Search

Background: The ratio of non-high-density lipoprotein cholesterol to high-density lipoprotein cholesterol (NHHR) is a novel lipid measure for assessing the risk of cardiovascular disease. Lipid metabolism disorders are reportedly associated with hearing impairment. This study aimed to investigate the potential association between NHHR and hearing. Methods: The data used in this study were obtained from the National Health and Nutrition Examination Survey (NHANES) cycles of 2005–2010 and 2017–2018, including 4,296 participants aged 6–19 years. The NHHR was calculated from lipid profiles, and hearing was assessed using pure-tone audiometry. Weighted multivariate logistic regression analyses were used to investigate the association between the NHHR and hearing loss. Subgroup and sensitivity analyses were performed to verify the robustness of the results. Results: Univariate analysis revealed significant associations between the NHHR and hearing threshold at all categorized frequency (low, speech, or high-frequency) (P < 0.001). Three models were used: an unadjusted model, a model adjusted for age, sex, and race, and a model further adjusted for PIR, BMI, and diabetes. Multiple regression analysis confirmed these associations consistently across all models. When considered as a continuous variable, NHHR had a significant association with enhanced hearing thresholds at all categorized frequencies: low-frequency (β:0.56, 95% CI: 0.36–0.75), speech-frequency (β:0.55, 95% CI: 0.36–0.7), and high-frequency (β:0.55, 95% CI: 0.36–0.74). The adjusted models showed persistent positive correlations after controlling for covariates. The NHHR was consistently positively associated with hearing loss. The NHHR and auditory thresholds showed a general dose-response association across all frequencies. Conclusions: NHHR is a promising biomarker for predicting adolescent hearing threshold shifts and hearing loss. The study highlights the importance of early lipid monitoring and management as strategies to prevent or reduce hearing impairment. [ABSTRACT FROM AUTHOR]

The Chinese stock market has a threefold segmented structure. Firstly, there is a division between floatable and nonfloatable shares, known as the split‐share structure. Before 2005, more than two‐thirds of the shares outstanding were nonfloatable. This structure limited shareholders' ability to exercise governance rights through stock trading. While largely dismantled by the 2005 reform, the split‐share structure has not been fully eliminated. Secondly, floatable shares can be issued in multiple currencies. However, shares denominated in the domestic currency often trade at a premium over those denominated in foreign currencies. This premium can be explained by the differences in target investors and the trading restrictions. Thirdly, stocks denominated in the domestic currency are sorted into different market tiers depending on the firms' profitability and market capitalization. The limited mobility of stocks across different tiers engenders tier‐specific characteristics, such as high family ownership and venture‐capital backing, which have not been sufficiently studied. In this paper, we delineate the three aspects of market segmentation, offer critical comments on the caveats of the extant studies, and propose topics for future research. [ABSTRACT FROM AUTHOR]

Oxidation flow reactors (OFRs) have been extensively utilized to examine the formation of secondary organic aerosol (SOA). However, the UV lamps typically employed to initiate the photochemistry in OFRs can result in an elevated reactor temperature when their implications are not thoroughly evaluated. In this study, we conducted a comprehensive investigation into the temperature distribution within an Aerodyne potential aerosol mass OFR (PAM-OFR) and then examined the subsequent effects on flow and chemistry due to lamp heating. A lamp-induced temperature increase was observed, which was a function of lamp-driving voltage, number of lamps, lamp types, OFR residence time, and positions within the PAM-OFR. Under typical PAM-OFR operational conditions (e.g., < 5 d of equivalent atmospheric OH exposure under low- NOx conditions), the temperature increase typically ranged from 1–5 °C. Under extreme (but less frequently encountered) conditions, the heating could reach up to 15 °C. The influences of the increased temperature over ambient conditions on the flow distribution, gas, and condensed-phase chemistry within PAM-OFR were evaluated. Our findings indicate that the increase in temperature altered the flow field, resulting in a diminished tail on the residence time distribution and corresponding oxidant exposure due to faster recirculation. According to simulation results from a radical chemistry box model, the variation in absolute oxidant concentration within PAM-OFR due to temperature increase was minimal (< 5 %). The temperature influences on seed organic aerosol (OA) and newly formed secondary OA were also investigated, suggesting that an increase in temperature can impact the yield, size, and oxidation levels of representative biogenic and anthropogenic SOA types. Recommendations for temperature-dependent SOA yield corrections and PAM-OFR operating protocols that mitigate lamp-induced temperature enhancement and fluctuations are presented. We recommend blowing air around the reactor's exterior with fans during PAM-OFR experiments to minimize the temperature increase within PAM-OFR. Temperature increases are substantially lower for OFRs utilizing less powerful lamps compared to the Aerodyne version. [ABSTRACT FROM AUTHOR]

An electrochemical CO2 reduction reaction (CO2RR) is an effective way to reduce greenhouse gases by converting CO2 into high-value-added chemical products using electricity generated from renewable energy. In this paper, a Cu2O spherical catalyst was prepared by ascorbic acid reduction. The precipitated Cu-Ag spherical catalyst (P-CuO-Ag) was successfully prepared by calcining Cu2O-Ag with the introduction of an Ag component as the substrate. During the electrochemical reduction of CO2, the FE of the P-CuO-Ag catalyst for C2H4 at a potential of −1.1 V vs. RHE was as high as 39.8%, which was nearly twice that of the CuO catalyst, while the local current density JC2H4 for C2H4 reached 6 mA cm−2. The incorporation of Ag gives the spherical CuO catalyst higher electrochemical activity and better kinetic performance than the catalyst without Ag. [ABSTRACT FROM AUTHOR]

To investigate the effect of hydrogen sulfide (H2S) on ferroptosis and functional impairment induced by oxidized high-density lipoprotein (ox-HDL) in human umbilical vein endothelial cells (HUVECs), and to explore its mechanisms. METHODS: The HUVECs were cultured in vitro and exposed to 200 mg/L ox-HDL, ferroptosis inhibitor ferrostatin-1 (Fer-1), protein kinase B (PKB/Akt) inhibitor MK-2206 2HCl (MK), Akt agonist SC79, and/or H2S for 24 h. Western blot was used to identify the relevant proteins. Intracellular levels of reactive oxygen species (ROS) were analyzed by flow cytometry and immunofluorescence staining. Intracellular iron was measured using an iron detectionkit. The number of monocytes adhering to endothelial cells was counted using the monocyte adhesion assay. RESULTS: Compared with control group, acyl-CoA synthetase long-chain family member 4 (ACSL4) protein expression in ox-HDL group was elevated by 1.45-fold (P<0. 01), glutathione peroxidase 4 (GPX4) protein expression was decreased by 29. 79% (P<0. 05), and ROS levels and iron ion content were elevated by 4. 81-fold and 1. 40-fold, respectively (P< 0.01). The ratios of p-PI3K/PI3K and p-Akt/Akt were decreased by 45. 65% and 41. 68%, respectively (P<0. 01), endothelial cell function-related protein IL-6, ICAM-1 and TNF-a expression was elevated 1. 18-fold, 1. 24-fold and 1. 41-fold (P<0. 05), respectively, eNOS protein expression was decreased by 35. 24% (P<0. 01), and monocyte adhesion was elevated 3. 43-fold (P<0. 01). Compared with ox-HDL group, the endothelial cell iron death-related protein ACSL4 was decreased by 22. 32% (P<0. 05), GPX4 was increased by 1. 27-fold (P<0. 01), and the p-Akt/Akt ratio was increased by 1.52-fold (P<0. 01) in ox-HDL+H2S group. The fluorescence microscopy results showed that the ROS was decreased by 50. 35% (P<0. 01). The IL-6, ICAM-1 and TNF-a protein expression was decreased by 13. 34%, 9. 83% and 13. 46% (P<0. 05), respectively, eNOS was elevated by 1. 22-fold (P<0. 01), and the number of monocyte adhesion was decreased by 59. 05% (P<0. 01). Compared with ox-HDL group, GPX4 protein expression in ox-HDL+SC79 group was elevated by 1. 49-fold (P<0. 01), ACSL4 expression was decreased by 20. 72% (P<0. 05), and ROS and iron ions were decreased by 59. 31% and 23. 85% (P<0. 05), respectively. Compared with ox-HDL+H2S group, GPX4 protein expression was decreased by 21.28%, and ACSL4 protein expression was increased by 1. 16-fold in ox-HDL+H2S+MK group (P< 0. 05). CONCLUSION: H,S activates Akt to inhibit ox-HDL-induced ferroptosis in HUVECs and alleviate their functional damage. [ABSTRACT FROM AUTHOR]

Aluminosilicates, abundant and crucial in both natural environments and industry, often involve uncontrollable chemical components when derived from minerals, making further chemical purification and reaction more complicated. This study utilizes pure alumina and fumed silica powders as more controllable sources, enhancing aluminosilicate reactivity through room temperature (non-firing) processing and providing a robust framework that resists mechanical stress and high temperature. By embedding iron-based metal–organic frameworks (Fe-MOF/non-firing aluminosilicate membranes) within the above matrix, these ceramic membranes not only preserve their mechanical robustness but also gain significant chemical functionality, enhancing their capacity to removing phytochromes from the vegetables. Sodium hydroxide and sodium silicate were selected as activators to successfully prepare high-strength, non-firing aluminosilicate membranes. These membranes demonstrated a flexural strength of 8.7 MPa under wet-culture conditions with a molar ratio of Al2O3:SiO2:NaOH:Na2SiO3 at 1:1:0.49:0.16. The chlorophyll adsorption of spinach conducted on these membranes showed a removal rate exceeding 90% at room temperature and pH = 9, highlighting its potential for the selective adsorption of chlorophyll. This study underscores the potential of MOF-enhanced aluminosilicate ceramic membranes in environmental applications, particularly for agricultural pollution control. [ABSTRACT FROM AUTHOR]

Sluggish transfer kinetics caused by solid–solid contact at the lithium (Li)/solid-state electrolyte (SE) interface is an inherent drawback of all-solid-state Li metal batteries (ASSLMBs) that not only limits the cell power density but also induces uneven Li deposition as well as high levels of interfacial stress that deteriorates the internal structure and cycling stability of ASSLMBs. Herein, a fast Li+ transfer scaffold is proposed to overcome the sluggish kinetics at the Li/SE interface in ASSLMBs using an α-MnO2-decorated carbon paper (CP) structure (α-MnO2@CP). At an atomic scale, the tunnel structure of α-MnO2 exhibits a great ability to facilitate Li+ adsorption and transportation across the inter-structure of α-MnO2@CP, leading to a high critical current density of 3.95 mA cm−2 at the Li/SE interface. Meanwhile, uniform Li deposition can be guided along the skeletons of α-MnO2@CP with minimized volume expansion, significantly improving the structural stability of the Li/SE interface. Based on these advantages, the ASSLMBs using α-MnO2@CP protected the Li anode and can stably cycle up to very high charge/discharge rates of 10C/10C, paving the way for developing high-power ASSLMBs. [ABSTRACT FROM AUTHOR]

Background: Nigeria is facing a severe malaria crisis, accounting for a significant proportion of global cases and deaths of malaria. This study aimed to investigate the differences between female-headed households (FHHs) and male-headed households (MHHs) and their impact on malaria risk among children under five (U5) in Nigeria. Methods: Data from the 2021 Nigeria Malaria Indicator Survey (NMIS) were used for this cross-sectional study. A representative sample of 10,988 households was analysed, with key variables subjected to frequency calculations, descriptive statistics, and bivariate analyses using t-tests and chi-square analyses to compare the differences between FHHs and MHHs. Results: Among all participants, 92.1% (N = 10,126) reported residing in male-headed households, while 7.8% (N = 862) reported living in female-headed households. MHHs were significantly more likely to own insecticide-treated bed nets (ITNs) than FHHs (64.7% vs. 53.6%, P < 0.001). U5 children in MHHs had a greater likelihood of sleeping under a bed net the night before the survey than U5 children in FHHs (35.3% vs. 30.0%, P < 0.05). The prevalence of fever in the previous two weeks among U5 children was similar in MHHs and FHHs (35.4% vs. 31.4%), and the testing rates for malaria among U5 children who experienced febrile episodes were higher in MHHs than FHHs (22.4% vs. 15.4%, P < 0.05). Although not statistically significant, FHHs exhibited a higher percentage of U5 children testing positive for malaria compared to MHHs (87.8% vs. 78.9%). On the other hand, FHHs had higher education levels, overall wealth index scores, and a larger presence in urban areas compared to MHHs (P < 0.001). Moreover, FHHs reported higher adherence to malaria prevention awareness (P < 0.001). Conclusion: In Nigeria, FHHs enjoy relatively better socioeconomic conditions and stronger awareness of malaria prevention compared to their male-headed counterparts. Contrary to expectations, FHHs are at an increased risk of malaria in children under 5 years old. This phenomenon is associated with entrenched gender inequality and the challenges women face in accessing critical assets. As women in FHHs bear the responsibility of income generation while caring for their children, it is crucial to prioritize interventions that address malaria management in FHHs to reduce both malaria incidence and mortality rates. [ABSTRACT FROM AUTHOR]

Lithium (Li) metal batteries (LMBs) are deemed as ones of the most promising energy storage devices for next electrification applications. However, the uneven Li electroplating process caused by the diffusion‐limited Li+ transportation at the Li metal surface inherently promotes the formation of dendritic morphology and instable Li interphase, while the sluggish Li+ transfer kinetic can also cause lithiation‐induced stress on the cathode materials suffering from serious structural stability. Herein, a novel electrolyte designing strategy is proposed to accelerate the Li+ transfer by introducing a trace of large organic polar molecules of lithium phytate (LP) without significantly altering the electrolyte structure. The LP molecules can afford a competitive solvent attraction mechanism against the solvated Li+, enhancing both the bulk and interfacial Li+ transfer kinetic, and creating better anode/cathode interfaces to suppress the side reactions, resulting in much improved cycling efficiency of LMBs. Using LP‐based electrolyte, the performance of LMB pouch cell with a practical capacity of ~1.5 Ah can be improved greatly. This strategy opens up a novel electrolyte designing route for reliable LMBs. [ABSTRACT FROM AUTHOR]

Lithium (Li) metal batteries (LMBs) are deemed as ones of the most promising energy storage devices for next electrification applications. However, the uneven Li electroplating process caused by the diffusion‐limited Li+ transportation at the Li metal surface inherently promotes the formation of dendritic morphology and instable Li interphase, while the sluggish Li+ transfer kinetic can also cause lithiation‐induced stress on the cathode materials suffering from serious structural stability. Herein, a novel electrolyte designing strategy is proposed to accelerate the Li+ transfer by introducing a trace of large organic polar molecules of lithium phytate (LP) without significantly altering the electrolyte structure. The LP molecules can afford a competitive solvent attraction mechanism against the solvated Li+, enhancing both the bulk and interfacial Li+ transfer kinetic, and creating better anode/cathode interfaces to suppress the side reactions, resulting in much improved cycling efficiency of LMBs. Using LP‐based electrolyte, the performance of LMB pouch cell with a practical capacity of ~1.5 Ah can be improved greatly. This strategy opens up a novel electrolyte designing route for reliable LMBs. [ABSTRACT FROM AUTHOR]

Recent advances in melanoma therapy have significantly improved the prognosis of metastasized melanoma. However, large therapeutic gaps remain that need to be closed by new strategies. Antiapoptotic Bcl-2 proteins critically contribute to apoptosis deficiency and therapy resistance. They can be targeted by BH3 mimetics, small molecule antagonists that mimic the Bcl-2 homology domain 3 (BH3) of proapoptotic BH3-only proteins. By applying in vitro experiments, we aimed to obtain an overview of the possible suitability of BH3 mimetics for future melanoma therapy. Thus, we investigated the effects of ABT-737 and ABT-263, which target Bcl-2, Bcl-xL and Bcl-w as well as the Bcl-2-selective ABT-199 and the Mcl-1-selective S63845, in a panel of four BRAF-mutated and BRAF-WT melanoma cell lines. None of the inhibitors showed significant effectiveness when used alone; however, combination of S63845 with each one of the three ABTs almost completely abolished melanoma cell survival and induced apoptosis in up to 50–90% of the cells. Special emphasis was placed here on the understanding of the downstream pathways involved, which may allow improved applications of these strategies. Thus, cell death induction was correlated with caspase activation, loss of mitochondrial membrane potential, phosphorylation of histone H2AX, and ROS production. Caspase dependency was demonstrated by a caspase inhibitor, which blocked all effects. Upregulation of Mcl-1, induced by S63845 itself, as reported previously, was blocked by the combinations. Indeed, Mcl-1, as well as XIAP (X-linked inhibitor of apoptosis), were strongly downregulated by combination treatments. These findings demonstrate that melanoma cells can be efficiently targeted by BH3 mimetics, but the right combinations have to be selected. The observed pronounced activation of apoptosis pathways demonstrates the decisive role of apoptosis in the loss of cell viability by BH3 mimetics. [ABSTRACT FROM AUTHOR]

Three‐dimensional (3D) reconstruction is a pivotal research area within computer vision and photogrammetry, offering a valuable foundation of data for the development of smart cities. However, existing methods for constructing 3D models from unmanned aerial vehicle (UAV) images often suffer from slow processing speeds and low central processing unit (CPU)/graphics processing unit (GPU) utilization rates. Furthermore, the utilization of cluster‐based distributed computing for 3D modelling frequently results in inefficient resource allocation across nodes. To address these challenges, this paper presents a novel approach to 3D modelling in clusters, incorporating a dynamic load‐balancing strategy. The method divides the 3D reconstruction process into multiple stages to lay the groundwork for distributing tasks across multiple nodes efficiently. Instead of traditional traversal‐based communication, this approach employs gossip communication techniques to reduce the network overhead. To boost the modelling efficiency, a dynamic load‐balancing strategy is introduced that prevents nodes from becoming overloaded, thus optimizing resource usage during the modelling process and alleviating resource waste issues in multidevice clusters. The experimental results indicate that in small‐scale data environments, this approach improves CPU/GPU utilization by 35.8%/23.4% compared with single‐machine utilization. In large‐scale data environments for cluster‐based 3D modelling tests, this method enhances the average efficiency by 61.4% compared with traditional 3D modelling software while maintaining a comparable model accuracy. [ABSTRACT FROM AUTHOR]

In recent years, China has introduced a series of trade and financial liberalization policies and taken a crucial step towards the internationalization of RMB. These new developments bring about one question: how has openness affected the RMB real exchange rate volatility? Our empirical results reveal that in the long term, both trade and financial openness reduce exchange rate volatility; in the short term, the effect of financial openness varies across the three financial sub-accounts. Financial development can magnify (mitigate) the impact of trade openness on volatility in the short (long) term, but its role in affecting the impact of financial openness depends on the financial sub-account involved. Economic policy uncertainty (EPU) weakens the impact of openness on exchange rate volatility. In addition, financial openness absorbs more external shocks than trade openness. Foreign exchange reserves, while offsetting financial crisis shocks, cannot adequately absorb current account balance shocks. [ABSTRACT FROM AUTHOR]

Background: Aedes aegypti is a vector that transmits various viral diseases, including dengue and Zika. The radiation-based sterile insect technique (SIT) has a limited effect on mosquito control because of the difficulty in irradiating males without reducing their mating competitiveness. In this study, the insect sex pheromone heptacosane was applied to Ae. aegypti males to investigate whether it could enhance the mating competitiveness of irradiated males. Methods: Heptacosane was smeared on the abdomens of Ae. aegypti males that were allowed to mate with untreated virgin females. The insemination rate was used to assess the attractiveness of heptacosane-treated males to females. The pupae were irradiated with different doses of X-rays and γ-rays, and the emergence, survival time, egg number, and hatch rate were detected to find the optimal dose of X-ray and γ-ray radiation. The males irradiated at the optimal dose were smeared with heptacosane, released in different ratios with untreated males, and mated with females. The effect of heptacosane on the mating competitiveness of irradiated mosquitoes was then evaluated by the hatch rate, induced sterility, and mating competitiveness index. Results: Applying heptacosane to Ae. aegypti males significantly increased the insemination rate of females by 20%. Pupal radiation did not affect egg number but significantly reduced survival time and hatch rate. The emergence of the pupae was not affected by X-ray radiation but was affected by γ-ray radiation. Pupae exposed to 60 Gy X-rays and 40 Gy γ-rays were selected for subsequent experiments. After 60 Gy X-ray irradiation or 40 Gy γ-ray irradiation, the average hatch rate was less than 0.1%, and the average survival time was more than 15 days. Moreover, at the same release ratio, the hatch rate of the irradiated group perfumed with heptacosane was lower than that of the group without heptacosane. Conversely, the male sterility and male mating competitiveness index were significantly increased due to the use of heptacosane. Conclusions: The sex pheromone heptacosane enhanced the interaction between Ae. aegypti males and females. Perfuming males irradiated by X-rays or γ-rays with heptacosane led to a significant increase in mating competitiveness. This study provided a new idea for improving the application effect of SIT. [ABSTRACT FROM AUTHOR]

Secondary organic aerosols (SOAs) formed by oxidation of typical precursors largely emitted by biomass burning, such as polycyclic aromatic hydrocarbons (PAHs) and furans, are still poorly characterized. We evaluated and compared the formation yields, effective density (ρeff) , absorption Ångström exponent (α) , and mass absorption coefficient (MAC) of laboratory-generated SOAs from three furan compounds and four PAHs. SOAs were generated in an oxidation flow reactor under day- (OH radicals) or nighttime (NO 3 radicals) conditions. The ρeff , formation yields, α , and MAC of the generated SOAs varied depending on the precursor and oxidant considered. The ρeff of SOAs formed with OH and NO 3 tended to increase with particle size before reaching a "plateau", highlighting potential differences in SOA chemical composition and/or morphology, according to the particle size. Three times lower SOA formation yields were obtained with NO 3 compared with OH. The yields of PAH SOAs (18 %–76 %) were five to six times higher than those obtained for furans (3 %–12 %). While furan SOAs showed low or negligible light absorption properties, PAH SOAs had a significant impact in the UV–visible region, implying a significant contribution to atmospheric brown carbon. No increase in the MAC values was observed from OH to NO 3 oxidation processes, probably due to a low formation of nitrogen-containing chromophores with NO 3 only (without NO x). The results obtained demonstrated that PAHs are significant SOA precursors emitted by biomass burning, through both, day- and nighttime processes, and have a substantial impact on the aerosol light absorption properties. [ABSTRACT FROM AUTHOR]

Ceramic fiber insulation tiles have the characteristics of low density, high temperature resistance, low thermal conductivity and excellent wave transmission performance. It is suitable to be used as thermal protection material in medium low temperature area of space vehicle. The application of high emissivity coating on the surface of ceramic fiber insulation tiles can effectively solve the problems of easy moisture absorption, low strength and easy performance degradation in the service process of ceramic fiber insulation tile. At the same time, it can block the high temperature erosion airflow and improve the energy reflectivity and thermal shock resistance. This paper mainly introduces the preparation methods of ceramic fiber insulation tiles and the influencing factors of their properties, summarizes the research progress of ceramic fiber insulation tiles and their high emission coatings in aerospace field, and looks forward to their future development. [ABSTRACT FROM AUTHOR]

Background: Age-related hearing loss, known as presbycusis, is the result of auditory system degeneration. Numerous studies have suggested that reactive oxygen species (ROS) and mitochondrial oxidative damage play important roles in the occurrence and progression of aging. The D-galactose (D-gal)-induced aging model is well known and widely utilized in aging research. Our previous studies demonstrate that administration of D-gal causes mitochondrial oxidative damage and causes subsequent dysfunction in the cochlear ribbon synapses, which in turn leads to hearing changes and early stage presbycusis. Stria vascularis (SV) cells are vital for hearing function. However, it is unclear to what extent D-gal induces oxidative damage and apoptosis in the cochlear SV of mice. In addition, the source of the causative ROS in the cochlear SV has not been fully investigated. Methods: In this study, we investigated ROS generation in the cochlear SV of mice treated with D-gal. Hearing function was measured using the auditory brainstem response (ABR). Immunofluorescence was used to examine apoptosis and oxidative damage. Transmission electron microscopy was also used to investigate the mitochondrial ultrastructure. DNA fragmentation was determined using the terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end-labeling (TUNEL) assay. Mitochondrial membrane potential (MMP) and ATP were also measured. Results: We found that D-gal-treated mice exhibited a significant shift in the mean amplitude and latency of the ABR; a remarkable increase in the levels of NADPH oxidase (NOX-2), Uncoupling protein 2 (UCP2) and cleaved caspase-3 (c-Cas3) was observed, as well as an increase in the number of TUNEL-positive cells were observed in the SV of mice. Both the expression of the DNA oxidative damage biomarker 8-hydroxy-2-deoxyguanosine (8-OHdG) and a commonly occurring mitochondrial DNA deletion were markedly elevated in the SV of mice that had been treated with D-gal to induce aging. Conversely, the ATP level and MMP were significantly reduced in D-gal-induced aging mice. We also found alterations in the mitochondrial ultrastructure in the SV of aging mice, which include swollen and distorted mitochondrial shape, shortened and thickened microvilli, and the accumulation of lysosomes in the SV. Conclusion: Our findings suggest that the impairment of cochlear SV during presbycusis may be caused by mitochondrial oxidative damage and subsequent apoptosis. [ABSTRACT FROM AUTHOR]

Secondary organic aerosols (SOA) formed by oxidation of typical precursors largely emitted by biomass burning, such as PAHs and furans, are still poorly characterized in terms of formation yields, physical and light absorption properties, particularly those generated at night following reaction with nitrate radicals (NO3). In the present study, we evaluated and compared the formation yields, effective density (ρeff), absorption Ångström exponent (α), and mass absorption coefficient (MAC) of laboratory-generated SOA from three furan compounds (furan, 2-methylfuran, and 2,5-dimethylfuran) and four PAHs (naphthalene, acenaphthylene, fluorene, and phenanthrene). SOA were generated in an oxidation flow reactor from the reaction between hydroxyl radicals (OH; 0.1–20 equivalent aging days) or NO3 radicals (0.05–6 equivalent aging nights of 14 h) with single furan or PAH. The ρeff , formation yields, α, and MAC of the generated SOA varied depending on the precursor and oxidant considered. The ρeff of SOA formed with OH and NO3 tended to increase with particle size before reaching a "plateau". This was particularly evident for the nighttime chemistry experiments with NO3 radicals (1.2 to 1.6 on average for particles > 100 nm). Such results highlighted potential differences in the chemical composition of the SOA, as well as probably in their morphology, according to the particle size. Three times lower SOA formation yields were obtained with NO3 compared to OH. The yields of PAH SOA (18 to 76 %) were 5 to 6 times higher than those obtained for furans (3–12 %). While furan SOA showed low or negligible light absorption properties, PAH SOA was found to have a significant impact in the UV-Visible region, implying a significant contribution to atmospheric brown carbon (BrC). No increase in the MAC values was observed from OH to NO3 oxidation processes, probably due to a low formation of nitrogen-containing chromophores through homogeneous gas phase oxidation processes with NO3 only (without NOx). Overall, the results obtained in this work demonstrated that PAHs are significant precursors of SOA emitted by biomass burning, through both, day- and nighttime processes, and have a substantial impact on the aerosol light absorption properties and so probably on climate. [ABSTRACT FROM AUTHOR]

Designing a stable interphase with lithium (Li) dendrite suppressing ability is a surging demand for high-energy-density Li metal batteries (LMBs). Here, a hybrid inorganic–organic interphase is achieved on a Li anode, on which the nanoscale phase separation between antimony nucleation sites and an interconnected Li+ conducting polymer matrix endows the Li growing behavior with high uniformity and stability, resulting in a long lifespan of LMB over 500 cycles with a practical capacity of ∼2.5 mA h cm−2. [ABSTRACT FROM AUTHOR]

Gaseous promotors have readily been adopted during the direct synthesis of graphene over insulators to enhance the growth quality and/or boost the growth rate. The understanding of the real functions of carbon-containing promotors has still remained elusive. In this study, we identify the critical roles of a representative CO2 promotor played in the direct growth of graphene. The comparative experimental trials validate CO2 as an effective modulator to decrease graphene nucleation density, improve growth kinetics, and mitigate adlayer formation. The first-principles calculations illustrate that the generation of gas-phase OH species in CO2-assisted system helps decrease the energy barriers of CH4 decomposition and carbon attachment to the growth front, which might be the key factor to allow high-quality direct growth. Such a CO2-promoted strategy enables the conformal coating of graphene film over curved insulators, where the sheet resistance of grown graphene on quartz reaches as low as 1.26 kΩ·sq−1 at an optical transmittance of ∼ 95.8%. The fabricated endoscope lens based on our conformal graphene harvests an apoptosis of 82.8% for noninvasive thermal therapy. The work presented here is expected to motivate further investigations in the controllable growth of high-quality graphene on insulating substrates. [ABSTRACT FROM AUTHOR]

China has been promoting the internationalisation of the RMB for two decades. As a result, its offshore foreign exchange market has been substantially revitalised, despite that China's capital market remains partially open. The movements of offshore exchange rates can provide crucial clues to understanding the offshore market structure and the effects of interventions by Chinese monetary authorities. Using the GARCH-MIDAS model, this paper examines how the degree of openness and economic fundamentals – both observed and unobserved – affect the long-term volatility of offshore exchange rates. We find that, first, trade openness attenuates the long-term volatility, while financial openness has no effect. Specifically, the use of bilateral currency swap agreements and the relaxation of capital control are associated with lower volatility, while stock market connect programs tend to increase the volatility. Second, observed fundamentals, including relative measures for growth, interest rate, and money supply, have significant negative effects on offshore volatility. Third, although economic policy uncertainty and market risk affect long-term volatility, liquidity does not appear to be a culprit of volatility. In terms of FX interventions, direct intervention decreases the volatility, while oral intervention increases volatility. [ABSTRACT FROM AUTHOR]

Background: Aedes aegypti is a vector that transmits various viral diseases, including dengue and Zika. The radiation-based sterile insect technique (SIT) has a limited effect on mosquito control because of the difficulty in irradiating males without reducing their mating competitiveness. In this study, the insect sex pheromone heptacosane was applied to Ae. aegypti males to investigate whether it could enhance the mating competitiveness of irradiated males. Methods: Heptacosane was smeared on the abdomens of Ae. aegypti males that were allowed to mate with untreated virgin females. The insemination rate was used to assess the attractiveness of heptacosane-treated males to females. The pupae were irradiated with different doses of X-rays and γ-rays, and the emergence, survival time, egg number, and hatch rate were detected to find the optimal dose of X-ray and γ-ray radiation. The males irradiated at the optimal dose were smeared with heptacosane, released in different ratios with untreated males, and mated with females. The effect of heptacosane on the mating competitiveness of irradiated mosquitoes was then evaluated by the hatch rate, induced sterility, and mating competitiveness index. Results: Applying heptacosane to Ae. aegypti males significantly increased the insemination rate of females by 20%. Pupal radiation did not affect egg number but significantly reduced survival time and hatch rate. The emergence of the pupae was not affected by X-ray radiation but was affected by γ-ray radiation. Pupae exposed to 60 Gy X-rays and 40 Gy γ-rays were selected for subsequent experiments. After 60 Gy X-ray irradiation or 40 Gy γ-ray irradiation, the average hatch rate was less than 0.1%, and the average survival time was more than 15 days. Moreover, at the same release ratio, the hatch rate of the irradiated group perfumed with heptacosane was lower than that of the group without heptacosane. Conversely, the male sterility and male mating competitiveness index were significantly increased due to the use of heptacosane. Conclusions: The sex pheromone heptacosane enhanced the interaction between Ae. aegypti males and females. Perfuming males irradiated by X-rays or γ-rays with heptacosane led to a significant increase in mating competitiveness. This study provided a new idea for improving the application effect of SIT. [ABSTRACT FROM AUTHOR]

Targeting of MAP kinase pathways by BRAF inhibitors has evolved as a key therapy for BRAF-mutated melanoma. However, it cannot be applied for BRAF-WT melanoma, and also, in BRAF-mutated melanoma, tumor relapse often follows after an initial phase of tumor regression. Inhibition of MAP kinase pathways downstream at ERK1/2, or inhibitors of antiapoptotic Bcl-2 proteins, such as Mcl-1, may serve as alternative strategies. As shown here, the BRAF inhibitor vemurafenib and the ERK inhibitor SCH772984 showed only limited efficacy in melanoma cell lines, when applied alone. However, in combination with the Mcl-1 inhibitor S63845, the effects of vemurafenib were strongly enhanced in BRAF-mutated cell lines, and the effects of SCH772984 were enhanced in both BRAF-mutated and BRAF-WT cells. This resulted in up to 90% loss of cell viability and cell proliferation, as well as in induction of apoptosis in up to 60% of cells. The combination of SCH772984/S63845 resulted in caspase activation, processing of poly (ADP-ribose) polymerase (PARP), phosphorylation of histone H2AX, loss of mitochondrial membrane potential, and cytochrome c release. Proving the critical role of caspases, a pan-caspase inhibitor suppressed apoptosis induction, as well as loss of cell viability. As concerning Bcl-2 family proteins, SCH772984 enhanced expression of the proapoptotic Bim and Puma, as well as decreased phosphorylation of Bad. The combination finally resulted in downregulation of antiapoptotic Bcl-2 and enhanced expression of the proapoptotic Noxa. In conclusion, combined inhibition of ERK and Mcl-1 revealed an impressive efficacy both in BRAF-mutated and WT melanoma cells, and may thus represent a new strategy for overcoming drug resistance. [ABSTRACT FROM AUTHOR]

Severe lithium (Li) dendrite growth caused by the uneven overpotential deposition is a formidable challenge for high energy density Li metal batteries (LMBs). Herein, we investigate a synergetic interfacial kinetic to regulate Li deposition behavior and stabilize Li metal anode. Through constructing Li alloying matrix with a bi‐functional silver (Ag)‐Li3N blended interface, fast Li+ conductivity and high Li affinity can be achieved simultaneously, resulting in both decreased Li nucleation and mass transfer‐controlled overpotentials. Beyond these properties, a more important feature is demonstrated herein; that is, the inward diffusion depth of the Li adatoms inside of the Ag site can be restricted by the Li+ solvation structure in a highly coordinating environment. The latter feature can ensure the durability of the operational Ag sites, thereby elongating the Li protection ability of the Ag‐Li3N interface greatly. This work provides a deep insight into the synergetic effect of functional alloying structure and Li+ solvation mediated interfacial kinetic on Li metal protection. [ABSTRACT FROM AUTHOR]

The mosquito Aedes albopictus can transmit various arboviral diseases, posing a severe threat to human health. As an environmentally friendly method, sterile insect technology (SIT) is considered an alternative to traditional methods such as chemical pesticides to control Ae. albopictus. In SIT, the sterility of male mosquitoes can be achieved by γ-ray or X-ray radiation. Compared with γ-rays, X-rays are easier to obtain, cheaper, and less harmful. However, there is a lack of comparative assessment of these two types of radiation for SIT under the same controlled conditions. Here, we compared the effects of X-ray and γ-ray radiation on the sterility of Ae. albopictus males under laboratory-controlled conditions. Neither type of radiation affected the number of eggs but significantly reduced the survival time and hatch rate. The same dose of γ-rays caused a higher sterility effect on males than X-rays but had a more significant impact on survival. However, X-rays could achieve the same sterility effect as γ-rays by increasing the radiation dose. For example, X-rays of 60 Gy induced 99% sterility, similar to γ-rays of 40 Gy. In the test of male mating competitiveness, the induced sterility and the male mating competitiveness index were also identical at the same release ratio (sterile males/fertile males). At a release ratio of 7:1, nearly 80% of eggs failed to hatch. Sterile males produced by X-ray and γ-ray radiation had similar male competitiveness in competition with field males. In conclusion, a higher dose of X-rays is required to achieve the same sterility effect, compared to γ-rays. When γ-rays are not readily available, high-dose X-rays can be used instead. This study provides data supporting the selection of more suitable radiation for the field release of sterile male mosquitoes. [ABSTRACT FROM AUTHOR]

Suppressing lithium (Li) dendrite growth is a central issue for achieving stable Li metal batteries (LMBs). Here, we propose a binary alloy interface that consists of Ag inner nucleation cores and Zn outer diffusion shells through which a Li solubility gradient is created appropriately to enable simultaneous high lithiophilicity and stability. These merits provide the superior cycling stability of the as-generated Li–Ag–Zn electrode compared with the bare Li or Li–Ag counterparts, resulting in the long-term cycling stability of LMBs. [ABSTRACT FROM AUTHOR]

Clinically oriented deep learning algorithms, combined with large-scale medical datasets, have significantly promoted computer-aided diagnosis. To address increasing ethical and privacy issues, Federated Learning (FL) adopts a distributed paradigm to collaboratively train models, rather than collecting samples from multiple institutions for centralized training. Despite intensive research on FL, two major challenges are still existing when applying FL in the real-world medical scenarios, including the performance degradation (i.e., retrogress) after each communication and the intractable class imbalance. Thus, in this paper, we propose a novel personalized FL framework to tackle these two problems. For the retrogress problem, we first devise a Progressive Fourier Aggregation (PFA) at the server side to gradually integrate parameters of client models in the frequency domain. Then, at the client side, we design a Deputy-Enhanced Transfer (DET) to smoothly transfer global knowledge to the personalized local model. For the class imbalance problem, we propose the Conjoint Prototype-Aligned (CPA) loss to facilitate the balanced optimization of the FL framework. Considering the inaccessibility of private local data to other participants in FL, the CPA loss calculates the global conjoint objective based on global imbalance, and then adjusts the client-side local training through the prototype-aligned refinement to eliminate the imbalance gap with such a balanced goal. Extensive experiments are performed on real-world dermoscopic and prostate MRI FL datasets. The experimental results demonstrate the advantages of our FL framework in real-world medical scenarios, by outperforming state-of-the-art FL methods with a large margin. The source code is available at https://github.com/CityU-AIM-Group/PRR-Imbalance https://github.com/CityU-AIM-Group/PRR-Imbalance. [ABSTRACT FROM AUTHOR]

Neuropathic pain is a distressing medical condition with few effective treatments. The role of Vascular endothelial growth factor A (VEGFA) in inflammation pain has been confirmed in many researches. However, the mechanism of VEGFA affects neuropathic pain remains unclear. In this study, we demonstrated that VEGFA plays an important role in spare nerve injury (SNI)-induced neuropathic pain, which is mediated by enhanced expression and colocalized of VEGFA, p-AKT and TRPV1 in SNI-induced neuropathic pain model. Soluble VEGFR1 (sFlt1) not only relieved mechanical hyperalgesia and the expression of inflammatory markers, but ameliorated the expression of VEGFA, VEGFR2, p-AKT, and TRPV1 in spinal cord. However, these effects of sFlt1 can be blocked by rpVEGFA and by 740 Y-P. Therefore, our study indication that targeting VEGFA with sFlt1 reduces neuropathic pain development via the AKT/TRPV1 pathway in SNI-induced nerve injury. This study elucidates a new therapeutic target for neuropathic pain. [ABSTRACT FROM AUTHOR]

Challenges from high‐energy‐density storage applications have boosted the pursuit of designing high‐rate and low‐temperature lithium (Li) metal batteries (LMBs). Formulating high‐concentration electrolytes (HCEs) with a high transference number (t+) is an alternative solution to satisfy these demands. However, the implementation of HCEs is impeded by their lower ionic conductivity, higher viscosity, poorer wettability, and higher melting point, which are harmful to the practical applications. Herein, an anionic coordination manipulation strategy is proposed to break the constraints presented by HCEs. By manipulating the anionic species with different coordinating abilities, a high t+ up to 0.9 can be achieved even in the low‐concentration electrolytes of 1 mol L−1. By further forming a multilayer solvation structure in the anion manipulated electrolyte using non‐polar diluents, high Li Coulombic efficiency superior to 99% can be maintained under a high current density of 3 mA cm−2, and much‐improved performance is also demonstrated in high‐loading Li metal pouch cells. Furthermore, when applying multilayer solvated structure in electrolyte engineering, Li metal anodes at subzero temperature and LMBs at 0 °C also exhibit impressive cycling stability. This work provides a new guideline for designing advanced electrolytes for high‐rate LMBs under practical conditions. [ABSTRACT FROM AUTHOR]

As a prevention tool for mosquito-borne diseases, mosquito repellents have received substantial attention. To make a convincing recommendation for repellent products to Chinese consumers, we compared the protection time (landing time and probing time) of the 26 best-selling commercial repellents in the Chinese market in a controlled laboratory environment. The data were analyzed by one-way ANOVA. Meanwhile, prices and favorable rates of repellents are also taken into consideration. In our study, N, N-diethyl-m-toluamide (DEET)-based products provided the longest protection time (0.5–3.88 h landing time and/or 1–5.63 h probing time) and lower prices (13.9–21.9 yuan) than other components (ethyl butylacetylaminopropionate (IR3535), picaridin, and botanical. Among the 26 selected products, only 17 repellents showed repellency, and the best repellent was Green Jungle (15% DEET), with a mean (±SD) landing and/or probing time of 3.88 ± 1.65 h and/or 5.63 ± 0.36 h. For botanicals, only ICE King, OMNIbaby, and Ren He showed a little repellency. Autan (20% picaridin) performed best in the picaridin group. Run Ben (7% IR3535) stood out from the IR3535 group. In conclusion, DEET repellent is highly recommended to consumers. The combination of botanicals and synthesized chemicals is a new prospect for eco-friendly repellents. [ABSTRACT FROM AUTHOR]

Histone deacetylases (HDACs) are key enzymes in epigenetics and promising targets for anticancer therapy. Although several drugs targeting HDAC have been approved for the treatment of tumors, their clinical use has been limited by their deleterious side effects and poor efficacy. Herein, we discover four potent HDAC inhibitors through pharmacophore model screening and molecular docking. These compounds are able to bind HDACs 1, 3, and 6 with nanomolar affinity. Among them, compound 3 shows greater inhibitory effect on HDACs 1, 3, and 6 than that of vorinostat (SAHA). Evaluation of anticancer activity indicates that compound 3 significantly inhibits the growth of solid cancer cells including HGC‐27, AGS, MDA‐MB‐231, A549, MCF‐7, and H460 cells. In vivo anticancer study suggests that compound 3 can also markedly inhibit the growth of HGC‐27 cells‐derived xenograft, with no observable toxicity. These findings suggest that compound 3 may be as a potential HDAC‐targeting inhibitor for solid tumor therapy. [ABSTRACT FROM AUTHOR]

Designing metal oxide hosts with multiple lithophilic sites has emerged as a promising strategy to stabilize lithium (Li) metal anode for Li metal batteries (LMBs). Through lowering Li nucleation overpotentials, metal‐oxide‐derived lithiophilic frameworks can guide uniform Li deposition. However, lithiophilic sites suffer from failure upon cycling due to the structural collapse, limiting their durability for practical applications. Herein, a heterointerfacing strategy is reported to stabilize the alloy‐type lithiophilic sites of zinc. Nondurable zinc oxide is closely jointed with durable cobalt oxide, forming a unique bimetallic oxide heterointerface that possesses both favorable Li affinity and high structural integrity. The roles of individual components and the interface are both investigated. The heterostructured framework serves as a buffer layer at the anode/electrolyte interface, enabling stable regulation of Li plating and stripping. The as‐modified Li metal anode achieves high coulombic efficiency and long‐term stability in practical LMBs. This work sheds a light on designing durable lithiophilic hosts for LMBs under practical conditions. [ABSTRACT FROM AUTHOR]

Background: Studies related to the SARS-CoV-2 spikes in the past few months, while there are limited studies on the entire outbreak-suppressed cycle of COVID-19. We estimate the cause-specific excess mortality during the complete circle of COVID-19 outbreak in Guangzhou, China, stratified by sociodemographic status.Methods: Guangzhou Center for Disease Control Prevention provided the individual data of deaths in Guangzhou from 1 January 2018 through 30 June 2020. We applied Poisson regression models to daily cause-specific mortality between 1 January 2018 and 20 January 2020, accounting for effects of population size, calendar time, holiday, ambient temperature and PM2.5. Expected mortality was estimated for the period from 21 January through 30 June 2020 assuming that the effects of factors aforementioned remained the same as described in the models. Excess mortality was defined as the difference between the observed mortality and the expected mortality. Subgroup analyses were performed by place of death, age group, sex, marital status and occupation class.Results: From 21 January (the date on which the first COVID-19 case occurred in Guangzhou) through 30 June 2020, there were three stages of COVID-19: first wave, second wave, and recovery stage, starting on 21 January, 11 March, and 17 May 2020, respectively. Mortality deficits were seen from late February through early April and in most of the time in the recovery stage. Excesses in hypertension deaths occurred immediately after the starting weeks of the two waves. Overall, we estimated a deficit of 1051 (95% eCI: 580, 1558) in all-cause deaths. Particularly, comparing with the expected mortality in the absence of COVID-19 outbreak, the observed deaths from pneumonia and influenza substantially decreased by 49.2%, while deaths due to hypertension and myocardial infarction increased by 14.5 and 8.6%, respectively. In-hospital all-cause deaths dropped by 10.2%. There were discrepancies by age, marital status and occupation class in the excess mortality during the COVID-19 outbreak.Conclusions: The excess deaths during the COVID-19 outbreak varied by cause of death and changed temporally. Overall, there was a deficit in deaths during the study period. Our findings can inform preparedness measures in different stages of the outbreak. [ABSTRACT FROM AUTHOR]

A growing body of research suggests that inflammatory insult contributes to the etiology of central nervous system diseases, such as depression, Alzheimer's disease, and so forth. However, the effect of prenatal systemic inflammation exposure on offspring brain development and cerebral susceptibility to inflammatory insult remains unknown. In this study, we utilized the prenatal inflammatory insult model in vivo and the neuronal damage model in vitro. The results obtained show that prenatal maternal inflammation exacerbates LPS-induced memory impairment, neuronal necrosis, brain inflammatory response, and significantly increases protein expressions of COX-2, DP2, APP, and Aβ, while obviously decreasing that of DP1 and the exploratory behaviors of offspring rats. Meloxicam significantly inhibited memory impairment, neuronal necrosis, oxidative stress, and inflammatory response, and down-regulated the expressions of APP, Aβ, COX-2, and DP2, whereas significantly increased exploring behaviors and the expression of DP1 in vivo. Collectively, these findings suggested that maternal inflammation could cause offspring suffering from inflammatory and behavioral disorders and increase the susceptibility of offspring to cerebral pathological factors, accompanied by COX-2/PGD-2/DPs pathway activation, which could be ameliorated significantly by COX-2 inhibitor meloxicam treatment. [ABSTRACT FROM AUTHOR]

Objectives: To evaluate the clinical effect of magnesium aluminum carbonate combined with rabeprazolebased triple therapy in the treatment of patients with Helicobacter pylori-positive gastric ulcer associated with hemorrhage. Methods: A total of 80 patients with Helicobacter pylori-positive gastric ulcer associated with hemorrhage admitted to the Baoding First Central Hospital from January 2019 to December 2020 were selected and randomly divided into two groups, with 40 cases in each group. The control group were given rabeprazolebased triple therapy, while the experimental group were treated with magnesium aluminum carbonate on the basis of the control group. The changes of symptoms and signs such as abdominal pain, abdominal distension, nausea, vomiting and hematochezia were compared between the two groups before and after treatment. Serological changes of the gastric mucosal microenvironment, such as the serum levels of extracellular regulatory protein kinase (ERK), superoxide dismutase (SOD) and epidermal growth factor receptor (EGFR), were compared between the two groups. Moreover, the differences in the results of gastroscopy between the two groups before and after treatment were compared and analyzed. Results: The scores of gastrointestinal symptoms in the experimental group after treatment were significantly improved compared with the control group (p=0.00). The levels of ERK and EGFR in the experimental group were significantly lower than those in the control group (ERK, p=0.01; EGRF, p=0.00), while the level of SOD was significantly increased (p=0.02). After treatment, the total effective rate of ulcer healing in the experimental group was 82.5%, which was significantly better than 60% in the control group (p=0.03). After treatment, moderate to severe gastric mucosal inflammation in the experimental group decreased to 10%, significantly better than that in the control group (decreased to 30%) (p=0.03). Conclusion: Magnesium aluminum carbonate combined with rabeprazole-based triple therapy is preferred for the treatment of patients with Helicobacter pylori-positive gastric ulcer associated with hemorrhage. With such a highly effective treatment regimen, the internal environment and blood supply of gastric mucosal cells can be significantly improved, gastric mucosal inflammation and gastrointestinal symptoms can be ameliorated, and the healing of ulcer surfaces can be accelerated. [ABSTRACT FROM AUTHOR]

The COVID-19 pandemic has brought a new appreciation of the importance of airborne disease transmission. Airborne transmission is caused by the inhalation of pathogen-containing aerosols that are produced by an infected person.1 Before the pandemic, the main accepted airborne diseases were tuberculosis, measles, and chickenpox. In principle, surface touch (fomites) can also lead to infection, although with low probability.6 THE EMISSION PLUS DILUTION DOMAINS OF AIRBORNE TRANSMISSION There are four spatial domains of airborne transmission: Indoors in close proximity, where the respiratory jet of the infected is inhaled by the susceptible with limited dilution. In terms of characterizing a new potentially airborne disease, the attack rate of different superspreading events can be plotted versus I H i SB r sb similar to Figure 1A. This provides a rapid empirical characterization of the potential of a given disease for shared-room airborne transmission. [Extracted from the article]

RNA interference (RNAi) is a major form of antiviral defense in host cells, and Ago2 and Dicer are the major proteins of RNAi. The Senecavirus A (SVA) is a reemerging virus, resulting in vesicular lesions in sows and a sharp decline in neonatal piglet production. In this study, CRISPR/Cas9 technology was used to knock out Ago2 and Dicer genes in BHK-21 cell lines used for SVA vaccine production. Cell clones with homozygous frameshift mutations of Ago2 and Dicer genes were successfully identified. The two knockout cell lines were named BHK-DicerΔ- and BHK-Ago2Δ-. Results showed that the two genes' knockout cell lines were capable of stable passage and the cell growth rate did not change significantly. The replication rate and virus titers of SVA were significantly increased in knockout cell lines, indicating that RNAi could inhibit SVA replication. In addition, compared with normal cells, autophagy was significantly enhanced after SVA-infected knockout cell lines, while there was no significant difference in autophagy between the knockout and normal cell lines without SVA. The results confirmed that SVA could enhance the autophagy in knockout cells and promote viral replication. The two knockout cell lines can obtain viruses with high viral titers and have good application prospects in the production of SVA vaccine. At the same time, the RNAi knockout cell lines provide convenience for further studies on RNAi and SVA resistance to RNAi, and it lays a foundation for further study of SVA infection characteristics and screening of new therapeutic drugs and drug targets. [ABSTRACT FROM AUTHOR]

Background and Objective: COVID-19 has struck our society as a great calamity, and the need for effective anti-viral drugs is more urgent than ever. Papain-like protease (PLpro) of SARS CoV-2 plays important roles in virus maturation, dysregulation of host inflammation, and antiviral immune responses, which is being regarded as a promising druggable target for the treatment of COVID-19. Here, we carried out a combined screening approach to identify novel and highly potent PLpro inhibitors for the treatment of COVID-19. Methods: We used a combined screening approach of structure-based pharmacophore modeling and molecular docking to screen an in-house database containing 35,000 compounds. SARS CoV-2 PLpro inhibition assay was used to carry out the biological evaluation of hit compounds. Molecular dynamics (MD) simulations were conducted to check the stability of the PLpro-hit complexes predicted by molecular docking. Results: We found that four hit compounds showed excellent inhibitory activities against PLpro with IC50 values ranging from 0.6 to 2.4 μM. Among them, the most promising compound, hit 2 is the best PLpro inhibitor and its inhibitory activity was about 4 times higher than that of the positive control (GRL0617). The study of MD simulations indicated that four hits could bind stably to the active site of PLpro. Further study of interaction analysis indicated that hit 2 could form hydrogen-bond interactions with the key amino acids such as Gln269 and Asp164 in the PLpro-active site. Conclusion: Hit 2 is a novel and highly potent PLpro inhibitor, which will open the way for the development of clinical PLpro inhibitors for the treatment of COVID-19. [ABSTRACT FROM AUTHOR]

Graphene films, fabricated by chemical vapor deposition (CVD) method, have exhibited superiorities in high crystallinity, thickness controllability, and large‐scale uniformity. However, most synthesized graphene films are substrate‐dependent, and usually fragile for practical application. Herein, a freestanding graphene film is prepared based on the CVD route. By using the etchable fabric substrate, a large‐scale papyraceous freestanding graphene fabric film (FS‐GFF) is obtained. The electrical conductivity of FS‐GFF can be modulated from 50 to 2800 Ω sq−1 by tailoring the graphene layer thickness. Moreover, the FS‐GFF can be further attached to various shaped objects by a simple rewetting manipulation with negligible changes of electric conductivity. Based on the advanced fabric structure, excellent electrical property, and high infrared emissivity, the FS‐GFF is thus assembled into a flexible device with tunable infrared emissivity, which can achieve the adaptive camouflage ability in complicated backgrounds. This work provides an infusive insight into the fabrication of large‐scale freestanding graphene fabric films, while promoting the exploration on the flexible infrared camouflage textiles. [ABSTRACT FROM AUTHOR]

Graphene films, fabricated by chemical vapor deposition (CVD) method, have exhibited superiorities in high crystallinity, thickness controllability, and large‐scale uniformity. However, most synthesized graphene films are substrate‐dependent, and usually fragile for practical application. Herein, a freestanding graphene film is prepared based on the CVD route. By using the etchable fabric substrate, a large‐scale papyraceous freestanding graphene fabric film (FS‐GFF) is obtained. The electrical conductivity of FS‐GFF can be modulated from 50 to 2800 Ω sq−1 by tailoring the graphene layer thickness. Moreover, the FS‐GFF can be further attached to various shaped objects by a simple rewetting manipulation with negligible changes of electric conductivity. Based on the advanced fabric structure, excellent electrical property, and high infrared emissivity, the FS‐GFF is thus assembled into a flexible device with tunable infrared emissivity, which can achieve the adaptive camouflage ability in complicated backgrounds. This work provides an infusive insight into the fabrication of large‐scale freestanding graphene fabric films, while promoting the exploration on the flexible infrared camouflage textiles. [ABSTRACT FROM AUTHOR]

Chemoresistance is a major therapeutic obstacle in the treatment of breast cancer. Therefore, how to overcome chemoresistance is a problem to be solved. Here, a glutathione (GSH)/cathepsin B (CB) dual-controlled nanomedicine formed by cyclic disulfide-bridged peptide (cyclic-1a) as a potent anticancer agent is reported. Under the sequential treatment of GSH and CB, cyclic-1a can efficiently self-assemble into nanofibers. In vitro studies show that cyclic-1a promotes the apoptosis of MCF-7/DOX cells by inducing the cleavages of caspase-3 and PARP. In vivo studies confirm that cyclic-1a significantly inhibits the progression of MCF-7/DOX cells-derived xenograft in nude mice, with no obvious adverse reactions. This study provides a paradigm of GSH/CB dual-controlled nanomedicine for high-efficacy and low-toxic DOX-resistant breast cancer therapy. [ABSTRACT FROM AUTHOR]