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Xiaolong Zhang,1,&ast; Zhiyin Lei,2,&ast; Ying Wu,3 Yuanyuan Song,4 Xiaoling Wu,3,5 Bo Yang,2 Jianmei Fan,2 Shixu Feng,2 Liping Wu,2 Lingyan Li,2 Qin Dai,2 Zhen Zeng,2 Mei Feng,3 Tingting Zhang3 1Department of Thoracic Surgery, West China Hospital, Sichuan University, Chengdu, Sichuan Province, People’s Republic of China; 2Department of Respiratory and Critical Care Medicine, Jiajia Central Health Center of Chengdu Eastern New Area, Chengdu Eastern New Area, Sichuan Province, People’s Republic of China; 3Department of Respiratory and Critical Care Medicine, West China Hospital, Sichuan University/West China School of Nursing, Sichuan University, Chengdu, Sichuan Province, People’s Republic of China; 4Department of Critical Care Medicine, West China Hospital, Sichuan University, Chengdu, Sichuan Province, People’s Republic of China; 5Department of Nursing, Sanya People’s Hospital/West China (Sanya) Hospital, Sichuan University, Sanya, Hainan Province, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Ying Wu, Department of Respiratory and Critical Care Medicine, West China Hospital, Sichuan University/West China School of Nursing, Sichuan University, No. 37 Guoxue Alley, Chengdu, Sichuan Province, 610041, People’s Republic of China, Tel +86-18980606932, Email 358383278@qq.comPurpose: To investigate the prevalence and risk factors for chronic obstructive pulmonary disease (COPD) in a rural area in western China with severe air pollution.Patients and Methods: 10% of local residents aged 40 years and above were included using a convenience sampling method. This was a cross-sectional study. A self-designed questionnaire was used to collect participants’ demographic data. The screening program was comprised of two steps: First, a portable electronic spirometer was used for COPD screening. Those participants with FEV1/FVC ratio < 0.7 were then referred to a confirmatory pulmonary function (PF) test. COPD was confirmed according to the 2020 Global Initiative for Chronic Obstructive Lung Disease criteria.Results: A total of 4577 participants aged 40 years old or above were included in the final analysis. Examination with a mobile spirometer identified 1159 individuals for confirmatory testing; after that, of the 1159 individuals, 889 were diagnosed with COPD by the confirmatory PF test. The prevalence of COPD among the target group was 19.4%. Older age, male sex (odds ratio [OR] = 1.537, 95% confidence interval [CI] 1.246– 1.894), smoking history (OR = 1.338, 95% CI 1.069– 1.675), family history of respiratory disease (OR = 1.625, 95% CI 1.350– 1.957), education level (OR = 0.735, 95% CI 0.617– 0.876), overweight (OR = 0.614, 95% CI 0.517– 0.730) and obesity (OR = 0.572, 95% CI 0.449– 0.721) were identified as independent factors associated with COPD. The screening program helped earlier detection of COPD in 719 participants.Conclusion: COPD was highly prevalent in the rural area studied. Rural residents who were older, current or ever-smokers, male and those who had a lower education level were more vulnerable to developing COPD. The COPD screening program may be helpful for earlier disease detection in rural health-care settings.Keywords: chronic obstructive pulmonary disease, prevalence, primary care, pulmonary function test, risk factors

Lithium-sulfur (Li-S) batteries are considered promising candidates for next-generation advanced energy storage systems due to their high theoretical capacity, low cost and environmental friendliness. However, the severe shuttle effect and weak redox reaction severely restrict the practical application of Li-S batteries. Herein, a functional catalytic material of tin disulfide on porous carbon spheres (SnS

Dynamic changes in the contribution of air pollution, meteorological conditions and aging to cardiovascular mortality.

In recent decades, three-dimensional (3D) cell culture technologies have been developed rapidly in the field of tissue engineering and regeneration, and have shown unique advantages and great prospects in the differentiation of stem cells. Herein, the article reviews the progress and advantages of 3D cell culture technologies in the field of stem cell differentiation. Firstly, 3D cell culture technologies are divided into two main categories: scaffoldless and scaffolds. Secondly, the effects of hydrogels scaffolds and porous scaffolds on stem cell differentiation in the scaffold category were mainly reviewed. Among them, hydrogels scaffolds are divided into natural hydrogels and synthetic hydrogels. Natural materials include polysaccharides, proteins, and their derivatives, focusing on hyaluronic acid, collagen and polypeptides. Synthetic materials mainly include polyethylene glycol (PEG), polyacrylic acid (PAA), polyvinyl alcohol (PVA), etc. In addition, since the preparation techniques have a large impact on the properties of porous scaffolds, several techniques for preparing porous scaffolds based on different macromolecular materials are reviewed. Finally, the future prospects and challenges of 3D cell culture in the field of stem cell differentiation are reviewed. This review will provide a useful guideline for the selection of materials and techniques for 3D cell culture in stem cell differentiation.

In order to reduce the dependence on fossil energy products, natural fiber/polymer hybrid composites have been increasingly researched. The high price of the quartz optical fibers and glass optical fibers has greatly inspired researchers to engage in the research on polymer optical fibers. Herein, transparent fibers based on plant fibers were innovatively prepared for the first time by delignification and impregnating epoxy diluted with acetone. The epoxy improved the thermal stability of the fiber without deteriorating its mechanical properties, and also endowed the fiber with the property of transparency. The tensile strength of transparent fibers of three diameters were 34.5, 58.6 and 100.3 MPa, respectively and the corresponding Young's modulus reached 1.1, 1.7 and 2.3 GPa, respectively. In addition, the light-conducting properties of transparent fibers were displayed with a green laser and the fibers displayed good light transmission along the fiber growth direction. Transparent fibers are expected to be used in optical fibers because of their high thermal stability, good mechanical properties and light-conducting properties.

Ginkgo seed is an important Chinese medicine and food resource in China, but the toxicity of ginkgo acid in it limits its application. Previous studies have found that salicylic acid decarboxylase (Sdc) has a decarboxylation degradation effect on ginkgo acid. In order to improve the decarboxylation ability of Sdc to Ginkgo acid, 11 residues of the Sdc around the substrate (salicylic acid) were determined as mutation targets according to the analysis of crystal structure of Sdc (PDB ID:6JQX), from Trichosporon moniliiforme WU-0401, and a total of 30 single point mutant enzymes and one compound mutant enzyme were obtained. With Ginkgo acid C15:1 as the substrate, it was found from activity assay that Sdc-Y64T and Sdc-P191A had higher decarboxylation activity, which increased by 105.18% and 116.74% compared with that of wild type Sdc, respectively. The optimal pH for Sdc Y64T and Sdc-P191A to decarboxylate Ginkgo acid C15:1 was 5.5, which is the same as the wild type Sdc. The optimal temperature of Sdc-P191A was 50 °C, which was consistent with that of the wild type Sdc, but the optimal temperature of the mutant Sdc-Y64T was 40 °C, which was 10 °C lower than that of wild type Sdc.

Swirl cooling can provide effective protection for the turbine vane leading edge (LE). In this paper, a swirl cooling model for improving the turbine vane heat transfer is established. The model includes the high-temperature mainstream region, LE region, and swirl cooling region. The conjugate heat transfer (CHT) method is used to examine the influence of wall structures on swirl cooling. Then, the best surface structure in the studied range is selected to further analyze the impact of the coolant inlet mass flow. The results show that the circumferential micro-rib structure has a more excellent performance in both fluid flow and cooling performance. The hindering effect of the micro-ribs can effectively avoid the development of axial cross-flow, thus enhancing the heat transfer with a small friction loss increment and providing a lower surface temperature and more uniform temperature distribution. When the inlet mass flowrate improves, the thermal performance factor increases and the LE temperature decreases gradually. Under the same pumping power condition, the circumferential micro-ribs structure has higher heat transfer efficiency. This investigation can provide a new design for further improving the thermal performance of swirl cooling for turbine vanes.

Soil moisture is a crucial component of the water cycle and plays an important role in regional weather and climate. However, owing to the lack of In Situ observations, an accurate understanding of the spatiotemporal variations of soil moisture (SM) on the Tibetan Plateau (TP) is still lacking. In this study, we used three gridded SM products to characterize the spatiotemporal features of SM on the TP during the warm season (May to August). We analyzed the fifth-generation European Centre for Medium-Range Weather Forecasts atmospheric reanalysis (ERA5), Global Land Data Assimilation System (GLDAS), and Soil Moisture Active Passive (SMAP) datasets and used station observation data and triple collocation to quantify product accuracy and consistency. Results of the evaluation based on observation data show that both ERA5 and GLDAS overestimate SM, while the accuracy of SMAP is high. In terms of capturing the temporal variations of SM measured at stations, the performance of ERA5 and that of SMAP are superior to that of GLDAS. According to the evaluation based on triple collocation, SMAP exhibits the smallest random error over the TP and the highest temporal correlation with the unknown true SM in eastern TP. For SMAP, SM variability is the largest in the southern TP. For ERA5 and GLDAS, variability in the western TP is substantially larger than that for SMAP. Low-frequency (30–90 days) variations are the largest contributor to TP SM intraseasonal variability. Relative to SMAP, the contribution of high-frequency variations is low in ERA5 and GLDAS. Land-atmosphere coupling is stronger (weaker) in the western (southeastern) TP, which is relatively dry (wet). Our evaluation of SM product performance over the TP may facilitate the use of these products for disaster monitoring and climate and hydrological studies.

A record-breaking Meiyu-Baiu rainfall hit East Asia in June–July 2020. The warm Indian Ocean (IO) has been identified as a primary cause, but it cannot explain the heavy rainfall in July, a striking characteristic of the 2020 Meiyu-Baiu rainfall. A remarkable retreat of Arctic sea ice in the late spring and early summer of 2020 also promoted Meiyu-Baiu rainfall by favoring North Asian blockings and cold air outbreaks. However, its importance compared with IO warming is unclear. Our result shows that the abundant moisture supply to the 2020 Meiyu-Baiu rainfall mainly stems from anomalous meridional wind convergence, while the excessive ascending motions are due to warm advection tied to enhanced mid-troposphere westerlies. AGCM experiments are used to examine the relative importance of IO warming and Arctic sea ice anomalies. In June, IO warming is responsible for the atmospheric circulation anomalies around the Meiyu-Baiu region and accounts for ~ 75% of the Meiyu-Baiu rainfall anomalies, despite the Arctic sea-ice loss explaining most circulation anomalies over Eurasian high latitudes. In July, both IO warming and Arctic sea-ice loss are necessary for meridional convergence, enhanced westerlies, and thus the heavy rainfall over the Meiyu-Baiu region. Their effects are interdependent rather than additive. Strong IO warming is rarely observed alongside severe Arctic sea-ice loss before 2020 because of their discordant interannual variations. In the future, the combined effects of IO warming and Arctic sea-ice loss on the Meiyu-Baiu rainfall may become more pronounced as their long-term trends continue.

The intrinsic origins and formation of atomic-scale structure in multicomponent alloys remain largely unknown owing to limited simulations and inaccessible experiments. Herein, we report the formation of three-dimensional periodicity from a disordered atomic-scale structure to an imperfect/perfect ordered cluster and finally to long-range translational and rotational symmetry coupled with Nb heterogeneity. Significant atomic-scale structural clustering and atomic arrangements involving solvent or solute atoms simultaneously occurred during isothermal annealing. A close relationship between atomic-scale structural evolution and composition variation has important implications in depicting the chemical and topological packing during the early crystallization stage in metallic glasses. This work can provide a comprehensive understanding of how short-range orders evolve into long-range periodicity and will further shed light on the origins and nature of metallic glasses.

Long noncoding RNA (lncRNA) plays an important role in multiple cancers. So far, the exact function of lncRNAs in papillary thyroid carcinoma (PTC) is unclear. The purposes of this work were to investigate the function and underlying mechanisms of RNF185 antisense RNA 1 (RNF185-AS1) in PTC. The expression of RNF185-AS1 was analyzed by quantitative real-time PCR (qRT-PCR). Colony formation, 5-ethynyl-2'-deoxyuridine, and Cell Counting Kit-8 assays were utilized to determine cell proliferation. Cell migration and invasion were tested using wound healing and transwell assays. A mouse transplantation tumor model was used for tumor growth analyses in vivo. The regulation of RNF185-AS1 on the downstream miR-429/lipoprotein receptor-related protein (LRP4) axis was predicted and identified through bioinformatic analysis, dual-luciferase reporter assay, and RNA immunoprecipitation (RIP) assay. RNF185-AS1 was dramatically overexpressed in PTC tumors and cells. High RNF185-AS1 expression was associated with bigger tumor size, lymph node metastasis, and advanced tumor-node-metastasis stage in PTC patients. Silencing of RNF185-AS1 impeded the proliferation, migration, and invasion in vitro and constrained tumorigenesis in vivo. Mechanistically, RNF185-AS1 could act as a sponge of miR-429 to regulate the expression of LRP4. In addition, downregulation of miR-429 or upregulation of LRP4 could relieve the proliferation, migration, and invasion of IHH-4 and TPC-1 cells that inhibited by RNF185-AS1 knockdown. Downregulation of RNF185-AS1 may suppress PTC progression through functioning as a sponge of miR-429 to hinder the expression of LRP4. The RNF185-AS1/miR-429/LRP4 axis will lay the groundwork for future therapeutic strategies in PTC.

The aim of this study was to evaluate factors influencing mindfulness among clinical nurses in China.Mindfulness has positive effects on nurses' negative emotions and job burnout. However, few studies have explored the antecedent variables of mindfulness.A total of 358 clinical nurses in Beijing Aerospace Center Hospital completed a cross-sectional survey between July and September 2020. The study employed self-report questionnaires covering social demographics, mindfulness, anxiety, job burnout, emotion regulation, stress perception, resilience, well-being and loneliness.The mean Mindful Attention Awareness Scale score was 66.82 ± 11.53, which is near the cut-off score between the high and medium mindfulness categories. Anxiety, stress perception, emotional exhaustion and expressive suppression negatively affected the level of mindfulness, while mental resilience and cognitive reappraisal positively influenced the level of mindfulness (all P .05).Hospital nurses have higher-than-normal levels of mindfulness. The mindfulness level of clinical nurses is related to anxiety, stress perception, resilience, cognitive reappraisal, emotional exhaustion and expressive suppression.Nursing managers should consider the role and mechanism of positive psychology and develop targeted intervention measures to improve nurses' mindfulness, in order to further reduce their negative emotions, improve their sense of professional benefit and thus ensure the quality and safety of nursing.

Colorado potato beetle (CPB; Leptinotarsa decemlineata) is a destructive quarantine pest that develops broad physiological adaptations to potato plants. During feeding, CPB deposits a copious amount of wet frass onto the surface of leaves and stems that remains in place for long periods. Insect behaviors such as feeding, crawling and oviposition are able to mediate plant defenses. However, the specific role of CPB defecation-associated cues in manipulating plant defenses remains unclear.CPB larval frass significantly suppressed potato polyphenol oxidase activity and enhanced larval growth on treated potato plants. The incorporation of antibiotics into larval frass triggered higher jasmonic acid (JA)-regulated defense responses in potato plants compared with antibiotic-free frass. Four bacterial symbionts belonging to the genera Acinetobacter, Citrobacter, Enterobacter and Pantoea were isolated from larval frass and suppressed plant defenses. After reinoculation of these bacteria into axenic larvae, Acinetobacter and Citrobacter were found to be highly abundant in the frass, whereas Enterobacter and Pantoea were less abundant probably due to the negative effect of potato steroidal glycoalkaloids (SGA) such as α-solanine. Furthermore, direct application of Acinetobacter and Citrobacter to wounded potato plants significantly inhibited the expression of genes associated with the JA-mediated defense signaling pathway and SGA biosynthesis.Our findings demonstrate that CPB exploits frass-associated bacteria as a deceptive strategy of plant defense suppression, adding an interesting dimension to our understanding of how CPB successfully specializes on potato plants. © 2022 Society of Chemical Industry.

This study investigated the interaction of Shewanella oneidensis MR-1 and CdS in azo dye decolorization, showing that CdS could act as a light-switch to achieve fast light-driven decolorization.

Heavy metal ions produced by industrial activity have been a serious environmental problem, and their detection is critical for treatment of the heavy metal pollution. Among the variable heavy metal detection methods, fluorescent indicator methods have attracted wide attention due to the advantage of the convenience and nondestructive detection process. Carbon quantum dots have great application in this respect. In this study, nitrogen and sulfur doped fluorescent carbon quantum dots (N,S-CDs) were prepared based on wool keratin using a hydrothermal method, of which the morphology, chemical composition and optical properties were characterized. The prepared N,S-CDs were spherical nanoparticles with a diameter of 2-6 nm, showing wide fluorescence excitation and emission wavelength range and considerable quantum yield, and have sensitive response to Cr

The modified separator with sandwich structure can efficiently promote electrochemical reactions, block the shuttle effect, and inhibit the lithium dendrite by excellent electrical conductivity, strong physical barrier and chemical adsorption.

Background Direct-acting antivirals (DAAs) for hepatitis C treatment in China became available since 2017. This study expects to generate evidence to inform decision-making in a nationwide scale-up of DAA treatment in China. Methods We described the number of standard DAA treatment at both national and provincial levels in China from 2017 to 2021 based on the China Hospital Pharmacy Audit (CHPA) data. We performed interrupted time series analysis to estimate the level and trend changes of the monthly number of standard DAA treatment at national level. We also adopted the latent class trajectory model (LCTM) to form clusters of the provincial-level administrative divisions (PLADs) with similar levels and trends of number of treatment, and to explore the potential enablers of the scale-up of DAA treatment at provincial level. Results The number of 3-month standard DAA treatment at national level increased from 104 in the last two quarters of 2017 to 49,592 in the year of 2021. The estimated DAA treatment rates in China were 1.9% and 0.7% in 2020 and 2021, which is far below the global target of 80%. The national price negotiation at the end of 2019 resulted in DAA inclusion by the national health insurance in January 2020. In that month, the number of treatment increased 3668 person-times (P Conclusions Central negotiations to reduce prices of DAAs resulted in inclusion of DAA treatment under the universal health insurance, which are critical elements that support scaling up access to hepatitis C treatment in China. However, the current treatment rates are still far below the global target. Targeting the PLADs lagged behind through raising public awareness, strengthening capacity of the healthcare providers by roving training, and integrate prevention, screening, diagnosis, treatment and follow-up management of hepatitis C into the existing services are needed.

Background The main protease (Mpro) is a crucial target for severe acute respiratory syndrome coronavirus (SARS-CoV-2). Chitooligosaccharide (CS) has broad-spectrum antiviral activity and can effectively inhibit the activity of SARS-CoV. Here, based on the high homology between SARS-CoV-2 and SARS-CoV, this study explores the effect and mechanism of CS with various molecular weights on the activity of SARS-CoV-2 Mpro. Methods We used fluorescence resonance energy transfer (FRET), UV–Vis, synchronous fluorescence spectroscopy, circular dichroism (CD) spectroscopy and computational simulation to investigate the molecular interaction and the interaction mechanism between CS and SARS-CoV-2 Mpro. Results Four kinds of CS with different molecular weights significantly inhibited the activity of Mpro by combining the hydrogen bonding and the salt bridge interaction to form a stable complex. Glu166 appeared to be the key amino acid. Among them, chitosan showed the highest inhibition effect on Mpro enzyme activity and the greatest impact on the spatial structure of protein. Chitosan would be one of the most potential anti-viral compounds. Conclusion This study provides the theoretical basis to develop targeted Mpro inhibitors for the screening and application of anti-novel coronavirus drugs.

Ageing in various tissues exhibits common and distinct features. It is critical to decipher the mechanisms underlying ageing in individual tissues. MicroRNAs (miRNAs) are essential regulators in ageing and are recently highlighted as a new class of intercellular signalling molecules. However, little is known about the tissue-specific transcriptomic changes of miRNAs during ageing. C. elegans is a well-established model organism in ageing research. In this study, we isolated five major somatic tissues in young and aged worms and profiled the age-dependent miRNAomic changes within these tissues. In addition to the diverse ageing-regulated miRNA expression across tissues, we discovered numerous miRNAs in the tissues without their transcription. We further profiled miRNAs in the extracellular vesicles (EVs) and found that worm miRNAs undergo inter-tissue trafficking via EVs in an age-dependent manner. Using these datasets, we uncovered the interaction between mir-1 from body wall muscle and DAF-16/FOXO in the intestine, suggesting mir-1 as a messenger in inter-tissue signalling. Taken together, our study systematically investigated miRNAs in the somatic tissues and EVs during ageing, providing a valuable resource to study tissue-autonomous and nonautonomous functions of miRNAs in ageing.

High-cholesterol diet (HCD) and fine particulate matter (PM2.5) are related to stroke. The comprehensive influence of two factors on stroke is not well known, especially for females. In this study, we investigated brain injury and behavioral changes in female mice exposed to HCD plus PM2.5 for three months and six months, respectively. We measured gene expression of some factors related to stroke and the blood-brain barrier (BBB) in different groups of mice and further explored molecular mechanisms of epigenetic regulation of hypoxia-inducible factor-1α (HIF-1α). The results showed that HCD and PM2.5 co-exposure altered brain-body weight ratio, induced brain pathology damage and behavioral abnormality and elevated inflammatory markers (IL-6 and TNF-α) in mice relative to exposure to PM2.5 or HCD alone. Six-month exposure caused more severe brain damage than that three-month exposure. Co-exposure significantly changed the expressions of HIF-1α and the key genes (VEGF/COX-2/MMP-9/ZO-1/Occludin) in the HIF-1α signaling pathway in the brains of mice compared to the single exposure. Interestingly, HIF-1α was epigenetic regulated by histone deacetylase 4 (HDAC4) and histone 3 lysine 9 acetylation (H3K9ac) by chromatin immunoprecipitation (ChIP) assay. It suggests that the HIF-1α pathway exerts a crucial regulatory role in brain injury and behavioral abnormality in female mice after six-month exposure to HCD plus PM2.5, which are potential mechanisms for HCD and PM2.5-triggering stroke risk in female individuals.

In steel structural steel construction, it is common to have non-protected ancillary members interface with fire protected members. Current guidance and accepted practice do not consider the actual fire exposure risk present in the building or size of the member. A practical design framework was established to consider applied fire scenarios and the resultant structural behaviour of a building in a combined setting. The application of coat-back was also discussed. The 500mm coat-back is only applicable up to a 2-hour rating based on a hydrocarbon or ISO 834 fire curve. Higher fire resistance ratings may require increased coat-back. A 1-D heat transfer calculation can be used in application for coat-back lengths. The 3,000mm2 per metre length rule, for ancillary members not to be protected, appears to be still valid, although its threshold is not strictly 3,000mm2. These findings should be further investigated ideally with a full parametric study, including testing.

Adaptation to phytochemicals in herbivorous insects can influence tolerance to insecticides. However, it is unclear how insects use phytochemicals as cues to activate their metabolic detoxification systems. In this study, we found that dietary exposure to xanthotoxin enhanced tolerance of Spodoptera litura larvae to λ-cyhalothrin. Xanthotoxin ingestion significantly elevated the mRNA levels of 35 detoxification genes as well as the transcription factors Cap 'n' collar isoform-C (CncC) and its binding factor small muscle aponeurosis fibromatosis isoform-K (MafK). Additionally, xanthotoxin exposure increased the levels of reactive oxygen species (ROS), while ROS inhibitor N-acetylcysteine (NAC) treatment blocked xanthotoxin-induced expression of CncC, MafK, and detoxification genes and also prevented xanthotoxin-enhanced larval tolerance to λ-cyhalothrin. The 20-hydroxyecdysone (20E) signaling pathway was effectively activated by xanthotoxin, while blocking of 20E signaling transduction prevented xanthotoxin-enhanced larval tolerance to λ-cyhalothrin. Application of 20E induced the expression of multiple xanthotoxin-induced detoxification genes and enhanced λ-cyhalothrin tolerance in S. litura. NAC treatment blocked xanthotoxin-induced 20E synthesis, while the CncC agonist curcumin activated the 20E signaling pathway. These results indicate that the ROS/CncC pathway controls the induction of metabolic detoxification upon exposure to xanthotoxin, at least in part, through its regulation of the 20E signaling pathway.

Proanthocyanin (PA) dimers isolated from Acacia mearnsii bark were enzymatically acylated with palmitic acid as the acyl donor by immobilized Candida antarctica lipase on acrylic resin (Novozym 435). The acylation reaction conditions were optimized by comparing the amount of enzyme, the temperature, the reaction solvents, initial water content, substrate molar ratios and reaction time. The highest acylation conversion of 96.53% was achieved under the follow conditions: PA dimers/palmitic acid at a molar ratio of 1: 10 in tert-amyl alcohol; initial water content of 5% at 60 ℃ for 12 h with 30 g/L enzyme dosage. Introducing palmitic acid into PA dimers significantly improved both the lipophilicity and antioxidant properties. The 1-octanol/water partition coefficient of the PA dimers and their derivatives showed that the lipophilicity of the derivatives were 2.4 times higher than that of the PA dimers. The derivatives exhibited strong antioxidant scavenging capacities, approximately 1.6 times greater than the original dimers. This work is of great significance to expand the application of natural PA dimers in cosmetic and food industries and also lay a foundation for the high value-added utilization of A. mearnsii.

Dysregulation of the gut microbiota by environmental factors is associated with a variety of autoimmune and immune-mediated diseases. In addition, naturally-occurring extracellular antibiotic resistance genes (eARGs) might directly enter the gut via the food chain. However, following gut microbiota exposure to eARGs, the ecological processes shaping the microbiota community assembly, as well as the interplay between the microbiota composition, metabolic function, and the immune responses, are not well understood. Increasing focus on the One Health approach has led to an urgent need to investigate the direct health damage caused by eARGs. Herein, we reveal the significant influence of eARGs on microbiota communities, strongly driven by stochastic processes. How eARGs-stimulate variations in the composition and metabolomic function of the gut microbiota led to cytokine responses in mice of different age and sex were investigated. The results revealed that cytokines were significantly associated with immunomodulatory microbes, metabolites, and ARGs biomarkers. Cytokine production was associated with specific metabolic pathways (arachidonic acid and tryptophan metabolic pathways), as confirmed by

Arbuscular mycorrhizal fungi (AMF) are considered biofertilizers for sustainable agriculture due to their ability to facilitate plant uptake of important mineral elements, such as nitrogen (N). However, plant mycorrhiza-dependent N uptake and interplant transfer may be highly context-dependent, and whether it is affected by aboveground herbivory remains largely unknown. Here, we used 15N labeling and tracking to examine the effect of aboveground insect herbivory by Spodoptera frugiperda on mycorrhiza-dependent N uptake in maize (Zea mays L.). To minimize consumption differences and 15N loss due to insect chewing, insect herbivory was simulated by mechanical wounding and oral secretion of S. frugiperda larvae. Inoculation with Rhizophagus irregularis (Rir) significantly improved maize growth, and N/P uptake. The 15N labeling experiment showed that maize plants absorbed N from soils via the extraradical mycelium of mycorrhizal fungi and from neighboring plants transferred by common mycorrhizal networks (CMNs). Simulated aboveground leaf herbivory did not affect mycorrhiza-mediated N acquisition from soil. However, CMN-mediated N transfer from neighboring plants was blocked by leaf simulated herbivory. Our findings suggest that aboveground herbivory inhibits CMN-mediated N transfer between plants but does not affect N acquisition from soil solutions via extraradical mycorrhizal mycelium.

Development of ionic polymer electrolytes (IPEs) without flammable organics is a critical strategy to enable safe and high-energy lithium metal batteries (LMBs). As critical components in IPEs, ionic liquids (ILs) with high ionic conductivity and wide electrochemical window are promising candidates to enable LMBs. Here, we describe a fast and robust machine learning workflow embedded with quantum chemistry calculation and graph convolutional neural network to discover promising ILs for IPEs. By selecting subsets of the recommended ILs, combining with a rigid-rod polyelectrolyte and a predetermined lithium salt, we develop a class of large area and mechanically strong IPE membranes with thickness ~ 50 μm. The symmetric cells exhibit stable cycling performance at 1 mA cm-1 (0.5 mAh cm-2) up to 800 h at room temperature (RT) and excellent reversibility at 6 mA cm-2 (3 mAh cm-2) at 80 °C. With LiFePO4 loading ~ 10.3 mg cm-2, the full cells deliver outstanding capacity retention for > 350 cycles (> 96% with 0.5 C at RT; > 80% with 2 C at 50 °C), fast charge/discharge capability (146 mAh g-1 with 5 C at 80 °C) and ultrahigh coulombic efficiency (> 99.92%). This performance is rarely reported by any single-layer polymer electrolytes without any organic plasticizers/oligomers for LMBs.

Unsaturated lipids containing single or more carbon-carbon double bonds (C═C) within tissues are closely associated with various types of diseases. Mass spectrometry imaging (MSI) has been used to study the spatial distribution of lipid C═C location isomers in tissue sections. However, comprehensive characterization of lipid C═C location isomers using MSI remains challenging. Herein, we established an on-tissue charge-switching Paternò-Büchi (PB) derivatization method using 3-acetylpyridine (3-AP) as a reaction reagent, which can be used to detect and assign C═C location of glycerophospholipids (GPLs) as well as neutral lipids, such as fatty acids (FAs), under the same experimental workflow using matrix-assisted laser desorption/ionization (MALDI)-MSI. High coverage of mono- and poly-unsaturated C═C location isomers among various lipid classes including FA, phosphatidylcholine (PC), and sulfatide (SHexCer) in distinct regions of the mouse brain and kidney was visualized using MALDI-MS/MS imaging. This method has also been applied to map the spatial distribution of lipid C═C location isomers in the Alzheimer's disease (AD) mice model for the first time, which provides a new tool to study the relationships between the distribution of lipid structural diversity and neurodegenerative diseases.

The wide use and continuous abrasion of rubber-related products appears to be leading to an incredible release of p-phenylenediamine (PPD) antioxidants in the environment. However, no related research has been conducted on the pollution characteristics and potential health risks of PM2.5-bound PPDs. We report for the first time the ubiquitous distributions of six emerging PPDs and a quinone derivative, N-(1,3-dimethylbutyl)-N'-phenyl-p-phenylenediamine quinone (6PPDQ), in PM2.5 from urban areas of China. Atmospheric contamination levels of PM2.5-bound PPDs were found to be mostly in pg m-3 amounts between 2018 and 2019. Urban vehicle rubber tire abrasion was found to probably contribute to the PPDs in PM2.5 and accounted for their significant spatiotemporal-dependent concentration variations. Furthermore, 6PPDQ, an emerging oxidation product of 6PPD in the environment, was first quantified (pg m-3) with a total detection rate of 81% in the urban PM2.5, demonstrating its broad existence. On the basis of the determined ambient concentrations, the annual intakes of PPDs and 6PPDQ for adults were not low, indicating their possible human health risks induced by long-term exposure. This study confirms the widespread occurrence of PPDs and 6PPDQ in PM2.5, showing that the pollution of such compounds in urban air should not be underestimated.

This paper examines the impact of Ural blocking (UB) on winter sub-seasonal Siberian cold anomalies under the different background conditions of the winter East Asian trough (EAT). It is found that the meridional displacement and the strength of the winter EAT possibly modulate the persistence or lifetime of UB and associated sub-seasonal cold anomalies over Siberia through changing background circulation conditions. Statistical analysis reveals that UB events tend to occur more frequently in strong or southward EAT winters than in weak or northward EAT winters. A composite analysis of UB events further shows that UB has larger amplitude and longer lifetime in strong or southward EAT winters (especially the latter) than in weak or northward EAT winters, thus more likely leading to stronger sub-seasonal cold anomalies over Siberia. Moreover, the possible physical cause of why a strong or southward EAT favors UB is further investigated. It is found that winter zonal wind and meridional gradient of potential vorticity (PVy) tend to be weakened on the upstream side of Siberia near the Ural Mountains when the EAT is stronger or located more southward, favoring the maintenance of UB due to the strengthening (weakening) of the nonlinearity (energy dispersion) of UB. In contrast, when the EAT is weak or northward-displaced, a strengthening of winter zonal wind and PVy is more likely seen over the Ural Mountains and adjacent regions, which may suppress UB through enhancing its energy dispersion and reducing its nonlinearity.

The effect of Cu-riched clusters on strength and impact toughness in a tempered Cu-bearing high-strength low-alloy (HSLA) steel is investigated. With increasing the tempering temperature, it is found that the yield strength increases firstly, achieving the maximum value (~ 1053 MPa) at the tempering temperature of 450 °C, and then decreases significantly with the rise of tempering temperature. The tempering temperature-dependent yield strength is closely related to the precipitation of Cu-riched clusters. When tempering at 450 °C, the peak strength will be reached as the nanoscale Cu-riched clusters with small size and high number density will cause a strong precipitation strengthening (~ 492 MPa) due to the dislocation shearing mechanism. However, the Cu-riched clusters will coarsen with further increasing tempering temperature, resulting in obvious decrement of yield strength owing to the dislocation bypassing mechanism. Compared with the yield strength, the variation in impact energy displays an inverse tendency and the impact energy is only 7 J for the sample tempered at 450 °C. The fracture mode can be well explained by the competition between the cleavage fracture strength (σF) and “yield strength” (σY). Although transgranular cleavage fracture can be found in samples tempered at 450 and 550 °C, the crack propagation along the lath boundaries is prevented in the sample tempered at 550 °C. The reason is that the number density of Cu-riched clusters at lath boundaries decreases and the segregation of Mo element at the lath boundaries is induced, which will increase the bonding energy.

Inflammation is a defense mechanism associated with a wide range of diseases. Celastrol is a small molecule isolated from traditional Chinese medicine with potent anti-inflammation activity. In this study, we established an integrated quantitative proteomics strategy to investigate the acute response to celastrol treatment in a rat macrophage cell line challenged with lipopolysaccharide (LPS). Both stable-isotopic based non-targeted quantitative profiling and PRM-based targeted quantitation methods were employed. Dimethyl-labeling based non-targeted profiling revealed 28 and 52 proteins that significantly up- and down-regulated by celastrol. Bioinformatics analysis pinpoint key signaling pathways affected. Seven proteins were selected for examining their time-dependent regulatory pattern in response to celastrol using targeted PRM quantitation. The abundance of mRNA at multiple time-points of selected proteins was also examined. Celastrol induced an acute response of selected key transcriptional factors in terms of mRNA or protein abundance within one hour. Interestingly, regulatory trend of mRNA and protein abundance suggested a novel dual mechanism of celastrol in the terms of acute anti-inflammation. The integrated quantitative proteomic strategy established in this study constitutes an efficient workflow to characterize key components and their time-dependent regulatory pattern for monitoring drug response.

The drugs of programmed cell death 1 and its ligand 1 immune checkpoint inhibitors have ushered in a new era of anti-tumor immunotherapy, which has shown outstanding efficacy in some tumors, such as Hodgkin lymphoma, but there is still low response rate in some kinds of tumors. In recent years, bispecific antibodies prepared by cell fusion, recombinant DNA, protein engineering and other technologies can specifically bind two antigens or epitopes at the same time or successively, play a synergistic role in tumor treatment, can effectively inhibit tumor immune escape, and improve the effect of anti-tumor treatment has become a hot spot in tumor research. This paper will summarize the clinical research and development of bispecific antibodies, to provide reference for the industry. .【中文题目：抗肿瘤双特异性抗体研究进展与临床研发 关注要点】 【中文摘要：以程序性死亡受体1及其配体1免疫检查点抑制剂为代表的药物上市，开启了抗肿瘤免疫治疗的新时代，该类药物在某些肿瘤中表现出较为突出的持续应答，如霍奇金淋巴瘤，但仍在部分肿瘤中应答率低。近年来，双特异性抗体是通过细胞融合、重组DNA、蛋白质工程等技术制备的人工抗体，可同时或先后特异性结合两个抗原或抗原表位，在肿瘤治疗中发挥协同作用，能够有效抑制肿瘤免疫逃逸，提高抗肿瘤治疗效果，成为肿瘤研发热点。本文就双特异抗体研究进展和临床研发关注要点进行综述，以期为药物研发的相关人员提供参考。 】 【中文关键词：双特异性抗体；研究进展；临床研发】.