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Geospatial data, especially remote sensing (RS) data, are of significant importance for public services and production activities. Expertise is critical in processing raw data, generating geospatial information, and acquiring domain knowledge and other remote sensing applications. However, existing geospatial service platforms are more oriented towards the professional users in the implementation process and final application. Building appropriate geographic applications for non-professionals remains a challenge. In this study, a geospatial data service architecture is designed that links desktop geographic information system (GIS) software and cloud-based platforms to construct an efficient user collaboration platform. Based on the scalability of the platform, four web apps with different themes are developed. Data in the fields of ecology, oceanography, and geology are uploaded to the platform by the users. In this pilot phase, the gap between non-specialized users and experts is successfully bridged, demonstrating the platform's powerful interactivity and visualization. The paper finally evaluates the capability of building spatial data infrastructures (SDI) based on GeoNode and discusses the current limitations. The support for three-dimensional data, the improvement of metadata creation and management, and the fostering of an open geo-community are the next steps. [ABSTRACT FROM AUTHOR]

Background: Although gender differences in major depressive disorder (MDD) have been widely reported, there has not been much focus on gender differences in comorbidity. In patients with MDD and comorbid metabolic syndrome (Mets), the goal of this study was to investigate potential gender differences in the prevalence and clinical correlates of concomitant anxiety. Methods: Seven hundred and ninety-four first-episode and drug-naïve patients (FEDN) patients with MDD and comorbid Mets were recruited. For each patient, sociodemographic data, thyroid function indicators, and Mets parameters were acquired. Each participant completed the 14-item Hamilton Assessment Scale for Anxiety (HAMA) and the 17-item Hamilton Assessment Scale for Depression (HAMD). Results: There were no gender differences in the prevalence of anxiety in patients with MDD and comorbid Mets. Female patients with MDD had a shorter duration of illness. Correlation analysis showed that HAMD score, TSH, TgAb, and TPOAb were associated with anxiety prevalence in female patients, whereas anxiety onset in male patients was only associated with TSH, TgAb, and TPOAb levels. In addition, multiple logistic regression analysis showed that TSH and TgAb predicted anxiety in male patients, whereas HAMD score and age of onset significantly predicted anxiety in female patients. Limitations: Cross-sectional design and no control for anxiety-related factors. Conclusions: Our study showed no gender differences in the prevalence of anxiety in patients with MDD and comorbid Mets. HAMD score was associated with anxiety in female patients, whereas TSH, TgAb, and TPOAb were associated with anxiety in male patients. [ABSTRACT FROM AUTHOR]

Hydrogen energy has a significant and incredible impact on emerging technologies. However, the eco-friendly and clean production of hydrogen energy is under examination and challenging. Water splitting has been considered a sparkling and substantial resource for hydrogen energy, which is strongly dependent on the efficiency of the electrocatalysts. Owing to low cost, rich surface chemistry, greater electrocatalytic active sites, electrical conductivity and weak Se–H strength, metal selenides have originated the efficient electrocatalysts among the chalcogenides family. Several strategies have been adopted to enhance their electrocatalytic characteristics for hydrogen evolution reactions, either in the form of single or multi-metals selenides or post-transition elements doped metal selenides. Herein, fundamentals, synthesis methodologies, and the detailed electrocatalytic activities of the metal selenides have been comprehensively presented. The existing drawbacks and market values have also been concisely summarized for fresh readers and researchers to describe metal selenide electrocatalysts for hydrogen evolution reaction. • Hydrogen energy has a remarkable significance for recent technologies. • Synthesis strategies have been discussed. • Different strategies for Single metal selenides have been discussed. • Multi-metals-based metal selenides have been summarized. • Post-transition elements doped metal selenides have been summarized. [ABSTRACT FROM AUTHOR]

Nickel oxide nanoparticles (NiO-NPs) are common nanomaterials that may be released into the environment, affecting the toxicity of other contaminants. Atrazine (ATZ) is a commonly used herbicide that can harm organisms due to its persistence and bioaccumulation in the environment. Although the toxicity of ATZ to earthworms is well-documented, the risk of co-exposure with NiO-NPs increases as more nanoparticles accumulate in the soil. In this study, we investigated the effects and mechanisms of NiO-NPs on the accumulation of ATZ in earthworms. The results showed that after day 21, the antioxidant system of the cells under ATZ treatment alone was adversely affected, with ROS content 36.05 % higher than that of the control (CK) group. However, the addition of NiO-NPs reduced the ROS contents in the earthworms by 0.6 %− 32.3 %. Moreover, analysis of earthworm intestinal sections indicates that NiO-NPs mitigated cellular and tissue damage caused by ATZ. High-throughput sequencing revealed that NiO-NPs in earthworm intestines increased the abundance of Pseudomonas aeruginosa and Aeromonas aeruginosa. Additionally, the enhanced function of the ABC transport system in the gut resulted in lower accumulation of ATZ in earthworms. In summary, NiO-NPs can reduce the accumulation and thus the toxicity of ATZ in earthworms. Our study contributes to a deeper understanding of the effects of NiO-NPs on co-existing pollutants. [Display omitted] • Suitable concentrations NiO-NPs inhibited the uptake of ATZ in earthworms. • NiO-NPs reduces oxidative stress of ATZ in earthworms. • NiO-NPs reduces intestine damage by ATZ in earthworms. • NiO-NPs increases the abundance of Aeromonas aeruginosa in the intestine. [ABSTRACT FROM AUTHOR]

The paper reports in silico three modified small molecules, two negatively charged E1C and E2C and one neutral TQ, which show more potent inhibitory effect than their parental molecules CQ3, TS0, and ER on the Cu2+ induced Aβ42 aggregation. In the acidic condition, TQ is the most powerful inhibitor, as it not only decreases the helix content of Cu2+‐Aβ42 complex but also increases the oxidizability; E1C/E2C however decreases the helix content of Cu2+‐Aβ42 complex but also with increased oxidizability, indicating that the inhibitory effect of the two charged molecules depends on the multiple factors, at least including the composite mechanism of helix decrease and oxidizability increase. In the basic condition, any of three modified molecules can increase the helix content of the Cu2+‐Aβ42 complex. Anyway, small molecules containing neutral and larger hydrophobic aromatic groups are always more effective in inhibiting Cu2+‐induced Aβ42 aggregation in both basic and acidic conditions. [ABSTRACT FROM AUTHOR]

Background: Short-chain enoyl-CoA hydratase (ECHS1) is a multifunctional mitochondrial matrix enzyme involved in the second step of mitochondrial fatty acid β-oxidation. Mitochondrial diseases resulting from ECHS1 mutations are often characterised by encephalopathy, deafness, epilepsy, optic atrophy, cardiomyopathy, dystonia, and lactic acidosis. In this study, we report two novel heterogeneous variants, c.414 + 5G > A (in intron 3) and c.310C > G (in CDS), of ECHS1 in an infant with mitochondrial encephalopathy.Case Presentation: The two novel variants, c.414 + 5G > A (Chr10:135183403) in intron 3 and c.310C > G (Chr10:135183512) in CDS, were identified by next generation sequencing (NGS). A minigene assay was used to analyse the function of the c.414 + 5G > A variant. ECHS1 enzyme activity was measured by spectrophotometry in the patient-derived myoblasts. The 2-year old patient presented with mitochondrial encephalopathy since birth. Clinical features were encephalopathy, epilepsy, and hindered psychomotor and language development. Serum lactate and blood ammonia levels were elevated, and brain magnetic resonance imaging showed abnormal signals in the bilateral frontal, parietal, and occipital cortices and brainstem and basal ganglia. We found two novel heterogeneous variants in ECHS1 in this patient. Minigene assay revealed the c.414 + 5G > A variant as the cause of intronic cryptic splice site activation and 39 bp deletion in mature mRNA. In silico analysis predicted that c.310C > G might change glutamine (Q) to glutamic acid (E) in the 104th amino acid sequence (p.Q104E). To investigate the impact of these two variants on protein function, we constructed a 3D model of human ECHS1 and showed that the variants might alter the highly conserved region in close proximity to the active site, which might hinder, or even halt, enzymatic activity. The experimental assay showed that ECHS1 enzyme activity in the patient-derived myoblasts decreased compared to that in control.Conclusions: Our findings are the first to report a mitochondrial encephalopathy infant carrying two novel ECHS1 variants, c.414 + 5G > A and c.310C > G, which might be deleterious variants, function as pathogenicity markers for mitochondrial encephalopathy, and facilitate disease diagnosis. [ABSTRACT FROM AUTHOR]

The time-dependent pollution routing problem (TDPRP) extends the pollution routing problem (PRP) cause it captures traffic congestion at peak periods in urban transportation. It concerns planning a fleet of homogeneous vehicles to serve all customers, jointly deciding their speed on every arc and the departure time from each node such that the total cost of routes reaches a minimum. To our knowledge, all solution methods for the TDPRP are founded on (meta-)heuristics. In this study, we propose an exact branch-and-price-and-cut (BPC) algorithm for the TDPRP. The master problem is a route selection problem formulated as a set-partitioning model, and the pricing problem is a time-dependent elementary shortest path problem with resource constraints (TDESPPRC), in which the speed and start time at each customer need to be decided. We devise a tailored label-setting algorithm to handle the pricing problem, and the master problem is solved by column generation. Then, two valid inequalities are employed to tighten the lower bound, and several accelerating techniques are used to speed up the label-setting algorithm. Meanwhile, we present an analytical characterization applied to different scenarios. Finally, extensive computational experiments show our algorithm outperform a commercial MIP solver, and the optimal solutions are found for more benchmark instances using less time. • This paper presents an exact solution based on a BPC algorithm for the TDPRP. The corresponding pricing problem is a TDESPPRC, which is tailored to solve by a label-setting algorithm. • This paper introduces an easy-to-check dominance rule by exploiting the structure of the departure time and the total cost function. The extensive computational experiments show the effectiveness and efficiency of our algorithm. • Our new dominance idea could be used to effectively solve the pricing problems of other VRP variants, where the dominance test needs to compare functions, for example, the PRP, the VRPSTW and the TDVRP. [ABSTRACT FROM AUTHOR]

The increased prevalence of obesity has been a major medical and public health problem in the past decades. In obese status, insulin resistance and sustained oxidative stress damage might give rise to behavioral deficits. The anti-obesity and anti-oxidant effects of allicin have been previously reported in peripheral tissues. In the present study, the functions and mechanisms of allicin involved in the prevention of high-fat diet (HFD)-induced depressive-like behaviors were investigated to better understand the pharmacological activities of allicin. Obese mice (five weeks of age) were treated with allicin (50, 100, and 200 mg/kg) by gavage for 15 weeks and behavioral test (sucrose preference, open field, and tail suspension) were performed. Furthermore, markers of oxidative stress, mitochondrial function, autophagy, and insulin resistance were measured in the hippocampal tissue. Finally, the levels of NADPH oxidase (NOX2, NOX4) and the nuclear factor erythroid 2-related factor 2 (Nrf2) pathway were evaluated in the hippocampus. The body weight, metabolic disorders, and depressive-like behaviors in obese mice were ameliorated by allicin. The depressive-like behaviors presented in the obese mice were accompanied by remarkably excessive reactive oxygen species (ROS) production and oxidative stress, damaged mitochondrial function, imbalanced autophagy, and enhanced insulin resistance in the hippocampus. We found that allicin improved the above undesirable effects in the obese mice. Furthermore, allicin significantly decreased NOX2 and NOX4 levels and activated the Nrf2 pathway. Allicin attenuated depressive-like behaviors triggered by long-term HFD consumption by inhibiting ROS production and oxidative stress, improving mitochondrial function, regulating autophagy, and reducing insulin resistance in the hippocampus via optimization of NOX/Nrf2 imbalance. [ABSTRACT FROM AUTHOR]

Aim: We investigated the effects of pentamethylquercetin (PMQ) on the tumor growth in monosodium glutamate (MSG)-induced obese mice. Materials and Methods: At the age of 5 weeks, control and MSG mice were, respectively, divided into five groups (n = 10): Vehicle group; PMQ 5, 10, 20 mg/kg; and metformin (MET) 300 mg/kg groups. All mice were administrated PMQ and MET by gastric gavage from 5- to 24-week age. 22-week-old mice were injection with H22 hepatic ascitic tumor cells. After 2 weeks, animals were anesthetized and blood, tumor, and liver tissues were harvested. Results: Compared with control mice, MSG mice showed obviously metabolic disorders and larger tumor weight and volume than those of control mice. PMQ and MET administration reduced body weight, improved glucose and lipid metabolism, and insulin resistance and inhibited tumor growth in MSG mice. However, PMQ and MET had a litter effect on the tumor growth and metabolic indexes in the control mice. Furthermore, there is significant positive correlation between improved insulin resistance and inhibited tumor growth by chronic PMQ and MET treatment. Further experiments showed PMQ and MET treatment upregulated mRNA expressions of sirtuin 6 (sirt6) both in tumor and liver tissues. Conclusion: Our results demonstrated PMQ decreased tumor growth in the MSG mice and the potential mechanisms might be attributed to upregulated mRNA expressions of sirt6. [ABSTRACT FROM AUTHOR]

Kaempferol (KFL), the major constituent of various fruits and vegetables, could attenuate oxidaitve stress and inflammation. The aims of the present study were to explore the ameliorative abilities of KFL on the depressive-like behaviors in a chronic social defeat stress (CSDS) mouse model, and to determine the potential mechanisms on oxidative stress, neuroinflammation, and AKT/β-catenin signaling pathway. Three behavioral tests, sucrose preference test (SPT), social interaction test (SIT), and tail suspension test (TST), were used to evaluate the antidepressive effects of KFL in CSDS mice. Activity levels of antioxidant enzyme, superoxide dismutase (SOD), glutathione peroxidase (GPx), catalase (CAT), glutathione s-transferase (GST), and concentrations of malonaldehyde (MDA) and protein carbonylation in the prefrontal cortex were assessed by commercial kits, respectively. Elisa was used to detect the levels of interleukin-1β (IL-1β) and tumor necrosis factor α (TNF-α). Q-PCR was used to determine the mRNA level of CD-11b. Furthermore, activity level of AKT/β-catenin signaling in the prefrontal cortex of CSDS mice was investigated by western blot. In addition, LY294002, a PI3-K inhibitor, was used to investigate the role of AKT/β-catenin signaling in the antidepressant effects of KFL. Social defeat stress reduced the bodyweights, sucrose consumptions, social interaction times, and the tail suspension mobility times in mice. CSDS mice were also exhibited remarkablely increased levels in oxidative stress markers, inflammatory mediators, and decreased activity of AKT/β-catenin cascade in the prefrontal cortex, which were reversed by treatment with KFL. Interestingly, LY294002 appeared to partly inhibit the overall KFL-mediated protective effects in the CSDS mice. These results confirmed that KFL exerted antidepressive effects, which might be mediated, at least in part, by enhanced antioxidant abilities and anti-inflammation effects via up-regulation AKT/β-catenin cascade activity in the prefrontal cortex of CSDS mice. Thus, KFL might be a promising, effective, and safe food medicine for depression treatment. [ABSTRACT FROM AUTHOR]

Allicin, one of the main biologically active compounds derived from garlic, was previously reported to possess multiple pharmacological activities. Whether allicin protected against chronic social defeat stress (CSDS) induced depressive-like behaviors remained unknown. Thus, our present study for the first time investigated the potential antidepressant effects and the mechanisms of allicin on the CSDS mice model. Thirty minutes before social defeat stress, allicin (2, 10, 50 mg/kg) was treated by intraperitoneal injection. The duration times of CSDS model establishment and allicin intervene were 10 days. Subsequently, the force swimming test (FST), social interaction test (SIT), and sucrose preference test (SPT) were applied for behavioral assessments. The levels of inflammation mediators were determined by commercial ELISA kits. The concentration of iron was tested, and relative protein expressions were measured by western blot. Oxidative stress and apoptosis markers were also detected by commercial kits and western blot. The behavioral defects induced by social defeat stress were obviously improved by allicin. Microglia activation, as well as inflammatory cytokines elevation in the hippocampus of CSDS also down-regulated by administration of allicin. Furthermore, content of iron and protein expressions of key components in iron metabolism were remarkably aberrant changed in the CSDS mice hippocampus, meanwhile, allicin ameliorated this phenomenon. Allicin decreased the production of reactive oxygen species (ROS), malondialdehyde (MDA), and protein carbonyl, and the protein expression of NOX4, as well as up-regulated the activities of superoxide dismutase (SOD) and Nrf2/HO-1 pathway. In addition, allicin attenuated the enhanced neuronal apoptosis. Finally, allicin supplementation inhibited the Nucleotide-binding oligomerization domain containing 3 (NLRP3) inflammasome hyperactivity, and the expressions of inflammasome components, such as ACS, caspase-1, and IL-1β in the hippocampus of CSDS mice. Allicin attenuated depressive-like behaviors of CSDS mice through reducing neuroinflammation, ameliorating iron abnromal accumulation, balacing oxidative stress, and attenuation neuronal apoptosis in the hippocampus via suppression of NLRP3 inflammasome. [ABSTRACT FROM AUTHOR]

Background Qing brick tea (QBT), traditional and popular beverage for Chinese people, is an important post-fermentation dark tea. Our present study was performed to investigate the ameliorative effects of QBT aqueous extract on metabolic syndrome (Mets) in monosodium glutamate-induced obese mice and the potential mechanisms. Method Monosodium glutamate-induced obese mice were used to evaluate the anti-Mets effects of QBT. Content levels of malonaldehyde (MDA), reactive oxygen species (ROS) and protein carbonylation, antioxidant enzyme activities of superoxide dismutase (SOD), glutathione peroxidase (GPx), catalase (CAT), glutathione reductase (GR) in the skeletal muscle were assessed by commercial kits, respectively. Western blot and Q-PCR were used to detect the expressions of Transcription Factor Nuclear Factor-Erythroid 2-Related Factor 2 (Nrf2) signaling pathway and downstream antioxidant factors. In addition, activity of AKT signaling and expression of glucose transporter type 4 (GLUT4) in the skeletal muscle were investigated by western blot. Result QBT treatment limited gain of body weight, waistline and LEE index, improved insulin resistance and glucose intolerance, reduced lipid level in MSG mice. Content levels of MDA, ROS and protein carbonylation in skeletal muscle of QBT group were significantly improved compared to those of MSG mice. The antioxidant enzyme activities of SOD, GPx, CAT, and GR were increased in skeletal muscle of MSG mice intervened with QBT. After 20-week QBT treatment, Nrf2 signaling pathway and downstream antioxidant factors were both increased in the skeletal muscle. In addition, QBT treatment improved insulin signaling by preferentially augmenting AKT signaling, as well as increased the protein expression of GLUT4 in the skeletal muscle. Conclusion Our results showed that QBT intake was effective in protecting monosodium glutamate-induced obese mice against metabolic syndrome and involved in the Nrf2 signaling pathway in the skeletal muscle. [ABSTRACT FROM AUTHOR]

Background: Studies have reported that depression is associated with increased level of oxidative stress and accompanied with decreased Kelch-like erythroid cell-derived protein with CNC homology-associated protein 1-nuclear factor (erythroid-derived 2)-like 2 (Keap1-Nrf2) signaling pathway. Berberine has been shown to possess properties on protection against neurodegenerative diseases, but its effects on chronic unpredictable mild stress (CUMS) induced depressive such as behaviors and Keap1-Nrf2 signaling pathway are unknown. Objective: This study was designed to evaluate the effect of berberine on CUMS induced depression animal model and investigate the underlying mechanisms. Materials and Methods: We established CUMS depressant rats model and treated CUMS rats with berberine. Sucrose preference test, forced swim test , and tail suspension test were used to measure behavioral changes. We used quantitative polymerase chain reaction and western blot to test the levels of cytokines in the hippocampus. Results: We found that CUMS rats displayed obvious depressive-like behaviors. Moreover, berberine treatment prevented depressive behaviors in CUMS rats accompanied with suppression of oxidative stress markers. Further experiments showed that berberine treatment up-regulated the expression of Keap1-Nrf2 antioxidant signaling pathway and its downstream neuroprotective factors. Conclusion: The present results suggested that treatment of berberine significantly ameliorated depressive-like behaviors in CUMS rats and enhanced Keap1-Nrf2 antioxidant signaling pathways in hippocampus. Abbreviations used: MDD: Major depressive disorder; CUMS: Chronic unpredictable mild stress; FST: Forced swim test; TST: Tail suspension test; Keap1: Kelch-like erythroid cell-derived protein with CNC homology-associated protein 1; Nrf2: nuclear factor (erythroid-derived 2)-like 2; ARE: Antioxidant response elements; SOD: Superoxide Dismutase; MDA: Malonic dialdehyde; IMI: Imipramine. [ABSTRACT FROM AUTHOR]

• PASP is a biodegradable protein-based retarder. • PASP has less strength loss compared with previous retarders. • PASP prolongs the dissolution of α-HH and crystallization process of gypsum. • The conformation of PASP affects the interaction between PASP and Ca2+ in calcium sulfate solution. Polyaspartic acid (PASP) was an environment-friendly and biodegradable polymer, with a protein-like structure composed of L-aspartic acid residues. In this work, PASP with different molecular weights (2000, 4000–5000 and 6000–8000) was utilized as the retarder for α-hemihydrate gypsum (α-HH), and the effect of PASP on the coagulation, hydration and crystallization process of gypsum were investigated. Results showed that the addition of PASP with a low dosage of 0.01% efficiently delayed the hydration of α-HH and prolonged the setting process. Among three polyaspartic acids, PASP with molecular weight of 4000–5000 (PASP 4–5) exhibited the best performance not only in postponing the setting time to 95 min, but also in decreasing the negative impact of retarder on the strength of gypsum. Significantly, the slightest loss of 2.65% in compressive strength was obtained here when compared with other retarders previously reported, under the lowest dosage of 0.01% PASP 4–5. Consequently, the effect of PASP chain length on the retardation of α-HH was analyzed in detail. The conductivity, heat of hydration, X-ray diffraction (XRD), EDTA titration method and scanning electron microscopy (SEM) characterization found that PASP prevented the dissolution of α-HH. Total organic carbon analyzer (TOC) and X-ray photoelectron spectroscopy (XPS) measurements showed that the carboxyl groups of PASP adsorbed on the surface of α-HH to hinder the dissolution of α-HH. The molecular dynamic simulation of PASP further exhibited that three kinds of PASPs presented different conformations in supersaturated calcium sulfate solution due to the interaction between PASP and Ca2+ ions, and affected their solvent accessible surface area (SASA). In particular PASP 4–5 exhibited the smallest SASA and the strongest interaction with Ca2+ ions, causing the longest setting time of α-HH. [ABSTRACT FROM AUTHOR]

The carbamate molecule rivastigmine was found to possess promising anti-acetylcholinesterase activity, enabling to target and occupy choline binding sites, and as a result, widely used to improve the treatment of Alzheimer's disease (AD). Higher dose of rivastigmine indicates rapid onset but more adverse effects, such as the large fluctuations in plasma concentration level and frequent incidence of gastrointestinal side effect. To solve the dilemma, we developed a three-dimensional quantitative structure-activity relationship (3D-QSAR), docking and molecular dynamics (MD) simulation strategy to construct a dismountable nanoplatform of inhibitor engineering, verification and application for improving the inhibitory activity per unit concentration. With the aid of 3D-QSAR method, we constructed a model by using 25 molecules reported, and verified well the rationality of these QSAR models by non-cross validation coefficient (r2 = 0.902). Docking and MD results show that rivastigmine, as a control, does target exactly the binding sites of acetylcholinesterase, those already observed experimentally, in turn, confirming the reliability of the present 3D-QSAR results. The method suggests that groups with electron-donating chemical property can improve the inhibitory activity, and screens out two novel inhibitors L-1 and L-2 with more activity from database (about 8000 compounds). Moreover, L-1 and L-2 not only target exactly the same binding sites of acetylcholinesterase as the rivastigmine does, but also hold stronger binding energy, showing a more powerful inhibitory ability. More broadly, this work showcases an approach in the engineering of carbamate inhibitors to enhance their inhibitory activity using electron-donating groups, which simplifies the design process of complex bioactive molecules. The 3D-quantitative structure-activity relationship (3D-QSAR) was used to find and screen the novel inhibitor of anti-acetylcholinesterase (AChE) activity, which was validated by its excellent r2 and q2 values, as well as by the available experiment results of Montanari et al. The docking and molecular dynamic simulation further provided mechanical details of AChE-inhibitor interaction. [Display omitted] • The integrated 3D-QSAR, Docking and MD approach identified potential inhibitors against Alzheimer's disease. • The inhibitory activity can be improved by Substituting the R groups with electron-donating property. • The approach would be of great value for optimizing bioactivity and studying the mechanisms of bioactive molecules. [ABSTRACT FROM AUTHOR]

Activationof the G-protein coupled receptor (GPCR) Takeda G-protein receptor5 (TGR5), also known as G-protein bile acid receptor 1 (GPBAR1), hasbeen shown to play a key role in pathways associated with diabetes,metabolic syndrome, and autoimmune disease. Nipecotamide 5was identified as an attractive starting point after a high-throughputscreen (HTS) for receptor agonists. A comprehensive hit-to-lead effortculminated in the discovery of 45has a potent, selective,and bioavailable TGR5 agonist to test in preclinical metabolic diseasemodels. In genetically obese mice (ob/ob), 45hwas aseffective as a dipeptidyl peptidase-4 (DPP-4) inhibitor at reducingpeak glucose levels in an acute oral glucose tolerance test (OGTT),but this effect was lost upon chronic dosing. [ABSTRACT FROM AUTHOR]

Ferroptosis is a new form of iron-dependent cell death and plays an important role during the occurrence and development of various tumors. Increasingly, evidence shows a convincing interaction between ferroptosis and tumor immunity, which affects cancer patients' prognoses. These two processes cooperatively regulate different developmental stages of tumors and could be considered important tumor therapeutic targets. However, reliable prognostic markers screened based on the combination of ferroptosis and tumor immune status have not been well characterized. Here, we chose the ssGSEA and ESTIMATE algorithms to evaluate the ferroptosis and immune status of a TCGA breast invasive ductal carcinoma (IDC) cohort, which revealed their correlation characteristics as well as patients' prognoses. The WGCNA algorithm was used to identify genes related to both ferroptosis and immunity. Univariate COX, LASSO regression, and multivariate Cox regression models were used to screen prognostic-related genes and construct prognostic risk models. Based on the ferroptosis and immune scores, the cohort was divided into three groups: a high-ferroptosis/low-immune group, a low-ferroptosis/high-immune group, and a mixed group. These three groups exhibited distinctive survival characteristics, as well as unique clinical phenotypes, immune characteristics, and activated signaling pathways. Among them, low-ferroptosis and high-immune statuses were favorable factors for the survival rates of patients. A total of 34 differentially expressed genes related to ferroptosis-immunity were identified among the three groups. After univariate, Lasso regression, and multivariate stepwise screening, two key prognostic genes (GNAI2, PSME1) were identified. Meanwhile, a risk prognosis model was constructed, which can predict the overall survival rate in the validation set. Lastly, we verified the importance of model genes in three independent GEO cohorts. In short, we constructed a prognostic model that assists in patient risk stratification based on ferroptosis-immune-related genes in IDC. This model helps assess patients' prognoses and guide individualized treatment, which also further eelucidatesthe molecular mechanisms of IDC. [ABSTRACT FROM AUTHOR]

Leukocyte immunoglobulin-like receptor B2 (LilrB2) is one of discovered cell surface β-amyloid (Aβ) receptors and taken as a promising therapeutic target for the treatment of Alzheimer's disease (AD). Aβ42 oligomer rather than monomer is toxic to neuronal cells and can directly bind to LilrB2, resulting in synaptic loss and cognitive impairment in the development of AD. Therefore, uncovering the mechanism of interaction between Aβ42 oligomer and LilrB2 becomes the first step to obtain a clear drug target and specific binding sites. Herein, a tetracoordinated mechanism for the Aβ oligomer-LilrB2 binding was first put forward by employing Aβ42 dimer mimic-antiparallel copies of Aβ42 core fragment 16KLVFFA21, to bind LilrB2 as models, in which four key residues (F5/F6/L12/F14) in the Aβ42 mimic are bound strongly with LilrB2 residue(s) or accommodated by four hydrophobic cavities in LilrB2 to generate a stable complex. Bi-dentate binding, however, cannot keep the complex Aβ42 mimic-LilrB2 stable. The inhibitor fluspirilene can disturb the binding of four key residues of Aβ42 to LilrB2, justifying the tetracoordinated zipper mechanism on the other hand. [ABSTRACT FROM AUTHOR]

Water absorption by the composite adsorbent includes physical adsorption of moisture by MIL-101(Cr), chemical reaction of CaCl 2 with water molecules to form hydrates, and absorption of water vapor by CaCl 2 solution. • The XRD analysis shows that the structure of the MIL-101(Cr) material does not change after the addition of CaCl 2. • The water vapor equilibrium adsorption capacities of MIL-101(Cr)/CaCl 2 -20% is 1.13 g/g without agglomeration when P/P 0 = 0.9. • MIL-101(Cr)/CaCl 2 -20% has great potential for application to adsorption heat pumps. In this article, MIL-101(Cr) powder material was successfully prepared by hydrothermal synthesis and combined with different mass fractions of CaCl 2 by immersion method to obtain MIL-101(Cr)/CaCl 2 composite materials. The physical properties of the adsorbent were determined by X-ray powder diffraction, N 2 adsorption/desorption isotherm, TGA and FTIR. The water vapor adsorption performance of MOFs was tested by a gravimetric instrument to analyze the underlying mechanism. Results indicated that the specific surface area, total pore volume, and pore size distribution of micropores and mesopores of MIL-101(Cr)/CaCl 2 composites decreased with increasing CaCl 2 content. When P/P 0 = 0.9, the water vapor equilibrium adsorption capacities of MIL-101(Cr), MIL-101(Cr)/CaCl 2 -10%, MIL-101(Cr)/CaCl 2 -20%, and MIL-101(Cr)/CaCl 2 -30% were 1.05, 0.88, 1.13, and 1.35 g/g, respectively. MIL-101(Cr)/CaCl 2 -30% agglomerated after water absorption, so MIL-101(Cr)/CaCl 2 -20% was selected as the final experimental material. The water vapor adsorption heat of MIL-101(Cr)/CaCl 2 -20% was 42–58 kJ/mol, which is close to the evaporation enthalpy of water (44 kJ/mol at 25 °C). The analysis of the adsorption kinetics showed the relatively uniform adsorption rate of MIL-101(Cr)/CaCl 2 -20%. Overall, MIL-101(Cr)/CaCl 2 -20% exhibited superior water vapor adsorption performance and have great potential for application to adsorption heat pumps. [ABSTRACT FROM AUTHOR]

Various strategies have been adopted to enhance the characteristics of the MoO 2 nanoparticles electrode structures. Meanwhile the alkaline medium exhibits the sluggish kinetic and an acidic medium can donate the excess protons to promote the hydrogen evolution reaction. The annealing temperature may sputter the environmental oxygen from the surface and enhance the characteristics of the electrocatalysts. MoO 2 nanoparticles have been synthesized successfully using the hydrothermal process; later on, the synthesized structure was treated at temperatures of 400 and 600 °C under the flow of N 2 gas for 6 h. The heat treatment process at 600 °C influenced the characteristics of MoO 2 nanoparticles and enhanced the electrical conductivity, electrochemical and specific surface area and mesoporous features of MoO 2 -600 nanoparticles. Owing to boosted characteristics, MoO 2 -600 nanoparticles reveal a good overpotential of 56 mV at the current density of 10 mA cm−2 in 0.5 M H 2 SO 4 due to the excess availability of the protons, which is better than pre-annealed MoO 2 -basic and MoO 2 -400 nanoparticles. MoO 2 -600 nanoparticles exhibit a good Tafel slope of 22 mV dec−1 and follow the Tafel mechanism, while MoO 2 -600 nanoparticles show a Tafel slope of 64 and 67 mV dec−1 in buffer solution and 1 M KOH electrolyte, respectively. Moreover, the turnover frequency of MoO 2 -600 nanoparticles has been found as 191 ms−1 at the fixed reversible hydrogen potential of 800 mV RHE in 0.5 M H 2 SO 4 , which is greater than the buffer solution and 1 M KOH electrolyte. The results indicate that MoO 2 -600 nanoparticles are an effective electrocatalyst for hydrogen evolution reactions. • The annealing temperature may sputter the environmental oxygen from the surface. • MoO 2 -600 nanoparticles exhibited a greater electrical conductivity area. • MoO 2 -600 nanoparticles reveal a good overpotential of 56 mV in 0.5 M H 2 SO 4. • MoO 2 -600 nanoparticles exhibit a good Tafel slope of 22 mV dec−1 in 0.5 M H 2 SO 4. • The electrocatalyst MoO 2 -600 nanoparticles showed a higher TOF of 191 m s−1. [ABSTRACT FROM AUTHOR]

Background: The relationship between Protein Convertase Subtilisin Kexin Type 9 inhibitor (PCSK9i) and psychiatric adverse events (AEs) remains unclear due to the limitations of clinical trials. In this study, PCSK9i‐related psychiatric AEs were realistically observed and systematically summarized in the real world by data mining the FDA AE Reporting System (FAERS). Method: Total AEs between the third quarter of 2015 and the first quarter of 2023 were obtained from FAERS. Psychiatric AEs were identified using disproportionality analysis and clinical prioritization of signals using a rating scale, followed by univariate logistic regression to explore factors influencing psychiatric AEs. Results: Psychiatric AEs accounted for 6.7% of the total number of PCSK9i reports. Eighteen psychiatric AEs were defined as PCSK9i‐related psychiatric adverse events (ppAEs) (lower 95% CI of both ROR >1 and IC025 > 0). The median age of ppAE reports was 68 years, and female patients accounted for 22.67% of reports, including 41.40% of reports with a serious outcome. Eleven (61.11%) and seven (38.89%) ppAEs were classified as weak and moderate clinical priority, respectively. The median time to onset of ppAEs was 149 and 196 days after treatment with evolocumab and alirocumab, respectively. Patients weighing ≥80 kg were 1.59 times more likely to experience ppAEs. Conclusion: The results of this study facilitate the prioritization of psychiatric AE signals by healthcare professionals with the goal of mitigating the risk of PCSK9i‐related psychiatric AEs. However, as an exploratory study, our findings need to be confirmed in large‐scale prospective studies. [ABSTRACT FROM AUTHOR]

Objective: Depression imposes a huge health problem in the world. Recent studies report that berberine has neuroprotective effects. This study was investigated to evaluate the effects of berberine on depression and the potential underlying mechanisms. Methods: This experimental study included 48 mice, 8 CD1 mice and 40 C57 mice. Experiments were performed in the Laboratory Animal Center of China Three Gorges University, between May 2016 and February 2017. Chronic social defeat stress (CSDS) was used to build the depressive-like behaviors model. Three behavior tests, quantitative polymerase chain reaction, and Western blot were used to assay the changes in vivo. Results: We found that, in mice model induced by CSDS, berberine treatment increased mobility times in forced swim test and tail suspension test and reduced corticosterone level in serum. Furthermore, berberine increased traveled distance, frequencies in enter the central square, and duration time on the center square in the open field test as well. Further experiments showed that berberine treatment upregulated neuronal PAS domain protein 4 (NPAS4) and brain-derived neurotrophic factor (BDNF) protein/mRNA expressions in hippocampus tissue of CSDS mice. Conclusion: The present results suggested that berberine possessed properties in antidepressive-like behaviors, which might be partly attributed to upregulation of NPAS4 and BDNF expressions in hippocampus. Abbreviations used: CSDS: Chronic social defeat stress; BDNF: Brain-derived neurotrophic factor; NPAS4: Neuronal PAS domain protein 4; FST: Force swim test; TST: Tail suspension test; OFT: Open field test. [ABSTRACT FROM AUTHOR]

Background: Nucleic acid is the carrier of genetic information and the keymolecule in life science. It is important to establish a simple and feasible method for nucleic acid quantification in complex biological samples. Methods: Four kinds of hydrogen bond acceptors (choline chloride (ChCl), L-carnitine, tetrabutylammonium chloride (TBAC) and cetyltrimethylammonium bromide (CTAB)) were used to synthesize deep eutectic solvents (DESs) with hexafluoroisopropanol (HFIP). DESs based manganese dioxide (MnO2) nanosheets composites was synthesized and characterized. DNA concentration was determined by a UVVis spectrometer. The mechanism of DNA-DES/MnO2 colorimetric system was further discussed. Results: The composite composed of DES/MnO2 exhibited excellent oxidase-like activity and could oxidize 3,3',5,5' -tetramethylbenzidine (TMB) to produce a clear blue change with an absorbance maximum at 652 nm. When DNA is introduced, the DNA can interact with the DES by hydrogen bonding and electrostatic interactions, thereby inhibiting the color reaction of DES/MnO2 with TMB. After condition optimization, ChCl/HFIP DES in 1:3 molar ratio was used for the colorimetric method of DNA determination. The linear range of DNA was 10–130 µg/mL and exhibited good selectivity. Conclusion: A colorimetric method based on DES/MnO2 was developed to quantify the DNA concentration. The proposed method can be successfully used to quantify DNA in bovine serum samples. [ABSTRACT FROM AUTHOR]

Alkaline pretreatment can improve the methane yields and dewatering performance of anaerobically digested sludge, but it still needs to be coupled with other conditioning methods in the practical dewatering process. This study utilized four different flocculants and a skeleton builder for conditioning of alkaline pretreatment-anaerobically digested sludge. Chitosan was found to be the most effective in dewatering the sludge. Chitosan coupled with rice husk powder further improved the dewatering performance, which reduced normalized capillary suction time, specific resistance to filtration, and moisture content by 98.7%, 82.0%, and 12.1%. For land use of biogas slurry as a fertilizer, chitosan conditioning promoted the growth of corn seedlings, while the other three flocculants diminished the growth of corn seedlings. Chitosan coupled with rice husk powder further promoted the growth of corn seedlings by 103.5%, 65.0%, and 53.7% in fresh weight, dry weight, and root length, respectively. Overall, chitosan coupled with rice husk powder not only enhanced the dewaterability of alkaline pretreatment-anaerobically digested sludge but also realized the resource utilization of agricultural waste. [Display omitted] • Alkaline pretreatment increased methane yield by 35.2%. • Alkaline pretreatment enhanced the dewaterability of anaerobically digested sludge. • The conditioning effect of chitosan was better than that of other flocculants. • The addition of rice husk powder can further improve the conditioning effect. • Both chitosan and rice husk powder promoted the growth of corn seedlings. [ABSTRACT FROM AUTHOR]

The comprehension of the electronic structure of an electrochemical catalyst, as a fundamental core content, has significantly accelerated advancements in competitive catalyst engineering since the adsorption and desorption abilities of an electrode are governed by its surface energy profile. However, achieving precise control over the electronic structure poses a significant challenge. Nanoporous materials, high-entropy systems, and layered double hydroxides frequently induce stoichiometric changes, leading to complexity such as electronic reconstruction, energy degeneracy disruption, and impurity energy levels. Here, we have successfully developed a stretchable freestanding single-crystal LaNiO 3 thin film electrocatalyst enabling the accurate manipulation of the electronic structure on a large scale. Different from the rigid epitaxial heterostructure catalyst, we observed that with every 1 % increase in strain, the OER current of freestanding LaNiO 3 is enhanced by ∼238 % compared to the pristine state. This is attributed to the dx 2 -y 2 orbital occupation increasing by ∼7 %, and the e g -center decreasing by ∼0.05 eV, resulting in a weakened Ni-O adsorption. [Display omitted] • A stretchable freestanding single-crystal LaNiO3 (LNO) catalyst is developed. • The d orbital polarization and center are tuned by the in-plane biaxial strain. • Every 1 % increase in strain facilitates a ∼238 % improvement in OER current. • LNO with 4 % tensile strain offers an ultrahigh OER activity of 6.3 mA cm-2 at 1.63 V. [ABSTRACT FROM AUTHOR]

The gradual increase in cattle farming has led to a huge production of cattle manure (CM), but the conventional treatment methods are less efficient. In this study, the treatment method of anaerobic digestion (AD) of high-solids CM by combining nanobubble water (NBW) with different gases was proposed to present a new idea for the reduction, harmlessness, and resourcefulness of CM. It was found that the performance of the digester with added NBW was better than the control. Among them, the cumulative methane yield T-Air: 227.09 mL g−1 VS added and T-CO 2 : 226.12 mL g−1 VS added increased by 17.72 % and 17.22 %, respectively, compared with the control T: 192.90 mL g−1 VS added under thermophilic conditions. Under mesophilic conditions, M-Air: 162.39 mL g−1 VS added increased by 9.68 % compared with control M: 148.05 mL g−1 VS added. Microbial communities analyzed at the genus level revealed that the relative abundance of bacteria favorable to hydrolysis and acid-producing processes, such as Defluviitalea , Haloplasma , and Bacillus , increased to varying degrees. Moreover, the relative abundance of archaea favorable for methanogenesis, such as Methanoculleus , Methanobrevibacter , and Methanosarcina , also increased to varying degrees. Therefore, the addition of NBW promoted the hydrolysis of high-solids CM, enhanced the stability of the reaction, improved the methanogenic performance, and increased the RA of favorable genera, which ultimately led to a better performance of the AD of high-solids CM. [Display omitted] • Compared with control, NBW increased CH 4 production by 5–17 %. • Compared with control, NBW contributes to the production/transformation of VFAs. • Incorporation of NBW improves stability of high solids anaerobic digestion. • Compared with control, NBW increased the RA of hydrolytic acidification-associated bacteria. • Compared with control, NBW increased the RA of methanogenic-associated archaea. [ABSTRACT FROM AUTHOR]

[Display omitted] • Four different NBWs were added to the sludge anaerobic digestion. • The hydrolysis of sludge anaerobic digestion can be enhanced by the addition of NBW. • Addition of NBW increased methane production by 9.0–27.8% compared with control. • Addition of NBW (Air, CO 2 , He, and N 2) improved the dewaterability of digestate. • Air-NBW was the most cost-effective additive for sludge anaerobic digestion. The subsequence anaerobic digestion (AD) of dewatered sludge (DWS) from wastewater treatment plants necessitates an emphasis on enhancing methane production and dewaterability. The effect of different nanobubble water (NBW) on AD of DWS was investigated under mesophilic conditions. Cumulative methane production was improved by 9.0–27.8% with the addition of different NBW (Air, CO 2 , He, and N 2). NBW improved methanogenic performance by significantly enhancing the hydrolysis of sludge AD. Results from the digestate, the capillary suction time, specific resistance to filtration, and moisture content could be decreased by 14.6–18.2%, 18.8–29.6%, and 13.6–19.5%, respectively. The addition of NBW can improve the dewaterability of digestate by reducing the digestate particle size and increasing the zeta potential of digestate. The addition of NBW significantly increased methane production and improved dewaterability in AD; Air-NBW showed the best improvement. [ABSTRACT FROM AUTHOR]

[Display omitted] • Microbial electrolysis cell was integrated in different phases of different TPAD. • Thermophilic conditions enhanced hydrolysis more than microbial electrolysis cell. • TPAD integrated microbial electrolysis cell improved the methane yield. • Microbial electrolysis cell was more effective in mesophilic-mesophilic TPAD. Temperature-phased anaerobic digestion (TPAD) and microbial electrolysis cell (MEC) are both able to improve hydrolysis and methane yield during anaerobic digestion (AD) of dewatered sludge. However, the effect of TPAD and MEC integration at different temperatures and different phases is unclear. This study investigated the effect of the integration of intermittent energization MEC in different phases of TPAD on the digestion of dewatered sludge. Thermophilic and MEC hydrolysis could release higher total ammonia nitrogen of 186.0% and 10.3% than control, mesophilic methanogenesis phase integrated with MEC relieved the ammonia inhibition and accelerated the acid utilization leading to the relief of acid accumulation. The ultimate methane yield of the TPAD integrated with MEC was increased by 118.9%, in which the relative abundance of Methanothermobacteria and Methanosarcina was increased. Therefore, intermittent energization MEC integrated TPAD synchronously improved the hydrolysis and methane yield. [ABSTRACT FROM AUTHOR]

Abstract: Through scaffold morphing of a known Smoothened antagonist Antag691, a series of novel phenyl imidazole derivatives were developed. Structure–activity-relationship studies and lead optimization led to the discovery of potent, selective and orally bioavailable Smoothened antagonist 19 that is suitable for in vivo studies. [Copyright &y& Elsevier]

Background: Major depressive disorder (MDD) is a debilitating mental illness and one of the primary causes of suicide. This study attempted to develop and validate a multigene joint signature for diagnosing MDD based on autophagy-related genes (ARGs) and to explore their biological role in MDD.Methods: We downloaded data from the Gene Expression Omnibus (GEO) database and retrieved ARGs from the Human Autophagy Database. The limma package in R software was used to identify differentially expressed genes (DEGs). We used CIBERSORT to analyze differences in the immune microenvironment between MDD patients and controls. Finally, we examined the correlation between diagnostic markers and infiltrating immune cells to better understand the molecular immune mechanism.Results: In this study, we identified 20 differentially expressed ARGs in MDD compared to controls. A signature of 4 autophagy-related genes (GPR18, PDK4, NRG1 and EPHB2) was obtained. ROC analysis showed that our model has good diagnostic performance (AUC=0.779, 95% CI=0.709-0.848). Bioinformatics analysis validated that GPR18 may represent a new candidate gene for MDD. Correlation analysis revealed that GPR18 was positively correlated with regulatory T cells (Treg), CD8+ T cells, naive B cells, and memory B cells and negatively correlated with M0 macrophages and neutrophils in MDD.Limitations: This was a second mining of previously published data sets. Independent studies are warranted to validate and improve the clinical utility of the identified signature.Conclusions: We identified a novel four-ARG gene signature that has good diagnostic performance and identified an association between ARG genes and the immune microenvironment in MDD. [ABSTRACT FROM AUTHOR]

Women with multiple pregnancies are vulnerable to experience postpartum depression (PPD). Emerging evidence indicates an association between poly- and perfluoroalkyl substances (PFAS) exposure and PPD in women delivering singletons. The health risks of PFAS may also be present in women delivering twins. To estimate the impacts of prenatal PFAS exposure on the risk of PPD in women with twin pregnancies. Our study included 150 mothers who gave birth to twins and were enrolled in the Wuhan Twin Birth Cohort. The concentrations of maternal plasma PFAS were measured in each trimester and averaged. Eight individual PFAS were included in analyses. We used Edinburgh Postnatal Depression Scale to evaluate maternal depression at early pregnancy and 1 and 6 months after childbirth. The outcome was dichotomized using a cutoff value of ≥10 for main analyses. Associations were examined using multiple informant models and modified Poisson regressions. PFAS mixture effects were estimated using quantile g-computation. Using quantile g-computation models, a quartile increase in the PFAS mixture during the first, second, third, and average pregnancy was significantly associated with a relative risk (RR) of 1.73 (95% CI: 1.42, 2.12), 1.54 (95% CI: 1.27, 1.84), 1.75 (95% CI: 1.49, 2.08), and 1.63 (95% CI: 1.35, 1.97) for PPD at 6 months after childbirth, respectively. The results of the single-PFAS models also indicated significant positive associations between individual PFAS and PPD at both 1 and 6 months. The first study of women with twin pregnancies suggests that prenatal exposure to PFAS increases PPD risk up to 6 months postpartum. Twin pregnant women should receive long-term follow-up after delivery and extensive social support. [Display omitted] [ABSTRACT FROM AUTHOR]

Neointimal hyperplasia resulting from pathological vascular smooth muscle cells (VSMCs) activation is a common pathophysiological basis for numerous proliferative vascular diseases, such as restenosis. Suv39h1, an important transcription suppressor, may be involved in this process. Herein, we investigated the role of Suv39h1 in pathological intimal hyperplasia and its possible mechanisms in vitro and in vivo. An adenovirus vector for Suv39h1 overexpression and a lentiviral vector for its downregulation were constructed and used to transfect cultured VSMCs in vitro. The functional changes in VSMCs stimulated by angiotensin II (Ang II) were observed and the possible mechanism was investigated. Additionally, rat carotid arteries with balloon injury were locally transfected with these viral vectors and changes in neointima formation, proliferating cell nuclear antigen (Pcna) expression and collagen deposition were examined. Upon Ang II stimulation, the expression of Suv39h1 and inhibitor of DNA binding 3 (Id3) was significantly increased. Suv39h1 downregulation inhibited Ang II-stimulated migration and proliferation of VSMCs, antagonized the production of Id3 and promoted p21 and p27Kip1 expression. In contrast, Suv39h1 overexpression had the opposite effects. Suv39h1 regulated the transcription of p21 and p27Kip1 by controlling H3K9me3 in the proximal promoter regions. Consistent with the VSMCs results, Suv39h1 and Id3 expression was significantly increased in blood vessels after balloon injury. Suv39h1 downregulation inhibited intimal hyperplasia, and attenuated Pcna expression and collagen synthesis in the intima, while Suv39h1 overexpression had the opposite effects. Suv39h1 downregulation effectively inhibited neointimal hyperplasia after vascular injury. Image 1 • Suv39h1 downregulation inhibits Ang II-stimulated migration and proliferation of VSMCs. • Suv39h1 downregulation attenuates neointimal hyperplasia after vascular injury. • Suv39h1 downregulation decreases Id3 production, and promotes p21 and p27Kip1 expression. [ABSTRACT FROM AUTHOR]

A series of 3-[2-(2-aminoethylamino)ethylamino]propyl-trimethoxysilane (PAPTS) grafted on Materials of Institute Lavoisier-101(Cr) [MIL-101(Cr)] porous adsorbent with varied PAPTS loadings were synthesized and characterized by powder X-ray diffraction patterns (PXRD), N 2 adsorption-desorption measurement at 77 K, Fourier transform infrared spectroscopy (FTIR), and thermal gravimetric analysis (TGA). The water vapor adsorption isotherms were obtained by gravimetric method. Water adsorption isotherms and dynamic on MIL-101 as well as PAPTS- MIL-101(Cr) are discussed simultaneously. Results indicated that even though the Brunauer-Emmett-Teller (BET) surface areas of PAPTS-MIL-101(Cr)-0.5 and PAPTS-MIL-101(Cr)-0.75 were reduced by approximately 50% compared with that of the original MIL-101(Cr), which have slightly higher water uptake capacities in a region of 0.30 <  P/P 0  < 0.40. The reduction in the BET surface area is offset by increasing hydrophilicity for the adsorption of water. PAPTS-MIL-101(Cr)-0.5 exhibited very fast adsorption rate, and the adsorption rate constants of water vapor were 0.0206 and 0.202 min −1 for the initial and final stages of the adsorption process, respectively. Therefore, these superior water vapor adsorption performances of PAPTS grafted on MIL-101(Cr) have great potential for application in adsorption heat pumps. [ABSTRACT FROM AUTHOR]

The rapid growth of the digital economy has driven economic development, but the massive demand for electricity from digital reforms, coupled with China's coal-based power generation, has created a significant CO 2 emission problem. Previous studies have assessed digital economy sectors with an incomplete scope and a lack of carbon emissions assessment at the intermediary-side. To fill these gaps, this study assessed CO 2 emissions using input–output modeling of the core industry sector of the digital economy and the industrial digitalization sector at the production, intermediary, and demand sides, and identified key CO 2 transmission centers. The results show the following: (1) Digital economy sectors had a high betweenness and were important CO 2 transmission centers in the economic system, transmitting more than 4.08 billion tonnes of betweenness-based CO 2 emissions; (2) specifically, the industrial digitalization sector transmitted the most CO 2 in the economic system, and the digital product manufacturing sector was the core industry sector with the highest betweenness and a strong transmission effect on the CO 2 emissions in the supply chain; (3) digital economy sectors had large CO 2 emissions on the production, intermediary, and demand sides, and transmitted CO 2 more through the demand-side and key transmission centers. These results suggest that digital economy sectors can decarbonize and reduce CO 2 emissions by (1) improving material use efficiency in the digital product manufacturing sector, (2) reducing the use of carbon-intensive energy and materials in the digital economy sectors, and (3) establishing CO 2 emission disclosure rules, incentives, and penalties. • The digital product manufacturing sector had high betweenness. • Industrial digitalization sector was the largest intermediary-side contributor. • Digital economy sectors had large CO2 emissions from three sides. • Digital economy sectors influenced upstream CO2 emissions more through demand. [ABSTRACT FROM AUTHOR]

• Piperine inhibits M5-induced psoriatic dermatitis. • Piperine inhibits IMQ-induced psoriasis-like skin lesions. • Piperine inhibits STAT3 phosphorylation and activity. Psoriasis is a common chronic inflammatory skin disease that is easy to relapse and difficult to cure. Piperine is the main alkaloid extracted from black pepper, and its role in psoriasis has not been previously reported. We identified that piperine ameliorated M5-induced psoriatic skin lesions. Furthermore, piperine alleviated psoriasis pathological features including epidermal hyperplasia and inflammatory cell infiltration, decreased the expression of psoriasis-characteristic cytokines, chemokines and proteins in IMQ-induced psoriasiform dermatitis. Moreover, we determined that piperine inhibited the phosphorylation of STAT3 in M5- and IMQ-induced psoriasis-like skin lesions. Our data demonstrated that piperine ameliorated psoriatic skin inflammation by inhibiting the phosphorylation of STAT3. Therefore, piperine may be one potential compound candidate for psoriasis therapy, providing new strategies for clinical intervention. [ABSTRACT FROM AUTHOR]

The prevalence of depression has increased dramatically in the past few decades, and pregnant women are at high risk for depression. It is widely thought that inflammation plays a critical role in the pathogenesis of depression. Therefore, we aimed to evaluate the association between the neutrophil-lymphocyte ratio (NLR), a marker of chronic immune inflammation, and perinatal depressive symptoms. A cohort study involving 535 pregnant women was conducted based on a prospective birth cohort in Wuhan, China. The Edinburgh Postnatal Depression Scale (EPDS) was used to assess antepartum depression (APD) and postpartum depression (PPD) during the second trimester of pregnancy and one month after delivery. The NLR during the second trimester was determined based on a routine blood test. The association between NLR and depressive symptoms was evaluated using logistic regression analysis and restricted cubic spline (RCS) regression. We found that the prevalence of APD and PPD was 8.4% and 15.1%, respectively. NLR levels were positively associated with APD (OR = 1.52, 95% CI: 1.20-–1.91). After adjusting for potential confounders, the OR (95% CI) of APD for the highest NLR quartile was 4.56 (1.58, 13.13) compared with the lowest quartile. No significant association was found between NLR and PPD. RCS regression model analysis indicated a linear correlation between NLR and APD (P for non-linearity = 0.58). Overall, elevated mid-trimester NLR is independently associated with APD but not PPD. • This study evaluated the association between NLR and perinatal depression. • NLR in pregnant women with depression is higher than those without depression. • Mid-trimester NLR is positively associated with Mid-trimester antepartum depression but not postpartum depression. • Our results indicate a cross-sectional association between inflammation and antepartum depression. [ABSTRACT FROM AUTHOR]

Influences of multiple environmental factors on water quality patterns is less studied in large rivers. Landscape analysis, multiple statistical methods, and the water quality index (WQI) were used to detect water quality patterns and influencing factors in China's largest river, the Yangtze River. Compared with the dry season, the wet season had significantly higher total phosphorus (TP), chemical oxygen demand (COD), total suspended solids (TSS), and turbidity (TUR). The WQI indicated "Moderate" and "Good" water quality in the wet and dry seasons, respectively. Compared with other sites, the upper reach sites that immediately downstream of the Three Gorges Dam had lower TP, TN, TSS and TUR in both seasons, and had lower and higher water temperature in the wet and dry seasons, respectively. Water quality patterns were mainly driven by heterogeneity in land use (i.e., wetland, cropland, and urban land), hydrology (i.e., water flow, water level), and climate (i.e., rainfall, air temperature). Water quality in the wet season was primarily driven by land use while the joint effect of land use and hydrology primarily drove in the dry season. Decision-makers and regulators of large river basin management may need to develop programs that consider influences from both human and natural drivers for water quality conservation. • The WQI showed Moderate to Good water quality in China's largest river. • Dam impoundment reduced nutrients and TSS downstream. • Land use was the main driver for water quality in the wet season. • Land use and hydrology jointly drove water quality in the dry season. • Management may consider prioritizing the 5 km riparian zone for conservation. [ABSTRACT FROM AUTHOR]

Summary: FTY720 is an immunomodulator with demonstrated efficacy in a phase II trial of relapsing multiple sclerosis. FTY720-phosphate, the active metabolite generated upon phosphorylation in vivo, acts as a potent agonist on four of the five known sphingosine-1-phosphate (S1P1) receptors. AUY954, an aminocarboxylate analog of FTY720, is a low nanomolar, monoselective agonist of the S1P1 receptor. Due to its selectivity and pharmacokinetic profile, AUY954 is an excellent pharmacological probe of S1P1-dependent phenomena. Oral administration of AUY954 induces a profound and reversible reduction of circulating lymphocytes and, in combination with RAD001 (Certican/Everolimus, an mTOR inhibitor), is capable of prolonging the survival of cardiac allografts in a stringent rat transplantation model. This demonstrates that a selective agonist of the S1P1 receptor is sufficient to achieve efficacy in an animal model of transplantation. [Copyright &y& Elsevier]

The Markam gneiss dome within the Songpan-Ganzi orogenic belt, eastern Tibetan Plateau, is cored by the Keryin-Taiyanghe granitoids and mantled by Upper Triassic, turbiditic, metasedimentary rocks, which have been intruded by numerous pegmatites and veins. The large-scale Markam detachment fault separates the granitoid core from the overlying Upper Triassic metasedimentary rocks. Microstructures and quartz fabrics from the Markam detachment fault show a top-to-the-south shearing sense and point to formation under high temperatures (>650 °C). New zircon U Pb geochronological data from the Markam gneiss dome reveal two stages for the granitoid core at ca. 226–212 Ma and ca. 224–218 Ma. In addition, zircon U Pb dating of syn -tectonically deformed pegmatites in the Markam detachment fault shows that the detachment fault was initiated at ca. 212–207 Ma. Later-stage, undeformed pegmatites (including spodumene-bearing varieties) that form sill- and dyke-networks have ages of ca. 200–190 Ma. Our data indicate that formation of the Markam gneiss dome was triggered by development of the Markam detachment fault after the emplacement of the granitoid core. And the following diapiric uplift of the granitoids continued the growth of the Markam gneiss dome, resulting in formation of a thermal domal structure, which further uplifted the magma to a more favorable metallogenic environment and controlled the occurrence of the ore veins. Thus, it indicates that the spodumene-bearing pegmatites emplaced under extensional and decompressional conditions during the Songpan-Ganzi exhumation orogeny. • The MGD is characterized by cored granites and metamorphic rocks. • A large-scale shearing Markam detachment was identified. • The two-phase pegmatites occurred between ca. 212 and 190 Ma. • Spodumene concentrates in the younger undeformed pegmatites. [ABSTRACT FROM AUTHOR]

Background: Mitofusin 2 (Mfn2) is outer membrane protein, as the inhibitor of Ras protein. This study aimed to investigate the effect of Mfn2 on cell proliferation, and cell-cycle in Hela cervical carcinoma cell lines. Methods: After treated with Adv-mfn2 or Adv-control for 48 h and 60 h, the RNA and protein of Mfn2 in Hela cells were detected by qRT-PCR and western blot. The immunofluorescence assay was performed to observe the expression and sub-location of Mfn2 in Hela cells. The flow cytometry was performed to detect the cell cycle of Hela cells, while western blots were performed to observe the Ras-NF-κB signal pathway. Then, the xenografted cervix carcinoma mouse model was used to confirm the effect of Mfn2 in Hela cells in vivo and the expression of Ras-NF-κB signaling pathway in vivo. Results: In immunofluorescence detection, Mfn2 was located in cytoplasmic, not in the nucleus. In addition, Mfn2 inhibited cell proliferation of Hela cells through reducing PCNA protein expression. Mfn2 induced arrest in G0/G1 phase of the cell cycle in Hela cells. Meanwhile, Mfn2 reduced Cyclin D1 protein expression. Moreover, Mfn2 decreased the Ras signal pathway proteins such as Myc, NF-κB p65, STAT3 in a dose-dependent manner. Then, the in vivo experiment also confirmed that Mfn2 could inhibit the tumor growth, and depress the Cyclin D1, Ras, Myc, NF-κB p65, Erk1/2 and mTOR protein expression. Conclusions: Mfn2 could significantly inhibit cell proliferation in Hela cells. It might be acted as an potential anti-cancer target through inducing cell cycle arrest in human cervical carcinoma cells. [ABSTRACT FROM AUTHOR]