Associations between postoperative cognitive dysfunction, serum interleukin-6 and postoperative delirium among patients after coronary artery bypass grafting: A mediation analysis.

BACKGROUND: POCD is a common complication among patients who underwent coronary artery bypass graft (CABG), it is linked to loss of independence and reduced quality of life. AIMS AND OBJECTIVES: To examine the association between postoperative cognitive dysfunction (POCD), postoperative delirium (POD) and interleukin-6 (IL-6). DESIGN: A prospective cohort study. METHODS: Patients who underwent elective isolated CABG were enrolled. POCD was assessed by a set of cognitive function tools. Delirium was assessed using the CAM-ICU. The logistic regression analyses were used to identify the predictive value of POD or IL-6 on POCD. The path analysis was used to analyse the relationship among POD, IL-6 and POCD. RESULTS: A total of 212 patients were enrolled, with 25.0% of patients developing POD and 32.5% developing POCD. The multiple logistic regression analysis revealed that patients with POD had a four-fold increased hazard of POCD (OR = 3.655), and patients with IL-6 ≥ 830.50 pg/mL at the 6th hours after surgery had a 5-fold increased risk of experiencing POCD (OR = 5.042). However, the mediation effect of POD between IL-6 and POCD was not statistically significant (ß = 0.059, p = .392). CONCLUSIONS: POD and IL-6 at the 6th hour after surgery (≥830.50 pg/mL) are two potent predictors for POCD, while POD did not play a mediation effect between IL-6 and POCD. RELEVANCE TO CLINICAL PRACTICE: Early identification of risk factors (e.g., delirium assessment and testing for serum IL-6 levels) by clinical nurses for POCD may contribute to the clinical practice for the targeted prevention nursing strategies.

Functional role of P2X7 purinergic receptor in cancer and cancer-related pain.

Numerous studies have revealed that the ATP-gated ion channel purinergic 2X7 receptor (P2X7R) plays an important role in tumor progression and the pathogenesis of cancer pain. P2X7R requires activation by extracellular ATP to perform its regulatory role functions. During tumor development or cancer-induced pain, ATP is released from tumor cells or other cells in the tumor microenvironment (such as tumor-associated immune cells), which activates P2X7R, opens ion channels on the cell membrane, affects intracellular molecular metabolism, and regulates the activity of tumor cells. Furthermore, peripheral organs and receptors can be damaged during tumor progression, and P2X7R expression in nerve cells (such as microglia) is significantly upregulated, enhancing sensory afferent information, sensitizing the central nervous system, and inducing or exacerbating pain. These findings reveal that the ATP-P2X7R signaling axis plays a key regulatory role in the pathogenesis of tumors and cancer pain and also has a therapeutic role. Accordingly, in this study, we explored the role of P2X7R in tumors and cancer pain, discussed the pharmacological properties of inhibiting P2X7R activity (such as the use of antagonists) or blocking its expression in the treatment of tumor and cancer pain, and provided an important evidence for the treatment of both in the future.

Integrating transcriptomics and machine learning for immunotherapy assessment in colorectal cancer.

Colorectal cancer (CRC) is a highly prevalent and lethal malignancy worldwide. Although immunotherapy has substantially improved CRC outcomes, intolerance remains a major concern among most patients. Considering the pivotal role of the tumor microenvironment (TME) in tumor progression and treatment outcomes, profiling the TME at the transcriptomic level can provide novel insights for developing CRC treatment strategies. Seventy-seven TME-associated signatures were acquired from previous studies. To elucidate variations in prognosis, clinical features, genomic alterations, and responses to immunotherapy in CRC, we employed a non-negative matrix factorization algorithm to categorize 2595 CRC samples of 27 microarrays from the Gene Expression Omnibus database. Three machine learning techniques were employed to identify a signature specific to immunotherapy. Subsequently, the mechanisms by which this signature interacts with TME subtypes and immunotherapy were investigated. Our findings revealed five distinct TME subtypes (TMESs; TMES1-TMES5) in CRC, each exhibiting a unique pattern of immunotherapy response. TMES1, TMES4, and TMES5 had relatively inferior outcomes, TMES2 was associated with the poorest prognosis, and TMES3 had a superior outcome. Subsequent investigations revealed that activated dendritic cells could enhance the immunotherapy response rate, with their augmentation effect closely associated with the activation of CD8+T cells. We successfully classified CRC into five TMESs, each demonstrating varying response rates to immunotherapy. Notably, the application of machine learning to identify activated dendritic cells helped elucidate the underlying mechanisms contributing to these differences. We posit that these TMESs hold promising clinical implications for prognostic evaluation and guidance of immunotherapy strategies, thereby providing valuable insights to inform clinical decision-making.

Integrated proteogenomic and metabolomic characterization of papillary thyroid cancer with different recurrence risks.

Although papillary thyroid cancer (PTC) has a good prognosis, its recurrence rate is high and remains a core concern in the clinic. Molecular factors contributing to different recurrence risks (RRs) remain poorly defined. Here, we perform an integrative proteogenomic and metabolomic characterization of 102 Chinese PTC patients with different RRs. Genomic profiling reveals that mutations in MUC16 and TERT promoter as well as multiple gene fusions like NCOA4-RET are enriched by the high RR. Integrative multi-omics analyses further describe the multi-dimensional characteristics of PTC, especially in metabolism pathways, and delineate dominated molecular patterns of different RRs. Moreover, the PTC patients are clustered into four subtypes (CS1: low RR and BRAF-like; CS2: high RR and metabolism type, worst prognosis; CS3: high RR and immune type, better prognosis; CS4: high RR and BRAF-like) based on the omics data. Notably, the subtypes display significant differences considering BRAF and TERT promoter mutations, metabolism and immune pathway profiles, epithelial cell compositions, and various clinical factors (especially RRs and prognosis) as well as druggable targets. This study can provide insights into the complex molecular characteristics of PTC recurrences and help promote early diagnosis and precision treatment of recurrent PTC.

Molecular mechanism analyses of post-traumatic epilepsy and hereditary epilepsy based on 10× single-cell transcriptome sequencing technology.

BACKGROUND: Single-cell RNA sequencing analysis has been usually conducted on post-traumatic epilepsy (PET) and hereditary epilepsy (HE) patients; however, the transcriptome of patients with traumatic temporal lobe epilepsy has rarely been studied. MATERIALS AND METHODS: Hippocampus tissues isolated from one patient with PTE and one patient with HE were used in the present study. Single cell isolates were prepared and captured using a 10× Genomics Chromium Single-Cell 3' kit (V3) according to the manufacturer's instructions. The libraries were sequenced on an Illumina NovaSeq 6000 sequencing system. Raw data were processed, and the cells were filtered and classified using the Seurat R package. Uniform Manifold Approximation and Projection was used for visualization. Differentially expressed genes (DEGs) were identified based on a p-value ≤0.01 and log fold change (FC) ≥0.25. Gene Ontology (GO, http://geneontology.org/) and KEGG (Kyoto Encyclopedia of Genes and Genomes, www.genome.jp/kegg) analyses were performed on the DEGs for enrichment analysis. RESULTS: The reads obtained from the 10× genomic platform for PTE and HE were 39.56 M and 30.08 M, respectively. The Q30 score of the RNA reads was >91.6%. After filtering, 7479 PTE cells and 9357 HE cells remained for further study. More than 96.4% of the reads were mapped to GRCh38/GRCm38. The cells were differentially distributed in two groups, with higher numbers of oligodendrocytes (6522 vs. 2532) and astrocytes (133 vs. 52), and lower numbers of microglial cells (2242 vs. 3811), and neurons (3 vs. 203) present in the HE group than in the PTE group. The DEGs in four cell clusters were identified, with 25 being in oligodendrocytes (13 upregulated and 12 downregulated), 87 in microglia cells (42 upregulated and 45 downregulated), 222 in astrocytes (115 upregulated and 107 downregulated), and 393 in neurons (305 upregulated and 88 downregulated). The genes MTND1P23 (downregulated), XIST (downregulated), and RPS4Y1 (upregulated) were commonly expressed in all four cell clusters. The DEGs in microglial cells and astrocytes were enriched in the IL-17 signaling pathway. CONCLUSION: Our study explored differences in cells found in a patient with PE compared to a patient with HE, and the transcriptome in the different cells was analyzed for the first time. Studying inflammatory and immune functions might be the best approach for investigating traumatic temporal lobe epilepsy in neurons.

Clonal integration of stress signal induces morphological and physiological response of root within clonal network.

Clonal integration of defense or stress signal induced systemic resistance in leaf of interconnected ramets. However, similar effects of stress signal in root are poorly understood within clonal network. Clonal fragments of Centella asiaticas with first-young, second-mature, third-old and fourth-oldest ramets were used to investigate transportation or sharing of stress signal among interconnected ramets suffering from low water availability. Compared with control, oxidative stress in root of the first-young, second-mature and third-old ramets was significantly alleviated by exogenous ABA application to the fourth-oldest ramets as well as enhancement of antioxidant enzyme (SOD, POD, CAT and APX) activities and osmoregulation ability. Surface area and volume in root of the first-young ramets were significantly increased and total length in root of the third-old ramets was significantly decreased. POD activity in root of the fourth-oldest and third-old ramets was significantly enhanced by exogenous ABA application to the first-young ramets. Meanwhile, total length and surface area in root of the fourth-oldest and third-old ramets were significantly decreased. Ratio of belowground to aboveground biomass in the whole clonal fragments was significantly increased by exogenous ABA application to the fourth-oldest or first-young ramets. It is suggested that transportation or sharing of stress signal may induce systemic resistance in root of interconnected ramets. Specially, transportation or sharing of stress signal against phloem flow was observed in the experiment. Possible explanation is that rapid recovery of foliar photosynthesis in first-young ramets subjected to exogenous ABA application can partially reverse phloem flow within clonal network. Thus, our experiment provides insight into ecological implication on clonal integration of stress signal.

The effect of subjective exercise experience on anxiety disorder in university freshmen: the chain-mediated role of self-efficacy and interpersonal relationship.

Background: Anxiety disorder is a significant concern in the context of mental health among university students. This study aimed to examine the impact of subjective exercise experience on anxiety disorder in freshmen and verify the mediating role of self-efficacy and interpersonal relationships between them. Methods: A total of 1,308 Chinese freshmen underwent an investigation using the Subjective Exercise Experience Scale (SEES), Generalized Anxiety Disorder Scale (GAD-7), General Self-Efficacy Scale (GSES), and Interpersonal Relationship Comprehensive Diagnostic Scale (IRIDS). Results: The outcomes of this study are as follows: (1) Boys exhibited marginally greater performance in physical activity assessments compared to girls while displaying somewhat lower scores than girls in measures of anxiety disorders, self-efficacy, and interpersonal relationship tests. Of these, 63.39% were diagnosed with mild anxiety, 51.73% were diagnosed with moderate anxiety, and 10% were diagnosed with severe anxiety; (2) The subjective exercise experience had a significant negative correlation with an anxiety disorder (r = -0.36, p < 0.01), and the subjective exercise experience had a direct negative impact on anxiety disorder (ß = -0.112, t = -11.776, p < 0.01). Furthermore, subjective exercise experience positively predicted self-efficacy (ß = 0.125, t = 13.236, p < 0.01) and interpersonal relationship (ß = 0.395, t = 12.359, p < 0.01). Self-efficacy had a substantial impact on interpersonal relationships (ß = 0.724, t = 12.172, p < 0.01) and anxiety disorders (ß = -0.148, t = -8.387, p < 0.01). Interpersonal relationships had a significant positive predictive effect on anxiety disorder (ß = -0.081, t = -10.441, p < 0.01); (3) Self-efficacy and interpersonal relationships were identified as important mediators between subjective exercise experience and anxiety disorder. The intermediary effect accounted for 18.84% of the total effect. Specifically, subjective exercise had a direct impact on anxiety disorders through self-efficacy mediators (2.90%), interpersonal mediators (1.45%), and self-efficacy and interpersonal chain mediators (14.49%). Conclusion: Subjective exercise experience has a significant positive predictive effect on university students' self-efficacy, interpersonal relationships, and anxiety disorder. Moreover, self-efficacy and interpersonal interactions serve as intermediaries between subjective exercise experiences and anxiety disorders. These findings have immense importance in advancing the mental well-being of freshmen and serve as a theoretical foundation for formulating intervention strategies. However, the study had certain limitations, such as the specificity of the sample and the use of self-reported data. Further research could enhance the sample size and utilize various assessment techniques to validate these findings.

Structure-based prediction and characterization of photo-crosslinking in native protein-RNA complexes.

UV-crosslinking of protein and RNA in direct contacts has been widely used to study protein-RNA complexes while our understanding of the photo-crosslinking mechanisms remains poor. This knowledge gap is due to the challenge of precisely mapping the crosslink sites in protein and RNA simultaneously in their native sequence and structural contexts. Here we systematically analyze protein-RNA interactions and photo-crosslinking by bridging crosslinked nucleotides and amino acids mapped using different assays with protein-RNA complex structures. We developed a computational method PxR3D-map which reliably predicts crosslink sites using structural information characterizing protein-RNA interaction interfaces. Analysis of the informative features revealed that photo-crosslinking is facilitated by base stacking with not only aromatic residues, but also dipeptide bonds that involve glycine, and distinct mechanisms are utilized by different RNA-binding domains. Our work suggests protein-RNA photo-crosslinking is highly selective in the cellular environment, which can guide data interpretation and further technology development for UV-crosslinking-based assays.

Preliminary investigation on the analysis of the whole components of Pogejiuxin decoction and its formulation pattern based on ultrahigh-performance liquid chromatography with quadrupole time-of-flight mass spectrometry.

RATIONAL: Pogejiuxin decoction (PGJXD) is one of the most important formulas for the treatment of heart failure. However, there is a great lack of research on the material basis of this formula, especially research on its compatibility laws, which restricts its clinical use. Studying the complete ingredients and compatibility rules of PGJXD has great significance for guiding clinical medication. METHODS: The entire formula, the major single herbs, the drug pairs and the disassembled formula were analyzed by ultrahigh-performance liquid chromatography with quadrupole time-of-flight mass spectrometry (UHPLC/QTOFMS/MS), matching the chemical composition database and global natural product social molecular networking to explain the chemical composition as well as the combination pattern of PGJXD. RESULTS: A total of 1048 chemical constituents were fully analyzed from the major single herbs, the drug pairs and the disassembled formula and 188 chemical constituents, including 13 potential novel compounds, were firstly identified from the whole formula. We found that the chemical compositions were reduced after the single herbs were matched to the other herbs, especially the significant reduction of highly toxic diester alkaloids after compatibility, indicating that the medicines of PGJXD were interdependent and controlled by each other. CONCLUSION: This study innovatively researches and compares the compositional differences between the entire formula of PGJXD, the single, paired and separated formulas, greatly extending our understanding of the chemical substance basis of these compounds, and preliminarily explores the compatibility laws of PGJXD, providing some theoretical guidance for clinical medication.

Positive benefit-risk ratio of Psoraleae Fructus: Comprehensive safety assessment and osteogenic effects in rats.

ETHNOPHARMACOLOGICAL RELEVANCE: Psoraleae Fructus (PF), the dried fruit of Psoralea corylifolia L., is a commonly used traditional medicine that has contributed to the treatment of orthopedic diseases for thousands of years in China. However, recent PF-related liver injury reports have drawn widespread attention regarding its potential hepatotoxicity risks. AIM OF THE STUDY: This study was aimed to evaluate the long-term efficacy and chronic toxicity of PF using a 26-week administration experiment on rats in order to simulate the clinical usage situation. MATERIALS AND METHODS: The PF aqueous extract was consecutively administrated to rats daily at dosages of 0.7, 2.0, and 5.6 g/kg (equivalent to 1-8 times the clinical doses for humans) for as long as 26 weeks. Samples were collected after 13, 26, and 32 weeks (withdrawal for 6 weeks) since the first administration. The chronic toxicity of PF was evaluated by conventional toxicological methods, and the efficacy of PF was evaluated by osteogenic effects in the natural growth process. RESULTS: In our experiments, only the H group (5.6 g/kg) for 26-week PF treatment demonstrated liver or kidney injury, which the injuries were reversible after 6 weeks of withdrawal. Notably, the PF treatment beyond 13 weeks showed significant benefits for bone growth and development in rats, with a higher benefit-risk ratio in female rats. CONCLUSIONS: PF displayed a promising benefit-risk ratio in the treatment and prevention of osteoporosis, a disease that lacks effective medicine so far. This is the first study to elucidate the benefit-risk balance associated with clinical dosage and long-term use of PF, thereby providing valuable insights for rational clinical use and risk control of PF.

Chinese herbal medicine Ginkgo biloba L. preparations for ischemic stroke: An overview of systematic reviews and meta-analyses.

BACKGROUND: Ginkgo biloba L. preparations (GBLPs) are a class of Chinese herbal medicine used in the adjuvant treatment of ischemic stroke (IS). Recently, several systematic reviews (SRs) and meta-analyses (MAs) of GBLPs for IS have been published. OBJECTIVE: This overview aims to assess the quality of related SRs and MAs. SEARCH STRATEGY: PubMed, Embase, Cochrane Library, Web of Science, Chinese Biological Medicine, China National Knowledge Infrastructure, Wanfang, and Chinese Science and Technology Journals databases were searched from their inception to December 31, 2022. INCLUSION CRITERIA: SRs and MAs of randomized controlled trials (RCTs) that explored the efficacy of GBLPs for patients with IS were included. DATA EXTRACTION AND ANALYSIS: Two independent reviewers extracted data and assessed the methodological quality, risk of bias (ROB), reporting quality, and credibility of evidence of the included SRs and MAs using A Measurement Tool to Assess Systematic Reviews 2 (AMSTAR 2), Risk of Bias in Systematic Reviews (ROBIS), the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA), and the Grading of Recommendations Assessment, Development and Evaluation (GRADE), respectively. Additionally, descriptive analysis and data synthesis were conducted. RESULTS: Twenty-nine SRs/MAs involving 119 outcomes were included in this review. The overall methodological quality of all SRs/MAs was critically low based on AMSTAR 2, and 28 had a high ROB based on the ROBIS. According to the PRISMA statement, the reporting items of the included SRs/MAs are relatively complete. The results based on GRADE showed that of the 119 outcomes, 8 were rated as moderate quality, 24 as low quality, and 87 as very low quality. Based on the data synthesis, GBLPs used in conjunction with conventional treatment were superior to conventional treatment alone for decreasing neurological function scores. CONCLUSION: GBLPs can be considered a beneficial supplemental therapy for IS. However, because of the low quality of the existing evidence, high-quality RCTs and SRs/MAs are warranted to further evaluate the benefits of GBLPs for treating IS. Please cite this article as: Meng TT, You YP, Li M, Guo JB, Song XB, Ding JY, Xie XL, Li AQ, Li SJ, Yin XJ, Wang P, Wang Z, Wang BL, He QY. Chinese herbal medicine Ginkgo biloba L. preparations for ischemic stroke: An overview of systematic reviews and meta-analyses. J Integr Med. 2024;22(2): 163-179.

Serum electrolyte concentrations and risk of atrial fibrillation: an observational and mendelian randomization study.

BACKGROUND: Atrial fibrillation (AF) is a prevalent arrhythmic condition resulting in increased stroke risk and is associated with high mortality. Electrolyte imbalance can increase the risk of AF, where the relationship between AF and serum electrolytes remains unclear. METHODS: A total of 15,792 individuals were included in the observational study, with incident AF ascertainment in the Atherosclerosis Risk in Communities (ARIC) study. The Cox regression models were applied to calculate the hazard ratio (HR) and 95% confidence interval (CI) for AF based on different serum electrolyte levels. Mendelian randomization (MR) analyses were performed to examine the causal association. RESULTS: In observational study, after a median 19.7 years of follow-up, a total of 2551 developed AF. After full adjustment, participants with serum potassium below the 5th percentile had a higher risk of AF relative to participants in the middle quintile. Serum magnesium was also inversely associated with the risk of AF. An increased incidence of AF was identified in individuals with higher serum phosphate percentiles. Serum calcium levels were not related to AF risk. Moreover, MR analysis indicated that genetically predicted serum electrolyte levels were not causally associated with AF risk. The odds ratio for AF were 0.999 for potassium, 1.044 for magnesium, 0.728 for phosphate, and 0.979 for calcium, respectively. CONCLUSIONS: Serum electrolyte disorders such as hypokalemia, hypomagnesemia and hyperphosphatemia were associated with an increased risk of AF and may also serve to be prognostic factors. However, the present study did not support serum electrolytes as causal mediators for AF development.

Availability and threshold of the vasoactive-inotropic score for predicting early extubation in adults after rheumatic heart valve surgery: a single-center retrospective cohort study.

BACKGROUND: Early extubation (EEx) is defined as the removal of the endotracheal tube within 8 h postoperatively. The present study involved determining the availability and threshold of the vasoactive-inotropic score (VIS) for predicting EEx in adults after elective rheumatic heart valve surgery. METHODS: The present study was designed as a single-center retrospective cohort study which was conducted with adults who underwent elective rheumatic heart valve surgery with CPB. The highest VIS in the immediate postoperative period was used in the present study. The primary outcome, the availability of VIS for EEx prediction and the optimal threshold value were determined using ROC curve analysis. The gray zone analysis of the VIS was performed by setting the false negative or positive rate R = 0.05, and the perioperative risk factors for prolonged EEx were identified by multivariate logistic analysis. The postoperative complications and outcomes were compared between different VIS groups. RESULTS: Among the 409 patients initially screened, 379 patients were ultimately included in the study. The incidence of EEx was determined to be 112/379 (29.6%). The VIS had a good predictive value for EEx (AUC = 0.864, 95% CI: [0.828, 0.900], P < 0.001). The optimal VIS threshold for EEx prediction was 16.5, with a sensitivity of 71.54% (65.85-76.61%) and a specificity of 88.39% (81.15-93.09%). The upper and lower limits of the gray zone for the VIS were determined as (12, 17.2). The multivariate logistic analysis identified age (OR, 1.060; 95% CI: 1.017-1.106; P = 0.006), EF% (OR, 0.798; 95% CI: 0.742-0.859; P < 0.001), GFR (OR, 0.933; 95% CI: 0.906-0.961; P < 0.001), multiple valves surgery (OR, 4.587; 95% CI: 1.398-15.056; P = 0.012), and VIS > 16.5 (OR, 12.331; 95% CI: 5.015-30.318; P < 0.001) as the independent risk factors for the prolongation of EEx. The VIS ≤ 16.5 group presented a greater success rate for EEx, a shorter invasive ventilation support duration, and a lower incidence of complications than did the VIS > 16.5 group, while the incidence of reintubation was similar between the two groups. CONCLUSION: In adults, after elective rheumatic heart valve surgery, the highest VIS in the immediate postoperative period was a good predictive value for EEx, with a threshold of 16.5.

MRI quantitative assessment of the effects of low-carbohydrate therapy on Hashimoto's thyroiditis.

Objective: Hashimoto's thyroiditis is an inflammatory disease, and research suggests that a low-carbohydrate diet may have potential anti-inflammatory effects. This study aims to utilize Dixon-T2-weighted imaging (WI) sequence for a semi-quantitative assessment of the impact of a low-carbohydrate diet on the degree of thyroid inflammation in patients with Hashimoto's thyroiditis. Methods: Forty patients with Hashimoto's thyroiditis were recruited for this study and randomly divided into two groups: one with a normal diet and the other with a low-carbohydrate diet. Antibodies against thyroid peroxidase (TPOAb) and thyroglobulin (TgAb) were measured for all participants. Additionally, thyroid water content was semi-quantitatively measured using Dixon-T2WI. The same tests and measurements were repeated for all participants after 6 months. Results: After 6 months of a low-carbohydrate diet, patients with Hashimoto's thyroiditis showed a significant reduction in thyroid water content (94.84 ± 1.57% vs 93.07 ± 2.05%, P < 0.05). Concurrently, a decrease was observed in levels of TPOAb and TgAb (TPOAb: 211.30 (92.63-614.62) vs 89.45 (15.9-215.67); TgAb: 17.05 (1.47-81.64) vs 4.1 (0.51-19.42), P < 0.05). In contrast, there were no significant differences in thyroid water content or TPOAb and TgAb levels for patients with Hashimoto's thyroiditis following a normal diet after 6 months (P < 0.05). Conclusion: Dixon-T2WI can quantitatively assess the degree of thyroid inflammation in patients with Hashimoto's thyroiditis. Following a low-carbohydrate diet intervention, there is a significant reduction in thyroid water content and a decrease in levels of TPOAb and TgAb. These results suggest that a low-carbohydrate diet may help alleviate inflammation in patients with Hashimoto's thyroiditis.

Preoperative anemia: impact on short- and long-term outcomes following curative-intent resection of gastroenteropancreatic neuroendocrine tumors.

BACKGROUND: The effect of preoperative anemia on clinical outcomes of patients undergoing resection of gastroenteropancreatic neuroendocrine tumors (GEP-NETs) has not been previously investigated. This study aimed to characterize how preoperative anemia affected short- and long-term outcomes of patients undergoing curative-intent resection of GEP-NETs. METHODS: Patients who underwent curative-intent resection for GEP-NETs between January 1990 and December 2020 were identified from 8 major institutions. The last preoperative hemoglobin level was recorded; anemia was defined as <13.5 g/dL in males or <12.0 g/dL in females based on the guides of the American Society of Hematology. The effect of anemia on postoperative outcomes was assessed on uni- and multivariate analyses. RESULTS: Among 1559 patients, the median age was 58 years (IQR, 48-66), and roughly one-half of the cohort was male (796 [51.1%]). Most patients had a pancreatic tumor (1040 [66.7%]), followed by small bowel (259 [16.6%]), duodenum (103 [6.6%]), stomach (66 [4.2%]), appendix (53 [3.4%]), and other locations (38 [2.6%]). The median preoperative hemoglobin level was 13.4 g/dL (IQR, 12.2-14.5). Overall, 101 (6.7%) and 119 (8.5%) patients received an intra- or postoperative packed red blood cell (pRBC) transfusion, respectively. A total of 972 patients (44.5%) experienced a postoperative complication. Although the overall incidence of complications was no different among patients who did (anemic: 48.7%) vs patients who did not (nonanemic: 47.3%) have anemia (P = .597), patients with preoperative anemia were more likely to develop a major (Clavien-Dindo grade ≥IIIa: 48.9% [anemic] vs 38.0% [nonanemic]; P = .006) and multiple (≥3 types of complications: 32.2% [anemic] vs 19.7% [anemic]; P < .001) complications. Of note, 1-, 3-, and 5-year overall survival (OS) rates were 96.7%, 90.5%, and 86.6%, respectively. On multivariable analysis, anemia (hazard ratio, 2.0; 95% CI, 1.2-3.2; P = .006) remained associated with worse OS; postoperative pRBC transfusion was associated with an OS (5-year OS: 75.0% vs 87.7%; P = .017) and recurrence-free survival (RFS; 5-year RFS: 66.9% vs 76.5%; P = .047). CONCLUSION: Preoperative anemia was commonly identified in roughly 1 in 3 patients who underwent curative-intent resection for GEP-NETs. Preoperative anemia was strongly associated with a higher risk of postoperative morbidity and worse long-term outcomes.

Eugenol Inhibits Ox-LDL-Induced Proliferation and Migration of Human Vascular Smooth Muscle Cells by Inhibiting the Ang II/MFG-E8/MCP-1 Signaling Cascade.

Objective: In this study, we investigated the effect and mechanism of action of eugenol on oxidized low-density lipoprotein (ox-LDL)-induced abnormal proliferation and migration of human vascular smooth muscle cells (HVSMCs). Methods: HVSMCs were treated with 100 ug/mL ox-LDL for 24 hours to establish a cell model. After 1-hour pretreatment, eugenol at concentrations of 5, 25, and 50 uM was added. Cell viability was assessed using an MTT assay, PCNA expression was detected using Western blot, cell cycle distribution was analyzed using flow cytometry, and cell migration ability was evaluated using wound healing and Transwell migration assays. To investigate the mechanisms, Ang II receptors were inhibited by 1000 nM valsartan, MFG-E8 was knocked down by shRNA, MCP-1 was inhibited by siRNA, and MFG-E8 was overexpressed using plasmids. Results: The findings from this study elucidated the stimulatory impact of ox-LDL on the proliferation and functionality of HVSMCs. Different concentrations of eugenol effectively mitigated the enhanced activity of HVSMCs induced by ox-LDL, with 50 uM eugenol exhibiting the most pronounced inhibitory effect. Flow cytometry and Western blot results showed ox-LDL reduced G1 phase cells and increased PCNA expression, while 50 uM eugenol inhibited ox-LDL-induced HVSMC proliferation. In wound healing and Transwell migration experiments, the ox-LDL group showed larger cell scratch filling and migration than the control group, both of which were inhibited by 50 uM eugenol. Inhibiting the Ang II/MFG-E8/MCP-1 signaling cascade mimicked eugenol's effects, while MFG-E8 overexpression reversed eugenol's inhibitory effect. Conclusion: Eugenol can inhibit the proliferation and migration of ox-LDL-induced HVSMCs by inhibiting Ang II/MFG-E8/MCP-1 signaling cascade, making it a potential therapeutic drug for atherosclerosis.

Identification and Regulation of Hypoxia-Tolerant and Germination-Related Genes in Rice.

In direct seeding, hypoxia is a major stress faced by rice plants. Therefore, dissecting the response mechanism of rice to hypoxia stress and the molecular regulatory network is critical to the development of hypoxia-tolerant rice varieties and direct seeding of rice. This review summarizes the morphological, physiological, and ecological changes in rice under hypoxia stress, the discovery of hypoxia-tolerant and germination-related genes/QTLs, and the latest research on candidate genes, and explores the linkage of hypoxia tolerance genes and their distribution in indica and japonica rice through population variance analysis and haplotype network analysis. Among the candidate genes, OsMAP1 is a typical gene located on the MAPK cascade reaction for indica-japonica divergence; MHZ6 is involved in both the MAPK signaling and phytohormone transduction pathway. MHZ6 has three major haplotypes and one rare haplotype, with Hap3 being dominated by indica rice varieties, and promotes internode elongation in deep-water rice by activating the SD1 gene. OsAmy3D and Adh1 have similar indica-japonica varietal differentiation, and are mainly present in indica varieties. There are three high-frequency haplotypes of OsTPP7, namely Hap1 (n = 1109), Hap2 (n = 1349), and Hap3 (n = 217); Hap2 is more frequent in japonica, and the genetic background of OsTPP7 was derived from the japonica rice subpopulation. Further artificial selection, natural domestication, and other means to identify more resistance mechanisms of this gene may facilitate future research to breed superior rice cultivars. Finally, this study discusses the application of rice hypoxia-tolerant germplasm in future breeding research.

Angiosperm-wide analysis of fruit and ovary evolution aided by a new nuclear phylogeny supports association of the same ovary type with both dry and fleshy fruits.

Fruit functions in seed protection and dispersal and belongs to many dry and fleshy types, yet their evolutionary pattern remains unclear in part due to uncertainties in the phylogenetic relationships among several orders and families. Thus we used nuclear genes of 502 angiosperm species representing 231 families to reconstruct a well supported phylogeny, with resolved relationships for orders and families with previously uncertain placements. Using this phylogeny as a framework, molecular dating supports a Triassic origin of the crown angiosperms, followed by the emergence of most orders in the Jurassic and Cretaceous and their rise to ecological dominance during the Cretaceous Terrestrial Revolution. The robust phylogeny allowed an examination of the evolutionary pattern of fruit and ovary types, revealing a trend of parallel carpel fusions during early diversifications in eudicots, monocots, and magnoliids. Moreover, taxa in the same order or family with the same ovary type can develop either dry or fleshy fruits with strong correlations between specific types of dry and fleshy fruits; such associations of ovary, dry and fleshy fruits define several ovary-fruit "modules" each found in multiple families. One of the frequent modules has an ovary containing multiple ovules, capsules and berries, and another with an ovary having one or two ovules, achenes (or other single-seeded dry fruits) and drupes. This new perspective of relationships among fruit types highlights the closeness of specific dry and fleshy fruit types, such as capsule and berry, that develop from the same ovary type and belong to the same module relative to dry and fleshy fruits of other modules (such as achenes and drupes). Further analyses of gene families containing known genes for ovary and fruit development identified phylogenetic nodes with multiple gene duplications, supporting a possible role of whole-genome duplications, in combination with climate changes and animal behaviors, in angiosperm fruit and ovary diversification.

Visible Light-Driven SnIn4S8 Photocatalyst Decorated on Polyurethane-Impregnated Microfiber Non-Woven Fabric for Pollutant Degradation.

In recent years, polyurethane has drawn great attention because of its many advantages in physical and chemical performance. In this work, firstly, polyurethane was impregnated in a non-woven fabric (NWF). Then, polyurethane-impregnated NWF was coagulated utilizing a wet phase inversion. Finally, after alkali treatment, microfiber non-woven fabrics with a porous polyurethane matrix (PNWF) were fabricated and used as substrates. SnIn4S8 (SIS) prepared by a microwave-assisted method was used as a photocatalyst and a novel SIS/PNWF substrate with multiple uses and highly efficient catalytic degradation ability under visible light was successfully fabricated. The surface morphology, chemical and crystal structures, optical performance, and wettability of SIS/PNWF substrates were observed. Subsequently, the photocatalytic performance of SIS/PNWF substrates was investigated by the decomposition of rhodamine B (RhB) under visible light irradiation. Compared with SIS/PNWF-2% (2%, the weight ratio of SIS and PNWF, same below), SIS/PNWF-5% as well as SIS/PNWF-15%, SIS/PNWF-10% substrates exhibited superior photocatalytic efficiency of 97% in 2 h. This may be due to the superior photocatalytic performance of SIS and the inherent hierarchical porous structure of PNWF substrates. Additionally, the hydrophobicity of SIS/PNWF substrates can enable them to float on the solution and further be applied on an open-water surface. Furthermore, tensile strength and recycle experiments demonstrated that SIS/PNWF substrates possessed superior mechanical strength and excellent recycle stability. This work provides a facile and efficient pathway to prepare SIS/PNWF substrates for the degradation of organic pollutants with enhanced catalytic efficiency.