Research on risk management incentive strategy based on the green financial ecosystem.

Taking the green financial ecosystem composed of innovators, green financial institutions and regulators as the object of research, it explores the issue of how to improve the level of efforts of the three types of subjects and the benefits of risk management in the green financial ecosystem. The optimal level of effort, optimal level of return, and optimal level of return on risk management of green financial ecosystems for innovators, green financial institutions, and regulators under the three modes of No-incentive Contract, Cost-sharing Contract, and Synergistic Cooperation Contract are investigated and analyzed respectively, and verified by numerical simulation analysis. The results show: (1) Compared to the No-incentive Contract, the Cost-sharing Contract and the Synergy Cooperation Contract generate more significant incentives, and returns increase over time in both models. (2) The effort level of the participating subjects under the Synergistic Cooperation Contract is the highest, which can realize the Pareto optimization of the participating subjects and the green financial ecosystem at the same time. The study's findings contribute to a deeper understanding of cooperation among innovators, green financial institutions and regulators in facilitating risk management in green financial ecosystems and provide a realistic reference for risk managers in green financial ecosystems.

End-of-Life Symptom Burden among Patients with Cancer Who Were Provided Medical Assistance in Dying (MAID): A Longitudinal Propensity-Score-Matched Cohort Study.

Cancer is the primary underlying condition for most Canadians who are provided Medical Assistance in Dying (MAID). However, it is unknown whether cancer patients who are provided MAID experience disproportionally higher symptom burden compared to those who are not provided MAID. Thus, we used a propensity-score-matched cohort design to evaluate longitudinal symptom trajectories over the last 12 months of patients' lives, comparing cancer patients in Alberta who were and were not provided MAID. We utilized routinely collected retrospective Patient-Reported Outcomes (PROs) data from the Edmonton Symptom Assessment System (ESAS-r) reported by Albertans with cancer who died between July 2017 and January 2019. The data were analyzed using mixed-effect models for repeated measures to compare differences in symptom trajectories between the cohorts over time. Both cohorts experienced increasing severity in all symptoms in the year prior to death (ß from 0.086 to 0.231, p ≤ .001 to .002). Those in the MAID cohort reported significantly greater anxiety (ß = -0.831, p = .044) and greater lack of appetite (ß = -0.934, p = .039) compared to those in the non-MAID cohort. The majority (65.8%) of patients who received MAID submitted their request for MAID within one month of their death. Overall, the MAID patients did not experience disproportionally higher symptom burden. These results emphasize opportunities to address patient suffering for all patients with cancer through routine collection of PROs as well as targeted and early palliative approaches to care.

Aging increases the particulate- and leachate-induced toxicity of tire wear particles to microalgae.

The toxic effects of tire wear particles (TWPs) on organisms have attracted widespread concerns over the past decade. However, the underlying toxicity mechanism of TWPs, especially aged TWPs to marine microalgae remains poorly understood. This study investigated the physiological and metabolic responses of Phaeodactylum tricornutum to different concentrations of TWPs (Experiment 1), virgin and differently aged TWPs (Experiment 2) as well as their leachates and leached particles (Experiment 3). Results demonstrated that TWPs promoted the growth of microalgae at low concentrations (0.6 and 3 mg L-1) and inhibited their growth at high concentrations (15 and 75 mg L-1). Moreover, aged TWPs induced more profound physiological effects on microalgae than virgin TWPs, including inhibiting microalgae growth, decreasing the content of Chla, promoting photosynthetic efficiency, and causing oxidative damage to algal cells. Untargeted metabolomics analysis confirmed that aged TWPs induced more pronounced metabolic changes than virgin TWPs. This study represented the first to demonstrate that both particulate- and leachate-induced toxicity of TWPs was increased after aging processes, which was confirmed by the changes in the surface morphology of TWPs and enhanced release of additives. Through the significant correlations between the additives and the microalgal metabolites, key additives responsible for the shift of microalgal metabolites were identified. These results broaden the understanding of the toxicity mechanism of aged TWPs to microalgae at the physiological and metabolic levels and appeal for considering the effects of long-term aging on TWP toxicity in risk assessment of TWPs.

Simultaneous determination of five constituents of areca nut extract in rat plasma using UPLC-MS/MS and its application in a pharmacokinetic study.

Areca nuts have been used as a traditional Chinese medicine (TCM) for thousands of years. Recent studies have shown that it exhibits good pharmacological activity and toxicity. In this study, the pharmacokinetics of five major components of areca nut extract in rats were investigated using a highly sensitive ultra-performance liquid chromatography coupled with triple quadrupole mass spectrometry (UPLC-MS/MS) method. Arecoline, arecaidine, guvacoline, guvacine, and catechin were separated and quantified accurately using gradient elution with mobile phases of (A) water containing 0.1 % formic acid-10 mM ammonium formate, and (B) methanol. The constituents were detected under a timing switch between the positive and negative ion modes using multiple reaction monitoring (MRM). Each calibration curve had a high R2 value of >0.99. The method accuracies ranged -7.09-11.05 % and precision values were less than 14.36 %. The recovery, matrix effect, selectivity, stability, and carry-over of the method were in accordance with the relevant requirements. It was successfully applied for the investigation of the pharmacokinetics of these five constituents after oral administration of areca nut extract. Pharmacokinetic results indirectly indicated a metabolic relationship between the four areca nut alkaloids in rats. For further clarification of its pharmacodynamic basis, this study provided a theoretical reference.

Molecular dynamics simulation of the initial stage induction of alkali-activated aluminosilicate minerals.

With the increasing global concern over carbon emissions, geopolymers have garnered significant attention due to their energy-saving, waste utilization, and eco-friendly advantages. Metakaolin and slag, as aluminum-containing mineral materials in geopolymer production, have been widely studied and applied. Previous research has mainly focused on performance design and theoretical development, while the underlying mechanisms at the microscopic level remain unclear. In this study, we employed molecular dynamics simulations to investigate the microscale reaction behavior of geopolymers, exploring the induction process and structural evolution during the initial stages, and revealing the similarities and differences under alkali activation for different materials. Our findings indicate that the alkali activation process can be divided into two stages: mineral crystal deconstruction and oligomer polymerization. The role of NaOH differs between low-calcium and high-calcium systems, where in the low-calcium system, Na+ substitutes Ca2+ due to Ca2+ deficiency, participating in the formation of the network framework. Moreover, the high-calcium system exhibits a faster formation of the gel phase during alkali activation compared to the low-calcium system. This study provides valuable insights into the research and application of geopolymers.

Z-Type Ligand Enables Efficient and Stable Deep-Blue Perovskite Light-Emitting Diodes.

During the synthesis of deep-blue perovskite quantum dots (PQDs), they generally emerge as a two-dimensional byproduct with poor yield and low photoluminescence quantum yield (PLQY) due to amine ligand enrichment-induced abundant surface defects. Herein, we provide a colloidal synthesis method to prepare deep-blue CsPbBr3 PQDs in a green nontoxic solvent via strategic Z-type ligand engineering. Z-type ligands of zinc octanoate enable the formation of robust coordination bonds with surface bromide ions of PQDs, maintaining acid-base equilibrium and reducing excess amine enrichment on the PQDs surface. Consequently, homogeneous and monodispersed PQDs with improved PLQY of 73% are successfully synthesized, achieving efficient deep-blue LEDs with a peak EQE of 5.46%, a maximum luminance of 847.6 cd/m2, and an operational half-lifetime of 14 min. The devices exhibit color coordinates of (0.137, 0.049), closely approximating the Rec. 2020 blue standard. Our work offers a potentially eco-friendly and viable route for realizing high-performance LEDs in the deep-blue region.

Exopolysaccharide production by Lactobacillus plantarum T10 is responsible for the probiotic activity in enhancing intestinal barrier function in vitro and in vivo.

Lactobacillus probiotics exert their effects in a strain-specific and metabolite-specific manner. This study aims to identify lactobacilli that can effectively enhance the intestinal barrier function both in vitro and in vivo and to investigate the underlying metabolite and molecular mechanisms involved. Nine Lactobacillus isolates were evaluated for their ability to enhance the IPEC-J2 cellular barrier function and for their anti-inflammatory and anti-apoptotic effects in IPEC-J2 cells after an enterotoxigenic Escherichia coli challenge. Of the nine isolates, L. plantarum T10 demonstrated significant advantages in enhancing the cellular barrier function and displayed anti-inflammatory and anti-apoptotic activities in vitro. The bioactivities of L. plantarum T10 were primarily attributed to the production of exopolysaccharides, which exerted their effects through the TLR-mediated p38 MAPK pathway in ETEC-challenged IPEC-J2 cells. Furthermore, the production of EPS by L. plantarum T10 led to the alleviation of dextran sulfate sodium-induced colitis by reducing intestinal damage and enhancing the intestinal barrier function in mice. The EPS is classified as a heteropolysaccharide with an average molecular weight of 23.0 kDa. It is primarily composed of mannose, glucose, and ribose. These findings have practical implications for the targeted screening of lactobacilli used in the production of probiotics and postbiotics with strain-specific features of exopolysaccharides.

Supplementation of citrus pectin with whole-cell pectinase PG5 on Pichia pastoris promotes recovery of colitis and enhances intestinal barrier function in DSS-treated mice.

A whole-cell biocatalyst was developed by genetically engineering pectinase PG5 onto the cell surface of Pichia pastoris using Gcw12 as the anchoring protein. Whole-cell PG5 eliminated the need for enzyme extraction and purification, while also exhibiting enhanced thermal stability, pH stability, and resistance to proteases in vitro compared to free PG5. Magnetic resonance mass spectrometry analysis revealed that whole-cell PG5 efficiently degraded citrus pectin, resulting in the production of a mixture of pectin oligosaccharides. The primary components of the mixture were trigalacturonic acid, followed by digalacturonic acid and tetragalacturonic acid. Supplementation of citrus pectin with whole-cell PG5 resulted in a more pronounced protective effect compared to free PG5 in alleviating colitis symptoms and promoting the integrity of the colonic epithelial barrier in a mouse model of dextran sulfate sodium-induced colitis. Hence, this study demonstrates the potential of utilizing whole-cell pectinase as an effective biocatalyst to promote intestinal homeostasis in vivo.

Nitrogen-rich Ce-N compounds under high pressure.

Four high-pressure N-rich compounds (Pmn21-CeN7, Amm2-CeN9, P1̄-CeN10, and P1̄-II-CeN10) are proposed using first-principles calculations. Novel polymeric units (a heart shaped layered structure, chain-like N8 rings, and two new banded structures) in four cerium nitrides are reported for the first time in this study. The analyses of electronic structures and bonding properties show that the charge transfer between Ce and N atoms promotes the formation of the Ce-N ionic bond and N-N covalent bond, which play an important role in stabilizing the nitrogen skeleton. Four new phases possess high energy densities (3.24-3.86 kJ g-1), indicating that they are favorable high-energy density materials. Moreover, P1̄-CeN10 possesses ultra-incompressibility along the [1 0 0] direction. Finally, infrared and Raman spectra are analyzed to provide guidance for experimental synthesis.

Effects of Herpud1 in Methamphetamine-Induced Neuronal Apoptosis.

INTRODUCTION: Methamphetamine (METH) is an illicit psychoactive substance that can damage various organs in the body, especially the nervous system. We hypothesized that expression of homocysteine-inducible endoplasmic reticulum-resident with ubiquitin-like domain member 1 (Herpud1) protein would alleviate the induction of apoptosis following METH administration. METHODS: To test this hypothesis, we analysed the changes in Herpud1 expression and apoptosis in PC12 cells under different concentrations and exposure times of METH. Moreover, we examined the effects of Herpud1 knockdown on METH-induced neuronal apoptosis. Flow cytometry and Western blot analyses were used to evaluate apoptosis levels and the expression of apoptotic markers (cleaved caspase-3) in PC12 cells following Herpud1 knockdown by synthetic small interfering RNA (siRNA). RESULTS: Our results showed that Herpud1 expression was upregulated in PC12 cells following METH treatment, while endoplasmic reticulum stress (ERS) and apoptosis were also increased. Conversely, Herpud1 knockdown reduced METH-induced ERS and apoptosis levels in vitro. CONCLUSIONS: These results suggest that Herpud1 plays an essential role in METH-induced neuronal ERS and apoptosis and may represent a potential therapeutic gene target in METH-induced neurotoxicity.

RFX1 regulates foam cell formation and atherosclerosis by mediating CD36 expression.

BACKGROUND AND AIMS: Atherosclerosis (AS) is a continuously low-grade inflammatory disease, and monocyte-derived macrophages play a vital role in AS pathogenesis. Regulatory factor X1 (RFX1) has been reported to participate in differentiation of various cells. Our previous report showed that RFX1 expression in CD14+ monocytes from AS patients was decreased and closely related to AS development. Macrophages mostly derive from monocytes and play an important role in AS plaque formation and stability. However, the functions of RFX1 in the formation of macrophage-derived foam cells and consequent AS development are unclear. METHODS: We explored the effects of RFX1 on oxidation low lipoprotein (ox-LDL)-stimulated foam cell formation and CD36 expression by increasing or silencing Rfx1 expression in mouse peritoneal macrophages (PMAs). The ApoE-/-Rfx1f/f or ApoE-/-Rfx1f/f Lyz2-Cre mice fed a high-fat diet for 24 weeks were used to further examine the effect of RFX1 on AS pathogenesis. We then performed dual luciferase reporter assays to study the regulation of RFX1 for CD36 transcription. RESULTS: Our results demonstrate that RFX1 expression was significantly reduced in ox-LDL induced foam cells and negatively correlated with lipid uptake in macrophages. Besides, Rfx1 deficiency in myeloid cells aggravated atherosclerotic lesions in ApoE-/- mice. Mechanistically, RFX1 inhibited CD36 expression by directly regulating CD36 transcription in macrophages. CONCLUSIONS: The reduction of RFX1 expression in macrophages is a vital determinant for foam cell formation and the initiation of AS, proving a potential novel approach for the treatment of AS disease.

Research Review: Grandparental care and child mental health - a systematic review and meta-analysis.

BACKGROUND: The number of children residing in grandfamilies is growing worldwide, leading to more research attention on grandparental care over the past decades. Grandparental care can influence child well-being in various forms and the effects vary across contexts. In this systematic review and meta-analysis, we synthesize the evidence on the relation between grandparental care and children's mental health status. METHODS: We identified 5,745 records from seven databases, among which 38 articles were included for review. Random effects meta-analyses were used to synthesize evidence from eligible studies. We also examined the variability across study and participant characteristics, including study design, recruitment method, child age, child gender, study region, family type, comparison group, and outcome rater. RESULTS: The meta-analysis consisted of 344,860 children from the included studies, whose average age was 10.29, and of which 51.39% were female. Compared with their counterparts, children being cared for by their grandparents had worse mental health status, including more internalizing problems (d = -0.20, 95% CI [-0.31, -0.09], p = .001), externalizing problems (d = -0.11, 95% CI [-0.21, -0.01], p = .03), overall mental problems (d = -0.37, 95% CI [-0.70, -0.04], p = .03), and poorer socioemotional well-being (d = -0.26, 95% CI [-0.49, -0.03], p = .03). The effects varied by study design and child gender. CONCLUSIONS: The findings highlight that grandparental care is negatively associated with child mental health outcomes with trivial-to-small effect sizes. More supportive programs and interventions should be delivered to grandfamilies, especially in disadvantaged communities.

The Role of Sgt1 in Methamphetamine/Hyperthermia-induced Necroptosis.

INTRODUCTION: Methamphetamine (METH) is a synthetic drug widely abused globally and can result in hyperthermia (HT) and psychiatric symptoms. Our previous studies showed that heat shock protein 90 alpha (HSP90α) plays a vital role in METH/HT-elicited neuronal necroptosis; however, the detailed mechanism of HSP90α regulation remained obscure. METHODS: Herein, we demonstrated a function of the suppressor of G-two allele of SKP1 (Sgt1) in METH/HT-induced necroptosis. Sgt1 was mainly expressed in neurons, co-located with HSP90α, and increased in rat striatum after METH treatment. METH/HT injury triggered necroptosis and increased Sgt1 expression in PC-12 cells. RESULT: Data from computer simulations indicated that Sgt1 might interact with HSP90α. Geldanamycin (GA), the specific inhibitor of HSP90α, attenuated the interaction between Sgt1 and HSP90α. Knockdown of Sgt1 expression did not affect the expression level of HSP90α. Still, it inhibited the expression of receptor-interacting protein 3 (RIP3), mixed lineage kinase domain-like protein (MLKL), p-RIP3, and p-MLKL, as well as necroptosis induced by METH/HT injury. CONCLUSION: In conclusion, Sgt1 may regulate the expression of RIP3, p-RIP3, MLKL, and p-MLKL by assisting HSP90α in affecting the METH/HT-induced necroptotic cell death.

The MRI radiomics signature can predict the pathologic response to neoadjuvant chemotherapy in locally advanced esophageal squamous cell carcinoma.

OBJECTIVES: To investigate the MRI radiomics signatures in predicting pathologic response among patients with locally advanced esophageal squamous cell carcinoma (ESCC), who received neoadjuvant chemotherapy (NACT). METHODS: Patients who underwent NACT from March 2015 to October 2019 were prospectively included. Each patient underwent esophageal MR scanning within one week before NACT and within 2-3 weeks after completion of NACT, prior to surgery. Radiomics features extracted from T2-TSE-BLADE were randomly split into the training and validation sets at a ratio of 7:3. According to the progressive tumor regression grade (TRG), patients were stratified into two groups: good responders (GR, TRG 0 + 1) and poor responders (non-GR, TRG 2 + 3). We constructed the Pre/Post-NACT model (Pre/Post-model) and the Delta-NACT model (Delta-model). Kruskal-Wallis was used to select features, logistic regression was used to develop the final model. RESULTS: A total of 108 ESCC patients were included, and 3/2/4 out of 107 radiomics features were selected for constructing the Pre/Post/Delta-model, respectively. The selected radiomics features were statistically different between GR and non-GR groups. The highest area under the curve (AUC) was for the Delta-model, which reached 0.851 in the training set and 0.831 in the validation set. Among the three models, Pre-model showed the poorest performance in the training and validation sets (AUC, 0.466 and 0.596), and the Post-model showed better performance than the Pre-model in the training and validation sets (AUC, 0.753 and 0.781). CONCLUSIONS: MRI-based radiomics models can predict the pathological response after NACT in ESCC patients, with the Delta-model exhibiting optimal predictive efficacy. CLINICAL RELEVANCE STATEMENT: MRI radiomics features could be used as a useful tool for predicting the efficacy of neoadjuvant chemotherapy in esophageal carcinoma patients, especially in selecting responders among those patients who may be candidates to benefit from neoadjuvant chemotherapy. KEY POINTS: • The MRI radiomics features based on T2WI-TSE-BLADE could potentially predict the pathologic response to NACT among ESCC patients. • The Delta-model exhibited the best predictive ability for pathologic response, followed by the Post-model, which similarly had better predictive ability, while the Pre-model performed less well in predicting TRG.

Moxibustion influences hippocampal microglia polarization via IL-33/ST2 pathway in Alzheimer's disease mice. / è‰¾ç¸é€šè¿‡ç™½ç»†èƒžä»‹ç´ -33/ç”Ÿé•¿åˆºæ¿€è¡¨è¾¾åŸºå› 2è›‹ç™½é€šè·¯å½±å“é˜¿å°”èŒ¨æµ·é»˜ç— å°é¼ æµ·é©¬å°èƒ¶è´¨ç»†èƒžæžåŒ–.

OBJECTIVES: To observe the effect of moxibustion on the polarization of microglia towards M2 direction in Alzheimer's disease (AD) mice through the interleukin-33 (IL-33)/growth stimulating gene 2 protein (ST2) signaling pathway. METHODS: Five-month-old APP/PS1 male mice were randomly divided into model and moxibustion (Moxi) groups, and C57BL/6J mice of the same age were as the control group, with 9 mice in each group. In the Moxi group, moxibustion was applied at "Baihui" (GV20) and "Yongquan" (KI1) for 30 min, once a day, 5 days a week for 4 weeks. The spatial learning memory ability was observed by the Morris water maze test. The relative expressions of IL-33 and ST2 in hippocampus were detected by Western blot. The positive expression of amyloid-ß (Aß), phosphorylated Tau (p-Tau), IL-33/ionized calcium binding adapter molecule 1(Iba-1), ST2/Iba-1, arginase 1 (Arg1)/Iba-1 and indu-cible nitric oxide synthase (iNOS)/Iba-1 in hippocampal CA1 region were detected by immunofluorescence. RESULTS: Compared with the control group, the escape latency of the mice in the model group was prolonged (P<0.001, P<0.01), the number of times to enter the effective area and the percentage of target quadrant swimming time were reduced (P<0.001), the positive expression of both Aß and p-Tau, the positive expression of iNOS/Iba-1 in the hippocampal CA1 region was increased (P<0.001), while the expression of IL-33 and ST2 protein in hippocampal tissue, the positive expression levels of IL-33/Iba-1, ST2/Iba-1 and Arg1/Iba-1 in hippocampal CA1 region were all decreased (P<0.05, P<0.001). After treatment, compared with the model group, the escape latency of the mice in the moxibustion group was shortened (P<0.001, P<0.01), the number of entries into the effective area and the percentage of target quadrant swimming time were increased (P<0.001), the positive expression of Aß and p-Tau in the hippocampal CA1 region, and the positive expression of iNOS/Iba-1 were decreased (P<0.001), while the expression of IL-33 and ST2 protein in the hippocampal tissue, the positive expression of IL-33/Iba-1, ST2/Iba-1 and Arg1/Iba-1 in hippocampal CA1 region were all increased (P<0.05, P<0.01, P<0.001). CONCLUSIONS: Moxibustion can improve the spatial learning and memory abilities, reduce the pathological deposition of Aß and p-Tau in APP/PS1 mice, which may be related to its function in up-regulating the IL-33/ST2 signaling pathway to regulate the polarization of microglia towards M2 direction.

Complex role of strain engineering of lattice thermal conductivity in hydrogenated graphene-like borophene induced by high-order phonon anharmonicity.

Strain engineering has been used as a versatile tool for regulating the thermal transport in various materials as a result of the phonon frequency shift. On the other hand, the phononic bandgap can be simultaneously tuned by the strain, which can play a critical role in wide phononic bandgap materials due to the high-order phonon anharmonicity. In this work, we investigate the complex role of uniaxial tensile strain on the lattice thermal conductivity of hydrogenated graphene-like borophene, by using molecular dynamics simulations with a machine learning potential. Our findings highlight a novel and intriguing phenomenon that the thermal conductivity in the armchair direction is non-monotonically dependent on the uniaxial armchair strain. Specifically, we uncover that the increase of phonon group velocity and the decrease of three-phonon scattering compete with the enhancement of four-phonon scattering under armchair strain, leading to the non-monotonic dependence. The enhanced four-phonon scattering originates from the unique bridged B-H bond that can sensitively control the phononic bandgap under armchair strain. This anomalous non-monotonic strain-dependence highlights the complex interplay between different mechanisms governing thermal transport in 2D materials with large phononic bandgaps. Our study offers valuable insights for designing innovative thermal management strategies based on strain.

Stachydrine Hydrochloride Regulates the NOX2-ROS-Signaling Axis in Pressure-Overload-Induced Heart Failure.

Our previous studies revealed the protection of stachydrine hydrochloride (STA) against cardiopathological remodeling. One of the underlying mechanisms involves the calcium/calmodulin-dependent protein kinase Ⅱ (CaMKII). However, the way STA influences CaMKII needs to be further investigated. The nicotinamide adenine dinucleotide phosphate oxidase 2 (NOX2)-coupled reactive oxygen species (ROS) overproduction putatively induces the oxidative activation of CaMKII, resulting in the occurrence of pathological cardiac remodeling and dysfunction in experimental models of mice. Thus, in this study, we assessed the role of the NOX2-ROS signal axis in STA cardioprotection. The transverse aortic constriction (TAC)-induced heart failure model of mice, the phenylephrine-induced hypertrophic model of neonatal rat primary cardiomyocytes, and the H2O2-induced oxidative stress models of adult mouse primary cardiomyocytes and H9c2 cells were employed. The echocardiography and histological staining were applied to assess the cardiac effect of STA (6 mg/kg/d or 12 mg/kg/d), which was given by gavage. NOX2, ROS, and excitation-contraction (EC) coupling were detected by Western blotting, immunofluorescence, and calcium transient-contraction synchronous recordings. ROS and ROS-dependent cardiac fibrosis were alleviated in STA-treated TAC mice, demonstrating improved left ventricular ejection fraction and hypertrophy. In the heart failure model of mice and the hypertrophic model of cardiomyocytes, STA depressed NOX2 protein expression and activation, as shown by inhibited translocation of its phosphorylation, p67phox and p47phox, from the cytoplasm to the cell membrane. Furthermore, in cardiomyocytes under oxidative stress, STA suppressed NOX2-related cytosolic Ca2+ overload, enhanced cell contractility, and decreased Ca2+-dependent regulatory protein expression, including CaMKⅡ and Ryanodine receptor calcium release channels. Cardioprotection of STA against pressure overload-induced pathological cardiac remodeling correlates with the NOX2-coupled ROS signaling cascade.

The change of green space well-being during rapid urbanization: A case study in Jinan, China, 2006-2018.

With the rapid advancement of urbanization, the green space well-being (GSWB) of developing countries faces drastic changes and is increasingly threatened. Green and residential spaces are the core elements of GSWB; however, we know very little about the interaction and combination of the two in terms of their effect on GSWB. This study identified the spatiotemporal features of GSWB and critically examined how patterns of residential-green combinations affect GSWB. Based on land-use data for Jinan from 2006 to 2018, and using the spatial measurement tool GeoDa, we found that both green and residential space have increased significantly in central Jinan. At the macro level, the spatial correlation between the two decreased significantly; meanwhile, at the micro level, there are obvious differences in time and geography. This led to differences in the distribution of GSWB between regions with high value and those with low value. We revealed that the development, preservation, and demolition of residential and green spaces influence changes in GSWB. The positive effects on GSWB come from (1) mountain park development policy in built-up areas, (2) theme park development policy in new urban areas, and (3) urban renewal and demolition policy. The negative effects on GSWB come from (1) issues remaining from prior extensive urban development, (2) the replacement of central areas driven by urban branding, and (3) the lack of supervision of nearby facilities for new housing development. To better understand changes in GSWB, it is necessary to consider its internal residential-green spatial collaboration and propose targeted response strategies. This can help to better safeguard the quality of human settlements in the process of urbanization in developing countries.

Icariin inhibits hypertrophy by regulation of GPER1 and CaMKII/HDAC4/MEF2C signaling crosstalk in ovariectomized mice.

Icariin (ICA), a flavonoid phytoestrogen, was isolated from traditional Chinese medicine Yin Yang Huo (Epimedium brevicornu Maxim.). Previous studies reporting the cardioprotective effects of ICA are available; however, little is known about the impact of ICA on cardioprotection under conditions of reduced estrogen levels. This study aimed to provide detailed information regarding the antihypertrophic effects of ICA in ovariectomized female mice. Female mice were subjected to ovariectomy (OVX) and transverse aortic constriction and then orally treated with ICA at doses of 30, 60 or 120 mg/kg/day for 4 weeks. Morphological assessments, echocardiographic parameters, histological analyses, and immunofluorescence were performed to evaluate cardiac hypertrophy. Cardiomyocytes from mice or rats were stimulated using phenylephrine, and cell surface and hypertrophy markers were tested using immunofluorescence and qPCR. Western blotting, qPCR, and luciferase reporter gene assays were used to assess the expression of proteins and mRNA and further investigate the proteins related to the G-protein coupled estrogen receptor (GPER1) and CaMKII/HDAC4/MEF2C signaling pathways in vivo and in vitro. ICA blocks cardiac hypertrophy induced by pressure overload in OVX mice. Additionally, we demonstrated that ICA activated GPER1 and inhibited the nuclear export or promoted the nuclear import of histone deacetylase 4 (HDAC4) through regulation of phosphorylation of calmodulin-dependent protein kinase II (CaMKII) and further improved the repression of myocyte enhancer factor-2C (MEF2C). ICA ameliorated cardiac hypertrophy in OVX mice by activating GPER1 and inhibiting the CaMKII/HDAC4/MEF2 signaling pathway.

In vitro bloodbrain barrier permeability study of four main active ingredients from Alpiniae oxyphyllae fructus.

The fruits of Alpinia oxyphylla Miq., a broadly utilized traditional Chinese medicine, have a number of effects on the central nervous system (CNS). The main active constituents of Alpiniae oxyphyllae fructus (AOF) were nootkatone, tectochrysin, chrysin and protocatechuic acid. An immortalized human brain microvascular endothelial cell (hCMEC/D3) and astrocyte (HA1800) coculture model was used to investigate the permeability of the blood-brain barrier (BBB). The validation of ultrahigh-performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) methods for the four compounds was conducted following industry guidelines. Calibration curves were generated with mean coefficients (R2) better than 0.99. The inter-day and intra-day precisions were less than 8.53% and 7.12%, respectively. The accuracies were lower than ± 11.57%, and recoveries were greater than 86.07%. The samples of the transport experiment were examined, and the apparent permeability coefficients (Papp) were calculated. The efflux ratios of the four compounds are all less than 2. The Papp values of protocatechuic acid, chrysin, nootkatone, tectochrysin were at the level of 10-5, 10-6, 10-6, and 10-7 cm/s, respectively. All four compounds crossed the BBB by passive diffusion, with protocatechuic acid having high permeability, and tectochrysin having poor permeability. This research indicated the permeability of protocatechuic acid, chrysin, nootkatone and tectochrysin through the BBB and offered a foundation for related research on AOF in the treatment of CNS illnesses.