Curcumin alleviates heatstroke-induced liver injury in dry-heat environments by inhibiting the expression of NF-κB, iNOS, and ICAM-1 in rats.

we aimed to monitor liver injury in rat model during heat stress and heatstroke in dry-heat environment and investigate the effects of curcumin on heatstroke-induced liver injury and the underlying mechanisms. Sprague-Dawley (SD) rats were randomly divided into four groups: normal saline (NS), and 50 (50-cur), 100 (100-cur), and 200 mg/kg curcumin (200-cur) groups. They were administered the indicated doses of curcumin by gavage once daily for 7 days. On day 8, the rats were transferred to a simulated climate cabin, At 0, 50, 100, and 150 min, the core temperature (Tc) was measured respectively. After sacrificing the rats, tissue samples were collected, measure histology indices, serum enzymes, lipopolysaccharides (LPSs), cytokines, nuclear factor-kappa B (NF-κB), inducible nitric oxide synthase (iNOS), and intercellular adhesion molecule-1 (ICAM-1). The Tc increased with time in all groups. Curcumin alleviation of symptoms and improvement in pathological scores. The level of enzymes, LPS, and cytokines increased during heatstroke in the NS group, but curcumin decreased the levels of these indicators. The differences of the indicators between NS and 200-cur groups at 150 min were significant (P < 0.05). The expression of NF-κB p65, iNOS, and ICAM-1 was upregulated in the NS group at 150 min, but their expression was relatively lower in the curcumin groups (P < 0.05). Thus, our findings indicate acute liver injury during heat stress and heatstroke. The mechanism involves cascade-amplification inflammatory response induced by the gut endotoxin. Furthermore, curcumin alleviated heatstroke-induced liver injury in a dose-dependent manner by downregulating NF-κB, iNOS, and ICAM-1.

Enhanced Dechlorination of the Herbicide Acetochlor by an Anaerobic Consortium via Sulfate Acclimation.

Acetochlor residues can contaminate anoxic habitats where anaerobic microbial transformation dominates. Herein, a highly efficient anaerobic acetochlor-degrading consortium ACT6 was enriched using sulfate and acetochlor as selection pressures. The acclimated consortium ACT6 showed an 8.7-fold increase in its ability to degrade acetochlor compared with the initial consortium ACT1. Two degradation pathways of acetochlor were found: reductive dechlorination and thiol-substitution dechlorination in the chloroacetyl group, in which the latter dominated. Acclimation enhanced the abundances of Desulfovibrio, Proteiniclasticum, and Lacrimispora from 0.7 to 28.0% (40-fold), 4.7 to 18.1% (4-fold), and 2.3 to 12.3% (5-fold), respectively, which were positively correlated with sulfate concentrations and acetochlor degradation ability. Three acetochlor-degrading anaerobes were isolated from the acclimated consortium ACT6, namely Cupidesulfovibrio sp. SRB-5, Proteiniclasticum sp. BAD-10, and Lacrimispora sp. BAD-7. This study provides new insights into the anaerobic catabolism of acetochlor and the anaerobic treatment of acetochlor in wastewater.

Curcumin-mediated enhancement of lung barrier function in rats with high-altitude-associated acute lung injury via inhibition of inflammatory response.

BACKGROUND: Exposure to a hypobaric hypoxic environment at high altitudes can lead to lung injury. In this study, we aimed to determine whether curcumin (Cur) could improve lung barrier function and protect against high-altitude-associated acute lung injury. METHODS: Two hundred healthy rats were randomly divided into standard control, high-altitude control (HC), salidroside (40 mg/kg, positive control), and Cur (200 mg/kg) groups. Each group was further divided into five subgroups. Basic vital signs, lung injury histopathology, routine blood parameters, plasma lactate level, and arterial blood gas indicators were evaluated. Protein and inflammatory factor (tumor necrosis factor α (TNF-α), interleukin [IL]-1ß, IL-6, and IL-10) concentrations in bronchoalveolar lavage fluid (BALF) were determined using the bicinchoninic acid method and enzyme-linked immunosorbent assay, respectively. Inflammation-related and lung barrier function-related proteins were analyzed using immunoblotting. RESULTS: Cur improved blood routine indicators such as hemoglobin and hematocrit and reduced the BALF protein content and TNF-α, IL-1ß, and IL-6 levels compared with those in the HC group. It increased IL-10 levels and reduced pulmonary capillary congestion, alveolar hemorrhage, and the degree of pulmonary interstitial edema. It increased oxygen partial pressure, oxygen saturation, carbonic acid hydrogen radical, and base excess levels, and the expression of zonula occludens 1, occludin, claudin-4, and reduced carbon dioxide partial pressure, plasma lactic acid, and the expression of phospho-nuclear factor kappa. CONCLUSIONS: Exposure to a high-altitude environment for 48 h resulted in severe lung injury in rats. Cur improved lung barrier function and alleviated acute lung injury in rats at high altitudes.

[Research Progresses on the Effects of CCL4 on Immune Escape 
in Tumor Microenvironment].

Immunotherapy has become the cornerstone of current malignant tumor treatment. However, the response of different patients to immunotherapy is highly heterogeneous, and not all patients can benefit from it. There is an urgent need to find biomarkers that can effectively predict the efficacy of immunotherapy. C-C chemokine ligand 4 (CCL4) is a cytokine, belonging to the inflammatory CCL subfamily. It is mainly secreted by immune cells and tumor cells and shows low or no expression in normal tissues but abnormally high expression in various malignant tumor tissues. After binding to CCL4 and its receptor C-C chemokine receptor type 5 (CCR5), it can recruit and mediate immune cell migration, destroy the stability of the tumor microenvironment (TME), participate in carcinogenesis and promote the development of tumors. In the tumor immune microenvironment, CCL4 can mediate and recruit the directed migration of key immune cells such as monocytes, macrophages, natural killer (NK) cells, and T cells, which makes it a potentially important element affecting the efficacy of immunotherapy and has specific value. This paper reviews the research progresses of CCL4's effects on immune escape in TME, in order to provide clues and references for basic research and clinical diagnosis and treatment.
.

Association Between Red Cell Distribution Width and Liver Injury after Cardiac and Aortic Aneurysm Surgery with Cardiopulmonary Bypass.

OBJECTIVES: This study aimed to investigate the association between preoperative red blood cell distribution width (RDW) levels and liver injury (LI) after cardiac surgery, to highlight RDW's usefulness in the early identification and intervention for patients at high risk of LI. DESIGN: A retrospective observational study. SETTING: A university-affiliated teaching hospital and tertiary referral center. PARTICIPANTS: Adult patients who underwent cardiac and aortic aneurysm surgery at Changhai Hospital in 2021. INTERVENTIONS: Postoperative LI was defined by increased liver enzyme levels and/or hyperbilirubinemia, noted from the time of surgery to discharge. Logistic regression analyses were conducted to examine the RDW-LI relationship, with stratified analyses based on age, gender, and anemia. Survival within 30 days was assessed using the Kaplan-Meier method, with survival curve differences analyzed via the log-rank test. The study included 3 sets of sensitivity analyses. MEASUREMENTS AND MAIN RESULTS: Postoperative LI was observed in 75 patients (10%). Multivariate regression analysis showed a significant association between high RDW levels and postoperative LI (adjusted odds ratio, 3.25; p = 0.033; 95% confidence intefal, 1.10-9.63), even after adjusting for all covariates. This association remained consistent across 3 sets of sensitivity analyses. Subgroup analysis showed men had a higher correlation with LI (p for interaction = 0.041). Kaplan-Meier analysis indicated a significantly lower survival rate in the LI group (76%) compared with the non-LI group (99.6%; p < 0.001). CONCLUSIONS: Preoperative RDW levels are significantly associated with postoperative LI. RDW could serve as a significant useful marker for early detection and intervention in patients at high risk of LI, thereby potentially improving patient outcomes.

Color category and inter-item interaction influence color working memory codependently.

Our brains do not always encode visual information in a veridical way. Visual working memory (WM) for features such as color can be biased. WM bias comes from several sources. Category priors can lead to WM bias. For example, color WM is biased toward or away from category prototypes. In addition to category knowledge, contextual factors can induce and modulate WM bias; however, these biases of different sources have usually been investigated independently with different tasks. The present study sought to explore how color WM is influenced by both color category and concurrent distractor. Specifically, we asked participants to retain two color items in WM to investigate how the WM representation of the target color is biased by learned category knowledge and contextual inter-item interactions. Our study found that the WM representation of the target color is biased toward or away from the category prototypes and away from the distractor color that is simultaneously held in WM, indicating that both color category and concurrent distractor bias color WM. More importantly, the weight of these two biases depends on the specific color category, suggesting that category priors and inter-item interaction biases are not simply additive but flexible. Furthermore, we revealed that both types of biases arise from perceptual processes.

M2-like tumor-associated macrophage-secreted CCL2 facilitates gallbladder cancer stemness and metastasis.

BACKGROUND: The predominant immune cells in solid tumors are M2-like tumor-associated macrophages (M2-like TAMs), which significantly impact the promotion of epithelial-mesenchymal transition (EMT) in tumors, enhancing stemness and facilitating tumor invasion and metastasis. However, the contribution of M2-like TAMs to tumor progression in gallbladder cancer (GBC) is partially known. METHODS: Immunohistochemistry was used to evaluate the expression of M2-like TAMs and cancer stem cell (CSC) markers in 24 pairs of GBC and adjacent noncancerous tissues from patients with GBC. Subsequently, GBC cells and M2-like TAMs were co-cultured to examine the expression of CSC markers, EMT markers, and migratory behavior. Proteomics was performed on the culture supernatant of M2-like TAMs. The mechanisms underlying the induction of EMT, stemness, and metastasis in GBC by M2-like TAMs were elucidated using proteomics and transcriptomics. GBC cells were co-cultured with undifferentiated macrophages (M0) and analyzed. The therapeutic effect of gemcitabine combined with a chemokine (C-C motif) receptor 2 (CCR2) antagonist on GBC was observed in vivo. RESULTS: The expression levels of CD68 and CD163 in M2-like TAMs and CD44 and CD133 in gallbladder cancer stem cells (GBCSCs) were increased and positively correlated in GBC tissues compared with those in neighboring noncancerous tissues. M2-like TAMs secreted a significant amount of chemotactic cytokine ligand 2 (CCL2), which activated the MEK/extracellular regulated protein kinase (ERK) pathway and enhanced SNAIL expression after binding to the receptor CCR2 on GBC cells. Activation of the ERK pathway caused nuclear translocation of ELK1, which subsequently led to increased SNAIL expression. GBCSCs mediated the recruitment and polarization of M0 into M2-like TAMs within the GBC microenvironment via CCL2 secretion. In the murine models, the combination of a CCR2 antagonist and gemcitabine efficiently inhibited the growth of subcutaneous tumors in GBC. CONCLUSIONS: The interaction between M2-like TAMs and GBC cells is mediated by the chemokine CCL2, which activates the MEK/ERK/ELK1/SNAIL pathway in GBC cells, promoting EMT, stemness, and metastasis. A combination of a CCR2 inhibitor and gemcitabine effectively suppressed the growth of subcutaneous tumors. Consequently, our study identified promising therapeutic targets and strategies for treating GBC.

Unveiling the unique role of TSPAN7 across tumors: a pan-cancer study incorporating retrospective clinical research and bioinformatic analysis.

BACKGROUND: TSPAN7 is an important factor in tumor progression. However, the precise function of TSPAN7 and its role in pan-cancer are not clear. METHODS: Based on Xinhua cohort incorporating 370 patients with kidney neoplasm, we conducted differential expression analysis by immunohistochemistry between tumor and normal tissues, and explored correlations of TSPAN7 with patients' survival. Subsequently, we conducted a pan-cancer study, and successively employed differential expression analysis, competing endogenous RNA (ceRNA) analysis, protein-protein interaction (PPI) analysis, correlation analysis of TSPAN7 with clinical characteristics, tumor purity, tumor genomics, tumor immunity, and drug sensitivity. Last but not least, gene set enrichment analysis was applied to identify enriched pathways of TSPAN7. RESULTS: In Xinhua cohort, TSPAN7 expression was significantly up-regulated (P-value = 0.0019) in tumor tissues of kidney neoplasm patients. High TSPAN7 expression was associated with decreases in overall survival (OS) (P-value = 0.009) and progression-free survival (P-value = 0.009), and it was further revealed as an independent risk factor for OS (P-value = 0.0326, HR = 5.66, 95%CI = 1.155-27.8). In pan-cancer analysis, TSPAN7 expression was down-regulated in most tumors, and it was associated with patients' survival, tumor purity, tumor genomics, tumor immunity, and drug sensitivity. The ceRNA network and PPI network of TSPAN7 were also constructed. Last but not least, the top five enriched pathways of TSPAN7 in various tumors were identified. CONCLUSION: TSPAN7 served as a promising biomarker of various tumors, especially kidney neoplasms, and it was closely associated with tumor purity, tumor genomics, tumor immunology, and drug sensitivity in pan-cancer level.

Nematode-trapping fungus Arthrobotrys oligospora recruited rhizosphere microorganisms to cooperate in controlling root-knot nematodes in tomato.

AIMS: The objective of this study was to elucidate the role and mechanism of changes in the rhizosphere microbiome following Arthrobotrys oligospora treatment in the biological control of root-knot nematodes and identify the key fungal and bacterial species that collaborate with A. oligospora to biocontrol root-knot nematodes. METHODS AND RESULTS: We conducted a pot experiment to investigate the impact of A. oligospora treatment on the biocontrol efficiency of A. oligospora against Meloidogyne incognita infecting tomatoes. We analyzed the rhizosphere bacteria and fungi communities of tomato by high-throughput sequencing of the 16S rRNA gene fragment and the internal transcribed spacer (ITS). The results indicated that the application of A. oligospora resulted in a 53.6% reduction in the disease index of M. incognita infecting tomato plants. The bacterial diversity of rhizosphere soil declined in the A. oligospora-treated group, while fungal diversity increased. The A. oligospora treatment enriched the tomato rhizosphere with Acidobacteriota, Firmicutes, Bradyrhizobium, Sphingomonadales, Glomeromycota, and Purpureocillium. These organisms are involved in the utilization of rhizosphere organic matter, nitrogen, and glycerolipids, or play the role of ectomycorrhiza or directly kill nematodes. The networks of bacterial and fungal co-occurrence exhibited a greater degree of stability and complexity in the A. oligospora treatment group. CONCLUSIONS: This study demonstrated the key fungal and bacterial species that collaborate with the A. oligospora in controlling the root-knot nematode and elaborated the potential mechanisms involved. The findings offer valuable insights and inspiration for the advancement of bionematicide based on nematode-trapping fungi.

NRP1 promotes osteo/odontogenic differentiation via shroom3 in dental pulp stem cells.

Neuropilin-1 (NRP1) is a single transmembrane glycoprotein involved in a variety of physiological events. However, the exact mechanisms by which NRP1 regulates dental pulp stem cells (DPSCs) to differentiate toward an osteo/odontogenic phenotype are poorly understood. Here, we determined the significantly increased expression of full-length NRP1 and glycosaminoglycan (GAG)-modified NRP1 during osteo/odontogenesis in DPSCs. NRP1 was confirmed to promote alkaline phosphatase (ALP) activity, mineralized nodule deposition, protein and mRNA expression of Runx2, DSPP and DMP1 in DPSCs via the loss-of-function and gain-of-function approaches. Further, a non-GAG-modified NRP1 mutant (NRP1 S612A) was generated and the suppression of osteo/odontogenic differentiation was observed in the NRP1 S612A overexpression cells. Knockdown of the adaptor protein shroom3 resulted in the inhibition of osteo/odontogenesis. The protein-protein interaction network, the protein-protein docking and confocal analyses indicated the interactions between NRP1 and shroom3. Furthermore, immunoprecipitation followed by western analysis confirmed the binding of NRP1 to shroom3, but overexpression of NRP1 S612A greatly influenced the recruitment of shroom3 by NRP1. These results provide strong evidence that NRP1 is a critical regulator for osteo/odontogenesis through interacting with shroom3. Moreover, our results indicate that NRP1 S612A attenuates osteo/odontogenesis, suggesting that GAG modification is essential for NRP1 in DPSCs.

Global, regional, and national burden of ischemic heart disease attributable to secondhand smoke from 1990 to 2019.

INTRODUCTION: Assessing the burden of ischemic heart disease (IHD) attributable to secondhand smoke (SHS) exposure is crucial for informing evidence-based healthcare practices, prevention strategies, and resource allocation planning. METHODS: The burden of IHD attributable to SHS from 1990 to 2019 was assessed using the comparative risk assessment method as part of the Global Burden of Disease (GBD) study 2019. RESULTS: Globally, the absolute number of deaths and disability-adjusted life-years (DALYs) from IHD due to SHS increased substantially from 270.0 thousand and 6971.3 thousand in 1990 to 397.4 thousand and 9566.1 thousand in 2019. The corresponding age-standardized mortality rates (ASMR) and age-standardized DALYs rates (ASDR) were both in a decreasing trend with estimate of the annual percentage change (EAPC) of -1.38 (-1.42 - -1.34) and -1.43 (-1.47 - -1.38). Central Asia has the highest ASMR (16 per 100000, 95% uncertainty interval, UI: 12.8-19.4), and Oceania has the highest ASDR (323.2 per 100000, 95% UI: 228.9-443.1 per 100000) in 2019. All sociodemographic index (SDI) category regions showed a decreasing trend in ASMR and ASDR, with the decrease being more obvious in high and high-middle SDI regions. Our analysis identified an escalating trend concerning ASMR and ASDR in Oceania from 1990 to 2019. In 2019, the most significant number of deaths and DALYs occurred in the age group of 80-84 years (5.4 thousand, 95% UI: 3.7-7.3 in thousands) and the age group of 55-59 years (1140.8 thousand, 95% UI: 876.1-1435 in thousands). CONCLUSIONS: Our study reveals an absolute global increase in deaths and DALYs from IHD due to SHS from 1990 to 2019. Despite a declining trend in ASMR and ASDR, regional disparities persist. The elderly and middle-aged populations bore the most significant burden. These findings highlight the ongoing global health impact of SHS on IHD and emphasize the need for targeted interventions in regions with rising trends and vulnerable age groups.

The incidence, risk factors, and prognosis of acute kidney injury in patients after cardiac surgery.

Background: Acute kidney injury (AKI) represents a significant complication following cardiac surgery, associated with increased morbidity and mortality rates. Despite its clinical importance, there is a lack of universally applicable and reliable methods for the early identification and diagnosis of AKI. This study aimed to examine the incidence of AKI after cardiac surgery, identify associated risk factors, and evaluate the prognosis of patients with AKI. Method: This retrospective study included adult patients who underwent cardiac surgery at Changhai Hospital between January 7, 2021, and December 31, 2021. AKI was defined according to the Kidney Disease: Improving Global Outcomes (KDIGO) criteria. Perioperative data were retrospectively obtained from electronic health records. Logistic regression analyses were used to identify independent risk factors for AKI. The 30-day survival was assessed using the Kaplan-Meier method, and differences between survival curves for different AKI severity levels were compared using the log-rank test. Results: Postoperative AKI occurred in 257 patients (29.6%), categorized as stage 1 (179 patients, 20.6%), stage 2 (39 patients, 4.5%), and stage 3 (39 patients, 4.5%). The key independent risk factors for AKI included increased mean platelet volume (MPV) and the volume of intraoperative cryoprecipitate transfusions. The 30-day mortality rate was 3.2%. Kaplan-Meier analysis showed a lower survival rate in the AKI group (89.1%) compared to the non-AKI group (100%, P < 0.001). Conclusion: AKI was notably prevalent following cardiac surgery in this study, significantly impacting survival rates. Notably, MPV and administration of cryoprecipitate may have new considerable predictive significance. Proactive identification and management of high-risk individuals are essential for reducing postoperative complications and mortality.

Root suberization in the response mechanism of melon to autotoxicity.

Continuous cropping obstacles poses significant challenges for melon cultivation, with autotoxicity being a primary inducer. Suberization of cells or tissues is a vital mechanism for plant stress response. Our study aimed to elucidate the potential mechanism of root suberization in melon's response to autotoxicity. Cinnamic acid was used to simulate autotoxicity. Results showed that autotoxicity worsened the root morphology and activity of seedlings. Significant reductions were observed in root length, diameter, surface area, volume and fork number compared to the control in the later stage of treatment, with a decrease ranging from 20% to 50%. The decrease in root activity ranged from 16.74% to 29.31%. Root suberization intensified, and peripheral suberin deposition became more prominent. Autotoxicity inhibited phenylalanineammonia-lyase activity, the decrease was 50% at 16 h. The effect of autotoxicity on cinnamylalcohol dehydrogenase and cinnamate 4-hydroxylase activity showed an initial increase followed by inhibition, resulting in reductions of 34.23% and 44.84% at 24 h, respectively. The peroxidase activity only significantly increased at 24 h, with an increase of 372%. Sixty-three differentially expressed genes (DEGs) associated with root suberization were identified, with KCS, HCT, and CYP family showing the highest gene abundance. GO annotated DEGs into nine categories, mainly related to binding and catalytic activity. DEGs were enriched in 27 KEGG pathways, particularly those involved in keratin, corkene, and wax biosynthesis. Seven proteins, including C4H, were centrally positioned within the protein interaction network. These findings provide insights for improving stress resistance in melons and breeding stress-tolerant varieties.

The role of sacubitril/valsartan in abnormal renal function patients combined with heart failure: a meta-analysis and systematic analysis.

AIMS: This study aimed to investigate the efficacy and safety of sacubitril/valsartan in abnormal renal function (eGFR < 60 ml/min/1.73m2) patients combined with heart failure based on randomized controlled trials (RCTs) and observational studies. METHODS: The Embase, PubMed and the Cochrane Library were searched for relevant studies from inception to December 2023. Dichotomous variables were described as event counts with the odds ratio (OR) and 95% confidence interval (CI) values. Continuous variables were expressed as mean standard deviation (SD) with 95% CIs. RESULTS: A total of 6 RCTs and 8 observational studies were included, involving 17335 eGFR below 60 ml/min/1.73m2 patients combined with heart failure. In terms of efficacy, we analyzed the incidence of cardiovascular events and found that sacubitril/valsartan significantly reduced the risk of cardiovascular death or heart failure hospitalization in chronic kidney disease (CKD) stages 3-5 patients with heart failure (OR: 0.65, 95%CI: 0.54-0.78). Moreover, sacubitril/valsartan prevented the serum creatinine elevation (OR: 0.81, 95%CI: 0.68-0.95), the eGFR decline (OR: 0.83, 95% CI: 0.73-0.95) and the development of end-stage renal disease in this population (OR:0.73, 95%CI:0.60-0.89). As for safety outcomes, we did not find that the rate of hyperkalemia (OR:1.31, 95%CI:0.79-2.17) and hypotension (OR:1.57, 95%CI:0.94-2.62) were increased in sacubitril/valsartan group among CKD stages 3-5 patients with heart failure. CONCLUSIONS: Our meta-analysis proves that sacubitril/valsartan has a favorable effect on cardiac function without obvious risk of adverse events in abnormal renal function patients combined with heart failure, indicating that sacubitril/valsartan has the potential to become perspective treatment for these patients.

The potential of organoids in renal cell carcinoma research.

Renal cell carcinoma, a leading cause of death in urological malignancies, arises from the nephron. Its characteristics include diversity in disease biology, varied clinical behaviors, different prognoses, and diverse responses to systemic therapies. The term 'organoids' is used to describe structures resembling tissues created through the three-dimensional cultivation of stem cells in vitro. These organoids, when derived from tumor tissues, can retain the diversity of the primary tumor, mirror its spatial tissue structure, and replicate similar organ-like functions. In contrast to conventional two-dimensional cell cultures and the transplantation of tumor tissues into other organisms, organoids derived from tumors maintain the complexity and microenvironment of the original tumor tissue. This fidelity makes them a more reliable model for the development of cancer drugs, potentially accelerating the translation of these drugs to clinical use and facilitating personalized treatment options for patients. This review aims to summarize the recent advancements in the use of organoids for studying renal cell carcinoma, focusing on their cultivation, potential applications, and inherent limitations.