Incorporation of Finasteride-Loaded Microspheres into Personalized Microneedle for Sustained Transdermal Delivery.

Although finasteride (FNS) tablets are considered the most effective drug for the treatment of androgenetic alopecia (AGA), their clinical applications are limited due to the associated side effects including decreased libido, breast enlargement, and liver dysfunction. In this study, we have developed a personalized microneedle (PMN) with a double-layer structure that incorporates FNS-loaded microspheres (MPs) to accommodate irregular skin surfaces. This design enables the sustained release of FNS, thereby reducing potential side effects. The needle body was synthesized with high-strength hyaluronic acid (HA) as the base material substrate. The backing layer utilized methacrylate gelatin (GelMA) with specific toughness, enabling PMN to penetrate the skin while adapting to various skin environments. The length of PMN needles (10 × 10) was approximately 600 µm, with the bottom of the needles measuring about 330 µm × 330 µm. The distance between adjacent tips was around 600 µm, allowing the drug to penetrate the stratum corneum of the skin. The results of the drug release investigation indicated the sustained and regulated release of FNS from PMN, as compared to that of pure FNS and FNS-MPs. Further, the cytotoxicity assay demonstrates that PMS displays good cytocompatibility. Altogether, this mode of administration has immense potential for the development of delivery of other drugs, as well as in the medical field.

How does new energy demonstration city pilot policy affect carbon dioxide emissions? Evidence from a quasi-natural experiment in China.

Energy transition policies are of great significance in adjusting the structure of energy supply and demand and coping with climate change. The new energy demonstration city pilot (NEDCP) policy, as an important pilot project in China's energy transition process, lacks a scientific assessment of the carbon reduction effect of the NEDCP policy and an in-depth explanation of the mechanism of the NEDCP. Based on panel data of 209 Chinese cities at the prefectural and higher levels from 2007 to 2019, this study takes the NEDCP policy as a quasi-natural experiment, using a difference-in-differences model combined with firm-level data to identify the impact of the NEDCP policy on urban carbon dioxide (CO2) emissions. This study analyzes the impact of heterogeneity of urban characteristics on the policy effect from multiple perspectives, and further investigates its mechanism. The conclusions are shown in the following aspects. (1) The implementation of the NEDCP policy decreases urban CO2 emissions significantly. Meanwhile, a series of robustness tests, including the instrumental variables method, propensity score matching difference-in-differences method, placebo test, exclusion of policy interference test, and machine learning method, support this conclusion. (2) The NEDCP policy achieves carbon reduction effects mainly through scale and structure effects. (3) The results of the heterogeneity test show that the NEDCP policy is more effective in cities with higher administrative levels, energy-demanding cities, cities in the southeast of Hu-line, and cities with a higher degree of nationalization. Therefore, the Chinese government should summarize the implementation experience of the NEDCP policy and expand its scope of application. The evaluation of the NEDCP policy in China has important reference value for the energy transition of other developing countries.

Mitochondrial KATP channel-mediated autophagy contributes to angiotensin II-induced vascular dysfunction in mice.

BACKGROUND AND AIM: The present study aimed to investigate whether the mitochondrial KATP channel contributes to angiotensin II (Ang II)-induced vascular dysfunction, the development of hypertension, and atherosclerosis. METHODS AND RESULTS: ApoE (-/-) mice fed a high-fat diet were chronically infused with Ang II for eight weeks and concomitantly treated with losartan (ARB), apocynin, or 5-hydroxy decanoate (5-HD), or 3-methyladenine (3-MA). Systolic blood pressure was measured, and pathological changes of aortic or liver tissue were observed. Nitric oxide (NO), superoxide dismutase 2 (SOD2) levels and vasorelaxation rate were measured, and protein and mRNA expressions were examined by western blot and RT-PCR. Ang II-induced development of hypertension was suppressed not only by ARB, and apocynin but also by 5-HD or 3-MA. Ang II infusion decreased aortic NO production and relaxation, as well as SOD2 activity in liver, which were improved by all treatments. In addition, Ang II-induced activation of autophagy was suppressed by 5-HD in aortic tissue, furthermore, Ang II increases the atherosclerotic index in plasma and exacerbates the development of atherosclerosis by increases of fat deposition in the aorta and liver. Lipid metabolism-related mRNA expressions (LXR-α, LDLR, SRBI, Acca, and FASN) were changed by Ang II. Similarly, not only ARB, and apocynin, but also 5-HD and 3-MA suppressed Ang II-induced these changes. CONCLUSIONS: Our present findings evidence that mitochondrial KATP channel-mediated autophagy contributes to Ang II-induced vascular dysfunction, development of hypertension, and atherosclerosis.

The Function and Regulation of Platelet P2Y12 Receptor.

In addition to the key role in hemostasis and thrombosis, platelets have also been wildly acknowledged as immune regulatory cells and involving in the pathogenesis of inflammation-related diseases. Since purine receptor P2Y12 plays a crucial role in platelet activation, P2Y12 antagonists such as clopidogrel, prasugrel, and ticagrelor have been widely used in cardiovascular diseases worldwide in recent decades due to their potent antiplatelet and antithrombotic effects. Meanwhile, the role of P2Y12 in inflammatory diseases has also been extensively studied. Relatively, there are few studies on the regulation of P2Y12. This review first summarizes the various roles of P2Y12 in the process of platelet activation, as well as downstream effects and signaling pathways; then introduces the effects of P2Y12 in inflammatory diseases such as sepsis, atherosclerosis, cancer, autoimmune diseases, and asthma; and finally reviews the current researches on P2Y12 regulation.

Contributions of cleaner production and end-of-pipe treatment to NOx emissions and intensity reductions in China, 1997-2018.

The Chinese experience of economic development and environmental protection provides an important reference for developing countries. Although changes in aggregate NOx emissions have been widely studied, there is a relative lack of studies analysing NOx intensity changes and their related development strategies in China. This study attempts to identify the socioeconomic drivers and change patterns for both NOx emissions and intensity considering the cleaner production and end-of-pipe treatments. Both structural decomposition analysis and structural path analysis were used to analyse the NOx emissions/intensity changes at different levels and transmission layers in China in the last two decades (1997-2018). The results indicate that construction contributes the most to NOx emissions/intensity, followed by transportation. The emission intensity effect is the primary driver of NOx emissions/intensity reduction, which mainly benefits from end-of-pipe treatment and energy efficiency improvement. Especially, during 2012-2018, they decreased 11,916 Kt-NOx and 8,103 Kt-NOx emissions and aggregate embodied intensity by 43.2% and 29.8%, respectively. The final demand effect is the primary deterrent, which is attributed to investment and consumption effects. The critical sectors for future NOx reduction are the construction and building materials industry, transportation and other services industry. The policy implications and recommendations for the future developments are discussed based on the study findings.

The pollution control effect of the atmospheric environmental policy in autumn and winter: Evidence from the daily data of Chinese cities.

The pollution control effect of seasonal environmental regulation policies in developing countries still lacks empirical evidence. In 2017, China implemented its first Atmospheric Environmental Policy in Autumn and Winter (AEPAW) to coordinate efforts among cities in reducing air pollutant emissions. Taking the daily panel data of 174 cities in northern China from July 2017 to July 2020 as samples, this paper empirically examines the pollution control effect of the AEPAW using a difference-in-differences model, a difference-in-difference-in-differences model, and a regression discontinuity design. The results show that the AEPAW significantly improves air quality in autumn and winter, with the air quality index decreasing by 5.6% on average by reducing PM2.5, PM10, SO2, and O3 emissions. However, the AEPAW only creates a short-term "policy-induced blue sky", and there exists a phenomenon of "retaliatory pollution" after the AEPAW ends. Besides, the pollution control effect of the AEPAW is moderated by the heterogeneity of the national "Two Sessions" and the Central Environmental Protection Inspection. The implementation of the AEPAW also has a significant spillover effect on air pollution control in surrounding areas. The net benefit from the AEPAW is estimated to be approximately US$ 670 million per year. These findings not only have practical significance for strengthening the comprehensive control of air pollution in China, but also give some important references for other developing countries.

Microbubbles for Effective Cleaning of Metal Surfaces Without Chemical Agents.

Traditional cleaning methods involving surfactants and ultrasound generate large amounts of wastewater. Microbubbles offer a more eco-friendly technology for interface cleaning. Here, we explored the efficiency of microbubbles for cleaning oil from metal surfaces. Air microbubbles at concentrations as high as 106 particles/mL were generated by hydrodynamic cavitation. Under optimal conditions, cleaning efficiencies for the removal of oil from carbon-steel and stainless-steel surfaces were 78.5 and 49.8% after 15 min, respectively, compared to only 6.5 and 9.9% without microbubbles. Additionally, combining microbubble treatment with the ultrasonic method achieved a higher efficiency than ultrasonic cleaning alone, achieving an efficiency of 85.5% after 3 min compared to 69.0%. The mechanism of microbubble cleaning was determined using a fluorescence observation system, and a model was established to describe the cleaning process. The use of microbubbles produced less emulsified oil wastewater because the oil that attaches to the microbubble surface floats with the bubbles to the surface of the cleaning water, where it can be removed, allowing for water recycling. This novel microbubble cleaning technology, which both enhances cleaning efficiency and reduces wastewater production, represents a viable and eco-friendly option for degreasing processes.

Autophagy contributes to angiotensin II induced dysfunction of HUVECs.

BACKGROUND: Signal transduction of Angiotensin II (Ang II) induced autophagy and its role in Ang II-induced dysfunction of HUVECs are still unclear. METHODS: HUVECs are stimulated with different doses of Ang II (10-9-10-5 mol/L) for different time (6-48 hours). Autophagy-related protein markers: LC3, Beclin-1 and SQSTM1/p62 are measured by western blot. RESULTS: Incubation with Ang II increases autophagic flux (Beclin-1, autophagosomes formation, and degradation of SQSTM1/p62, LC3-I). Increased autophagic levels are inhibited by pretreatment with Ang II type 1 receptor (AT1) blocker (Candesartan), NADPH Oxidase inhibitor (apocycin), mitochondrial KATP channels inhibitor (5-hydroxydecanoate, 5HD). 3-Methyladenine (inhibitors of autophagy) and rapamycin (activator of autophagy) respectively inhibits or activates Ang II-induced autophagy levels. Ang II decreases phosphorylation of endothelial nitric oxide synthase (eNOS) and NO production in HUVECs. L-NAME (NOS inhibitor) totally mimics the actions of Ang II on eNOS, NO production and autophagy levels. Rapamycin further decreases NO production combined with Ang II. Silence Atg5 completely reverses Ang II-activated autophagy levels. CONCLUSIONS: Our results demonstrate that Ang II stimulation increases autophagy levels via AT1 receptor, NADPH oxidase, mitochondrial KATP channel, eNOS, Atg5 signal pathway in HUVECs, and activation of autophagy contributes to Ang II induced dysfunction of HUVECs.

Treatment with 2-methoxyestradiol increases endothelial nitric oxide synthase activity via scavenger receptor class BI in human umbilical vein endothelial cells.

Concentrations of 2-methoxyestradiol (2ME2), a principal metabolite of estradiol, are significantly lower in women with severe preeclampsia. Nitric oxide (NO) released by endothelial nitric oxide synthase (eNOS) plays an important role in regulating cardiovascular homeostasis. Importantly, high-density lipoprotein (HDL) stimulates eNOS activity via endothelial human scavenger receptor class B type I (hSR-BI/CLA-1). Here, we aimed to determine the effect of 2ME2 on hSR-BI/CLA-1 expression in human umbilical vein endothelial cells (HUVECs). hSR-BI/CLA-1 expression was measured by real-time PCR, western blotting and reporter gene assays; eNOS activity was assessed by the measurement of eNOS phosphorylation. Both the mRNA and protein concentrations of hSR-BI/CLA-1 were significantly increased by 2ME2 in HUVECs. 2ME2 also dose-dependently increased the transcriptional activity of the hSR-BI/CLA-1 promoter. The effect of 2ME2 treatment on the promoter activity of hSR-BI/CLA-1 was abrogated by treatment with LY294002, a specific inhibitor of phosphatidylinositol 3-kinase, as was the increase in HDL-induced eNOS activation. Notably, constitutively active Akt increased the activity of the hSR-BI/CLA-1 promoter, whereas dominant-negative Akt abolished the effect of 2ME2 treatment on hSR-BI/CLA-1 promoter activity. The nuclear Sp1 protein concentration was significantly increased by exposure to 2ME2 and Sp1 overexpression increased the promoter activity of the hSR-BI/CLA gene. Furthermore, knockdown of Sp1 inhibited the effect of 2ME2 treatment on hSR-BI/CLA-1 protein expression. These results indicate that 2ME2 treatment increases HDL-dependent eNOS phosphorylation by upregulating endothelial hSR-BI/CLA-1 expression, suggesting that 2ME2 has a potential therapeutic value in the treatment of preeclampsia.

[Assay of 18 amino acids in Chuanmingshen violaceum roots by pre-column derivative HPLC].

The roots of Chuanmingshen violaceum is a commonly used Chinese herb and food, which contains rich amino acids. However, the kinds and amounts of amino acids are variety in this herb among the geographical location and ecological environment. Therefore, this study firstly developed a new pre-column derived HPLC method to quantify the levels of 18 amino acids in Ch. violaceum roots. Then 24 Ch. violaceum samples were harvested from its main cultivating areas in Sichuan, China. These samples were divided into 4 producing areas based on their geographical sites. The 18 kinds of amino acids were quantified in these sample by the developed method. The differences of these amino acids were further analyzed among these herbal samples and the 4 producing areas by t-test and principal component analysis(PCA). The result indicated the peaks of the 18 kinds of amino acids were separated well in 70 min.The correlation coefficients between peak areas and concentration of these amino acids were more than 0.999 1(n=6). All of their recoveries were in the range of 97.38%-101.3%(n=6).Their detection limit was in the range of 0.003-0.379 µg·mL~(-1).It demonstrates that the developed HPLC method can accurately quantify the amounts of multi-amino acids in this herb. The results of t-test analysis showed the contents of histidine, cystine, leucine, valine, tryptophan, phenylalanine and threonine were significantly different(P<0.05) among the 4 producing areas. But the differences of other amino acids were not significant.The first five factors were extracted by PCA to calculate the comprehensive score. The order of comprehensive score for the 4 producing areas was B(0.603, n=10), C(0.206, n=3), A(-0.283, n=7) and D(-1.167, n=4). The total content of amino acids in Ch. violaceum collected in B producing area was largest(12.5 mg·g~(-1)). It is concluded the Ch. violaceum contains multi-kinds of amino acids. On the basis of amino acid amount, Langzhong city and Cangxi county in Sichuan province(producing area B) is the suitable areas for cultivating Ch. violaceum.

Prognostic significance of long noncoding RNA Z38 as a candidate biomarker in breast cancer.

BACKGROUND: Long noncoding RNA (lncRNA) Z38 has been shown to promote cell proliferation and tumorigenesis in breast cancer. However, expression pattern and prognostic value of lncRNA Z38 in breast cancer patients remain elusive. METHODS: The expression levels of SPRY4-IT1 in 110 self-paired specimens of breast cancer and adjacent normal breast tissues were measured by quantitative real-time PCR (qRT-PCR), and its correlation with overall survival of patients with breast cancer was further statistically analyzed. RESULTS: Compared with normal breast tissues, Z38 was upregulated in breast cancer tissues. Furthermore, of 110 breast cancer patients, high Z38 expression was significantly associated with tumor-node-metastasis stage and lymph node metastasis. Further analysis using the Cox regression model revealed that Z38 expression was an independent prognostic factor of overall survival in patients with breast cancer (hazard ratio=4.74, 95% confidence interval 2.41-9.32). The nomogram presents a good prediction of the probability of overall survival of breast cancer patients (c-index: 0.792), and its predictive efficiency was further confirmed by the calibration curve. CONCLUSION: Our data highlighted the potential of lncRNA Z38 as novel candidate biomarker to identify patients with breast cancer at high risk of tumor death.

Immediate placement of dental implants into infected versus noninfected sites in the esthetic zone: A systematic review and meta-analysis.

STATEMENT OF PROBLEM: Immediate implantation has been established to shorten waiting time before definitive restoration, offering the ability to deliver a predictable esthetic and functional outcome for patients. However, this approach remains controversial for a tooth with a periodontal or periapical lesion. PURPOSE: The purpose of this systematic review was to analyze the treatment outcomes of immediate implant placement into extraction sockets with or without infection of periodontal or periapical origin in the esthetic zone and to provide treatment protocols based on current studies. MATERIAL AND METHODS: An electronic search was performed in PubMed, ISI Web of Knowledge, and the Cochrane Library between January 2009 and October 2017. A subsequent manual search included all clinical studies published in the English language and excluded any reviews or animal studies. An article quality assessment scale, Newcastle-Ottawa Scale (NOS), was used to evaluate the quality of studies enrolled. The implant survival rate was expressed as risk ratio, whereas bone level changes and gingiva level changes were expressed as mean differences in millimeters with 95% confidence intervals. The meta-analysis was conducted by using commercial software. RESULTS: The search initially found 1171 references. The manual search of the reference lists of identified articles yielded additional papers. Altogether, 9 studies were identified within the selection criteria, with NOS scores between 5 and 8. Compared with the healthy sites, immediate implant placement in infected sites in the esthetic zone showed similar survival rates (97.6% vs. 98.4%, respectively; risk ratio [RR], 0.99; 95% confidence interval [CI], 0.97 to 1.00; P=.138). No statistically significant differences were found in bone level changes (mean difference [MD], 0.03; 95%CI, -0.09 to 0.14; P=.667) or in gingiva level changes (MD, -0.06; 95% CI, -0.13 to 0.01; P=.070) between the 2 groups. CONCLUSIONS: Meta-analysis showed that immediate implant placement into infected sites and noninfected sites in esthetic zone had similar survival rates, bone level changes, and gingiva level changes.

Morroniside on anti-inflammation activities in rats following acute myocardial infarction.

Our previous studies have confirmed that morroniside has neuroprotective effects. However, the effects of morroniside on cardiac myocardium remain unknown. Rats were anaesthetized with 10% chloral hydrate (0.35~0.4 mL/kg) and an acute myocardial infarction (AMI) was induced by ligating the anterior descending coronary artery (LAD). Following AMI, morroniside was administered intragastrically for 3 consecutive days at doses of 45, 90 and 180 mg/kg, respectively. Lactate dehydrogenase (LDH) and cardiac troponin T (cTnT) activities in AMI rats in the serum were detected with commercial kits. The expression of IL-6, IL-1ß and TNF-α in myocardium was detected by Western blotting analysis. We observed a significant decline in the Q(q) wave amplitude in morroniside-treated rats after 72 h. Additionally, treatment of morroniside decreased the levels of LDH and cTnT in AMI rats. We also observed that morroniside reduced the expression of IL-6, IL-1ß and TNF-α in myocardium. Taken together, our findings demonstrate that morroniside had effective anti-inflammatory properties in AMI rats.

The modified Yi qi decoction protects cardiac ischemia-reperfusion induced injury in rats.

BACKGROUND: To investigate the effects and involved mechanisms of the modified Yi Qi decoction (MYQ) in cardiac ischemia-reperfusion (IR) induced injury. METHODS: Male Sprague-Dawley rats were subjected to a 30-min coronary arterial occlusion followed by reperfusion, low or high dose decoction of MYQ was administrated orally for 1 week or 1 month. RESULTS: Both in 1 week and 1 month IR rat groups, cardiac function indexes were significantly impaired compared with sham group rats, accompanied with higher ratio of infarct size to risk size, decreased expressions of sodium calcium exchanger (NCX1) and sarcoplasmic reticulum Ca2+-ATPase (Serca2a), and different expressions of autophagic proteins, Beclin-1 and LC3. Treatment with MYQ (low or high dose) for 1 week showed no marked beneficial effects on cardiac function and cardiac injury (ratio of infarct size to risk size), although expressions of anti-apoptotic protein, Bcl-2, NCX1 and Serca2a were increased. Treatment with MYQ (low or high dose) for 1 month showed significantly improved effects on cardiac function and cardiac injury (ratio of infarct size to risk size), accompanied with increase of Bcl-2, NCX1 and Serca2a expressions, and decrease of Bax (a pro-apoptotic protein) and Beclin-1 expressions. CONCLUSIONS: The results show that MYQ have potential therapeutic effects on IR-induced cardiac injury, which may be through regulation of apoptotic proteins, cytosolic Ca2+ handling proteins and autophagic proteins signal pathways.

Disruption of cardiogenesis in human embryonic stem cells exposed to trichloroethylene.

Trichloroethylene (TCE) is ubiquitous in our living environment, and prenatal exposure to TCE is reported to cause congenital heart disease in humans. Although multiple studies have been performed using animal models, they have limited value in predicting effects on humans due to the unknown species-specific toxicological effects. To test whether exposure to low doses of TCE induces developmental toxicity in humans, we investigated the effect of TCE on human embryonic stem cells (hESCs) and cardiomyocytes (derived from the hESCs). In the current study, hESCs cardiac differentiation was achieved by using differentiation medium consisting of StemPro-34. We examined the effects of TCE on cell viability by cell growth assay and cardiac inhibition by analysis of spontaneously beating cluster. The expression levels of genes associated with cardiac differentiation and Ca2+ channel pathways were measured by immunofluorescence and qPCR. The overall data indicated the following: (1) significant cardiac inhibition, which was characterized by decreased beating clusters and beating rates, following treatment with low doses of TCE; (2) significant up-regulation of the Nkx2.5/Hand1 gene in cardiac progenitors and down regulation of the Mhc-7/cTnT gene in cardiac cells; and (3) significant interference with Ca2+ channel pathways in cardiomyocytes, which contributes to the adverse effect of TCE on cardiac differentiation during early embryo development. Our results confirmed the involvement of Ca2+ turnover network in TCE cardiotoxicity as reported in animal models, while the inhibition effect of TCE on the transition of cardiac progenitors to cardiomyocytes is unique to hESCs, indicating a species-specific effect of TCE on heart development. This study provides new insight into TCE biology in humans, which may help explain the development of congenital heart defects after TCE exposure. © 2015 Wiley Periodicals, Inc. Environ Toxicol 31: 1372-1380, 2016.

[Role of renal sympathetic nerve and oxidative stress in foot shock-induced hypertension in rats].

The present study was aimed to investigate the roles of renal sympathetic nerve and oxidative stress in the development of foot shock-induced hypertension. Ninety rats were divided into 6 groups (the number of each group was 15): control group, foot shock group, denervation of renal sympathetic nerve group, denervation of renal sympathetic nerve + foot shock group, Tempol treatment + foot shock group, denervation of renal sympathetic nerve + Tempol treatment + foot shock group. Rats were received electrical foot shock for 14 days (2-4 mA, 75 V, shocks of 50-100 ms every 30 s, for 4 h each session through an electrified grid floor every day). Renal sympathetic ablation was used to remove bilateral renal sympathetic nerve in rats (rats were allowed to recover for one week before the beginning of the foot shock procedure). The antioxidant Tempol was injected intraperitoneally at 1 h before foot shock. Systolic blood pressure was measured at 1 h after foot shock on day 0, 3, 7, 10 and 14. Contents of thiobarbituric acid reactive substance (TBARS), renin, angiotensin II (AngII) and glutathione peroxidase (GSH-Px) in plasma were measured by ELISA after 14-day foot shock. The results showed that systolic blood pressure of foot shock group was significantly increased (P < 0.05) compared with that of control group from day 7 to day 14 of foot shock. Denervation of renal sympathetic nerve and/or Tempol treatment significantly reduced the increase of systolic blood pressure induced by foot shock. Levels of TBARS, renin and AngII in plasma were increased significantly in foot shock group compared with that of control group (P < 0.05). Plasma GSH-Px concentration was decreased in foot shock group rats compared with that of control group (P < 0.05). Denervation of renal sympathetic nerve and/or tempol treatment significantly reduced the increase in TBARS, renin, AngII levels induced by foot shock in comparison with that of foot shock group (P < 0.05), but had no effects on the reduction of GSH-Px concentration. The results suggest that renal sympathetic nerve may play an important role in the development of foot shock-induced hypertension, and renal sympathetic nerve may influence oxidative stress and directly or indirectly activate renin-angiotensin-aldosterone system, so the foot shock-induced high blood pressure may be maintained and hypertension may therefore be produced.

Mitochondrial KATP channel involvement in angiotensin II-induced autophagy in vascular smooth muscle cells.

Autophagy has emerged as a powerful process in the response to cellular injury. The present study was designed to investigate signal transduction pathways in angiotensin II (Ang II)-induced autophagy. Rat vascular smooth muscle cells (VSMCs) were stimulated with different doses of Ang II (10(-9)-10(-5) mol/L) for different time periods (6-72 h). Incubation with Ang II increased the production of reactive oxygen species (ROS), increased the LC3-II to LC3-I ratio, increased beclin-1 expression, and decreased SQSTM1/p62 expression in a dose- and time-dependent manner. In addition, Ang II increased autophagosome formation. Increased ROS production induced by Ang II was inhibited by Ang II type 1 receptor (AT1) blockers (Olmesartan and Candesartan, ARB), a NADPH Oxidase inhibitor (apocynin), and mitochondrial KATP channels inhibitor (5-hydroxydecanoate, 5HD). Ang II (10(-7) mol/L, 48 h)-induced increase in the LC3-II to LC3-I ratio, the formation of autophagosomes, expression of beclin-1 and decrease in the expression of SQSTM1/p62 were also inhibited by pretreatment with 3-methyladenine or bafilomycin A1 (inhibitors of autophagy), olmesartan and candesartan (in dose-dependent manners), apocynin, 5HD, and siRNA Atg5. Our results indicate that Ang II increases autophagy levels via activation of AT1 receptor and NADPH oxidase. Mitochondrial KATP channels also play an important role in Ang II-induced autophagy. Our results may provide a new strategy for treatment of cardiovascular diseases with Ang II.

[Role of hippocampal neuronal intracellular calcium overload in modulating cognitive dysfunction and the neuronprotective effect of mematine in a mouse model of chronic intermittent hypoxia].

OBJECTIVE: To investigate the role of hippocampal intracellular calcium overload in modulating cognitive dysfunction and the neuronprotective effect of mematine in a mouse model of chronic intermittent hypoxia. METHODS: 45 ICR male mice were randomly divided into 3 groups: the unhandled control group (UC group, n = 15), the chronic intermittent hypoxia (CIH group, n = 15) and the pretreatment memantine group (MEM group, n = 15). CIH and MEM mice were subjected to intermittent hypoxia while UC mice to room air for 8 h per day during 4 weeks. Mice in the MEM group were pretreated with memantine (5 mg/kg) by intraperitoneal injection before the cycle started, and those in the UC group and the CIH group were treated with same volume of physiological saline. Neurobehavioral assessments were performed by Open filed and Morris water maze, [Ca²âº]i in hippocampal neurons was evaluate by flow cytometry, and the expression of cleaved caspase-3, phospho-ERK1/2 in hippocampus were detected by Western blotting. RESULTS: Compared with the UC group, CIH mice displayed markedly more locomotor activity (P < 0.05) in Open filed test, longer mean escape latency (P < 0.05), less number of times of crossing the platform (P < 0.01) and less percentage of time in target quadrant (P < 0.01). Furthermore, exposure to CIH enhanced [Ca²âº]i (vs. UC mice, 155 ± 12 vs. 92 ± 8, P < 0.01), and up-regulated the expression of cleaved caspase-3 (P < 0.01), but down-regulated the level of phospho-ERK1/2 (P < 0.05) in the hippocampus. Pre-treatment with memantine significantly decreased hyperlocomotion (P < 0.05), attenuated memory deficit (P < 0.05), mitigated [Ca²âº]i (vs. CIH mice, 90 ± 8 vs. 155 ± 12, P < 0.01), decrease the expression of cleaved caspase-3 (P < 0.01), but increased the level of phospho-ERK1/2(P < 0.05) comparing to the CIH group. CONCLUSION: The neurobehavioral impairments induced by CIH are mediated, at least in part, by intracellular calcium concentration overload, neuron apoptosis, dephosphorylation of ERK1/2, which can be attenuated by memantine. Memantine may have a therapeutic effect in the neurocognitive impairment associated with OSAHS.

Wekemo Bioincloud: A user-friendly platform for meta-omics data analyses.

The increasing application of meta-omics approaches to investigate the structure, function, and intercellular interactions of microbial communities has led to a surge in available data. However, this abundance of human and environmental microbiome data has exposed new scalability challenges for existing bioinformatics tools. In response, we introduce Wekemo Bioincloud-a specialized platform for -omics studies. This platform offers a comprehensive analysis solution, specifically designed to alleviate the challenges of tool selection for users in the face of expanding data sets. As of now, Wekemo Bioincloud has been regularly equipped with 22 workflows and 65 visualization tools, establishing itself as a user-friendly and widely embraced platform for studying diverse data sets. Additionally, the platform enables the online modification of vector outputs, and the registration-independent personalized dashboard system ensures privacy and traceability. Wekemo Bioincloud is freely available at https://www.bioincloud.tech/.

Quantifying US air pollution policy: How political and regional factors influence pollutant mitigation.

Air pollution control in the United States has evolved into a comprehensive policy system spanning from the federal to the state level over time. A unified quantitative analysis of policy intensity can shed light on the policy evolution across different levels, the influence of partisan and regional factors on policy, and the relationships with emissions of major pollutants. By harnessing the policy text of the Clean Air Act (CAA) at the federal level and State Implementation Plans (SIPs) at the state governments (1955-2020), we deployed a Natural Language Processing approach to define a policy intensity index to systematically quantify the US air policy landscape. Our findings highlight that the 1970 CAA amendment carries the most vigorous intensity as it established a holistic control system for the first time. Subsequent years witnessed a general trend of partisan polarization, eventually leading to a graduate convergence between red and blue states. Blue states demonstrated a closer alignment with federal directives and a superior efficacy in pollutant reduction. Regionally, the Northeast displays the highest overall policy intensity, and the West exhibits the highest coordination with the federal benchmarks, making these regions outperform others in air pollution control. Our study not only discusses policy implications for air pollutant reductions considering partisan and regional differences but also provides a novel measurement tool to quantify policies for assessing disparities and synergies.