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Lactic acid (LA) metabolism in the tumor microenvironment contributes to the establishment and maintenance of immune tolerance. This pathway is characterized in tumor associated macrophages. However, the role and pathway of LA metabolism at maternal-fetal interface during early pregnancy, especially in decidual macrophage differentiation, are still unclear. Herein, for the first time, we discovered that LA can trigger either M2 or M1 macrophage polarization via oxidative phosphorylation and glycolysis regulation under normoxia or hypoxia, respectively. Also, LA metabolism played a vital role in decidual macrophages-mediated recurrent pregnancy loss (RPL), through HIF-1α/SRC/LDHA pathway. Moreover, blockade of LA intake with AZD3965 (MCT-1 inhibitor) could rescue pregnancy in an abortion-prone mouse model, suggesting a potential therapeutic target in RPL. Collectively, the present study identifies the previously unknown functions of LA metabolism in the differentiation of decidual macrophages in early normal pregnancy and RPL, and provides a potential therapeutic strategy in RPL by manipulating decidual macrophages' functions through LA metabolic pathway.

INTRODUCTION Urokinase plasminogen activator (uPA) is a serine protease and it also demonstrates proinflammatory properties. We thus hypothesized that uPA is involved in immunity of Sertoli cells in the rat testis. MATERIALS AND METHODS The uPA gene(PLAU) promoter was cloned by RT-PCR and the transcriptional activation of core domain was screened by using Dual-Luciferase Reporter Assay System. The Sertoli cells were harvested from 20-day-old Sprague-Dawley male rats and total RNA was isolated. The uPA mRNA levels and MyD88 pathway were tested by qPCR. RESULTS We successfully cloned the 1517-bp rat uPA gene and screened the core domain (-455/+40) in five different fragments of uPA promoter. The uPA expression and uPA promoter activity were upregulated in lipopolysaccharide (LPS)-stimulated Sertoli cells. Furthermore, the uPA expression was regulated through the MyD88-independent pathway by interdicting IRF3 and interferon β. CONCLUSION uPA expression is likely induced by LPS through the core promoter domain of uPA. This finding implied that uPA played a role in the immune function of Sertoli cells in rat testis, which might provide the development of new treatments for male infertility.

A new flavonoid named saniculamin C (1), together with six known compounds (2-7), were isolated from the whole plants of Sanicula lamelligera Hance. The chemical structures were elucidated by spectroscopic and physico-chemical analyses. All isolates were evaluated for in vitro cytotoxic activities against four human cancer cell lines, HepG2, SGC-7901 gastric cancer, Hela and A-549 lung cancer. Compound 1 showed potent antiproliferative activities against SGC-7901 cells with IC50 value of 7.45 μM. In addition, compound 6 exhibited weak antiproliferative activities against HepG2, SGC-7901, Hela cancer cells with IC50 values of 10.43, 8.24 and 15.32 μM, respectively.

Caused by a novel type of virus, severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2), coronavirus disease 2019 (COVID‐19) constitutes a global public health emergency. Pregnant women are considered to have a higher risk of severe morbidity and even mortality due to their susceptibility to respiratory pathogens and their particular immunologic state. Several studies assessing SARS‐CoV‐2 infection during pregnancy reported adverse pregnancy outcomes in patients with severe conditions, including spontaneous abortion, preterm labor, fetal distress, cesarean section, preterm birth, neonatal asphyxia, neonatal pneumonia, stillbirth, and neonatal death. However, whether these complications are causally related to SARS‐CoV‐2 infection is not clear. Here, we reviewed the scientific evidence supporting the contributing role of Treg/Th17 cell imbalance in the uncontrolled systemic inflammation characterizing severe cases of COVID‐19. Based on the recognized harmful effects of these CD4+ T‐cell subset imbalances in pregnancy, we speculated that SARS‐CoV‐2 infection might lead to adverse pregnancy outcomes through the deregulation of otherwise tightly regulated Treg/Th17 ratios, and to subsequent uncontrolled systemic inflammation. Moreover, we discuss the possibility of vertical transmission of COVID‐19 from infected mothers to their infants, which could also explain adverse perinatal outcomes. Rigorous monitoring of pregnancies and appropriate measures should be taken to prevent and treat early eventual maternal and perinatal complications.

The accurate fruit recognition in the field was one of the key technologies of fruit picking agricultural robots. An improved Single Shot Multi-Box Detector (SSD) model based on the color and morphological characteristics of fruit was proposed in this paper when aimed at the large collection workload and low secondary transfer efficiency of fruit such as palm fruit, durian, pineapple and other fruits grown in a complex field environment. A binocular depth camera RealSense D435i was used to collect images of the fruit to be picked in the field. Meanwhile, the MobileNet was replaced with the VGG16 basic network based on the Tensor-flow deep learning framework to reduce the amount of convolution operations for extracting image features in the SSD model, and a spatial positioning system for pineapple fruit was designed. Furtherly, experiments showed that the improved SSD depth detection model had a smaller size and it was more convenient to be deployed on the mobile end of agricultural robots, which the model had a high accuracy in the effective recognition of the fruits to be picked under the weed occlusion and overlapping scenes. The frame rate of the video reading and detection for the binocular depth camera reached 16.74 Frames Per Second (FPS), which had good robustness and real-time, and a good solution for the automatic picking of agricultural picking robots could be provided in the field.

Background In 2005, the FDA cautioned that exposure to paroxetine, a selective serotonin reuptake inhibitor (SSRI), during the first trimester of pregnancy may increase the risk of cardiac malformations. Since then, the association between maternal use of SSRIs during pregnancy and congenital malformations in infants has been the subject of much discussion and controversy. The aim of this study is to systematically review the associations between SSRIs use during early pregnancy and the risk of congenital malformations, with particular attention to the potential confounding by indication. Methods The study protocol was registered with PROSPERO (CRD42018088358). Cohort studies on congenital malformations in infants born to mothers with first-trimester exposure to SSRIs were identified via PubMed, Embase, Web of Science, and the Cochrane Library databases through 17 January 2018. Random-effects models were used to calculate summary relative risks (RRs). Results Twenty-nine cohort studies including 9,085,954 births were identified. Overall, use of SSRIs was associated with an increased risk of overall major congenital anomalies (MCAs, RR 1.11, 95% CI 1.03 to 1.19) and congenital heart defects (CHD, RR 1.24, 95% CI 1.11 to 1.37). No significantly increased risk was observed when restricted to women with a psychiatric diagnosis (MCAs, RR 1.04, 95% CI 0.95 to 1.13; CHD, RR 1.06, 95% CI 0.90 to 1.26). Similar significant associations were observed using maternal citalopram exposure (MCAs, RR 1.20, 95% CI 1.09 to 1.31; CHD, RR 1.24, 95% CI 1.02 to 1.51), fluoxetine (MCAs, RR 1.17, 95% CI 1.07 to 1.28; CHD, 1.30, 95% CI 1.12 to 1.53), and paroxetine (MCAs, RR 1.18, 95% CI 1.05 to 1.32; CHD, RR 1.17, 95% CI 0.97 to 1.41) and analyses restricted to using women with a psychiatric diagnosis were not statistically significant. Sertraline was associated with septal defects (RR 2.69, 95% CI 1.76 to 4.10), atrial septal defects (RR 2.07, 95% CI 1.26 to 3.39), and respiratory system defects (RR 2.65, 95% CI 1.32 to 5.32). Conclusions The evidence suggests a generally small risk of congenital malformations and argues against a substantial teratogenic effect of SSRIs. Caution is advisable in making decisions about whether to continue or stop treatment with SSRIs during pregnancy. Electronic supplementary material The online version of this article (10.1186/s12916-018-1193-5) contains supplementary material, which is available to authorized users.

Background. Copeptin has been implicated as an effective prognostic biomarker of stroke outcome; however, few studies have investigated whether copeptin could be used as an etiological factor for stroke or not. The aim of our study was to evaluate the association of serum copeptin with stroke. Methods. In total, 238 participants including 119 cases (87 ischemic stroke and 32 hemorrhagic stroke) and 119 controls were included in this 1 : 1 matched case-control study. Conditional multivariate logistic regression was conducted to assess the Odds Ratios (ORs) and 95% confidence intervals (CI); restricted cubic spline in logistic regression model was used to evaluate the dose-response association between serum copeptin and total stroke, ischemic stroke, and hemorrhagic stroke. Results. The median serum copeptin was 20.90 pmol/L, 20.90 pmol/L, 6.53 pmol/L, and 8.42 pmol/L for total stroke, ischemic stroke, hemorrhagic stroke, and healthy subjects, respectively. The corresponding ORs (95% CIs) for the highest compared with the lowest quartile were 1.23 (0.62–2.44) for total stroke, 4.01 (1.47–10.96) for ischemic stroke, and 0.13 (0.22–0.69) for hemorrhagic stroke. No nonlinear dose-response relationship was found between serum copeptin and total stroke (Pnonlinear=0.278), ischemic stroke (Pnonlinear=0.362), and hemorrhagic stroke (Pnonlinear=0.314). Compared with the reference copeptin level, a significantly increasing trend was found between serum copeptin and ischemic stroke (Poverall=0.002), and a decreasing trend was found between serum copeptin and hemorrhagic stroke (Poverall=0.007). Conclusions. Elevated serum copeptin levels were positively associated with ischemic stroke and adversely associated with hemorrhagic stroke. Additional prospective studies with larger sample size are needed to confirm the present findings.

In the wake of big data and Internet plus era, continuous infiltration of digital technology has been happening in various fields of social and economic development. As the most important material carrier of historical culture, the historical value of historical buildings is produced and accumulated in its historical evolution, and it can only be protected from being created again. Based on the background of digitization of cultural resources, this paper summarizes the relevant digital technologies for the digital translation of information on buildings of historical and cultural heritage, as a means to promote the spread of the PDA+APPS mobile terminal, so as to achieve the purpose of preservation, protection, management and publicity. Meanwhile, this paper analyzes the application of digital technology in this field and the prospect of its function.

Myocardial ischemia/reperfusion (I/R) can induce lethal ventricular arrhythmia and myocardial infarction. One of the clinical strategies for managing patients with high risk of myocardial I/R is to prevent the occurrence of arrhythmias and limit the size of infarction following a coronary episode. Tongguan Capsule (TGC) is one of the popular herbal remedies in treating coronary artery disease in the clinics of Chinese medicine. However, the potential roles and mechanisms of TGC in reducing I/R injury are still unclear. The present study statistically assessed the effectiveness of TGC in reducing I/R injury by comparing the infarct size (IS), risk region (RR), and arrhythmia (in electrocardiogram) among four groups of surgically created mice models of myocardial I/R: SHAM, I/R, VER (I/R with verapamil 20 mg/kg pretreatment), and TGC (I/R with TGC 5 g/kg/d pretreatment). We found that IS was significantly smaller in the TGC and VER groups than I/R group, and the incidence of arrhythmias was reduced in the TGC group compared with I/R group, although there were no differences in RR among the four groups. We conclude that TGC is effective in reducing I/R injury in mice. These results provided an experimental basis for clinical application of TGC in reducing I/R injury.

Circular RNAs (circRNAs) have emerged as novel molecules of interest in gene regulation as other noncoding RNAs. Though they have been explored in some species and tissues, the expression and functions of circRNAs in human reproductive systems remain unknown. Here we revealed the expression profiles of circRNAs in human testis tissue using high-throughput sequencing. The conformation of these testis-derived circRNAs in seminal plasma was also investigated, aiming to provide a non-invasive liquid biopsy surrogate for testicular biopsy. We predicted >15,000 circRNAs in human testis, with most of them (10,792; 67%) new. In all the 5,928 circRNA forming genes, 1,017 are first reported by us to generate circRNAs. Interestingly, these genes are mostly related to spermatogenesis, sperm motility, fertilization, etc. The sequence feature, chromosome location, alternative splicing and other characteristics of the circRNAs in human testis were also explored. Moreover, we found that these testis-derived circRNAs could be stably detected in seminal plasma. Most of them were probably bound with proteins in seminal plasma and were very stable at room temperature. Our work has laid the foundations to decipher regulation mechanisms of circRNAs in spermatogenesis and to develop circRNAs as novel noninvasive biomarkers for male infertile diseases.

The in vitro effects of Candida albicans and its filtrates on the motility and ultrastructure of human spermatozoa from healthy donors were studied. A significant reduction in sperm progressive motility and signs of membrane alteration, directly related to contact time were observed. Distinct adhesion of spermatozoa to C. albicans and agglutination were observed. Light and transmission electron microscopy examinations showed that spermatozoa attached to C. albicans mainly via the head. Multiple ultrastructural lesions were present, which were the possible morphological reasons for spermatozoan immobilization observed in the present study. It is concluded that C. albicans as well as its filtrates had an inhibitory effect on human sperm motility and impaired the ultrastructure of human spermatozoa, which could be associated with male infertility.

C-type natriuretic peptide (CNP) is a newly discovered type of local regulatory factor that mediates its biological effects through the specific, membrane-bound natriuretic peptide receptor-B (NPR-B). Recent studies have established that CNP is closely related to male reproductive function. The aims of this study were to determine the distribution of CNP/NPR-B in human ejaculated spermatozoa through different methods (such as immunolocalization, real time polymerase chain reaction and Western Blot), and then to evaluate the influence of CNP on sperm function in vitro, such as motility and acrosome reaction. Human semen samples were collected from consenting donors who met the criteria of the World Health Organization for normozoospermia. Our results show that the specific receptor NPR-B of CNP is localized in the acrosomal region of the head and the membrane of the front-end tail of the sperm, and there is no signal of CNP in human sperm. Compared with the control, CNP can induce a significant dose-dependent increase in spermatozoa motility and acrosome reaction. In summary, CNP/NPR-B can affect sperm motility and acrosome reaction, thus regulating the reproductive function of males. CNP may be a new key factor in regulating sperm function.

Background The radial forearm free flap (RFFF) has been widely used with increasing frequency in head and neck reconstruction following extirpative surgery. The controversy of the venous anastomoses patterns still exists. Thus, we conducted a meta-analysis to assess the relationship between the venous anastomoses patterns and venous compromise. Methods MEDLINE, PubMed, Web of Science, and Wanfang databases were searched for studies reporting the different venous anastomoses patterns of the RFFF. A meta-analysis was conducted using the random effects models. Publication bias and sensitivity analysis were also assessed. Results 6 studies with 992 cases were included in this meta-analysis. The dual anastomosis group tended to have a lower incidence of venous compromise (RR = 1.39). However, the difference was not statistically significant (95%CI: 0.59, 3.24). Conclusions This meta-analysis indicated that performing dual venous anatomoses consisting of superficial and deep systems conferred a tendency of the reduction with regard to venous compromise.

The air flow field of the dual slot die on an HDF-6D melt blowing non-woven equipment is computed numerically. A temperature measurement system is built to measure air temperatures. The computation results tally with the measured results proving the correctness of the computation. The results have great valuable significance in the actual melt blowing production.

C-type natriuretic peptide (CNP) is a 22-amino acid peptide and act as a local paracrine or autocrine regulator. There is growing evidence that CNP is involved in male reproductive processes. To investigate the role of CNP during spermatogenesis, we measured the mRNA expression of CNP and its specific membrane-bound natriuretic peptide receptor-B (NPR-B) using real-time RT-PCR in the testes of normal rats on different postnatal days. After that spermatogenesis dysfunction model induced by ornidazole was established with the aim to study the correlation of CNP with spermatogenic dysfunction. Then, Sertoli cells from 18- to 22-day-old healthy male rats were cultured in the presence of different CNP concentrations (1×10(-6), 1×10(-7) and 1×10(-8) mol l(-1)), and the mRNA expression levels of androgen-binding protein, inhibin B and transferrin were examined at 0 min, 30 min, 1 h, 2 h, 4 h, 8 h, 12 h, 24 h and 48 h. During the postnatal development of rat testes, the highest mRNA expression levels of CNP and NPR-B were found at postnatal D(0), and the levels then declined gradually, with a second CNP peak at postnatal D(35). In the ornidazole-induced infertile rat testes, CNP gene expression was lower than in the uninduced rats (P

Aim: To investigate the gene expression changes of urokinase plasminogen activator (uPA)/urokinase receptor (uPAR) in rat testes at postnatal stages and explore the effects of uPA/uPAR system on the rat spermatogenesis. Methods: The mRNAs of uPA and uPAR in rat testes were measured by using real-time quantitative polymerase chain reaction (PCR) at postnatal days 0, 5, 10, 15, 21, 28, 35, 42, 49 and 56, respectively. Results: The tendencies of uPA and uPAR mRNA expression were similar at most postnatal stages except for D0. The expression of uPAR mRNA in rats testes was relatively higher than that of uPA at postnatal D0, and both were decreased until D21, increased obviously at postnatal D28, reached a peak at postnatal D35, then declined sharply at postnatal D42 and retained at a low level afterwards. Conclusion: The uPA/uPAR system may be strongly linked to spermiation and spermatogenesis via regulating germ cell migration and proliferation, as well as promoting the spermiation and detached residual bodies from the mature spermatids. (Asian J Androl 2007 Sep; 9: 679–683)