the lowest prevalence was observed at the marriage age of 22 in 19% of the cases. This trend remained stable up to the age of 28 but it increased afterwards. The mean age of the subjects at the first marriage was 18.1±3.8 and a median of 18 years. Conclusions: About one fourth of Iranian couples experience primary infertility in their lives and 3.4% of them have this problem at any time in their life. In interpreting the pre. [ABSTRACT FROM AUTHOR]

Background: Single sperm cryopreservation (SSC) is a specific technique especially used in individuals with small numbers of sperm who suffered from non-obstructive azoospermia (NOA). Testicular specimens possess poor motility and low population of viable spermatozoa. Therefore, sperm selection methods such as applying pentoxifylline (PTX) may improve motility in these cases. The main aim of this study was to evaluate the protective effects of PTX on testicular spermatozoa before and after performing SSC., Methods: Thirty testicular samples were obtained from men with azoospermia. This study was conducted in two phases. Phase 1 evaluated the effect of PTX for sperm selection before SSC. Twenty testicular samples were divided to two experimental groups: SSC without (I) and with PTX treatment (II). For PTX treatment spermatozoa were incubated with PTX at 37°C for 30 min and only motile spermatozoa were selected for SSC. In phase 2, ten testicular samples were cryopreserved with SSC and warming procedure was carried out in droplet with and without PTX. Motility and viability rates, morphology by motile sperm organelle morphology examination (MSOME), DNA fragmentation by sperm chromatin dispersion test (SCD) and mitochondrial membrane potential (MMP) were evaluated., Results: In phase 1, post warm motility rate was higher in PTX exposed group compared to the unexposed group (25.6 ± 8.13 vs. 0.85 ± 2.1) (p > 0.00). Recovery rate, viability and morphology were not significantly different between groups. DNA integrity and MMP were also similar between both groups. In phase 2 although motility increased in PTX group compared to without PTX group (29.30 ± 12.73 vs. 1.90 ± 2.64) (p > 0.00), the viability rate was not different (70.40 ± 12.12 vs. 65.30 ± 11.87). All above mentioned parameters were similar between the two SSC groups., Conclusions: Supplementation of testicular spermatozoa with PTX before cryopreservation increases motility and did not have adverse effects on viability, morphology, DNA integrity and MMP. PTX could be used as sperm selection method before single sperm cryopreservation, but PTX could not maintain motile the most of viable testicular sperms.

Objective: Platelet-rich plasma (PRP) is enriched with active biological components which showed proliferative and cytoprotective properties in healing different injuries in medicinal fields. This study was designed to assess cryoprotective effects of autologous PRP on quality of oligoasthenoteratospermia (OAT) samples during freezing and thawing procedure., Materials and Methods: The present study is an experimental research. Twenty OAT semen samples were obtained from individuals and prepared by discontinuous density - gradients technique. Control group is sperm samples after DGC. After the procedure, the specimen divided into four groups. Freeze group which has no additive and other three groups were cryopreserved with different concentrations of PRP (1×105/µL, 0.5×105/µL and 0.25×105/µL). Autologous PRP was provided by each participant. After thawing, sperm parameters, DNA fragmentation by sperm chromatin dispersion test (SCD), protamine deficiency by (Chromomycin A3) CMA3 staining, acrosome integrity and malondialdehyde (MDA) level were evaluated., Results: Cryopreservation resulted in significant decreased in all factors compared to the control group. There were no significant changes on sperm count, morphology, non-progressive motility and acrosome reaction by adding PRP as cryoprotectant in comparison with freeze group. PRP at all three concentrations showed significant increase in progressive motility (3.05±2.01 vs. 14.05±4.13, 12.35±4.90 and 12.15±9.65, P<0.001) and viability (36.85±10.25 vs. 47.85±5.86, 51.30±5.54 and 50.05±5.67, P<0.001) compared to the sperm samples without PRP. The percentage of immotile sperms decreased at all PRP concentrations compared to the freeze group. Moreover, PRP at 1×105/µL concentration showed cryoprotective effects on DNA fragmentation, protamine deficiency and MDA level compared to the other three concenterations., Conclusion: Cryopreservation and thawing procedures may exert adverse effects on biological factors of sperm samples. Therefore, adding PRP as cryoprotectant at all three concentrations especially 1×105/µL can be promising strategy to reduce adverse effects of cryopreservation on OAT samples.

Bladder cancer is the most common urinary tract neoplasm, affecting many people annually. Current diagnostic and surveillance methods for bladder cancer are frequently invasive and lack sensitivity and specificity. This study aimed to develop an accurate and non-invasive urine-based gene expression assay, including fibroblast growth factor receptor 3 (FGFR3), homeobox A13 (HOXA13), and polo-like kinase 1 (PLK1), to diagnose non-muscle-invasive bladder cancer (NMIBC) at stages Ta and T1. The samples were acquired from 62 patients with NMIBC, 31 control individuals, and 31 patients with non-cancerous genitourinary tract diseases. The expression levels of three relevant genes were determined using quantitative RT-PCR. In addition, the sensitivity and specificity of the data for these genes were computed. Our results showed that PLK1, HOXA13, and FGFR3 expressions of genes were significantly elevated in patients compared to the control groups (p = 0.0001; p = 0.039). The sensitivity and specificity for the FGFR3 gene were 55% and 76%, respectively (p = 0.39). These parameters for HOXA13 were 100% and 93% (p = 0.0001) and for PLK1 were 100% and 86% (p = 0.0001) for diagnosing and monitoring NMIBC. HOXA13 and PLK 1 exhibited adequate specificity and sensitivity for diagnosis. The results of this research showed that despite the higher expression of these genes in urine, only HOXA13 and PLK1 had sufficient and proper specificity and sensitivity, so the urinary expression of these two genes can be used in future studies for diagnosis and monitoring in cancer bladder., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Introduction: APC and TP53 are the two most regularly mutated genes in colon adenocarcinoma (COAD), especially in progressive malignancies and antitumoral immune response. The current bioinformatics analysis investigates the APC and TP53 gene expression profile in colon adenocarcinoma as a prognostic characteristic for survival, particularly concentrating on the correlated immune microenvironment., Methods: Clinical and genetic data of colon cancer and normal tissue samples were obtained from The Cancer Genome Atlas (TCGA)-COAD and Genotype-Tissue Expression (GTEx) online databases, respectively. The genetic differential expressions were analyzed in both groups via the one-way ANOVA test. Kaplan-Meier survival curves were applied to estimate the overall survival (OS). P < 0.05 was fixed as statistically significant. On Tumor Immune Estimation Resource and Gene Expression Profiling Interactive Analysis databases, the linkage between immune cell recruitment and APC and TP53 status was assessed through Spearman's correlation analysis., Results: APC and TP53 were found mutated in 66.74% and 85.71% of the 454 and 7 TCGA-COAD patients in colon and rectosigmoid junction primary sites, respectively with a higher log2-transcriptome per million reads compared to the GTEx group (318 samples in sigmoid and 368 samples in transverse). Survival curves revealed a worse significant OS for the high-APC and TP53 profile colon. Spearman's analysis of immune cells demonstrated a strong positive correlation between the APC status and infiltration of T cell CD4+, T cell CD8+, NK cell, and macrophages and also a positive correlation between status and infiltration of T cell CD4+, T cell CD8+., Conclusions: APC and TP53 gene mutations prevail in colon cancer and are extremely associated with poor prognosis and shortest survival. The infiltrating T cell CD4+, T cell CD8+, NK cell, and macrophages populate the colon microenvironment and regulate the mechanisms of tumor advancement, immune evasion, and sensitivity to standard chemotherapy. More comprehensive research is needed to demonstrate these results and turn them into new therapeutic outlooks.

Immunotherapy has revolutionized cancer treatment by harnessing the power of the immune system to eliminate tumors. Immune checkpoint inhibitors (ICIs) block negative regulatory signals that prevent T cells from attacking cancer cells. Two key ICIs target the PD-1/PD-L1 pathway, which includes programmed death-ligand 1 (PD-L1) and its receptor programmed death 1 (PD-1). Another ICI targets cytotoxic T-lymphocyte-associated protein 4 (CTLA-4). While ICIs have demonstrated remarkable efficacy in various malignancies, only a subset of patients respond favorably. MicroRNAs (miRNAs), small non-coding RNAs that regulate gene expression, play a crucial role in modulating immune checkpoints, including PD-1/PD-L1 and CTLA-4. This review summarizes the latest advancements in immunotherapy, highlighting the therapeutic potential of targeting PD-1/PD-L1 and CTLA-4 immune checkpoints and the regulatory role of miRNAs in modulating these pathways. Consequently, understanding the complex interplay between miRNAs and immune checkpoints is essential for developing more effective and personalized immunotherapy strategies for cancer treatment., (© 2024. The Author(s).)

Background: Clomiphene citrate (CC) has been suggested to increase the chance of sperm retrieval withmicrodissection testicular sperm extraction (micro-TESE). Objective: This study aimed to evaluate the effect of CC on micro-TESE results, due to the great controversy in this regard. Materials and Methods: 112 participants were included in this cross-sectional study and were divided into a case (n = 54) and a control group (n = 58) diagnosed with non-abstractive azoospermia. The case group received 25 mg of CC daily for 3 months, while the control group did not receive anything. All participants underwent micro-TESE by an andrologist, and at the end, the results were compared between groups. Hormone tests, including follicle-stimulating hormone, luteinizing hormone, testosterone, and prolactin were analyzed. Results: The mean age of participants was the same in the case and the control groups, and no significant relationship was observed between the 2 groups (p = 0.16). 25.9% of sperm and 31.0% of sperm were observed and extracted in the CC-treated and the control group, respectively. Conclusion: Our findings showed that after receiving CC, the number of sperm extraction did not increase but it rather decreased. However, the initial level of hormones such as testosterone, follicle-stimulating hormone, luteinizing hormone, and prolactin, and the men's age, testicle size, smoking, and opium addiction, underlying diseases had no significant relationship in the 2 groups and did not affect the results., Competing Interests: The authors declare that they have no conflict of interest., (Copyright © 2023 Vahidi et al.)

Background: Polycystic ovary syndrome (PCOS) is a complicated endocrine disorder with widespread symptoms that reduce women's quality of life. The adverse effect of associated obesity on this reduction is unclear, therefore the impact of weight loss on health-related quality of life (HRQOL) in obese women with PCOS is unknown. This study aimed to compare the impact of weight loss following a 24-week dietary intervention on HRQOL in obese women with and without PCOS., Methods: In a 24-week hypocaloric LGI (low glycemic index) diet intervention study, 286 women were recruited (140 PCOS, 146 controls) and 216 participants (PCOS = 105, non-PCOS = 111) completed the study. HRQOL was assessed using the SF-36 questionnaire (Short Form Health Survey). Physical activity was measured using the short form of the International Physical Activity Questionnaire (IPAQ). Anthropometric assessments, dietary intake, physical activity levels, and HRQOL scores, according to the Iranian version of SF-36, were compared at baseline and 24 weeks with intervention., Results: At the end of the intervention, there was no significant difference in the percentages of weight loss between the two groups (PCOS: 6.29 ± 3.32% vs. non-PCOS: 7 ± 3.62%, p = 0.1). At baseline, women with PCOS had lower mean scores in aspects of physical function (PF), general health perception (GH), role limitation due to emotional problem (RE), vitality (VT), mental health (MH), physical (PCS) and mental component summary scales (MCS), compared to non-PCOS (P < 0.01). At 24 weeks, the percentage of improvement in HRQOL in the non-PCOS group was higher compared to the PCOS group but this difference didn't reach statistical significance except for PCS. In both groups, greater weight loss was associated with further improvement in the physical aspects of HRQOL and vitality. In the non-PCOS group, with trivial exception, greater weight loss was associated with greater improvement in the mental aspects of HRQOL., Conclusions: Both obese PCOS and non-PCOS women achieved nearly similar levels of improvement in HRQOL due to weight loss induced by a hypocaloric LGI diet., Trial Registration: This study is registered in the Iranian Randomized Clinical Trials Registry (IRCT, code: IRCT2016092129909N1)., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Energy conversion by electron transport chains occurs through the sequential transfer of electrons between protein complexes and intermediate electron carriers, creating the proton motive force that enables ATP synthesis and membrane transport. These protein complexes can also form higher order assemblies known as respiratory supercomplexes (SCs). The electron transport chain of the opportunistic pathogen Pseudomonas aeruginosa is closely linked with its ability to invade host tissue, tolerate harsh conditions, and resist antibiotics but is poorly characterized. Here, we determine the structure of a P. aeruginosa SC that forms between the quinol:cytochrome c oxidoreductase (cytochrome bc ) and one of the organism's terminal oxidases, cytochrome 1 ) and one of the organism's terminal oxidases, cytochrome cbb 3 , which is found only in some bacteria. Remarkably, the SC structure also includes two intermediate electron carriers: a diheme cytochrome c 4 and a single heme cytochrome c 5 . Together, these proteins allow electron transfer from ubiquinol in cytochrome bc 1 to oxygen in cytochrome cbb 3 . We also present evidence that different isoforms of cytochrome cbb 3 can participate in formation of this SC without changing the overall SC architecture. Incorporating these different subunit isoforms into the SC would allow the bacterium to adapt to different environmental conditions. Bioinformatic analysis focusing on structural motifs in the SC suggests that cytochrome bc 1 - cbb 3 SCs also exist in other bacterial pathogens.

Deep eutectic solvents (DESs) are one of the most interesting research subjects in green chemistry nowadays. Due to their low toxicity, simple synthesis, and lower prices, they have gradually taken the place of other green solvents such as ionic liquids (ILs) in sustainable processes. However, problems such as high viscosity and high polarity limit the applications of DESs in areas such as extraction, catalysis, and biocatalysis. In this work, we introduce and evaluate the potential application of scCO 2 /DES for the first time. Molecular dynamics simulations were used to examine the phase behavior, polarity, molecular mobilities, and microstructure of this system. Results show that CO 2 molecules can significantly diffuse to the DES phase, while DES components do not appear in the scCO 2 phase. The diffused CO 2 molecules significantly enhanced the molecular mobility of the DES components. The presence of CO 2 molecules changes the DES polarity so that hexane can be solubilized and dispersed in the DES phase. Radial distribution functions show that the solubilized CO 2 molecules have negligible effects on the microstructure of DES. It was shown that chloride and urea are the main interaction sites of CO 2 in DES. The results of this study show that scCO 2 /DES as a new class of green and versatile solvents can open a new promising window for research in sustainable chemistry and engineering.

Background: Spermatozoa retrieved from the testis and epididymis are deprived of the beneficial effects of seminal fluid. Thus applying an artificial medium with normal seminal fluid characteristics, known as artificial seminal fluid (ASF), may provide an appropriate condition for improving some sperm parameters in azoospermia. The objective was to investigate the impact of in vitro exposure of testicular and epididymal spermatozoa to ASF on sperm quality. The study was conducted on testicular (n = 20) and epididymal (n = 20) sperm specimens obtained from azoospermic men. Each sample was divided into two equal parts: Part I) for processing and incubation with Ham's F10 medium; Part II) for processing and incubation with ASF., Results: After 2 h incubation, testicular sperm motility was significantly higher in ASF than in Ham's F10 medium. In comparison to 0 h, mitochondrial membrane potential levels of testicular spermatozoa were significantly higher after 2 h and 24 h in ASF and after 24 h in Ham's F10 medium. Furthermore, the data indicated significantly lower rates of epididymal spermatozoa with high MMP in both media after 24 h. There were no significant differences in the DNA fragmentation index of testicular and epididymal spermatozoa between ASF and Ham's F10 medium at different time points., Conclusion: The results demonstrated that in vitro incubation of testicular spermatozoa improved their motility more effectively than Ham's F10 medium in the short term (2 h), but had no effect on epididymal spermatozoa. Since the physiology of testicular spermatozoa is different from that of ejaculated spermatozoa, it seems that a special environment should be designed and used for each of them., (© 2023. The Author(s).)

In December 2019, severe acute respiratory syndrome COVID-19 was found in China. This virus can affect different organs depending on the coronavirus receptors on the cell surface, which allows the organ to be attacked by the coronavirus. Psychological distress and impaired pulmonary hemodynamics seem to be the cause of decreasing libido or sexual dysfunction after contracting COVID-19. This study was performed to assess the effect of coronavirus on the sexual activity of men. We enrolled 200 men with COVID-19, confirmed by an oropharyngeal sample, who had recovered from the coronavirus for 3 months. These men filled out the International Index of Erectile Function 5 (IIEF-5) questionnaire for their current and previous sexual status. Then, according to their IIEF-5 score, sexual activity before and after corona infection was compared. The mean age of the participants was 31.5 ±3.2 years. This study showed a significant difference between the IIEF-5 mean scores before and after COVID-19, which were 20.4 and 18.6, respectively ( p = .000). The condition of 56.1% of the patients did not change; however, coronavirus did have a negative effect on 39.6% of the patients. 4.1% of patients reported improvement in sexual performance. 45% of the patients reported no erectile dysfunction (ED) before contracting the coronavirus; while only 27.7% reported no ED after getting COVID-19. Our findings show that COVID-19 could influence the sexual activity of infected men, who also showed a higher ED prevalence after COVID-19 infection; however, hormonal assessment should be observed in the follow-up.

Oxidative phosphorylation, the combined activity of the electron transport chain (ETC) and adenosine triphosphate synthase, has emerged as a valuable target for the treatment of infection by Mycobacterium tuberculosis and other mycobacteria. The mycobacterial ETC is highly branched with multiple dehydrogenases transferring electrons to a membrane-bound pool of menaquinone and multiple oxidases transferring electrons from the pool. The proton-pumping type I nicotinamide adenine dinucleotide (NADH) dehydrogenase (Complex I) is found in low abundance in the plasma membranes of mycobacteria in typical in vitro culture conditions and is often considered dispensable. We found that growth of Mycobacterium smegmatis in carbon-limited conditions greatly increased the abundance of Complex I and allowed isolation of a rotenone-sensitive preparation of the enzyme. Determination of the structure of the complex by cryoEM revealed the "orphan" two-component response regulator protein MSMEG&#95;2064 as a subunit of the assembly. MSMEG&#95;2064 in the complex occupies a site similar to the proposed redox-sensing subunit NDUFA9 in eukaryotic Complex I. An apparent purine nucleoside triphosphate within the NuoG subunit resembles the GTP-derived molybdenum cofactor in homologous formate dehydrogenase enzymes. The membrane region of the complex binds acyl phosphatidylinositol dimannoside, a characteristic three-tailed lipid from the mycobacterial membrane. The structure also shows menaquinone, which is preferentially used over ubiquinone by gram-positive bacteria, in two different positions along the quinone channel, comparable to ubiquinone in other structures and suggesting a conserved quinone binding mechanism.

Background: Colorectal cancer (CRC) is one of the most important cancers in the world, and its prevalence varies depending on the geographical area. Genetically, tumor regeneration in CRC as a multi-step process involves activating mutations in protocogenes and losing the function of tumor suppressor genes as well as DNA repair and recovery genes. Occur in this way, our goal was to investigate the expression of KLF6 genes as a tumor suppressor and MUTYH involved in the DNA repair process in colorectal cancer., Methods: This research was conducted during the years 2019-2018 in Razi Hospital, Rasht. The subjects included 30 tumoral and 30 non-tumoral tissues of colorectal cancer and 20 healthy controls. The real-time PCR method was used to investigate the gene expression. For data analysis by SPSS, parametric statistical tests ANOVA and T test and regression analysis were used and p value values less than 0.05 were considered significant., Results: The expression of KLF6 gene in tumoral tissues showed a significant decrease compared to non-tumoral tissues (P = 0.04). Also, the expression of MUTYH gene in tumor tissue showed a significant decrease compared to non-tumoral (P = 0.02) and this decrease in MUTYH gene expression had a significant relationship with increasing tumor stage (P = 0.01)., Conclusion: These findings suggest that decreased expression of KLF6 and MUTYH genes in the study population has a significant relationship with colorectal cancer and can be considered as tumor marker in diagnostic purpose., (© 2022. The Author(s).)

BACKGROUND Langerhans cell histiocytosis (LCH) is a rare condition caused by a neoplastic proliferation of myeloid cells. It can present as a single-system or multi-system disorder. Worse prognosis is associated with the hematopoietic system (spleen, liver, bone marrow), which is routinely observed in multi-system disease. Because of the varied presentation of this disorder, diagnosis can be difficult, and therefore suitable treatment can be delayed. CASE REPORT We report a case of hepatic LCH in a 51-year-old man who presented with epigastric abdominal pain, with imaging demonstrating a hepatic nodule. A low ejection fraction on hepatobiliary iminodiacetic acid scan suggested chronic cholecystitis. Therefore, the patient underwent a cholecystectomy for biliary dyskinesia, in which liver nodules were noted, and biopsies were taken. The biopsies demonstrated characteristic findings of LCH along with positive immunohistochemical markers and negative BRAF V600E mutation. Radiologic and pathologic findings were consistent with LCH within the liver, associated with bile duct injury and mild biliary obstruction. The patient was placed on a cladribine regimen. His abdominal pain improved. CONCLUSIONS LCH limited to the liver is uncommon and can appear as chronic biliary disease, as was suspected in this case. Despite the poor prognosis of hematopoietic LCH, early recognition can lead to better outcome and chemotherapy susceptibility. This patient was most likely in the first stage of liver LCH, given his presentation, which could have aided his response to chemotherapy. The lack of BRAF V600E mutation could have contributed to a positive prognosis and more possibilities for treatment.

Background: In December 2019, a severe acute respiratory syndrome (SARS-COV-2) was found in China. The coronavirus can impact different organs, as shown by the virus having been detected in urine, blood, oropharyngeal, and feces. This study was done to assess the impact of COVID-19 on semen analysis and to evaluate the existence of the virus in the semen of infected men. Methodology . Forty fertile men with COVID-19 were confirmed by an oropharyngeal sample. The men were divided into two groups. The semen of twenty men in the acute stage of COVID-19 and twenty men in the clinical recovery stage was analyzed, and the parameters of semen were compared between two groups. In addition, a PCR test of patients' semen was done., Result: The analysis showed that all patients' semen specimens tested negative. Semen analysis revealed no significant difference in sperm count, concentration, or motility, and the sperm of both groups was found to be normal. However, viability and morphology parameters were significantly lower in men with the acute disease., Conclusion: Coronavirus (COVID-19) was not secreted in the semen of infected men but had a negative effect on the morphology and viability of the sperm of men in the acute stage., Competing Interests: The authors have no conflicts of interest., (Copyright © 2022 Serajoddin Vahidi et al.)

Gastric cancer (GC) is a significant cause of cancer mortality which has led to focused exploration of the pathology of GC. The advent of genome-wide analysis methods has made it possible to uncover genetic and epigenetic fluctuation such as abnormal DNA methylation in gene promoter regions that is expected to play a key role in GC. The study of gastric malignancies requires an etiological perspective, and Helicobacter pylori ( H. pylori ) was identified to play a role in GC. H. pylori infection causes chronic inflammation of the gastric epithelium causing abnormal polyclonal methylation, which might raise the risk of GC. In the last two decades, various pathogenic factors by which H. pylori infection causes GC have been discovered. Abnormal DNA methylation is triggered in several genes, rendering them inactive. In GC, methylation patterns are linked to certain subtypes including microsatellite instability. Multiple cancer-related processes are more usually changed by abnormal DNA methylation than through mutations, according to current general and combined investigations. Furthermore, the amount of acquired abnormal DNA methylation is heavily linked to the chances of developing GC. Therefore, we investigated abnormal DNA methylation in GC and the link between methylation and H. pylori infection., Competing Interests: CONFLICT OF INTEREST There is no conflict of interest., (© 2022 Korean Pharmacopuncture Institute.)

Background: The sperm DNA fragmentation index (DFI) is one of the men's reproductive health criteria that affects assisted reproductive technique outcomes. Efforts in obtaining high-quality mature sperms seem to be necessary. Advanced sperm selection techniques (including physiological intracytoplasmic sperm injection [PICSI], zeta potential, microfluidic, etc.) have gained popularity in this regard., Objective: The study aimed to compare the efficacy of zeta potential and PICSI sperm selection in obtaining sperms with better DNA integrity., Materials and Methods: In this cross-sectional study, 48 couples were enrolled where the male partner had increased sperm DFI in his ejaculated sample and the female was in normal reproductive health. For each male partner, the semen sample was processed with zeta potential and PICSI techniques, then the sperm DFI of neat semen was compared to zeta and PICSI samples by the sperm chromatin dispersion test., Results: Data showed that both the zeta potential and PICSI technique decreased sperm DFI in comparison with the neat semen sample (p < 0.001 for both). In addition, there was a statistically significant difference in sperm DFI between the PICSI and zeta potential samples (p < 0.01)., Conclusion: The current study showed that both zeta potential and PICSI could result in sperm with a lower DFI. However, PICSI seems to be superior to zeta potential in this regard., Competing Interests: The authors declare that there is no conflict of interest., (Copyright © 2022 Vahidi et al.)

Epigenetic modifications, particularly DNA methylation, is commonplace and a remarkable factor in carcinogenesis transformation. Conspicuously, previous findings have presented a cluster of irregular promoter methylation alterations related with silencing of tumor suppressor genes, little is accepted regarding their sequential DNA methylation (hypo and hyper) modifications during the cancer progression. In this way, fluctuations of DNA methylation of many genes, especially MYC, SMAD2/3, and DNMT3A, have an impressive central key role in many different cancers, including colorectal cancer (CRC). CRC is distinguished by DNA methylation, which is related to tumorigenesis and also genomic instability. Importantly, molecular heterogeneity between multiple adenomas in different patients with CRC may show diverse developmental phenotypes for these kinds of tumors. Conclusively, studying factors that are involved in CRC carcinogenesis, especially the alterations in epigenetic elements, such as DNA methylation besides RNA remodeling, and histone modification, acetylation and phosphorylation, can be influential to find new therapeutic and diagnostic biomarkers in this type of malignancy. In this account, we discuss and address the potential significant methylated modifications of these genes and their importance during the development of CRC carcinogenesis., (The OMJ is Published Bimonthly and Copyrighted 2021 by the OMSB.)

Purpose: Polyvinylpyrrolidone (PVP) is a chemical material used in intracytoplasmic sperm injection (ICSI) program.  The aim of this study was to investigate the ideal time that sperm can be safely incubated in PVP with less structure and DNA damage., Method: Thirty-one Oligoasthenoteratospermia (OAT) samples were used. Sperm samples were prepared by discontinuous density-gradients method and incubated in 10% PVP at different time intervals (0, 5, 10, 15, 20, and 30 min). The effect of PVP was assessed on sperm DNA fragmentation and viability via SCD assay and Eosin-nigrosin staining respectively., Results: Data showed there was a significant increase in sperm DNA fragmentation at 10 min compared to 0 min. The viability rate also significantly reduced at 10 min  compared to 0 min., Conclusion: As a result, sperm samples could be incubated with PVP for less than 10 min.  While prolonged incubation may significantly damage the sperm DNA integrity and viability.

Background: Outcomes of intracytoplasmic sperm injection (ICSI) may be different in azoospermic men who undergo testicular sperm extraction (TESE) vs. microdissection-TESE (micro-TESE)., Objective: This study was conducted to compare the ICSI outcomes in men who underwent TESE vs. micro-TESE due to obstructive azoospermia and nonobstructive azoospermia, respectively., Materials and Methods: A total of310azoospermic men who underwent ICSI from September 2016 to September 2020 were enrolled in this cross-sectional study and divided into two groups (172 cases in the TESE and 138 cases in the micro-TESE group). The paternal and maternal age, and the fertilization, biochemical pregnancy, abortion and live birth rates were compared between the two groups., Results: Maternal mean age was significantly higher in the TESE group (34.9 ± 4.2 yr vs. 32.3 ± 5.7 yr). The fertilization and biochemical pregnancy rates were significantly higher in the TESE group, but the abortion rate was similar in the two groups. The live birth rate was higher in the TESE group, but this difference was not significant (p = 0.06). Also, the maternal and paternal age did not affect ICSI outcomes., Conclusion: Individuals who underwent TESE had higher fertilization and biochemical pregnancy rates than those who underwent micro-TESE, but the live birth rate was not significantly different., Competing Interests: There is no conflict of interest., (Copyright © 2021 Vahidi et al.)

Background: The management of non-obstructive azoospermia (NOA) disease relies on microdissection testicular sperm extraction (micro-TESE). Few studies have assessed the role of micro-TESE in men with NOA in our country., Objective: The aim of the current study was to investigate the success rate of micro-TESE., Materials and Methods: This retrospective descriptive-analytical study was conducted on 463 men with NOA in Yazd Reproductive Sciences Institute during September 2017 through September 2019. Sperm were retrieved and frozen according to the rapid sperm freezing protocol. After preparing the oocyte of the male partner's spouse, sperms were thawed and then entered the intracytoplasmic sperm injection process. The clinical pregnancy of individuals was confirmed via ultrasound. Demographic data were extracted from medical records., Results: The success rate of micro-TESE was 38% and successful fertilization, biochemical pregnancy, clinical pregnancy, and live birth were observed in 111 (85.4%), 29 (22.3%), 29 (22.3%) and 14 (10.7%) men, respectively. A significant difference was seen between the two groups, regarding age (p = 0.01). In addition, the mean follicle-stimulating hormone in men with positive micro-TESE was significantly lower than in men with negative micro-TESE (p = 0.02)., Conclusion: The success of pregnancy in couples with NOA managed via micro-TESE was significant. The study found that the success rate of micro-TESE was higher in older men and in those with lower follicle-stimulating hormone levels., Competing Interests: There was no conflict of interest., (Copyright © 2021 Vahidi et al.)

Purpose: To investigate the effect of short abstinence on sperm function tests and semen parameters., Materials and Methods: This prospective study included 65 male patients with increased DNA injury in their ejaculated sperm and a history of recurrent pregnancy loss and/or assisted reproductive techniques failures. The effects of antioxidants medical therapy and short abstinence on semen quality were assessed (TUNEL test and CMA3 staining)., Results: Antioxidants have statistically significant effects on mean sperm concentration (untreated, 67.51 ± 44.40 million/ml, vs. treated, 56.09 ± 37.85 million/ml; P-value=0.005) and mean TUNEL score (untreated, 24.56% ± 9.49%, vs. treated, 20.64% ± 10.28%; P-value = 0.013). Moreover, a short abstinence period might have positive effects as shown on the TUNEL assay (20.64% ± 10.28 vs. 17.38% ± 8.59 ; P-value = 0.028) and CMA3 staining (47.79% ± 20.78, vs. short 41.92% ± 18.49; P-value = 0.019), when considering all study subjects. However, different results were obtained using more precise analysis based on a TUNEL cutoff score of 20%. The analysis showed that short abstinence might improve sperm DNA integrity in patients with TUNEL score > 20% (mean TUNEL score from 27.85% ± 8.32% to 19.14% ± 8.90% ; P-value =0.001%). However, it might have deleterious effects on sperm DNA integrity in patients with TUNEL score < 20% (mean TUNEL score from 11.89% ± 3.21% to 15.17% ± 7.79%; P-value = 0.045%) Conclusion: Our results showed that short abstinence may not be beneficial in all infertile males, and it should only be used in selected patients with abnormal DNA integrity.

Background: Despite numerous reports about temporal changes in semen quality from all over the world, the debates continue. The latest systemic review has shown an overtime decrease in semen quality worldwide., Objective: To assess the temporal changes in the semen quality among Iranian population referred to an infertility center., Materials and Methods: In this retrospective cross-sectional study, semen parameters including concentration, motility, and morphology were compared between Iranian men reffered to Research and Clinical Center for Infertility, Yazd between 1990 to 1992 (group 1, n = 707) and 2010 to 2012 (group 2, n = 1108). Demographic characteristics and semen analysis were collected from the records. The effect of age on semen parameters was also investigated., Results: Despite the increase in sperm concentration l in group 2, sperm with normal morphology decreased significantly (p < 0.001). Grade-A motility decreased (p < 0.001), grade B motility increased (p < 0.001), and grade C and D motile sperm remained constant (p = 0.303 and p = 0.315, respectively). Also, no significant correlation between the age and semen parameters were observed., Conclusion: This study showed inconsistent temporal changes in the participant semen quality. Significant temporal decline were obtained between various semen parameters, sperm morphology and grade A motility. These results should be further evaluated by larger studies in the future., Competing Interests: No conflict of interest, (Copyright © 2020 Vahidi et al.)

The 300-kDa ClpP1P2 protease from Mycobacterium tuberculosis collaborates with the AAA+ (ATPases associated with a variety of cellular activities) unfoldases, ClpC1 and ClpX, to degrade substrate proteins. Unlike in other bacteria, all of the components of the Clp system are essential for growth and virulence of mycobacteria, and their inhibitors show promise as antibiotics. MtClpP1P2 is unique in that it contains a pair of distinct ClpP1 and ClpP2 rings and also requires the presence of activator peptides, such as benzoyl-leucyl-leucine (Bz-LL), for function. Understanding the structural basis for this requirement has been elusive but is critical for the rational design and improvement of antituberculosis (anti-TB) therapeutics that target the Clp system. Here, we present a combined biophysical and biochemical study to explore the structure-dynamics-function relationship in MtClpP1P2. Electron cryomicroscopy (cryo-EM) structures of apo and acyldepsipeptide-bound MtClpP1P2 explain their lack of activity by showing loss of a key β-sheet in a sequence known as the handle region that is critical for the proper formation of the catalytic triad. Methyl transverse relaxation-optimized spectroscopy (TROSY)-based NMR, cryo-EM, and biochemical assays show that, on binding Bz-LL or covalent inhibitors, MtClpP1P2 undergoes a conformational change from an inactive compact state to an active extended structure that can be explained by a modified Monod-Wyman-Changeux model. Our study establishes a critical role for the handle region as an on/off switch for function and shows extensive allosteric interactions involving both intra- and interring communication that regulate MtClpP1P2 activity and that can potentially be exploited by small molecules to target M. tuberculosis ., Competing Interests: The authors declare no competing interest.

The ClpXP degradation machine consists of a hexameric AAA+ unfoldase (ClpX) and a pair of heptameric serine protease rings (ClpP) that unfold, translocate, and subsequently degrade client proteins. ClpXP is an important target for drug development against infectious diseases. Although structures are available for isolated ClpX and ClpP rings, it remains unknown how symmetry mismatched ClpX and ClpP work in tandem for processive substrate translocation into the ClpP proteolytic chamber. Here, we present cryo-EM structures of the substrate-bound ClpXP complex from Neisseria meningitidis at 2.3 to 3.3 Å resolution. The structures allow development of a model in which the sequential hydrolysis of ATP is coupled to motions of ClpX loops that lead to directional substrate translocation and ClpX rotation relative to ClpP. Our data add to the growing body of evidence that AAA+ molecular machines generate translocating forces by a common mechanism., Competing Interests: ZR, SV, WH, JR No competing interests declared, LK Reviewing editor, eLife, (© 2020, Ripstein et al.)

Bacterial ClpP is a highly conserved, cylindrical, self-compartmentalizing serine protease required for maintaining cellular proteostasis. Small molecule acyldepsipeptides (ADEPs) and activators of self-compartmentalized proteases 1 (ACP1s) cause dysregulation and activation of ClpP, leading to bacterial cell death, highlighting their potential use as novel antibiotics. Structural changes in Neisseria meningitidis and Escherichia coli ClpP upon binding to novel ACP1 and ADEP analogs were probed by X-ray crystallography, methyl-TROSY NMR, and small angle X-ray scattering. ACP1 and ADEP induce distinct conformational changes in the ClpP structure. However, reorganization of electrostatic interaction networks at the ClpP entrance pores is necessary and sufficient for activation. Further activation is achieved by formation of ordered N-terminal axial loops and reduction in the structural heterogeneity of the ClpP cylinder. Activating mutations recapitulate the structural effects of small molecule activator binding. Our data, together with previous findings, provide a structural basis for a unified mechanism of compound-based ClpP activation., Competing Interests: Competing interestsThe authors declare no competing interests., (© The Author(s) 2019.)

Protein homeostasis is critically important for cell viability. Key to this process is the refolding of misfolded or aggregated proteins by molecular chaperones or, alternatively, their degradation by proteases. In most prokaryotes and in chloroplasts and mitochondria, protein degradation is performed by the caseinolytic protease ClpP, a tetradecamer barrel-like proteolytic complex. Dysregulating ClpP function has shown promise in fighting antibiotic resistance and as a potential therapy for acute myeloid leukemia. Here we use methyl-transverse relaxation-optimized spectroscopy (TROSY)-based NMR, cryo-EM, biochemical assays, and molecular dynamics simulations to characterize the structural dynamics of ClpP from Staphylococcus aureus (SaClpP) in wild-type and mutant forms in an effort to discover conformational hotspots that regulate its function. Wild-type SaClpP was found exclusively in the active extended form, with the N-terminal domains of its component protomers in predominantly β-hairpin conformations that are less well-defined than other regions of the protein. A hydrophobic site was identified that, upon mutation, leads to unfolding of the N-terminal domains, loss of SaClpP activity, and formation of a previously unobserved split-ring conformation with a pair of 20-Å-wide pores in the side of the complex. The extended form of the structure and partial activity can be restored via binding of ADEP small-molecule activators. The observed structural plasticity of the N-terminal gates is shown to be a conserved feature through studies of Escherichia coli and Neisseria meningitidis ClpP, suggesting a potential avenue for the development of molecules to allosterically modulate the function of ClpP., Competing Interests: The authors declare no conflict of interest.