XYA-2: a marine-derived compound targeting apoptosis and multiple signaling pathways in pancreatic cancer.

Background: Pancreatic cancer is a highly aggressive and fatal disease with limited treatment options and poor prognosis for patients. This study aimed to investigate the impact of XYA-2 {N-(3,7-dimethyl-2,6-octadienyl)-2-aza-2-deoxychaetoviridin A}, a nitrogenated azaphilon previously reported from a deep-sea-derived fungus on the progression of pancreatic cancer cells. Methods: The inhibitory effects of XYA-2 on cell proliferation, clonogenic potential, cell cycle progression, apoptosis, migration, and invasion were assessed using various assays. The CCK-8 assay, clone formation assay, flow cytometry assay, wound healing assay, and transwell assay were employed to evaluate cell proliferation, clonogenic potential, cell cycle progression, apoptosis, migration, and invasion, respectively. Moreover, we employed RNA-seq and bioinformatics analyses to uncover the underlying mechanism by which XYA-2 influences pancreatic cancer cells. The revealed mechanism was subsequently validated through qRT-PCR. Results: Our results demonstrated that XYA-2 dose-dependently inhibited the proliferation of pancreatic cancer cells and induced cell cycle arrest and apoptosis. Additionally, XYA-2 exerted a significant inhibitory effect on the invasion and migration of cancer cells. Moreover, XYA-2 was found to regulate the expression of genes involved in multiple cancer-related pathways based on our RNA-seq and bioinformatics analysis. Conclusion: These findings highlight the potential of XYA-2 as a promising therapeutic option for the treatment of pancreatic cancer.

A benzochalcone derivative synchronously induces apoptosis and ferroptosis in pancreatic cancer cells.

Background: Pancreatic cancer is a highly aggressive and lethal disease with limited treatment options. In this study, we investigated the potential therapeutic effects of compound KL-6 on pancreatic cancer cells. Methods: The study involved assessing the inhibitory effects of KL-6 on cell proliferation, clonogenic potential, cell cycle progression, apoptosis, migration, and invasion. Additionally, we examined the action mechanism of KL-6 by RNA-seq and bioinformatic analysis and validated by qRT-PCR and western blot in pancreatic cancer cells. Results: Our results demonstrated that KL-6 effectively inhibited the growth of pancreatic cancer cells in a dose-dependent manner. It induced G2/M phase cell cycle arrest and apoptosis, disrupting the cell cycle progression and promoting cell death. KL-6 also exhibited inhibitory effects on cell migration and invasion, suggesting its potential to suppress the metastatic properties of pancreatic cancer cells. Furthermore, KL-6 modulated the expression of genes involved in various cancer-related pathways including apoptosis and ferroptosis. Conclusion: These findings collectively support the potential of KL-6 as a promising therapeutic option for pancreatic cancer treatment. Further research is needed to fully understand the underlying mechanisms and evaluate the clinical efficacy of KL-6 in pancreatic cancer patients.

Polydatin prevent lung epithelial cell from Carbapenem-resistant Klebsiella pneumoniae injury by inhibiting biofilm formation and oxidative stress.

Carbapenem-resistant Klebsiella pneumoniae (CRKP) causes severe inflammation in various infectious diseases, such as bloodstream infections, respiratory and urinary tract infections, which leads to high mortality. Polydatin (PD), an active ingredient of Yinhuapinggan granule, has attracted worldwide attention for its powerful antioxidant, anti-inflammatory, antitumor, and antibacterial capacity. However, very little is known about the effect of PD on CRKP. In this research, we evaluated the inhibitory effects of PD on both the bacterial level and the bacterial-cell co-culture level on anti-biofilm and efflux pumps and the other was the inhibitory effect on apoptosis, reactive oxygen species (ROS), mitochondrial membrane potential (MMP) after CRKP induction. Additionally, we validated the mechanism of action by qRT-PCR and western blot in human lung epithelial cells. Firstly, PD was observed to have an inhibitory effect on the biofilm of CRKP and the efflux pump AcrAB-TolC. Mechanically, CRKP not only inhibited the activation of Nuclear Factor erythroid 2-Related Factor 2 (Nrf-2) but also increased the level of ROS in cells. These results showed that PD could inhibit ROS and activate Nrf-2 production. Together, our research demonstrated that PD inhibited bacterial biofilm formation and efflux pump AcrAB-TolC expression and inhibited CRKP-induced cell damage by regulating ROS and Nrf-2-regulated antioxidant pathways.

Heat waves accelerate the spread of infectious diseases.

COVID-19 pandemic appeared summer surge in 2022 worldwide and this contradicts its seasonal fluctuations. Even as high temperature and intense ultraviolet radiation can inhibit viral activity, the number of new cases worldwide has increased to >78% in only 1 month since the summer of 2022 under unchanged virus mutation influence and control policies. Using the attribution analysis based on the theoretical infectious diseases model simulation, we found the mechanism of the severe COVID-19 outbreak in the summer of 2022 and identified the amplification effect of heat wave events on its magnitude. The results suggest that approximately 69.3% of COVID-19 cases this summer could have been avoided if there is no heat waves. The collision between the pandemic and the heatwave is not an accident. Climate change is leading to more frequent extreme climate events and an increasing number of infectious diseases, posing an urgent threat to human health and life. Therefore, public health authorities must quickly develop coordinated management plans to deal with the simultaneous occurrence of extreme climate events and infectious diseases.

Divergent sensitivity of vegetation to aridity between drylands and humid regions.

The land surface has been drying over recent decades, which is inconsistent with the greening of the Earth. The extent and spatial variation in the sensitivity of vegetation to aridity changes in drylands and humid regions remain unclear. In this study, satellite observation and reanalysis data were used to analyze the relationship between vegetation growth and atmospheric aridity changes in different climatological regions on a global scale. Our results showed that the leaf area index (LAI) increased at a rate of 0.032/decade from 1982 to 2014, while the aridity index (AI) increased slightly at a rate of 0.005/decade. Over the past three decades, the sensitivity of the LAI to AI has decreased in drylands and increased in humid regions. Thus, the LAI and AI were decoupled in drylands, whereas the effect of aridity on vegetation was enhanced in humid regions during the study period. The physical and physiological effects of increasing CO2 concentration are responsible for the divergent responses of vegetation sensitivity to aridity in drylands and humid regions. The results of the structural equation models showed that the effect of increasing CO2 concentration via LAI and temperature, with respect to decreasing AI, enhanced the negative relationship between LAI and AI in humid regions. The greenhouse effect of increasing CO2 concentration resulted in an increase in temperature and a reduction in aridity, whereas the fertilization effect of CO2 increased LAI, thus creating an inconsistent trend with LAI and AI in drylands.

The evolution of ecological security and its drivers in the Yellow River Basin.

Ecological security is the state achieved once an ecosystem maintains its stability under external stress. The Yellow River Basin (YRB) is the largest river basin in northwest and north China and an important area for grain and energy production. The assessment and attribution of ecological security in the YRB are important for protecting the natural environment and ensuring sustainable development. Here, the ecological security of the YRB was assessed by the ecological security index (ESI), a comprehensive index based on the oxygen cycle, and its drivers were attributed to climate change, human activities, vegetation, and soil factors. The spatial pattern of ecological security in the YRB showed high heterogeneity. Ecological insecurity occurred mainly in the middle reaches and regions where the major stream of the Yellow River passes through. The ESI decreased at a rate of - 0.82/year since 2000, which indicated the natural environment continued to be improved in the YRB. Climate change dominated the evolution of ecological security in the upper reaches. The level of ecological security has been improved in the middle reaches after a series of ecological restoration projects conducted. With higher intensity of industrial activity, human activities played a more critical role in ecological security in the lower reaches. Our results suggested that government and local people need to adopt different strategies and actions based on the dominant drivers in the upper, middle, and lower reaches to ensure protection of the natural environment and achieve sustainable development targets.

Glycyrrhetinic acid prevents carbapenem-resistant Klebsiella pneumoniae-induced cell injury by inhibiting mitochondrial dysfunction via Nrf-2 pathway.

OBJECTIVES: Due to the abuse of antibiotics, the high reoccurrence of drug-resistance strains, such as carbapenem-resistant Klebsiella pneumoniae (CRKP), deteriorates CRKP-infected pneumonia in the clinic, suggesting it is necessary to find new alternatives. Glycyrrhetinic acid (GA), an active ingredient of Yinhuapinggan granule, has antioxidant & anti-inflammatory capacity. Little, however, is known about the effects of GA on CRKP-induced epithelial injury. METHODS: In this research, we examined the protective effects of GA against pulmonary epithelium damage caused by CRKP infection and potential molecular mechanisms. RESULTS: Our results noted GA significantly promoted cell survival and reduced pro-inflammatory cytokines production, during CRKP-induced human pulmonary epithelial cell. Mechanically, GA alleviated mitochondrial-damage-induced apoptosis amid CRKP infection by inhibiting mitochondrial damage. Additionally, we found GA inhibited the expression of pro-apoptotic proteins Cyto-c, the Bax, and Caspase-3 while increasing the expression of anti-apoptotic protein Bcl-2. Further exploration found GA could trigger Nrf-2 expression at both gene and protein levels, activating antioxidative proteins to diminish CRKP-induced oxidative stress. CONCLUSION: Together, our results demonstrated that GA was a promising candidate to alleviate CRKP-infected lung injury as well as a synergist to treat CRKP infection with antibiotics.

Community-Based Physical Rehabilitation After Percutaneous Coronary Intervention for Acute Myocardial Infarction.

To determine whether a community-based physical rehabilitation program could improve the prognosis of patients who had undergone percutaneous coronary intervention after acute myocardial infarction, we randomly divided 164 consecutive patients into 2 groups of 82 patients. Patients in the rehabilitation group underwent 3 months of supervised exercise training, then 9 months of community-based, self-managed exercise; patients in the control group received conventional treatment. The primary endpoint was major adverse cardiac events (MACE) during the follow-up period (25 ± 15.4 mo); secondary endpoints included left ventricular ejection fraction, 6-minute walk distance, and laboratory values at 12-month follow-up. During the study period, the incidence of MACE was significantly lower in the rehabilitation group (13.4% vs 24.4%; P <0.01). Cox proportional hazards regression analysis indicated a significantly lower risk of MACE in the rehabilitation group (hazard ratio=0.56; 95% CI, 0.37-0.82; P=0.01). At 12 months, left ventricular ejection fraction and 6-minute walk distance in the rehabilitation group were significantly greater than those in the control group (both P <0.01), and laboratory values also improved. These findings suggest that community-based physical rehabilitation significantly reduced MACE risk and improved cardiac function and physical stamina in patients who underwent percutaneous coronary intervention after acute myocardial infarction.

Increased ZNF84 expression in cervical cancer.

PURPOSE: Little is known about ZNF84 gene. This study aims to investigate ZNF84 expression in cervical cancer (CC) and the effects of ZNF84 on CC. MATERIALS AND METHODS: Cervical cancer tissue specimens were collected from The First People's Hospital of Foshan. ZNF84 and Akt expression were detected by immunohistochemistry. The influence of ZNF84 on cell proliferation was detected by CCK-8 kits. The effects of ZNF84 on Akt protein and mRNA expression were detected by western blotting and qPCR, respectively. RESULTS: High expression of ZNF84 protein (80.0%) was detected within CC tissues while negative expression was found in normal cervical tissues. ZNF84 was specifically associated with tumor size (p = 0.018) and negatively associated with other indicators. Further, in squamous cell carcinoma, ZNF84 was associated with both TNM staging (p = 0.041) and tumor size (p = 0.041). In vitro, we used shZNF84 to inhibit the mRNA and protein expression of ZNF84, and showed marked inhibition of cancer cell proliferation by shZNF84. Furthermore, inhibition of ZNF84 down-regulated Akt. Ly294002 (an Akt inhibitor) decreased the cell inhibition ability of shZNF84, indicating the involvement of Akt. Finally, the relationship between ZNF84 and Akt in vivo showed positive correlation (p = 0.023). CONCLUSION: ZNF84 expression was increased in CC tissues and associated with tumor size. ZNF84 promoted cell proliferation which might involve Akt signal.

Mechanism of non-appearance of hiatus in Tibetan Plateau.

In the recent decade, hiatus is the hottest issue in the community of climate change. As the area of great importance, the Tibetan Plateau (TP), however, did not appear to have any warming stoppage in the hiatus period. In fact, the TP showed a continuous warming in the recent decade. To explore why the TP did not show hiatus, we divide the surface air temperature into dynamically-induced temperature (DIT) and radiatively-forced temperature (RFT) by applying the dynamical adjustment method. Our results show that DIT displayed a relatively uniform warming background in the TP, with no obvious correlations with dynamic factors. Meanwhile, as the major contribution to warming, the RFT effect over the TP played the dominant role. The warming role is illustrated using the temperature change between perturbed and control simulation responses to CO2 or black carbon (BC) forcing via Community Earth System Model (CESM). It shows that an obvious warming in the TP is induced by the CO2 warming effect, and BC exhibits an amplifying effect on the warming. Therefore, the continuous warming in the TP was a result of uniform DIT warming over a large scale and enhanced RFT warming at a regional scale.

The role of dynamically induced variability in the recent warming trend slowdown over the Northern Hemisphere.

Since the slowing of the trend of increasing surface air temperature (SAT) in the late 1990 s, intense interest and debate have arisen concerning the contribution of human activities to the warming observed in previous decades. Although several explanations have been proposed for the warming-trend slowdown (WTS), none has been generally accepted. We investigate the WTS using a recently developed methodology that can successfully identify and separate the dynamically induced and radiatively forced SAT changes from raw SAT data. The dynamically induced SAT changes exhibited an obvious cooling effect relative to the warming effect of the adjusted SAT in the hiatus process. A correlation analysis suggests that the changes are dominated primarily by the North Atlantic Oscillation (NAO), Pacific Decadal Oscillation (PDO), and Atlantic Multidecadal Oscillation (AMO). Our results confirm that dynamically induced variability caused the WTS. The radiatively forced SAT changes are determined mainly by anthropogenic forcing, indicating the warming influence of greenhouse gases (GHGs), which reached levels of 400 ppm during the hiatus period. Therefore, the global SAT will not remain permanently neutral. The increased radiatively forced SAT will be amplified by increased dynamically induced SAT when the natural mode returns to a warming phase in the next period.