Expression of transforming growth factor-ß1 and autophagy markers in the bladder of rats with neurogenic lower urinary tract injury.

OBJECTIVE: This study was conducted to explore the expression of transforming growth factor-beta 1 (TGF-ß1) and its correlation with autophagy markers in the bladder of rats with neurogenic lower urinary tract dysfunction (NLUTD) post spinal cord injury (SCI). STUDY DESIGN: A total of 36 male Wistar rats were randomly divided into the SCI group and control group. Rats in the SCI group were subjected to T10-T11 spinal cord transection. At day 1, 4, and 7, 6 rats were euthanized daily and the Basso, Beattie and Bresnahan score (BBB score), post-void residual (PVR), urinary bladder function score (UBFS) and bladder weight were assessed. The expression TGF-ß1 and autophagy markers were evaluated by immunofluorescence staining, Western bolt, and qRT-PCR. SETTING: A total of 36 male Wistar rats were randomly divided into the SCI group and control group, with three time points in each group. PARTICIPANTS: Not applicable. RESULTS: SCI modeling impaired the motor function of the hind limbs and the bladder function of rats. NLUTD muscle exhibited a punctated immunostaining pattern for LC3, suggesting the accumulation of autophagosomes. Our results further indicated that compared with the control group, the expression levels of TGF-ß1 and LC3 were increased, while the level of P62 was decreased after SCI modeling. CONCLUSION: TGF-ß1 was significantly increased in SCI rats with NLUTD and was correlated with autophagy markers LC3 and p62.

Aluminum sheet induced flower-like carbon nitride anchored with silver nanowires for highly efficient SERS detection of trace malachite green.

The sensitive detection of malachite green (MG) in aquaculture wastewater is necessary for its residual poses a great threat to the living systems. Herein, the flower-like C3N4 (f-C3N4) nanostructure induced by Al sheet in the hydrothermal process is constructed. Subsequently, Ag nanowires (AgNWs) supported on Al/f-C3N4 and the strong interaction between AgNWs and Al/f-C3N4 are confirmed by XPS, Raman spectroscopy, UV-vis diffuse reflectance and fluorescence spectroscopy. Importantly, the portable Al/f-C3N4/AgNWs substrate shows the outstanding SERS response for MG, which is attributed to enhanced electromagnetic effect of AgNWs on large amount of corrugated and creviced regions in the flower-like Al/f-C3N4 and the charge transfer among the components. Also, the prepared Al/f-C3N4 nanostructure provides large specific surface area and abundant "N" active sites for AgNWs, and the high enrichment ability of Al/f-C3N4 towards MG molecules by the strong π-π stacking interaction. The detection limit of Al/f-C3N4/AgNWs for MG is as low as 8.38 × 10-12 mol L-1. The substrate can be reproduced and reused for at least 7 cycles, and the activity can still be kept after laid up for 49 days. Importantly, it unfolds a good sensitivity and selectivity for MG in actual water sample. Results indicate that the Al/f-C3N4/AgNWs substrate has a promising potential in practical application for trace detection of MG.

Photocatalytic activity and the electron transport mechanism of titanium dioxide microsphere/porphyrin implanted with small size copper.

To obtain efficient photocatalysts by coupling architectures, developing novel materials and elucidating the charge transport mechanism at the semiconductor interface are vital. Herein, a special nanocomposite (TiO2 microsphere/CuNPs/THPP) for photocatalytic hydrogen production was facilely fabricated with copper nanoparticles (CuNPs) as the interfacial linker of the TiO2 microspheres and meso-tetra(p-hydroxypheny)porphyrin (THPP). The assembly mode of the nanocomposite was studied in detail. It was found that the CuNPs implanted at the interface of the TiO2 microspheres and THPP can dramatically strengthen the interaction between the TiO2 microspheres and THPP, and improve the separation and transfer of photo-produced charges. Therefore, the nanocomposite displayed excellent performance for photocatalytic hydrogen production. Moreover, by recycling hydrogen production, it is demonstrated that the nanocomposite was a highly efficient and long-term stable photocatalyst. By investigating the energy band location and the charge transfer, the photocatalytic mechanism over the special nanocomposite was explored and proposed to explain the better activity of the TiO2 microsphere/CuNPs/THPP photocatalytic system. It will be helpful to provide deep insights into the construction of efficient photocatalytic systems.

Lysozyme improves gut performance and protects against enterotoxigenic Escherichia coli infection in neonatal piglets.

Diarrhea remains one of the leading causes of morbidity and mortality globally, with enterotoxigenic Escherichia coli (ETEC) constituting a major causative pathogen. The development of alternative treatments for diarrhea that do not involve chemotherapeutic drugs or result in antibiotic resistance is critical. Considering that lysozyme is a naturally occurring antimicrobial peptide, in a previous study we developed a transgenic pig line that expresses recombinant human lysozyme (hLZ) in its milk. In the present study, we examined the protective effects of the consumption of this milk against ETEC infection in neonatal piglets. We found that consuming hLZ milk facilitated faster recovery from infection and decreased mortality and morbidity following an ETEC oral inoculation or infection acquired by contact-exposure. The protective effect of hLZ was associated with the enrichment of intestinal bacteria that improve gut health, such as Lactobacillus, and the enhancement of the mucosal IgA response to the ETEC-induced diarrhea. Our study revealed potential protective mechanisms underlying the antimicrobial activity of human lysozyme, validating the use of lysozyme as an effective preventive measure for diarrhea.

PCSK9 Inhibitor with Statin Therapy for Intracranial Artery Stenosis ( PISTIAS): Rationale and design of a multicenter randomized controlled trial.

RATIONALE: Proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors enable an additional 54-75% reduction in low-density lipoprotein cholesterol (LDL-C) in statin-treated patients, demonstrating plaque regression in coronary artery disease. However, the impact of achieving an extremely low level of LDL-C with PCSK9 inhibitors (e.g. Evolocumab) on symptomatic intracranial atherosclerosis remains unexplored. AIM AND HYPOTHESIS: To determine whether combining Evolocumab and statins achieves a more significant symptomatic intracranial plaque regression than statin therapy alone. SAMPLE SIZE ESTIMATES: With a sample size of 1000 subjects, a two-sided α of 0.05, and 20% lost to follow-up, the study will have 83.3% power to detect the difference in intracranial plaque burden. METHODS AND DESIGN: This is an investigator-initiated multicenter, randomized, open-label, outcome assessor-blinded trial, evaluating the impact of combining Evolocumab and statins on intracranial plaque burden assessed by high-resolution magnetic resonance imaging at baseline in patients undergoing a clinically indicated acute stroke or transient ischemic attack due to intracranial artery stenosis, and after 24 weeks of treatment. Subjects (n = 1000) were randomized 1:1 into two groups to receive either Evolocumab 140 mg every 2 weeks with statin therapy or statin therapy alone. STUDY OUTCOMES: The primary endpoint is the change in intracranial plaque burden assessed by high-resolution magnetic resonance imaging, performed at baseline and at the end of the 24-week treatment period. DISCUSSION: This trial will explore whether more significant intracranial plaque regression is achievable with the treatment of combining Evolocumab and statins, providing information about efficacy and safety data. TRIAL REGISTRATION NUMBER: ChiCTR2300068868; https://www.chictr.org.cn/.

Synaptic-like transmission between neural axons and arteriolar smooth muscle cells drives cerebral neurovascular coupling.

Neurovascular coupling (NVC) is important for brain function and its dysfunction underlies many neuropathologies. Although cell-type specificity has been implicated in NVC, how active neural information is conveyed to the targeted arterioles in the brain remains poorly understood. Here, using two-photon focal optogenetics in the mouse cerebral cortex, we demonstrate that single glutamatergic axons dilate their innervating arterioles via synaptic-like transmission between neural-arteriolar smooth muscle cell junctions (NsMJs). The presynaptic parental-daughter bouton makes dual innervations on postsynaptic dendrites and on arteriolar smooth muscle cells (aSMCs), which express many types of neuromediator receptors, including a low level of glutamate NMDA receptor subunit 1 (Grin1). Disruption of NsMJ transmission by aSMC-specific knockout of GluN1 diminished optogenetic and whisker stimulation-caused functional hyperemia. Notably, the absence of GluN1 subunit in aSMCs reduced brain atrophy following cerebral ischemia by preventing Ca2+ overload in aSMCs during arteriolar constriction caused by the ischemia-induced spreading depolarization. Our findings reveal that NsMJ transmission drives NVC and open up a new avenue for studying stroke.

Effect of plasticity of the cladding with different thicknesses on the bearing capacity of the brittle base wall of RPV under PTS loads.

In the research field of reactor pressure vessel (RPV) subjected to pressurized thermal shock (PTS), the traditional linear elastic analytical method generally ignores the plastic properties of cladding. In fact, the neutron irradiation in RPV is easy to cause the embrittlement of the base material rather than cladding. So the elastic-plastic parameters of cladding are introduced into the FE model of the RPV with a sub-clad crack. The stress distributions in the thermal-mechanical coupling fields related to the base wall and cladding of different thicknesses are then obtained. The XFEM is used to simulate the crack growth in the nozzle area. The allowable internal pressure in the dangerous moment of the PTS is calculated to show the ultimate bearing capacity of the structure. The numerical results are compared with those only considering the elasticity of cladding. Furthermore, the law of the effect of plasticity of cladding on the structural safety is summarized.

Selective surface enhanced Raman detection and effective photocatalytic degradation of sulfonamides antibiotic based on a flexible three-dimensional chitosan/carbon nitride/silver substrate.

The prevalence of sulfonamide residues in aquatic environments poses serious environmental risks, and the sensitive detection and effective degradation of sulfonamides have attracted widespread attention. Here, the environmentally friendly chitosan (CS)/carbon nitride (CN) with three-dimensional porous structure is fabricated by freeze-drying method, and subsequently a new bifunctional flexible substrate (CS/CN/Ag) is prepared by anchoring of small sized AgNPs (6 ∼ 12 nm) on CS/CN. Importantly, the CS/CN/Ag substrate shows high adsorption capacity (∼ 83.06%) for sulfamethoxazole (SMX) solution within 20 mins and the limit of detection can be as low as 7.46 × 10-9 mol·L-1 with an enhancement factor of 3.3 × 105. Also, the CS/CN/Ag substrate displays highly selective for surface-enhanced Raman spectroscopy (SERS) detection of sulfonamides and also shows excellent SERS response for SMX in hospital wastewater samples. In addition, the photocatalytic degradation efficiency of SMX could reach as high as 99.22% within 20 mins of irradiation and the CS/CN/Ag still maintains outstanding photocatalytic performance after six cycles. Moreover, the Ag content in the CS/CN/Ag substrate is only 2.35%, and also the CS/CN/Ag exhibits good uniformity, repeatability, recyclability and stability. Therefore, this flexible and cost-effectively substrate of CS/CN/Ag shows great potential for the simultaneous SERS detection and photocatalytic degradation of pollutants in actual wastewater samples.

A portable architectonics of Al/carbon nitride/metal-organic frameworks anchored Ag nanoparticles for SERS detection and photocatalytic degradation of fungicide.

In recent years, it is urgent to develop bi-functional materials for highly sensitive SERS detection and photocatalytic degradation of contaminants in water of fish pond. Herein, using 5-mercapto-1-methyltetrazole as the ligand, the tree-trunk like zeolitic imidazolate framework (ZIF-8) is induced and in-situ grown on the surface of aluminum/flower carbon nitride (Al/f-C3N4). Then, AgNPs are tightly anchored in ZIF-8 of Al/f-C3N4/ZIF-8 by strong Ag-N and Ag-S bonds, and a portable architecture of Al/f-C3N4/ZIF-8/Ag is successfully prepared. Results indicate that the Al/f-C3N4/ZIF-8/Ag architecture exhibits excellent SERS activity and the detection limit can as low as 2.15 × 10-11 mol⋅L-1 for crystal violet (CV, a typical fungicide). Also, the Al/f-C3N4/ZIF-8/Ag substrate presents good photocatalytic activity for CV molecule, and the degradation efficiency reaches 98.58% after illumination for 90 min. This is mainly due to the good adsorption capacity of ZIF-8 which can enrich more CV molecules and pull them to "hot spots" generated by Ag in Al/f-C3N4/ZIF-8/Ag, and thus SERS response are enhanced significantly. Besides, the strong synergistic effect of f-C3N4, ZIF-8 and AgNPs is also important which facilitates the separation of photogenerated electrons and holes. Thus, the designed portable and bi-functional substrate could be used as a potential material for the detection and removal of CV in practical application.

A high-throughput fully automatic biosensing platform for efficient COVID-19 detection.

We propose a label-free biosensor based on a porous silicon resonant microcavity and localized surface plasmon resonance. The biosensor detects SARS-CoV-2 antigen based on engineered trimeric angiotensin converting enzyme-2 binding protein, which is conserved across different variants. Robotic arms run the detection process including sample loading, incubation, sensor surface rinsing, and optical measurements using a portable spectrometer. Both the biosensor and the optical measurement system are readily scalable to accommodate testing a wide range of sample numbers. The limit of detection is 100 TCID50/ml. The detection time is 5 min, and the throughput of one single robotic site is up to 384 specimens in 30 min. The measurement interface requires little training, has standard operation, and therefore is suitable for widespread use in rapid and onsite COVID-19 screening or surveillance.

Characterization of multidrug resistance 1a/P-glycoprotein knockout rats generated by zinc finger nucleases.

The development of zinc finger nuclease (ZFN) technology has enabled the genetic engineering of the rat genome. The ability to manipulate the rat genome has great promise to augment the utility of rats for biological and pharmacological studies. A Wistar Hannover rat model lacking the multidrug resistance protein Mdr1a P-glycoprotein (P-gp) was generated using a rat Mdr1a-specific ZFN. Mdr1a was completely absent in tissues, including brain and small intestine, of the knockout rat. Pharmacokinetic studies with the Mdr1a P-gp substrates loperamide, indinavir, and talinolol indicated that Mdr1a was functionally inactive in the blood-brain barrier and intestine in Mdr1a(-/-) rats. To identify possible compensatory mechanisms in Mdr1a(-/-) rats, the expression levels of drug-metabolizing enzyme and transporter-related genes were compared in brain, liver, kidney, and intestine of male and female Mdr1a(-/-) and control rats. In general, alterations in gene expression of these genes in Mdr1a(-/-) rats seemed to be modest, with more changes in female than in male rats. Taken together, our studies demonstrate that the ZFN-generated Mdr1a(-/-) rat will be a valuable tool for central nervous system drug target validation and determining the role of P-gp in drug absorption and disposition.

High-level expression of bioactive recombinant human lysozyme in the milk of transgenic mice using a modified human lactoferrin BAC.

Transgenesis has been used for expressing human lysozyme (hLZ) in the milk of livestock to improve their disease resistance. Here we describe a human lactoferrin (hLF) BAC as a candidate vector for high-level expression of hLZ in the milk of transgenic mice. Using recombineering, hLF genomic DNA in the hLF BAC was replaced by the hLZ gene (from the ATG start codon to the TAA stop codon), and flanking regions of the hLF gene (a 90-kb 5' and a 30-kb 3') were used as transcriptional control elements for hLZ expression. When this construct was used to generate transgenic mice, rhLZ was highly expressed in the milk of four transgenic mouse lines (1.20-1.76 g/L), was expressed at a lower level in one additional line (0.21 g/L). rhLZ from the milk of these transgenic mice exhibited the same antibacterial activity as native hLZ. Our results suggest a potential approach for producing large amounts of hLZ in the milk of livestock.

Metabolic syndrome in mice induced by expressing a transcriptional activator in adipose tissue.

Metabolic syndrome is a combination of medical disorders that increases the risk of developing cardiovascular disease and diabetes. Constitutive overexpression of 11ß-HSD1 in adipose tissue in mice leads to metabolic syndrome. In the process of generating transgenic mice overexpressing 11ß-HSD1 in an inducible manner, we found a metabolic syndrome phenotype in control, transgenic mice, expressing the reverse tetracycline-transactivator (rtTA) in adipose tissue. The control mice exhibited all four sequelae of metabolic syndrome (visceral obesity, insulin resistance, dyslipidemia, and hypertension), a pro-inflammatory state and marked hepatic steatosis. Gene expression profiling of the adipose tissue, muscle and liver of these mice revealed changes in expression of genes involved in lipid metabolism, insulin resistance, and inflammation. Transient transfection of rtTA, but not tTS, into 3T3-L1 cells resulted in lipid accumulation. We conclude that expression of rtTA in adipose tissue causes metabolic syndrome in mice.

Team Social Media Usage and Team Creativity: The Role of Team Knowledge Sharing and Team-Member Exchange.

Given that work teams have been widely used in a variety of organizations to complete critical tasks and that the use of social media in work teams has been growing, investigating whether and how team social media usage (TSMU) affects team creativity is imperative. However, little research has empirically explored how TSMU affects team creativity. This study divides TSMU into two categories, namely, work-related TSMU and relationship-related TSMU. Basing on communication visibility theory and social exchange theory, this study constructs a moderating mediation model to understand how TSMU affects team creativity. In this model, team knowledge sharing is used as mediating role and team-member exchange (TMX) is used as moderating role. Two-wave research data collected from 641 employees in 102 work teams in Chinese organizations are used for regression analysis. Results show that (1) Work-related TSMU and relationship-related TSMU are positively affect team creativity. (2) Team knowledge sharing plays a partly mediating effect on the relationship between work-related TSMU and team creativity and that between relationship-related TSMU and team creativity. (3) TMX not only positively moderates the indirect effect of work-related TSMU and relationship-related TSMU on team creativity through team knowledge sharing. Theoretical and practical implications are also discussed.

Moderating Multiple Mediation Model of the Impact of Inclusive Leadership on Employee Innovative Behavior.

Leadership is an important antecedent variable of employee innovative behavior. In previous studies, the influence of inclusive leadership on employee innovative behavior mainly focus on one mediating variable, which may lead to a deviation in parameter estimation due to the omission of other mediating variables. According to the social cognitive theory and motivation theory and from the perspective of cognitive-motivation integration, this study establishes a moderating multi-mediation model to understand the impact of inclusive leadership on employee innovative behavior. Psychological safety and creative self-efficacy are used as mediating variables, and innovation rewards are used as moderating variables. The data are collected from 418 employees of the manufacturing industry in China. The results show that, at first, inclusive leadership has a positive effect on employee innovative behavior. Secondly, both psychological safety and creative self-efficacy play partial mediating effects between inclusive leadership and employee innovative behavior, with the effect of the former being significantly smaller than that of the latter. Thirdly, innovation rewards positively moderate the relationships of "psychological safety-employee innovative behavior" and of "creative self-efficacy-employee innovative behavior." Fourthly, innovation rewards positively moderate the indirect effect of inclusive leadership on employee innovative behavior through psychological safety and creative self-efficacy. These findings are not only helpful to expand how inclusive leadership influences the innovative behavior of employees but also provides some suggestions for enterprise innovation development.

Boosting charge separation and nitrogen vacancies in graphitic carbon nitride by implanted strontium vanadate for highly efficient photocatalytic reduction of hexavalent chromium.

Strontium vanadate nanoparticles embedded graphitic carbon nitride (g-C3N4/Sr2V2O7) was facilely prepared in situ via a hydrothermal method. It was shown that the Sr2V2O7 nanoparticles implanted into g-carbon nitride had a small size and high distribution. Importantly, compared with some other photocatalysts, the as-prepared g-C3N4/Sr2V2O7 nanohybrid showed excellent photocatalytic activity for reduction of Cr(vi), and as high as 99% efficiency for Cr(vi) reduction (100 mg L-1) was reached within 8 min. Moreover, its activity was hardly changed after five cycles, demonstrating that the developed g-C3N4/Sr2V2O7 nanohybrid was highly stable and promising an efficacious disposal of Cr(vi) in water. It was confirmed that the improved charge separation owing to more nitrogen vacancies in the hybrid was the main reason for the improved performance of the g-C3N4-Sr2V2O7 nanohybrid.

A stable and plug-and-play aluminium/titanium dioxide/metal-organic framework/silver composite sheet for sensitive Raman detection and photocatalytic removal of 4-aminothiophenol.

The sensitive detection and rapid removal of 4-aminothiophenol (4-ATP, a poisonous pesticide) demand special design to potential substrates. Herein, a metal-organic framework (ZIF-8) and Ag nanoparticles were fabricated one by one on the TiO2 coated Al sheet, and thus the Al-TiO2-ZIF-8-Ag sheet with sandwich structure was successfully synthesized. The cost-effective Al-TiO2-ZIF-8-Ag sheet (3.7 wt% Ag) possessed a low detection concentration of 1 × 10-9 M towards 4-ATP, and surface-enhanced Raman scattering (SERS) analytical enhanced factor (AEF) of the Al-TiO2-ZIF-8-Ag was 2.6 × 106, which was higher than other similar substrates. Furthermore, 4-ATP can be selectively and repeatedly detected on the Al-TiO2-ZIF-8-Ag even through it was in real samples. It indicated that the Al-TiO2-ZIF-8-Ag was a very active and stable SERS materials for the monitoring of 4-ATP. Importantly, the substrate exhibited faster and more efficient photocatalytic activity for 4-ATP degradation. The SERS and photocatalytic mechanisms of 4-ATP on the Al-TiO2-ZIF-8-Ag substrate were proposed. The cost-effective Al-TiO2-ZIF-8-Ag sheet with double function is plug-and-play, and could be used in the detection and treatment of pollutants in wastewater.

Design and optimization of an advanced time-of-flight neutron spectrometer for deuterium plasmas of the large helical device.

A time-of-flight neutron spectrometer based on the Time-Of-Flight Enhanced Diagnostic (TOFED) concept has been designed and is under development for the Large Helical Device (LHD). It will be the first advanced neutron spectrometer to measure the 2.45 MeV D-D neutrons (DDNs) from helical/stellarator plasmas. The main mission of the new TOFED is to study the supra-thermal deuterons generated from the auxiliary heating systems in helical plasmas by measuring the time-of-flight spectra of DDN. It will also measure the triton burnup neutrons (TBNs) from the d+t reactions, unlike the original TOFED in the EAST tokamak. Its capability of diagnosing the TBN ratios is evaluated in this work. This new TOFED is expected to be installed in the basement under the LHD hall and shares the collimator with one channel of the vertical neutron camera to define its line of sight. The distance from its primary scintillators to the equatorial plane of LHD plasmas is about 15.5 m. Based on Monte Carlo simulation by a GEANT4 model, the resolution of the DDN energy spectra is 6.6%. When projected onto the neutron rates that are typically obtained in LHD deuterium plasmas (an order of 1015 n/s with neutral beam injection), we expect to obtain the DDN and TBN counting rates of about 2.5 · 105 counts/s and 250 counts/s, respectively. This will allow us to analyze the DDN time-of-flight spectra on time scales of 0.1 s and diagnose the TBN emission rates in several seconds with one instrument, for the first time in helical/stellarator plasmas.

Cubeben induces autophagy via PI3K-AKT-mTOR pathway to protect primary neurons against amyloid beta in Alzheimer's disease.

Autophagy is a lysosomal degradative process by which it recycles cytosolic components and degrades protein aggregates inside cells. Here, we identified cubeben as an inducer of autophagy in primary neuronal cells. Autophagy induction was accompanied the upregulation of autophagic proteins like Beclin, ATG5, ATG12 and lipidation of LC3-II in primary neuronal cells. Cubeben induces autophagy by the inhibition of PI3K-AKT pathway in a dose dependent manner. Constitutive active P110α abrogates cubeben induced autophagic induction in primary neuronal cells. Furthermore, cubeben inhibits amyloid beta induced toxicity in primary neuronal cells. Thus our data suggests that cubeben as a potential anti-Alzheimer therapeutic lead.