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This study aims to explain the effect of adding the bioactive substance (alpha enzyme) to the electrolyte solution using electrochemical deposition. Through which copper nanoparticles are manufactured, the originality of the research lies in the presence of this addition as a new method in manufacturing nanoparticles in an electrochemical manner, as the alpha-amylase enzyme is extracted from camel saliva, and the product has been diagnosed using (EDX) and scanning electron microscope (FE-SEM) techniques. , Dynamic Light Scattering (DLS) technology, and Zeta potential. The proposed method is an easy, inexpensive, and environmentally friendly method where the alpha enzyme was used as a feedstock at concentrations of (0.25, 0.50, 0.57, and 1) g added to a solution containing the ideal sample obtained through the electrochemical precipitation process before adding the enzyme, as the solution before The addition process contains concentrated sulfuric acid (H2SO4) at concentrations of (20, 30, 40, 50 and 60) g/ml. The regular shape and stable distribution can be observed after the addition compared to the shape of the particles before the addition in terms of shape and size. The process was carried out under constant conditions, including the current. Direct, voltage and temperature, and after the addition process, sulfuric acid was dispensed with, while the process conditions with the addition were at a temperature of 37 degrees Celsius and an incubation period that lasted a full hour before the electrodeposition process was carried out in accordance with the enzyme activity conditions, where a nanosized copper powder of a granular size was obtained. Approximately 44 nanometers. It is worth noting that the nanoparticle size was modulated using the experimental conditions, e.g., pH, reducing step, enzyme amount, or incubation time. This controlled synthesis allows the preparation of CuNP bionanoparticles at Cu 3.13 powder at a concentration of 80 g CuSO4 + 0.50 α-amylase.

This study aimed to investigate the level of student engagement in online courses in the Instructional and Learning Technologies Department (ILT) at the Sluat Sultan Qaboos University (SQU) during the COVID-19 pandemic. The study also explored the challenges that impeded student engagement in online courses. The study followed a descriptive design using a purposive sample of 111 students and five instructors. Mixed methods were used for gathering the data of the study. The level of student engagement was measured through the survey of student engagement and the analysis of Moodle reports. Moreover, semi-structured interviews were conducted with six students and five instructors to investigate the challenges that hindered student engagement. Although, the study revealed some challenges that impeded student engagement in online courses such as, heavy workload on students, students' inability to manage their study time, low-level of class participation, and increase of instructors' burdens, the findings of the study indicated that the ILT students still showed a high level of engagement. Thus, the revealed challenges would help educators to plan for better strategies for student engagement. The study presents some recommendations and avenues for further research.

Summary: Background: We compared the efficacy and safety profiles of ainuovirine (ANV), a new-generation non-nucleoside reverse transcriptase inhibitor (NNRTI), with boosted elvitegravir (EVG), both coformulated with two nucleoside reverse transcriptase inhibitors (NRTIs), in people living with HIV-1 (PLWH) who had achieved virological suppression on previous NNRTI-based antiretroviral (ARV) regimen. Methods: This study was a multi-centre, randomised, double-blind, active-controlled, non-inferiority trial recruiting PLWH from 10 clinical centres across China. Main inclusion criteria included age of 18–65 years (inclusive), and stably staying on an ARV regimen combining an NNRTI with a two-drug NRTI backbone for at least 12 months. Eligible participants must have maintained plasma HIV-1 ribonucleic acid (RNA) titre below 50 copies per mL confirmed on two successive tests at an interval of at least one month prior to randomisation. Participants were randomly assigned to receive ANV 150 mg plus lamivudine (3TC) 300 mg, and tenofovir disoproxil fumarate (TDF) 300 mg (ANV/3TC/TDF), or cobicistat (Cobi) 150 mg boosted EVG plus emtricitabine (FTC) 200 mg, and tenofovir alafenamide (TAF) 10 mg. The primary efficacy endpoint was the proportion of participants with HIV-1 RNA titre at 50 copies per mL or above at week 48 using the US Food and Drug Administration snapshot algorithm, with a non-inferiority margin of 4 percentage points at a two-side 95% confidence level. This trial is active, but not recruiting, and is registered with Chinese Clinical Trial Registry (ChiCTR), number ChiCTR2100051605. Findings: Between October 2021 and February 2022, 923 patients were screened for eligibility, among whom 762 participants were randomized and had received at least one dose of ANV/3TC/TDF (n = 381) or EVG/Cobi/FTC/TAF (n = 381). At week 48, 7 (1.8%) participants on ANV/3TC/TDF and 6 (1.6%) participants on EVG/Cobi/FTC/TAF had plasma HIV-1 RNA titre at 50 copies per mL or above, including missing virological data within the time window (the Cochran-Mantel-Haenszel method, estimated treatment difference [ETD], 0.3%, 95% CI −1.6 to 2.1), establishing the non-inferiority of ANV/3TC/TDF to EVG/Cobi/FTC/TAF. The proportions of participants experiencing at least one treatment-emergent adverse events (AEs) were comparable between the two arms (97.6% versus 97.6%). A small proportion of participants discontinued study drug due to AEs (0.3% versus 0.3%). Serious AEs occurred in 11 (2.9%) participants on ANV/3TC/TDF and 9 (2.4%) participants on EVG/Cobi/FTC/TAF, respectively, none of which was considered related to study drug at the jurisdiction of the investigator. At week 48, participants on ANV/3TC/TDF showed a significantly less weight gain from baseline compared to those on EVG/Cobi/FTC/TAF (least square mean, 1.16 versus 2.05 kg, ETD −0.90 kg, 95% CI, −1.43 to −0.37). The changes in serum lipids from baseline also favoured ANV/3TC/TDF over EVG/Cobi/FTC/TAF. Interpretation: In virologically suppressed PLWH on previous NNRTI-based ARV regimen, switch to ANV/3TC/TDF resulted in less weight gain, and improved lipid metabolism while maintaining virological suppression non-inferior to that to EVG/Cobi/FTC/TAF. Funding: Jiangsu Aidea Pharmaceutical & the National “Thirteenth Five-year Period” Major Innovative Drugs Research and Development Key Project of the People's Republic of China Ministry of Science and Technology.

Abstract Background This updated systematic review and meta-analysis aims to evaluate the efficacy and safety of perioperative corticosteroid administration versus placebo for esophageal cancer patients following scheduled esophagectomy. Methods We searched databases through June 30, 2023. We included articles on randomized controlled trials (RCTs) comparing perioperative corticosteroid administration with placebo in esophageal cancer patients with esophagectomy. The outcomes were the death rate during hospitalization, length of hospital stay, and short-term complications. Risk ratios (RRs) and corresponding 95% confidence interval (CIs) for each estimated effect size were applied for dichotomous outcomes, and the mean difference (MD) and corresponding 95% CIs for each estimated effect size were applied for continuous outcomes. We used GRADE to evaluate the quality of each of the outcome and the level of recommendations. Results Nine RCTs with 508 participants were included in this study. Severe outcomes, including the length of hospital stay, leakage, mortality during the hospitalization period in the corticosteroid group was comparable to that in the control group, but positive effects of corticosteroid administration were observed on the length of intensive care unit stay (MD -3.1, 95% CI − 5.43 to − 0.77), cardiovascular disorders (RR 0.44, 95% CI 0.21–0.94) and other general complications (RR 0.49, 95% CI 0.29–0.85). Conclusions Peri-operative intravenous corticosteroid administration may reduce cardiovascular disorders, other general complications and the length of ICU stay without carrying severe outcomes. More high quality RCTs are warranted to further investigate the effects of corticosteroids on postoperative mortality and complications for esophageal cancer patients with esophagectomy. Systematic review registration Cochrane, registration number: 196.

Mobile applications are now being used for 21st-century learning, including alphabet learning. There are numerous mobile application products for online learning, particularly those relating to the alphabet ABC. It was revealed that previous mobile applications did not provide interactive activities that suited preschool students. Therefore, this study aims to develop Hooray! Hooray! ABC for learning the alphabet. This study employed Design and Development Research (DDR) as the research design, which is divided into three phases: Phase I - the needs of the application; Phase II - the design and development; and Phase III - the evaluation. ADDIE model is used as the instructional design to design and develop the mobile application. Two experts were chosen to validate the application. It was tested for usability and student performance on 35 preschool students. The results reveal that Hooray! Hooray! ABC can be used for learning the alphabet based on experts' agreement in terms of usefulness (96%), ease of use (97%), ease of learning (94%), and satisfaction (100%). In addition, the result shows that Hooray! Hooray! ABC can increase students' performance (t = 13.271, p = 0.00) in learning the alphabet, making it beneficial for preschool students, teachers, and schools. This study also acknowledged the limitations and future suggestions of this study.

Tea residue was used for preparing activated carbon (AC) which was used as an adsorbent to remove Ciprofloxacin (CIP) from synthetic contaminated water. This study investigates the physicochemical properties and adsorption efficiency of the prepared activated carbon. The activated carbon was prepared via two steps: Activation step using phosphoric acid (H3PO4) followed by carbonization at a temperature of 450 °C. Different factors were investigated to show their effects on the adsorption efficiency of (CIP). These factors were initial concentration of (CIP), pH, Absorption time, and adsorbent dosage. The maximum adsorption efficiency was 94.4% which was obtained when pH=8.75, contact time =454 min, adsorbent dosage =0.194 g/ 25 ml, and initial concentration of 200 ppm. The prepared activated carbon was characterized using Fourier transform infrared spectroscopy (FTIR), scanning electron microscopy (SEM), X-ray diffraction (XRD), and Brunauer-Emmett-Teller (BET). The prepared activated carbon was found to have a specific surface area of 774 m2/g. It was found that the Langmuir model well fit the adsorption isotherm of (CIP) on the prepared activated carbon. The produced activated carbon can adsorb Ciprofloxacin, with a maximum adsorption capacity of 256.41 mg g-1. A pseudo-second-order reaction model is effective at describing the kinetics of adsorption. The examination of adsorption thermodynamics reveals that the process of CIP adsorption on TAC is characterized by being both endothermic and spontaneous.

Abstract Background Although stimulating autophagy caused by UV has been widely demonstrated in skin cells to exert cell protection, it remains unknown the cellular events in UVA-treated retinal pigment epithelial (RPE) cells. Methods Human ARPE-19 cells were used to measure cell viability, mitochondrial reactive oxygen species (ROS), mitochondrial membrane potential (MMP), mitochondrial mass and lysosomal mass by flow cytometry. Mitochondrial oxygen consumption rate (OCR) was recorded using Seahorse XF flux analyzer. Confocal microscopic images were performed to indicate the mitochondrial dynamics, LC3 level, and AMPK translocation after UVA irradiation. Results We confirmed mitochondrial ROS production and DNA damage are two major features caused by UVA. We found the cell death is prevented by autophagy inhibitor 3-methyladenine and gene silencing of ATG5, and UVA induces ROS-dependent LC3II expression, LC3 punctate and TFEB expression, suggesting the autophagic death in the UVA-stressed RPE cells. Although PARP-1 inhibitor olaparib increases DNA damage, ROS production, and cell death, it also blocks AMPK activation caused by UVA. Interestingly we found a dramatic nuclear export of AMPK upon UVA irradiation which is blocked by N-acetylcysteine and olaparib. In addition, UVA exposure gradually decreases lysosomal mass and inhibits cathepsin B activity at late phase due to lysosomal dysfunction. Nevertheless, cathepsin B inhibitor, CA-074Me, reverses the death extent, suggesting the contribution of cathepsin B in the death pathway. When examining the role of EGFR in cellular events caused by UVA, we found that UVA can rapidly transactivate EGFR, and treatment with EGFR TKIs (gefitinib and afatinib) enhances the cell death accompanied by the increased LC3II formation, ROS production, loss of MMP and mass of mitochondria and lysosomes. Although AMPK activation by ROS-PARP-1 mediates autophagic cell death, we surprisingly found that pretreatment of cells with AMPK activators (A769662 and metformin) reverses cell death. Concomitantly, both agents block UVA-induced mitochondrial ROS production, autophagic flux, and mitochondrial fission without changing the inhibition of cathepsin B. Conclusion UVA exposure rapidly induces ROS-PARP-1-AMPK-autophagic flux and late lysosomal dysfunction. Pre-inducing AMPK activation can prevent cellular events caused by UVA and provide a new protective strategy in photo-oxidative stress and photo-retinopathy.

Fournier’s gangrene (FG), also known as necrotizing fasciitis, is a condition that affects the genitalia and perineum, resulting in the rapid development of necrosis and gangrene in infected tissues and potentially spreading to adjacent tissues, including the abdominal wall. It mainly affects males and requires prompt treatment to prevent potentially life-threatening complications. In Case 1, a 64-year-old man with type 2 diabetes was diagnosed with FG due to a scrotal skin injury after scratching his scrotal skin. The patient underwent radical debridement, treatment with broad-spectrum antibiotics, negative pressure wound treatment, and skin transplantation. In Case 2, a 79-year-old man suffered from a sebaceous cyst of the scrotum that had been scratched for seven days, resulting in black and necrotic skin of the scrotum. He was diagnosed with FG and underwent radical debridement and drainage of pus, followed by anti-infection treatment, negative pressure wound treatment, and skin transplantation. In Case 3, a 48-year-old male injured at the scrotum’s base developed swelling, pain, foul odor and pus discharge and was diagnosed with FG. The patient underwent emergency treatment, including incision and drainage of the scrotum and right lower abdominal wall abscess, as well as wound debridement. Ultimately, all three patients’ scrotal wounds returned to normal, but Case 2 was complicated by blood vessel thrombosis in both lower limbs. Early surgical debridement is a necessary intervention for FG, along with active postoperative anti-infection treatment and measures to prevent the occurrence of complications.

Recently, although stigma and mental health among patients with diabetes have garnered significant research attention, there are still limited investigations into the stigma and mental health of patients with erectile dysfunction (ED) and diabetes. In this study, we aimed to examine the stigma and mental health of patients with ED and diabetes to provide insights for improving the treatment and nursing of patients with ED and diabetes. We selected 82 patients with ED and diabetes and 82 patients with ED. Patients were evaluated using the Basic Information Scale, Symptom Checklist 90 (SCL-90) and Social Impact Scale (SIS). Patients with ED and diabetes had higher scores than the national norm in all dimensions of shame (p < 0.05), while patients with ED scored higher than the national norm in the dimensions of social exclusion, economic discrimination and internal shame (p < 0.05). Further, patients with ED and diabetes had higher scores of disease shame regarding social exclusion, internal shame and social isolation dimensions than patients with ED (p < 0.05). The score of interpersonal relationship factors of patients with ED was lower than that of the national norm (p < 0.05), while for patients with ED, the score of interpersonal relationship factors in patients’ SCL-90 was lower (p < 0.05) and the score of psychotic factors was higher than that of the national norm (p < 0.05). A positive correlation was observed between the paranoid factor score in the SCL-90 of patients with ED and diabetes, the social exclusion dimension score, and the total score in the sense of shame (p < 0.05). Both patients with ED and diabetes and patients with ED exhibited abnormally higher rates of SCL-90 scores, indicating the presence of psychological distress and urging the need to strengthen psychological care.

This study investigated how a group of twenty seven Wuhan citizens (coronavirus patients and their family member, medical staff, college students, social workers, teacher, journalist) employed metaphors to communicate about their experiences of COVID-19 pandemic through in-depth individual interviews. The analysis of metaphors captured the different kinds of emotional states and psychological conditions of the research participants, focusing on their mental imagery of COVID-19, extreme emotional experiences, and symbolic behaviors under the pandemic. The results show that multiple metaphors were used to construe emotionally-complex, isolating experiences of the COVID-19 pandemic. Most metaphorical narratives are grounded in embodied sensorimotor experiences such as body parts, batting, fighting, hit, weight, temperature, spatialization, motion, violence, light, and journey. Embodied metaphors were manifested in both verbal expressions and nonlinguistic behaviors (e.g., patients’ symptom of obsessive-compulsive behaviors). These results suggest that the bodily experiences of the pandemic, the environment, and the psychological factors combine to shape people’s metaphorical thinking processes.

The activation of microglia and the production of cytokines are key factors contributing to progressive neurodegeneration. Despite the well-recognized neuronal programmed cell death regulated by microglial activation, the death of microglia themselves is less investigated. Nucleotide-binding oligomerization domain, leucine-rich repeat-containing X1 (NLRX1) functions as a scaffolding protein and is involved in various central nervous system diseases. In this study, we used the SM826 microglial cells to understand the role of NLRX1 in lipopolysaccharide (LPS)-induced cell death. We found LPS-induced cell death is blocked by necrostatin-1 and zVAD. Meanwhile, LPS can activate poly (ADP-ribose) polymerase-1 (PARP-1) to reduce DNA damage and induce heme oxygenase (HO)-1 expression to counteract cell death. NLRX1 silencing and PARP-1 inhibition by olaparib enhance LPS-induced SM826 microglial cell death in an additive manner. Less PARylation and higher DNA damage are observed in NLRX1-silencing cells. Moreover, LPS-induced HO-1 gene and protein expression through the p62-Keap1-Nrf2 axis are attenuated by NLRX1 silencing. In addition, the Nrf2-mediated positive feedback regulation of p62 is accordingly reduced by NLRX1 silencing. Of note, NLRX1 silencing does not affect LPS-induced cellular reactive oxygen species (ROS) production but increases mixed lineage kinase domain-like pseudokinase (MLKL) activation and cell necroptosis. In addition, NLRX1 silencing blocks bafilomycin A1-induced PARP-1 activation. Taken together, for the first time, we demonstrate the role of NLRX1 in protecting microglia from LPS-induced cell death. The underlying protective mechanisms of NLRX1 include upregulating LPS-induced HO-1 expression via Nrf2-dependent p62 expression and downstream Keap1-Nrf2 axis, mediating PARP-1 activation for DNA repair via ROS- and autophagy-independent pathway, and reducing MLKL activation.

Calcium/calmodulin-dependent serine protein kinase (CASK) is a scaffold protein and plays critical roles in neuronal synaptic formation and brain development. Previously, CASK was shown to associate with EGFR to maintain the vulval cell differentiation in C. elegans. In this study, we explored the role of CASK in CHME3 microglial cells. We found that CASK silencing protects cells from H2O2-induced cell death by attenuating PARP-1 activation, mitochondrial membrane potential loss, reactive oxygen species production, and mitochondrial fission, but it increases oxidative phosphorylation. The PARP-1 inhibitor olaparib blocks H2O2-induced cell death, suggesting the death mode of parthanatos. CASK silencing also increases AKT activation but decreases AMPK activation under H2O2 treatment. Pharmacological data further indicate that both signaling changes contribute to cell protection. Different from the canonical parthanatos pathway, we did not observe the AIF translocation from mitochondria into the nucleus, suggesting a non-canonical AIF-independent parthanatos in H2O2-treated CHME3 cells. Moreover, we found that CASK silencing upregulates the EGFR gene and protein expression and increases H2O2-induced EGFR phosphorylation in CHME3 microglia. However, EGFR activation does not contribute to cell protection caused by CASK silencing. In conclusion, CASK plays a crucial role in microglial parthanatos upon H2O2 treatment via stimulation of PARP-1 and AMPK but the inhibition of AKT. These findings suggest that CASK might be an ideal therapeutic target for CNS disorders.

BackgroundMechanical thrombectomy (MT) is effective for acute ischemic stroke with large vessel occlusion (AIS-LVO) within an extended therapeutic window. However, successful reperfusion does not guarantee positive prognosis, with around 40–50% of cases yielding favorable outcomes. Preoperative prediction of patient outcomes is essential to identify those who may benefit from MT. Although machine learning (ML) has shown promise in handling variables with non-linear relationships in prediction models, its “black box” nature and the absence of ML models for extended-window MT prognosis remain limitations.ObjectiveThis study aimed to establish and select the optimal model for predicting extended-window MT outcomes, with the Shapley additive explanation (SHAP) approach used to enhance the interpretability of the selected model.MethodsA retrospective analysis was conducted on 260 AIS-LVO patients undergoing extended-window MT. Selected patients were allocated into training and test sets at a 3:1 ratio following inclusion and exclusion criteria. Four ML classifiers and one logistic regression (Logit) model were constructed using pre-treatment variables from the training set. The optimal model was selected through comparative validation, with key features interpreted using the SHAP approach. The effectiveness of the chosen model was further evaluated using the test set.ResultsOf the 212 selected patients, 159 comprised the training and 53 the test sets. Extreme gradient boosting (XGBoost) showed the highest discrimination with an area under the curve (AUC) of 0.93 during validation, and maintained an AUC of 0.77 during testing. SHAP analysis identified ischemic core volume, baseline NHISS score, ischemic penumbra volume, ASPECTS, and patient age as the top five determinants of outcome prediction.ConclusionXGBoost emerged as the most effective for predicting the prognosis of AIS-LVO patients undergoing MT within the extended therapeutic window. SHAP interpretation improved its clinical confidence, paving the way for ML in clinical decision-making.

Based on the modified gravity model and social network analysis method, the evolution characteristics and driving mechanism of logistics network spatial structure in the Zhengzhou metropolitan area (ZMA) from 2008 to 2019 are analyzed at a county (district) scale. Research findings reveal that the following: (1) The distribution of logistics links in ZMA counties (districts) has significant spatial heterogeneity, with a spatial pattern of “sparse in the east and dense in the west,” and the counties (districts) logistics links are concentrated in Zhengzhou. (2) The overall level of the logistics network density in ZMA is low, but it is fluctuating and rising. The overall realization is the logistics radiation effect. The logistics network layout’s core area is primarily concentrated in Zhengzhou’s main urban area and surrounding counties (districts), and the spatial scope is expanding and merging into one piece. The contact density of counties (districts) in the core area is high, whereas that between counties (districts) in the edge area is low. (3) With obvious spatial correlation characteristics, the logistics connection intensity of counties (districts) in ZMA plays a positive role in promoting the logistics connection intensity of surrounding areas. (4) The main factors that promote the formation of the local logistics network structure are the upgrading of industrial structure (ln Ind), the level of economic development (ln GDP), and the size of the population (ln Pop). The ln Ind and ln GDP restrain the logistics network structure and internal logistics network structure in the surrounding areas, whereas the ln Pop and government intervention (ln Gov) promote the formation of the external logistics network structure in the surrounding areas.

People commonly hypothesize that an independent variable follows a Gamma distribution in many areas,including hydrology,meteorology and insurance claim.Under the Gamma distribution assumption,Gamma regression model enables an outstanding fitting effect,compared with multivariate linear-regression model.Previous studies may be able to obtain a Gamma regression model trained only on a public dataset.However,when the datasets are provided by multiple parties,how to seek to address the problem of data privacy by training Gamma regression model without exchanging the data itself? A secure multi-party federated Gamma regression algorithm has been applied to this area.Firstly,the log-likelihood function is derived with the iterative method.Secondly,the link function is determined according to the fact,and the gradient updating strategy is constructed by the loss function.Finally,the parameters with homomorphic encryption are updated,then the training is completed.The model is tested on two public datasets,and the results show that under the premise of privacy protection our method can effectively use the value of multi-party data to generate Gamma regression model.The fitting performance of our method is better than that of Gamma regression model implements in a single part,and is close to the result yielded by centralized data learning model.

Rationale and objective: Demographic data collected about Canadian radiologists and trainees has been limited primarily to binary gender and geographic location. The purpose of this study was to investigate: (1) demographic characteristics of Canadian radiologists and trainees; (2) types of diversity important to radiologists; (3) relationship of radiologist demographics to practice characteristics; and (4) relationship of radiologist demographics to years in practice, (YIP). Materials and methods: French and English surveys were distributed via email through radiology associations and social media. Frequency counts of demographic variables were calculated, and chi-square and Fisher's Exact tests were performed to explore the relationships between demographic characteristics and role. Results: 611 individuals responded to the survey. 573 respondents were included in the analysis. 454 (78.8%) were practicing radiologists and 119 (20.7%) were residents/fellows. Half identified as women (50.4%). English was the primary language for most respondents. There was an association between role and sexual orientation (p = 0.02), visible minority (χ2 = 4.79, p

Diabetic retinopathy (DR) is a major cause of blindness in adult, and the accumulation of advanced glycation end products (AGEs) is a major pathologic event in DR. Methylglyoxal (MGO), a highly reactive dicarbonyl compound, is a precursor of AGEs. Although the therapeutic potential of metformin for retinopathy disorders has recently been elucidated, possibly through AMPK activation, it remains unknown how metformin directly affects the MGO-induced stress response in retinal pigment epithelial cells. Therefore, in this study, we compared the effects of metformin and the AMPK activator A769662 on MGO-induced DR in mice, as well as evaluated cytotoxicity, mitochondrial dynamic changes and dysfunction in ARPE-19 cells. We found MGO can induce mitochondrial ROS production and mitochondrial membrane potential loss, but reduce cytosolic ROS level in ARPE-19 cells. Although these effects of MGO can be reversed by both metformin and A769662, we demonstrated that reduction of mitochondrial ROS production rather than restoration of cytosolic ROS level contributes to cell protective effects of metformin and A769662. Moreover, MGO inhibits AMPK activity, reduces LC3II accumulation, and suppresses protein and gene expressions of MFN1, PGC-1α and TFAM, leading to mitochondrial fission, inhibition of mitochondrial biogenesis and autophagy. In contrast, these events of MGO were reversed by metformin in an AMPK-dependent manner as evidenced by the effects of compound C and AMPK silencing. In addition, we observed an AMPK-dependent upregulation of glyoxalase 1, a ubiquitous cellular enzyme that participates in the detoxification of MGO. In intravitreal drug-treated mice, we found that AMPK activators can reverse the MGO-induced cotton wool spots, macular edema and retinal damage. Functional, histological and optical coherence tomography analysis support the protective actions of both agents against MGO-elicited retinal damage. Metformin and A769662 via AMPK activation exert a strong protection against MGO-induced retinal pigment epithelial cell death and retinopathy. Therefore, metformin and AMPK activator can be therapeutic agents for DR.

OBJECTIVE:Cisplatin is a chemotherapeutic drug known to induce hearing loss. Although corticosteroids may help to mitigate the ototoxic side effects of cisplatin, there are complications associated with their systemic and prolonged use. The goal of this study is to test the efficacy of extended-release fluticasone propionate intracochlear implant particles to protect against cisplatin-induced hearing loss. METHODS:We used guinea pigs (n = 9) injected with cisplatin (IP, 12 mg/kg weight). Fluticasone particles were delivered to the cochlear scala tympani through the round window membrane into the right ears of the guinea pigs (left ears being used as a control) two weeks prior to cisplatin administration, and hearing function was evaluated by ABR and DPOAE before implantation, immediately before cisplatin administration, and 2 weeks after the challenge with cisplatin. Data was statistically evaluated using paired t-test analysis. RESULTS:No significant differences were observed in ABR threshold between control and implanted ears on day 14 (23.9 ± 2.3 dB vs. 25.6 ± 1.3 dB, P = 0.524), whereas the significant cisplatin-induced hearing loss in control animals (23.9 ± 2.3 dB at day 14 vs. 40.7 ± 2.5 dB at day 28, P ≤ 0.0001) was prevented in implanted animals (25.6 ± 1.3 dB at day 14 vs. 25.0 ± 3.1 at day 28, P ≥ 0.85). A similar, though not statistically significant, trend was observed in DPOAE responses in untreated ears (7.9 ± 5.8 dB at day14 vs. -0.5 ± 5.3 dB at day 28, P = 0.654) as compared to treatment (11.1 ± 3.4 dB at day 14 vs. 13.6 ± 4.8 dB at day 28, P = 0.733). CONCLUSION:These results suggest that fluticasone intracochlear implants are safe and able to provide effective otoprotection against cisplatin-induced hearing loss in the guinea pig model.

Whether amino acids act on cellular insulin signaling remains unclear. Here, the authors find that phenylalanine modifies insulin receptor beta (IRβ) and inactivates insulin signaling and glucose uptake and positively correlated with T2D onset.

Polyurea is widely used in marine anti-corrosion engineering because it has the physical advantages of high tensile strength, strong adhesion, excellent waterproof and anti-corrosion performance as well as mature construction technology. In this paper, the origin, characteristics and development direction of polyurea coating technology were first introduced, and then the applications of polyurea coating in the fields of concrete protection and metal protection in marine atmospheric environment and seawater environment in recent years were summarized, respectively. Aiming at the problems of coating performance degradation and failure caused by complex environmental factors such as temperature, corrosive medium erosion and collision during service, the research progress of new polyurea coatings was discussed, including the research on improving the performance of coatings such as corrosion resistance, wetting and hardness with organic and inorganic nanoparticles as fillers, and the research on new polyurea microcapsule coatings that could respond intelligently and repair microcracks independently, and the research on the processing and preparation technology of new self-healing materials such as electrospinning. Finally, the shortcomings and challenges of the current research on polyurea coating were pointed out, and the future research trend of polyurea coating in marine environment was prospected.

Electrocatalytic nitrate reduction to ammonia (NRA) seriously suffers from slow kinetics and low selectivity due to its eight-electron transfer process and complex reaction intermediates. Herein, Ru-based nanotubes (NTs) were designed to enhance the electrocatalytic activity of NRA. Significantly, the metallic Ru NTs endowed remarkable ammonia (NH3) yield rate (vNH3) of 40.6 mg h–1 mgcat.–1 at −1.20 V vs SCE and the highest NH3 Faradaic efficiency (FENH3) of 98.4% at −1.10 V vs SCE under ambient conditions, which are superior to those of RuO2 NTs (vNH3 : 0.52 mg h–1 mgcat.–1, FENH3 : 18.2%). Both experimental and theoretical results have proved that the Ru metallic state is more beneficial to N–O bond breaking and hydrogenation than the oxidized state, improving the kinetics and selectivity of NRA. [ABSTRACT FROM AUTHOR]

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ObjectiveInvestigate a new polymer-based drug coating suitability for safe intracochlear delivery and ability to maintain long-term physiologically active levels of the corticosteroid fluticasone propionate.Study designIn vitro dissolution study to evaluate release profiles of polymer-coated drug particles and in vivo studies using a guinea pig model to measure perilymph drug concentrations at specific time points after implantation with polymer-coated drug particles and evaluate their effect on hearing function.MethodsPolymer-coated fluticasone propionate (FP) particles were surgically implanted in guinea pigs through the round window membrane into the cochlear scala tympani. In the pilot study, pre- and post-op hearing thresholds were conducted on days 7, 14, and 42. In a second study, post-op hearing thresholds were conducted on days 90, 120, and 180. Perilymph drug concentrations were measured on the same time points.ResultsIn 15 of 16 animals from day 7 through day 90, drug levels were within the targeted range, with no initial burst release detected. Drug was present in all animals on day 90 and was detected in some animals at 120 and 180 days. Hearing was tested and compared with non-implanted ears. Very good hearing preservation was observed in ears implanted with intracochlear particles when compared with contralateral ears.ConclusionsThe polymer-based extended release system is effective in providing long-term, stable drug delivery for at least 90 days with good hearing outcomes. The results of this study support the potential for achieving long-term drug delivery with a single intracochlear administration.

Autophagy and apoptosis are two different physiological phenomena, however they are closely related in function. This paper introduces the classification and process of autophagy and apoptosis, and discusses the effects of some key regulatory proteins in the formation of autophagosome and the dual role of apoptosis and anti-apoptosis proteins on autophagy and apoptosis, so as to explore the relationship between autophagy and apoptosis, and to provide theoretical basis for further study of autophagy and apoptosis related diseases.

In order to effectively resolve the conflicts between environmental protection,output and benefit during grain cleaning,the vibration screening,specific gravity air separation,cyclone separation,pulse dust removal,closed-loop air circulation and other dust removal technologies are integrated.Efficient dust-free cleaning screens are developed.To achieve effective impurity removal,the problems of excessive dust concentration in grain depots and enterprises’ grain processing and cleaning sites are aimed to be solved.Field tests on the grain depots show that the average impurity content of the grain can be controlled under 0.7% after cleaning,and the dust suppression effect is as follows:dust concentration at 5 m of the operation range lower than 30 mg/m³,15 m lower than 20 mg/m³ while 25 m lower than 10 mg/m³.Therefore,the cleaning effect and dust removal effect are better than common cleaning mechine.