Renal dysfunction, including acute renal failure (ARF) and chronic kidney disease (CKD), continues to present significant health challenges, with renal ischemia-reperfusion injury (IRI) being a ...pivotal factor in their development and progression. This condition, notably impacting kidney transplantation outcomes, underscores the urgent need for innovative therapeutic interventions. The role of opioid agonists in this context, however, remains a subject of considerable debate. Current reviews tend to offer limited perspectives, focusing predominantly on either the protective or detrimental effects of opioids in isolation. Our review addresses this gap through a thorough and comprehensive evaluation of the existing literature, providing a balanced examination of the dualistic nature of opioids’ influence on renal health. We delve into both the nephroprotective and nephrotoxic aspects of opioids, dissecting the complex interactions and paradoxical effects that embody the “two sides of the same coin” phenomenon. This comprehensive analysis is vital for understanding the intricate roles of opioids in renal pathophysiology, potentially informing the development of novel therapeutic strategies for preventing or treating hypoxic kidney injury.
Gut microbiota and short‐chain fatty acids (SCFAs) are associated with the development of various human diseases. In this study, we examined the role of astragaloside IV in modulating mouse gut ...microbiota structure and the generation of SCFAs, as well as in slow transit constipation (STC). An STC model was established by treating mice with loperamide, in which the therapeutic effects of astragaloside IV were evaluated. The microbiota community structure and SCFA content were analysed by 16S rRNA gene sequencing and gas chromatography‐mass spectrometry, respectively. The influence of butyrate on STC was assessed using a mouse model and Cajal cells (ICC). Astragaloside IV promoted defecation, improved intestinal mobility, suppressed ICC loss and alleviated colonic lesions in STC mice. Alterations in gut microbiota community structure in STC mice, such as decreased Lactobacillus reuteri diversity, were improved following astragaloside IV treatment. Moreover, astragaloside IV up‐regulated butyric acid and valeric acid, but decreased isovaleric acid, in STC mouse stools. Butyrate promoted defecation, improved intestinal mobility, and enhanced ICC proliferation by regulating the AKT–NF‐κB signalling pathway. Astragaloside IV promoted intestinal transit in STC mice and inhibited ICC loss by regulating the gut microbiota community structure and generating butyric acid.
•Climate change have adverse effects on the crop productivity.•Melatonin reduces the damage of heat stress in potato plant.•Melatonin also improves the heat tolerance in potato seedlings.•It ...regulates the significant photosynthetic and related genes.•Other crops could be made temperature tolerant with melatonin.
In the era of climate change, the rise in temperature can adversely impact the potato growth, yield and even threaten food security. Temperature both as high and long-term have always retarded growth and development of potatoes. Based on this, overall study provides experimental proof of potato (Solanum tuberosum L.) heat tolerance mechanisms. Plant hormone melatonin (MT) elicits and improves potato tolerance against high temperature, but scarce information is present about detailed mechanisms. Therefore, introduction of exogenous MT in potato seedlings (Lishu 6) together with high-temperature stress was investigated to find the physiological and molecular mechanisms. Temperature stress results in wilting of basal leaves and inhibits photosynthesis in potato seedlings. Interestingly, we found distinct effects of introduced MT with increase in the actual photosynthetic quantum yield (ΦPSII), apparent photosynthetic electron transport rate (ETR), chlorophyll content, intercellular CO2 concentration (Ci), net photosynthetic rate (Pn), photochemical quenching (qP), and transpiration rate (Tr). Further, hydrogen peroxide (H2O2) content and activities of antioxidant enzymes in potato seedling leaves reduced after introduction of exogenous MT. Through transcriptome analysis, we found that during temperature stress, MT significantly upregulated the expression of genes involved in photosynthesis and antioxidant enzymes, and plant hormone signal transduction. Importantly, it also augmented antioxidant capacity in potato seedlings and alleviated the damage at high temperature. In summary, we provide evidence that identifying factors could modulate the potential interaction of temperature stress with introduced MT to improve the heat tolerance of potato seedlings for maximum function.
Purpose:
Intravenous patient-controlled analgesia (IV-PCA) has been widely used; however, regimen criteria have not yet been established. In China, the most often used opioid is sufentanil, for which ...repeated doses are a concern, and empirical flurbiprofen axetil (FBP) as an adjuvant. We hypothesized that hydromorphone would be a better choice and also evaluated the effectiveness of FBP as an adjuvant.
Methods:
This historical cohort study was conducted in two tertiary hospitals in China and included 12,674 patients using hydromorphone or sufentanil for IV-PCA between April 1, 2017, and January 30, 2021. The primary outcome was analgesic insufficiency at static (AIS). The secondary outcomes included analgesic insufficiency with movement (AIM) and common opioid-related adverse effects such as postoperative nausea and vomiting (PONV) and dizziness.
Results:
Sufentanil, but not the sufentanil-FBP combination, was associated with higher risks of AIS and AIM compared to those for hydromorphone (OR 1.64 1.23, 2.19,
p
< 0.001 and OR 1.42 1.16, 1.73,
p
< 0.001). Hydromorphone combined with FBP also decreased the risk of both AIS and AIM compared to those for pure hydromorphone (OR 0.74 0.61, 0.90,
p
= 0.003 and OR 0.80 0.71, 0.91,
p
< 0.001). However, the risk of PONV was higher in patients aged ≤35 years using FBP (hydromorphone-FBP vs. hydromorphone and sufentanil-FBP vs. hydromorphone, OR 1.69 1.22, 2.33,
p
= 0.001 and 1.79 1.12, 2.86,
p
= 0.015).
Conclusion:
Hydromorphone was superior to sufentanil for IV-PCA in postoperative analgesia. Adding FBP may improve the analgesic effects of both hydromorphone and sufentanil but was associated with an increased risk of PONV in patients <35 years of age.
Remifentanil protects against intestinal ischemia/reperfusion (I/R) injury; however, its exact mechanism remains to be elucidated. The objective of this study was to investigate the underlying ...molecular mechanism of remifentanil in intestinal I/R injury in mice.
We evaluated the intestine-protective effect of remifentanil in adult male mice with 45 min superior mesenteric artery occlusion followed by 4 h reperfusion by determining the following: intestinal Chiu's scores, diamine oxidase, and intestinal fatty acid binding protein in serum; the apoptotic index, lipid peroxidation product malondialdehyde (MDA), and superoxide dismutase (SOD) activity in the intestinal mucosa; and the intestinal mRNA and protein expressions of Bip, CHOP, caspase-12, and cleaved caspase-3, reflecting endoplasmic reticulum (ER) stress. Furthermore, conditional knockout mice, in which the protein disulfide isomerase A3 (PDIA3) gene was deleted from the intestinal epithelium, and SB203580 (a selective p38MAPK inhibitor) were used to determine the role of PDIA3 and p38MAPK in I/R progression and intestinal protection by remifentanil.
Our data showed that intestinal I/R induced obvious oxidative stress and endoplasmic reticulum stress-related cell apoptosis, as evidenced by an increase in the intestinal mucosal malondialdehyde, a decrease in the intestinal mucosal SOD, and an increase in the apoptotic index and the mRNA and protein expression of Bip, CHOP, caspase-12, and cleaved caspase-3. Remifentanil significantly improved these changes. Moreover, the deletion of intestinal epithelium PDIA3 blocked the protective effects of remifentanil. SB203580 also abolished the intestinal protection of remifentanil and downregulated the mRNA and protein expression of PDIA3.
Remifentanil appears to act
p38MAPK to protect the small intestine from intestinal I/R injury by its PDIA3-mediated antioxidant and anti-ER stress properties.
Recent observational studies have reported a negative association between physical activity and chronic back pain (CBP), but the causality of the association remains unknown. We introduce ...bidirectional Mendelian randomization (MR) to assess potential causal inference between physical activity and CBP.
This two-sample MR used independent genetic variants associated with physical activity and CBP as genetic instruments from large genome-wide association studies (GWASs). The effects of both directions (physical activity to CBP and CBP to physical activity) were examined. Inverse variance-weighted meta-analysis and alternate methods (weighted median and MR-Egger) were used to combine the MR estimates of the genetic instruments. Multiple sensitivity analyses were conducted to examine the robustness of the results.
The MR set parallel GWAS cohorts, among which, those involved in the primary analysis were comprised of 337,234 participants for physical activity and 158,025 participants (29,531 cases) for CBP. No evidence of a causal relationship was found in the direction of physical activity to CBP odds ratio (OR), 0.98; 95% CI, 0.85-1.13;
= 0.81. In contrast, a negative causal relationship in the direction of CBP to physical activity was detected (
= -0.07; 95% CI, -0.12 to -0.01;
= 0.02), implying a reduction in moderate-vigorous physical activity (approximately 146 MET-minutes/week) for participants with CBP relative to controls.
The negative relationship between physical activity and CBP is probably derived from the reduced physical activity of patients experiencing CBP rather than the protective effect of physical activity on CBP.
The changing climate and intensifying human activities have made an impact on the hydrological processes in the upper Yangtze River (UYR), but quantifying their effects remains uncertain. This study ...used the Budyko framework to investigate the response of runoff (Q) to climate change and human activities during 1956–2017 and evaluate the impacts of human activities, including land use/cover change, water use, dam construction, and vegetation change, on watershed characteristic. Results show that climate change is the dominant driver of Q variations in the Wujiang River (WJR), Jialing River (JLR), and Jinsha River (JSR) watersheds, with contributions of 58.6%, 66.9%, and 67.6%, respectively. However, in Mingjiang River (MJR) and UYR watersheds, human activities contribute more to Q variations with 55.2% and 51.2%, respectively. Human activities play important roles in variation of watershed characteristics, and they can explain 22%, 26%, 36%, 25%, and 53% of the watershed character change in UYR, WJR, JLR, MJR, and JSR, respectively. This study conducts a comprehensive analysis of the causes of Q change in UYR, and provides a new perspective to explore the effects of specific human activities on watershed characteristics.
Plain Language Summary
With climate change and intensifying human activities, the water cycle has been changed. Runoff is an essential component of the water cycle, and its response to changing environments has drawn broad attention. This study aims to quantify the contributions of climate change and human activities to runoff changes in the upper Yangtze River (UYR) and its four sub‐watersheds over the past half‐century. According to the results, human activities and climate change have been responsible for approximately 51.2% and 48.8% of the observed runoff changes in UYR, respectively. It suggests that both human activities and climate change have played significant roles, and their contributions are remarkably comparable. In addition, the impacts of human activities on watershed environment changes are analyzed. The results suggest that increased settlement area and industrial water use are the dominant influencing factors.
Key Points
Human activities and climate change have made comparable contributions to the runoff reduction in the upper Yangtze River
Water use, land use/cover change, vegetation change, and dam construction together explain 22% of the watershed environment changes
Human settlements and increased industrial water use have been the principal factors contributing to the changes in watershed environment
Background Hypotension is a risk factor for postoperative complications, but evidence from randomized trials does not support that a higher blood pressure target always leads to optimized outcomes. ...The heterogeneity of underlying hemodynamics during hypotension may contribute to these contradictory results. Exploring the subtypes of hypotension can enable optimal management of intraoperative hypotension. Methods This is a prospective, observational pilot study. Patients who were ≥ 45 years old and scheduled to undergo moderate-to-high-risk noncardiac surgery were enrolled in this study. The primary objective of this pilot study was to investigate the frequency and distribution of perioperative hypotension and its subtypes (hypotension with or without cardiac output reduction). The exposure of hypotension and its subtypes in patients with and without myocardial or acute kidney injury were also explored. Results Sixty patients were included in the analysis. 83% (50/60) of the patients experienced perioperative hypotension. The median duration of hypotension for each patient was 8.0 interquartile range, 3.1–23.3 minutes. Reduced cardiac output was present during 77% of the hypotension duration. Patients suffering from postoperative myocardial or acute kidney injury displayed longer duration and more extensive exposure in all hypotension subtypes. However, the percentage of different hypotension subtypes did not differ in patients with or without postoperative myocardial or acute kidney injury. Conclusion Perioperative hypotension was frequently accompanied by cardiac output reduction in moderate-to-high-risk noncardiac surgical patients. However, due to the pilot nature of this study, the relationship between hypotension subtypes and postoperative myocardial or acute kidney injury still needs further exploration. Clinical trial registration https://www.chictr.org.cn/showprojEN.html?proj=134260 , CTR2200055929.
The cellular characteristics of intestinal cells involved in the therapeutic effects of astragaloside IV (AS-IV) for treating slow transit constipation (STC) remain unclear. This study aimed to ...determine the dynamics of colon tissue cells in the STC model and investigate the effects of AS-IV treatment by single-cell RNA sequencing (scRNA-seq). STC mouse models were developed using loperamide, with subsequent treatment using AS-IV. Colon tissues and feces were collected for scRNA-seq and targeted short-chain fatty acid quantification. We integrated scRNA-seq data with network pharmacology to analyze the effect of AS-IV on constipation. AS-IV showed improvement in defecation for STC mice induced by loperamide. Notably, in STC mice, epithelial cells, T cells, B cells, and fibroblasts demonstrated alterations in cell proportions and dysfunctions, which AS-IV partially rectified. AS-IV has the potential to modulate the metabolic pathway of epithelial cells through its interaction with peroxisome proliferator-activated receptor gamma (PPARγ). AS-IV reinstated fecal butyrate levels and improved energy metabolism in epithelial cells. The proportion of naïve CD4+T cells is elevated in STC, and the differentiation of these cells into regulatory T cells (Treg) is regulated by B cells and fibroblasts through the interaction of ligand-receptor pairs. AS-IV treatment can partially alleviate this trend. The status of fibroblasts in STC undergoes alterations, and the FB_C4_Adamdec1 subset, associated with angiogenesis and the Wingless-related integration (Wnt) pathway, emerges. Our comprehensive analysis identifies perturbations of epithelial cells and tissue microenvironment cells in STC and elucidates mechanisms underlying the therapeutic efficacy of AS-IV.
Evapotranspiration (ET) is regulated by vapor pressure deficit (VPD) and soil moisture (SM) which are expected to change in global climate change. Understanding the impacts of VPD and SM on maize ET ...is essential for global food security and water cycle. Here, we estimate the actual maize ET in Southwest China during 2001–2011 based on Mapping Evapotranspiration at High Resolution with Internalized Calibration (METRIC) model using remote-sensing data and reanalysis data. Then, we define the extreme drought events in 2009–2011 using the smoothed standardized anomaly of the three-month Standardized Precipitation Evapotranspiration Index (SPEI) to investigate the responses of maize ET to VPD and SM during extreme drought events in Southwest China. We detected the lag times of maize ET responses to VPD and SM, and then analyzed the sensitivity of maize ET to VPD and SM with lagged effects. We found pervasive lagged responses of maize ET with a shorter lag time of VPD (1.12 ±0.006 months, P < 0.05) than SM (1.28±0.006 months, P < 0.05). We analyzed the lag times of maize ET in relation to elevation, temperature, and precipitation to investigate the abiotic impacts on the lagged responses and found the lagged responses were more prevalent in areas at higher altitudes with lower temperatures but there was less variation across precipitation gradients. Maize ET was more sensitive to VPD than SM with lagged effects. High VPD enhanced maize ET under sufficient SM but during an extreme drought event, maize ET might be dramatically reduced due to SM depletion in spite of high VPD. The study highlights the significance of atmospheric water demand for crop water consumption under extreme climate events.
•Maize ET had a shorter lag time to VPD (1.12 months) than SM (1.28 months).•The lagged response was prevalent at high altitudes with low temperatures.•Maize ET was more sensitive to VPD than SM with lagged effects.•Maize ET rose under high VPD with ample SM but might decrease due to SM depletion.
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