Effects of N, N-bis (carboxymethyl)-L-glutamic acid and polyaspartic acid on the phytoremediation of cadmium in contaminated soil at the presence of pyrene: Biochemical properties and transcriptome analysis.

Chelator-assisted phytoremediation is an efficacious method for promoting the removal efficiency of heavy metals (HMs). The effects of N, N-bis(carboxymethyl)-L-glutamic acid (GLDA) and polyaspartic acid (PASP) on Cd uptake and pyrene removal by Solanum nigrum L. (S. nigrum) were compared in this study. Using GLDA or PASP, the removal efficiency of pyrene was over 98%. And PASP observably raised the accumulation and transport of Cd by S. nigrum compared with GLDA. Meanwhile, both GLDA and PASP markedly increased soil dehydrogenase activities (DHA) and microbial activities. DHA and microbial activities in the PASP treatment group were 1.05 and 1.06 folds of those in the GLDA treatment group, respectively. Transcriptome analysis revealed that 1206 and 1684 differentially expressed genes (DEGs) were recognized in the GLDA treatment group and PASP treatment group, respectively. Most of the DEGs found in the PASP treatment group were involved in the metabolism of carbohydrates, the biosynthesis of brassinosteroid and flavonoid, and they were up-regulated. The DEGs related to Cd transport were screened, and ABCG3, ABCC4, ABCG9 and Nramp5 were found to be relevant with the reduction of Cd stress in S. nigrum by PASP. Furthermore, with PASP treated, transcription factors (TFs) related to HMs such as WRKY, bHLH, AP2/ERF, MYB were down-regulated, while more MYB and bZIP TFs were up-regulated. These TFs associated with plant stress resistance would work together to induce oxidative stress. The above results indicated that PASP was more conducive for phytoremediation of Cd-pyrene co-contaminated soil than GLDA.

Monocytes to lymphocytes multiplying platelets ratio as an early indicator of acute kidney injury in cardiac surgery with cardiopulmonary bypass: a retrospective analysis.

OBJECTIVE: The monocyte-to-lymphocyte multiplying platelets ratio (MLPR) is a novel systemic inflammatory marker, deriving from the monocyte-to-lymphocyte ratio (MLR). However, the link between MLPR and acute kidney injury following cardiac surgery (CSA-AKI) with cardiopulmonary bypass (CPB) has not been investigated yet. We comprehensively explored the potential linear and nonlinear relationship between MLPR or MLR and CSA-AKI. METHODS: Data of patients who underwent cardiac surgery with CPB between December 2018 and April 2021 were retrospectively collected at Fuwai Hospital, Beijing, China. MLPR was defined as monocyte count (×109/L) × 1000/(lymphocyte count (×109/L) × platelets (×109/L)). MLR was defined as monocyte count (×109/L)/lymphocyte count (×109/L). Logistic regression and restricted cubic spline (RCS) were used for linear and nonlinear analysis. The primary outcome was postoperative AKI within 48 h of after cardiac surgery. RESULTS: Of the 2420 patients screened, 2387 eligible patients were enrolled in the final analysis; the mean age was 54.7 years, and 1501 [62.9%] were men. The incidence of AKI was 25.8%. Logistic regression showed that MLPR (odds ratio [OR] = 1.31, 95% confidence interval [CI]: 1.16-1.48, p < .001) and MLR (OR = 3.06, 95% CI: 1.29-7.29, p = .012) were independent risk factors for AKI. Moreover, in the RCS model with adjustment for age (median: 56), female sex, and history of diabetes, a significant statistical difference was detected between preoperative MLPR, MLR, and AKI (p for non-linearity <.001). The subgroup analyses revealed similar results. CONCLUSIONS: The study revealed a nonlinear relationship between MLPR and MLR with AKI. MLPR exhibited a J-shaped curve, and MLR showed a favorable S-shaped curve in relation to AKI. Particularly, MLPR emerges as a promising clinical composite index for early CSA-AKI prediction. These findings emphasize the significance of MLPR as a valuable tool in clinical practice for timely identification and management of CSA-AKI.

Development and validation of a machine learning predictive model for perioperative myocardial injury in cardiac surgery with cardiopulmonary bypass.

BACKGROUND: Perioperative myocardial injury (PMI) with different cut-off values has showed to be associated with different prognostic effect after cardiac surgery. Machine learning (ML) method has been widely used in perioperative risk predictions during cardiac surgery. However, the utilization of ML in PMI has not been studied yet. Therefore, we sought to develop and validate the performances of ML for PMI with different cut-off values in cardiac surgery with cardiopulmonary bypass (CPB). METHODS: This was a second analysis of a multicenter clinical trial (OPTIMAL) and requirement for written informed consent was waived due to the retrospective design. Patients aged 18-70 undergoing elective cardiac surgery with CPB from December 2018 to April 2021 were enrolled in China. The models were developed using the data from Fuwai Hospital and externally validated by the other three cardiac centres. Traditional logistic regression (LR) and eleven ML models were constructed. The primary outcome was PMI, defined as the postoperative maximum cardiac Troponin I beyond different times of upper reference limit (40x, 70x, 100x, 130x) We measured the model performance by examining the area under the receiver operating characteristic curve (AUROC), precision-recall curve (AUPRC), and calibration brier score. RESULTS: A total of 2983 eligible patients eventually participated in both the model development (n = 2420) and external validation (n = 563). The CatboostClassifier and RandomForestClassifier emerged as potential alternatives to the LR model for predicting PMI. The AUROC demonstrated an increase with each of the four cutoffs, peaking at 100x URL in the testing dataset and at 70x URL in the external validation dataset. However, it's worth noting that the AUPRC decreased with each cutoff increment. Additionally, the Brier loss score decreased as the cutoffs increased, reaching its lowest point at 0.16 with a 130x URL cutoff. Moreover, extended CPB time, aortic duration, elevated preoperative N-terminal brain sodium peptide, reduced preoperative neutrophil count, higher body mass index, and increased high-sensitivity C-reactive protein levels were identified as risk factors for PMI across all four cutoff values. CONCLUSIONS: The CatboostClassifier and RandomForestClassifer algorithms could be an alternative for LR in prediction of PMI. Furthermore, preoperative higher N-terminal brain sodium peptide and lower high-sensitivity C-reactive protein were strong risk factor for PMI, the underlying mechanism require further investigation.

Leaching potentials of microplastic fibers and UV stabilizers from coastal-littered face masks.

Synthetic fibrous textiles are ubiquitous plastic commodities in everyday existence. Nevertheless, there exists a dearth of understanding regarding their environmental occurrence and the releasing capacities of associated additives. In this study, ten additives were determined in twenty-eight kinds of daily used plastic products including face masks, synthetic clothing, and food containers. Our results revealed that a typical kind of fibrous plastic, face masks, contained a greater variety of additives with UV stabilizers in particular, when compared to other plastic commodities. The above phenomena triggered our field investigation for the occurrence and release potentials of face mask fibers and the co-existing UV stabilizers into the environment. We further collected 114 disposed masks from coastal areas and analyzed their UV stabilizer concentrations. Results showed that the abundance of littered face masks ranged from 40-1846 items/km2 along the Yangtze Estuary, China; and UV stabilizers were of 0.3 ± 0.7 ng/g and 0.7 ± 1.7 ng/g in main bodies and ear ropes, respectively. The UV stabilizer concentrations in the field collected masks were only ∼7 % of their new counterparts, implying their potential leaching after disposal. By simulating the weathering scenario, we predict that a substantial amount of microplastics, with 1.1 × 1010 polypropylene fibers and 3.7 × 1010 polyester fibers, are probably be released daily into the coastal environment after face masks disposal; whereas the accompanied leaching amount of UV stabilizers was relatively modest under the current scenario.

Hybrid feature selection in a machine learning predictive model for perioperative myocardial injury in noncoronary cardiac surgery with cardiopulmonary bypass.

BACKGROUND: Perioperative myocardial injury (PMI) is associated with increased mobility and mortality after noncoronary cardiac surgery. However, limited studies have developed a predictive model for PMI. Therefore, we used hybrid feature selection (FS) methods to establish a predictive model for PMI in noncoronary cardiac surgery with cardiopulmonary bypass (CPB). METHODS: This was a single-center retrospective study conducted at the Fuwai Hospital in China. Patients aged 18-70 years who underwent elective noncoronary surgery with CPB at our institution from December 2018 to April 2021 were enrolled. The primary outcome was PMI, defined as the postoperative cardiac troponin I (cTnI) levels exceeding 220 times of upper reference limit (URL). Statistical analyses were conducted by Python (Python Software Foundation, version 3.9.7 and integrated development environment Jupyter Notebook 1.1.0) and SPSS software version 26.0 (IBM Corp., Armonk, New York, USA). RESULTS: A total of 1130 patients were eventually eligible for this study. The incidence of PMI was 20.3% (229/1130) in the overall patients, 20.6% (163/791) in the training dataset, and 19.5% (66/339) in the testing dataset. The logistic regression model performed the best AUC of 0.6893 (95 CI%: 0.6371-0.7382) by the traditional selection method, and the random forest model performed the best AUC of 0.6937 (95 CI%: 0.6416-0.7423) by the union of Wrapper and Embedded method, and the CatBoost model performed the best AUC of 0.6828 (95 CI%: 0.6304-0.7320) by the union of Embedded and forward logistic regression technique, and the Naïve Bayes model achieved the best AUC with 0.7254 (95 CI%: 0.6746-0.7723) by forwarding logistic regression method. Moreover, the decision tree, KNeighborsClassifier, and support vector machine models performed the worse AUC in all selection forms. Furthermore, the SHapley Additive exPlanations plot showed that prolonged CPB, aortic clamp time, and preoperative low platelets count were strongly related to the PMI risk. CONCLUSIONS: In total, four category feature selection methods were utilized, comprising five individual selection techniques and 15 combined methods. Notably, the combination of logistic regression and embedded methods demonstrated outstanding performance in predicting PMI risk. We also concluded that the machine learning model, including random forest, catboost, and Naive Bayes, were suitable candidates for establishing PMI predictive model. Nevertheless, additional investigation and validation are imperative for substantiating these finding.

Effect of Perioperative Nicorandil on Myocardial Protection in Patients Undergoing Cardiac Surgery with Cardiopulmonary Bypass, a Retrospective Study.

Background: The potential myocardial protective effect of nicorandil (NICD) in patients undergoing percutaneous coronary intervention has been established. However, its efficacy in the context of cardiac surgery remains controversial. The present study aimed to evaluate the myocardial protective effect of perioperative NICD use in patients undergoing cardiac surgery with cardiopulmonary bypass (CPB). Methods: We retrospectively gathered data from patients undergoing cardiac bypass surgery between 12/2018 and 04/2021 in Fuwai Hospital. Subsequently, the patients were divided into two groups, NICD group and non-nicorandil (non-NICD) group. A 1, 3 propensity score matching (PSM) was conducted. The primary outcome was the incidence of myocardial injury. The secondary outcomes included the mechanical ventilation (MV) duration, intensive care unit (ICU) length of stay (LOS), hospital LOS, duration of chest drainage, the drainage volume, the total cost, the incidence of acute kidney injury (AKI), and the incidence of acute liver injury (ALI). Subsequently, we divided the entire population into two distinct subgroups based on their administration of NICD, and performed a comprehensive subgroup analysis. Results: A total of 2406 patients were ultimately included in the study. After PSM, 250 patients in NICD group and 750 patients in non-NICD group were included in the analysis. Perioperative NICD reduced the incidence of myocardial injury (47.2% versus 38.8%, P=0.025). Our subgroup analysis revealed that preoperative NICD administration not only provided myocardial protection benefits (45.7% vs 35.8%, OR 0.66, 95% CI [0.45-0.97], P=0.041), but also demonstrated statistically significant reduction in ALI, the ICU and hospital LOS, and the duration of chest drainage (all P<0.05). Conclusion: The perioperative NICD administration may confer myocardial protection in patients undergoing cardiac surgery with CPB. Furthermore, the preoperative utilization of NICD has the potential to mitigate the incidence of postoperative ALI, a reduction in the ICU and hospital LOS, and the duration of chest drainage.

Development and validation of a machine learning prediction model for perioperative red blood cell transfusions in cardiac surgery.

OBJECTIVE: Several machine learning (ML) models have been used in perioperative red blood cell (RBC) transfusion risk for cardiac surgery with limited generalizability and no external validation. Hence, we sought to develop and comprehensively externally validate a ML model in a large dataset to estimate RBC transfusion in cardiac surgery with cardiopulmonary bypass (CPB). DESIGN: A retrospective analysis of a multicenter clinical trial (NCT03782350). PATIENTS: The study patients who underwent cardiac surgery with CPB came from four cardiac centers in China and Medical Information Mart for Intensive Cared (MIMIC-IV) dataset. MEASUREMENTS: Data from Fuwai Hospital were used to develop an individualized prediction model for RBC transfusion. The model was externally validated in the data from three other centers and MIMIC-IV dataset. Twelve models were constructed. MAIN RESULTS: A total of 11,201 eligible patients were included in the model development (2420 in Fuwai Hospital) and external validation (563 in the other three centers and 8218 in the MIMIC-IV dataset). A significant difference was observed between the Logistic Regression and CatboostClassifier (0.72 Vs. 0.74, P = 0.031) or RandomForestClassifier (0.72 Vs. 0.75 p = 0.012) in the external validation and MIMIV-IV datasets (age ≤ 70:0.63 Vs. 0.71, p < 0.001; age > 70:0.63 Vs. 0.70, 0.63 Vs. 0.71, p < 0.001). The CatboostClassifier and RandomForestClassifier model was comparable in development (0.83 Vs. 0.82, p = 0.419), external (0.74 Vs. 0.75, p = 0.268), and MIMIC-IV datasets (age ≤ 70: 0.71 Vs. 0.71, p = 0.574; age > 70: 0.70 Vs. 0.71, p = 0.981). Of note, they outperformed other ML models with excellent discrimination and calibration. The CatboostClassifier and RandomForestClassifier models achieved higher area under precision-recall curve and lower brier loss score in validation and MIMIC-IV datasets. Additionally, we confirmed that low preoperative hemoglobin, low body mass index, old age, and female sex increased the risk of RBC transfusion. CONCLUSIONS: In our study, enrolling a broad range of cardiovascular surgeries with CPB and utilizing a restrictive RBC transfusion strategy, robustly validates the generalizability of ML algorithms for predicting RBC transfusion risk. Notably, the CatboostClassifier and RandomForestClassifier exhibit strong external clinical applicability, underscoring their potential for widespread adoption. This study provides compelling evidence supporting the efficacy and practical value of ML-based approaches in enhancing transfusion risk prediction in clinical practice.

Activation of mitochondrial DNA-mediated cGAS-STING pathway contributes to chronic postsurgical pain by inducing type I interferons and A1 reactive astrocytes in the spinal cord.

Chronic postsurgical pain (CPSP) is increasingly recognized as a public health issue. Recent studies indicated the innate immune pathway of cyclic guanosine monophosphate-adenosine monophosphate synthase (cGAS)-stimulator of interferon genes (STING) was involved in pain regulation. However, the detailed mechanisms remain unclear. Previous studies found A1 reactive astrocytes in the spinal cord contributed to CPSP. This study aimed to investigate the roles and mechanisms of the cGAS-STING pathway in regulating the generation of A1 reactive astrocytes during CPSP. First, CPSP model was established using skin/muscle incision and retraction (SMIR) in rats. We found that cGAS-STING pathway was activated accompanied with an increase in mitochondrial DNA in the cytosol in the spinal cord following SMIR. Second, a STING inhibitor C-176 was intrathecally administrated. We found that C-176 decreased the expression of type I interferons and A1 reactive astrocytes in the spinal cord, and alleviated mechanical allodynia in SMIR rats. Third, cyclosporin A as a mitochondrial permeability transition pore blocker was intrathecally administrated. We found that cyclosporin A decreased the leakage of mitochondrial DNA and inhibited the activation of cGAS-STING pathway. Compared with C-176, cyclosporin A exhibits similar analgesic effects. The expression of type I interferons and A1 reactive astrocytes in the spinal cord were also down-regulated after intervention with cyclosporin A. Moreover, simultaneous administration of cyclosporin A and C-176 did not show synergistic effects in SMIR rats. Therefore, our study demonstrated that the cGAS-STING pathway activated by the leakage of mitochondrial DNA contributed to chronic postsurgical pain by inducing type I interferons and A1 reactive astrocytes in the spinal cord.

The bidirectional roles of the cGAS-STING pathway in pain processing: Cellular and molecular mechanisms.

Pain is a common clinical condition. However, the mechanisms underlying pain are not yet fully understood. It is known that the neuroimmune system plays a critical role in the pathogenesis of pain. Recent studies indicated that the cyclic-GMP-AMP synthase-stimulator of interferon genes (cGAS-STING) pathway can activate the innate immune system by sensing both extrinsic and intrinsic double-stranded DNA in the cytoplasm, which is involved in pain processing. In this review, we summarise (1) the roles of the cGAS-STING pathway in different pain models, (2) the effect of the cGAS-STING pathway in different cells during pain regulation, and (3) the downstream molecular mechanisms of the cGAS-STING pathway in pain regulation. This review provides evidence that the cGAS-STING pathway has pro- and anti-nociceptive effects in pain models. It has different functions in neuron, microglia, macrophage, and T cells. Its downstream molecules include IFN-I, NF-κB, NLRP3, and eIF2α. The bidirectional roles of the cGAS-STING pathway in pain processing are mediated by regulating nociceptive neuronal sensitivity and neuroinflammatory responses. However, their effects in special brain regions, activation of astrocytes, and the different phases of pain require further exploration.

Sciatic Nerve Block Combined with Flurbiprofen Inhibits Spinal Cord Inflammation and Improves Postoperative Pain in Rats with Plantar Incision.

Background and Purpose: Peripheral nerve block is often used to relieve postoperative pain. But the effect of nerve block on inflammatory response is not fully understood. Spinal cord is the primary center of pain processing. This study is to investigate the effect of single sciatic nerve block on the inflammatory response of the spinal cord in rats with plantar incision and the combined effect with flurbiprofen. Methods: The plantar incision was used to establish a postoperative pain model. Single sciatic nerve block, intravenous flurbiprofen or the combination of both were used for intervention. The sensory and motor functions after nerve block and incision were evaluated. The changes of IL-1ß, IL-6, TNF-α, microglia and astrocytes in the spinal cord were examined by qPCR and immunofluorescence respectively. Results: Sciatic nerve block with 0.5% ropivacaine in rats induced sensory block for 2h and motor block for 1.5h. In the rats with plantar incision, the single sciatic nerve block did not alleviate postoperative pain or inhibit the activation of spinal microglia and astrocytes, but the levels of IL-1ß and IL-6 in spinal cord were decreased when the nerve block wore off. The combined effect of a single sciatic nerve block and intravenous flurbiprofen not only decreased the levels of IL-1ß, IL-6, and TNF-α, but also relieved the pain and alleviated the activation of microglia and astrocytes. Conclusion: The single sciatic nerve block cannot improve postoperative pain or inhibit the activation of spinal cord glial cells, but can reduce the expression of spinal inflammatory factors. Nerve block combined with flurbiprofen can inhibit spinal cord inflammation and improve postoperative pain. This study provides a reference for rational clinical application of nerve block.

Development and Validation of a Machine Learning Predictive Model for Cardiac Surgery-Associated Acute Kidney Injury.

OBJECTIVE: We aimed to develop and validate a predictive machine learning (ML) model for cardiac surgery associated with acute kidney injury (CSA-AKI) based on a multicenter randomized control trial (RCT) and a Medical Information Mart for Intensive Care-IV (MIMIC-IV) dataset. METHODS: This was a subanalysis from a completed RCT approved by the Ethics Committee of Fuwai Hospital in Beijing, China (NCT03782350). Data from Fuwai Hospital were randomly assigned, with 80% for the training dataset and 20% for the testing dataset. The data from three other centers were used for the external validation dataset. Furthermore, the MIMIC-IV dataset was also utilized to validate the performance of the predictive model. The area under the receiver operating characteristic curve (ROC-AUC), the precision-recall curve (PR-AUC), and the calibration brier score were applied to evaluate the performance of the traditional logistic regression (LR) and eleven ML algorithms. Additionally, the Shapley Additive Explanations (SHAP) interpreter was used to explain the potential risk factors for CSA-AKI. RESULT: A total of 6495 eligible patients undergoing cardiopulmonary bypass (CPB) were eventually included in this study, 2416 of whom were from Fuwai Hospital (Beijing), for model development, 562 from three other cardiac centers in China, and 3517 from the MIMICIV dataset, were used, respectively, for external validation. The CatBoostClassifier algorithms outperformed other models, with excellent discrimination and calibration performance for the development, as well as the MIMIC-IV, datasets. In addition, the CatBoostClassifier achieved ROC-AUCs of 0.85, 0.67, and 0.77 and brier scores of 0.14, 0.19, and 0.16 in the testing, external, and MIMIC-IV datasets, respectively. Moreover, the utmost important risk factor, the N-terminal brain sodium peptide (NT-proBNP), was confirmed by the LASSO method in the feature section process. Notably, the SHAP explainer identified that the preoperative blood urea nitrogen level, prothrombin time, serum creatinine level, total bilirubin level, and age were positively correlated with CSA-AKI; preoperative platelets level, systolic and diastolic blood pressure, albumin level, and body weight were negatively associated with CSA-AKI. CONCLUSIONS: The CatBoostClassifier algorithms outperformed other ML models in the discrimination and calibration of CSA-AKI prediction cardiac surgery with CPB, based on a multicenter RCT and MIMIC-IV dataset. Moreover, the preoperative NT-proBNP level was confirmed to be strongly related to CSA-AKI.

High accumulation of microplastic fibers in fish hindgut induces an enhancement of triphenyl phosphate hydroxylation.

Fiber shedding from artificial textiles is among the primary sources of pervasive microplastics in various aquatic habitats. To avoid molten drop burning, triphenyl phosphate (TPhP), a typical flame retardant additive, is commonly incorporated into textile fibers. However, the role of microplastic fibers (MFs) as a vehicle for TPhP remains largely unknown. In this study, we investigated the effects of MFs on the bioaccumulation and metabolism of TPhP in zebrafish. We applied the compound spinning technique for a non-disruptive in situ measurement of fluorescent MFs in fish, and the desorption electrospray ionization mass spectrometry (DESI-MS) to display the tissue distribution of TPhP and its metabolites vividly. Laboratory results showed that ingested MFs did not change the TPhP distribution in fish; however, they statistically increased the metabolite p-OH-TPhP concentration in the fish hindgut, which was probably because the high accumulation of MFs there enhanced the TPhP hydroxylation. Field investigation further supported the lab-based analyses. Higher concentrations of MFs did cause a higher ratio of [p-OH-TPhP]/[TPhP] in the wild fish gut, particularly in the hindgut. Collectively, our results demonstrated that MFs can change the distribution and bioavailability of TPhP metabolites, which was confirmed by both laboratory and fieldwork. Therefore, the ingestion of MFs can indirectly but substantially influence the bioaccumulation and biotransformation of co-existing pollutants.

Total Syntheses of Calyciphylline A-Type Alkaloids (-)-10-Deoxydaphnipaxianine A, (+)-Daphlongamine E and (+)-Calyciphylline R via Late-Stage Divinyl Carbinol Rearrangements.

Among the famous Daphniphyllum alkaloids family, the calyciphylline A-type subfamily has triggered particular interest from the organic synthesis community in recent years. Here, we report divergent total syntheses of three calyciphylline A-type alkaloids, namely, (-)-10-deoxydaphnipaxianine A, (+)-daphlongamine E, and (+)-calyciphylline R. Our work highlights an efficient, divergent strategy via late-stage divinyl carbinol rearrangements, including an unprecedented oxidative Nazarov electrocyclization using an unfunctionalized tertiary divinyl carbinol and an unusual allylic alcohol rearrangement. A highly efficient "donor-acceptor" platinum catalyst was used for a critical nitrile hydration step. Moreover, the power of selective amide reductions has also been showcased by novel and classic tactics.

Incidence, risk factors, and outcomes in electroencephalographic seizures after mechanical circulatory support: A systematic review and meta-analysis.

Purpose: To estimate the overall incidence, risk factors, and clinical outcomes of electroencephalographic (EEG) seizures for adults and children after mechanical circulatory support (MCS). Method and measurements: This systematic review and meta-analysis were carried out in accordance with the PRISMA (Preferred Reporting Items for Systematic Review and Meta-Analysis) guidance document. MEDLINE EMBASE and CENTRAL were investigated for relevant studies. The related information was retrieved by two independent reviewers and all analyses were conducted by STATA (version 16.0; Stata Corporation, College Station, TX, United States). Result: Sixty studies including 36,191 adult and 55,475 pediatric patients with MCS were enrolled for evaluation. The study showed that the overall incidence of EEG seizures in adults was 2% (95%CI: 1-3%), in which 1% (95%CI: 1-2%) after cardiopulmonary bypass (CPB), and 3% (95%CI: 1-6%) after extracorporeal membrane oxygenation (ECMO). For pediatrics patients, the incidence of EEG seizures was 12% (95%CI: 11-14%), among which 12% (9-15%) after CPB and 13% (11-15%) after ECMO. The major risk factors of EEG seizures after MCS in adults were redo surgery (coefficient = 0.0436, p = 0.044), and COPD (coefficient = 0.0749, p = 0.069). In addition, the gestational week of CPB (coefficient = 0.0544, p = 0.080) and respiratory failure of ECMO (coefficient = -0.262, p = 0.019) were also indicated to be associated with EEG seizures in pediatrics. Conclusion: EEG seizures after MCS were more common in pediatrics than in adults. In addition, the incidence of EEG seizure after ECMO was higher than CPB both in adults and children. It is expected that appropriate measures should be taken to control modifiable risk factors, thus improving the prognosis and increasing the long-term survival rate of MCS patients. Systematic Review Registration: [https://www.crd.york.ac.uk/prospero], identifier [CRD42021287288].

Naples prognostic score: a novel predictor of survival in patients with HER2-positive breast cancer.

Purpose: The predictive significance of the Naples prognostic score (NPS) in HER2-positive breast cancer is unclear. Hence we sought to evaluate the relationship between NPS and the clinical outcomes in HER2-positive breast cancer patients. Methods: This study retrospectively collected and analyzed data from 173 HER2-positive breast cancer patients between August 2004 and February 2014. The Cox regression model was applied in univariate and multivariate statistical analysis. Results: In multivariate analysis, increased NPS score correlated significantly with poor overall survival (p = 0.001) and disease-free survival (p < 0.001). Conclusion: Our findings may point to NPS being a novel and reliable prognostic score system with favorable predictive ability for HER2-positive breast cancer patients.

Breast cancer is one of the most frequent cancers in females and the second leading cause of death among women worldwide. HER2-positive breast cancer has the characteristics of rapid growth, high risk of relapse and cancer migration and spreading. The predictive significance of the Naples prognostic score (NPS) in HER2-positive breast cancer is unknown. We hypothesized that NPS may improve prediction of outcomes in HER2-positive patients. A statistical analysis was conducted. Our results revealed that NPS was an independent predictive factor of overall survival and disease-free survival in patients with HER2-positive breast cancer.

Total Synthesis of Daphniphyllum Alkaloids: From Bicycles to Diversified Caged Structures.

Native to the Asia-Pacific region and widely applied in traditional Chinese medicine, the genus Daphniphyllum has produced over 330 known Daphniphyllum alkaloids. Investigations into these alkaloids have shown an exceptional range of interesting bioactivities. Challenging and caged polycyclic architectures and the promising biological profiles make Daphniphyllum alkaloids intriguing synthetic targets. Based on their backbones, these alkaloids can be categorized into 13-35 structurally distinct subfamilies. In addition to our work, almost 30 impressive total syntheses of Daphniphyllum alkaloids from seven subfamilies, namely, daphniphylline-type, secodaphniphylline-type, daphnilactone A-type, bukittinggine-type, daphmanidin A-type, calyciphylline A-type, and calyciphylline B-type alkaloids, have been reported by 11 research groups. However, many Daphniphyllum alkaloid subfamilies remain inaccessible by chemical synthesis.In this Account, we summarize our recent endeavors in the total synthesis of Daphniphyllum alkaloids commencing from simple chiral bicyclic synthons. Daphniphyllum alkaloids with diversified skeletons from four different subfamilies, namely, calyciphylline A-type, daphnezomine A-type, bukittinggine-type, and yuzurimine-type alkaloids, have been achieved. Furthermore, the tricyclic core structure of daphniglaucin C-type alkaloids daphnimacropodines was also synthesized. First, we describe a 14-step synthesis of calyciphylline A-type alkaloid (-)-himalensine A, which features a mild Cu-mediated nitrile hydration, an intramolecular Heck reaction to assemble the pivotal 2-azabicyclo[3.3.1]nonane moiety, and a Meinwald rearrangement to introduce the critical oxidative state into the skeleton. We then introduce the synthesis of daphnezomine A-type alkaloid dapholdhamine B, which possesses a unique aza-adamantane core. This target molecule was fabricated using key reactions including Huang's amide-activation-annulation. An unexpected radical detosylation during the synthesis of dapholdhamine B further inspired an ambitious radical cyclization cascade strategy, which eventually led to an efficient total synthesis of bukittinggine-type alkaloid (-)-caldaphnidine O. This highly chemo-, regio-, and stereoselective radical reaction cascade also shed light on the synthetic strategy of other alkaloids with caged structures. We next describe the first total synthesis of yuzurimine-type alkaloid (+)-caldaphnidine J. The key steps in our approach include a Pd-catalyzed regioselective hydroformylation and a novel Swern oxidation/ketene dithioacetal Prins reaction cascade. The work has achieved the first synthesis of a member of the largest subfamily of Daphniphyllum alkaloids. Finally, we show our efforts toward the total synthesis of daphniglaucin C-type alkaloids. Overall, we hope that the interesting strategies and synthetic methods demonstrated in our efforts could inspire a wide variety of additional applications to natural product synthesis.

A fluorescein-gold nanoparticles probe based on inner filter effect and aggregation for sensing of biothiols.

Cysteine (Cys), homocysteine (HCys) and glutathione (GSH) are sulfhydryl-containing amino acids known as biothiols being able to bind to gold nanoparticles (AuNPs) via sulfhydryl group, resulting in the aggregation of AuNPs. Owning to their inner filter effect, AuNPs can weaken or even quench the fluorescence of fluorescein. However, the introduction of biothiols to fluorescein-AuNPs leads to the recovery of fluorescein fluorescence. Thus, a simple and reliable turn on fluorescence method was developed for monitoring biothiols with fluorescein-AuNPs as a probe. Several factors, including AuNPs concentration, pH value and incubation time, which might influence the fluorescence reclamation of fluorescein-AuNPs probe, were optimized by taking Cys as an example at room temperature. Under the optimal conditions, sensitive sensing of Cys, HCys and GSH was achieved. The detection limits for Cys, GSH, and HCys were 0.027, 0.023, and 0.030µΜ, respectively. This method was used to the determination of Cys in human serum samples with high precision and accuracy, indicating the potential of the method in practical applications with simple operation, good accuracy and high sensitivity.

Asymmetric total synthesis of yuzurimine-type Daphniphyllum alkaloid (+)-caldaphnidine J.

Ever since Hirata's report of yuzurimine in 1966, nearly fifty yuzurimine-type alkaloids have been isolated, which formed the largest subfamily of the Daphniphyllum alkaloids. Despite extensive synthetic studies towards this synthetically challenging and biologically intriguing family, no total synthesis of any yuzurimine-type alkaloids has been achieved to date. Here, the first enantioselective total synthesis of (+)-caldaphnidine J, a highly complex yuzurimine-type Daphniphyllum alkaloid, is described. Key transformations of this approach include a highly regioselective Pd-catalyzed hydroformylation, a samarium(II)-mediated pinacol coupling, and a one-pot Swern oxidation/ketene dithioacetal Prins reaction. Our approach paves the way for the synthesis of other yuzurimine-type alkaloids and related natural products.

Switch on fluorescence mode for determination of l-cysteine with carbon quantum dots and Au nanoparticles as a probe.

Citric acid and urea were used as precursors for the preparation of carbon quantum dots (CQDs) which exhibited a maximum emission wavelength at 515 nm when excited at 410 nm. Upon addition of citrate-stabilized Au nanoparticles (AuNPs) with the maximum absorption wavelength at 520 nm, the fluorescence of the CQDs could be efficiently quenched, attributed to the energy transfer between CQDs and AuNPs. However, the further introduction of l-cysteine (Cys) could cause the aggregation of AuNPs along with a drop in absorption at 520 nm, resulting in the fluorescence recovery of the CQDs-AuNPs system. Therefore, a simple and reliable switch on fluorescence sensing platform for determination of Cys was constructed. The significant factors, such as pH and incubation time, that affected the detection of Cys were optimized with the AuNP concentration set as 2.50 nM at room temperature. Under the optimized conditions, the fluorescence recoveries (ΔF) were strongly correlated with Cys concentration in the 0.20 to 4.0 µM range, and the detection limit is 0.012 µM. More importantly, our CQD-based sensing platform was successfully used for the detection of Cys in milk samples with high precision and accuracy, indicating the potential of the probe in practical applications.

Synthesis of the Core Structure of Daphnimacropodines.

Daphniphyllum alkaloids daphnimacropodines A-C possess a highly congested ring system and share a common tetracyclic ring skeleton. To access the challenging chemical structure of daphnimacropodines, a divergent synthetic approach toward their total synthesis is described. A stereoselective synthesis of the core structure of daphnimacropodines has been achieved from a simple diketone building block. Our approach features an intramolecular carbamate aza-Michael addition and a hydropyrrole synthesis via a Au-catalyzed alkyne hydration followed by an aldol condensation, whereas all the other attempts failed.