New Electrocardiographic Score for Predicting the Site of Coronary Artery Occlusion in Inferior Wall Acute Myocardial Infarction.

Background: An electrocardiogram (ECG) was used to determine the type of acute myocardial infarction (MI) and locate the culprit vessel. Inferior wall myocardial infarction (IWMI) patients with the right coronary artery (RCA) as the culprit vessel may have a worse clinical prognosis than the left circumflex artery (LCx). We aimed to develop a new, simple, accurate scoring system to localize the RCA. Methods: From January 2018 to January 2020, patients were admitted to the Department of Cardiology of TEDA International Cardiovascular Hospital and the Second Hospital of Tianjin Medical University due to IWMI and coronary angiography confirmed that the infarct-related vessel was a single RCA or LCx. ECG of patients before percutaneous coronary intervention (PCI) was collected to quantitatively analyze the characteristics of ST-segment deviation in non-inferior wall leads (N-IWL) and establish the RCA score in N-IWL. Results: 149 patients were enrolled, including 83 in the RCA group and 66 in the LCx group. Finally, ST-segment depression (ST↓) lead I, aVR, V1, and V6, and ST↓≥ 1mm in lead V4 were found to be associated with the location of the RCA. The sensitivity, specificity, and area under the curve (AUC) of the N-IWL RCA scoring system were 77.1%, 72.7%, and 0.83, respectively. The diagnostic ability of the scoring system was better than that of other algorithms and scoring systems. Conclusion: ECG helps identify the RCA in patients with IWMI before PCI. The N-IWL RCA score may help identify the culprit vessel as the RCA in patients with IWMI.

Bicyclol attenuates pulmonary fibrosis with silicosis via both canonical and non-canonical TGF-ß1 signaling pathways.

BACKGROUND: Silicosis is an irreversible fibrotic disease of the lung caused by chronic exposure to silica dust, which manifests as infiltration of inflammatory cells, excessive secretion of pro-inflammatory cytokines, and pulmonary diffuse fibrosis. As the disease progresses, lung function further deteriorates, leading to poorer quality of life of patients. Currently, few effective drugs are available for the treatment of silicosis. Bicyclol (BIC) is a compound widely employed to treat chronic viral hepatitis and drug-induced liver injury. While recent studies have demonstrated anti-fibrosis effects of BIC on multiple organs, including liver, lung, and kidney, its therapeutic benefit against silicosis remains unclear. In this study, we established a rat model of silicosis, with the aim of evaluating the potential therapeutic effects of BIC. METHODS: We constructed a silicotic rat model and administered BIC after injury. The FlexiVent instrument with a forced oscillation system was used to detect the pulmonary function of rats. HE and Masson staining were used to assess the effect of BIC on silica-induced rats. Macrophages-inflammatory model of RAW264.7 cells, fibroblast-myofibroblast transition (FMT) model of NIH-3T3 cells, and epithelial-mesenchymal transition (EMT) model of TC-1 cells were established in vitro. And the levels of inflammatory mediators and fibrosis-related proteins were evaluated in vivo and in vitro after BIC treatment by Western Blot analysis, RT-PCR, ELISA, and flow cytometry experiments. RESULTS: BIC significantly improved static compliance of lung and expiratory and inspiratory capacity of silica-induced rats. Moreover, BIC reduced number of inflammatory cells and cytokines as well as collagen deposition in lungs, leading to delayed fibrosis progression in the silicosis rat model. Further exploration of the underlying molecular mechanisms revealed that BIC suppressed the activation, polarization, and apoptosis of RAW264.7 macrophages induced by SiO2. Additionally, BIC inhibited SiO2-mediated secretion of the inflammatory cytokines IL-1ß, IL-6, TNF-α, and TGF-ß1 in macrophages. BIC inhibited FMT of NIH-3T3 as well as EMT of TC-1 in the in vitro silicosis model, resulting in reduced proliferation and migration capability of NIH-3T3 cells. Further investigation of the cytokines secreted by macrophages revealed suppression of both FMT and EMT by BIC through targeting of TGF-ß1. Notably, BIC blocked the activation of JAK2/STAT3 in NIH-3T3 cells required for FMT while preventing both phosphorylation and nuclear translocation of SMAD2/3 in TC-1 cells necessary for the EMT process. CONCLUSION: The collective data suggest that BIC prevents both FMT and EMT processes, in turn, reducing aberrant collagen deposition. Our findings demonstrate for the first time that BIC ameliorates inflammatory cytokine secretion, in particular, TGF-ß1, and consequently inhibits FMT and EMT via TGF-ß1 canonical and non-canonical pathways, ultimately resulting in reduction of aberrant collagen deposition and slower progression of silicosis, supporting its potential as a novel therapeutic agent.

The Restriction Activity Investigation of Rv2528c, an Mrr-like Modification-Dependent Restriction Endonuclease from Mycobacterium tuberculosis.

Mycobacterium tuberculosis (Mtb), as a typical intracellular pathogen, possesses several putative restriction-modification (R-M) systems, which restrict exogenous DNA's entry, such as bacterial phage infection. Here, we investigate Rv2528c, a putative Mrr-like type IV restriction endonuclease (REase) from Mtb H37Rv, which is predicted to degrade methylated DNA that contains m6A, m5C, etc. Rv2528c shows significant cytotoxicity after being expressed in Escherichia coli BL21(DE3)pLysS strain. The Terminal deoxynucleotidyl transferase dUTP Nick-End Labeling (TUNEL) assay indicates that Rv2528c cleaves genomic DNA in vivo. The plasmid transformation efficiency of BL21(DE3)pLysS strain harboring Rv2528c gene was obviously decreased after plasmids were in vitro methylated by commercial DNA methyltransferases such as M.EcoGII, M.HhaI, etc. These results are consistent with the characteristics of type IV REases. The in vitro DNA cleavage condition and the consensus cleavage/recognition site of Rv2528c still remain unclear, similar to that of most Mrr-family proteins. The possible reasons mentioned above and the potential role of Rv2528c for Mtb were discussed.

Unique Plant Resources and Distribution Patterns in the Valley Forest of the Irtysh River Basin.

The river valley forests of the Irtysh River Basin are a germplasm bank of Salicaceae species and rare plant resources in China, and the distribution varies with the river and is highly distinctive. However, there is a dearth of systematic research on the characteristics of plant resources. In this study, a comprehensive investigation was conducted in the trunk stream and six tributaries with valley forest distribution in the Irtysh River Basin, and 244 quadrats were set up. The analysis focused on the composition of the flora and resource characteristics. The results reveal the following: (1) The valley forests of the Irtysh River Basin contain 256 species of plants belonging to 57 families and 178 genera, among which 19 species of trees, 23 species of shrubs, and 214 species of herbs were investigated. (2) Among the identified species, 226 (88.67%) were recognized as resource plants, with medicinal plants being the most abundant (176 species, 68.75% of the total). (3) The distribution patterns of trees, shrubs, and herbs of each resource type vary across rivers. Elevation drop, river length, and river distance all significantly affect the number of specie. This study elucidated the current status and distributional characteristics of plant resources in the valley forests of the Irtysh River Basin, which is essential for both biodiversity conservation and sustainable resource utilization.

Quantitative Effects of Anthropogenic and Natural Factors on Heavy Metals Pollution and Spatial Distribution in Surface Drinking Water Sources in the Upper Huaihe River Basin in China.

The water quality of sources in the Huaihe River Basin significantly affects the lives and health of approximately 16.7% of China's population. Identifying and quantifying pollution sources and risks is essential for effective water resource management. This study utilized Monte Carlo simulations and Geodetector to assess water quality and eutrophication, as well as to evaluate the sources of heavy metals and the associated health risks for both adults and children. The results showed that eutrophication of water sources in Huaihe River was severe, with an overall EI value of 37.92; 67.8% of the water sources were classified as mesotrophic and 32.2% classified as eutrophic. Water quality and eutrophication levels in the southern mountainous regions were better than those in the densely populated northern areas. Adults were found to have a higher carcinogenic risk than children, whereas children faced a higher noncarcinogenic risk than adults. Cr presented the highest carcinogenic risk, affecting more than 99.8% of both adults and children at levels above 1 × 10-6 but not exceeding 1 × 10-4. The noncarcinogenic risk from metals did not surpass a level of 1, except for Pb. As was primarily influenced by agricultural activities and transportation, whereas Cd, Cr, and Pb were mainly affected by industrial activities, particularly in local textile industries such as knitting and clothing manufacturing. The analysis demonstrated that the influence of anthropogenic factors on heavy metal distribution was significantly enhanced by indirect natural factors. For example, the explanatory power of Precipitation and Road Network Density on As was 0.362 and 0.189, respectively, whereas their interaction had an explanatory power as high as 0.673. This study indicates that the geodetector method is effective in elucidating the factors influencing heavy metal distribution in water, thereby providing valuable insights into pollution sources in global drinking water.

Association between dietary quality and accelerated aging: a cross-sectional study of two cohorts.

Background: Diet quality significantly influences aging processes and age-related health outcomes. This study aims to explore the association between dietary quality and accelerated aging in two large cohorts. Methods: This study collected data from the Kailuan and National Health and Nutrition Examination Survey (NHANES) cohorts; participants' dietary quality was evaluated using the American Heart Association (AHA) dietary score and Healthy Eating Index-2015 (HEI-2015), respectively. Accelerated aging in participants was determined by calculating the difference between phenotypic age and chronological age. Logistic regression models were used to explore the association between dietary quality scores and accelerated aging. Additionally, variations in this association across different subgroups were investigated. To minimize the influence of excessive aging, individuals aged 75 and above were excluded in sensitivity analyses. Results: In this study, we included 33 701 participants (27.3% female, mean age 57.29 ± 11.88) from the Kailuan study and 9285 participants (50.6% female, mean age 49.83 ± 17.62) from NHANES. In the Kailuan cohort, individuals with dietary scores ranging from 3 to 5 exhibited a 22% lower risk of accelerated aging compared to those scoring between 0 and 2 (OR = 0.78, 95% CI = 0.72-0.85). Similarly, in the NHANES cohort, participants in the highest quartile of HEI-2015 experienced a 34% reduction in the risk of accelerated aging compared to those in the lowest quartile (OR = 0.66, 95% CI = 0.52-0.84). Subgroup analyses underscored a more pronounced association between dietary quality and accelerated aging among males and individuals with unhealthy lifestyles. Sensitivity analyses confirmed the robustness of the association between dietary quality and accelerated aging. Conclusion: In summary, our study found a significant association between dietary quality and accelerated aging. Better dietary quality was associated with a reduced risk of accelerated aging, particularly among males, smokers, and participants with unhealthy lifestyles.

Metformin exposure and the incidence of lactic acidosis in critically ill patients with T2DM: A retrospective cohort study.

OBJECTIVE: The objective of this study was to investigate the correlation between metformin exposure and the incidence of lactic acidosis in critically ill patients. METHODS: The patients with type 2 diabetes mellitus (T2DM) were included from Medical Information Mart for Intensive Care IV database (MIMIC-IV). The primary outcome was the incidence of lactic acidosis. The secondary outcomes were lactate level and in-hospital mortality. Propensity score matching (PSM) method was adopted to reduce bias of the confounders. The multivariate logistic regression was used to explore the correlation between metformin exposure and the incidence of lactic acidosis. Subgroup analysis and sensitivity analysis were used to test the stability of the conclusion. RESULTS: We included 4939 patients. There were 2070 patients in the metformin group, and 2869 patients in the nonmetformin group. The frequency of lactic acidosis was 5.7% (118/2070) in the metformin group and it was 4.3% (122/2869) in the nonmetformin group. There was a statistically significant difference between the two groups (P < 0.05). The lactate level in the metformin group was higher than in the nonmetformin group (2.78 ± 2.23 vs. 2.45 ± 2.24, P < 0.001). After PSM, the frequency of lactic acidosis (6.3% vs. 3.7%, P < 0.001) and lactate level (2.85 ± 2.38 vs. 2.40 ± 2.14, P < 0.001) were significantly higher in the metformin group compared with the nonmetformin group. In multivariate logistic models, the frequency of lactic acidosis was obviously increased in metformin group, and the adjusted odds ratio (OR) of metformin exposure was 1.852 (95% confidence interval (CI) = 1.298-2.643, P < 0.001). The results were consistent with subgroup analysis except for respiratory failure subgroup. Metformin exposure increased lactate level but did not affect the frequency of lactic acidosis in patients of respiratory failure with hypercapnia. However, the in-hospital mortality between metformin and nonmetformin group had no obvious difference (P = 0.215). In sensitivity analysis, metformin exposure showed similar effect as the original cohort. CONCLUSIONS: In critically ill patients with T2DM, metformin exposure elevated the incidence of lactic acidosis except for patients of respiratory failure with hypercapnia, but did not affect the in-hospital mortality.

Mst1-mediated phosphorylation of FoxO1 and C/EBP-ß stimulates cell-protective mechanisms in cardiomyocytes.

The molecular mechanisms by which FoxO transcription factors mediate diametrically opposite cellular responses, namely death and survival, remain unknown. Here we show that Mst1 phosphorylates FoxO1 Ser209/Ser215/Ser218/Thr228/Ser232/Ser243, thereby inhibiting FoxO1-mediated transcription of proapoptotic genes. On the other hand, Mst1 increases FoxO1-C/EBP-ß interaction and activates C/EBP-ß by phosphorylating it at Thr299, thereby promoting transcription of prosurvival genes. Myocardial ischemia/reperfusion injury is larger in cardiac-specific FoxO1 knockout mice than in control mice. However, the concurrent presence of a C/EBP-ß T299E phospho-mimetic mutation reduces infarct size in cardiac-specific FoxO1 knockout mice. The C/EBP-ß phospho-mimetic mutant exhibits greater binding to the promoter of prosurvival genes than wild type C/EBP-ß. In conclusion, phosphorylation of FoxO1 by Mst1 inhibits binding of FoxO1 to pro-apoptotic gene promoters but enhances its binding to C/EBP-ß, phosphorylation of C/EBP-ß, and transcription of prosurvival genes, which stimulate protective mechanisms in the heart.

High-throughput method for screening pendimethalin-degrading bacteria from one microbial bank.

The extensive use of chemical pesticides, such as herbicides, has resulted in significant environmental pollution. Microbial degradation represents a crucial approach for managing this pesticide-associated pollution, with enrichment culturing serving as a method for isolating pesticide-degrading microorganisms. However, the efficiency of this strategy is limited, often yielding only a few isolated strains. In this study, a new mineral salt medium (MSM) was developed, and a high-throughput method was used for screening pendimethalin-degrading bacteria by measuring the bacterial growth in the MSM. The utilization of this method resulted in the isolation of 56 pendimethalin-degrading bacteria from approximately 2000 bacterial strains, including 37 Bacillus spp., 10 Alcaligenes spp., 5 Pseudomonas spp., and other 4 strains identified for the first time as pendimethalin-degrading strains. This method may hold promise not only for isolating bacterial strains capable of degrading other pesticides but also for facilitating the utilization of the substantial bacterial strains stored in bacterial banks.

Prognostic value of cardiovascular magnetic resonance in immune checkpoint inhibitor-associated myocarditis: A systematic review and meta-analysis.

Background: Immune checkpoint inhibitors (ICI) are increasingly used in the first-line treatment of malignant tumors. There is increasing recognition of their cardiotoxicity and, in particular, their potential to lead to myocarditis. Cardiovascular magnetic resonance (CMR) can quantify pathological changes, such as myocardial edema and fibrosis. The purpose of this systematic review and meta-analysis was to examine the evidence for the roles of CMR in predicting prognosis in ICI-associated myocarditis. Methods: PubMed, Cochrane Library, and Web of Science databases were searched until October 2023 for published works investigating the relationship between CMR parameters and adverse events in patients with ICI-associated myocarditis. The analysis included studies reporting the incidence of late gadolinium enhancement (LGE), T1 values, T2 values, and CMR-derived left ventricular ejection fraction (LVEF). Odds ratios (OR) and weighted mean differences (WMD) were combined for binary and continuous data, respectively. Newcastle-Ottawa Scale was used to assess the methodological quality of the included studies. Results: Five cohort studies were included (average age 65-68 years; 25.4% female). Of these, four studies were included in the meta-analysis of LGE-related findings. Patients with major adverse cardiovascular events (MACE) had a higher incidence of LGE compared with patients without MACE (OR = 4.18, 95% CI: 1.72-10.19, p = 0.002). A meta-analysis, incorporating data from two studies, showed that patients who developed MACE exhibited significantly higher T1 value (WMD = 36.16 ms, 95% CI: 21.43-50.89, p < 0.001) and lower LVEF (WMD = - 8.00%, 95% CI: -13.60 to -2.40, p = 0.005). Notably, T2 value (WMD = -0.23 ms, 95% CI: -1.86 to -1.39, p = 0.779) was not associated with MACE in patients with ICI-related myocarditis. Conclusions: LGE, T1 value, and LVEF measured by CMR imaging have potential prognostic value for long-term adverse events in patients with ICI-related myocarditis.

Long-term, 13-year survival after immune cell therapy combined with chemotherapy for extensive-stage small-cell lung cancer: a case report.

While the incidence of small-cell lung cancer is low, it has a poor prognosis. Patients with extensive small-cell lung cancer account for about 70% of all cases of small-cell lung cancer, with a median overall survival duration of 8-13 months and a 5-year overall survival rate of only 1%-5%. Herein, we report small-cell lung cancer diagnosed by bronchoscopic biopsy in an adult male patient in 2011. The patient had a clinical stage of cT2N2M1 and stage IV disease (i.e., extensive small-cell lung cancer). Still, he survived for 13 years through a combination of chemotherapy, radiotherapy, and cytokine-induced killer (CIK) immunocell thera. Comprehensive tumor markers, lymphocyte subsets, and lung CT images were obtained through long-term follow-up. After 12 cycles of chemotherapy (CE/IP regimen) and 5940cgy/33f radiotherapy, we found that the patient was in an immunosuppressive state, so the patient was given CIK cell therapy combined with chemotherapy. After 2 years of immunocell-combined chemotherapy, there were no significant changes in the primary lesion or other adverse events. In the 13 years since the patient's initial diagnosis, we monitored the changes in the patient's indicators such as CEA, NSE, CD4/CD8 ratio, and CD3+CD4+ lymphocytes, suggesting that these may be the factors worth evaluating regarding the patient's immune status and the effectiveness of combination therapy. In this case, CIK cell immunotherapy combined with chemotherapy was applied to control tumor progression. With a good prognosis, we concluded that CIK cell immunotherapy combined with chemotherapy can prolong patient survival in cases of extensive small-cell lung cancer, and the advantages of combined therapy are reflected in improving the body's immune capacity and enhancing the killing effect of immune cells.

Neuropeptide natalisin regulates reproductive behaviors in Spodoptera frugiperda.

Natalisin (NTL) is a conserved neuropeptide, only present in insects, that has been reported to regulate their sexual activity. In this study, we investigated the involvement of NTL in the reproductive behaviors of a major invasive pest, Spodoptera frugiperda. We identified NTL precursor-encoded transcripts, and evaluated their transcript levels in different stages and tissues of S. frugiperda. The results showed that the NTL transcript level was expressed in both male and female pupae and both male and female adults in the later stage. It was highly expressed in male pupae, 3-day-old male and female adults, and 5-day-old male adults. In different tissues, the expression level is higher in the male and female adult brain and male testis. Immunohistochemical staining of the brain of S. frugiperda female and male adults revealed that three pairs of brain neurons of S. frugiperda adults of both sexes secreted and expressed NTL. To study the role of NTL in reproductive behaviors, NTL was silenced in S. frugiperda male and female adults by RNA interference (RNAi) technology, the results showed that silencing NTL could significantly affect the sexual activity behavior of the adults, reducing the calling rate of females, the courtship rate of males, and the mating rate. In summary, this study emphasizes the important role of NTL in regulating the mating behavior and sexual activity of S. frugiperda in both male and female adults, potentially laying a foundation to employ NTL as a new insect-specific target to control populations of pest insects.

Postoperative QRS duration to left ventricular end-diastolic diameter ratio as a predictor for the risk of postoperative atrial fibrillation in cardiac surgery: A single-center prospective study.

Background and aims: Postoperative atrial fibrillation (POAF) is a frequent complication following cardiac surgery and is associated with adverse clinical outcomes. Our study aimed at determining the clinical and echocardiographic predictors of POAF in patients with cardiac surgery and management of this group of patients may improve their outcome. Methods: We prospectively enrolled patients from the department of cardiovascular surgery in the Second Hospital of Tianjin Medical University from October 23, 2020 to October 30, 2022, without a history of atrial fibrillation. Cox regression was used to identify significant predictors of POAF. Results: A total of 217 patients (79 [36.41 %] were female, 63.96 ± 12.32 years) were included. 88 (40.55 %) patients met the criteria for POAF. Cox regression showed that preoperative left atrial diameter (LAD) (HR: 1.040, 95 % CI 1.008-1.073, p = 0.013) and postoperative QRS/LVEDD (HR: 0.398, 95 % CI 0.193-0.824, p = 0.013) and E/e' (HR: 1.029, 95 % CI 1.002-1.057，p = 0.033) were predictors of POAF. Conclusion: Preoperative LAD and postoperative QRS/LVEDD and E/e' were predictors of POAF in patients undergoing cardiac surgery. Trial registration site: http://www.chictr.org.cn. Registration number: ChiCTR2200063344.

Redefining Accuracy: Underwater Depth Estimation for Irregular Illumination Scenes.

Acquiring underwater depth maps is essential as they provide indispensable three-dimensional spatial information for visualizing the underwater environment. These depth maps serve various purposes, including underwater navigation, environmental monitoring, and resource exploration. While most of the current depth estimation methods can work well in ideal underwater environments with homogeneous illumination, few consider the risk caused by irregular illumination, which is common in practical underwater environments. On the one hand, underwater environments with low-light conditions can reduce image contrast. The reduction brings challenges to depth estimation models in accurately differentiating among objects. On the other hand, overexposure caused by reflection or artificial illumination can degrade the textures of underwater objects, which is crucial to geometric constraints between frames. To address the above issues, we propose an underwater self-supervised monocular depth estimation network integrating image enhancement and auxiliary depth information. We use the Monte Carlo image enhancement module (MC-IEM) to tackle the inherent uncertainty in low-light underwater images through probabilistic estimation. When pixel values are enhanced, object recognition becomes more accessible, allowing for a more precise acquisition of distance information and thus resulting in more accurate depth estimation. Next, we extract additional geometric features through transfer learning, infusing prior knowledge from a supervised large-scale model into a self-supervised depth estimation network to refine loss functions and a depth network to address the overexposure issue. We conduct experiments with two public datasets, which exhibited superior performance compared to existing approaches in underwater depth estimation.

Optimization of concentrations of different n-3PUFAs on antioxidant capacity in mouse hepatocytes.

Omega-3 polyunsaturated fatty acids (n-3 PUFAs), mainly including α-linolenic acid (ALA), eicosapentaenoic acid (EPA), and docosahexaenoic acid (DHA), possess antioxidant properties and play a crucial role in growth and development. However, the combined effects of ALA, EPA, and DHA at different concentrations have rarely been reported. This work explored the effects of EPA, ALA, and DHA on the viability and antioxidant capacity of mouse hepatocytes, with the objective of enhancing the antioxidant capacity. Within the appropriate concentration range, cell viability and the activity of glutathione S-transferase, superoxide dismutase, and catalase were increased, while the oxidation products of malondialdehyde and the level of intracellular reactive oxygen species were obviously reduced. Thus, oxidative stress was relieved, and cellular antioxidant levels were improved. Finally, response surface optimization was carried out for EPA, ALA, and DHA, and the model was established. The antioxidant capacity of the cells was highest at EPA, ALA, and DHA concentrations of 145.46, 405.05, and 551.52 µM, respectively. These findings lay the foundation for further exploration of the interactive mechanisms of n-3 PUFAs in the body, as well as their applications in nutraceutical food.

Associations Between Social Determinants of Health and Cardiovascular Health of U.S. Adult Cancer Survivors.

Background: Relationships between the social determinants of health (SDOH) and cardiovascular health (CVH) of cancer survivors are underexplored. Objectives: This study sought to investigate associations between the SDOH and CVH of adult cancer survivors. Methods: Data from the U.S. National Health Interview Survey (2013-2017) were used. Participants reporting a history of cancer were included, excluding those with only nonmelanotic skin cancer, or with missing data for any domain of SDOH or CVH. SDOH was quantified with a 6-domain, 38-item score, consistent with the Centers for Disease Control and Prevention recommendations (higher score indicated worse deprivation). CVH was quantified based on the American Heart Association's Life's Essential 8, but due to unavailable detailed dietary data, a 7-item CVH score was used, with a higher score indicating worse CVH. Survey-specific multivariable Poisson regression was used to test associations between SDOH quartiles and CVH. Results: Altogether, 8,254 subjects were analyzed, representing a population of 10,887,989 persons. Worse SDOH was associated with worse CVH (highest vs lowest quartile: risk ratio 1.30; 95% CI: 1.25-1.35; P < 0.001), with a grossly linear relationship between SDOH and CVH scores. Subgroup analysis found significantly stronger associations in younger participants (P interaction = 0.026) or women (P interaction = 0.001) but without significant interactions with race (P interaction = 0.051). Higher scores in all domains of SDOH were independently associated with worse CVH (all P < 0.001). Higher SDOH scores were also independently associated with each component of the CVH score (all P < 0.05 for highest SDOH quartile). Conclusions: An unfavorable SDOH profile was independently associated with worse CVH among adult cancer survivors in the United States.

Recent advancements in chitosan-based intelligent food freshness indicators: Categorization, advantages, and applications.

With an increasing emphasis on food safety and public health, there is an ongoing effort to develop reliable, non-invasive methods to assess the freshness of diverse food products. Chitosan-based food freshness indicators, leveraging properties such as biocompatibility, biodegradability, non-toxicity, and high stability, offer an innovative approach for real-time monitoring of food quality during storage and transportation. This review introduces intelligent food freshness indicators, specifically those utilizing pH-sensitive dyes like anthocyanins, curcumin, alizarin, shikonin, and betacyanin. It highlights the benefits of chitosan-based intelligent food freshness indicators, emphasizing improvements in barrier and mechanical properties, antibacterial activity, and composite film solubility. The application of these indicators in the food industry is then explored, alongside a concise overview of chitosan's limitations. The paper concludes by discussing the challenges and potential areas for future research in the development of intelligent food freshness indicators using chitosan. Thus, chitosan-based smart food preservation indicators represent an innovative approach to providing real-time data for monitoring food quality, offering valuable insights to both customers and retailers, and playing a pivotal role in advancing the food industry.

In vivo functional analysis of the cotton bollworm Helicoverpa armigera 24-dehydrocholesterol reductase (HaDHCR24) in phytosterol metabolism.

Insects have to obtain sterols from food due to the inability to synthesize this essential nutrient de novo. For lepidopteran insects, they can convert a variety of phytosterols into cholesterol to meet their growth needs. The final step of the cholesterol biosynthesis is the metabolism of desmosterol catalyzed by 24-dehydrocholesterol reductase (DHCR24). In this study, we identified a DHCR24 homolog in the cotton bollworm Helicoverpa armigera, designated as H. armigera 24-dehydrocholesterol reductase (HaDHCR24)-1. The quantitative expression analyses indicated that HaDHCR24-1 was highly enriched in the midgut where dietary sterol uptake occurs. Compared to the control, the DHCR24-1 mutant larvae generated by clustered regularly interspaced palindromic repeats (CRISPR) / CRISPR-associated nuclease 9 technology accumulated more desmosterol in the gut, while the content of cholesterol was significantly reduced. A similar phenomenon was observed when the DHCR24 inhibitor, amiodarone, was applied to the insects. Moreover, DHCR24-1 played an important role for the usage of ß-sitosterol, a major sterol in plants, in H. armigera, and loss of function of DHCR24-1 resulted in higher mortality on ß-sitosterol. However, the DHCR24 homolog does not necessarily exist in the genomes of all insects. The loss of this gene occurred more frequently in the insects feeding on animals, which further support the role of DHCR24-1 in using phytosterols. This gene may have important potential in developing new strategies to control herbivory pests in Lepidoptera and other insect orders.

[Recent advances in protein precipitation-based methods for drug-target screening].

Drug targets are biological macromolecules that bind drug molecules in vivo. Therefore, the system-wide identification of drug targets plays a vital role in fully understanding the mechanism of drug action, efficacy, and side effects. The unbiased screening of drug targets may accelerate the process of drug discovery and candidate screening. Mass spectrometry is a key tool for large-scale protein identification and accurate quantification owing to its high acquisition speed, resolution, and sensitivity. Mass spectrometry-based proteomics has been widely used for drug-target screening. It can systematically identify the protein-target landscape of a drug and elucidate drug-protein interactions. Commonly used drug-target characterization methods, such as labeling-based affinity enrichment, require the chemical derivatization of drug molecules, which is not only time-consuming but may also affect the affinity of the drug towards its targets. Furthermore, the spatial effects of the derivatization groups may block interactions between the drug and its targets. Considering the disadvantages of affinity-enrichment methods, strategies that do not require chemical derivatization have received widespread attention. Proteins may undergo denaturation, unfolding, and precipitation under different conditions such as high temperatures, extreme pH, denaturants, and mechanical stress. Binding to small-molecule drugs may alter the folding balance of target proteins. The conformational stability of target proteins can be stabilized by binding with drugs, and protein-drug complexes are more resistant than free proteins to the precipitation induced by different conditions. Based on this mechanism, various large-scale drug-target identification methods using protein precipitation have been developed by combining proteomics and mass spectrometry analysis, including thermal proteome profiling and solvent-, mechanical stress-, and pH-induced protein precipitation. These methods have been successfully applied to the characterization of small-molecule drug targets. In this review, we describe the protein precipitation-based methods used for the high-throughput discovery of drug targets and elucidation of the interactions between drugs and proteins in the past decade. We also summarize the characteristics of each method and discuss their application potential in drug-efficacy evaluation and drug discovery.