Rational Construction of a N, F Co-doped Mesoporous Cobalt Phosphate with Rich-Oxygen Vacancies for Oxygen Evolution Reaction and Supercapacitors.

Transition-metal phosphates have been widely applied as promising candidates for electrochemical energy storage and conversion. In this study, we report a simple method to prepare a N, F co-doped mesoporous cobalt phosphate with rich-oxygen vacancies by in-situ pyrolysis of a Co-phosphate precursor with NH4 + cations and F- anions. Due to this heteroatom doping, it could achieve a current density of 10 mA/cm2 at lower overpotential of 276 mV and smaller Tafel slope of 57.11 mV dec-1 on glassy carbon. Moreover, it could keep 92 % of initial current density for 35 h, indicating it has an excellent stability and durability. Furthermore, the optimal material applied in supercapacitor displays specific capacitance of 206.3 F g-1 at 1 A ⋅ g-1 and maintains cycling stability with 80 % after 3000 cycles. The excellent electrochemical properties should be attributed to N, F co-doping into this Co-based phosphate, which effectively modulates its electronic structure. In addition, its amorphous structure provides more active sites; moreover, its mesoporous structure should be beneficial to mass transfer and electrolyte diffusion.

Ebselen alleviates testicular pathology in mice with Zika virus infection and prevents its sexual transmission.

Despite the low case fatality, Zika virus (ZIKV) infection has been associated with microcephaly in infants and Guillain-Barré syndrome. Antiviral and vaccine developments against ZIKV are still ongoing; therefore, in the meantime, preventing the disease transmission is critical. Primarily transmitted by Aedes species mosquitoes, ZIKV also can be sexually transmitted. We used AG129 mice lacking interferon-α/ß and -γ receptors to study the testicular pathogenesis and sexual transmission of ZIKV. Infection of ZIKV progressively damaged mouse testes, increased testicular oxidative stress as indicated by the levels of reactive oxygen species, nitric oxide, glutathione peroxidase 4, spermatogenesis-associated-18 homolog in sperm and pro-inflammatory cytokines including IL-1ß, IL-6, and G-CSF. We then evaluated the potential role of the antioxidant ebselen (EBS) in alleviating the testicular pathology with ZIKV infection. EBS treatment significantly reduced ZIKV-induced testicular oxidative stress, leucocyte infiltration and production of pro-inflammatory response. Furthermore, it improved testicular pathology and prevented the sexual transmission of ZIKV in a male-to-female mouse sperm transfer model. EBS is currently in clinical trials for various diseases. ZIKV infection could be on the list for potential use of EBS, for alleviating the testicular pathogenesis with ZIKV infection and preventing its sexual transmission.

Dengue Virus Impairs Mitochondrial Fusion by Cleaving Mitofusins.

Mitochondria are highly dynamic subcellular organelles participating in many signaling pathways such as antiviral innate immunity and cell death cascades. Here we found that mitochondrial fusion was impaired in dengue virus (DENV) infected cells. Two mitofusins (MFN1 and MFN2), which mediate mitochondrial fusion and participate in the proper function of mitochondria, were cleaved by DENV protease NS2B3. By knockdown and overexpression approaches, these two MFNs showed diverse functions in DENV infection. MFN1 was required for efficient antiviral retinoic acid-inducible gene I-like receptor signaling to suppress DENV replication, while MFN2 participated in maintaining mitochondrial membrane potential (MMP) to attenuate DENV-induced cell death. Cleaving MFN1 and MFN2 by DENV protease suppressed mitochondrial fusion and deteriorated DENV-induced cytopathic effects through subverting interferon production and facilitating MMP disruption. Thus, MFNs participate in host defense against DENV infection by promoting the antiviral response and cell survival, and DENV regulates mitochondrial morphology by cleaving MFNs to manipulate the outcome of infection.

Does the Level of Syndesmotic Screw Insertion Affect Clinical Outcome after Ankle Fractures with Syndesmotic Instability?

OBJECTIVE: Ankle fractures are often combined with syndesmotic instability, requiring reduction and stabilization. However, the optimal level for syndesmotic screw positioning remains unclear. This study aims to evaluate the effect of different syndesmotic screw insertion levels on postoperative clinical outcomes and determine whether an optimal level exists. METHODS: This retrospective study included data from 43 adult patients with acute closed ankle fractures combined with intraoperative evidence of unstable syndesmotic injuries who underwent open reduction internal fixation from January 1, 2017 to March 1, 2018 according to the inclusion and exclusion criteria. All 43 patients were divided into three groups based on the syndesmotic screw placement level: trans-syndesmotic group: screw level of 2-3 cm; inferior-syndesmotic group: screw level <2 cm; and supra-syndesmotic group: screw level >3 cm. Clinical outcomes were measured at the final follow-up, including the American Orthopedic Foot and Ankle Society (AOFAS) ankle-hindfoot score, Olerud-Molander Ankle Score (OMAS), short-form 36-item questionnaire (SF-36), visual analogue scale (VAS) score and restrictions in ankle range of motion (ROM). The relationships between screw placement level and clinical outcomes were analyzed with the Kruskal-Wallis H-test and Spearman correlation analysis. RESULTS: The median follow-up duration was 15 months (range, 10-22 months). No patients developed fracture nonunion or malunion or experienced hardware failure. The outcome scoring systems showed an overall score for the entire group of 94.91 points for the AOFAS ankle-hindfoot score, 83.14 for the OMAS, 96.65 for the SF-36, 1.77 for the VAS, 9.14° for the restrictions in dorsiflexion, and 1.30° for the restrictions in plantarflexion. There were no significant differences among three groups in clinical outcomes (P > 0.05). Neither the AOFAS score nor OMAS had significant correlations with screw insertion level (P = 0.825 and P = 0.585, respectively). No postoperative arthritis or widening of the tibiofibular space was observed at the final follow-up. CONCLUSION: Different syndesmotic screw placement levels appear not to affect the clinical outcomes of ankle fractures with syndesmotic instability. No optimal level was observed in this study. Our findings suggest other clinically acceptable options apart from syndesmotic screw placement 2-3 cm above the ankle.

CO2 bubble-assisted in-situ construction of mesoporous Co-doped Cu2(OH)2CO3 nanosheets as advanced electrodes towards fast and highly efficient electrochemical reduction of nitrate to N2 in wastewater.

The development of high-efficient and cost-effective electrocatalysts is crucial to remove nitrate pollutant in wastewater. Herein, we design and prepare mesoporous Co-doped Cu2(OH)2CO3 malachite nanosheets as an electrocatalyst toward highly efficient nitrate reduction using a facile CO2 bubble-assisted coprecipitation synthesis. The electrocatalytic performance is subject to the Co/Cu ratio of this malachite. Remarkably, compared with the pristine monometal Cu or Co-based electrocatalyst, the optimal electrocatalyst, 0.3Co@Cu2(OH)2CO3, displays fast and highly efficient removal capacity of nitrate with an impressive high total nitrogen (TN) removal of 8628.99 mg N g-1CoCu (398.79 mg N gcat-1 h-1), N2 selectivity of 97.11% as well as negligible nitrite product at 100 mg L-1 NO3--N and 2000 mg L-1 Cl- neutral electrolyte. Above all, high total nitrogen removal efficiency (81.92%) and chemical oxygen demand (73.74%) in actual wastewater. Its excellent electrocatalytic performance is achieved by regulating the electronic structure and the adsorption/desorption of the intermediate. This study discovers a new type of electrode materials for nitrate removal in wastewater.

Novel AR-12 derivatives, P12-23 and P12-34, inhibit flavivirus replication by blocking host de novo pyrimidine biosynthesis.

The genus Flavivirus contains many important pathogens, including dengue virus (DENV), Zika virus (ZIKV), and Japanese encephalitis virus (JEV). AR-12 is a celecoxib-derived anticancer agent that possesses antiviral activity against a broad range of viruses. We pharmacologically exploited this unique activity to develop additional antiviral agents, resulting in the production of the AR-12 derivatives P12-23 and P12-34. At nanomolar concentrations, these compounds were effective in suppressing DENV, ZIKV and JEV replication, exhibiting 10-fold improvements in the efficacy and selectivity indices as compared to AR-12. Regarding the mode of antiviral action, P12-23 and P12-34 inhibited viral RNA replication but had no effect on viral binding, entry or translation. Moreover, these AR-12 derivatives co-localized with mitochondrial markers, and their antiviral activity was lost in mitochondria-depleted cells. Interestingly, exogenous uridine or orotate, the latter being a metabolite of the mitochondrial enzyme dihydroorotate dehydrogenase (DHODH), abolished the antiviral activity of AR-12 and its derivatives. As DHODH is a key enzyme in the de novo pyrimidine biosynthesis pathway, these AR-12 derivatives may act by targeting pyrimidine biosynthesis in host cells to inhibit viral replication. Importantly, treatment with P12-34 significantly improved the survival of mice that were subcutaneously challenged with DENV. Thus, P12-34 may warrant further evaluation as a therapeutic to control flaviviral outbreaks.

[Facilitation of Shengjingbao to spermatogenesis in oligospermia mouse models and its action mechanisms].

OBJECTIVE: To investigate the effects of Shengjingbao on spermatogenesis in the mouse model of oligospermia and its action mechanisms. METHODS: Sixty male mice were randomly divided into 4 groups, Shengjingbao (Group 1), Vitamin E (Group 2), blank model control (Group 3) and normal blank control (Group 4). The first three groups were treated by celiac injection of cyclophosphamide for 5 successive days to make models, followed by intragastric administration of Shengjingbao and Vitamin E to Group I and 2, respectively, for 36 days. And then all the mice were sacrificed. The serum testosterone (T) level was determined by radioimmunology, and a suspension was made from the testis and epididymis of one side for sperm analysis, while the testis of the other side was sliced up and stained by HE method and TUNEL technique to detect the count of Leydig cells, the layers of spermatogenic epithelia and the apoptosis of spermatogenic cells. RESULTS: Compared with Group 3, the serum T level, the layers of spermatogenic epithelia and the count of Leydig cells were obviously improved and even exceeded those in Group 2. The positive expression rate of spermatogenic cell apoptosis in Group 1 was evidently lower than Group 2 and 3. The above differences were statistically significant (P < 0.01 or P < 0.05), but no significant difference was noted between Group 1 and 4. CONCLUSION: Shengjingbao can significantly increase the count of Leydig cells, elevate the T level that influences the layers of spermatogenic epithelia, and thus enhance spermatogenesis. The action mechanisms of Shengjingbao may lie in its capacity of inhibiting the apoptosis of spermatogenic cells, increasing the layers of spermatogenic epithelia and facilitating spermatogenesis. T may play a role in inhibiting the apoptosis of spermatogenic cells.

Autophagy is involved in the early step of Japanese encephalitis virus infection.

Japanese encephalitis virus (JEV), an enveloped Flavivirus with a positive-sense RNA genome, causes acute encephalitis with high mortality in humans. We used a virulent (RP-9) and an attenuated (RP-2ms) JEV strain to assess the role of autophagy in JEV infection. By monitoring the levels of lipidated LC3, we found that autophagy was induced in human NT-2 cells infected with RP-2ms, especially at the late stage, and to a lesser extent with RP-9. The induction of autophagy by rapamycin increased viral production, whereas the inhibition of autophagy by 3-methyladenine reduced viral yields for both RP-9 and RP-2ms. The viral replication of RP-9 and RP-2ms was also reduced in cells with downregulated ATG5 or Beclin 1 expression, suggesting a proviral role of autophagy in JEV replication. To determine the step of JEV life cycle affected by autophagy, we used an mCherry-LC3 fusion protein as the autophagosome marker. Little of no colocalization of LC3 puncta with dsRNA was noted, whereas the input JEV particles were targeted to autophagosomes stained positive for early endosome marker. Overall, we show for the first time that the cellular autophagy process is involved in JEV infection and the inoculated viral particles traffic to autophagosomes for subsequent steps of viral infection.