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Objectives Cigarette smoking is an established risk factor for illness severity and adverse outcomes in patients with COVID-19. Alcohol drinking may also be a potential risk factor for disease severity. However, the combined and interactive effects of drinking and smoking on COVID-19 have not yet been reported. This study aimed to examine the combined and interactive effects of alcohol drinking and cigarette smoking on the risk of severe illness and poor outcomes in patients with COVID-19. Study design Multicentre retrospective cohort study. Methods This study retrospectively reviewed the data of 1399 consecutive hospitalised COVID-19 patients from 43 designated hospitals. Patients were grouped according to different combinations of drinking and smoking status. Multivariate mixed-effects logistic regression models were used to estimate the combined and interactive effects of drinking and smoking on the risk of severe COVID-19 and poor clinical outcomes. Results In the study population, 7.3% were drinkers/smokers, 4.3% were drinkers/non-smokers and 4.9% were non-drinkers/smokers. After controlling for potential confounders, smokers or drinkers alone did not show a significant increase in the risk of severe COVID-19 or poor clinical outcomes compared with non-drinkers/non-smokers. Moreover, this study did not observe any interactive effects of drinking and smoking on COVID-19. Drinkers/smokers had a 62% increased risk (odds ratio = 1.62, 95% confidence interval: 1.01, 2.60) of severe COVID-19, but did not have a significant increase in the risk for poor clinical outcomes compared with non-drinkers/non-smokers. Conclusions Combined exposure to drinking and smoking increases the risk of severe COVID-19, but no direct effects of drinking or smoking, or interaction effects of drinking and smoking, were detected.

Recent theoretical predictions have indicated that BiTeX (X = Cl, Br, I) type strong spin orbital coupling semiconductor compounds with strong Rashba effects are suitable for use as topological insulators under compressed conditions and novel phenomena have been identified in experiments. The compound BiTeCl is expected to exhibit a topological nontrivial state under pressure. In this study, we obtained measurements based on the resistivity, Hall coefficient, synchrotron X-ray diffraction, and Raman spectroscopy using the Rashba semiconductor BiTeCl crystal at high pressures up to 54.8 GPa. Our experiments indicated that the Rashba semiconductor BiTeCl exhibited a pressure-induced metal to insulator-like transition at 2.8 GPa. A pressure-induced structural phase transition was observed above 5.5 GPa, which was followed by a superconducting transition. The superconducting transition temperature ( T C ) increased to a maximum 4.2 K with pressures up to 32 GPa. Compared with BiTeI, the structural phase transition of BiTeCl occurs at a relatively lower pressure due to the weaker Rashba effects, where the inner chemical pressure is affected by the replacement of I with Cl.

Hefei Light Source II (HLS-II) is a vacuum ultraviolet synchrotron light source. The control system of HLS-II is a distributed system based on the experimental physics and industrial control system (EPICS). The alarm system of HLS-II is responsible for monitoring the alarm state of the facility and distributing the alarm message in time. It facilitates the operator to troubleshoot problem efficiently, so as to improve the availability of HLS-II. Phoebus/Alarms (Alarms) is the latest alarm software released in EPICS community. Based on Alarms, the alarm system of HLS-II is designed, developed and deployed. The alarm distribution strategy is designed from the perspective of the HLS-II operation mode, alarm severity and alarm representative to overcome alarm floods. The 3 ways to distribute the alarm message are added to the HLS-II alarm system, which include WeChat, SMS and web-based GUI. In order to configure alarm options efficiently and conveniently, an alarm configuration management tool is developed based on the MySQL database and Browser/Server architecture. The alarm system of HLS-II has been deployed since November 2021. The result indicates that the alarm system is effective and convenient to operate.

We study human perception of gaze rendered by popular semi-virtual robotic heads, which use a screen to render a robot’s face. It is known that when these heads are stationary, the screen may induce the Mona Lisa gaze effect, which widens the robot’s apparent cone of direct gaze. But how do people perceive gaze when the head can move as well? To study this question, we conducted a laboratory experiment that investigated human perception of robot gaze when a semi-virtual platform looked in different directions. We varied the way in which the robot conveyed gaze, using several behaviors involving 2D eye and head motion. Our results suggest that the interplay between these motions can regulate how wide users perceive the robot’s cone of direct gaze. Also, our findings suggest that the location of observers can affect the perception of gaze by semi-virtual robotic heads. We discuss the implications of our findings for social interaction.

An 11-channel Far-InfaRed (FIR) three-wave POlarimeter-INTerferometer (POINT) system has been successfully operated in 2015 EAST experimental campaign. For high accuracy measurement of POINT system, optimized optical system to reduce the stray light and crosstalk is very important. Optical design is done and improved by using ZEMAX software, in which spot size and energy distribution can be calculated in any position. The crosstalk and stray light can be reduced by optimized design of optical components and putting high extinction ratio materials in some key positions. Vibration isolation coefficient of optical platform is set to 90%. The optical platform and vibration isolation system are about 5 and 20 tons in weight respectively. To reduce vibration caused by the EAST hall, a more than 30 tons in weight stainless steel tower, filled with sand and mounted independent of the EAST machine, is constructed to ensure the stability of optics. Based on the optimized opto-mechanical design, the POINT system resolutions for Faraday rotation and line integral electron density measurements are 0.1° and 1 × 10 16 m −2 , respectively.

Drebrin is a family of actin-binding proteins with two known members called drebrin A and E. Apart from the ability to stabilize F-actin microfilaments via their actin-binding domains near the N-terminus, drebrin also regulates multiple cellular functions due to its unique ability to recruit multiple binding partners to a specific cellular domain, such as the seminiferous epithelium during the epithelial cycle of spermatogenesis. Recent studies have illustrated the role of drebrin E in the testis during spermatogenesis in particular via its ability to recruit branched actin polymerization protein known as actin-related protein 3 (Arp3), illustrating its involvement in modifying the organization of actin microfilaments at the ectoplasmic specialization (ES) which includes the testis-specific anchoring junction at the Sertoli-spermatid (apical ES) interface and at the Sertoli cell-cell (basal ES) interface. These data are carefully evaluated in light of other recent findings herein regarding the role of drebrin in actin filament organization at the ES. We also provide the hypothetical model regarding its involvement in germ cell transport during the epithelial cycle in the seminiferous epithelium to support spermatogenesis.

A modified antenna based on fractal split ring resonators (FSRRs) is presented. The antenna is composed of two layers of Teflon with a low permittivity (e=2.2). The inner and outer ring of FSRRS are connected with ground plane by two metal pins by which way the antenna is similarly to planar inverted-F antennas (PIFAs). The modified antenna with fractal split ring resonators (FSRRs) make the size of antenna to 0.06λ× 0.06λ for the low frequency and 0.11λ×0.11λ for the high frequency while the gain of antenna is higher about 2dB than antenna with SRRS. Simulated and measured results of return losses and gains of this modified antenna are provided.

The Toll and IMD pathways are known to be induced upon Plasmodium berghei and Plasmodium falciparum infection, respectively. It is unclear how Plasmodium or other pathogens in the blood meal and their invasion of the midgut epithelium would trigger the innate immune responses in immune cells, in particular hemocytes. Gap junctions, which can mediate both cell-to-cell and cell-to-extracellular communication, may participate in this signal transduction. This study examined whether innexins, gap junction proteins in insects, are involved in anti-Plasmodium responses in Anopheles gambiae. Inhibitor studies using carbenoxolone indicated that blocking innexons resulted in an increase in Plasmodium oocyst number and infection prevalence. This was accompanied by a decline in TEP1 levels in carbenoxolone-treated mosquitoes. Innexin AGAP001476 mRNA levels in midguts were induced during Plasmodium infection and a knockdown of AGAP001476, but not AGAP006241, caused an induction in oocyst number. Silencing AGAP001476 caused a concurrent increase in vitellogenin levels, a TEP1 inhibitor, in addition to a reduced level of TEP1-LRIM1-APL1C complex in hemolymph. Both vitellogenin and TEP1 are regulated by Cactus under the Toll pathway. Simultaneous knockdown of cactus and AGAP001476 failed to reverse the near refractoriness induced by the knockdown of cactus, suggesting that the AGAP001476-mediated anti-Plasmodium response is Cactus-dependent. These data demonstrate a critical role for innexin AGAP001476 in mediating innate immune responses against Plasmodium through Toll pathway in mosquitoes.

Spermatogenesis, the process of spermatozoa production, is regulated by several endocrine factors, including testosterone, follicle stimulating hormone, luteinizing hormone and estradiol 17β. For spermatogenesis to reach completion, developing germ cells must traverse the seminiferous epithelium while remaining transiently attached to Sertoli cells. If germ cell adhesion were to be compromised for a period of time longer than usual, germ cells would slough from the seminiferous epithelium and infertility would result. Presently, Sertoli-germ cell adhesion is known to be mediated largely by classical and desmosomal cadherins. More recent studies, however, have begun to expand long-standing concepts and to examine the roles of other proteins such as intercellular adhesion molecules. In this review, we focus on the biology of intercellular adhesion molecules in the mammalian testis, hoping that this information is useful in the design of future studies.

According to the example of using a common grinding and composition of parts processing movement and achievement elements, the design of construction of special NC technologies in ordinary grinding machine was formulated. . The grinding and polish-grinding were performed by using two NC systems in series to achieve multi-axis movement. The function and application scope of NC technology were expanded because the instantaneous compensation of the grinding wheel and the polish-grinding wheel were performed under a rectangular coordinate system and a polar coordinate system by using an open loop NC system. The application of surface recovery of grinding wheel by NC reconstruction and extension applications of processing the track of involute curve were referred.

There is great practical significance in error compensation of CNC machine tools. In this dissertation, the measurement theory and application methods of some advanced measure were analyzed. From those measurement methods, we found the drawback of comprehensive error measurement. Further more, this paper has detailed a new defined as single-measurement for the sake of the double-frequency laser interferometer to measure 14 geometric errors of three-axis system. The method facilitates measurements and shortens the machine shutdown time.

The actin-based cytoskeleton plays a critical role in the seminiferous epithelium during spermatogenesis by conferring cell shape, adhesion, structural support and cell polarity to both Sertoli and developing germ cells, which are essential for spermatogonial stem cell renewal, maintenance of the stem cell niche, cell cycle progression, mitosis, meiosis, spermiogenesis and spermiation. However, few functional studies are found in the literature, which explore the functional significance of actin dynamics in these events. This by and large is due to a lack of information on the proteins that regulate actin dynamics. Herein, we report drebrin E is an integrated component of the apical ectoplasmic specialization (apical ES) and the basal ES at the blood-testis barrier (BTB) in the seminiferous epithelium of the adult rat testis. Using immunohistochemistry and dual-labeled immunofluorescence analysis, drebrin E was found to display a stage-specific localization at the apical ES, as well as at the basal ES at the BTB during the seminiferous epithelial cycle of spermatogenesis. Drebrin E was first detected in stage V tubules at the basal ES with the highest expression at the BTB at stages V and VI, but it diminished considerably by stages VII and VIII and was almost non-detectable until stage IV. At the apical ES, drebrin E was also first detected at stage V, surrounding the entire head of the elongating spermatid, but by stage VI its localization had 'shifted' to localize most intensely and almost exclusively to the concave side of the spermatid head. In stage VII tubules, drebrin E co-localized with actin, as well as with two other actin regulatory proteins Eps8 (epidermal growth factor receptor pathway substrate 8, an actin capping and bundling protein) and Arp3 (actin-related protein 3, a component of the Arp2/3 complex known to regulate actin nucleation and branching). The localization of drebrin E at the apical ES was compromised following treatment of rats with adjudin, which is known to exert its destructive effects primarily at the apical ES by inducing premature loss of elongating/elongated spermatids from the epithelium, mimicking 'spermiation.' Instead of being restricted to the concave side of spermatid heads, drebrin E was found to be mis-localized in the seminiferous epithelium of adjudin-treated rats; it was also present on the convex side of elongating spermatids, but these cells were mis-oriented so that their heads no longer pointed toward the basement membrane. The expression of drebrin E by Sertoli cells was also found to be modulated by TGFbeta3 and TNFalpha. Since Arp3, but not Eps8, was found to bind drebrin E; and cytokines were also shown to affect the cellular distribution of drebrin E and enhance the interaction between drebrin E and Arp3, these findings illustrate that cytokines may regulate BTB dynamics during the epithelial cycle by recruiting drebrin E and Arp3 to the BTB microenvironment to induce changes in the configuration of actin filament bundles at the basal ES. In summary, these findings illustrate drebrin E is working in concert with Arp3 to regulate actin filament bundles at both the apical and the basal ES in the testis, conferring adhesion and cell polarity at both sites during spermatogenesis., link_to_OA_fulltext

Bisphenol A, an estrogenic environmental toxicant, has been implicated to have hazardous effects on reproductive health in humans and rodents. However, there are conflicting reports in the literature regarding its effects on male reproductive function. In this study, it was shown that in adult rats treated with acute doses of bisphenol A, a small but statistically insignificant percentage of seminiferous tubules in the testes displayed signs of germ cell loss, consistent with some earlier reports. It also failed to disrupt the blood-testis barrier in vivo. This is possibly due to the low bioavailability of free bisphenol A in the systemic circulation. However, bisphenol A disrupted the blood-testis barrier when administered to immature 20-day-old rats, consistent with earlier reports concerning the higher susceptibility of immature rats towards bisphenol A. This observation was confirmed using primary Sertoli cells cultured in vitro with established tight junction-permeability barrier that mimicked the blood-testis barrier in vivo. The reversible disruption of Sertoli cell tight junction barrier by bisphenol A was associated with an activation of ERK, and a decline in the levels of selected proteins at the tight junction, basal ectoplasmic specialization, and gap junction at the blood-testis barrier. Studies by dual-labeled immunofluorescence analysis and biotinylation techniques also illustrated declining levels of occludin, connexin 43, and N-cadherin at the cell-cell interface following bisphenol A treatment. In summary, bisphenol A reversibly perturbs the integrity of the blood-testis barrier in Sertoli cells in vitro, which can also serve as a suitable model for studying the dynamics of the blood-testis barrier.

Recent studies have shown that male reproductive function is modulated via the mitogen-activated protein kinase (MAPK) cascade. The MAPK cascade is involved in numerous male reproductive processes, including spermatogenesis, sperm maturation and activation, capacitation and acrosome reaction, before fertilization of the oocyte. In this review, we discuss the latest findings in this rapidly developing field regarding the role of MAPK in male reproduction in animal models and in human spermatozoa in vitro. This research will facilitate the design of future studies in humans, although much work is needed before this information can be used to manage male infertility and environmental toxicant-induced testicular injury in men, such as blood-testis-barrier disruption.

A dielectric embedded monopole antenna is proposed for super wideband(SWB)applications. The antenna is designed become inverted cone in order to expand the bandwidth, and the SWB antenna possesses a method to minimize the size of antenna by dielectric embedded to lower the height. The antenna is simulated and measured after practically fabricated. Measured results show a good agreement with simulated results that a −10dB bandwidth of 43.5GHz (4.5–48GHz) is achieved with ratio bandwidth 10.7∶1.The antenna prototype shows good impedance matching, stable far-field radiation patterns, and constant group delay over the super wideband.

Earlier studies have shown that rats treated with an acute dose of 1-(2,4-dichlorobenzyl)-1H-indazole-3-carbohydrazide (adjudin, a male contraceptive under development) causes permanent infertility due to irreversible blood-testis barrier (BTB) disruption even though the population of undifferentiated spermatogonia remains similar to normal rat testes, because spermatogonia fail to differentiate into spermatocytes to enter meiosis. Since other studies have illustrated the significance of connexin 43 (Cx43)-based gap junction in maintaining the homeostasis of BTB in the rat testis and the phenotypes of Sertoli cell-conditional Cx43 knockout mice share many of the similarities of the adjudin-treated rats, we sought to examine if overexpression of Cx43 in these adjudin-treated rats would reseal the disrupted BTB and reinitiate spermatogenesis. A full-length Cx43 cloned into mammalian expression vector pCI-neo was used to transfect testes of adjudin-treated rats versus empty vector. It was found that overexpression of Cx43 indeed resealed the Sertoli cell tight junction–permeability barrier based on a functional in vivo assay in tubules displaying signs of meiosis as noted by the presence of round spermatids. Thus, these findings suggest that overexpression of Cx43 reinitiated spermatogenesis at least through the steps of meiosis to generate round spermatids in testes of rats treated with an acute dose of adjudin that led to aspermatogenesis. It was also noted that the round spermatids underwent eventual degeneration with the formation of multinucleated cells following Cx43 overexpression due to the failure of spermiogenesis because no elongating/elongated spermatids were detected in any of the tubules examined. The mechanism by which overexpression of Cx43 reboots meiosis and rescues BTB function was also examined. In summary, overexpression of Cx43 in the testis with aspermatogenesis reboots meiosis and reseals toxicant-induced BTB disruption, even though it fails to support round spermatids to enter spermiogenesis.—Li, N., Mruk, D. D., Mok, K.-W., Li, M. W. M., Wong, C. K. C., Lee, W. M., Han, D., Silvestrini, B., Cheng, C. Y. Connexin 43 reboots meiosis and reseals blood-testis barrier following toxicant-mediated aspermatogenesis and barrier disruption.

Hefei light source (HLS) is mainly composed of an 800 MeV electron storage ring and a 200 MeV Linac functioning as its injector. A new RF cavity has been developed successfully for the HLS storage ring in NSRL phase II project. In this paper, the design, fabrication and measurement of the cavity are described in detail. The results and some analyses are presented.

This paper deduces the relationship between the frequency response and loads for a structure within the frequency domain, and puts forward a new method for identifying the random loads spectrum. Firstly, the response power spectrum of structural control points is calculated based on the white noise loads spectrum. Then in order to get the corresponding random loads spectrum, the response power spectrum and the desired output response spectrum are compared. Finally, a specific cabin structure is analyzed by using the above method. The FEA (Finite Element Analysis) simulation results show that the method is valid in identifying the fundamental acceleration loads spectrum. Keywords-frequency response; random load spectrum; response power spectrum; FEA

This is a preliminary study in which both acute and chronic oral administration of bis(maltolato)oxovanadium (IV) (BMOV) was examined in the Zucker diabetic fatty (ZDF) rat, an animal model that develops overt hyperglycemia in the presence of hyperinsulinemia followed by beta-cell depletion. At 9-10 weeks of age, in the presence of hyperglycemia, hyperinsulinemia and hyperlipidemia, an acute oral gavage dose response was conducted to determine glucose-lowering properties of BMOV, time of response and effect of BMOV on plasma insulin levels. Doses of BMOV greater than 0.2 mmol/kg resulted in plasma glucose levels of less than 9 mmol/l. The highest dose administered (0.8 mmol/kg) significantly reduced plasma insulin (initial: 2.83+/-0.2, final: 1.23+/-0.09 nmol/l, P0.05) and plasma triglyceride (initial: 4.94+/-0.33, final: 1.55+/-0.07 mmol/l, P0.05) levels. At 15 weeks of age, in the presence of hyperglycemia, hyperlipidemia and normal insulin levels, BMOV was administered orally in the drinking water for a 10-week period to determine the effect of treatment on glucose, insulin and lipid levels. BMOV treatment significantly reduced plasma glucose levels (final BMOV-treated: 13.25+/-1.43, untreated: 28.71+/-0.6 mmol/l, P0.05) and effectively preserved pancreatic beta-cell function. These data suggest a role for BMOV as a therapeutic agent in non-insulin-dependent diabetes mellitus through improvement in glucose homeostasis and preservation of insulin reserves.

Two important events that occur during mammalian spermatogenesis are the release of elongated spermatids at late stage VIII of the seminiferous epithelial cycle and the restructuring of the blood-testis barrier (BTB) during stages VIII-XI. Still, it is not completely understood how these cellular events are accomplished within the seminiferous epithelium. In the present study, we investigate how sertolin, a protein that was initially identified, cloned, and partially characterized by our laboratory, functions in these critical events. Sertolin was found at the BTB, as well as at the apical ectoplasmic specialization and apical tubulobulbar complex, where it colocalized with epidermal growth factor receptor kinase substrate 8 and actin-related protein 3, two actin-regulatory proteins. Knockdown of sertolin by RNA interference showed Sertoli cell barrier function to be enhanced when assessed by transepithelial electrical resistance measurements and immunolocalization experiments. By contrast, the integrity of the BTB was disrupted when sertolin was overexpressed in vitro and in vivo. Sertolin overexpression also prompted germ cell loss from the seminiferous epithelium. Taken collectively, these results suggest that sertolin may be involved in coordinating spermatid release and BTB restructuring during spermatogenesis in the rat.

Streptozotocin (STZ)-diabetic rats treated with vanadium can remain euglycemic for up to 20 weeks following withdrawal from vanadium treatment. In this study, we examined the effects of short-term vanadium treatment in preventing or reversing the STZ-induced diabetic state. Male Wistar rats were untreated (D) or treated (DT) with vanadyl sulfate for 1 week before administering STZ. Treatment was subsequently maintained for 3 days (DT3) or 14 days (DT14) post-STZ, after which vanadium was withdrawn. At 4 to 5 weeks post-STZ and following long-term withdrawal from vanadium, DT14 rats demonstrated levels of food and fluid intake and glucose tolerance that were not significantly different from those of age-matched untreated nondiabetic rats, and had significantly reduced glycemic levels in the fed state compared with D and DT3 groups. The proportion of animals that were euglycemic (fed plasma glucose9.0 mmol/L) was significant in DT14 (five of 10) relative to D (one of 10) and DT3 (one of 10) (P = .01). All euglycemic animals had an improved pancreatic insulin content that, albeit low (12% of control), was strongly linked to euglycemia in the fed state (r = -.91, P.0001). Moreover, the highly significant correlation persisted with the analysis of untreated STZ-rats alone (r = -.95, P.0001). Similarly, improvements in glucose tolerance and insulin secretory function in euglycemic rats were strongly correlated with small changes in residual insulin content. Hence, as vanadium pretreatment did not prevent STZ-induced beta-cytotoxicity, the vanadium-induced amelioration of the diabetic state appears to be secondary to the preservation of a functional portion of pancreatic beta cells that initially survived STZ toxicity. The partial preservation of pancreatic beta cells, albeit small in proportion to the total insulin store, was both critical and sufficient for a long-term reversal of the diabetic state. These results suggest that apparently modest effects in preserving residual pancreatic insulin content can have profound consequences on glucose homeostasis and may bear important implications for interventions that have "limited" protective effects on beta cells.

Malaria, a mosquito-borne disease caused by Plasmodium species, causes substantial morbidity and mortality throughout the world. Plasmodium sporozoites mature in oocysts formed in the mosquito gut wall and then invade the salivary glands, where they remain until transmitted to the vertebrate host during a mosquito bite. The Plasmodium circumsporozoite protein (CSP) binds to salivary glands and plays a role in the invasion of this organ by sporozoites. We identified an Anopheles salivary gland protein, named CSP-binding protein (CSPBP), that interacts with CSP. Downregulation of CSPBP in mosquito salivary glands inhibited invasion by Plasmodium organisms. In vivo bioassays showed that mosquitoes that were fed blood with CSPBP antibody displayed a 25% and 90% reduction in the parasite load in infected salivary glands 14 and 18 days after the blood meal, respectively. These results suggest that CSPBP is important for the infection of the mosquito salivary gland by Plasmodium organisms and that blocking CSPBP can interfere with the Plasmodium life cycle.

Dimethylditelluride has been used as a dopant source for GaAs epilayers grown by atmospheric pressure oganometallic vapor phase epitaxy. The highest electron concentration obtained, n = 2.7 × 10 19 cm −3 , appears to be the highest electron concentration ever obtained in VPE GaAs consistent with mirror-like morphology. The electron and Te concentrations are virtually the same, as determined by SIMS, CV, and Hall effect. Electron concentrations are routinely obtained above 1 × 10 19 cm −3 over a range of growth temperatures and low frsol |V/III ratios of 5–10. The relationship between electron concentration and dopant mole fraction, group V mole fraction, growth temperature and growth rate have been studied. A model of Fermi-level pinning at the surface is consistent with the observed Te incorporation. Excellent morphology combined with high electron concentration requires the use of high growth rates, r g ≥ 6 μ m/h. We have extended the measured mobility vs electron concentration curve to n = 3.3 × 10 19 cm −3 . Our results also indicate that the highest Te concentrations obtained are in excess of the solubility limit.

The blood-testis barrier (BTB) is a unique ultrastructure in the mammalian testis. Unlike other blood-tissue barriers, such as the blood-brain barrier and the blood-ocular (or blood-retina) barrier which formed by tight junctions (TJ) between endothelial cells of the microvessels, the BTB is constituted by coexisting TJ, basal ectoplasmic specialization (basal ES), desmosomes and gap junctions between adjacent Sertoli cells near the basement membrane of the seminiferous tubule. The BTB also divides the seminiferous epithelium into the apical (or adluminal) and basal compartments so that meiosis I and II and post-meiotic germ cell development can all take place in a specialized microenvironment in the apical compartment behind the BTB. While the unusual anatomical features of the BTB have been known for decades, the physiological function of the coexisting junctions, in particular the desmosome and gap junction, that constitute the BTB was unknown until recently. Based on recently published findings, we critically evaluate the role of the desmosome and gap junction that serve as a signaling platform to coordinate the 'opening' and 'closing' of the TJ-permeability barrier conferred by TJ and basal ES during the seminiferous epithelial cycle of spermatogenesis. This is made possible by polarity proteins working in concert with nonreceptor protein tyrosine kinases, such as focal adhesion kinase (FAK) and c-Src, at the site to regulate endosome-mediated protein trafficking events (e.g., endocytosis, transcytosis, recycling or protein degradation). These events not only serve to destabilize the existing 'old' BTB above preleptotene spermatocytes in transit in 'clones' at the BTB, but also contribute to the assembly of 'new' BTB below the transiting spermatocytes. Furthermore, hemidesmosomes at the Sertoli cell-basement membrane interface also contribute to the BTB restructuring events at stage VIII of the epithelial cycle. Additionally, the findings that a gap junction at the BTB provides a possible route for the passage of toxicants [e.g., bisphenol A (BPA)] and potential male contraceptives (e.g., adjudin) across the BTB also illustrate that these coexisting junctions, while helpful to maintain the immunological barrier integrity during the transit of spermatocytes, can be the 'gateway' to making the BTB so vulnerable to toxicants and/or chemicals, causing male reproductive dysfunction., link_to_OA_fulltext

Environmental toxicants, such as cadmium and bisphenol A (BPA) are endocrine disruptors. In utero, perinatal or neonatal exposure of BPA to rats affect the male reproductive function, such as the blood-testis barrier (BTB) integrity. This effect of BPA on BTB integrity in immature rats is likely mediated via a loss of gap junction function at the BTB, failing to coordinate tight junction and anchoring junction function at the site to maintain the immunological barrier integrity. This in turn activates the extracellular signal-regulated kinases 1/2 (Erk1/2) downstream and an increase in protein endocytosis, destabilizing the BTB. The cadmium-induced disruption of testicular dysfunction is mediated initially via its effects on the occludin/ZO-1/focal adhesion kinase (FAK) complex at the BTB, causing redistribution of proteins at the Sertoli-Sertoli cell interface, leading to the BTB disruption. The damaging effects of these toxicants to testicular function are mediated by mitogen-activated protein kinases (MAPK) downstream, which in turn perturbs the actin bundling and accelerates the actin-branching activity, causing disruption of the Sertoli cell tight junction (TJ)-barrier function at the BTB and perturbing spermatid adhesion at the apical ectoplasmic specialization (apical ES, a testis-specific anchoring junction type) that leads to premature release of germ cells from the testis. However, the use of specific inhibitors against MAPK was shown to block or delay the cadmium-induced testicular injury, such as BTB disruption and germ cell loss. These findings suggest that there may be a common downstream p38 and/or Erk1/2 MAPK-based signaling pathway involving polarity proteins and actin regulators that is shared between different toxicants that induce male reproductive dysfunction. As such, the use of inhibitors and/or antagonists against specific MAPKs can possibly be used to "manage" the illnesses caused by these toxicants and/or "protect" industrial workers being exposed to high levels of these toxicants in their work environment.

In mammalian testes, the blood-testis barrier (BTB) or Sertoli cell barrier created by specialized junctions between Sertoli cells near the basement membrane confers an immunological barrier by sequestering the events of meiotic division and postmeiotic germ cell development from the systemic circulation. The BTB is constituted by coexisting tight junctions (TJs), basal ectoplasmic specializations, desmosomes, and gap junctions. Despite being one of the tightest blood-tissue barriers, the BTB has to restructure cyclically during spermatogenesis. A recent study showed that gap junction protein connexin 43 (Cx43) and desmosome protein plakophilin-2 are working synergistically to modulate the BTB integrity by regulating the distribution of TJ-associated proteins at the Sertoli-Sertoli cell interface. However, the precise role of Cx43 in regulating the cyclical restructuring of junctions remains obscure. In this report, the calcium switch and the bisphenol A (BPA) models were used to induce junction restructuring in primary cultures of Sertoli cells isolated from rat testes that formed a TJ-permeability barrier that mimicked the BTB in vivo. The removal of calcium by EGTA perturbed the Sertoli cell tight junction barrier, but calcium repletion allowed the "resealing" of the disrupted barrier. However, a knockdown of Cx43 in Sertoli cells by RNAi significantly reduced the kinetics of TJ-barrier resealing. These observations were confirmed using the bisphenol A model in which the knockdown of Cx43 by RNAi also perturbed the TJ-barrier reassembly following BPA removal. In summary, Cx43 is crucial for TJ reassembly at the BTB during its cyclic restructuring throughout the seminiferous epithelial cycle of spermatogenesis., link_to_OA_fulltext

Recent declines in male fertility, as evidenced by decreased sperm counts, in industrialized nations have been attributed partly to the exposure of men to environmental toxicants, such as cadmium, bisphenol A, and others. These environmental toxicants are found in drinking water, food, dairy products, and many utensils (e.g., plastics and glass bottles). It is of interest to note that while animal models clearly show effects of environmental toxicants on male reproductive function, linking specific environmental exposures in humans to adverse effects on the male reproductive system is very tenuous for the vast majority of environmental chemicals since human exposure is often orders of magnitude lower than dose levels used in animal studies. Nonetheless, environment toxicants have become an integrated part of our day-to-day routine and food/water intakes. This thus sparks interest in the field to assess if acute and chronic exposure of these toxicants to laboratory animals would cause reproductive damage, and whether such damage can be reversed and/or rescued. In this review, we summarize recent findings in the field regarding damage that are caused by these toxicants to the testis via their actions at the cell–cell interface, thereby inducing premature loss of germ cells from the seminiferous epithelium which leads to reduced sperm counts in semen. Some of these studies have identified specific signaling pathways that are used by these toxicants to induce disruption at the Sertoli–Sertoli and/or Sertoli–germ cell interface, perturbing the blood–testis barrier (BTB) function and germ cell adhesion. This information should be helpful in future studies to design compounds that can ‘reverse’ and/or ‘reduce’ toxicant toxicity to the testis.

The blood-testis barrier (BTB) formed by adjacent Sertoli cells is composed of coexisting tight junction (TJ), basal ectoplasmic specialization (ES), and desmosome-like junction. Desmosome-like junctions display structural features of desmosome and gap junctions, but its function at the BTB remains unknown. Herein, we demonstrate that connexin 43 (Cx43), a gap junction integral membrane protein, structurally interacts with desmosomal protein plakophilin-2 (PKP2), basal ES proteins N-cadherin and β-catenin, and signaling molecule c-Src, but not with the TJ proteins occludin and ZO-1 in the seminiferous epithelium of adult rats. The localization of Cx43 in the seminiferous epithelium during (i) the normal epithelial cycle of spermatogenesis and (ii) anchoring junction restructuring at the Sertoli-spermatid interface induced by adjudin which mimics junction restructuring events during spermatogenesis have suggested that Cx43 is involved in cell adhesion. The knockdown of Cx43 by RNAi technique using specific siRNA duplexes was performed in primary Sertoli cell cultures with an established TJ permeability barrier that mimicked the BTB in vivo. This knockdown of Cx43 affected neither the TJ barrier function nor the steady-state levels of junction proteins of TJ, basal ES, and desmosome-like junction. However, after the knockdown of both Cx43 and PKP2, the Sertoli cell TJ barrier function was perturbed transiently. This perturbation was concomitant with a mislocalization of occludin and ZO-1 from the cell-cell interface. In summary, Cx43 and PKP2 form a protein complex within the desmosome-like junction to regulate cell adhesion at the BTB, partly through its effects on the occludin/ZO-1 complex, so as to facilitate the transit of primary preleptotene spermatocytes., link_to_OA_fulltext

During spermatogenesis, spermiation takes place at the adluminal edge of the seminiferous epithelium at stage VIII of the epithelial cycle during which fully developed spermatids (i.e. spermatozoa) detach from the epithelium in adult rat testes. This event coincides with the migration of preleptotene/leptotene spermatocytes across the blood–testis barrier from the basal to the apical (or adluminal) compartment. At stage XIV of the epithelial cycle, Pachytene spermatocytes (diploid, 2n) differentiate into diplotene spermatocytes (tetraploid, 4n) in the apical compartment of the epithelium, which begin meiosis I to be followed by meiosis II to form spermatids (haploid, 1n) at stage XIV of the epithelial cycle. These spermatids, in turn, undergo extensive morphological changes and traverse the seminiferous epithelium until they differentiate into elongated spermatids. Thus, there are extensive changes at the Sertoli–Sertoli and Sertoli–germ cell interface via protein ‘coupling’ and ‘uncoupling’ between cell adhesion protein complexes, as well as changes in interactions between integral membrane proteins and their peripheral adaptors, regulatory protein kinases and phosphatases, and the cytoskeletal proteins. These precisely coordinated protein–protein interactions affect cell adhesion and cell movement. In this review, we focus on the 14-3-3 protein family, whose members have different binding partners in the seminiferous epithelium. Recent studies have illustrated that 14-3-3 affects protein–protein interactions in the seminiferous epithelium, and regulates cell adhesion possibly via its effects on intracellular protein trafficking and cell-polarity proteins. This review provides a summary on the latest findings regarding the role of 14-3-3 family of proteins and their potential implications on spermatogenesis. We also highlight research areas that deserve attentions by investigators.

During spermatogenesis in mammalian testes, junction restructuring takes place at the Sertoli-Sertoli and Sertoli-germ cell interface, which is coupled with germ cell development, such as cell cycle progression, and translocation of the germ cell within the seminiferous epithelium. In the rat testis, restructuring of the blood-testis barrier (BTB) formed between Sertoli cells near the basement membrane and disruption of the apical ectoplasmic specialization (apical ES) between Sertoli cells and fully developed spermatids (spermatozoa) at the luminal edge of the seminiferous epithelium occur concurrently at stage VIII of the seminiferous epithelial cycle of spermatogenesis. These two processes are essential for the translocation of primary spermatocytes from the basal to the apical compartment to prepare for meiosis, and the release of spermatozoa into the lumen of the seminiferous epithelium at spermiation, respectively. Cytokines, such as TNFα and TGFβ3, are present at high levels in the microenvironment of the epithelium at this stage of the epithelial cycle. Since these cytokines were shown to disrupt the BTB integrity and germ cell adhesion, it was proposed that some cytokines released from germ cells, particularly primary spermatocytes, and Sertoli cells, would induce restructuring of the BTB and apical ES at stage VIII of the seminiferous epithelial cycle. In this review, the intricate role of cytokines and testosterone to regulate the transit of primary spermatocytes at the BTB and spermiation will be discussed. Possible regulators that mediate cytokine-induced junction restructuring, including gap junction and extracellular matrix, and the role of testosterone on junction dynamics in the testis will also be discussed. © 2009 Elsevier Ltd. All rights reserved., link_to_OA_fulltext

Polarity proteins have been implicated in regulating and maintaining tight junction (TJ) and cell polarity in epithelia. Here we report 14-3-3θ, the homolog of Caenorhabditis elegans Par5 in mammalian cells, which is known to confer cell polarity at TJ, is found at the apical ectoplasmic specialization (ES), a testis-specific adherens junction type restricted to the Sertoli cell-elongating spermatid interface, in which TJ is absent. 14-3-3θ was shown to play a critical role in conferring cell adhesion at the apical ES. A loss of 14-3-3θ expression at the apical ES was detected in the seminiferous epithelium before spermiation. Involvement of 14-3-3θ in Sertoli cell adhesion was confirmed by its knockdown by RNA interference in Sertoli cells cultured in vitro with established TJ permeability barrier that mimicked the blood-testis barrier (BTB) in vivo. Mislocalization of N-cadherin and zonula occludens-1, but not α- and β-catenins, was observed after 14-3-3θ knockdown in Sertoli cells, moving from the cell-cell interface to cytosol, indicating a disruption of cell adhesion. Studies by endocytosis assay illustrated that this loss of cell adhesion was mediated by an increase in the kinetics of endocytosis of N-cadherin and junctional adhesion molecule-A at the BTB, which may represent a general mechanism by which polarity proteins regulate cell adhesion. In summary, the testis is using 14-3-3θ to regulate cell adhesion at the apical ES to facilitate spermiation and at the BTB to facilitate the transit of preleptotene spermatocytes at stages VIII-IX of the epithelial cycle. 14-3-3θ may act as a molecular switch that coordinates these two cellular events in the seminiferous epithelium during spermatogenesis. Copyright © 2009 by The Endocrine Society., link_to_OA_fulltext

In order to cure and damp coupled bunch instabilities (CBI), a bunch-by-bunch (BxB) measurement and transverse feedback system is under commission at Hefei light source (HLS). In this paper we introduce the overview of the measurement and analogy transverse BxB feedback system in emphases. The measurement system is dedicated to observe the beam instability and works as a part of the analogy and digital transverse BxB feedback system. The development of several characterized components and stripline feedback kicker as well as the experiment result of the feedback system in HLS ring is also presented in this paper.

Several novel approaches are summarized, which are from our EMC project practices for recent years. These include: (1) A universal near/far field algorithm,; (2) A deductive method for near/far field estimate; (3) Element technique combined with GTD approaches to predict near/far field. Some examples are shown to support these approaches. They may be widely used in the antenna analysis and EMC prediction.