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Changes in the levels of circulating proteins are associated with Alzheimer's disease (AD), whereas their pathogenic roles in AD are unclear. Here, we identified soluble ST2 (sST2), a decoy receptor of interleukin-33-ST2 signaling, as a new disease-causing factor in AD. Increased circulating sST2 level is associated with more severe pathological changes in female individuals with AD. Genome-wide association analysis and CRISPR-Cas9 genome editing identified rs1921622 , a genetic variant in an enhancer element of IL1RL1, which downregulates gene and protein levels of sST2. Mendelian randomization analysis using genetic variants, including rs1921622 , demonstrated that decreased sST2 levels lower AD risk and related endophenotypes in females carrying the Apolipoprotein E (APOE)-ε4 genotype; the association is stronger in Chinese than in European-descent populations. Human and mouse transcriptome and immunohistochemical studies showed that rs1921622 /sST2 regulates amyloid-beta (Aβ) pathology through the modulation of microglial activation and Aβ clearance. These findings demonstrate how sST2 level is modulated by a genetic variation and plays a disease-causing role in females with AD.

Objective: To establish a HPLC method for simultaneous determination of rutin, hyperoside, quercetin in Xiang lotus. Methods: The HPLC method was performed on an Agilent ZORBAX SB-C18 column (4.6 mm×250 mm, 5 m) with gradient elution of methanol and 0.6% phosphoric acid solution. The flow rate was 1.0 mL/min. The column temperature was 30 ℃ and the detection wavelength was set at 255 nm. Results: The contents of rutin, hypericin and quercetin in 20 batches of lotus samples were 1.32~2.06, 1.36~2.43, 1.41~3.26 mg/kg, respectively. The linear range of the concentration of rutin, hypericin and quercetin was 5~200 g/mL (R2=0.999 9), the three flavonoids showed a good linearity, a high sensitivity, and good serviceability. The relative standard deviation (RSD) for precision, stability, repeatability, and recoveries test were all less than 4.0%, and the average recovery rate of added standard were 96.6%, 96.9%, 97.4%, respecitvely. Conclusion: The method is convenient and accurate, and can be used for the content determination and quality evaluation of flavonoids in Xiang lotus.

Triphenyltin is an environmental contaminant widely used in antifouling paints and can cause toxicity in various organs in living organisms. However, its effects on intestinal function and the microbiome of the gut remain unknown. The objective of this study was to explore the intestinal toxicity of triphenyltin in mice by orally administering 0, 1.875, 3.75, and 7.5 mg/Kg to adult male mice for 8 weeks. Results showed that triphenyltin caused ileum tissue damage, induced oxidative stress, upregulated inflammation-related gene expression and increased serum tumor-necrosis factor α (TNF-α) levels in mice. Triphenyltin impaired ileum barrier function by downregulating Muc2, ZO-1, Occludin and their protein levels at 3.75 and 7.5 mg/Kg. TPT exposure led to partial inflammation and decreased mucin mRNA expression in the colon. Triphenyltin altered intestinal micro-ecological balance and fecal metabolome in mice. In conclusion, triphenyltin alters the mouse gut microbiota and fecal metabolome.

Abstract The energy‐efficient optimization of the train timetable should be carried out on the basis of meeting passenger demand and determining the train operation plan. This paper proposes an integrated energy‐efficient optimization framework for the train timetable. Firstly, two energy‐efficient optimization strategies for this problem are proposed: inter‐station running time allocation and regenerative braking energy utilization. The first strategy aims to reduce the traction energy consumption, realized by selecting the profile based on a given set of speed profiles for each inter‐station sector when ensuring a stable travel time of train routing. The second strategy is intended to fully utilize the regenerative energy feedback from braking trains, realized by setting the departure time of trains based on a small‐range headway adjustment. Then, an integrated energy‐efficient optimization model of the timetable is developed and solved using the genetic algorithm. Finally, a case study of the Guangzhou Metro Line 8 is presented to verify the effectiveness of the method. The results show that the utilization rate of regenerative braking energy in the optimized timetable increases by 8.60%, and the total energy consumption decreases by 9.52%. Regenerative energy utilized roughly doubles during peak hours and increases more than twice as much during off‐peak hours.

The rapid development of new energy vehicles places a more and more urgent demand for high-performance lithium-ion batteries. As an important part of lithium-ion battery, the electrode performance has a significant impact on the overall performance of lithium-ion battery. In the electrode, the uniformity and stability of the slurry, which is a multi-component mixture, own a great influence on the performance of the electrode sheet. However, most of the current researchers’ interests are usually placed after the slurry process, that is, only focus on the performance of the electrode, but ignore the slurry which is the preconditions of the performance of the electrode. Uniformity of the electrode is determined by the uniformity and stability of slurries. However, as a complicated mixture of multicomponent suspended particles, it’s hard to measure the uniformity and stability of the slurry directly. At present, the rheological property test of the slurry is the most effective method to characterize the uniformity and stability of the slurry. In this paper, the effects of active materials, binders, conductive agents, solvents, dispersing additives, pH value, temperature, mixing steps on the rheological properties of the slurry during the manufacturing of lithium ion battery electrode pastes were reviewed. The influence of these factors on the rheological properties of the slurry was summarized, which provides a certain guiding role for fabricating slurries with higher uniformity and stability and developing high performance Li-ion batteries.

To design a new type of fully automatic intelligent milk dispenser that is different from traditional milk preparation methods, which is based on Internet technology and combined with artificial intelligence. Its structure mainly includes: shell, water tank, milk powder bucket, cover, mixing bin, sealer, control panel and heating transfer plate. Among them, the control panel includes a main control circuit board, a music sound and light module, a temperature display module, a milk/flush module, a temperature control module, and a wireless receiving module. The controls of these control panels are all connected to the main control circuit board. Compared with the traditional intelligent milk dispenser, this method incorporates functions such as high-pressure steam sterilization, automatic micro-stirring, remote control, and automatic bottle sealing in the operation, making the process more scientific and reasonable. More importantly, it helps to reduce the tedious workload of medical staff, reduce environmental pollution, and reduce the risk of intestinal infections in infants and young children. (本文介绍一种区别于传统配奶方式、基于互联网技术并结合人工智能的一种新型全自动智能配奶机的研制和应用方法。其结构主要包括: 壳体、水箱、奶粉桶、罩体、混合仓、封口器、控制面板以及加热传送板。其中, 控制面板包括主控电路板、音乐声光模块、温度显示模块、冲奶/冲水模块、温度控制模块和无线接收模块等, 这些控制面板的控件均与主控电路板相接。与传统的智能配奶机相比较, 该方式在操作中融入了紫外线消毒、自动微型搅拌、远程遥控、自动封瓶等功能, 使过程更为科学合理。更重要的是, 有利于减少医护人员繁琐的工作量, 减少对环境的污染, 降低婴幼儿肠道感染的风险。)

Reactive oxygen species (ROS) have become an effective tool for tumor treatment. The combination of photodynamic therapy (PDT) and chemodynamic therapy (CDT) takes advantage of various ROS and enhances therapeutic effects. However, the activation of CDT usually occurs before PDT, which hinders the sustained maintenance of hydroxyl radicals (⋅OH) and reduces the treatment efficiency. Herein, we present a light‐triggered nano‐system based on molecular aggregation regulation for converting cancer therapy from PDT/photothermal therapy (PTT) to a long‐lasting CDT. The ordered J‐aggregation enhances the photodynamic properties of the cyanine moiety while simultaneously suppressing the chemodynamic capabilities of the copper‐porphyrin moiety. Upon light irradiation, Cu‐PCy JNPs demonstrate strong photodynamic and photothermal effects. Meanwhile, light triggers a rapid degradation of the cyanine backbone, leading to the destruction of the J‐aggregation. As a result, a long‐lasting CDT is sequentially activated, and the sustained generation of ⋅OH is observed for up to 48 hours, causing potent cellular oxidative stress and apoptosis. Due to their excellent tumor accumulation, Cu‐PCy JNPs exhibit effective in vivo tumor ablation through the converting therapy. This work provides a new approach for effectively prolonging the chemodynamic activity in ROS‐based cancer therapy. [ABSTRACT FROM AUTHOR]

To better understand the pollution characteristics and formation mechanisms of atmospheric carbonyl compounds, continuous measurements of carbonyl compounds in Jinan were taken for one month at a sampling frequency of 2 h. The sources, pollution characteristics, and concentration changes of carbonyl compounds during the summers of 2018 and 2020 were compared. The total concentrations of carbonyl compounds were 10.51 ± 0.13 ppbV and 6.30 ± 1.08 ppbV in 2018 and 2020, respectively. In both years, formaldehyde, acetone, and acetaldehyde were the major carbonyls. Diurnal variations and correlation analyses showed that exhaust emissions from motor vehicles during peak traffic periods significantly contributed to the concentrations of carbonyl compounds in Jinan, with formaldehyde exhibiting net production. The ratio of formaldehyde/acetaldehyde (C1/C2) was 2.64 in 2018 and 2.03 in 2020, indicating that carbonyl compounds are jointly affected by anthropogenic sources and photochemical reactions. Master Chemical Mechanism model analyses showed that the formation of formaldehyde in Jinan was controlled by RO + O2 reactions, and formaldehyde was mainly consumed via photolysis and its reaction with the hydroxyl radical. In situ photochemistry can further promote formaldehyde production. The comparison of the reactivities of different carbonyl compounds revealed that formaldehyde, acetaldehyde, butyraldehyde, and propionaldehyde play an important role in hydroxyl radical reactions and ozone generation. Among all the measured carbonyl compounds, benzaldehyde contributed the most to secondary organic aerosols (SOAs). Overall, this study provides new insights into the formation mechanisms of carbonyl compounds as well as their pollution characteristics.

Nuclear magnetic resonance (NMR) technology provides an innovative method employed in detecting the porous structures in frozen rock and soil masses. On the basis of NMR relaxation theory, fuzzy random characteristics of the NMR T2 spectrum and pore structure are deeply analyzed in accordance with the complex and uncertain distribution characteristics of the underground rock and soil structure. By studying the fuzzy random characteristics of the NMR T2 spectrum, the fuzzy random conversion coefficient and conversion method of the T2 spectrum and pore size distribution are generated. Based on the niche principle, the traditional genetic algorithm is updated by the fuzzy random method, and the improved niche genetic algorithm is proposed. Then, the fuzzy random inversion of the conversion coefficient is undertaken by using the improved algorithm. It in turn makes the conversion curve of the T2 spectrum and pore size distribution align with the mercury injection test curve in diverse pore apertures. Compared with the previous least square fitting method, it provides a more accurate approach in characterizing complicated pore structures in frozen rock and soil masses. In addition, the improved niche genetic algorithm effectively overcomes the shortcomings of the traditional genetic algorithm, such as low effectiveness, slow convergence, and weak controllability, which provides an effective way for parameter inversion in the section of frozen geotechnical engineering. Finally, based on the T2 spectrum test of frozen sandstone, the fuzzy random characterization of frozen sandstone pore distribution is carried out by using this transformation method. The results illustrate that the conversion coefficient obtained through the improved algorithm indirectly considers the different surface relaxation rates of different pore sizes and effectively reduces the diffusion coupling effects, and the pore characteristics achieved are more applicable in engineering practices than previous methods.

In this paper, numerical simulations are conducted to study the smoke diffusion characteristics in the V-shaped slope tunnel with different slopes. The smoke diffusion characteristics and the ceiling temperature distribution with three kinds of heat release rates (HRR) and three kinds of slopes are considered without mechanical ventilation. The simulation results show that the smoke diffusion symmetrically on both sides of the symmetrical V-shaped tunnel. The smoke diffusion speed is mainly affected by the HRR, while it is less affected by the slope. The smoke diffusion speed increases with the increase of HRR. The maximum ceiling temperature increases with the increase of HRR and decreases with the increase of slope. The HRR is constant, the ceiling temperature decreases with the increase of the slope within 150 m away from fire source. Beyond 150 m from fire source, the ceiling temperature distribution are in opposite tendency and the overall temperature has a little difference between both sides of V-shaped tunnel.

Abstract Background Induced pluripotent stem cells (iPS) represent an innovative source for the standardized in vitro generation of macrophages (Mφ). Mφ show great promise in disease pathogenesis, particularly tuberculosis. However, there is no information about human iPS-derived (hiPS) macrophages (hiPS-Mφ) in response to tuberculosis infection. Methods In the present study, macrophages derived from hiPS were established via embryoid body (EB) formation by using feeder-free culture conditions, and the human monocyte cell line THP-1 (THP-1-Mφ) was used as control. iPS-Mφ were characterized by using morphology, Giemsa staining, nonspecific esterase staining (α-NAE), phagocytosis, and surface phenotype. Additionally, after treatment with Bacillus Calmette-Guérin (BCG) for 24 h, cell apoptosis was detected by using an Annexin V-FITC Apoptosis Detection assay. The production of nitric oxide (NO), expression of tumor necrosis factor alpha (TNF-α), activity of apoptosis-related protein cysteine-3 (Caspase-3) and expression of B-cell lymphoma-2 (Bcl-2) were analyzed. Results With respect to morphology, surface phenotype, and function, the iPS-Mφ closely resembled their counterparts generated in vitro from a human monocyte cell line. iPS-Mφ exhibited the typically morphological characteristics of macrophages, such as round, oval, fusiform and irregular characteristics. The cells were Giemsa-stained-positive, α-NAE-positive, and possessed phagocytic ability. iPS-Mφ express high levels of CD14, CD11b, CD40, CD68, and major histocompatibility complex II (MHC-II). Moreover, with regard to the apoptotic rate, the production of NO, expression of TNF-α, and activity of Caspase-3 and Bcl-2, iPS-Mφ closely resemble that of their counterparts generated in vitro from human monocyte cell line in response to BCG infection. The rate of apoptosis of BCG-treated iPS-Mφ was 37.77 ± 7.94% compared to that of the untreated group at 4.97 ± 1.60% (P < 0.01) by using Annexin V-FITC Apoptosis Detection. Additionally, the rate of apoptosis of BCG-treated THP-1-Mφ was 37.1 ± 2.84% compared to that of the untreated group at 6.19 ± 1.68% (P < 0.001). The expression of TNF-α and the production of NO were significantly increased (P < 0.001), and the activity of Caspase-3 was increased. However, the expression of Bcl-2 was inhibited (P < 0.001). Conclusions Our results demonstrate that Mφ derived from hiPS perform the immunological function in response to Bacillus Calmette-Guérin infection by undergoing apoptosis, increasing the production of NO and expression of TNF-α. Thus, our study may help to overcome the limitations of research into certain rare diseases due to the lack of adequate supply of disease-specific primary cells.