Suppression of mir-150-5p attenuates the anti-inflammatory effect of glucocorticoids in mice with ulcerative colitis.

Glucocorticoids have been widely used in the treatment of ulcerative colitis, but not all patients benefit from this therapy due to hormone resistance. Mir-150-5p has been reported to enhance the efficacy of glucocorticoids, and low serum mir-150-5p expression has been linked to glucocorticoid resistance in ulcerative colitis patients. The aim of this study was to elucidate the mechanisms of mir-150-5p regulation on glucocorticoid resistance. An ulcerative colitis mouse model was used to evaluate changes in ulcerative colitis symptoms, inflammatory factors, and glucocorticoid resistance-related gene expression. The results showed that mir-150-5p suppression with antagomirs did not significantly interfere with or enhance the induction of ulcerative colitis symptoms by dextran sulfate sodium, but it did attenuate the inflammation inhibitory effect of dexamethasone by abnormally regulating the expression of IL-17a, IL-10, IL-2 and IL-6 levels and myeloperoxidase activity. Mir-150-5p inhibition also induced a glucocorticoid-resistant gene expression profile in colon tissues of ulcerative colitis mice, with upregulation of p-ERK, p-JNK, and HSP90 and downregulation of p-GRa, FKBP4, and HDAC2 expression. Our results indicate that mir-150-5p suppression attenuates the anti-inflammatory effect of glucocorticoids and may function as a driver element in ulcerative colitis glucocorticoid resistance. AVAILABILITY OF DATA AND MATERIALS: All data and figures analyzed in this study are available from the corresponding author by request.

Microbial Community Characterization and Molecular Resistance Monitoring in Geriatric Intensive Care Units in China Using mNGS.

Background: Surface pathogens in the ICU pose a global public health threat, especially to elderly patients who are immunocompromised. To detect these pathogens, unbiased methods such as metagenomic next-generation sequencing (mNGS) are increasingly utilized for environmental microbiological surveillance. Methods: In a six-month study from January to July 2022, we investigated microbial communities in Chinese geriatric ICUs by regularly monitoring multiple surfaces at three-month intervals. Using mNGS sequencing, we analyzed microorganisms present at eight specific locations within the ICU. Additionally, we compared pathogen profiles and drug resistance genes between patient cultures and environmental samples collected during the same period. Results: The microbial composition remained relatively stable over time, but significant differences in alpha diversities were observed among various surfaces such as floors, hands, pumps, trolleys, and ventilator inlets/outlets. Surfaces with high contact frequency for healthcare workers, including workstations, ventilator panels, trolleys, pumps, and beds, harbored pathogenic microorganisms such as Acinetobacter baumannii, Cutibacterium acnes, Staphylococcus haemolyticus, Pseudomonas aeruginosa, and Enterococcus faecium. Acinetobacter baumannii, particularly the carbapenem-resistant strain (CRAB), was the most frequently identified pathogen in geriatric ICU patients regardless of testing method used. The mNGS approach enabled detection of viruses, fungi, and parasites that are challenging to culture. Additionally, an abundance of drug resistance genes was found in almost all environmental samples. Conclusion: The microbial composition and abundance in the ICU remained relatively constant over time. The floor exhibited the highest microbial diversity and abundance in the ICU environment. Drug-resistant genes in the ICU environment may migrate between patients. Overall, mNGS is an emerging and powerful tool for microbiological monitoring of the hospital environment.

Does agricultural factor misallocation hinder agricultural green production efficiency? Evidence from China.

The sustainable development of agriculture is challenged by two major issues: increasing resource constraints and environmental pollution. Sustainable agricultural development is achievable by improving green total factor productivity from the perspective of resource allocation. To promote the green development of agriculture, this paper utilizes the SBM super-efficiency mode and thus calculates the agricultural resource misallocation index and agricultural green production efficiency index in China between 2001 and 2019. Furthermore, this paper discusses the temporal and spatial evolution characteristics of agricultural green production efficiency, using a fixed model and spatial econometric models to estimate the influence effect of agricultural resource misallocation on green production efficiency. Below are the results. First, China's agricultural green total factor productivity is growing at an impressive rate, with high efficiency in the northeast, northwest, and southeast coastal areas and low efficiency in the central and inland areas. Second, agricultural capital misallocation, labor misallocation, and land misallocation all negatively impact agricultural green production efficiency. Accordingly, the misallocation of agricultural factors will hamper the growth of agricultural green production efficiency in this region and also in the surrounding areas. Third, the indirect impact on the own agricultural green production efficiency exceeds its direct impact on neighboring regions' efficiency. Fourth, the mechanisms are the upgrading of agricultural industry structure and green technology innovation. According to the findings, reducing resource misallocation can substantially enhance agricultural green productivity, which is an imperative step in addressing agricultural green production. Hence, policies should be formulated that highlight the regional allocation of agricultural production factors and green production-oriented concept of agricultural production. Also, the government should promote the transformation and upgrading of the agricultural industrial structure, as well as the application of green agricultural technologies.

Urban growth boundary: a revolution for low-carbon development.

A major environmental concern today is the carbon emissions caused by rapid urbanization. As the largest developing country and carbon emitter, China has controlled the urban growth boundary (UGB) as a quasi-experimental policy to achieve carbon neutrality. Therefore, this paper employs the difference in differences (DID) method, for panel data from 2000 to 2019 in China to shed light on the effects on carbon emissions. Results show that the UGB can reduce carbon emissions considerably. After the implementation of the policy, the carbon emissions of the pilot cities decreased by 23.91%. Additionally, a series of robustness tests such as PSM-DID and Placebo tests support the conclusions. Moreover, the greater influence is reflected in the scope of the whole city and the intensity of the permanent plan. The UGB is more susceptible to cities in the central and western areas and cities with weak environmental regulations. Through the mechanism tests, the emission reduction effect of the UGB will be greater in cities with larger vegetation coverage and advanced industry structure. Furthermore, our analysis suggests the UGB needs to be adequately promoted as a policy to achieve carbon neutrality in cities. To make the policy more effective, vegetation cover and industrial structure ought to be taken into consideration.

How would the carbon tax on energy commodities affect consumer welfare? Evidence from China's household energy consumption system.

Although carbon tax policies can effectively restrain energy consumption and reduce pollution, they will also affect the welfare of residents through a price mechanism. We explore the impact of energy price increases that are caused by possible carbon tax policies on the welfare of residents in China with a quadratic almost ideal demand system (QUAIDS) model. The estimated elasticities show that the income elasticity of coal demand is -0.741 for urban residents, compared to 0.392 for rural residents. The cross-price elasticity shows that China's residential energy consumption has moved up the clean energy ladder. Based on the above reliable elasticity estimates, the welfare effects are analyzed in the residential consumption system. The overall welfare loss for residents increases with the level of carbon tax. A carbon tax on all energy sources is a regressive policy for China, and when the carbon tax rate reaches the world average, of 30 USD/tCO2e, the welfare loss for low-income and high-income residents is 1.55% and 0.62% respectively. However, the separate imposition of carbon taxes on different energy sources shows the heterogeneity of the welfare impacts of carbon taxes. At the national and urban levels, the distribution effects of carbon taxes are regressive for coal, LPG, and electricity, progressive for gasoline, and distributional neutral for natural gas. In rural areas, however, the welfare distribution effect of the carbon tax on diesel, LPG, and natural gas are progressive, and the welfare effects of carbon taxes on electricity show an inverted U-shaped distribution. Our findings are conducive to the development of a differentiated carbon tax policy by the Chinese government.

Measuring China's agricultural green total factor productivity and its drivers during 1998-2019.

Improving agricultural green total factor productivity (AGTFP) is essential to China's agricultural sustainable development. Although several studies have focused on China's AGTFP, its measurement and drivers are not fully investigated yet. More specifically, the published research examining the drivers of China's AGTFP at both the production and factor levels is still scarce. To fill this gap, this study constructs two different data envelopment analysis models combined with green Luenberger productivity indicator (GLPI), the biennial weight modified Russell model and the biennial bounded adjusted model, to measure China's AGTFP as well as check the robustness. We further decompose the AGTFP growth at both production and factor levels to investigate its drivers. The main findings are as follows. First, during 1998-2019, the central region with its GLPI at 0.0377 had the largest AGTFP growth, followed by the western (0.0281) and eastern regions (0.0254). Second, in terms of production-decomposition, technical progress was crucial driver to AGTFP growth, energy conservation and emission reduction (ECER) and market performance. Third, in terms of factors-decomposition, the contributions of these factors to the AGTFP growth were positive and the contribution rates ranged from 1.01% (pesticide) to 38.51% (agricultural carbon emissions). Additionally, ECER performance was the primary driver of AGTFP, accounting for about 51.35% of the growth. Finally, according to the decompositions, Porter effect was discovered in China's agricultural sector. ECER drove China's agriculture to achieve win-win development between the environment and economic production.

Effect of PM2.5 pollution on perinatal mortality in China.

Using ArcGIS to analyze satellite derived PM2.5 estimates, this paper obtains the average concentration and maximum concentration of fine particulate matter (PM2.5) in China's 31 provinces from 2002 to 2015. We adopt fixed effects model and spatial Durbin model to investigate the association between PM2.5 and perinatal mortality rates. The results indicate that PM2.5 has a significantly positive association with perinatal mortality rates. A 1% increase of log-transformed average concentration and maximum concentrations of PM2.5 is associated with 1.76‰ and 2.31‰ increase of perinatal mortality rates, respectively. In spatial econometrics analysis, we find PM2.5 has significant spatial autocorrelation characteristics. The concentrations of log-transformed average and maximum PM2.5 increase 1% is associated with a 2.49% increase in a 2.49‰ and 2.19‰ increase of perinatal mortality rates, respectively. The potential mechanism is that air pollution has an impact on infant weight to impact perinatal mortality rates.

Baicalin Improves Cardiac Outcome and Survival by Suppressing Drp1-Mediated Mitochondrial Fission after Cardiac Arrest-Induced Myocardial Damage.

Myocardial injury after cardiac arrest (CA) often results in severe myocardial dysfunction and death involving mitochondrial dysfunction. Here, we sought to investigate whether baicalin, a natural flavonoid compound, exerts cardioprotection against CA-induced injury via regulating mitochondrial dysfunction. We subjected the rats to asphyxia CA after a daily baicalin treatment for 4 weeks. After the return of spontaneous circulation, baicalin treatment significantly improved cardiac function performance, elevated survival rate from 35% to 75%, prevented necrosis and apoptosis in the myocardium, which was accompanied by reduced phosphorylation of Drp1 at serine 616, inhibited Drp1 translocation to the mitochondria and mitochondrial fission, and improved mitochondrial function. In H9c2 cells subjected to simulated ischemia/reperfusion, increased phosphorylation of Drp1 at serine 616 and subsequently enhanced mitochondrial Drp1 translocation as well as mitochondrial fission, augmented cardiomyocyte death, increased reactive oxygen species production, released cytochrome c from mitochondria and injured mitochondrial respiration were efficiently improved by baicalin and Drp1 specific inhibitor with Mdivi-1. Furthermore, overexpression of Drp1 augmented excessive mitochondrial fission and abolished baicalin-afforded cardioprotection, indicating that the protective impacts of baicalin are linked to the inhibition of Drp1. Altogether, our findings disclose for the first time that baicalin offers cardioprotection against ischemic myocardial injury after CA by inhibiting Drp1-mediated mitochondrial fission. Baicalin might be a prospective therapy for the treatment of post-CA myocardial injury.

Endovascular hypothermia improves post-resuscitation myocardial dysfunction by increasing mitochondrial biogenesis in a pig model of cardiac arrest.

The aim of the study was to investigate the effects of endovascular hypothermia on mitochondrial biogenesis in a pig model of prolonged cardiac arrest (CA). Ventricular fibrillation was electrically induced, and animals were left untreated for 10 min; then after 6min of cardiopulmonary resuscitation (CPR), defibrillation was attempted. 25 animals that were successfully resuscitated were randomized into three groups: Sham group (SG, 5, no CA), normal temperature group (NTG, 5 for 12 h observation and 5 for 24 h observation), and endovascular hypothermia group (EHG, 5 for 12 h observation and 5 for 24 h observation). The core temperatures (Tc) in the EHG were maintained at 34 ±â€¯0.5 °C for 6 h by an endovascular hypothermia device (Coolgard 3000), then actively increased at the speed of 0.5 °C per hour during the next 6 h to achieve a normal body temperature, while Tc were maintained at 37.5 ±â€¯0.5 °C in the NTG. Cardiac and mitochondrial functions, the quantification of myocardial mitochondrial DNA (mtDNA), peroxisome proliferator-activated receptor coactivator-1α (PGC-1α), nuclear respiratory factor (NRF)-1, and NRF-2 were examined. Results showed that myocardial and mitochondrial injury and dysfunction increased significantly at 12 h and 24 h after CA. Endovascular hypothermia offered a method to rapidly achieve the target temperature and provide stable target temperature management (TTM). Cardiac outcomes were improved and myocardial injuries were alleviated with endovascular hypothermia. Compared with NTG, endovascular hypothermia significantly increased mitochondrial activity and biogenesis by amplifying mitochondrial biogenesis factors' expressions, including PGC-1α, NRF-1, and NRF-2. In conclusions, endovascular hypothermia after CA alleviated myocardial and mitochondrial dysfunction, and was associated with increasing mitochondrial biogenesis.

Activation of Sigma-1 Receptor by Cutamesine Attenuates Neuronal Apoptosis by Inhibiting Endoplasmic Reticulum Stress and Mitochondrial Dysfunction in a Rat Model of Asphyxia Cardiac Arrest.

BACKGROUND: Global cerebral ischemic/reperfusion (I/R) injury after cardiac arrest (CA) is a major cause of mortality and morbidity in survivors of resuscitation. We utilized a rat model of asphyxia CA to explore the functional effects and mechanisms of Sigma-1 receptor (Sig-1R) activation in cerebral protection using the Sig-1R agonist cutamesine (SA-4503). METHODS: After resuscitation, the surviving rats were randomly divided into three groups (n = 18 each): the cardiopulmonary resuscitation (CPR) group (0.9% saline at 1 mL/kg); the SA4503 low-dose group (1 mg/kg SA4503); and the SA4503 high-dose group (2.5 mg/kg SA4503). The neurological deficit scores were recorded, and the cerebral cortex was harvested for western blotting. Mitochondrial transmembrane potential, adenosine triphosphate (ATP) concentrations, calcium homeostasis, and mitochondrial ultrastructure were also studied. RESULTS: The SA4503 treatment groups exhibited improved neurological outcomes compared with the CPR group. The protein levels of caspase-3 and the endoplasmic reticulum stress markers C/EBP homologous protein and caspase-12 were lower in the SA4503 treatment groups compared with the CPR group. SA4503 treatment also normalized mitochondrial membrane potential, tissue ATP concentrations, intracellular Ca overload, and upregulated Sig-1R protein level compared with the CPR group. The SA4503 high dose treatment showed significant cerebral protective effects compared with the SA4503 low dose treatment. The therapeutic effect of SA4503 was dose-dependent. CONCLUSIONS: CA downregulated Sig-1R protein expression. Activating Sig-1R using SA4503 protected against global cerebral I/R injury in a rat model of asphyxia CA by alleviating endoplasmic reticulum stress and mitochondrial dysfunction and eventually inhibiting neuronal apoptosis.

Dynamic Changes of Mitochondrial Fusion and Fission in Brain Injury after Cardiac Arrest in Rats.

Mitochondria change their morphology dynamically by continual fusion and fission processes to fulfill their function. However, little is known about the effect of cardiac arrest on mitochondrial dynamics. This study aimed to investigate time-dependent change of the mitochondrial dynamics after brain ischemic injury in rats of cardiac arrest. After resuscitation, obvious neuronal injury, reduced adenosine triphosphate (ATP) levels, excessive reactive oxygen species (ROS) generation, decreased mitochondrial membrane potential (MMP), and increased release of mitochondrial cytochrome c were observed at 12 h and 24 h after cardiac arrest. Moreover, we found that elongation of mitochondria was observed at 4 h after cardiac arrest, whereas fragmented mitochondria were significantly increased, along with concomitant increase in the fission proteins Drp1 and Fis1 and a reduction in the fusion proteins Mfn1 and Mfn2 at 12 h and 24 h after cardiac arrest. Taken together, these findings suggest that imbalance in mitochondrial dynamics probably contributes to brain injury after cardiac arrest.