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.

Dexmedetomidine attenuates ferroptosis by Keap1-Nrf2/HO-1 pathway in LPS-induced acute kidney injury.

Previous research has demonstrated that Dexmedetomidine (DEX), an α2 adrenergic agonist commonly used for its sedative and analgesic properties, can attenuate lipopolysaccharide (LPS)-induced acute kidney injury (AKI). This study explores the possibility that DEX's protective effects in LPS-induced AKI are mediated through the inhibition of ferroptosis, a form of regulated cell death characterized by iron-dependent lipid peroxidation, and the activation of the antioxidant response through the Keap1/Nrf2/HO-1 signaling pathway. We induced AKI in 42 mice using LPS and divided them into six groups: saline control, LPS, LPS + DEX, LPS + Ferrostatin-1 (LPS + Fer-1; a ferroptosis inhibitor), LPS + DEX with α2-receptor antagonist Altipamizole (LPS + DEX + ATI), and LPS + DEX with Nrf2 inhibitor ML385 (LPS + DEX + ML385). After 24 h, we analyzed blood and kidney tissues. LPS exposure resulted in AKI, with increased serum creatinine, BUN, and cystatin C, and tubular damage, which DEX and Fer-1 ameliorated. However, Altipamizole and ML385 negated these improvements. The LPS group exhibited elevated oxidative stress markers and mitochondrial damage, reduced by DEX and Fer-1, but not when α2-adrenergic or Nrf2 pathways were blocked. Nrf2 and HO-1 expression declined in the LPS group, rebounded with LPS + DEX and LPS + Fer-1, and fell again with inhibitors; inversely, Keap1 expression varied. Our results demonstrate that DEX may protect against LPS-induced AKI, at least partially by regulating ferroptosis and the α2-adrenergic receptor/Keap1/Nrf2/HO-1 pathway, suggesting a potential therapeutic role for DEX in AKI management by modulating cell death and antioxidant defenses.

6PPDQ induces cardiomyocyte senescence via AhR/ROS-mediated autophagic flux blockage.

Recently, attention has been drawn to the adverse outcomes of N-(1,3-Dimethylbutyl)-N'-phenyl-p-phenylenediamine quinone (6PPDQ) on human health, but its cardiac toxicity has been relatively understudied. This work aims to investigate the effects of 6PPDQ on differentiated H9c2 cardiomyocytes. Our findings demonstrated that exposure to 6PPDQ altered cellular morphology and disrupted the expression of cardiac-specific markers. Significantly, 6PPDQ exposure led to cardiomyocyte senescence, characterized by elevated ß-Galactosidase activity, upregulation of cell cycle inhibitor, induction of DNA double-strand breaks, and remodeling of Lamin B1. Furthermore, 6PPDQ hindered autophagy flux by promoting the formation of autophagosomes while inhibiting the degradation of autolysosomes. Remarkably, restoration of autophagic flux using rapamycin counteracted 6PPDQ-induced cardiomyocyte senescence. Additionally, our study revealed that 6PPDQ significantly increased the ROS production. However, ROS scavenger effectively reduced the blockage of autophagic flux and cardiomyocyte senescence caused by 6PPDQ. Furthermore, we discovered that 6PPDQ activated the Aryl hydrocarbon receptor (AhR) signaling pathway. AhR antagonist was found to reverse the blockage of autophagy and alleviate cardiac senescence, while also reducing ROS levels in 6PPDQ-treated group. In conclusion, our research unveils that exposure to 6PPDQ induces ROS overproduction through AhR activation, leading to disruption of autophagy flux and ultimately contributing to cardiomyocyte senescence.

Characteristics and outcomes of cancer patients admitted to intensive care units in cancer specialized hospitals in China.

PURPOSE: Standard intensive care unit (ICU) admission policies and treatment strategies for patients with cancer are still lacking. To depict the current status of admission, characteristics, and outcomes of patients with cancer in the ICU. METHODS: A multicenter cross-sectional study was performed from May 10, 2021 to July 10, 2021, in the ICU departments of 37 cancer-specialized hospitals in China. Clinical records of all admitted patients aged ≥ 14 years and ICU duration > 24 h with complete data were included. Demographic information, clinical history, severity score at admission, ICU critical condition diagnosis and treatment, ICU and in-hospital outcomes and 90 days survival were also collected. A total of 1455 patients were admitted and stayed for longer than 24 h. The most common primary cancer diagnoses included lung, colorectal, esophageal, and gastric cancer. RESULTS: Patients with lung cancer were admitted more often because of worsening complications that occurred in the clinical ward. However, other cancer patients may be more likely to be admitted to the ICU because of postoperative care. ICU-admitted patients with lung or esophageal cancer tended to have more ICU complications. Patients with lung cancer had a poor overall survival prognosis, whereas patients with colorectal cancer appeared to benefit the most according to 90 days mortality rates. CONCLUSION: Patients with lung cancer require more ICU care due to critical complications and the overall survival prognosis is poor. Colorectal cancer may benefit more from ICU management. This information may be considered in ICU admission and treatment strategies.

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 social network perspective on power system co-evolution: responses to "double carbon target" realization in China.

The introduction of dual carbon targets will significantly impact power system development. Despite this, there is currently limited research on achieving system evolution and transition while ensuring safety, low-carbon output, and efficiency, as well as quantitatively analyzing the resulting changes dual carbon targets will have on the power system. Co-evolution of the power system offers a solution to balance the impact of dual carbon goals and enhance interaction among system entities, thereby facilitating the achievement of these goals. Our study focuses on constructing an evolutionary topological network by analyzing the dynamic evolution rule of power systems. We investigate the co-evolution pattern of power systems by analyzing the relationship between the role of power system agents and their dynamic structures. Furthermore, we analyze the future structural changes of power systems, which can provide theoretical support for achieving dual carbon goals in the power system. Our findings highlight key measures to promote synergistic evolution, including increasing energy storage capabilities, stabilizing renewable energy supply, breaking inter-provincial barriers in electricity transmission, and developing a multi-level intelligent power system. Through link analysis, we discover that future power systems will maintain a mild coordination among agents rather than implementing large-scale realignment and reconfiguration. We posit that overcoming obstacles can be achieved by fostering cohesion between the network and agents through technological innovation and widespread market diffusion to drive co-evolution.

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.

Impermeability and Durability of Self-Compacting Concrete Prepared with Aeolian Sand and Recycled Coarse Aggregate.

Self-compacting concrete has seen extensive application in both engineering and construction. In order to save building resources, aeolian sand-recycled coarse aggregate self-compacting concrete (ARSCC) is created by partially substituting recycled coarse aggregates (RCA) and aeolian sand (AS) for natural coarse aggregates. For ten groups with different mechanical and durable properties, this study examined the effects of sulfate erosion, chloride penetration resistance, and related impermeability, as well as AS replacement ratios of 20%, 40%, and 60% and RCA replacement ratios of 25%, 50%, and 75% in ARSCC and a control group (A0-R0). According to the study's findings, after sulfate attack, the highest relative dynamic elastic modulus and corrosion resistance factor were obtained with the 20% AS replacement ratio and 50% RCA replacement ratio (A20-R50). The highest impermeability grade and lowest electric flux were obtained with the 20% AS replacement ratio and 25% RCA replacement ratio (A20-R25). X-ray diffraction (XRD) and mercury intrusion porosimetry (MIP) revealed that the addition of aeolian sand and recycled coarse aggregates improved the pore structure of the SCC and increased the densification of the self-compacting concrete, particularly following sulfate attack. This study highlights the importance of recycled aggregates and aeolian sand in engineering applications and the sustainable growth of the concrete industry, both of which support resource conservation and environmental protection.

Prognostic and risk factor analysis of cancer patients after unplanned ICU admission: a real-world multicenter study.

To investigate the occurrence and 90-day mortality of cancer patients following unplanned admission to the intensive care unit (ICU), as well as to develop a risk prediction model for their 90-day prognosis. We prospectively analyzed data from cancer patients who were admitted to the ICU without prior planning within the past 7 days, specifically between May 12, 2021, and July 12, 2021. The patients were grouped based on their 90-day survival status, and the aim was to identify the risk factors influencing their survival status. A total of 1488 cases were included in the study, with an average age of 63.2 ± 12.4 years. The most common reason for ICU admission was sepsis (n = 940, 63.2%). During their ICU stay, 29.7% of patients required vasoactive drug support (n = 442), 39.8% needed invasive mechanical ventilation support (n = 592), and 82 patients (5.5%) received renal replacement therapy. We conducted a multivariate COX proportional hazards model analysis, which revealed that BMI and a history of hypertension were protective factors. On the other hand, antitumor treatment within the 3 months prior to admission, transfer from the emergency department, general ward, or external hospital, high APACHE score, diagnosis of shock and respiratory failure, receiving invasive ventilation, and experiencing acute kidney injury (AKI) were identified as risk factors for poor prognosis within 90 days after ICU admission. The average length of stay in the ICU was 4 days, while the hospital stay duration was 18 days. A total of 415 patients died within 90 days after ICU admission, resulting in a mortality rate of 27.9%. We selected 8 indicators to construct the predictive model, which demonstrated good discrimination and calibration. The prognosis of cancer patients who are unplanned transferred to the ICU is generally poor. Assessing the risk factors and developing a risk prediction model for these patients can play a significant role in evaluating their prognosis.

Exosomes derived from mesenchymal stromal cells exert a therapeutic effect on hypoxia-induced pulmonary hypertension by modulating the YAP1/SPP1 signaling pathway.

OBJECTIVE: Hypoxic pulmonary hypertension (HPH) is a progressive and life-threatening disease characterized by perivascular inflammation, pulmonary vascular remodeling, and occlusion. Mesenchymal stromal cell-derived exosomes (MSC-exo) have emerged as potential therapeutic agents due to their role in cell communication and the transportation of bioactive molecules. In this study, we aimed to investigate the therapeutic effects of MSC-exo against HPH and elucidate the underlying molecular mechanism. METHODS: Exosomes were isolated from conditioned media of human bone mesenchymal stromal cells using ultracentrifugation and characterized through western blotting, transmission electron microscopy (TEM), and nanoparticle tracking analysis (NTA). An HPH animal model was established in male SD rats, and MSC-exo or phosphate-buffered saline (PBS) were administered via the tail vein for three weeks. Subsequently, right ventricular systolic pressure (RVSP), right ventricular hypertrophy index (RVHI), and pulmonary vascular remodeling were evaluated. Lung tissues from HPH rats and normal rats underwent high-throughput sequencing and transcriptomic analysis. Gene Ontology (GO) analysis was employed to identify upregulated differentially expressed genes. Additionally, rat pulmonary artery smooth muscle cells (PASMC) exposed to platelet-derived growth factor-BB (PDGF-BB) were used to simulate HPH-related pathological behavior. In vitro cellular models were established to examine the molecular mechanism of MSC-exo in HPH. RESULTS: MSC-exo administration protected rats from hypoxia-induced increases in RVSP, RVHI, and pulmonary vascular remodeling. Additionally, MSC-exo alleviated PDGF-BB-induced proliferation and migration of PASMC. Transcriptomic analysis revealed 267 upregulated genes in lung tissues of HPH rats compared to control rats. Gene Ontology analysis indicated significant differences in pathways associated with Yes Associated Protein 1 (YAP1), a key regulator of cell proliferation and organ size. RT-qPCR and western blot analysis confirmed significantly increased expression of YAP1 in HPH lung tissues and PASMC, which was inhibited by MSC-exo treatment. Furthermore, analysis of datasets demonstrated that Secreted Phosphoprotein 1 (SPP1), also known as Osteopontin (OPN), is a downstream binding protein of YAP1 and can be upregulated by PDGF-BB. MSC-exo treatment reduced the expression of both YAP1 and SPP1. Lentivirus-mediated knockdown of YAP1 inhibited PDGF-BB-induced PASMC proliferation, migration, and SPP1 protein levels. CONCLUSION: Our findings demonstrate that MSC-exo exert a therapeutic effect against hypoxia-induced pulmonary hypertension by modulating the YAP1/SPP1 signaling pathway. The inhibition of YAP1 and downstream SPP1 expression by MSC-exo may contribute to the attenuation of pulmonary vascular remodeling and PASMC proliferation and migration. These results suggest that MSC-exo could serve as a potential therapeutic strategy for the treatment of HPH. Further investigations are warranted to explore the clinical applicability of MSC-exo-based therapies in HPH patients.

Alterations of the intestinal microbiome and metabolome in women with rheumatoid arthritis.

Rheumatoid arthritis (RA) is more common in women, and many reports of sex differences have been reported in various aspects of RA. However, there has been a lack of specific research on women's gut flora. To assess the association between the gut flora and RA patients, this study combined the microbiome with metabolomics. Fecal samples from RA patients and healthy controls were collected for 16S rRNA sequencing. Nontargeted liquid chromatography-mass spectrometry was used to detect metabolites in fecal samples. We comprehensively used various analytical methods to reveal changes in intestinal flora and metabolites in female patients. The gut flora of RA patients was significantly different from that of healthy women. The abundance of Bacteroides, Megamonas and Oscillospira was higher in RA patients, while the abundance of Prevotella, Gemmiger and Roseburia was lower than that of healthy women. Gemmiger, Bilophila and Odoribacter represented large differences in microflora between RA and healthy women and could be used as potential microorganisms in the diagnosis. Fatty acid biosynthesis was significantly different between RA patients and healthy women in terms of metabolic pathways. There were different degrees of correlation between the gut flora and metabolites. Lys-Phe-Lys and heptadecasphin-4-enine can be used as potential markers for RA diagnosis. There was an extremely significant positive correlation between Megamonas, Dialister and rheumatoid factors, which was found for the first time. These findings indicated that alterations of these gut microbiome and metabolome may contribute to the diagnosis and treatment of RA patients.

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.

Highly efficient CsPbBr3@glass@polyurethane composite film as flexible liquid crystal display backlight.

Inorganic lead halide perovskite quantum dots (CsPbX3 QDs (X = Cl, Br, or I)) have attracted more and more attention due to their high absorption coefficient, narrow emission band, high quantum efficiency, and tunable emission wavelength. However, CsPbX3 QDs are decomposed when exposed to bright light, heat, moisture, etc., which leads to severe luminous attenuation and limits their commercial application. In this paper, CsPbBr3@glass materials were successfully synthesized by a one-step self-crystallization method, including melting, quenching and heat treatment processes. The stability of CsPbBr3 QDs was improved by embedding CsPbBr3 QDs into zinc-borosilicate glass. Then, the CsPbBr3@glass was combined with polyurethane (PU) to form a flexible composite luminescent film CsPbBr3@glass@PU. This strategy enables the transformation of rigid perovskite quantum dot glass into flexible luminescent film materials and further improves the photoluminescence quantum yield (PLQY) from 50.5% to 70.2%. The flexible film has good tensile properties, and its length can be strained 5 times as long as the original length. Finally, a white LED was encapsulated by combining CsPbBr3@glass@PU film and red phosphor K2SiF6:Mn4+ with a blue LED chip. The good performance of the obtained CsPbBr3@glass@PU film indicates that it has potential application in flexible liquid crystal displays (LCDs) as a backlight source.

China's ambitious low-carbon goals require fostering city-level renewable energy transitions.

Cities in China, as elsewhere, are increasingly playing a crucial role in mitigating climate change. We developed a panel dataset on renewable energy transition in Chinese cities, and assessed the CO2 emissions reduction of city-level renewable energy transition. We found that city-level renewable energy transition only reduced 446 million tonnes of CO2 emissions from 2005 to 2019. Moreover, the 2030 carbon peak target will be missed in the business-as-usual scenario. The CO2 emissions reduction of city-level renewable energy transition will significantly increase in the policy constraint scenario and in the technology breakthrough scenario, and the 2030 carbon peak target will likely be reached in both these scenarios, with a range of possible CO2 emissions in 2030 equal to 8.34-10.43 and 8.00-10.07 billion tonnes, respectively. In this study, we were the first to assess the historical contribution and prospective trajectory of CO2 emissions reduction of China's city-level renewable energy transition.

Interaction Between the Glymphatic System and α-Synuclein in Parkinson's Disease.

The glymphatic system contributes to the clearance of amyloid-ß from the brain and is disrupted in Alzheimer's disease. However, whether the system is involved in the removal of α-synuclein (α-syn) and whether it is suppressed in Parkinson's disease (PD) remain largely unknown. In mice receiving the intranigral injection of recombinant human α-syn, we found that the glymphatic suppression via aquaporin-4 (AQP4) gene deletion or acetazolamide treatment reduced the clearance of injected α-syn from the brain. In mice overexpressing the human A53T-α-syn, we revealed that AQP4 deficiency accelerated the accumulation of α-syn, facilitated the loss of dopaminergic neurons, and accelerated PD-like symptoms. We also found that the overexpression of A53T-α-syn reduced the expression/polarization of AQP4 and suppressed the glymphatic activity of mice. The study demonstrates a close interaction between the AQP4-mediated glymphatic system and parenchymal α-syn, indicating that restoring the glymphatic activity is a potential therapeutic target to delay PD progression.

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 spatial impact of atmospheric environmental policy on public health based on the mediation effect of air pollution in China.

The topic of air pollution and its effect on public health has become a hot policy issue that has attracted worldwide attention, but this attention has seldom been extended to the causal relationship between atmospheric environmental policy (AEP), air pollution, and public health. This paper uses panel data from 30 provinces in China to construct spatial econometric models that analyze the impact of AEP on air pollution, the impact of air pollution on public health, and the mediation effect that air pollution may have between AEP and public health. The results demonstrate that there is a significant positive spatial spillover effect of soot and dust (SD) emission intensity and the overall air pollution level as measured by the Air Pollution Index (API). The AEP has significant inhibitory effects on the intensity of sulfur dioxide and SD emissions, as well as on overall air pollution. An increase in the overall air pollution level has a significant detrimental effect on public health as measured by average life expectancy. Air pollution as measured by API is a mediating factor in the relationship between AEP and public health. The study results could help to effectively control air pollution and promote public health by leading to improvements in regional pollution prevention and control mechanisms and strengthening of the central government's policy formulation and local governments' policy implementation process.

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.

Dexmedetomidine Alleviates Ischemia/Reperfusion-Associated Acute Kidney Injury by Enhancing Autophagic Activity via the α2-AR/AMPK/mTOR Pathway.

BACKGROUND: Dexmedetomidine (DEX) reportedly protects against ischemia-reperfusion (I/R) injury and associated damage to the kidneys, but the underlying mechanisms have yet to be established. METHODS: Unilateral nephrectomy was performed in Wistar rats, and the remaining kidney was clamped for 1 h prior to reperfusion to establish an experimental model system. These animals were then randomized into Sham, DEX + Sham, DEX + I/R, ATI (Altepamizole, α2-adrenergic receptor inhibitor) + DEX + I/R, and 3-MA (3-methyladenine, autophagy inhibitor) + DEX + I/R groups. Serum renal function biomarkers, acute kidney injury (AKI) histopathological scores, serum inflammatory factors, redox biomarkers, markers of autophagic flux, and autophagosome numbers were assessed. Levels of proteins related to the autophagic pathway, including mTOR and AMPK, were also analyzed. RESULTS: Serum creatinine and urea nitrogen levels in the I/R group were significantly elevated over those in sham control rats, as were AKI scores, serum inflammatory cytokine concentrations (IL-6, IL-1ß, and TNF-α), and serum levels of the oxidative stress biomarker malondialdehyde (MDA). All of these parameters were significantly reduced in the DEX + I/R group relative to I/R model rats. I/R group rats also exhibited significant decreases in renal levels of autophagic flux-related biomarkers and autophagosome numbers relative to sham controls, while DEX administration partially restored normal autophagic flux in these rats. Acute I/R also suppress the expression of AMPK in the kidney while increasing mTOR expression, and DEX reversed these effects. The beneficial impact of DEX on I/R-associated AKI was ablated by ATI or 3-MA administration. CONCLUSIONS: These analyses provide strong evidence for the ability of DEX to protect against I/R-associated AKI via the α2-AR/AMPK/mTOR pathway-mediated enhancement of autophagic activity.