BindingSiteDTI: Differential-scale binding site modelling for Drug-Target interaction prediction.

MOTIVATION: Enhanced by contemporary computational advances, the prediction of drug-target interactions (DTIs) has become crucial in developing de novo and effective drugs. Existing deep learning approaches to DTI prediction are frequently beleaguered by a tendency to overfit specific molecular representations, which significantly impedes their predictive reliability and utility in novel drug discovery contexts. Furthermore, existing DTI networks often disregard the molecular size variance between macro molecules (targets) and micro molecules (drugs) by treating them at an equivalent scale that undermines the accurate elucidation of their interaction. RESULTS: We propose a novel DTI network with a differential-scale scheme to model the binding site for enhancing DTI prediction, which is named as BindingSiteDTI. It explicitly extracts multiscale substructures from targets with different scales of molecular size and fixed-scale substructures from drugs, facilitating the identification of structurally similar substructural tokens, and models the concealed relationships at the substructural level to construct interaction feature. Experiments conducted on popular benchmarks, including DUD-E, human and BindingDB, shown that BindingSiteDTI contains significant improvements compared with recent DTI prediction methods. AVAILABILITY: The source code of BindingSiteDTI can be accessed at https://github.com/MagicPF/BindingSiteDTI. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

Pharmacokinetics and tissue distribution of Yigong San in rats.

ETHNOPHARMACOLOGICAL RELEVANCE: In traditional Chinese medicine (TCM), Yigong San (YGS) is mainly used to treat dyspepsia caused by deficiency of spleen and stomach qi. Although the chemical composition and bioactivity of YGS has been well studied, the main in vivo compounds and their distribution in tissues still need to be made clearer. AIM OF THE STUDY: To elucidate the pharmacokinetic profiles and tissue distribution of eight main compounds of YGS in rats, and provide a reference for clinical application and new drug development. MATERIALS AND METHODS: UPLC-Q-Exactive-Orbitrap-MS was used to qualitatively characterize the parent compounds and their metabolites in the plasma of rats after oral administration of YGS. A sensitive, reliable, and accurate ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method using UPLC-AB Sciex QTRAP 5500 MS was established to quantitatively determine eight main compounds of YGS in rat plasma and tissues, including liquiritin, isoliquiritin, hesperidin, ginsenosides Rb1, Re and Rg1, atractylenolides I and II. RESULTS: The mean area under the concentration-time curve (AUC) values of ginsenoside Rb1, hesperidin, and liquiritin at low, medium, and high doses were greater than 150 ng h/mL. The elimination half-life (t1/2) values of ginsenoside Rb1, atractylenolides I and II (low and medium doses) were longer than 10 h. Peak time (Tmax) values of all compounds were shorter than 10 h. Except for atractylenolides, the maximum concentration (Cmax) values of the compounds were greater than 10 ng/mL. The eight compounds were detected in the heart, brain, liver, spleen and kidney at 0.25 h after oral administration. Liquiritin and isoliquiritin had higher exposure in the liver and heart. Hesperidin and ginsenosides Rb1, Re, and Rg1 are mainly distributed in the spleen and kidney. Atractylenolides I and II are mainly distributed in spleen, liver and kidney. CONCLUSION: All main compounds of YGS, i.e., liquiritin, isoliquiritin, hesperidin, ginsenosides Rb1, Re, and Rg1, and atractylenolides I and II are absorbed into plasma and widely distributed in various tissues. Among them, hesperidin, ginsenoside Rb1, and atractylenolide I are main in vivo compounds. They are mainly distributed in spleen, liver and kidney. The results of this study provide a basis for further in-depth development and application of YGS.

Engineering Carbon Nanotube Yarns with Polyaniline Coating toward Enhanced Thermoelectric Performance.

The growing demand for wearable electronics has driven the development of flexible thermoelectric (TE) generators which can harvest waste body heat as a renewable power source. Despite carbon nanotube (CNT) yarns have attracted significant attention as a promising candidate for TE materials, challenges still exist in improving their TE efficiency for commercial applications. Herein, we developed high performance CNT/polyaniline (PANI) yarns by engineering the coating of polyaniline emeraldine base (PANIeb), in which CNT yarns were firstly coated by PANIeb layer and further doped by HCl vapor treatment. With the incorporation of PANIeb, σ and S were simultaneously increased to 1796 S cm-1 and 74.8 µV K-1 for CNT/PANIeb 4-2d fibers, respectively. Further HCl vapor treatment induced greatly increased σ to 3194 S cm-1, but maintained be 83 % value before doping, giving rise to the highest power factor of 1224 µW m-1K-2, higher than pristine CNT yarns of 576 µW m-1K-2. Combining outstanding high TE performance and bending durability, a flexible TE generator was constructed to deliver high out power of 187 nW with temperature gradients of about 30 K. These results demonstrate the potential promise of high-performance CNT/PANI-HCl yarns to harvest waste body heat for sustainable power supply.

The Asthma Risk Gene, GSDMB, Promotes Mitochondrial DNA-induced ISGs Expression.

Released mitochondrial DNA (mtDNA) in cells activates cGAS-STING pathway, which induces expression of interferon-stimulated genes (ISGs) and thereby promotes inflammation, as frequently seen in asthmatic airways. However, whether the genetic determinant, Gasdermin B (GSDMB), the most replicated asthma risk gene, regulates this pathway remains unknown. We set out to determine whether and how GSDMB regulates mtDNA-activated cGAS-STING pathway and subsequent ISGs induction in human airway epithelial cells. Using qPCR, ELISA, native polyacrylamide gel electrophoresis, co-immunoprecipitation and immunofluorescence assays, we evaluated the regulation of GSDMB on cGAS-STING pathway in both BEAS-2B cells and primary normal human bronchial epithelial cells (nHBEs). mtDNA was extracted in plasma samples from human asthmatics and the correlation between mtDNA levels and eosinophil counts was analyzed. GSDMB is significantly associated with RANTES expression in asthmatic nasal epithelial brushing samples from the Genes-environments and Admixture in Latino Americans (GALA) II study. Over-expression of GSDMB promotes DNA-induced IFN and ISGs expression in bronchial epithelial BEAS-2B cells and nHBEs. Conversely, knockout of GSDMB led to weakened induction of interferon (IFNs) and ISGs in BEAS-2B cells. Mechanistically, GSDMB interacts with the C-terminus of STING, promoting the translocation of STING to Golgi, leading to the phosphorylation of IRF3 and induction of IFNs and ISGs. mtDNA copy number in serum from asthmatics was significantly correlated with blood eosinophil counts especially in male subjects. GSDMB promotes the activation of mtDNA and poly (dA:dT)-induced activation of cGAS-STING pathway in airway epithelial cells, leading to enhanced induction of ISGs.

Unveiling the activity difference cause and ring-opening reaction routes of typical radicals induced degradation of toluene.

This study employs five UV-AOPs (PMS, PDS, H2O2, NaClO and NaClO2) to produce radicals (•OH, SO4•-, ClO•, O2•- and 1O2) and further comparatively studies their activity sequence and activity difference cause in toluene degradation. The toluene mineralization efficiency as a descending order is 73 % (UV-PMS) > 71 % (UV-PDS) > 70 % (acidified-UV-NaClO) > 55 % (UV-H2O2) > 36 % (UV-NaClO) > 35 % (UV-NaClO2); that of conversion efficiency is 99 % (acidified-UV-NaClO) > 95 % (UV-PMS) > 90 % (UV-PDS) > 74 % (UV-H2O2) > 44 % (UV-NaClO) > 41 % (UV-NaClO2). Acidic pretreatment significantly boosts the reactivity of UV-NaClO. ESR combined with radical quenching tests reveals the radicals' generation and evolution, and their contribution rates to toluene conversion, i.e. ClO• > SO4•- > O2•- > 1O2 > â€¢OH. Theoretical calculations further unveil the ring-opening reaction routes and the nature of the activity difference of different radicals. The minimum energy required for ring-opening reaction is 116.77, 150.63, 168.29 and 191.92 kJ/mol with respect to ClO•, SO4•-, 1O2 and •OH, and finding that the ClO•-HO• pair is the best for toluene mineralization. The difficulty for eliminating typical VOCs by using UV-AOPs method is determined as toluene > chlorobenzene > benzene > ethyl acetate.

Mitochondrial-dependent oxidative phosphorylation is key for postnatal metabolic adaptation of alveolar macrophages in the lung.

Alveolar macrophages (AMs) seed in lung during embryogenesis and become mature in perinatal period. Establishment of acclimatization to environmental challenges is important, whereas the detailed mechanisms that drive metabolic adaptation of AMs remains to be elucidated. Here, we showed that energy metabolism of AMs was transformed from glycolysis prenatally to oxidative phosphorylation (OXPHOS) postnatally accompanied by up-regulated expression of mitochondrial transcription factor A (TFAM). TFAM deficiency disturbed mitochondrial stability and decreased OXPHOS, which finally impaired AM maintenance and function, but not AM embryonic development. Mechanistically, Tfam-deletion resulted in impaired mitochondrial respiration and decreased ATP production, which triggered endoplasmic reticulum (ER) stress to cause B cell lymphoma 2 ovarian killer (BOK) accumulation and abnormal distribution of intracellular Ca2+, eventually led to induce AM apoptotic death. Thus, our data illustrated mitochondrial-dependent OXPHOS played a key role in orchestrating AM postnatal metabolic adaptation.

A theoretical study on toluene oxidization by OH radical.

Toluene, a prominent member of volatile organic compounds (VOCs), exerts a substantial adverse influence on both human life and the environment. In the context of advanced oxidation processes, the ·OH radical emerges as a highly efficient oxidant, pivotal in the elimination of VOCs. This study employs computational quantum chemistry methods (G4MP2//B3LYP/6-311++G(d,p)) to systematically investigate the degradation of toluene by ·OH radicals in an implicit solvent model, and validates the rationale of choosing a single-reference method using T1 diagnostics. Our results suggest three possible reaction mechanisms for the oxidation of toluene by ·OH: firstly, the phenyl ring undergoes a hydrogen abstraction reaction followed by direct combination with ·OH to form cresol; secondly, ·OH directly adds to the phenyl ring, leading to ring opening; thirdly, oxidation of sidechain to benzoic acid followed by further addition and ring opening. The last two oxidation pathways involve the ring opening of toluene via the addition of ·OH, significantly facilitating the process. Therefore, both pathways are considered feasible for the degradation of toluene. Subsequently, the UV-H2O2 system was designed to induce the formation of ·OH for toluene degradation and to identify the optimal reaction conditions. It was demonstrated that ·OH and 1O2 are the primary active species for degrading toluene, with their contribution ranking as ·OH > 1O2. The intermediates in the mixture solution after reactions were characterized using GC-MS, demonstrating the validity of theoretical predictions. A comparative study of the toluene consumption rate revealed an experimental comprehensive activation energy of 10.33 kJ/mol, which is consistent with the preliminary activation energies obtained via theoretical analysis of these three mechanisms (0.56 kJ/mol to 13.66 kJ/mol), indicating that this theoretical method can provide a theoretical basis for experimental studies on the oxidation of toluene by ·OH.

Efficient red thermally activated delayed fluorescence emitters achieved through precise control of excited state energy levels.

The variety of highly efficient red/near-infrared (NIR) materials with thermally activated delayed fluorescence (TADF) feature is extremely limited so far, and it is necessary to expand the candidate pool of excellent red/deep-red emitters. However, how to control the energy level alignment of the 1CT (singlet charge transfer) state and the 3LE (triplet local excitation) state to improve the emission efficiency of materials remains a challenge. Herein, based on our previously reported green fluorescent material 67dTPA-FQ, three new donor-acceptor type TADF materials (TQ-oMeOTPA, TsQ-oMeOTPA and SQ-oMeOTPA) were designed by introducing 4,4'-dimethoxy triphenylamine (MeOTPA) as the donor, and introduced S atoms on the acceptors to enhance the spin-orbit coupling (SOC) and CT effects. The theoretical calculations showed that the newly introduced MeOTPA and S atom successfully enhanced the CT effect of the materials, not only shifting the luminescence peak to the deep red region but also effectively adjusting the energy level alignment of the excited state, accelerating the reverse intersystem crossing process. Finally, the organic light-emitting diodes based on SQ-oMeOTPA exhibit an external quantum efficiency of 19.1%, with an emission peak at 619 nm. This work not only expands the candidate inventory of red TADF materials, but also proves the feasibility of designing emitters by adjusting the excited state energy levels, greatly broadening the diversity of TADF emitters in design, and providing a powerful means for rapidly screening efficient emitters in the future.

Research on Chinese medicinal materials cultivation: A bibliometric and visual analysis.

Chinese medicinal materials (CMMs) are important strategic resource in China. The cultivation process of medicinal plants is the key link which directly affect the quality and efficacy. The literatures of CMMs cultivation were acquired from China National Knowledge Infrastructure (CNKI) database and State Intellectual Property Office (SIPO) patent database for the years between 2001 and 2021. All the articles found were subjected to bibliometric analysis. The development trends and key topics were analyzed and visualized by VOSviewer and CiteSpace software. The results indicate that ecological planting, under-forest economy, intercropping patterns and industrialization production are the research hotspots in this field; cultivation technology and nutritional fertilization technology are the main areas addressed in recent years. Therefore, the high-quality and sustainable development of CMMs cultivation should be examined in terms of theoretical approaches, technical innovation, multi-cooperation, and intellectual property protection.

7-Hydroxyflavone improves nonalcoholic fatty liver disease by acting on STK24.

The escalating incidence of nonalcoholic fatty liver disease (NAFLD) is closely associated with a high-fat diet, leading to a decline in quality of life and significant health impairment. 7-Hydroxyflavone (7-HY) is a flavonoid known for its anti-inflammatory, anticarcinogenic, and antioxidant effects. This study aims to assess the ameliorative effects of 7-HY on NAFLD induced by a high-fat diet and elucidate underlying mechanisms. Oleic acid/palmitic acid-induced HepG2 cells and C57BL/6 mice on a high-fat diet were utilized as in vitro and in vivo models. In animal experiments, 7-HY was utilized as a dietary supplement. The 15-week in vivo experiment monitored body weight, body fat percentage, glucose tolerance, insulin tolerance, and metabolic indexes. Commercial kits assessed triglyceride (TG) and total cholesterol levels in cells, liver tissue, and blood. Discovery Studio identified potential targets of 7-HY, compared with NAFLD-associated targets in the GeneCards database. Results indicated 7-HY mitigated fat accumulation, hepatic steatosis, and oxidative stress induced by a high-fat diet. Furthermore, 7-HY showed potential efficacy in ameliorating abnormal glucose metabolism and promoting energy metabolism. Reverse target finding and molecular docking demonstrated a robust interaction between 7-HY and serine/threonine kinase 24 (STK24). Subsequent experimental results confirmed 7-HY's ability to inhibit TG deposition in HepG2 cells through interaction with STK24. In conclusion, 7-HY demonstrated the capacity to alleviate high-fat diet-induced NAFLD, presenting a novel strategy for the prevention and treatment of NAFLD.

Proteomics study of primary and recurrent adamantinomatous craniopharyngiomas.

BACKGROUND: Adamantinomatous craniopharyngiomas (ACPs) are rare benign epithelial tumours with high recurrence and poor prognosis. Biological differences between recurrent and primary ACPs that may be associated with disease recurrence and treatment have yet to be evaluated at the proteomic level. In this study, we aimed to determine the proteomic profiles of paired recurrent and primary ACP, gain biological insight into ACP recurrence, and identify potential targets for ACP treatment. METHOD: Patients with ACP (n = 15) or Rathke's cleft cyst (RCC; n = 7) who underwent surgery at Sanbo Brain Hospital, Capital Medical University, Beijing, China and received pathological confirmation of ACP or RCC were enrolled in this study. We conducted a proteomic analysis to investigate the characteristics of primary ACP, paired recurrent ACP, and RCC. Western blotting was used to validate our proteomic results and assess the expression of key tumour-associated proteins in recurrent and primary ACPs. Flow cytometry was performed to evaluate the exhaustion of tumour-infiltrating lymphocytes (TILs) in primary and recurrent ACP tissue samples. Immunohistochemical staining for CD3 and PD-L1 was conducted to determine differences in T-cell infiltration and the expression of immunosuppressive molecules between paired primary and recurrent ACP samples. RESULTS: The bioinformatics analysis showed that proteins differentially expressed between recurrent and primary ACPs were significantly associated with extracellular matrix organisation and interleukin signalling. Cathepsin K, which was upregulated in recurrent ACP compared with that in primary ACP, may play a role in ACP recurrence. High infiltration of T cells and exhaustion of TILs were revealed by the flow cytometry analysis of ACP. CONCLUSIONS: This study provides a preliminary description of the proteomic differences between primary ACP, recurrent ACP, and RCC. Our findings serve as a resource for craniopharyngioma researchers and may ultimately expand existing knowledge of recurrent ACP and benefit clinical practice.

Survival benefits of human papillomavirus 16 infection in patients with esophageal squamous cell carcinoma undergoing chemoradiotherapy: A retrospective cohort study.

The role of human papillomavirus 16 (HPV 16) in esophageal squamous cell carcinoma (ESCC) remains uncertain. Therefore, this study aimed to investigate the prevalence of HPV 16 in patients with ESCC and its impact on theirprognosis. HPV 16 was detected using FISH, and TP53 status was evaluated via immunohistochemistry. The factors influencing prognosis were ananalyzed using the Log-rank test and Cox regression analyses. Among 178 patients with ESCC, 105 and 73 patients were categorized into concurrent chemoradiotherapy (CCRT) and postoperative chemoradiotherapy (POCRT) cohorts, respectively. Among 178 patients, 87 (48.87%) tested positive for HPV 16. Log-rank tests revealed that the overall survival (OS) of patients with ESCC who were HPV 16-positive was longer than that of those who were HPV 16-negative (median OS: 57 months vs. 27 months, p < 0.01**). HPV 16 infection and TP53 mutation status were identified as independent events. The OS of patients with mutant TP53 who were HPV 16-positive was longer than that of those who were HPV 16-negative in both CCRT and POCRT cohorts (p = 0.002** for CCRT cohorts and p = 0.0023** for POCRT cohorts). Conversely, HPV 16 infection had no effect on OS in the wild-type TP53 subgroup (p = 0.13 and 0.052 for CCRT and POCRT cohorts, respectively). As a conclusion, the positive rate of HPV 16 in ESCC in this study was 48.87% (87/178). Among the patients with ESCC who had TP53 mutation, those who were HPV 16-positive exhibited a better prognosis than those who were HPV 16-negative.

Functional phases define the response of the soil microbiome to environmental change.

A major challenge in microbiome research is understanding how natural communities respond to environmental change. The ecological, spatial, and chemical complexity of soils makes understanding the metabolic response of these communities to perturbations particularly challenging. Here we measure the dynamics of respiratory nitrate utilization in >1,500 soil microcosms from 20 soil samples subjected to pH perturbations. Despite the complexity of the soil microbiome a minimal mathematical model with two parameters, the quantity of active biomass and the availability of a limiting nutrient, quantifies observed nitrate utilization dynamics across soils and pH perturbations. Across environmental perturbations, the model reveals the existence of three functional phases each with distinct qualitative dynamics of nitrate utilization over time: a phase where acidic perturbations induce cell death that limits metabolic activity, a nutrient-limiting phase where nitrate uptake is performed by dominant taxa that utilize nutrients released from the soil matrix, and a resurgent growth phase in basic conditions, where nutrients are in excess and rare taxa rapidly outgrow dominant populations. The underlying mechanism of each phase is predicted by our interpretable model and tested via amendment experiments, nutrient measurements, and sequencing. Finally, our data suggest that how soils transition between functional phases depends on the long-term history of environmental variation in the wild. Therefore, quantitative measurements and a minimal mathematical formalism reveal the existence of qualitative phases that capture the mechanisms and dynamics of a community responding to environmental change.

Applications of Exosomal miRNAs from Mesenchymal Stem Cells as Skin Boosters.

The skin is the outer layer of the human body, and it is crucial in defending against injuries and damage. The regenerative capacity of aging and damaged skin caused by exposure to external stimuli is significantly impaired. Currently, the rise in average life expectancy and the modern population's aesthetic standards have sparked a desire for stem-cell-based therapies that can address skin health conditions. In recent years, mesenchymal stem cells (MSCs) as therapeutic agents have provided a promising and effective alternative for managing skin regeneration and rejuvenation, attributing to their healing capacities that can be applied to damaged and aged skin. However, it has been established that the therapeutic effects of MSC may be primarily mediated by paracrine mechanisms, particularly the release of exosomes (Exos). Exosomes are nanoscale extracellular vesicles (EVs) that have lipid bilayer and membrane structures and can be naturally released by different types of cells. They influence the physiological and pathological processes of recipient cells by transferring a variety of bioactive molecules, including lipids, proteins, and nucleic acids such as messenger RNAs (mRNAs) and microRNAs (miRNAs) between cells, thus playing an important role in intercellular communication and activating signaling pathways in target cells. Among them, miRNAs, a type of endogenous regulatory non-coding RNA, are often incorporated into exosomes as important signaling molecules regulating protein biosynthesis. Emerging evidence suggests that exosomal miRNAs from MSC play a key role in skin regeneration and rejuvenation by targeting multiple genes and regulating various biological processes, such as participating in inflammatory responses, cell migration, proliferation, and apoptosis. In this review, we summarize the recent studies and observations on how MSC-derived exosomal miRNAs contribute to the regeneration and rejuvenation of skin tissue, with particular attention to the applications of bioengineering methods for manipulating the miRNA content of exosome cargo to improve their therapeutic potential. This review can provide new clues for the diagnosis and treatment of skin damage and aging, as well as assist investigators in exploring innovative therapeutic strategies for treating a multitude of skin problems with the aim of delaying skin aging, promoting skin regeneration, and maintaining healthy skin.

Hypoxia-induced TRPM7 promotes glycolytic metabolism and progression in hepatocellular carcinoma.

BACKGROUND: Hypoxia disrupts glucose metabolism in hepatocellular carcinoma (HCC). Transient receptor potential cation channel, subfamily M, member 7 (TRPM7) plays an ontogenetic role. Thus, we aimed to explore the regulation of TRPM7 by hypoxia-induced factor (HIF) and its underlying mechanisms in HCC. METHODS: hypoxia was induced in multiple HCC cells using 1% O2 or CoCl2 treatment, and subsequently blocked using siRNAs targeting HIF-1α or HIF-2α as well as a HIF-1α protein synthesis inhibitor. The levels of HIF-1α and TRPM7 were assessed using quantitative PCR (qPCR) and Western blot analysis. Chromatin immunoprecipitation (ChIP) and luciferase assays were performed to observe the regulation of TRPM7 promoter regions by HIF-1α. A PCR array was utilized to screen glucose metabolism-related enzymes in HEK293 cells overexpressing TRPM7 induced by tetracycline, and then verified in TRPM7-overexpressed huh7 cells. Finally, CCK-8, transwell, scratch and tumor formation experiments in nude mice were conducted to examine the effect of TRPM7 on proliferation and metastasis in HCC. RESULTS: Exposure to hypoxia led to increase the levels of TRPM7 and HIF-1α in HCC cells, which were inhibited by HIF-1α siRNA or enhanced by HIF-1α overexpression. HIF-1α directly bound to two hypoxia response elements (HREs) in the TRPM7 promoter. Several glycolytic metabolism-related enzymes, were simultaneously upregulated in HEK293 and huh7 cells overexpressing TRPM7 during hypoxia. In vitro and in vivo experiments demonstrated that TRPM7 promoted the proliferation and metastasis of HCC cells. CONCLUSIONS: TRPM7 was directly transcriptionally regulated by HIF-1α, leading to glycolytic metabolic reprogramming and the promotion of HCC proliferation and metastasis in vitro and in vivo. Our findings suggest that TRPM7 might be a potential diagnostic indicator and therapeutic target for HCC.

Amyloplast is involved in the MIZ1-modulated root hydrotropism.

Roots exhibit hydrotropism in response to moisture gradients, with the hydrotropism-related gene Mizu-kussei1 (MIZ1) playing a role in regulating root hydrotropism in an oblique orientation. However, the mechanisms underlying MIZ1-regulated root hydrotropism are not well understood. In this study, we employed obliquely oriented experimental systems to investigate root hydrotropism in Arabidopsis. We found that the miz1 mutant displays reduced root hydrotropism but increased root gravitropism following hydrostimulation, as compared to wild-type plants. Conversely, overexpression of AtMIZ1 leads to enhanced root hydrotropism but decreased root gravitropism following hydrostimulation, as compared to wild-type plants. Using co-immunoprecipitation followed by mass spectrometry (IP-MS), we explored proteins that interact with AtMIZ1, and we identified PGMC1 co-immunoprecipitated with MIZ1 in vivo. Furthermore, the miz1 mutant exhibited higher expression of the PGMC1 gene and increased phosphoglucomutase (PGM) activity, while AtMIZ1 overexpressors resulted in lower expression of the PGMC1 gene, reduced amyloplast amount, and reduced PGM activity in comparison to wild-type roots. In addition, different Arabidopsis natural accessions having difference in their hydrotropic response demonstrated expression level of PGMC1 was negatively correlated with hydrotropic root curvature and AtMIZ1 expression. Our results provide valuable insights into the role of amyloplast in MIZ1-regulated root hydrotropism.

Associations of residential greenness exposure and ambient air pollutants with newly-diagnosed drug-resistant tuberculosis cases.

Growing evidence has found the health protective effects of greenness exposure on tuberculosis (TB) and the impact of ambient air pollutants on TB drug-resistance. However, it remains unclear whether residential greenness is also beneficial to reduce TB drug-resistance, and whether air pollution modify the greenness-TB resistance relationship. We enrolled 5006 newly-diagnosed TB patients from Shandong, China, during 2014 to 2021. Normalized Difference Vegetation Index (NDVI) in 250 m and 500 m buffer around individuals' residential zone was used to assess greenness exposure. All patients were divided by quartiles of NDVI250-m and NDVI500-m (from low to high: Q1, Q2, Q3, Q4) respectively. Six logistic regression models (NDVI, NDVI + PM2.5/PM10/SO2/NO2/O3) were used to estimate the association of NDVI and TB drug-resistance when adjusting different air pollutants or not. All models were adjusted for age, gender, body mass index, complications, smoking, drinking, population density, nighttime light index, road density. Compared with participants in NDVI250-m Q1 and NDVI500-m Q1, other groups had lower rates of MDR-TB, PDR-TB, RFP-resistance, SM-resistance, RFP + SM resistance, INH + RFP + EMB + SM resistance. NDVI500-m reduced the risk of multidrug resistant tuberculosis (MDR-TB) and the adjusted odds ratio (aOR, 95% confidence interval, CI) compared with NDVI500-m Q1 were 0.736 (0.547-0.991) in NDVI + PM10 model, 0.733 (0.544-0.986) in NDVI + PM2.5 model, 0.735(0.546-0.99) in NDVI + SO2 model, 0.736 (0.546-0.991) in NDVI + NO2 model, respectively, P < 0.05. NDVI500-m contributed to a decreased risk of streptomycin (SM)-resistance. The aOR of rifampicin (RFP) + SM resistance were 0.132 (NDVI250-m, Q4 vs Q1, 95% CI: 0.03-0.578), 0.199 (NDVI500-m, Q3 vs. Q1, 95% CI: 0.057-0.688) and 0.264 (NDVI500-m, Q4 vs. Q1, 95% CI: 0.087-0.799). The adjusted ORs (Q2 vs. Q1, 95% CI) of isoniazid (INH) + RFP + ethambutol (EMB) + SM resistance in 500 m buffer were 0.276 (0.119-0.639) in NDVI model, 0.279 (0.11-0.705) in NDVI + PM10 model, 0.281 (0.111-0.713) in NDVI + PM2.5 model, 0.279 (0.11-0.709) in NDVI + SO2 model, 0.296 (0.117-0.754) in NDVI + NO2 model, 0.294 (0.116-0.748) in NDVI + O3 model, respectively. The study showed, for the first time, that residential greenness exposure in 500 m buffer is beneficial for reducing newly-diagnosed DR-TB (including PDR-RB, MDR-TB, MR-TB), and ambient air pollutants may partially mediate this association.

Global trends and burden of stroke attributable to particulate matter pollution from 1990 to 2019.

OBJECTIVE: To investigate the association between particulate matter and the incidence, disability, and mortality of stroke, we reported the burden of stroke attributable to particulate matter (PM2.5) pollution, including ambient particulate matter pollution (APMP) and household air pollution from solid fuels (HAP), from 1990 to 2019. METHODS: We retrieved the detailed data on the burden of stroke attributable to PM2.5 from the Global Burden of Disease (GBD) 2019. The number of disability-adjusted life-years (DALYs) and deaths, age-standardized death rates (ASMR), and age-standardized disability-adjusted life-years rates (ASDR) attributable to PM2.5 were estimated by age, sex, geographical location, socio-demographic index (SDI), and stroke subtypes (ischemic stroke, intracerebral hemorrhage, and subarachnoid hemorrhage). The estimated annual percentage change (EAPC) was calculated to assess the trends in ASDR and ASMR during the period 1990-2019. RESULTS: Regarding stroke subtypes, the proportion of ischemic stroke burden is increasing, while intracerebral hemorrhage carries the heaviest burden. Both APMP and HAP contributed the most to stroke-related deaths and DALYs of stroke among the elderly populations and males. The highest ASDR and ASMR of stroke attributable to APMP were in the middle SDI regions, especially in East Asia. For HAP, the highest ASDR and ASMR were in the low SDI regions, mainly in Oceania. From 1990-2019, in terms of the EAPC results, APMP caused an increased burden of stroke, whereas the impact of HAP significantly fell. The most pronounced increase in ASDR and ASMR for strokes attributed to APMP were in the low-middle SDI and low SDI regions, particularly among the 25-35 age group. CONCLUSIONS: Stroke attributed to PM2.5 is a global health problem, and the patterns and trends were heterogeneous across APMP and HAP. Targeted interventions should be formulated for APMP and HAP.

Same allocation proposed by an individual or a group elicits distinct responses: Evidence from event-related potentials and neural oscillation.

People tend to perceive the same information differently depending on whether it is expressed in an individual or a group frame. It has also been found that the individual (vs. group) frame of expression tends to lead to more charitable giving and greater tolerance of wealth inequality. However, little is known about whether the same resource allocation in social interactions elicits distinct responses depending on proposer type. Using the second-party punishment task, this study examined whether the same allocation from different proposers (individual vs. group) leads to differences in recipient behavior and the neural mechanisms. Behavioral results showed that reaction times were longer in the unfair (vs. fair) condition, and this difference was more pronounced when the proposer was the individual (vs. group). Neural results showed that proposer type (individual vs. group) influenced early automatic processing (indicated by AN1, P2, and central alpha band), middle processing (indicated by MFN and right frontal theta band), and late elaborative processing (indicated by P3 and parietal alpha band) of fairness in resource allocation. These results revealed more attentional resources were captured by the group proposer in the early stage of fairness processing, and more cognitive resources were consumed by processing group-proposed unfair allocations in the late stage, possibly because group proposers are less identifiable than individual proposers. The findings provide behavioral and neural evidence for the effects of "individual/group" framing leading to cognitive differences. They also deliver insights into social governance issues, such as punishing individual and/or group violations.

CYP1B1 affects the integrity of the blood-brain barrier and oxidative stress in the striatum: An investigation of manganese-induced neurotoxicity.

AIMS: Excessive influx of manganese (Mn) into the brain across the blood-brain barrier induces neurodegeneration. CYP1B1 is involved in the metabolism of arachidonic acid (AA) that affects vascular homeostasis. We aimed to investigate the effect of brain CYP1B1 on Mn-induced neurotoxicity. METHOD: Brain Mn concentrations and α-synuclein accumulation were measured in wild-type and CYP1B1 knockout mice treated with MnCl2 (30 mg/kg) and biotin (0.2 g/kg) for 21 continuous days. Tight junctions and oxidative stress were analyzed in hCMEC/D3 and SH-SY5Y cells after the treatment with MnCl2 (200 µM) and CYP1B1-derived AA metabolites (HETEs and EETs). RESULTS: Mn exposure inhibited brain CYP1B1, and CYP1B1 deficiency increased brain Mn concentrations and accelerated α-synuclein deposition in the striatum. CYP1B1 deficiency disrupted the integrity of the blood-brain barrier (BBB) and increased the ratio of 3, 4-dihydroxyphenylacetic acid (DOPAC) to dopamine in the striatum. HETEs attenuated Mn-induced inhibition of tight junctions by activating PPARγ in endothelial cells. Additionally, EETs attenuated Mn-induced up-regulation of the KLF/MAO-B axis and down-regulation of NRF2 in neuronal cells. Biotin up-regulated brain CYP1B1 and reduced Mn-induced neurotoxicity in mice. CONCLUSIONS: Brain CYP1B1 plays a critical role in both cerebrovascular and dopamine homeostasis, which might serve as a novel therapeutic target for the prevention of Mn-induced neurotoxicity.