Analysis of the multiple drivers of vegetation cover evolution in the Taihangshan-Yanshan region.

The Taihangshan-Yanshan region (TYR) is an important ecological barrier area for Beijing-Tianjin-Hebei, and the effectiveness of its ecological restoration and protection is of great significance to the ecological security pattern of North China. Based on the FVC data from 2000 to 2021, residual analysis, parametric optimal geodetector technique (OPGD) and multi-scale geographically weighted regression analysis (MGWR) were used to clarify the the multivariate driving mechanism of the evolution of FVC in the TYR. Results show that: (1) FVC changes in the TYR show a slowly fluctuating upward trend, with an average growth rate of 0.02/10a, and a spatial pattern of "high in the northwest and low in the southeast"; more than half of the FVC increased during the 22-year period. (2) The results of residual analysis showed that the effects of temperature and precipitation on FVC were very limited, and a considerable proportion (80.80% and 76.78%) of the improved and degraded areas were influenced by other factors. (3) The results of OPGD showed that the main influencing factors of the spatial differentiation of FVC included evapotranspiration, surface temperature, land use type, nighttime light intensity, soil type, and vegetation type (q > 0.2); The explanatory rates of the two-factor interactions were greater than those of the single factor, which showed either nonlinear enhancement or bifactorial enhancement, among which, the interaction of evapotranspiration with mean air and surface temperature has the strongest effect on the spatial and temporal evolution of FVC (q = 0.75). Surface temperature between 4.98 and 10.4 °C, evapotranspiration between 638 and 762 mm/a, and nighttime light between 1.96 and 7.78 lm/m2 favoured an increase in vegetation cover, and vegetation developed on lysimetric soils was more inclined to be of high cover. (4) The correlation between each variable and FVC showed different performance, GDP, elevation, slope and FVC showed significant positive correlation in most regions, while population size, urban population proportion, GDP proportion of primary and secondary industries, and nighttime light intensity all showed negative correlation with FVC to different degrees. The results can provide data for formulating regional environmental protection and restoration policies.

Pin1 Downregulation Is Involved in Excess Retinoic Acid-Induced Failure of Neural Tube Closure.

Neural tube defects (NTDs), which are caused by impaired embryonic neural tube closure, are one of the most serious and common birth defects. Peptidyl-prolyl cis/trans isomerase 1 (Pin1) is a prolyl isomerase that uniquely regulates cell signaling by manipulating protein conformation following phosphorylation, although its involvement in neuronal development remains unknown. In this study, we explored the involvement of Pin1 in NTDs and its potential mechanisms both in vitro and in vivo. The levels of Pin1 expression were reduced in NTD models induced by all-trans retinoic acid (Atra). Pin1 plays a significant role in regulating the apoptosis, proliferation, differentiation, and migration of neurons. Moreover, Pin1 knockdown significantly was found to exacerbate oxidative stress (OS) and endoplasmic reticulum stress (ERs) in neuronal cells. Further studies showed that the Notch1-Nrf2 signaling pathway may participate in Pin1 regulation of NTDs, as evidenced by the inhibition and overexpression of the Notch1-Nrf2 pathway. In addition, immunofluorescence (IF), co-immunoprecipitation (Co-IP), and GST pull-down experiments also showed that Pin1 interacts directly with Notch1 and Nrf2. Thus, our study suggested that the knocking down of Pin1 promotes NTD progression by inhibiting the activation of the Notch1-Nrf2 signaling pathway, and it is possible that this effect is achieved by disrupting the interaction of Pin1 with Notch1 and Nrf2, affecting their proteostasis. Our research identified that the regulation of Pin1 by retinoic acid (RA) and its involvement in the development of NTDs through the Notch1-Nrf2 axis could enhance our comprehension of the mechanism behind RA-induced brain abnormalities.

Pin1 Exacerbates Non-Alcoholic Fatty Liver Disease by Enhancing Its Activity through Binding to ACC1.

Non-alcoholic fatty liver disease (NAFLD) is a clinicopathological syndrome characterized by diffuse hepatocellular steatosis due to fatty deposits in hepatocytes, excluding alcohol and other known liver injury factors. However, there are no specific drugs for the clinical treatment of NAFLD. Therefore, research on the pathogenesis of NAFLD at the cellular and molecular levels is a promising approach to finding therapeutic targets and developing targeted drugs for NAFLD. Pin1 is highly expressed during adipogenesis and contributes to adipose differentiation, but its specific mechanism of action in NAFLD is unclear. In this study, we investigated the role of Pin1 in promoting the development of NAFLD and its potential mechanisms in vitro and in vivo. First, Pin1 was verified in the NAFLD model in vitro using MCD diet-fed mice by Western Blot, RT-qPCR and immunohistochemistry (IHC) assays. In the in vitro study, we used the oleic acid (OA) stimulation-induced lipid accumulation model and examined the lipid accumulation in each group of cells by oil red O staining as well as BODIPY staining. The results showed that knockdown of Pin1 inhibited lipid accumulation in hepatocytes in an in vitro lipid accumulation model and improved lipid indices and liver injury levels. Moreover, in vivo, WT and Pin1-KO mice were fed a methionine-choline deficient (MCD) diet for 4 weeks to induce the NAFLD model. The effects of Pin1 on lipid accumulation, hepatic fibrosis, and oxidative stress were evaluated by biochemical analysis, glucose and insulin tolerance tests, histological analysis, IHC, RT-qPCR and Western blot assays. The results indicate that Pin1 knockdown significantly alleviated hepatic steatosis, fibrosis and inflammation in MCD-induced NAFLD mice, improved glucose tolerance and alleviated insulin resistance in mice. Further studies showed that the AMPK/ACC1 signalling pathway might take part in the process by which Pin1 regulates NAFLD, as evidenced by the inhibition of the AMPK/ACC1 pathway. In addition, immunofluorescence (IF), coimmunoprecipitation (Co-IP) and GST pull-down experiments also showed that Pin1 interacts directly with ACC1 and inhibits ACC1 phosphorylation levels. Our study suggests that Pin1 promotes NAFLD progression by inhibiting the activation of the AMPK/ACC1 signalling pathway, and it is possible that this effect is achieved by Pin1 interacting with ACC1 and inhibiting the phosphorylation of ACC1.

Disorders of the central nervous system: Insights from Notch and Nrf2 signaling.

The functional complexity of the central nervous system (CNS) is unparalleled in living organisms. It arises from neural crest-derived cells that migrate by the exact route, leading to the formation of a complex network of neurons and glial cells. Recent studies have shown that novel crosstalk exists between the Notch1 and Nrf2 pathways and is associated with many neurological diseases. The Notch1-Nrf2 axis may act on nervous system development, and the molecular mechanism has recently been reported. In this review, we summarize the essential structure and function of the CNS. The significance of interactions between signaling pathways and between developmental processes like proliferation, apoptosis and migration in ensuring the correct development of the CNS is also presented. We primarily focus on research concerning possible mechanism of interaction between Notch1 and Nrf2 and the functions of Notch1-Nrf2 in neurons. There may be a direct interaction between Notch1 and NRF2, which is closely related to the crosstalk that occurs between them. The significance and potential applications of the Notch1-Nrf2 axis in abnormal development of the nervous system are been highlighten. We also discuss the molecular mechanisms by which the Notch1-Nrf2 axis controls the apoptosis, antioxidant pathway and differentiation of neurons to modulate the development of the nervous system. This information will lead to a better understanding of Notch1-Nrf2 axis signaling pathways in the nervous system and may facilitate the development of new therapeutic strategies.

The role of peptidyl-prolyl isomerase Pin1 in neuronal signaling in epilepsy.

Epilepsy is a common symptom of many neurological disorders and can lead to neuronal damage that plays a major role in seizure-related disability. The peptidyl-prolyl isomerase Pin1 has wide-ranging influences on the occurrence and development of neurological diseases. It has also been suggested that Pin1 acts on epileptic inhibition, and the molecular mechanism has recently been reported. In this review, we primarily focus on research concerning the mechanisms and functions of Pin1 in neurons. In addition, we highlight the significance and potential applications of Pin1 in neuronal diseases, especially epilepsy. We also discuss the molecular mechanisms by which Pin1 controls synapses, ion channels and neuronal signaling pathways to modulate epileptic susceptibility. Since neurotransmitters and some neuronal signaling pathways, such as Notch1 and PI3K/Akt, are vital to the nervous system, the role of Pin1 in epilepsy is discussed in the context of the CaMKII-AMPA receptor axis, PSD-95-NMDA receptor axis, NL2/gephyrin-GABA receptor signaling, and Notch1 and PI3K/Akt pathways. The effect of Pin1 on the progression of epilepsy in animal models is discussed as well. This information will lead to a better understanding of Pin1 signaling pathways in epilepsy and may facilitate development of new therapeutic strategies.

[Preparation and catalytic properties of catalase-inorganic hybrid nanoflowers].

Catalase is widely used in the food, medical, and textile industries. It possesses exceptional properties including high catalytic efficiency, high specificity, and environmental friendliness. Free catalase cannot be recycled and reused in industry, resulting in a costly industrial biotransformation process if catalase is used as a core ingredient. Developing a simple, mild, cost-effective, and environmentally friendly approach to immobilize catalase is anticipated to improve its utilization efficiency and enzymatic performance. In this study, the catalase KatA derived from Bacillus subtilis 168 was expressed in Escherichia coli. Following separation and purification, the purified enzyme was prepared as an immobilized enzyme in the form of enzyme-inorganic hybrid nanoflowers, and the enzymatic properties were investigated. The results indicated that the purified KatA was obtained through a three-step procedure that included ethanol precipitation, DEAE anion exchange chromatography, and hydrophobic chromatography. Then, by optimizing the process parameters, a novel KatA/Ca3(PO4)2 hybrid nanoflower was developed. The optimum reaction temperature of the free KatA was determined to be 35 ℃, the optimum reaction temperature of KatA/Ca3(PO4)2 hybrid nanoflowers was 30-35 ℃, and the optimum reaction pH of both was 11.0. The free KatA and KatA/Ca3(PO4)2 hybrid nanoflowers exhibited excellent stability at pH 4.0-11.0 and 25-50 ℃. The KatA/Ca3(PO4)2 hybrid nanoflowers demonstrated increased storage stability than that of the free KatA, maintaining 82% of the original enzymatic activity after 14 d of storage at 4 ℃, whereas the free KatA has only 50% of the original enzymatic activity. In addition, after 5 catalytic reactions, the nanoflower still maintained 55% of its initial enzymatic activity, indicating that it has good operational stability. The Km of the free KatA to the substrate hydrogen peroxide was (8.80±0.42) mmol/L, and the kcat/Km was (13 151.53± 299.19) L/(mmol·s). The Km of the KatA/Ca3(PO4)2 hybrid nanoflowers was (32.75±2.96) mmol/L, and the kcat/Km was (4 550.67±107.51) L/(mmol·s). Compared to the free KatA, the affinity of KatA/Ca3(PO4)2 hybrid nanoflowers to the substrate hydrogen peroxide was decreased, and the catalytic efficiency was also decreased. In summary, this study developed KatA/Ca3(PO4)2 hybrid nanoflowers using Ca2+ as a self-assembly inducer, which enhanced the enzymatic properties and will facilitate the environmentally friendly preparation and widespread application of immobilized catalase.

Trends and challenges of emergency and acute care in Chinese mainland: 2005-2017.

BACKGROUND: Emergency medical service system (EMSS) is essential in providing acute care services for health conditions. However, trends of emergency and acute care in China haven't been studied systematically. METHODS: Relevant literature was carefully reviewed, including original and review articles, letters, government reports, yearbooks, both in Chinese and in English. Data on the number of emergency visits, physicians and beds in emergency departments (EDs), and the workforce of pre-hospital emergency care were summarized and analyzed from China Health and Family Planning Statistical Yearbooks (2006-2018). RESULTS: Over the past decade, the number of ED visits tripled from 51.9 million to 166.5 million; and utilization of pre-hospital emergency care increased from 3.2 million to 6.8 million. In response to rapid increases in demand, the number of licensed emergency physicians raised from 20,058 to 59,409; the beds' number increased from 10,783 to 42,367. For pre-hospital emergency care, the volume of health workforce increased from 3,687 to 8,671, with a 109% increase in the number of physicians from 1,774 to 3,712. However, overcrowding, the long length of stay in EDs, poor work environment, and work exhaustion were still the critical challenges faced by China's EMSS. CONCLUSIONS: The number of emergency visits has grown with continual capability enhancement during the past decade. However, overcrowding, the long length of stay in EDs, poor work environment, and work exhaustion still need to be solved by China's EMSS. These findings and comparison with the USA could offer experiences and lessons to EMSS development worldwide, especially for developing countries.

Trends in mortality of emergency departments patients in China.

BACKGROUND: Emergency medical service system (EMSS) in China is becoming more important. However, studies on mortality of emergency departments (EDs) patients in tertiary hospitals and on the trends in mortality of ED patients all over China are stagnant. The objective of this study was to quantify and describe the trends in mortality of ED patients in China. METHODS: Nine tertiary teaching hospitals were selected from tertiary teaching hospitals in different regions. The annual numbers of ED visits and deaths of these hospitals in 2004, 2009 and 2014 were recorded and analyzed. Chi-square test was used to compare the mortality of the EDs' visits. Moreover, data on the mortality of ED patients in China from 2005 to 2015 were summarized and analyzed from the China Health and Family Planning Statistical Yearbooks (2006-2016). RESULTS: From 2004 to 2014, the overall annual mortalities in EDs increased among the tertiary hospitals (P<0.001). However, the overall annual mortality in EDs all over China decreased from 0.12% in 2005 to 0.08% in 2015. And the mortalities of EDs patients in the eastern, central and western regions of China all decreased. In addition, the average mortality of EDs patients in northern China was obviously higher than that in southern China (P<0.05). CONCLUSION: The ED mortality was increased in tertiary hospitals while decreased all over China during the past decade, which may be partly caused by some critical challenges faced by China's EMSS, such as overcrowding and long length of stay in EDs of tertiary hospitals.

Mitochondrial aldehyde dehydrogenase in myocardial ischemia-reperfusion injury: from bench to bedside.

Acute myocardial infarction is one of the major causes of mortality worldwide. Reperfusion in a timely fashion is the most effective way to limit infarct size. However, reperfusion can itself prompt further myocardial injury. This phenomenon is commonly known as myocardial ischemia-reperfusion (IR) injury. Mitochondrial aldehyde dehydrogenase (ALDH2) is an enzyme metabolizing acetaldehyde and toxic aldehydes. Increasing evidence has revealed a cardioprotective role of ALDH2 in myocardial IR injury. Evidence from animal studies has shown that ALDH2 diminishes acute myocardial infarct size, ameliorates cardiac dysfunction and prevents reperfusion arrhythmias. The activity of ALDH2 is severely compromised if it is encoded by the mutant ALDH2*2 gene, with an incidence of approximately 40% in Asian populations. Epidemiological surveys in the Asian population have depicted that ALDH2 polymorphism is closely associated with higher prevalence of acute myocardial infarction and coronary artery disease. Therefore, targeting ALDH2 may represent a promising avenue to protect against IR injury. This review recapitulates the underlying mechanisms involved in the protective effect of ALDH2 in cardiac IR injury. Translational potential of ALDH2 in the management of coronary heart disease is also discussed.

Alpha-lipoic acid ameliorates oxidative stress by increasing aldehyde dehydrogenase-2 activity in patients with acute coronary syndrome.

Aldehyde dehydrogenase-2 (ALDH2) is the main enzyme responsible for acetaldehyde oxidation in ethanol metabolism and also provides protection against oxidative stress. Alpha-lipoic acid (α-LA), a natural dithiol compound with antioxidant properties, has been reported to increase ALDH2 activity in cultured cells. We analyzed the therapeutic efficacy of α-LA in 63 patients with confirmed acute coronary syndrome (ACS). These patients (52 men and 11 women, with age range 49-72 years) were randomized into two groups: untreated group (n = 30) and α-LA group (n = 33). Patients in the α-LA group were given an intravenous injection of 600 mg α-LA every day for 5 days while the patients in the untreated group were given saline. An isoprostane, 8-iso-prostaglandin F2α (8-iso-PGF2α), one product of arachidonic acid metabolism, was measured as a marker for oxidative stress. The serum levels of 8-iso-PGF2α and ALDH2 activity were determined at admission to the hospital (time 0), and at 24 hours and 1 week after treatment. At 24 hours and 1 week after treatment, ALDH2 activity was significantly higher in the α-LA group than in the untreated group (P < 0.05), whereas the levels of 8-iso-PGF2α were significantly lower in the α-LA group than in the untreated group (all P < 0.05). Importantly, the decrease of 8-iso-PGF2α levels correlated with the increased ALDH2 activity at both 24 hours (r = 0.6234, P < 0.001) and 1 week after treatment (r = -0.3941, P = 0.0014). α-LA may ameliorate oxidative stress through up-regulating ALDH2 activity in patients with ACS.

[Effects of nitrogen application and ridge film furrow planting on water use of winter wheat in dry land of south Shanxi].

A 2-year (2008-2010) field experiment was conducted to study the effects of basal dressing nitrogen, topdressing nitrogen, and ridge film furrow planting on the 0-2 m soil moisture status and the grain yield and water use efficiency of winter wheat in rain-fed area of South Shanxi Province. In all treatments, the soil moisture status during winter wheat growth period had the same change trend, being increased steadily from pre-sowing to revival stage and decreased sharply from revival stage to heading stage, and then increased gradually till maturity stage. From revival stage to heading stage, the soil water consumption was the most. Increasing nitrogen basal application rate or topdressing nitrogen increased the soil water consumption, widened the soil moisture active layer, and deepened the relatively stable layer. Topdressing nitrogen increased grain yield significantly; ridge film furrow planting decreased soil water consumption obviously. The water use efficiency under ridge film furrow planting was 23.4% and 39.1% higher than that under conventional planting system in 2009 and 2010 (P < 0.01). The grain yield under ridge film furrow planting plus top-dressing nitrogen was 3643 kg x hm(-2), which was significantly higher than that under single ridge film furrow planting or topdressing nitrogen, displaying a preferable water-fertilizer coupling effect.