Search

The impact of depression on spermatogenic function and protein expression was investigated by reference to a bioinformatics database for the prediction of key targets and pathways. Experimental validation was performed using a rat model established using the chronic restraint stress method. Organ coefficients and semen parameters were measured. Hematoxylin and eosin (HE) staining was performed to compare testicular tissue between model and control rats. Western blotting and RT–qPCR were conducted to evaluate protein and mRNA expression. As a result, depression and male infertility (MI) were found to share 81 common targets, and the PI3K/Akt/FOXO1 signaling pathway was involved in both conditions. Animal experiments showed testis and epididymis coefficients to be lower in the model group. HE staining showed damage to the seminiferous tubules of model rats. PI3K and p-Akt mRNA and protein were present at lower levels and FOXO1 at higher levels in the model group. Depression led to reduced spermatogenic function in rats and might be associated with differential expression of the PI3K/Akt/FOXO1 signaling pathway.

MEMS acceleration sensors are widely used in Internet of Things, electronic machinery, aerospace and other fields with outstanding advantages such as small size, high reliability, intelligence and high integration. Traditional MEMS acceleration sensors limit their applications due to high-power consumption and low-precision; the standby time and service life are being increased in order to study the low-power and high-precision MEMS acceleration sensor readout, this paper adopts the Fully Differential Switched Capacitor-Variable Gain Amplifier (FDSC-VGA) instead of the traditional high-power Capacitance-to-Voltage Converter (CVC-VGA), Sample-and-Hold Circuit (S&H) and Anti-Aliasing Filter (AAF) as front-end modules. At the same time, a high-precision four-phase non-crossover clock is designed to precisely control the timing switch, thus effectively reducing the power consumption of the MEMS acceleration sensor readout circuit; then, the overall readout circuit is simulated and verified by Dong Bu HiTek 0.18 μm process. The results show that the error rate of the output voltage of FDSC-VGA is reduced from 8.03% to 0.88% compared with the conventional readout circuit, and the noise power consumption of MEMS acceleration sensor readout circuit can be reduced by 65%.

分析了带隙基准电压分段补偿技术与基本原理, 提出一种具有预稳压功能的高低温补偿带隙基准电路。应用高低温补偿电路优化了温度系数, 设置预稳压电路提高了带隙基准电路的电源抑制比。基于0.35 μm标准CMOS工艺设计并绘制了电路及版图。仿真结果表明, 在-55~125℃范围内, 温漂系数仅为1.8×10-6/℃; 电源抑制比为-84.6 dB(在1 kHz下); 在2.6~5 V的电源幅度范围下, 电源抑制性能为19.6 μV/V。该电路可应用于高精度系统设计中。

Background and aim: Achyranthis Bidentatae Radix plus Semen Vaccariae are traditional Chinese medicines, which have been widely applied in the treatment of migraine and Erectile Dysfunction (ED) for many years. This study verified the effect of Achyranthis Bidentatae Radix plus Semen Vaccariae in improving migraine-induced ED and explored its potential mechanism. Methods: Key targets and signaling pathways of Achyranthis Bidentatae Radix plus Semen Vaccariae in migraine-induced erectile dysfunction treatment were predicted by network pharmacology. A rat model of migraine was established by nitroglycerin injection. Apomorphine was injected into rats to screen the migraine-induced erectile dysfunction model, Achyranthis Bidentatae Radix-Semen Vaccariae granule suspension administered, and erectile function evaluated. Hematoxylin and eosin staining was used to compare the histological structure of the penile tissue, while RT-qPCR and Western blotting were used to determine mRNA and protein levels, respectively. Results: Screening allowed us to identify common targets for migraine and ED; the signaling pathway exhibiting the greatest change was the Myosin light chain kinase- Calcium (MLCK-CaM) signal pathway. From Western blotting and RT-qPCR, we found that the levels of MLCK mRNA and protein in rats from Group B rats were significantly higher (P Conclusion: Data indicate that the regulatory effects of Achyranthis Bidentatae Radix plus Semen Vaccariae on migraine-induced ED in a rat model are mediated by the MLCK-CaM signaling pathway.

This study is to verify the effect of asthma on sperm quality and explore its potential underlying mechanism. We randomly categorized the Sprague-Dawley (SD) rats into control (Group C) and asthma model (Group M) groups. Rats in the asthma model group were induced allergic asthma by intraperitoneal injection of ovalbumin solution. We evaluated the sperm motility and sperm concentration. The expression of the Interleukin-6 (IL6), phosphorylation-signal transducer and activator of transcription 3 (p-Stat3), and hypoxia-inducible factor-1α (HIF-1α) proteins and mRNAs in the testicular tissue was detected by western blotting and RT-qPCR. Compared with group C, sperm concentration and sperm motility in group M rats were significantly decreased ( P < 0.05 ). Meanwhile, compared with group C, the expression levels of IL6, Stat3, and HIF-1α proteins and mRNAs in group M rats were significantly increased ( P < 0.05 ). Asthma can regulate the HIF-1 signaling pathway, promoting the expression of IL6, Stat3, and HIF-1α protein and mRNAs, so as to promote sperm apoptosis and ultimately causing male infertility.

Glycerol hydrogenated rosin (GEHR) and d-limonene were prepared for micro-particles by electrostatic spray method. When the GEHR/d-limonene ratio is 5.5:4.5 and the electrostatic spray extrusion speed is 1 mL/h, the best particle size (177.24 ± 17.09 μm) and embedding rate of d-limonene (41.74 ± 9.88%) are achieved. Then, rock bean protein (RP) was extracted from wild rock beans and combined with GEHR/d-limonene particles and corn starch (CS) to prepare a new type of edible film. The prepared film was characterized using Fourier transform infrared spectroscopy in terms of structural changes and physical, optical, mechanical, and thermal properties. The results show that the edible film with a ratio of 1:1 exhibited more optimized thermal (179.2 °C) and mechanical properties (TS 0.88 MPa, EAB 54.36%). Studies on freshly prepared glutinous rice cake as an object for preservation using edible film show that the films can prolong shelf life by ~2-4 d. Through this experiment, it can serve as a reference for the development of a new type of edible film.

Background. Over recent years, an increasing body of literature has focused on the relationship between erectile dysfunction (ED) and migraine. However, the specific mechanism is unclear. Materials and Methods. We used a bioinformatic database to predict the targets and pathways associated with migraine and ED. Twenty male SD rats were randomly divided into a blank group (Group A, n = 10 ) and a migraine model group (Group B, n = 10 ). The rats in Group A were subcutaneously injected with normal saline (2 ml/kg) into the back of the neck. Rats in Group B were subcutaneously injected with nitroglycerin 10 mg/kg (5 mg/ml) into the back of the neck in order to create an animal model of migraine. Next, we carried out the measurement of erectile function. We used hematoxylin and eosin (HE) to compare the tissue structure of the cavernous body of the penis. Western blotting was used to determine the expression levels of PI3K, p-AKT, and p-mTOR in the protein; Reverse Transcription-Polymerase Chain Reaction (RT-qPCR) was used to determine the expression levels of PI3K, AKT, and mTOR in the messenger ribonucleic acid (mRNA). Results. There are 117 intersection targets of migraine and ED, involving 188 cell biological processes (BP), 21 cellular components (CC), 31 molecular functions (MF), and 65 signaling pathways. HE staining results show that there were no significant differences between Group A and Group B with regard to any of the parameters. Compared with Group A, the levels of the PI3K, p-AKT, and p-mTOR proteins and PI3K, AKT, and mTOR mRNAs in Group B decreased ( P < 0.01 ). Conclusions. The decline of erectile function in a rat model of migraine was associated with the PI3K/Akt/mTOR signaling pathway.

Ji-sheng Wang,1,2,* Xue-feng Gong,3,4,* Jun-long Feng,1,2,* Hai-song Li,2 Xiao Li,5 Sheng Deng,1,2 Pei-zhong Ren,3,4 Jia-mei Wang,3,4 Ming-sheng Lv,3,4 Rui-feng Jin,3,4 Qiu-yi Chen,3,4 Bin Wang,2 Hong-sheng Cui4 1First Clinical Medical College, Beijing University of Chinese Medicine, Beijing, 100029, People’s Republic of China; 2Andrology Department, Dongzhimen Hospital, Beijing University of Chinese Medicine, Beijing, 100700, People’s Republic of China; 3The Third Affiliated Hospital of Beijing University of Chinese Medicine, Beijing, 100029, People’s Republic of China; 4Pneumology Department, The Third Affiliated Hospital of Beijing University of Chinese Medicine, Beijing, 100029, People’s Republic of China; 5Department of Andrology, The First Affiliated Hospital of Henan University of Chinese Medicine, Zhengzhou, 450046, People’s Republic of China*These authors contributed equally to this workCorrespondence: Bin WangAndrology Department, Dongzhimen Hospital, Beijing University of Chinese Medicine, Beijing, 100700, People’s Republic of ChinaEmail dayiwangbln@sina.comHong-sheng CuiPneumology Department, The Third Affiliated Hospital of Beijing University of Chinese Medicine, Beijing, 100029, People’s Republic of ChinaEmail Hshcui@sina.comBackground: Jiawei Shengjiang Powder (JWSJP) is a classical Chinese medicinal formula, which has been widely applied in the treatment of asthma and complications for many years due to its curative effect.Aim: To verify the effect of JWSJP in improving abnormal sperm motility caused by asthma and to explore its potential mechanism.Materials and Methods: The active compounds of JWSJP were obtained from high performance liquid chromatography tandem mass spectrometry and the Traditional Chinese Medicine System Pharmacology. The key active components and targets of JWSJP were predicted based on network pharmacological analysis and bioinformatics research. Rats were randomly divided into normal, model and treatment groups. The rat model of allergic asthma was induced by intraperitoneal injection of ovalbumin solution. The experiment judged improvement of semen quality by evaluating sperm motility, and detected the expression of related proteins in testicular tissue of Sprague-Dawley rats by RT-qPCR and Western blot methods. Hematoxylin and eosin (HE) staining was used to observe the changes in testicular tissue structure in rats.Results: Through the analysis of network pharmacology and bioinformatics, it was found that beta-sitosterol, quercetin, gallic acid, pelargonidin and kaempferol were the key active components of Jiawei Shengjiang Powder. Tumor necrosis factor (TNF), interleukin-6 (IL-6) and insulin (INS) genes are crucial targets of JWSJP in the treatment of spermatogenic dysfunction caused by acute asthma. After 8 weeks of intervention, compared with the model group, the treatment group had significantly improved sperm motility (P < 0.05). There were significant differences in TNF, IL6, and INS proteins in the treatment group, and the HE staining of testicular tissue structure in the treatment group was significantly improved.Conclusion: JWSJP can improve the abnormal sperm motility induced by asthma, and its mechanism may be related to the expression of related proteins and mRNA of TNF, IL6, and INS.Keywords: Jiawei Shengjiang Powder, asthmatic attack, asthenospermia, network pharmacology

Context Achyranthes bidentata Blume (Amaranthaceae) (ABR) and semen vaccariae (SV) are used commonly in the clinical treatment of erectile dysfunction in males with diabetes mellitus (DMED) to strengthen the kidney and promote blood circulation, and often achieve good curative effects. Objective Explore mechanistic details of ABR + SV treatment against DMED. Materials and methods Prediction of key targets by network pharmacology. A rat model of DM was established by streptozotocin injection (55 mg/kg). Apomorphine (100 μg/kg) was injected into rats to screen the DMED model. Group C (n = 6) and group M (n = 6) were gavaged with deionized water; group T (n = 6) was given Achyranthis bidentatae radix–semen vaccariae granule suspension (2.5 g/kg). It lasted 8 weeks. Real-time reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and western blotting (WB) were used to measure the expression of tissue-related proteins and mRNA. Results The predicted key targets are albumin (ALB), caspase-3 (CASP3), vascular endothelial growth factor A (VEGFA), angiotensin-converting enzyme (ACE), and endothelial nitric oxide synthase (eNOS). Compared with the M group (0.52 ± 0.04; 0.50 ± 0.03; 0.49 ± 0.02; 0.23 ± 0.03), CASP3, VEGFA, and ACE protein expression reduced in the T group (0.39 ± 0.06; 0.34 ± 0.03; 0.39 ± 0.03), and eNOS protein expression increased (0.34 ± 0.03). Conclusion ABR + SV can improve erectile function in DMED rats. This study provides a potential mechanism for the treatment of DMED with ABR + SV and can benefit from more patients.

Zuogui Wan (ZGW) is a common prescription medication used in traditional Chinese medicine (TCM) to significantly improve the sperm quality and treat male infertility. This study evaluated the repair effect of ZGW and Levocarnitine (LEV) on GC1-spg cell injury induced by Glucosides of Tripterygium WilforDII Hook (GTW). The results showed that the ultrastructure and apoptosis rate of GC1- spg cells in LEV and ZGW group were considerably better than GTW. The transcriptional and translational level of CYP1A1, CYP17A1, androgen receptor (AR), SRD5A2 and proliferating cell nuclear antigen (PCNA) in GC-1spg cells of the LEV group were considerably elevated than GTW group (p 0.05 or 0.01). Furthermore, the transcriptional and translational levels of CYP19A1, CYP17A1, AR, SRD5A2 and PCNA in GC-1spg cells in ZGW group were found to be considerably elevated than the LEV group (p 0.05 or 0.01). The findings indicate that ZGW and LEV could increase the expression of PCNA, CYP17A1, CYP19A1, SRD5A2 and AR at transcriptional and translational levels, inhibit GC-1spg cell apoptosis and promoting cell proliferation, and the effect of ZGW was found to be significantly better than that of LEV.

Background The current evidence on the association between obesity-associated markers and semen quality, serum reproductive hormones and lipids remains inconsistent. In this study, we tested the hypothesis that, in infertile Chinese men, body mass index (BMI) negatively correlates with sperm concentration, serum total testosterone (TT), and high-density lipoprotein cholesterol (HDL-C). The relationship between other obesity-associated markers and semen quality parameters, serum reproductive hormones, lipids and leptin were also investigated. Methods 181 Chinese infertile men were recruited from September 2018 to September 2019. Their obesity-associated markers, semen parameters, and serum reproductive hormones, lipids and leptin were detected. Statistical analysis was performed to assess the relationship between obesity-associated markers and semen quality, serum reproductive hormones, lipids and leptin. Result(s) Statistically negative correlation was found between other obesity-associated markers (e.g. waist-to-hip ratio and waist-to-height ratio) and semen parameters (e.g. sperm concentration, ratio of progressive motility and ratio of non-progressive motility), while no significant correlation was found between BMI and semen quality, serum reproductive hormones, lipids and leptin. Ratio of morphologically normal sperm was negatively correlated with serum lipids including total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C), leptin and seminal superoxide dismutase. Ratio of progressive sperm, sperm concentration and ratio of morphologically normal sperm exhibited significantly lower values in overweight group than normal group. Estradiol (E2) and E2/TT were significantly higher in obese group than normal group, while TT level was significantly lower in obese group than normal group. Univariate and multivariate analysis indicated that TC was significantly associated with BMI. Serum leptin concentration was positively correlated with seminal leptin concentration in overweight and obese groups. Conclusion(s) No significant correlation was found between BMI and sperm concentration, serum TT and HDL-C, while other obesity-associated markers were found to negatively correlate with sperm concentration, ratio of progressive motility and ratio of non-progressive motility. Statistically significant correlations between serum reproductive hormones, lipids and leptin also existed in Chinese infertile men.

In this study, a simultaneous fill/draw SBR was applied to investigate the feasibility of partial nitrification process with inoculation of matured aerobic granular sludge. The system operated stably over 120 days with the relatively high ammonium removal efficiency (≥ 98.83%) and nitrite accumulation rate (≥ 89.60%). Moreover, a hybrid flocs/granules system was formed stably after long-term operation. The nitrite-oxidizing bacteria (NOB) was suppressed effectively because of the combined effect of simultaneous fill/draw mode and intermittent aeration conditions. Furthermore, batch tests were separately tested with isolated granules (200 μm) and flocs (200 μm), showing that the specific ammonia oxidation rate of granules and flocs were 15.94 ± 2.85 and 66.77 ± 0.83 mg N/(g MLSS·h), respectively. Correspondingly, the abundance of Nitrosomonas as a typical AOB in granules (6.24%) and flocs (11.94%) was obtained via the microbial diversity analysis, while NOB was almost hardly detected in granules and flocs.

To explore the mechanism through which liver cirrhosis (LC) causes erectile dysfunction (ED). Bioinformatic analysis was used to predict the potential signalling pathways in LC-induced ED, and N-nitrosodiethylamine was used to establish a rat model of LC. HE staining, Western blotting and RT-qPCR were used to detect pathological tissue damage and changes in mRNA and protein expression levels. In addition, the expression levels of sex hormones such as estradiol (E2), prolactin (PRL) and testosterone (T) were measured. The hypoxia-inducible factor (HIF) pathway was an important pathway in our bioinformatics prediction. Pathological damages were detected in the liver and penile tissues of the model rats. Compared with the normal group's serum hormone levels, E2 and PRL were increased in LC rats, while T was decreased (p 0.01). The mRNA and protein expression results from penis tissues showed that endothelial nitric oxide synthase (eNOS) and inducible nitric oxide synthase (iNOS) were both downregulated, and HIF-1α was upregulated in the model group compared to the normal group (p 0.01). These data suggest that LC hinders erectile function and causes histopathological changes in the penis by affecting the expression of HIF-1α, eNOS, iNOS, E2, PRL and T.

Microorganisms in activated sludge from wastewater treatment plants (WWTPs) form complex networks to convert a wide variety of pollutants, thus ensuring water purification and environmental protection. In this study, activated sludge samples were collected from three full-scale WWTPs: a petrochemical WWTP (PWWTP), a municipal WWTP treating domestic wastewater (MWWTP_D), and a municipal WWTP treating a mixture of domestic wastewater and multiple industrial effluents (MWWTP_I+D). These samples were analyzed by high-throughput sequencing of 16S rRNA gene PCoA and CPCoA indicated that the samples from three WWTPs were separated, suggesting that each WWTP had unique microbiome characters (P0.05). This was also evidenced by the different predominant bacteria (PDB), biomarkers, and key nodes of co-occurrence network in the three WWTPs. Microorganisms with all three above mentioned characteristics were defined the core bacteria, specifically: Georgfuchsia, Thauera and GP4 in PWWTP, Phaeodactylibacter and Hyphomicrobiuml in MWWTP_D, and Otheakwangia, Terrimonas, Phenylobacterium, etc. in MWWTP_I + D. Furthermore, in accordance with the functional profile prediction, the functional groups in PWWTP metabolized aromatic compound, sulfur compounds and heavy metal typically present in petrochemical wastewater. In contrast, the microbiome in MWWTP_D was represented by the population breaking down macromolecular biodegradable organic matter and the nitrogen nutrients that constitute the vast majority of domestic wastewater pollutants. Both functional groups coexist in MWWTP_I + D. These results revealed that the specific composition of incoming wastewaters produced distinct ecological niches and modulated the ecological structure of activated sludge microbial communities in real-world WWTPs. However, the generalization of the results of this study will require further research.

LEV improves the percentage of forward-motion spermatozoon and total sperm motility in patients with oligozoospermia or asthenospermia in clinical settings. However, the mechanism of action of levocarnitine (LEV) in the treatment of spermatogenic dysfunction was unclear. Based on in vitro and in vivo experiments, we used Glucosides of Tripterygium wilfordii Hook F (GTW) to construct a cell model (using spermatogenic GC-1 spg cells) and an animal model (using rats) of spermatogenic dysfunction. LEV and LY294002 (a PI3K pathway inhibitor) were then administered. By assessing apoptosis and sperm quality and motility, the underlying mechanism was explored. We found that GTW induced spermatogenic dysfunction, and LEV ameliorated the GTW-induced spermatogenic dysfunction. LEV inhibited GC-1 spg cell apoptosis and improved the sperm count and percentages of PR (forward motion) + NP (non-forward motion) (p

Temozolomide (TMZ) is the mainstream chemotherapeutic drug for treating glioblastoma multiforme (GBM), but the intrinsic or acquired chemoresistance to TMZ has become the leading clinical concern, which is related to the repair of DNA alkylation sites by O6-methylguanine-DNA methyltransferase (MGMT). Pyrvinium pamoate (PP), the FDA-approved anthelminthic drug, has been reported to inhibit the Wnt/β-catenin pathway within numerous cancer types, and Wnt/β-catenin signaling pathway can modulate the expression of MGMT gene. However, whether PP affects the expression of MGMT and enhances TMZ sensitivity in GBM cells remains unclear. In the present study, we found that PP and TMZ had synergistic effect on inhibiting the viability of GBM cells, and PP induced inhibition of MGMT and enhanced the TMZ chemosensitivity of GBM cells through down-regulating Wnt/β-catenin pathway. Moreover, the overexpression of MGMT or β-catenin weakened the synergy between PP and TMZ. The mechanism of PP in inhibiting the Wnt pathway was indicated that PP resulted in the degradation of β-catenin via the AKT/GSK3β/β-catenin signaling axis. Moreover, Ser552 phosphorylation in β-catenin, which promotes its nuclear accumulation and transcriptional activity, is blocked by PP that also inhibits the Wnt pathway to some extent. The intracranial GBM mouse model also demonstrated that the synergy between PP and TMZ could be achieved through down-regulating β-catenin and MGMT, which prolonged the survival time of tumor-bearing mice. Taken together, our data suggest that PP may serve as the prospect medicine to improve the chemotherapeutic effect on GBM, especially for chemoresistant to TMZ induced by MGMT overexpression.

This study aimed to verify that Xuefu Zhuyu decoction (XFZYD) can improve asthenozoospermia caused by asthma, and explore its potential mechanism. Ovalbumin solution is used to induce asthma rat models. Sperm concentration and motility are used to evaluate semen quality. Immunohistochemistry (IHC), Western blotting and real-time reverse transcription-quantitative polymerase chain reaction (RT-qPCR) are used to detect proteins and mRNA related to rat testis tissue. Haematoxylin and eosin (H&E) staining was used to observe changes in testicular tissues. Through network pharmacology, eriodictyol, 18-β-glycyrrhetinic acid, naringenin, chrysin and Hispidulin were prominent active ingredients of XFZYD. We found that XFZYD regulates the expression levels of albumin (ALB), vascular endothelial growth factor A (VEGFA), interleukin 6 (IL-6) protein and mRNA, thereby improving the histopathological morphology of the testis, increasing the concentration and motility of spermatozoa. We suggest that future research can increase the detection of hormones and oxidative stress and other related indicators, so as to conduct more in-depth exploration.

Glioblastoma multiforme (GBM) is the most common and aggressive primary brain tumor with a high mortality rate. Immunotherapy has achieved promising clinical results in multiple cancers, but shows unsatisfactory outcome in GBM patients, and poor drug delivery across the blood-brain barrier (BBB) is believed to be one of the main limitations that hinder the therapeutic efficacy of drugs. Herein, a new cationic lipid nanoparticle (LNP) that can efficiently deliver siRNA across BBB and target mouse brain is prepared for modulating the tumor microenvironment for GBM immunotherapy. By designing and screening cationic LNPs with different ionizable amine headgroups, a lipid (named as BAMPA-O16B) is identified with an optimal acid dissociation constant (pKa) that significantly enhances the cellular uptake and endosomal escape of siRNA lipoplex in mouse GBM cells. Importantly, BAMPA-O16B/siRNA lipoplex is highly effective to deliver siRNA against CD47 and PD-L1 across the BBB into cranial GBM in mice, and downregulate target gene expression in the tumor, resulting in synergistically activating a T cell-dependent antitumor immunity in orthotopic GBM. Collectively, this study offers an effective strategy for brain targeted siRNA delivery and gene silencing by optimizing the physicochemical property of LNPs. The effectiveness of modulating immune environment of GBM could further be expanded for potential treatment of other brain tumors.

Context: Zuogui Wan is a classic traditional Chinese prescription. Preliminary studies have confirmed that it could improve sperm quality significantly. Objective: To investigate the effect of Zuogui Wan on testis structure and c-kitproto-oncogeneprotein (c-Kit) and octamer-binding transcription factor-4 (Oct4) expression in a rat model of impaired spermatogenesis. Material and methods: Thirty-six Sprague-Dawley (SD) rats were divided into Blank control, Tripterygium glycosides (GTW) and Zuogui Wan groups (n = 12). GTW was used to generate models of impaired spermatogenesis. Then Zuogui Wan group was administered 6 g/kg/d of Zuogui Wan granules for 4 weeks. Changes in the pathological structure and ultrastructure were observed with optical microscope and transmission electron microscope. Expression of c-Kit and Oct4 were quantified by RT qPCR and Western blots. Results: Both the pathological damage and the damages in the ultrastructure of spermatogenic epithelium had improved in Zuogui Wan group. Compared with the GTW model group (0.47 ± 0.19; 0.38 ± 0.14), c-Kit and Oct4 protein expression increased in the Zuogui Wan group (0.75 ± 0.27; 0.65 ± 0.23). C-Kit and Oct4 mRNA expression increased in Zuogui Wan group (1.06 ± 0.16; 1.85 ± 1.04) compared to the GTW model group (0.66 ± 0.23; 0.46 ± 0.29). Conclusions: Zuogui Wan is capable of restoring the damage to the testis structure and ultrastructure and regulates the expression of c-Kit and Oct4 at protein and mRNA levels, inhibiting apoptosis and promoting proliferation of spermatogenic cells.

Ethnopharmacological relevance Huoxue Tongluo Qiwei Decoction is a classical herbal formula, which can improve the symptoms of erectile dysfunction (ED) patients and has a good therapeutic effect on patients with diabetic erectile dysfunction (DIED). The main function of Huoxue Tongluo Qiwei Decoction is to stimulate the blood circulation and dredge collaterals, remove blood stasis, and calm wind. Rationale To further explore the mechanism of Huoxue Tongluo Qiwei Decoction in the treatment of DIED, related animal experiments were designed. Materials and methods The chemical constituents of Huoxue Tongluo Qiwei Decoction were identified with the help of high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS). A rat model was induced by streptozotocin (STZ) and screened by apomorphine (APO). Serum sE-selectin, lysyl oxidase-1 (LOX-1), malondialdehyde (MDA) and other markers of vascular endothelial injury and related indicators of oxidative stress were studied through enzyme-linked immunosorbent assay (ELISA). The endothelial cells and ultrastructure of the corpus cavernosum were examined by electron microscopy and HE staining. The expression of protein and mRNA was detected by western blotting (WB) and real-time quantitative polymerase chain reaction (RT-qPCR). Results The results of the study revealed that the sE-selectin, LOX-1, intercellular adhesion molecule-1 (sICAM-1), endothelial microparticles (EMPs), P-selectin (CD62P), and MDA levels in the serum of group M rats were considerably higher than rats of group K, while the superoxide dismutase (SOD) level showed a significant decrease. In addition, the PKC pathway was activated, and the expression of related proteins and mRNA was increased. After 8 weeks of intervention with Huoxue Tongluo Qiwei Decoction and LY333531, serum level of sE-selectin, LOX-1, sICAM-1, EMPs, CD62P and MDA in L, D and G groups were remarkably lower than group M while SOD level increased significantly, protein kinase C (PKC) pathway was inhibited with the improved erectile function of rats. Conclusion Huoxue Tongluo Qiwei Decoction can inhibit the expression of protein and mRNA of the PKCβ signaling pathway related molecules in DIED rats to cure the injury of vascular endothelial, enhance antioxidant capacity, and prevent the activation of platelet, thus improving erectile function in rats with DIED.

Background: A network meta-analysis (NMA) of the current recommended drugs for the treatment of acute heart failure (AHF), was performed to compare the relative efficacy.Methods: We used PubMed, EMBASE, Cochrane Clinical Trials Register, and Web of Science systems to search studies of randomized controlled trials (RCT) for the treatment of AHF recommended by the guidelines and expert consensus until 1 December 2020. The primary outcome was all-cause mortality within 30 days. The secondary outcomes included 30-days all-cause rehospitalization, rates of HF-related rehospitalization, rates of adverse events, and rates of serious adverse events. A Bayesian NMA based on random effects model was performed.Results: After screening 14,888 citations, 23 RCTs (17,097 patients) were included, focusing on nesiritide, placebo, serelaxin, rhANP, omecamtiv mecarbil, tezosentan, KW-3902, conivaptan, tolvaptan, TRV027, chlorothiazide, metolazone, ularitide, relaxin, and rolofylline. Omecamtiv mecarbil had significantly lower all-cause mortality rates than the placebo (odds ratio 0.04, 0.01–0.22), rhANP (odds ratio 0.03, 0–0.40), serelaxin (odds ratio 0.05, 0.01–0.38), tezosentan (odds ratio 0.04, 0–0.22), tolvaptan (odds ratio 0.04, 0.01–0.30), and TRV027 (odds ratio 0.03, 0–0.36). No drug was superior to the other drugs for the secondary outcomes and safety outcomes.Conclusion: No drug was superior to the other drugs for the secondary outcomes and safety outcomes. Current drugs for AHF show similar efficacy and safety.

Through network pharmacology research, we found that CYP19, CYP17, AR and SRD5A2 were potential targets for lycium chinense-cuscutae semen (LC-CS) treatment of oligoasthenozoospermia. Using in vitro and in vivo experiments, tripterygium glycosides were used to induce spermatogenic dysfunction models in GC-1spg cells and SD male rats, respectively, and LC-CS was used to intervene in a spermatogenic dysfunction model. In vitro, LC-CS could repair the ultrastructure of GC-1spg cells damaged by tripterygium glycosides (TG). Compared with TG group, LC-CS could upregulate protein and mRNA expression of CYP19, CYP17, AR and SRD5A2. In vivo, compared with TG, the body mass, testicular mass and epididymal weights of rats in TG + LC-CS increased. Progressive motility + nonprogressive motility spermatozoon (PR + NP) of TG + LC-CS were upregulate than TG. The levels of FSH, LH and testosterone in TG + LC-CS were upregulate than TG. LC-CS can repair the ultrastructure of spermatogonia damaged by TG (the above results are statistically significant, p

Background Many infertile couples might experience erectile dysfunction (ED) and significant changes in the quality of sexual life and psychological state though information is limited in secondary infertile men in China. To determine whether primary or secondary infertility is associated with ED, psychological disorders, and sexual performance. Methods This was a cross-sectional survey conducted at the Dongzhimen Hospital of Beijing University of Chinese Medicine (06/2019-01/2020). The participants completed a questionnaire including general information, sexual life, simplified International Index of Erectile Function (IIEF-5), Patient Health Questionnaire-9 (PHQ-9), and 7-item Generalized Anxiety Disorder Scale (GAD-7). Multivariable logistic regression was used to identify the factors associated with ED, depression, and anxiety. Results ED was more frequent in secondary vs. primary infertility (46.5 % vs. 26.7 %, P P P = 0.001), had a higher awareness of partner’s ovulation when having ED (P = 0.001), lower GAD-7 scores (P = 0.016), lower libido (P = 0.005), fewer intercourses per month (P = 0.001) and a lower sexual satisfaction score (P = 0.027). In the multivariate analysis, primary infertility was found to be an independent risk factor of anxiety (OR: 1.812, 95 %CI: 1.015–3.236). Some overlap is observed in factors associated with ED, psychological disorders, and sexual performance between primary and secondary infertility, but some factors are distinct. Conclusions The prevalence of ED in secondary infertility men was higher than that of primary infertility men, and the quality of sexual life was decreased. Primary infertility is an independent risk factor of anxiety.

The mechanism of action of levocarnitine (LEV) in the treatment of spermatogenic dysfunction was unclear. We used GTW to construct a cell model (using spermatogenic GC-1 spg cells) and an animal model (using rats) of spermatogenic dysfunction. LEV and LY294002 (a PI3K pathway inhibitor) were then administered. By assessing proliferation, mitochondrial membrane potential, apoptosis, and sex hormone levels, the underlying mechanism was explored. We found that (I) by regulating PI3K/AKT pathway-related protein expression, LEV increased the percentages of GC-1 spg cells in the G0/G1 and G2/M phases, increased the mitochondrial membrane potential, and decreased apoptosis, thereby improving the sperm count and motility and (II) LEV and significantly increased the T, FSH, and LH serum levels, thereby improving the spermatogenic function of rats.

Context The leech and centipede granules have good curative effects on many diabetic vascular diseases, including diabetes-induced erectile dysfunction (DIED). Objective To explore the effect of leech and centipede on erectile function in rats with diabetes-induced erectile dysfunction and its possible mechanism. Materials and methods Thirty male Sprague–Dawley DIED rats were randomly divided into the model group (Group M), low-dose group (Group DD), high-dose group (Group DG) and tadalafil group (Group T) (n = 6); diabetic rats were induced by streptozotocin. Apomorphine was used to induce diabetic erectile dysfunction. The ‘leech-centipede’ granules (0.15 and 0.6 g/kg) were intragastrically administered in the DD and DG groups for 8 weeks. Blood glucose, serum insulin, testosterone, cGMP levels and protein expression changes were measured in each group. Results After 8 weeks, the erectile function of rats in the DG group significantly improved (1.26 ± 0.73). Penis tissue cGMP levels were higher in the DG group (1.48 ± 0.11) than in the M group (0.58 ± 0.15). Protein and mRNA expression levels of NOS were significantly higher (0.77 ± 0.05; 0.61 ± 0.02) but those of PDE5 (0.43 ± 0.05; 0.61 ± 0.03) were lower in the DG group than in the M group (0.37 ± 0.06; 0.51 ± 0.01; 0.78 ± 0.06; 0.81 ± 0.04). Conclusion The leech-centipede can improve erectile dysfunction in DIED rats by regulating the expression of cGMP, NOS, and PDE5-related molecules in the PDE5 pathway. This study provides a potential mechanism for the treatment of DIED with leech-centipede.

Achyranthis Bidentatae Radix plus Semen Vaccariae are traditional Chinese medicines, which have been widely applied in the treatment of migraine and Erectile Dysfunction (ED) for many years. This study verified the effect of Achyranthis Bidentatae Radix plus Semen Vaccariae in improving migraine-induced ED and explored its potential mechanism.Key targets and signaling pathways of Achyranthis Bidentatae Radix plus Semen Vaccariae in migraine-induced erectile dysfunction treatment were predicted by network pharmacology. A rat model of migraine was established by nitroglycerin injection. Apomorphine was injected into rats to screen the migraine-induced erectile dysfunction model, Achyranthis Bidentatae Radix-Semen Vaccariae granule suspension administered, and erectile function evaluated. Hematoxylin and eosin staining was used to compare the histological structure of the penile tissue, while RT-qPCR and Western blotting were used to determine mRNA and protein levels, respectively.Screening allowed us to identify common targets for migraine and ED; the signaling pathway exhibiting the greatest change was the Myosin light chain kinase- Calcium (MLCK-CaM) signal pathway. From Western blotting and RT-qPCR, we found that the levels of MLCK mRNA and protein in rats from Group B rats were significantly higher (P0.05) than those in Groups A and C. Furthermore, the mRNA and protein levels of CaM were significantly higher in Group B (P0.05) than in Groups A and C.Data indicate that the regulatory effects of Achyranthis Bidentatae Radix plus Semen Vaccariae on migraine-induced ED in a rat model are mediated by the MLCK-CaM signaling pathway.

BACKGROUND Studies have shown that diabetes mellitus (DM) has a negative impact on male reproductive function, which may lead to changes in the testis and epididymis and a decline in semen quality. MATERIAL AND METHODS We performed animal experiments with 6 diabetic db/db mice as the model group (group B) and 6 C57BL/6J mice as the control group (group A). After adaptive feeding for 7 days, the sperm quality of each group was measured. Concurrently, the morphology of the mouse testis was observed by hematoxylin-eosin (H&E) staining. The expression of the PI3K, Akt, FoxO1, FasL, IL-6, and Stat3 proteins and mRNAs in the testicular tissue was detected by western blotting and RT-qPCR. RESULTS The number of spermatozoa and sperm motility of group A was significantly higher than that of group B (P

A strategy that integrates the anammox and hydroxyapatite crystallization in an up-flow anaerobic fixed-bed reactor (UAFB) was investigated to simultaneously remove nitrogen and recover phosphorus. During the 430 days of operation, 73.1 ± 6.6% of influent phosphorus was removed with an efficient nitrogen removal efficiency of 87.8 ± 1.7%. After long-term operation, numerous acicular and micron-sized crystals were observed on the matured biofilm, of which the phosphorus content was around 10.21% (wt%) and hydroxyapatite was the main form of crystals through SEM-EDS, FT-IR and XRD analysis. The variation of substrates along the axial length of UAFB showed that phosphate removal was positively correlated with anammox and pH. Moreover, three anammox bacteria including Candidatus Brocadia (19.73%), Candidatus Jettenia (0.49%) and Candidatus Kuenenia (0.85%) were detected at the bottom of UAFB, while Candidatus Jettenia (4.67%) was dominant at the top. Hence, the anammox-based biofilm system could be alternative for the recovery of phosphorus from nutrient-rich wastewater.

Many technical problems are being encountered in roadway tunneling processes, especially at fault bundles and fault-dense zones and in vicinity of the Ordovician carbonate confined aquifers. These complicated tectonic conditions increase the difficulty of water inrush prediction and prevention. This paper takes the roadways tunneling at Jiangzhuang Coal Mine of Shandong Province, China, as a case study. The presence of fault bundles and fault-dense zones reduces the distance between roadway tunneling and the Ordovician carbonate confined aquifer and thus increases the potential risk of water inrush. Based on characteristics of the structure and water bearing formation and hydraulic conductivity in the fault zones, a trinity technique consisting of exploration, grouting, and supporting was proposed to ensure roadway safety tunneling. Underground mine seismic prediction (MSP), underground transient electromagnetic (TEM), underground drilling, numerical simulation evaluations and roadway grouting and supporting were used to understand, reduce, and mitigate the risk of poor stability and water inrush in the roadway tunneling process. Site construction has verified that the fault position was basically consistent with the results from MSP and TEM and drilling. Conclusions from risk evaluation and numerical simulation contributed to the grouting reinforcement and road supporting. Grouting reinforcement of the fracture zone reduced hydraulic conductivity, whereas the reasonable supporting was implemented for the weak part of the surrounding rock, which effectively controlled the roadway deformations. The comprehensive application of the trinity technique provided accurate and defensible geological data for roadway tunneling in this mining area, created favorable conditions for safe and efficient construction, and provided an important reference for research on similar type of roadway construction.

Cuscuta chinensis Lam. and Lycium barbarum L. (SC-FL) is a commonly used kidney tonic Chinese medicine combination that is widely used in the clinical treatment of oligoasthenospermia.However, its specific mechanism remains unclear and requires in-depth study.To explore the potential targets of SC-FL in the treatment of oligoasthenospermia using network pharmacology, and to verify the results with in vivo and in vitro experiments.A herb-compound-target-disease network and PPI network were constructed with Cytoscape software. The targets of SC-FL for the treatment of male sterility were introduced into a bioinformatics annotation database, and the GO and KEGG databases were used for pathway enrichment analysis. Subsequently, Tripterygium wilfordii Hook. f. (GTW) polyglycoside was used to induce a spermatogenic dysfunction model in GC-1 spg cells and SD male rats in in vitro and in vivo experiments, respectively. The SC-FL and PI3K pathway inhibitor LY294002 was used to intervene in the spermatogenic dysfunction model to detect the expression of proteins and mRNA related to the PI3K pathway and to detect the indicators related to proliferation and apoptosis.In in vitro experiments, the percentage of spermatogenic cells and the proportion of GC-1 spg cells at G0/G1 and G2/M stages in the model group (GTW group) and the inhibitor group (LY group) were significantly decreased (P 0.01) compared with the blank control group (NC group). The apoptosis rate of the GTW group was significantly increased (P 0.01). The ultrastructures of GC-1 spg cells in the GTW group and LY group were obviously destroyed. Compared with the GTW group, the SC-FL group had a significantly reduced apoptosis rate of GC-1 spg cells, reduced percentage of cells in S phase, and a significantly improved mitochondrial membrane potential. SC-FL can repair the ultrastructure of GC-1 spg cells damaged by GTW. The above effects of SC-FL are closely related to up-regulation of GFRa1, RET, PI3K, p-AKT, and Bcl-2 and down-regulation of BAD and BAX proteins and mRNA expression. In vivo, compared with the GTW group, the body mass, testicular mass, and epididymal weight of the GTW + SC-FL group were significantly increased (P 0.01). Sperm concentrations and the PR + NP of GTW + SC-FL were significantly higher than in the GTW group (P 0.01 or P 0.05). FSH, LH, and T levels in the GTW + SC-FL and LY + SC-FL groups were significantly higher than those in the GTW and LY group (P 0.01 or P 0.05). HE staining results showed that the morphology of testicular tissue in the GTW + SC-FL and LY + SC-FL groups was superior to that in the GTW and LY group. The above effects of SC-FL are closely related to the up-regulation of proteins and mRNA expression of PI3K, p-AKT, and Bcl-2.Through the PI3K/Akt signaling pathway, SC-FL up-regulates GFRa1, RET, PI3K, p-AKT, and Bcl-2, and down-regulates the expression of BAD and BAX proteins and mRNA, thus reducing the percentage of GC-1 spg cells in S-phase, significantly increasing the mitochondrial membrane potential, significantly reducing cell apoptosis, and improving sperm counts and viability.

Aerobic granular sludge process as a promising biotechnology has been one of the research hotspots in the area of wastewater treatment during the last two decades. In our study, after around 60 days' operation, filamentous granular sludge (FGS) was formed under low aeration (SAV = 0.085 cm/s) and multi-feeding conditions. The characteristics of FGS and the performance of the FGS system for organic matter and nutrients removal were investigated. The results showed that COD and TOC removal efficiencies were relatively stable, while COD removal efficiency increased from 82% to 94% in the presence of sulfamethoxazole (SMZ) at low concentration (1 mg/L). At the same time, the TP removal efficiency could be improved and maintained at around 75%, while TN removal efficiency was flocculated at around 50%. The analysis of microbial diversity showed that Thiothrix and Trichococcus as typical filamentous species were detected and dominant in the FGS system. The abundance of Thiothrix increased from 15% to 34%, while Trichococcus decreased from 23% to 3% in the presence of SMZ.