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Alzheimer’s disease (AD) is a complex neurodegenerative disease that affects elderly individuals, characterized by senile plaques formed by extracellular amyloid beta (Aβ). Autophagy dysfunction is a manifestation of protein homeostasis imbalance in patients with AD, but its relationship with Aβ remains unclear. Here, we showed that in Aβ transgenic Caenorhabditis elegans, Aβ activated the TOR pathway and reduced the nuclear entry of HLH-30, leading to autophagy dysfunction characterized by autophagosome accumulation. Then, utilizing RNA-seq, we investigated the regulatory mechanisms by which HLH-30 modulates autophagy in C. elegans. We found that HLH-30 elevated the transcript levels of v-ATPase and cathepsin, thus enhancing lysosomal activity. This led to an increase in autophagic flux, facilitating more pronounced degradation of Aβ. Moreover, HLH-30 reduced the level of ROS induction by Aβ and enhanced the antioxidant stress capacity of the worms through the gsto-1 gene. Additionally, we identified two HLH-30/TFEB activators, saikosaponin B2 and hypericin, that improved autophagic flux, thereby enhancing protein homeostasis in C. elegans. Overall, our findings suggested that HLH-30/TFEB plays a key role in modulating autophagy and can be considered a promising drug target for AD treatments.

Considering the serious risks posed by the heavy metals present in pig diets, monitoring and controlling the amount of these metals is crucial. The laser-induced breakdown spectroscopy (LIBS) is a promising technique for performing elemental analysis due to its unique advantages, such as rapid, in situ, nondestructive, and online detection of various minerals. In order to improve the detection accuracy and detection limit (LOD) of elements, the spatial constraint combined with laser-induced breakdown spectroscopy (CC-LIBS) is used to detect the quantity of zinc in pig feed and achieve the detection of samples with lower concentrations. Zn I 480.86 nm is selected as the characteristic spectral line, and the effects of different two-dimensional (cylindrical) and three-dimensional (hemispherical, truncated cone) cavities on the enhancement factor are compared under different time delays. The results show that the optimal conditions include a truncated cone cavity D5H3, a delay time of 2.08, and an enhancement factor of 3.01 associated with the analytical spectral line. The detection limit of zinc in samples under CC-LIBS is 62.67 mg/kg (the recommended quantity of zinc in pig diet mentioned in the safe use of feed additives is 43–80 mg/kg), which is 35.65% lower than that under the LIBS (97.39 mg/kg). Therefore, this work provides a new test basis and idea for the detection of zinc in pig feed.

Antibiotics are extensively applied in the pharmaceutical industry, while posing a tremendous hazard to the ecosystem and human health. In this study, the degradation performance of ciprofloxacin (CIP), one of the typical contaminants of antibiotics, in an oxidation system of peroxymonosulfate (PMS) activated by magnetic graphene oxide (MGO) was investigated. The effects of the MGO dosage, PMS concentration and pH on the degradation of CIP were evaluated, and under the optimal treatment conditions, the CIP degradation rate was up to 96.5% with a TOC removal rate of 63.4%. A kinetic model of pseudo-secondary adsorption indicated that it involves an adsorption process with progressively intensified chemical reactions. Furthermore, the MGO exhibited excellent recyclability and stability, maintaining strong catalytic activity after three regenerative cycles, with a CIP removal rate of 87.0%. EPR and LC-MS experiments suggested that •OH and SO4−• generated in the MGO/PMS system served as the main reactants contributing to the decomposition of the CIP, whereby the CIP molecule was effectively destroyed to produce other organic intermediates. Results of this study indicate that organic pollutants in the aqueous environment can be effectively removed in the MGO/PMS system, in which MGO has excellent catalytic activity and stabilization for being recycled to avoid secondary pollution, with definite research value and application prospects in the field of water treatment.

Self-excited vibrations of offshore structures interacting with sea ice, characterized by low frequency and high amplitudes, pose significant hazards to offshore wind turbines (OWTs) in cold seas. This study employs the discrete element method (DEM) with a parallel bonding model to investigate the interaction between sea ice and OWTs. Two bond-failure models are compared, with the results showing that the model considering stiffness softening and fracture energy provides better alignment with field data in the Bohai Sea. The DEM is employed to analyze the ice-induced vibration of OWTs under varying ice velocities, revealing that brittle failure of sea ice occurs at higher ice speeds, leading to random structure vibration. At slower ice speeds, both brittle and ductile sea ice failure modes result in self-excited vibrations. This suggests a strong connection between self-excited vibration and the brittle-ductile failure of sea ice, influenced by the relative speeds between ice and the structure. This study employs the DEM to elucidate the mechanism of self-excited vibrations in OWTs from the perspective of brittle-ductile sea ice failure. The results show that the DEM model accurately describes the brittle-ductile transition in sea ice failure, and that the structural motion aligns well with field measurements.

Abstract Background As patients with cervical cancer and precancerous lesions can be diagnosed at early stage and live longer, it is imperative to understand their health-related quality of life so that better cancer-related policies could be promoted and reasonable distribution of limited resources could be implemented. We conducted a cross-sectional study in the Third Affiliated Hospital of Kunming Medical University to assess the health-related quality of life in our targeted population. Due to the characteristics of Yunnan nationality, our study population includes both Han people and ethnic minorities. Methods A cross-sectional study was conducted from January 2019 to December 2020, and 300 patients were selected, who were initially diagnosed with cervical cancer and cervical intraepithelial neoplasia (CIN) pathologically. EQ-5D questionnaire was used to evaluate their quality of life. Results Patients in Han and ethnic minorities showed good comparability. EQ-5D VAS score was statistically significant between Han and ethnic minorities (mean, 85.42 vs. 81.01; P0.05). Nationality, economic trouble, menopause status and participation of China National Cervical Cancer Screening Program (CNCCSP) are influencing factors of HRQoL among women with cervical cancer and precancerous lesions. Besides, we also found low awareness in the CNCCSP and human papilloma virus vaccine, as well as low participation in the national screening program. Conclusion The results of our study imply that the difference of HRQoL does exist between Han people and ethnic minorities with cervical cancer and precancerous lesions. Health providers and health-related departments need to invest more health and financial resources to expand the awareness and participation of the screening project. More efforts should be made in underdeveloped minority areas to assure the accessibility of health resources and interventions. To mitigate economic trouble caused by the diseases, more equal insurance reimbursement should be suggested and implemented in people with or without employee insurance.

Abstract Background The hypolipidemic effect of phytosterols has been wildely recognized, but its application is limited due to its insolubility in water and low solubility in oil. In this study, β-sitosterol ester with linoleic acids and β-sitosterol self-microemulsions were prepared and their hypolipidemic effects on hyperlipidemia mice were studied. Methods Firstly, the mice were randomly divided into normal group and model group,they were fed with basic diet and high-fat diet for 70 days respectively. After high-fat model mice was successfully established, the model group was further divided into eight groups: HFD (high-fat diet feeding), SELA-TSO(8 ml/kg, SELA:700 mg/kg), TSO (8 ml/kg), SSSM (8 ml/kg,SS:700 mg/kg), NLSM (8 ml/kg), SSHT-TSO (8 ml/kg, SS: 700 mg/kg) and SS-TSO (8 ml/kg, SS: 700 mg/kg) groups, and treated with β-sitosterol ester with linoleic acid, β-sitosterol self-microemulsion, commercial β-sitosterol health tablets and β-sitosterol powder for 35 days, respectively, and blank control groups were established. At the end of the treatment period, the blood lipid level, tissues, cholesterol and lipids in feces of mice in each group were investigated. Statistical and analytical data with SPSS 17.0 Software,statistical significance was set at p* SELA-TSO > SSHT-TSO > SS-TSO, which shows that β-sitosterolself-microemulsion have the highest treatment effect among the experimental groups. Conclusions In this study, a new formulation of β-sitosterol was developed, and its hypolipidemic effect was investigated. The results showed that β-sitosterol self-microemulsion has a good blood lipid lowering effect.

In cold regions, ice pressure poses a serious threat to the safe operation of ship hulls and fixed offshore platforms. In this study, a discrete element method (DEM) with bonded particles was adapted to simulate the generation and distribution of local ice pressures during the interaction between level ice and vertical structures. The strength and failure mode of simulated sea ice under uniaxial compression were consistent with the experimental results, which verifies the accuracy of the discrete element parameters. The crushing process of sea ice acting on the vertical structure simulated by the DEM was compared with the field test. The distribution of ice pressure on the contact surface was calculated, and it was found that the local ice pressure was much greater than the global ice pressure. The high-pressure zones in sea ice are mainly caused by its simultaneous destruction, and these zones are primarily distributed near the midline of the contact area of sea ice and the structure. The contact area and loading rate are the two main factors affecting the high-pressure zones. The maximum local and global ice pressures decrease with an increase in the contact area. The influence of the loading rate on the local ice pressure is caused by the change in the sea ice failure mode. When the loading rate is low, ductile failure of sea ice occurs, and the ice pressure increases with the increase in the loading rate. When the loading rate is high, brittle failure of sea ice occurs, and the ice pressure decreases with an increase in the loading rate. This DEM study of sea ice can reasonably predict the distribution of high-pressure zones on marine structures and provide a reference for the anti-ice performance design of marine structures.

Nuclear transporter importin-β1 is emerging as an attractive target by virtue of its prevalence in many cancers. However, the lack of druggable inhibitors restricts its therapeutic proof of concept. In the present work, we optimized a natural importin-β1 inhibitor DD1 to afford an improved analog DD1-Br with better tolerability (>25 folds) and oral bioavailability. DD1-Br inhibited the survival of castration-resistant prostate cancer (CRPC) cells with sub-nanomolar potency and completely prevented tumor growth in resistant CRPC models both in monotherapy (0.5 mg/kg) and in enzalutamide-combination therapy. Mechanistic study revealed that by targeting importin-β1, DD1-Br markedly inhibited the nuclear accumulation of multiple CRPC drivers, particularly AR-V7, a main contributor to enzalutamide resistance, leading to the integral suppression of downstream oncogenic signaling. This study provides a promising lead for CRPC and demonstrates the potential of overcoming drug resistance in advanced CRPC via targeting importin-β1.

Chaos-modulation-based ultra wide band （UWB） communication was addressed.A new structure for the pseudo-chaotic encoder was presented,and some decoding schemes were also given accordingly.The performances of such decoding schemes were compared in the AWGN channel.Simulation results verify and demonstrate the effectiveness of the proposed method.

In recent decades, human exploration of space has gradually deepened, and more and more countries and regions have successfully sent astronauts into space. How to complete the space experiment as efficiently and safely as possible in the shortest time with limited resources has become an important issue in the field of aerospace technology. Taking full account of such matter, we consider that ergonomics in design stage is one of the most effective ways to solve this problem. The microgravity environment is the biggest difference between ground and space. Therefore, the study of ergonomics under the microgravity environment is of great significance. This article deeply analyses and summarizes the physiological differences between human and normal gravity under microgravity environment. From the ergonomics point of view, the requirements for spacecraft design and space mission planning are put forward for the reference of engineers and scholars.

The incidence of ischemic stroke has increased and that of hemorrhagic stroke has decreased in urban China; however, the trends in rural areas are unknown. We aimed to explore the secular trends in incidence and transition of stroke subtypes among rural Chinese.This was a population-based stroke surveillance through the Tianjin Brain Study. A total of 14,538 residents in a township of Ji County in Tianjin, China participated in the study since 1985. We investigated the age-standardized stroke incidence (sex-specific, type-specific, and age-specific), the annual proportion of change in the incidence of stroke, and the proportion of intracerebral hemorrhage in the periods 1992-1998, 1999-2005, and 2006-2012, because the neuroimaging technique was available since 1992 in this area.The age-standardized incidence per 100,000 person-years increased significantly for both intracerebral hemorrhage (37.8 in 1992-1998, 46.5 in 1999-2005, and 76.5 in 2006-2012) and ischemic stroke (83.9 in 1992-1998, 135.3 in 1999-2005, and 238.0 in 2006-2012). The age-standardized incidence of first-ever stroke increased annually by 4.9% for intracerebral hemorrhage and by 7.3% for ischemic stroke. The greatest increase was observed in men aged 45-64 years for both stroke types (P < 0.001). The proportion of intracerebral hemorrhage was stable overall, increased among men aged 45-64 years, and decreased among men aged ≥65 years. The average age of intracerebral hemorrhage in men reduced by 7.5 years from 1992 to 2012.The age-standardized incidence of main stroke subtypes increased significantly in rural China over the past 21 years; the overall proportion of intracerebral hemorrhage was stable, but the incidence increased significantly among middle-aged men. These findings imply that it is crucial to control stroke risk factors in middle-aged men for stroke prevention in future decades.