Bioinspired Heterocoordination in Adaptable Cobalt Metal-Organic Framework for DNA Epigenetic Modification Detection.

Metal-organic frameworks (MOFs) show unique advantages in simulating the dynamics and fidelity of natural coordination. Inspired by zinc finger protein, a second linker was introduced to affect the homogeneous MOF system and thus facilitate the emergence of diverse functionalities. Under the systematic identification of 12 MOF species (i.e., metal ions, linkers) and 6 second linkers (trigger), a dissipative system consisting of Co-BDC-NO2 and o-phenylenediamine (oPD) was screened out, which can rapidly and in situ generate a high photothermal complex (η = 36.9%). Meanwhile, both the carboxylation of epigenetic modifications and metal ion (Fe3+, Ni2+, Cu2+, Zn2+, Co2+ and Mn2+) screening were utilized to improve the local coordination environment so that the adaptable Co-MOF growth on the DNA strand was realized. Thus, epigenetic modification information on DNA was converted to an amplified metal ion signal, and then oPD was further introduced to generate bimodal dissipative signals by which a simple, high-sensitivity detection strategy of 5-hydroxymethylcytosine (LOD = 0.02%) and 5-formylcytosine (LOD = 0.025‰) was developed. The strategy provides one low-cost method (< 0.01 $/sample) for quantifying global epigenetic modifications, which greatly promotes epigenetic modification-based early disease diagnosis. This work also proposes a general heterocoordination design concept for molecular recognition and signal transduction, opening a new MOF-based sensing paradigm.

Overexpression of COX7A1 Promotes the Resistance of Gastric Cancer to Oxaliplatin and Weakens the Efficacy of Immunotherapy.

Gastric cancer (GC) is one of the most common clinical malignant tumors worldwide, with high morbidity and mortality. Presently, the overall response rate to immunotherapy is low, and current methods for predicting the prognosis of GC are not optimal. Therefore, novel biomarkers with accuracy, efficiency, stability, performance ratio and wide clinical application are needed. Based on public data sets, the Chemotherapy Cohort and the Immunotherapy Cohort from Sun Yat-sen University Cancer Center, a series of bioinformatics analyses, such as differential expression analysis, survival analysis, drug sensitivity prediction, enrichment analysis, tumor immune dysfunction and exclusion (TIDE) analysis, single-sample gene set enrichment analysis (ssGSEA), stemness index calculation, immune cell infiltration analysis, were performed for screening and preliminary exploration. Immunohistochemical staining and in vitro experiments were performed for further verification. Overexpression of COX7A1 promoted the resistance of GC cells to Oxaliplatin. COX7A1 may induce immune escape by regulating the number of fibroblasts and their cellular communication with immune cells. In summary, measuring the expression levels of COX7A1 in the clinic may be useful to predict the prognosis of GC patients, the degree of chemotherapy resistance and the efficacy of immunotherapy.

Engineering an Organic Nanoplatform for Augmented Pyroeletroimmunotherapy.

Photothermal immunotherapy has shown great promise in the treatment of tumor metastasis. However, the thermal resistance of tumor cells substantially compromises the treatment effect of photothermal immunotherapy. Herein, a high-performance organic pyroelectric nanoplatform, tBu-TPAD-BF2 nanoparticles (NPs), is rationally engineered for the effective pyroelectroimmunotherapy of tumor metastasis. Biocompatible tBu-TPAD-BF2 NPs with excellent pyroelectric and photothermal conversion properties are constructed by assembling organic, low-bandgap pyroelectric molecules with amphiphilic polymers. After internalization by tumor cells, treatment with tBu-TPAD-BF2 NPs causes an apparent temperature elevation upon near-infrared (NIR) laser irradiation, inducing potent immunogenic cell death (ICD). Additionally, the temperature variations under alternating NIR laser irradiation facilitate reactive oxygen species production for pyroelectric therapy, thus promoting ICD activation and lowering thermal resistance. Importantly, in vivo assessments illustrate that tBu-TPAD-BF2 NPs in combination with NIR laser exposure notably inhibit primary and distant tumor proliferation and prominently retarded lung metastasis. RNA profiling reveals that treatment with tBu-TPAD-BF2 NPs markedly suppresses metastasis under NIR laser illumination by downregulating metastasis-related genes and upregulating immune response-associated pathways. Therefore, this study provides a strategy for designing high-performance pyroelectric nanoplatforms to effectively cure tumor metastasis, thereby overcoming the inherent shortcomings of photothermal immunotherapy.

Synchronous papillary and follicular thyroid carcinomas: the first retrospective cohort study and literature review.

Background: Papillary thyroid carcinoma (PTC) and follicular thyroid carcinoma (FTC) contribute to more than 95% of thyroid malignancies. However, synchronous PTC and FTC are less common; it is most commonly discovered incidentally as synchronous malignancies during operation, which adds difficulties to intraoperative decision-making and postoperative treatment. Therefore, we analyzed the clinicopathological characteristics and prognosis of patients with PTC and FTC in our center. Methods: We conducted a search of single PTC, single FTC, and synchronous PTC/FTC patients who received initial surgery treatment at Fudan University Shanghai Cancer Center from 2006 to 2018 and collected paraffin-embedded samples of synchronous patients. Clinicopathological characteristics were collected from the electronic medical record system. Follow-up was performed through telephone contact or medical records. Exome sequencing was performed by ThyroLead panel. Results: Total of 42 synchronous PTC/FTC patients, 244 single FTC patients, and 2,959 single PTC patients were included. It showed a similarity between the clinicopathological features of synchronous thyroid cancer patients and single PTC patients, with a greater proportion of females, higher probabilities of lymph node metastasis, and higher rate of concurrence of Hashimoto's disease. The disease-free survival (DFS) curve indicated a worse prognosis of the synchronous group and single PTC group compared to the single FTC group, who had a propensity for neck lymph node recurrence; however, logistic multivariate regression analysis did not find any factor related to recurrence in the synchronous group. After re-checking pathology, DNA extraction, and quality control, genetic alteration information of 62 samples including primary tumors and metastatic lymph nodes from 35 synchronous cancer patients was displayed. In total, 81 mutations and 1 fusion gene were identified, including mutations related to outcomes and targeted therapy. Besides, some rare mutations in thyroid cancer were found in these patients. Conclusions: To conclude, synchronous PTC/FTC tend to be incidentally discovered during or after operation, behaving more like single PTC. The prognosis of synchronous patients is worse than that of single FTC patients and supplemental cervical lymph node dissection, total thyroidectomy, and postoperative radioiodine therapy should be taken into consideration after diagnosis. The next-generation sequencing (NGS) showed a unique molecular feature of synchronous patients with some rare mutations.

Profiling and optimized extraction of bioactive polyphenolic compounds from young, red-fleshed apple using eco-friendly deep eutectic solvents.

Red-fleshed apple cultivars with an enhanced content of polyphenolic compounds have attracted increasing interest due to their promising health benefits. Here, we have analysed the polyphenolic content of young, red-fleshed apples (RFA) and optimised extraction conditions of phenolics by utilising natural deep eutectic solvents (NDES). We also compare the antioxidant, neuroprotective and antimicrobial activities of NDES- and methanol-extracted phenolics from young RFA. High-performance liquid chromatography coupled to high-resolution mass spectrometry (HPLC-HRMS) was used for phenolics identification and quantification. Besides young RFA, ripe red-fleshed, young and ripe white-fleshed apples were analysed, revealing that young RFA possess the highest phenolic content (2078.4 ± 4.0 mg gallic acid equivalent/100 g), and that ripe white-fleshed apples contain the least amount of phenolics (545.0 ± 32.0 mg gallic acid equivalent/100 g). The NDES choline chloride-glycerol containing 40 % w/w H2O gave similar yields at 40 °C as methanol. In addition, the polyphenolics profile, and bioactivities of the NDES extract from young RFA were comparable that of methanol extracts. Altogether, our data show that NDES extracts of young RFA are a promising source of bioactive polyphenolics with potential applications in diverse sectors, e.g., for functional food production, smart material engineering and natural therapies.

Development and validation of a nomogram to predict postoperative delirium in older patients after major abdominal surgery: a retrospective case-control study.

BACKGROUND: Postoperative delirium is a common complication in older patients, with poor long-term outcomes. This study aimed to investigate risk factors and develop a predictive model for postoperative delirium in older patients after major abdominal surgery. METHODS: This study retrospectively recruited 7577 patients aged ≥ 65 years who underwent major abdominal surgery between January 2014 and December 2018 in a single hospital in Beijing, China. Patients were divided into a training cohort (n = 5303) and a validation cohort (n = 2224) for univariate and multivariate logistic regression analyses and to build a nomogram. Data were collected for 43 perioperative variables, including demographics, medical history, preoperative laboratory results, imaging, and anesthesia information. RESULTS: Age, chronic obstructive pulmonary disease, white blood cell count, glucose, total protein, creatinine, emergency surgery, and anesthesia time were associated with postoperative delirium in multivariate analysis. We developed a nomogram based on the above 8 variables. The nomogram achieved areas under the curve of 0.731 and 0.735 for the training and validation cohorts, respectively. The discriminatory ability of the nomogram was further assessed by dividing the cases into three risk groups (low-risk, nomogram score < 175; medium-risk, nomogram score 175~199; high-risk, nomogram score > 199; P < 0.001). Decision curve analysis revealed that the nomogram provided a good net clinical benefit. CONCLUSIONS: We developed a nomogram that could predict postoperative delirium with high accuracy and stability in older patients after major abdominal surgery.

Efficacy of Huoxue Qianyang Qutan Recipe on essential hypertension: A randomized, double-blind, placebo-controlled trial.

BACKGROUND: Hypertension, a prevalent disease, is a significant risk factor for coronary heart disease. Huoxue Qianyang Qutan Recipe (HQQR), a traditional Chinese herbal remedy, has been used for treating hypertension over several years. OBJECTIVE: This study assesses HQQR's efficacy for controlling blood pressure among patients with hypertension related to blood stasis, yang hyperactivity and phlegm. DESIGN, SETTING, PARTICIPANTS AND INTERVENTIONS: A randomized controlled trial was conducted at the Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, China, from July 2020 to June 2022. Major components of HQQR were identified using thin-layer chromatography and high-performance liquid chromatography. Participants aged 18-80 years, exhibiting traditional Chinese medicine syndromes of blood stasis, yang hyperactivity or phlegm, along with grades 1 or 2 hypertension, were randomly categorized into two groups. The intervention group was given HQQR granules alongside conventional hypertension treatment, while the control group was given placebo granules in addition to conventional treatment for 12 weeks. MAIN OUTCOME MEASURES: The primary outcome was clinic blood pressure, whereas secondary outcomes included metabolic indices (e.g., homeostasis model assessment of insulin resistance [HOMA-IR], total cholesterol [TC], low-density lipoprotein cholesterol and triglyceride), target organ damage indices (left ventricular mass index and urinary albumin creatinine ratio [UACR]) and inflammation indices (interleukin-6 [IL-6] and high-sensitivity C-reactive protein [hs-CRP]). RESULTS: HQQR's primary components were identified as salvianolic acid B, emodin and ferulic acid. Of the 216 participants (108 in each group), compared to the control, the intervention group exhibited significant improvements (P < 0.001) in clinic systolic blood pressure ([136.24 ± 7.63] vs [130.06 ± 8.50] mmHg), clinic diastolic blood pressure ([84.34 ± 8.72] vs [80.46 ± 6.05] mmHg), home systolic blood pressure ([131.64 ± 8.74] vs [122.36 ± 8.45] mmHg) and home diastolic blood pressure ([78.47 ± 9.53] vs [71.79 ± 6.82] mmHg). HQQR demonstrated a reduction in ambulatory blood pressure (24-hour systolic blood pressure: [133.75 ± 10.49] vs [132.46 ± 8.84] mmHg and 24-hour diastolic blood pressure: [84.12 ± 8.01] vs [82.11 ± 7.45] mmHg) and an improvement in HOMA-IR ([4.09 ± 1.72] vs [3.98 ± 1.44]), TC ([4.66 ± 1.47] vs [3.75 ± 1.81] mmol/L) and UACR (75.94 [5.12, 401.12] vs 45.61 [4.26, 234.26]). Moreover, HQQR demonstrated a decrease in hs-CRP (1.46 [0.10, 10.53] vs 0.57 [0.12, 3.99] mg/L) and IL-6 (6.69 [2.00, 29.74] vs 5.27 [2.00, 9.73] pg/mL), with no reported side effects (P < 0.001). CONCLUSION: This study highlights the therapeutic potential of HQQR use in ameliorating blood pressure, glycolipid metabolism, and inflammation in patients with hypertension. TRIAL REGISTRATION: ChiCTR2000035092 (https://www.chictr.org.cn/). Please cite this article as: Xie J, Ma YL, Gui MT, Yao L, Li JH, Wang MZ, Zhou XJ, Wang YF, Zhao MY, Cao H, Lu B, Fu DY. Efficacy of Huoxue Qianyang Qutan Recipe on essential hypertension: A randomized, double-blind, placebo-controlled trial. J Integr Med. 2024; Epub ahead of print.

Molecular structure and characterization of the Thermochromatium tepidum light-harvesting 1 photocomplex produced in a foreign host.

Purple phototrophic bacteria possess light-harvesting 1 and reaction center (LH1-RC) core complexes that play a key role in converting solar energy to chemical energy. High-resolution structures of LH1-RC and RC complexes have been intensively studied and have yielded critical insight into the architecture and interactions of their proteins, pigments, and cofactors. Nevertheless, a detailed picture of the structure and assembly of LH1-only complexes is lacking due to the intimate association between LH1 and the RC. To study the intrinsic properties and structure of an LH1-only complex, a genetic system was constructed to express the Thermochromatium (Tch.) tepidum LH1 complex heterologously in a modified Rhodospirillum rubrum mutant strain. The heterologously expressed Tch. tepidum LH1 complex was isolated in a pure form free of the RC and exhibited the characteristic absorption properties of Tch. tepidum. Cryo-EM structures of the LH1-only complexes revealed a closed circular ring consisting of either 14 or 15 αß-subunits, making it the smallest completely closed LH1 complex discovered thus far. Surprisingly, the Tch. tepidum LH1-only complex displayed even higher thermostability than that of the native LH1-RC complex. These results reveal previously unsuspected plasticity of the LH1 complex, provide new insights into the structure and assembly of the LH1-RC complex, and show how molecular genetics can be exploited to study membrane proteins from phototrophic organisms whose genetic manipulation is not yet possible.

Survival and disease burden analyses of occupational pneumoconiosis during 1958-2021 in Huangshi city, China: a retrospective cohort study.

BACKGROUND: Pneumoconiosis, a chronic disease stemming from prolonged inhalation of dust particles, stands as a significant global burden of occupational diseases. This study aims to investigate the survival outcomes of pneumoconiosis patients in Huangshi city, China, while also evaluating the disease burden on afflicted patients. METHODS: Data for this study were sourced from the Huangshi Center for Disease Control and Prevention. Survival analyses of pneumoconiosis patients were conducted employing life tables and the Kaplan-Meier method. The Cox proportional hazards models were deployed to identify factors influencing pneumoconiosis patients' survival duration. Competing risks models were employed to confirm the validity of the model outcomes. Additionally, in the disease burden assessment, disability-adjusted life years (DALYs) were computed for various demographic groups and time frames. RESULTS: A total of 5,641 pneumoconiosis cases, diagnosed in Huangshi City, Hubei Province between 1958 and 2021, were incorporated into the cohort analysis. The probability of mortality and the risk ratio increased with advancing age. Notably, the median survival time of stage III pneumoconiosis patients was significantly shorter compared with those in stages I and II. The Cox proportional hazards model and competing risks analyses underscored several significant factors influencing survival time, including dust exposure duration (HR = 1.197, 95% CI: 1.104-1.298), age at first diagnosis (HR = 3.149, 95% CI: 2.961-3.349), presence of silicosis (HR = 1.378, 95% CI: 1.254-1.515), and stage II-III pneumoconiosis (HR = 1.456, 95% CI: 1.148-1.848). Cumulatively, DALYs amounted to 7,974.35 person-years, with an average of 1.41 person-years. The period between 2000 and 2019 witnessed the highest disease burden. CONCLUSION: Our findings highlight the urgent need for improved prevention, earlier detection, and more effective management strategies for the occupational pneumoconiosis population. This study not only underscores the persistent issue of pneumoconiosis in industrial environments but also serves as a crucial call to action for policymakers and healthcare providers.

Near-death experiences after cardiac arrest: a scoping review.

BACKGROUND: This scoping review aimed to characterise near-death experiences in the setting of cardiac arrest, a phenomenon that is poorly understood and may have clinical consequences. METHOD: PubMed/MEDLINE was searched to 23 July 2023 for prospective studies describing near-death experiences in cardiac arrest. PRISMA-ScR guidelines were adhered to. Qualitative and quantitative data were synthesised. Meta-analysis was precluded due to data heterogeneity. RESULTS: 60 records were identified, of which 11 studies involving interviews were included from various countries. Sample size ranged from 28-344, and proportion of female patients (when reported) was 0-50%, with mean age (when reported) ranging 54-64 years. Comorbidities and reasons for cardiac arrest were heterogeneously reported. Incidence of near-death experiences in the included studies varied from 6.3% to 39.3%; with variation between in-hospital (6.3-39.3%) versus out-of-hospital (18.9-21.2%) cardiac arrest. Individual variables regarding patient characteristics demonstrated statistically significant association with propensity for near-death experiences. Reported content of near-death experiences tended to reflect the language of the questionnaires used, rather than the true language used by individual study participants. Three studies conducted follow-up, and all suggested a positive life attitude change, however one found significantly higher 30-day all-cause mortality in patients with near-death experiences versus those without, in non-controlled analysis. CONCLUSIONS: From prospective studies that have investigated the phenomenon, near-death experiences may occur in as frequent as over one-third of patients with cardiac arrest. Lasting effects may follow these events, however these could also be confounded by clinical characteristics.

Advancing Integration of Direct C-H Arylation-Derived Star-Shaped Oligomers as Second Acceptors for Ternary Organic Solar Cells.

Organic solar cells (OSCs) could benefit from the ternary bulk heterojunction (BHJ), a method that allows for fine-tuning of light capture, cascade energy levels, and film shape, in order to increase their power conversion efficiency (PCE). In this work, the third components of PM6:Y6 and PM6:BTP-eC9 BHJs are a set of four star-shaped unfused ring electron acceptors (SSUFREAs), i.e., BD-IC, BFD-IC, BD-2FIC, and BFD-2FIC, that are facilely synthesized by direct C-H arylation. The four SSUFREAs all show complete complementary absorption with PM6, Y6, and BTP-eC9, which facilitates light harvesting and exciton collection. When BFD-2FIC is added as a third component, the PCEs of PM6:Y6 and PM6:BTP-eC9 binary BHJs are able to be improved from 15.31% to 16.85%, and from 16.23% to 17.23%, respectively, showing that BFD-2FIC is useful for most effective ternary OSCs in general, and increasing short circuit current (JSC) and better film morphology are two additional benefits. The ternary PM6:Y6:BFD-2FIC exhibits a 9.7% percentage of increase in PCE compared to the PM6:Y6 binary BHJ, which is one of the highest percentage increases among the reported ternary BHJs, showing the huge potential of BFD-2FIC for ternary BHJ OSCs.

A novel fluorescence platform for specific detection of tetracycline antibiotics based on [MQDA-Eu3+] system.

Tetracycline antibiotics (TCs) are extensively used in clinical medicine, animal husbandry, and aquaculture because of their cost-effectiveness and high antibacterial efficacy. However, the presence of TCs residues in the environment poses risks to humans. In this study, an inner filter effect (IFE) fluorescent probe, 2,2'-(ethane-1,2-diylbis((2-((2-methylquinolin-8-yl)amino)-2-oxoethyl)azanediyl))diacetic acid (MQDA), was developed for the rapid detection of Eu3+ within 30 s. And its complex [MQDA-Eu3+] was successfully used for the detection of TCs. Upon coordination of a carboxyl of MQDA with Eu3+ to form a [MQDA-Eu3+] complex, the carboxyl served as an antenna ligand for the effective detection of Eu3+ to intensify the emission intensity of MQDA via "antenna effect", the process was the energy absorbed by TCs via UV excitation was effectively transferred to Eu3+. Fluorescence quenching of the [MQDA-Eu3+] complex was caused by the IFE in multicolor fluorescence systems. The limits of detection of [MQDA-Eu3+] for oxytetracycline, chlorotetracycline hydrochloride, and tetracycline were 0.80, 0.93, and 1.7 µM in DMSO/HEPES (7:3, v/v, pH = 7.0), respectively. [MQDA-Eu3+] demonstrated sensitive detection of TCs in environmental and food samples with satisfactory recoveries and exhibited excellent imaging capabilities for TCs in living cells and zebrafish with low cytotoxicity. The proposed approach demonstrated considerable potential for the quantitative detection of TCs.

Involvement of circRNA Regulators MBNL1 and QKI in the Progression of Esophageal Squamous Cell Carcinoma.

OBJECTIVES: To investigate the role of circRNA regulators MBNL1 and QKI in the progression of esophageal squamous cell carcinoma. BACKGROUND: MBNL1 and QKI are pivotal regulators of pre-mRNA alternative splicing, crucial for controlling circRNA production - an emerging biomarker and functional regulator of tumor progression. Despite their recognized roles, their involvement in ESCC progression remains unexplored. METHODS: The expression levels of MBNL1 and QKI were examined in 28 tissue pairs from ESCC and adjacent normal tissues using data from the GEO database. Additionally, a total of 151 ESCC tissue samples, from stage T1 to T4, consisting of 13, 43, 87, and 8 cases per stage, respectively, were utilized for immunohistochemical (IHC) analysis. RNA sequencing was utilized to examine the expression profiles of circRNAs, lncRNAs, and mRNAs across 3 normal tissues, 3 ESCC tissues, and 3 pairs of KYSE150 cells in both wildtype (WT) and those with MBNL1 or QKI knockouts. Transwell, colony formation, and subcutaneous tumorigenesis assays assessed the impact of MBNL1 or QKI knockout on ESCC cell migration, invasion, and proliferation. RESULTS: ESCC onset significantly altered MBNL1 and QKI expression levels, influencing diverse RNA species. Elevated MBNL1 or QKI expression correlated with patient age or tumor invasion depth, respectively. MBNL1 or QKI knockout markedly enhanced cancer cell migration, invasion, proliferation, and tumor growth. Moreover, the absence of either MBNL1 or QKI modulated the expression profiles of multiple circRNAs, causing extensive downstream alterations in the expression of numerous lncRNAs and mRNAs. While the functions of circRNA and lncRNA among the top 20 differentially expressed genes remain unclear, mRNAs like SLCO4C1, TMPRSS15, and MAGEB2 have reported associations with tumor progression. CONCLUSIONS: This study underscores the tumor-suppressive roles of MBNL1 and QKI in ESCC, proposing them as potential biomarkers and therapeutic targets for ESCC diagnosis and treatment.

Outcomes of patients in nasopharyngeal adenoid cystic carcinoma in the IMRT era: a single-center experience.

OBJECTIVE: Nasopharyngeal adenoid cystic carcinoma (NACC) is a rare malignancy with special biological features. Controversies exist regarding the treatment approach and prognostic factors in the IMRT era. This study aimed to evaluate the long-term outcomes and management approaches in NACC. METHODS: Fifty patients with NACC at our institution between 2010 and 2020 were reviewed. Sixteen patients received primary radiotherapy (RT), and 34 patients underwent primary surgery. RESULTS: Between January 2010 and October 2020, a total of 50 patients with pathologically proven NACC were included in our analysis. The median follow-up time was 58.5 months (range: 6.0-151.0 months). The 5-year overall survival rate (OS) and progression-free survival rate (PFS) were 83.9% and 67.5%, respectively. The 5-year OS rates of patients whose primary treatment was surgery and RT were 90.0% and 67.3%, respectively (log-rank P = 0.028). The 5-year PFS rates of patients whose primary treatment was surgery or RT were 80.8% and 40.7%, respectively (log-rank P = 0.024). Multivariate analyses showed that nerve invasion and the pattern of primary treatment were independent factors associated with PFS. CONCLUSIONS: Due to the relative insensitivity to radiation, primary surgery seemed to provide a better chance of disease control and improved survival in NACC. Meanwhile, postoperative radiotherapy should be performed for advanced stage or residual tumours. Cranial nerve invasion and treatment pattern might be important factors affecting the prognosis of patients with NACC.

Construction of blackberry polysaccharide nano-selenium particles: Structure features and regulation effects of glucose/lipid metabolism in HepG2 cells.

In this study, blackberry polysaccharide-selenium nanoparticles (BBP-24-3Se) were first prepared via Na2SeO3/Vc redox reaction, followed by coating with red blood cell membrane (RBC) to form core-shell structure polysaccharide-selenium nanoparticles (RBC@BBP-24-3Se). The particle size of BBP-24-3Se (167.1 nm) was increased to 239.8 nm (RBC@BBP-24-3Se) with an obvious core-shell structure after coating with RBC. FT-IR and XPS results indicated that the interaction between BBP-24-3 and SeNPs formed a new C-O···Se bond with valence state of Se0. Bioassays indicated that RBC coating markedly enhanced both the biocompatibility and bioabsorbability of RBC@BBP-24-3Se, and the absorption rate of RBC@BBP-24-3Se in HepG2 cells was 4.99 times higher than that of BBP-24-3Se at a concentration of 10 µg/mL. Compared with BBP-24-3Se, RBC@BBP-24-3Se possessed significantly heightened protective efficacy against oxidative damage and better regulation of glucose/lipid metabolism disorder induced by palmitic acid in HepG2 cells. Mechanistic studies demonstrated that RBC@BBP-24-3Se could effectively improve PI3K/AKT signaling pathway to promote glucose metabolism, inhibit the expression of lipid synthesis genes and up-regulate the expression of lipid-decomposing genes through AMPK signaling pathway to improve lipid metabolism. These results provided a theoretical basis for developing a new type of selenium supplement for the treatment of insulin resistance.

Efficacy of a sepsis clinical decision support system in identifying patients with sepsis in the emergency department.

BACKGROUND: Early prediction of sepsis onset is crucial for reducing mortality and the overall cost burden of sepsis treatment. Currently, few effective and accurate prediction tools are available for sepsis. Hence, in this study, we developed an effective sepsis clinical decision support system (S-CDSS) to assist emergency physicians to predict sepsis. METHODS: This study included patients who had visited the emergency department (ED) of Taipei Tzu Chi Hospital, Taiwan, between January 1, 2020, and June 31, 2022. The patients were divided into a derivation cohort (n = 70,758) and a validation cohort (n = 27,545). The derivation cohort was subjected to sixfold stratified cross-validation, reserving 20% of the data (n = 11,793) for model testing. The primary study outcome was a sepsis prediction (International Classification of Diseases, Tenth Revision, Clinical Modification) before discharge from the ED. The S-CDSS incorporated the LightGBM algorithm to ensure timely and accurate prediction of sepsis. The validation cohort was subjected to multivariate logistic regression to identify the associations of S-CDSS-based high- and medium-risk alerts with clinical outcomes in the overall patient cohort. For each clinical outcome in high- and medium-risk patients, we calculated the sensitivity, specificity, positive and negative predictive values, positive and negative likelihood ratios, and accuracy of S-CDSS-based predictions. RESULTS: The S-CDSS was integrated into our hospital information system. The system featured three risk warning labels (red, yellow, and white, indicating high, medium, and low risks, respectively) to alert emergency physicians. The sensitivity and specificity of the S-CDSS in the derivation cohort were 86.9% and 92.5%, respectively. In the validation cohort, high- and medium-risk alerts were significantly associated with all clinical outcomes, exhibiting high prediction specificity for intubation, general ward admission, intensive care unit admission, ED mortality, and in-hospital mortality (93.29%, 97.32%, 94.03%, 93.04%, and 93.97%, respectively). CONCLUSION: Our findings suggest that the S-CDSS can effectively identify patients with suspected sepsis in the ED. Furthermore, S-CDSS-based predictions appear to be strongly associated with clinical outcomes in patients with sepsis.

Exosomes derived from mesenchymal stem cells in diabetes and diabetic complications.

Diabetes, a group of metabolic disorders, constitutes an important global health problem. Diabetes and its complications place a heavy financial strain on both patients and the global healthcare establishment. The lack of effective treatments contributes to this pessimistic situation and negative outlook. Exosomes released from mesenchymal stromal cells (MSCs) have emerged as the most likely new breakthrough and advancement in treating of diabetes and diabetes-associated complication due to its capacity of intercellular communication, modulating the local microenvironment, and regulating cellular processes. In the present review, we briefly outlined the properties of MSCs-derived exosomes, provided a thorough summary of their biological functions and potential uses in diabetes and its related complications.

A Rotating Cathode with Periodical Changes in Electrolyte Layer Thickness for High-Rate Li‒O2 Batteries.

Li-O2 batteries (LOBs) possess the highest theoretical gravimetric energy density among all types of secondary batteries, but they are still far from practical applications. The poor rate performance resulting from the slow mass transfer is one of the primary obstacles in LOBs. To solve this issue, a rotating cathode with periodic changes in the electrolyte layer thickness is designed, decoupling the maximum transfer rate of Li+ and O2. During rotation, the thinner electrolyte layer on the cathode facilitates the O2 transfer, and the thicker electrolyte layer enhances the Li+ transfer. As a result, the rotating cathode enables the LOBs to undergo 58 cycles at 2.5 mA cm-2 and discharge stably even at a high current density of 7.5 mA cm-2. Besides, it also makes the batteries exhibit a large discharge capacity of 6.8 mAh cm-2, and the capacity decay is much slower with increasing current density. Notably, this rotating electrode holds great promise for utilization in other electrochemical cells involving gas-liquid-solid triple-phase interfaces, suggesting a viable approach to enhance the mass transfer in such systems.

Direct synthesis of branched amines enabled by dual-catalyzed allylic C─H amination of alkenes with amines.

Direct conversion of hydrocarbons into amines represents an important and atom-economic goal in chemistry for decades. However, intermolecular cross-coupling of terminal alkenes with amines to form branched amines remains extremely challenging. Here, a visible-light and Co-dual catalyzed direct allylic C─H amination of alkenes with free amines to afford branched amines has been developed. Notably, challenging aliphatic amines with strong coordinating effect can be directly used as C─N coupling partner to couple with allylic C─H bond to form advanced amines with molecular complexity. Moreover, the reaction proceeds with exclusive regio- and chemoselectivity at more steric hinder position to deliver primary, secondary, and tertiary aliphatic amines with diverse substitution patterns that are difficult to access otherwise.

Use of Reverse Shock Index Multiplied by Simplified Motor Score in a Five-Level Triage System: Identifying Trauma in Adult Patients at a High Risk of Mortality.

Background and Objectives: The Taiwan Triage and Acuity Scale (TTAS) is reliable for triaging patients in emergency departments in Taiwan; however, most triage decisions are still based on chief complaints. The reverse-shock index (SI) multiplied by the simplified motor score (rSI-sMS) is a more comprehensive approach to triage that combines the SI and a modified consciousness assessment. We investigated the combination of the TTAS and rSI-sMS for triage compared with either parameter alone as well as the SI and modified SI. Materials and Methods: We analyzed 13,144 patients with trauma from the Taipei Tzu Chi Trauma Database. We investigated the prioritization performance of the TTAS, rSI-sMS, and their combination. A subgroup analysis was performed to evaluate the trends in all clinical outcomes for different rSI-sMS values. The sensitivity and specificity of rSI-sMS were investigated at a cutoff value of 4 (based on previous study and the highest score of the Youden Index) in predicting injury severity clinical outcomes under the TTAS system were also investigated. Results: Compared with patients in triage level III, those in triage levels I and II had higher odds ratios for major injury (as indicated by revised trauma score < 7 and injury severity score [ISS] ≥ 16), intensive care unit (ICU) admission, prolonged ICU stay (≥14 days), prolonged hospital stay (≥30 days), and mortality. In all three triage levels, the rSI-sMS < 4 group had severe injury and worse outcomes than the rSI-sMS ≥ 4 group. The TTAS and rSI-sMS had higher area under the receiver operating characteristic curves (AUROCs) for mortality, ICU admission, prolonged ICU stay, and prolonged hospital stay than the SI and modified SI. The combination of the TTAS and rSI-sMS had the highest AUROC for all clinical outcomes. The prediction performance of rSI-sMS < 4 for major injury (ISS ≥ 16) exhibited 81.49% specificity in triage levels I and II and 87.6% specificity in triage level III. The specificity for mortality was 79.2% in triage levels I and II and 87.4% in triage level III. Conclusions: The combination of rSI-sMS and the TTAS yielded superior prioritization performance to TTAS alone. The integration of rSI-sMS and TTAS effectively enhances the efficiency and accuracy of identifying trauma patients at a high risk of mortality.