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Sertoli cells are crucial for spermatogenesis in the seminiferous epithelium because their actin cytoskeleton supports vesicular transport, cell junction formation, protein anchoring, and spermiation. Here, we show that a junction-mediating and actin-regulatory protein (JMY) affects the blood-tissue barrier (BTB) function through remodeling of the Sertoli cell junctional integrity and it also contributes to controlling endocytic vesicle trafficking. These functions are critical for the maintenance of sperm fertility since loss of Sertoli cell-specific Jmy function induced male subfertility in mice. Specifically, these mice have (a) impaired BTB integrity and spermatid adhesion in the seminiferous tubules; (b) high incidence of sperm structural deformity; and (c) reduced sperm count and poor sperm motility. Moreover, the cytoskeletal integrity was compromised along with endocytic vesicular trafficking. These effects impaired junctional protein recycling and reduced Sertoli cell BTB junctional integrity. In addition, JMY interaction with actin-binding protein candidates α-actinin1 and sorbin and SH3 domain containing protein 2 was related to JMY activity, and in turn, actin cytoskeletal organization. In summary, JMY affects the control of spermatogenesis through the regulation of actin filament organization and endocytic vesicle trafficking in Sertoli cells.

Because the strategy of stopping bus lines during an epidemic can negatively impact residents, this study proposes a bus passenger flow control model to optimize the safety of and access to bus transport. The information interaction environment can provide a means for the two-way regulation of buses and passengers. In this model, passengers first request their pick-up and drop-off location, and then the bus feeds back information on whether it accepts the request. Through this method, passenger flow control can be realized through complete information interaction. The study aimed to establish a multi-objective function that minimizes the weighted total cost of the safety cost, the passenger travel cost, and the bus travel cost during an epidemic. The constraints were the full load and riding rates of urban buses in peak periods under the condition of epidemic prevention and control. The results showed that, in the morning peak period, the passenger flow control scheme reduced the passenger infection probability by 17.89%, compared with no passenger flow control scheme. The weighted total cost of the epidemic safety cost, the passenger travel cost, and the bus operation cost was reduced by 8.04%. The optimization effect of the passenger flow control scheme of this model is good, and not only reduces the probability of passengers being infected, but also meets the requirements of epidemic prevention and the travel needs of residents.

Understanding the genetic quality of the gerbil, Meriones meridianus, plays an important role in the study of medical biology. However, no effective system has been established for evaluating a population's genetic diversity to date. In the present study, we established a set of reasonable evaluative systems based on microsatellite markers of the Mongolian gerbil by using the method of cross-amplification of species. Following electrophoresis analysis, short tandem repeat (STR) scanning, and sequencing, 11 microsatellite loci were identified by matching the criteria characteristics and were used to evaluate the genetic diversity of two stocks of Meriones meridianus: Meriones meridianus jei Wang, 1964 (M. m. jei) and Meriones meridianus cryptorhinus Blanford, 1875 (M. m. cryptorhinus) from Xinjiang, China. The microsatellite loci screened were highly polymorphic and were suitable for genetic quality control of Meriones meridianus. In addition, the quality of the non-bred M. m. jei and M. m. cryptorhinus strains in our study is sufficient for them to be promising stocks in the future for the farmed animal industry.

BACKGROUND Brucella infection induces brucellosis, a zoonotic disease. The intracellular circulation process and virulence of Brucella mainly depend on its type IV secretion system (T4SS) expressing secretory effectors. Secreted protein BspJ is a nucleomodulin of Brucella that invades the host cell nucleus. BspJ mediates host energy synthesis and apoptosis through interaction with proteins. However, the mechanism of BspJ as it affects the intracellular survival of Brucella remains to be clarified. OBJECTIVES To verify the functions of nucleomodulin BspJ in Brucella's intracellular infection cycles. METHODS Constructed Brucella abortus BspJ gene deletion strain (B. abortus ΔBspJ) and complement strain (B. abortus pBspJ) and studied their roles in the proliferation of Brucella both in vivo and in vitro. RESULTS BspJ gene deletion reduced the survival and intracellular proliferation of Brucella at the replicating Brucella-containing vacuoles (rBCV) stage. Compared with the parent strain, the colonization ability of the bacteria in mice was significantly reduced, causing less inflammatory infiltration and pathological damage. We also found that the knockout of BspJ altered the secretion of cytokines (interleukin [IL]-6, IL-1β, IL-10, tumor necrosis factor-α, interferon-γ) in host cells and in mice to affect the intracellular survival of Brucella. CONCLUSIONS BspJ is extremely important for the circulatory proliferation of Brucella in the host, and it may be involved in a previously unknown mechanism of Brucella's intracellular survival.

Series of UV excited Ba3Lu(PO4)3:Tb3+,Mn2+ phosphors with tunable green to red emissions had been prepared using solid state reactions. Powder X-ray diffraction and Rietveld structure refinement were used to investigate the phase purity and crystal structure of the prepared samples. Under UV excitation, the Ba3Lu(PO4)3:Tb3+,Mn2+ samples exhibited not only the typical Tb3+ emission peaks but also the broad emission band of Mn2+ ions due to the efficient Tb3+→Mn2+ energy transfer which had been verified by luminescence spectra and decay curves. Utilizing the Inokuti-Hirayama model, the Tb3+→Mn2+ energy transfer mechanism was determined to be the electronic dipole–quadrupole interaction. Moreover, the emission spectra of Ba3Lu(PO4)3:0.80Tb3+,0.015Mn2+ sample at different temperatures manifested that our prepared phosphors possessed good thermal stability. The luminescence properties investigation results revealed the potential value of Ba3Lu(PO4)3F:Tb3+,Mn2+ in application for UV excited phosphor converted white light emitting diodes.

With the integration of information technology and manufacturing industry and the improvement of equipment monitoring data and computer computing ability, equipment fault diagnosis has entered the era of “big data”. Using big data analysis method for fault diagnosis, the fault diagnosis model can learn its own characteristics and complete fault identification, so that the fault diagnosis is more intelligent and automatic on the basis of high identification accuracy. This paper mainly studies the application of fault diagnosis method and big data analysis method in pump product fault diagnosis.

The BiOCl-SL was prepared by a simple hydrothermal reaction between Bi(NO3)3·5H2O and KCl using sodium lignosulfonate (SL) as a structure-directing agent. The standard tetragonal structure of the BiOCl has been confirmed by X-ray powder diffraction. The scanning electron microscopy results revealed that a suitable amount of SL is favorable for the formation of hollow sphere-Like BiOCl. The fourier transform infrared spectroscopy (FT-IR) of the BiOCl-SL showed the BiOCl samples have been cleaned thoroughly, and the following photocatalytic experiment will not be affected by SL. In comparison with the pure BiOCl, the UV–Vis diffuse reflectance spectroscopy (UV–Vis-DRS) of the BiOCl-SL showed a red shift of absorption edge. The Brunauer–Emmett–Teller surface area measurement indicated that the surface area of BiOCl-SL is much bigger than that of pure BiOCl. The photocatalytic activity of BiOCl was tested on the degradation of Rodamine B (RhB) under visible light irradiation, and the result showed that the BiOCl-SL-0.3 had excellent photocatalytic activity for RhB after visible light irradiation for 2 h.

Tryptophan hydroxylase (TPH) is the initial and rate-limiting enzyme in serotonin biosynthesis. The enzyme activity is dependent on molecular oxygen, a tetrahydropterin cosubstrate, and ferrous iron. The present study demonstrates that TPH is inhibited by a novel compound, p-ethynylphenylalanine (pEPA), produced by the Heck reaction of trimethylsilylacetylene with N-tertbutyloxycarbonyl-4-iodo-L-phenylalanine methyl ester. pEPA is a more potent and specific inhibitor of TPH than p-chlorophenylalanine (pCPA). In the present study, pEPA was demonstrated to inhibit competitively and reversibly TPH in vitro (Ki = 32.6 +/- 6.2 microM vs. tryptophan). pEPA displayed little inhibitory activity toward tyrosine hydroxylase (EC 1.14.16.2), the initial and rate-limiting enzyme for catecholamine biosynthesis, and no inhibition of phenylalanine hydroxylase or tyrosinase. In addition, pEPA was a poor ligand for the serotonin transporter and several serotonin receptors. Administration of pEPA (30 mg/kg) to rats produced a 95 +/- 5% decrease in TPH activity in brain homogenates and a concomitant decrease in serotonin and 5-hydroxyindole-3-acetic acid levels (85%) at 24 h after injection. In contrast, pCPA produced a similar effect (87 +/- 5% decrease in TPH activity) only at 10 times the concentration (300 mg/kg). These results suggest that pEPA is a selective, reversible, and potent inhibitor of TPH both in vitro and in vivo. The potential for pEPA to inhibit selectively and reversibly the biosynthesis of serotonin may contribute to the characterization of the role of serotonin in behavioral and physiological activities.

Although synapsins are abundant synaptic vesicle proteins that are widely used as markers of presynaptic terminals, the mechanisms that target synapsins to presynaptic terminals have not been elucidated. We have addressed this question by imaging the targeting of green fluorescent protein-tagged synapsins in cultured hippocampal neurons. Whereas all synapsin isoforms targeted robustly to presynaptic terminals in wild-type neurons, synapsin Ib scarcely targeted in neurons in which all synapsins were knocked-out. Coexpression of other synapsin isoforms significantly strengthened the targeting of synapsin Ib in knock-out neurons, indicating that heterodimerization is required for synapsin Ib to target. Truncation mutagenesis revealed that synapsin Ia targets via distributed binding sites that include domains B, C, and E. Although domain A was not necessary for targeting, its presence enhanced targeting. Domain D inhibited targeting, but this inhibition was overcome by domain E. Thus, multiple intermolecular and intramolecular interactions are required for synapsins to target to presynaptic terminals.

Synapsin III is the most recently identified member of the synapsin family, a group of synaptic vesicle proteins that play essential roles in neurotransmitter release and neurite outgrowth. Here, through the generation and analysis of synapsin III knock-out mice, we demonstrate that synapsin III regulates neurotransmitter release in a manner that is distinct from that of synapsin I or synapsin II. In mice lacking synapsin III, the size of the recycling pool of synaptic vesicles was increased, and synaptic depression was reduced. The number of vesicles that fuse per action potential was similar between synapsin III knock-out and wild-type mice, and there was no change in the quantal content of EPSCs; however, IPSCs were greatly reduced in synapsin III-deficient neurons. The density and distribution of synaptic vesicles in presynaptic terminals did not appear to be different in synapsin III knock-out mice in comparison to wild-type littermates. In addition to the changes in neurotransmitter release, we observed a specific delay in axon outgrowth in cultured hippocampal neurons from synapsin III knock-out mice. Our data indicate that synapsin III plays unique roles both in early axon outgrowth and in the regulation of synaptic vesicle trafficking.

We examined the role of SNAPs, soluble proteins that attachN-ethylmaleimide-sensitive factor (NSF), in regulating exocytosis in single rat adrenal chromaffin cells. Whole-cell dialysis of Ca2+-buffered solution or photolysis of caged-Ca2+was used to manipulate cytosolic Ca2+concentration ([Ca2+]i), whereas exocytosis was measured via carbon fiber amperometry or membrane capacitance. Buffering [Ca2+]ito ∼170 nmproduced a mean rate of exocytosis of approximately one amperometric event per minute. Including α-SNAP (60 or 500 nm) in the intracellular solution dramatically increased the mean rate of exocytosis. The stimulatory action of α-SNAP requires ATP hydrolysis mediated via NSF, because this action was blocked by intracellular dialysis of ATP-γ-S (2 mm) and could not be mimicked by a mutant α-SNAP that does not stimulate the ATPase activity of NSF. This action of α-SNAP was significant only at [Ca2+]ibetween 100 and 300 nmand was not shared by β-SNAP (500 nm), suggesting that α-SNAP enhanced a component of exocytosis that is regulated by a high-affinity Ca2+sensor. In cells dialyzed with both α- and β-SNAP, the rate of exocytosis was smaller than that produced by α-SNAP alone, suggesting that α- and β-SNAP interact competitively. Although only α-SNAP stimulated exocytosis at [Ca2+]ibetween 100 and 300 nm, both α- and β-SNAP isoforms equally slowed the time-dependent rundown of the exocytic response. Our results indicate that α- and β-SNAP have different actions in exocytosis. Thus, the ratio of different isoforms of SNAPs can determine release probability at the levels of [Ca2+]ithat are involved in regulation of exocytosis.

Objectives Loperamide is a peripherally acting μ opioid receptor agonist and an avid substrate for P-glycoprotein. This may give rise to drug–drug interactions and increased risk for central adverse effects. The objective of this study was to re-evaluate the predictability of non-clinical data using loperamide as a probe P-glycoprotein substrate. We searched the literature for papers containing data on drug–drug interactions of loperamide-containing products in humans. We also reviewed the internal worldwide safety database of Johnson & Johnson for spontaneous case reports suggestive of a central opioid effect after coadministration of loperamide with a P-glycoprotein inhibitor or substrate. Key findings Only one of the ten studies in our review supported the finding that inhibition of P-glycoprotein is associated with clinically relevant signs or symptoms of central nervous system (CNS) depression/opioid toxicity of loperamide. None of the 25 spontaneous case reports of interest were suggestive of signs or symptoms of CNS depression/opioid toxicity due to coadministration of loperamide and a P-glycoprotein inhibitor or substrate. Summary Based on a review of the literature and a cumulative review of the sponta-neous case reports, there is insufficient evidence that an interaction between loperamide and a P-glycoprotein inhibitor or substrate is associated with clinical symptoms of CNS depression/opioid toxicity when loperamide is taken at the recommended dose.

We examined the role of SNAPs, soluble proteins that attach N-ethylmaleimide-sensitive factor (NSF), in regulating exocytosis in single rat adrenal chromaffin cells. Whole-cell dialysis of Ca2+-buffered solution or photolysis of caged-Ca2+ was used to manipulate cytosolic Ca2+ concentration ([Ca2+]i), whereas exocytosis was measured via carbon fiber amperometry or membrane capacitance. Buffering [Ca2+]i to approximately 170 nm produced a mean rate of exocytosis of approximately one amperometric event per minute. Including alpha-SNAP (60 or 500 nm) in the intracellular solution dramatically increased the mean rate of exocytosis. The stimulatory action of alpha-SNAP requires ATP hydrolysis mediated via NSF, because this action was blocked by intracellular dialysis of ATP-gamma-S (2 mm) and could not be mimicked by a mutant alpha-SNAP that does not stimulate the ATPase activity of NSF. This action of alpha-SNAP was significant only at [Ca2+]i between 100 and 300 nm and was not shared by beta-SNAP (500 nm), suggesting that alpha-SNAP enhanced a component of exocytosis that is regulated by a high-affinity Ca2+ sensor. In cells dialyzed with both alpha- and beta-SNAP, the rate of exocytosis was smaller than that produced by alpha-SNAP alone, suggesting that alpha- and beta-SNAP interact competitively. Although only alpha-SNAP stimulated exocytosis at [Ca2+]i between 100 and 300 nm, both alpha- and beta-SNAP isoforms equally slowed the time-dependent rundown of the exocytic response. Our results indicate that alpha- and beta-SNAP have different actions in exocytosis. Thus, the ratio of different isoforms of SNAPs can determine release probability at the levels of [Ca2+]i that are involved in regulation of exocytosis.