Enhancing ferroelectric performance in hafnia-based MFIS capacitor through interface passivation and bulk doping.

In recent times, there has been a notable surge of interests in hafnia (HfO2)-based ferroelectrics, primarily due to their remarkable ferroelectric properties employed in ultra-thin configurations, alongside their compatibility with the conventional CMOS manufacturing process. In order to harness the full potential of HfO2-based films for high-performance non-volatile memory applications, it is imperative to enhance their ferroelectric characteristics and durability. This study introduces a straightforward approach aimed at augmenting the ferroelectric performance of HfxZr1-xO2(HZO) films deposited on silicon (Si) substrates through the engineering of oxygen vacancies (VO). The results of this endeavor demonstrate a significant enhancement in ferroelectric performance, characterized by a 2Pr value of 47µC cm-2and impressive endurance, enduring up to 108cycles under an 8 MV cm-1electric field without the need of a wake-up process. This marked improvement can be attributed to a dual-pronged approach, involving the incorporation of an Al2O3interlayer and the introduction of Al atoms into the HZO film. The Al2O3interlayer primarily serves to mitigate the presence of oxygen vacancies at the interface, while the introduction of Al dopants elevates the concentration of oxygen vacancies within the bulk material. This modulation of oxygen vacancy concentration proves instrumental in facilitating the formation of a ferroelectric o-III phase within the HZO-based films, thereby further augmenting their ferroelectric performance. This innovative and effective strategy offers an alternative avenue for enhancing the ferroelectric properties of materials characterized by a fluorite crystal structure.

De novo design of a nanoregulator for the dynamic restoration of ovarian tissue in cryopreservation and transplantation.

The cryopreservation and transplantation of ovarian tissue underscore its paramount importance in safeguarding reproductive capacity and ameliorating reproductive disorders. However, challenges persist in ovarian tissue cryopreservation and transplantation (OTC-T), including the risk of tissue damage and dysfunction. Consequently, there has been a compelling exploration into the realm of nanoregulators to refine and enhance these procedures. This review embarks on a meticulous examination of the intricate anatomical structure of the ovary and its microenvironment, thereby establishing a robust groundwork for the development of nanomodulators. It systematically categorizes nanoregulators and delves deeply into their functions and mechanisms, meticulously tailored for optimizing ovarian tissue cryopreservation and transplantation. Furthermore, the review imparts valuable insights into the practical applications and obstacles encountered in clinical settings associated with OTC-T. Moreover, the review advocates for the utilization of microbially derived nanomodulators as a potent therapeutic intervention in ovarian tissue cryopreservation. The progression of these approaches holds the promise of seamlessly integrating nanoregulators into OTC-T practices, thereby heralding a new era of expansive applications and auspicious prospects in this pivotal domain.

Decreased GDF9 and BMP15 in follicle fluid and granulosa cells and outcomes of IVF-ET among young patients with low prognosis.

PURPOSE: To analyze the level of growth differentiation factor 9 (GDF9) and bone morphogenetic protein 15 (BMP15) in follicle fluid (FF) and granulosa cells (GCs) derived from young patients with low prognosis for in vitro fertilization and embryo transfer (IVF-ET) treatment. METHODS: A prospective cohort study was carried out by enrolling 52 young patients with low prognosis according to the POSEIDON classification group 3 (low prognosis group) and 51 young patients with normal ovarian reserve (control group). The concentration of the GDF9 and BMP15 proteins in FF was determined by enzyme-linked immunosorbent assay. The mRNA level of the GDF9 and BMP15 in the GCs was measured by quantitative real-time PCR. RESULTS: The concentration of GDF9 (1026.72 ± 159.12 pg/mL vs. 1298.06 ± 185.41 pg/mL) and BMP15 (685.23 ± 143.91 pg/mL vs. 794.37 ± 81.79 pg/mL) in FF and the mRNA level of GDF9 and BMP15 in the GCs and the live birth rate per treatment cycle started (30.77% vs. 50.98%) and oocytes retrieved (4.25 ± 1.91 vs.12.04 ± 4.24) were significantly lower, whereas the canceled cycle rate was significantly higher (9.62% vs. 0) in the low prognosis group compared with the control group (P < 0.05). The expression of GDF9 and BMP15 in the ovary was positively correlated with live birth (P < 0.05). CONCLUSION: The expression of GDF9 and BMP15 in the ovary was decreased in young patients with low prognosis accompanied by a poorer outcome of IVF-ET treatment. TRIAL REGISTRATION: ChiCTR1800016107 (Chinese Clinical Trial Registry), May 11, 2018. ( http://www.chictr.org.cn/edit.aspx?pid=27216&htm=4 ).

Reduction of Rhizoctonia cerealis Infection on Wheat Through Host- and Spray-Induced Gene Silencing of an Orphan Secreted Gene.

Rhizoctonia cerealis is a soilborne fungus that can cause sharp eyespot in wheat, resulting in massive yield losses found in many countries. Due to the lack of resistant cultivars, fungicides have been widely used to control this pathogen. However, chemical control is not environmentally friendly and is costly. Meanwhile, the lack of genetic transformation tools has hindered the functional characterization of virulence genes. In this study, we attempted to characterize the function of virulence genes by two transient methods, host-induced gene silencing (HIGS) and spray-induced gene silencing (SIGS), which use RNA interference to suppress the pathogenic development. We identified ten secretory orphan genes from the genome. After silencing these ten genes, only the RcOSP1 knocked-down plant significantly inhibited the growth of R. cerealis. We then described RcOSP1 as an effector that could impair wheat biological processes and suppress pathogen-associated molecular pattern-triggered immunity in the infection process. These findings confirm that HIGS and SIGS can be practical tools for researching R. cerealis virulence genes. [Formula: see text] Copyright © 2022 The Author(s). This is an open access article distributed under the CC BY-NC-ND 4.0 International license.

Growth hormone alleviates oxidative stress and improves the IVF outcomes of poor ovarian responders: a randomized controlled trial.

BACKGROUND: Oxidative stress (OS), defined as an imbalance between excessive reactive oxygen species (ROS) and/or reactive nitrogen species (RNS) production and antioxidant insufficiency, has been suggested to be involved in the pathogenesis of poor ovarian response (POR). Growth hormone (GH) can reduce OS in some cell types. This study investigated whether GH can improve OS and the in vitro fertilization and embryo transfer (IVF-ET) outcomes of poor ovarian responders. METHODS: This study enrolled 105 patients with POR and 58 patients without POR (controls) who were diagnosed according to the Bologna criteria and underwent conventional IVF-ET. Poor ovarian responders were randomly assigned to two groups: the POR-GH group, which received pretreatment with GH 4 IU/d on day 2 of the previous menstrual cycle before IVF until the trigger day, and the POR-C group, which received no pretreatment. OS markers in follicular fluid (FF), ROS levels in granulosa cells (GCs), and the IVF outcomes of the groups were compared. RESULTS: Endometrial thickness on trigger day, the number of cleaved embryos, the number of higher-quality embryos, and the rates of embryo formation, higher-quality embryo formation, implantation and clinical pregnancy were significantly increased in the POR-GH group compared with the POR-C group (P < 0.05). Moreover, compared to those in the non-POR group, FF malondialdehyde (MDA), total oxidant status (TOS), oxidative stress index (OSI) and ROS levels in GCs were significantly higher, whereas superoxide dismutase (SOD) and the total antioxidant capacity (TAC) were significantly lower in the POR-C group (P < 0.05). Furthermore, compared with those in the POR-C group, the FF TAC was significantly increased in the POR-GH group, and TOS, OSI and intracellular ROS levels were significantly reduced (P < 0.05). CONCLUSIONS: Pretreatment with GH alleviates OS and improves oocyte quality and IVF outcomes of poor ovarian responders. TRIAL REGISTRATION: Chinese Clinical Trial Registry. ChiCTR1900021269 . Registered 8 February 2019, http://www.chictr.org.cn/edit.aspx?pid=35837&htm=4 .

Triclocarban at environmentally relevant concentrations induces the endoplasmic reticulum stress in zebrafish.

Triclocarban (TCC) is an antibacterial agent commonly found in environmental, wildlife, and human samples. However, with in-depth study of TCC, its negative effects are increasingly presented. Toxicological studies of TCC at environmentally relevant concentrations have been conducted in zebrafish embryos and indicated that TCC leads to deformity of development causes developmental deformities. However, the molecular mechanisms underlying the toxicity of TCC in zebrafish embryos have not been entirely elucidated. We investigated whether exposure to TCC at environmentally relevant concentrations induces endoplasmic reticulum (ER) stress and unfolded protein response (UPR) in zebrafish. Zebrafish embryos were grown to 32 hours post fertilization and exposed to 2.5, 5, and 10 µg/L TCC and used in whole-mount in situ hybridization to visualize the expression of ER chaperone hspa5 and ER stress-related apoptosis factor chop. Zebrafish livers were exposed to different concentrations of TCC to elaborate the relationships between fatty degeneration and ER stress. Then, a human hepatic cell line (HL-7702) was used to test whether TCC induced ER stress in human livers similar to those of zebrafish. In zebrafish embryos, TCC induced high hspa5 expression, which could defend against external stimulations. Furthermore, hapa5, hsp90b1, and chop exhibited ectopic expressions in the neuromast, intestinal tract, and tail tip of zebrafish embryos. On the one hand, significant differences were observed in the mRNA and protein expressions of the ER stress molecular chaperone pPERK-pEIF2a-ATF4 and ATF6 pathways in HL-7702 cells exposed to TCC. On the other hand, lipid droplet accumulation slightly increased in zebrafish livers exposed to 10 µg/L TCC in vitro. These results demonstrate that TCC not only damages the development of zebrafish embryos and structure of zebrafish liver but also influences human hepatic cells by activating ER stress and the UPR signaling pathway.

Systematic analyses of the factors influencing sperm quality in patients with SARS-CoV-2 infection.

To figure out how does SARS-CoV-2 affect sperm parameters and what influencing factors affect the recovery of sperm quality after infection? We conducted a prospective cohort study and initially included 122 men with SARS-CoV-2 infection. The longest time to track semen quality after infection is 112 days and 58 eligible patients were included in our study eventually. We subsequently exploited a linear mixed-effects model to statistically analyze their semen parameters at different time points before and after SARS-CoV-2 infection. Semen parameters were significantly reduced after SARS-CoV-2 infection, including total sperm count (211 [147; 347] to 167 [65.0; 258], P < 0.001), sperm concentration (69.0 [38.8; 97.0] to 51.0 [25.5; 71.5], P < 0.001), total sperm motility (57.5 [52.3; 65.0] to 51.0 [38.5; 56.8], P < 0.001), progressive motility (50.0 [46.2; 58.0] to 45.0 [31.5; 52.8], P < 0.001). The parameters displayed the greatest diminution within 30 days after SARS-CoV-2 infection, gradually recovered thereafter, and exhibited no significant difference after 90 days compared with prior to COVID-19 infection. In addition, the patients in the group with a low-grade fever showed a declining tendency in semen parameters, but not to a significant degree, whereas those men with a moderate or high fever produced a significant drop in the same parameters. Semen parameters were significantly reduced after SARS-CoV-2 infection, and fever severity during SARS-CoV-2 infection may constitute the main influencing factor in reducing semen parameters in patients after recovery, but the effect is reversible and the semen parameters gradually return to normal with the realization of a new spermatogenic cycle.

Predicting ovarian responses to the controlled ovarian hyperstimulation in elderly infertile women using clinical measurements and random forest regression.

During the past decades, the number of elderly infertile women is obviously increasing in China, and more and more of them are likely to seek medical assisted reproductive technologies. As the in vitro fertilization/embryo transfer (IVF/ET) treatment presents special medical and psychological challenges to elderly infertile women, it is extremely helpful to perform the clinical evaluation and outcome prediction regarding IVF/ET outcomes. In this study, we retrospectively collected 12 clinical measurements in prior to the oocyte recovery for 689 elderly infertile patients (≥35 years of old), and used for predicting ovarian responses to the controlled ovarian hyperstimulation based on random forest regression models. Using different predictor sets and 10-fold cross validation approach, the Mean Square Error (±standard deviation) of prediction models varied from 7.56 ± 0.31 to 13.90 ± 0.37 in the training datasets, and the correlation coefficients between observed and predicted values ranged from 0.86 ± 0.02 to 0.72 ± 0.05 in the testing datasets. Among all clinical measurements involved in this study, the preovulatory follicle count (PFC), antral follicle count (AFC), and anti-Müllerian hormone (AMH) were revealed to be the most important features in prediction models. In conclusion, we successfully established the machine learning approach that could help the elderly infertile patients to better understand the most possible outcomes in subjecting to the controlled ovarian hyperstimulation.

Can fiscal decentralization and farmers' use of internent be the route to the digitalization performance in China? A novel approach towards unlocking the role of online marketing behavior and performance of agricultural products.

It is believed that the respondents' disadvantageous positions and the information asymmetry that exists between them are the bottlenecks that contribute to the stagnation of trades and the poor revenue that respondents receive from agro-products. Digitalization and fiscal decentralization both play an important part in helping to increase the information literacy of respondents who live in rural areas. The purpose of this study is to investigate the theoretical effects that the digital revolution has had on environmental behavior and performance, and it also analyzes the part that digitalization plays in the process of fiscal decentralization. This study investigates the impact that farmers' usage of the Internet has on their information literacy, online sales behavior, and online sales performance using research data collected from 1338 farmers in China primarily produce pears. Primary data was collected and utilized to develop a structural equation model, using the partial least squares (PLS) and bootstrapping methods; according to the findings, the use of the Internet by farmers has a significant positive effect on the improvement of their information literacy, and it will promote their online sales of pear through the improvement of their information literacy. The results show that the use of the Internet by farmers will improve the online sales performance of pear due to the improvement of farmers' information literacy.

Age-related decline in the expression of GDF9 and BMP15 genes in follicle fluid and granulosa cells derived from poor ovarian responders.

BACKGROUND: Growth differentiation factor 9 (GDF9) and bone morphogenetic protein 15 (BMP15) genes play important roles in folliculogenesis. Altered expression of the two have been found among patients with poor ovarian response (POR). In this prospective cohort study, we have determined the expression of the GDF9 and BMP15 genes in follicle fluid (FF) and granulosa cells (GCs) derived from poor ovarian responders grouped by age, and explored its correlation with the outcome of in vitro fertilization and embryo transfer (IVF-ET) treatment. METHODS: A total of 196 patients with POR were enrolled from a tertiary teaching hospital. The patients were diagnosed by the Bologna criteria and sub-divided into group A (< 35 year old), group B (35-40 year old), and group C (> 40 year old). A GnRH antagonist protocol was conducted for all patients, and FF and GCs were collected after oocyte retrieval. Expression of the GDF9 and BMP15 genes in the FF and GCs was determined with enzyme-linked immunosorbent assay (ELISA), quantitative real-time polymerase chain reaction (qRT-PCR) and Western blotting. RESULTS: Compared with group C, groups A and B had significantly more two pronuclei (2PN) oocytes and transplantable embryos, in addition with higher rates of implantation and clinical pregnancy (P <  0.05). The expression level of GDF9 and BMP15 genes in the FF and GCs differed significantly among the three groups (P <  0.05), showing a trend of decline along with age. The ratio of GDF9/BMP15 mRNA levels were similar among the three groups (P > 0.05). The relative levels of GDF9 and BMP15 proteins in GCs have correlated with the relative mRNA levels in GCs and protein concentrations in FF (P <  0.05). CONCLUSIONS: For poor ovarian responders, in particular those over 40, the expression of GDF9 and BMP15 is declined along with increased age and in accompany with poorer oocyte quality and IVF outcome, whilst the ratio of GDF9/BMP15 mRNA levels remained relatively constant. TRIAL REGISTRATION: Chinese Clinical Trial Registry Center ( ChiCTR1800016107 ). Registered on 11 May 2018.

Evaluation of 3,4,4,9-trichlorocarbanilide to zebrafish developmental toxicity based on transcriptomics analysis.

Triclocarban (TCC), considered an endocrine-disrupting, persistent, and bioaccumulating organic matter, has attracted a great deal of attention for its pollution and health risks. However, studies on its toxicological mechanism, especially for embryo development are limited. This article explores the cardiac developmental toxicity induced in zebrafish embryos after exposure to different TCC concentrations. First, liquid chromatography-tandem mass spectrometry was used in detecting TCC in embryos in vivo after exposure to various TCC. Results showed that embryonic TCC content reached 9.23 ng after exposure to 300 µg/L TCC, the heart rates of the embryos markedly decreased, heart abnormalities significantly increased. In addition, obvious pericardial effusion was observed in the larvae. Through transcriptome sequencing, 200 differential gene expression (DGE) patterns were detected in the TCC (300 µg/L) experimental and control groups. The results of GO function analysis and KEGG pathway of DGE showed that aryl hydrocarbon receptor (AhR) activation and cyp-related genes (cyp1a, cyp1b1 and cyp1c) were significantly up-regulated. these affected the normal development of zebrafish embryonic heart, tissue edema, and hemorrhage. TCC exhibited strong cardiac teratogenic effects and developmental toxicity, which is partly related to AhR activation. Transcriptome-based results are helpful in precisely determining the risk of TCC exposure. The potential mechanism between TCC and AhR should be further investigated.

tmbim4 protects against triclocarban-induced embryonic toxicity in zebrafish by regulating autophagy and apoptosis.

Triclocarban (TCC), an antibacterial agent widely used in personal care products, can affect embryonic development. However, the specific molecular mechanism of TCC-induced embryonic developmental damage remains unclear. In this study, TCC exposure was found to increase the expression of tmbim4 gene in zebrafish embryos. The tmbim4 mutant embryos are more susceptible to TCC exposure than wild-type (WT) embryos, with tmbim4 overexpression reducing TCC-induced embryonic death in the former. Exposure of tmbim4 mutant larvae to 400 µg/L TCC substantially increased apoptosis in the hindbrain and eyes. RNA-sequencing of WT and tmbim4 mutant larvae indicated that knockout of the tmbim4 gene in zebrafish affects the autophagy pathway. Abnormalities in autophagy can increase apoptosis and TCC exposure caused abnormal accumulation of autophagosomes in the hindbrain of tmbim4 mutant zebrafish embryos. Pretreatment of TCC-exposed tmbim4 mutant zebrafish embryos with autophagosome formation inhibitors, substantially reduced the mortality of embryos and apoptosis levels. These results indicate that defects in the tmbim4 gene can reduce zebrafish embryo resistance to TCC. Additionally, apoptosis induced by abnormal accumulation of autophagosomes is involved in this process.

Prokineticin 2 overexpression induces spermatocyte apoptosis in varicocele in rats.

Varicocele is one of the most important causes of male infertility, as this condition leads to a decline in sperm quality. It is generally believed that the presence of varicocele induces an increase in reactive oxygen species levels, leading to oxidative stress and sperm apoptosis; however, the specific pathogenic mechanisms affecting spermatogenesis remain elusive. Prokineticin 2 (PK2), a secretory protein, is associated with multiple biological processes, including cell migration, proliferation, and apoptosis. In the testis, PK2 is expressed in spermatocytes under normal physiological conditions. To investigate the role of PK2 in varicocele, a rat varicocele model was established to locate and quantify the expression of PK2 and its receptor, prokineticin receptor 1 (PKR1), by immunohistochemistry and quantitative real-time PCR assays (qPCR). Moreover, H2O2 was applied to mimic the oxidative stress state of varicocele through coculturing with a spermatocyte-derived cell line (GC-2) in vitro, and the apoptosis rate was detected by flow cytometry. Here, we illustrated that the expression levels of PK2 and PKR1 were upregulated in the spermatocytes of the rat model. Administration of H2O2 stimulated the overexpression of PK2 in GC-2. Transfection of recombinant pCMV-HA-PK2 into GC-2 cells promoted apoptosis by upregulating cleaved-caspase-3, caspase-8, and B cell lymphoma 2-associated X; downregulating B cell lymphoma 2; and promoting the accumulation of intracellular calcium. Overall, we revealed that the varicocele-induced oxidative stress stimulated the overexpression of PK2, leading to apoptosis of spermatocytes. Our study provides new insight into the mechanisms underlying oxidative stress-associated male infertility and suggests a novel therapeutic target for male infertility.

CSE1L participates in regulating cell mitosis in human seminoma.

OBJECTIVES: CSE1L has been reported to be highly expressed in various tumours. Testicular germ cell tumours are common among young males, and seminoma is the major type. However, whether CSE1L has functions in the seminoma is unclear. MATERIALS AND METHODS: The expression of CSE1L was detected by immunohistochemistry in seminoma tissues and non-tumour normal testis tissues from patients. CSE1L distribution during cell mitosis was determined by immunofluorescent staining with CSE1L, α-tubulin and γ-tubulin antibodies. The effects of Cse1L knockdown on cell proliferation and cell cycle progression were determined by Cell Counting Kit-8 assay, flow cytometry, PH3 staining and bromodeoxyuridine incorporation assay. RESULTS: CSE1L was significantly enriched in the seminoma tissue compared with the non-tumour normal testis tissue. CSE1L also co-localized with α-tubulin in the cells with a potential to divide. In the seminoma cell line TCam-2, CSE1L was associated with the spindles and the centrosomes during cell division. The knockdown of CSE1L in TCam-2 cells attenuated the cells' proliferative capacity. Cell cycle assay revealed that the CSE1L-deficient cells were mainly arrested in the G0/G1 phase and moderately delayed in the G2/M phase. The proportion of cells with multipolar spindle and abnormal spindle geometry was obviously increased by CSE1L expression silencing in the TCam-2 cells. CONCLUSIONS: Overall, these findings showed that CSE1L plays a pivotal role in maintaining cell proliferation and cell division in seminomas.

Activation of the NLRP3 Inflammasome Pathway by Prokineticin 2 in Testicular Macrophages of Uropathogenic Escherichia coli- Induced Orchitis.

Infections of the reproductive tract are known to contribute to testicular inflammatory impairment, leading to an increase of pro-inflammatory cytokines such as IL-1ß, and a decline in sperm quality. Prokineticin 2 (PK2), a secretory protein, is closely associated with the secretion of pro-inflammatory cytokines in inflamed tissue. It was reported that increased PK2 is related to the upregulation of IL-1ß, but the underlying mechanism remains elusive. Here, we illustrated that PK2 was upregulated in testicular macrophages (TM) in a rat model of uropathogenic Escherichia coli (UPEC) infection, which induced the activation of the NLRP3 inflammasome pathway to boost IL-1ß secretion. Administration of PK2 inhibitor alleviated the inflammatory damage and suppressed IL-1ß secretion. Moreover, PK2 promoted NLRP3 expression and the release of cleaved IL-1ß from TM to the supernatants after the challenge with UPEC in vitro. IL-1ß in the supernatants affected Leydig cells by suppressing the expression of genes encoding for the enzymes P450scc and P450c17, which are involved in testosterone production. Overall, we revealed that increased PK2 levels in TM in UPEC-induced orchitis may impair testosterone synthesis via the activation of the NLRP3 pathway. Our study provides a new insight into the mechanisms underlying inflammation-associated male infertility and suggests an anti-inflammatory therapeutic target for male infertility.

Effects of triclocarban on oxidative stress and innate immune response in zebrafish embryos.

Triclocarban (TCC) is used in many household and personal hygiene products. TCC has been widely detected in wastewater around the world. The present study reveals that TCC can activate oxidative stress, induce total antioxidant capacity expression and lipid peroxidation, and increase the activities of superoxide dismutase and other antioxidant enzymes to resist oxidative damage. A significant induction of concentrations of proinflammatory mediator and nitric oxide (NO), accompanied by an upregulated expression of inducible NO synthase gene, was detected in zebrafish embryos exposed to TCC. The transcription of immune-response-related genes, including tnf-α, il-1ß, il-4, il-8, and cxcl-clc, was significantly upregulated on exposure to TCC. Furthermore, we found that the exposure of zebrafish embryos to TCC decreased immune cell recruiting in the head. Expressions of nf-κb, trif, myd88, irak4, and traf6 were altered on exposure to TCC. These results demonstrated that exposure to TCC at environmental concentrations significantly affects the expression of immune-response-related genes in zebrafish embryos following oxidative stress and the release of proinflammatory mediators through Toll-like receptor signaling pathway. Thus, we assumed that the ecological risk of TCC on aquatic organisms could not be ignored.

Effects of Testosterone Supplementation on Body Composition in HIV Patients: A Meta-analysis of Double-blinded Randomized Controlled Trials.

This study was designed to evaluate the effects of testosterone supplementation (TS) on body composition in patients with HIV and the side effects of TS. A comprehensive literature search strategy was used to retrieve relevant randomized controlled trials (RCTs) examining the effects of TS on body composition. Atotal of 14 eligible studies were included, enrolling 388 and 349 randomized patients in TS and control groups, respectively. The quality of studies included was assessed, and data on total body weight (BW), lean body mass (LBM), fat mass (FM), serum total testosterone (TT), free testosterone (FT) levels, and adverse events were extracted and analyzed using Review Manager software 5.3. Meta-analysis results showed that TS was associated with a small but significant modification in total BW, serum TT, and FT levels in HIV-infected patients and in patients given various drug administrations. TS also significantly increased LBM in male patients, but no significant difference in LBM was observed between female counterparts treated with TS or not. Conversely, TS relative to placebo did not lead to a significant reduction in FM. No significant difference was observed between the two groups in terms of adverse effects. Our findings suggested that TS may be recommended to improve body composition in patients with HIV-related weight loss. However, owing to the high heterogeneity across included trials, further evaluations using large-scale, multi-center, blinded RCTs are needed.

Effect of folate deficiency on promoter methylation and gene expression of Esr1, Cav1, and Elavl1, and its influence on spermatogenesis.

This study aims to investigate the effect of folate deficiency on the male reproductive function and the underlying mechanism. A total of 269 screened participants from 421 recruitments were enrolled in this study. An animal model of folate deficiency was constructed. Folate concentration was measured in the ejaculate, and its association with semen parameters was then determined. The expression and promoter methylation status of ESR1, CAV1, and ELAVL1 were also evaluated. Results showed that seminal plasma folate level was significantly lower among subjects with azoospermia than those with normozoospermia. Low folate level was significantly correlated with low sperm concentration in men with normozoospermia. Folate deficiency significantly reduced the expression of ESR1, CAV1, and ELAVL1, which are critical to spermatogenesis. However, low folate levels did not increase the methylation levels of the promoter regions of ESR1, CAV1, and ELAVL1 in human sperm DNA. Thus, folate deficiency impairs spermatogenesis may partly due to inhibiting the expression of these genes. Thus future research should determine the significance of sufficient folate status in male fertilization and subsequent pregnancy outcomes.