A stable low-temperature H2-production catalyst by crowding Pt on α-MoC.

The water-gas shift (WGS) reaction is an industrially important source of pure hydrogen (H2) at the expense of carbon monoxide and water1,2. This reaction is of interest for fuel-cell applications, but requires WGS catalysts that are durable and highly active at low temperatures3. Here we demonstrate that the structure (Pt1-Ptn)/α-MoC, where isolated platinum atoms (Pt1) and subnanometre platinum clusters (Ptn) are stabilized on α-molybdenum carbide (α-MoC), catalyses the WGS reaction even at 313 kelvin, with a hydrogen-production pathway involving direct carbon monoxide dissociation identified. We find that it is critical to crowd the α-MoC surface with Pt1 and Ptn species, which prevents oxidation of the support that would cause catalyst deactivation, as seen with gold/α-MoC (ref. 4), and gives our system high stability and a high metal-normalized turnover number of 4,300,000 moles of hydrogen per mole of platinum. We anticipate that the strategy demonstrated here will be pivotal for the design of highly active and stable catalysts for effective activation of important molecules such as water and carbon monoxide for energy production.

Improving drug-drug interactions prediction with interpretability via meta-path-based information fusion.

Drug-drug interactions (DDIs) are compound effects when patients take two or more drugs at the same time, which may weaken the efficacy of drugs or cause unexpected side effects. Thus, accurately predicting DDIs is of great significance for the drug development and the drug safety surveillance. Although many methods have been proposed for the task, the biological knowledge related to DDIs is not fully utilized and the complex semantics among drug-related biological entities are not effectively captured in existing methods, leading to suboptimal performance. Moreover, the lack of interpretability for the predicted results also limits the wide application of existing methods for DDIs prediction. In this study, we propose a novel framework for predicting DDIs with interpretability. Specifically, we construct a heterogeneous information network (HIN) by explicitly utilizing the biological knowledge related to the procedure of inducing DDIs. To capture the complex semantics in HIN, a meta-path-based information fusion mechanism is proposed to learn high-quality representations of drugs. In addition, an attention mechanism is designed to combine semantic information obtained from meta-paths with different lengths to obtain final representations of drugs for DDIs prediction. Comprehensive experiments are conducted on 2410 approved drugs, and the results of predictive performance comparison show that our proposed framework outperforms selected representative baselines on the task of DDIs prediction. The results of ablation study and cold-start scenario indicate that the meta-path-based information fusion mechanism red is beneficial for capturing the complex semantics among drug-related biological entities. Moreover, the results of case study demonstrate that the designed attention mechanism is able to provide partial interpretability for the predicted DDIs. Therefore, the proposed method will be a feasible solution to the task of predicting DDIs.

EIF4A3-negatively driven circular RNA ß-catenin (circß-catenin) promotes colorectal cancer progression via miR-197-3p/CTNND1 regulatory axis.

BACKGROUND: Circß-catenin, our first reported circRNA, has been reported to mediate tumorigenesis in various cancers. However, its biological functions and underlying mechanisms in colorectal cancer (CRC) remain unknown. METHODS: The qRT-PCR examination was used to detect the expression of circß-catenin, miR-197-3p, and CTNND1 in cells and human tissues. Western blot was conducted to detect the protein expression levels. The biological function of circß-catenin was verified by MTT, colony formation, wound healing, and transwell assays. The in vivo effects of circß-catenin were verified by nude mice xenograft and metastasis models. The regulatory network of circß-catenin/miR-197-3p/CTNND1 was confirmed via dual-luciferase reporter and RIP assays. RESULTS: In the present study, circß-catenin was found to promote CRC cell proliferation and metastasis in vitro and in vivo. Mechanistically, circß-catenin served as miRNA decoy to directly bind to miR-197-3p, then antagonized the repression of the target gene CTNND1, and eventually promoted the malignant phenotype of CRC. More interestingly, the inverted repeated Alu pairs termed AluJb1/2 and AluY facilitated the biogenesis of circß-catenin, which could be partially reversed by EIF4A3 binding to Alu element AluJb2. CONCLUSIONS: Our findings illustrated a novel mechanism of circß-catenin in modulating CRC tumorigenesis and metastasis, which provides a potential therapeutic target for CRC patients.

Plasma-Constructed Co2P-Ni2P Heterointerface for Electro­Upcycling of Polyethylene Terephthalate Plastic to Co-Produce Hydrogen and Formate.

Integrating electrochemical upcycling of polyethylene-terephthalate (PET) and the hydrogen evolution reaction (HER) is an energy-saving approach for electrolytic hydrogen (H2) production, along with the coproduction of formate. Herein, a novel and rapid strategy of cold plasma phosphating is employed to synthesize Co2P-Ni2P heterointerface decorated on carbon cloth (Co2P-Ni2P/CC) to catalyze H2 generation and reform PET. Notably, the obtained Co2P-Ni2P/CC exhibits eminent ethylene glycol oxidation reaction (EGOR) and HER activities, effectuating low potentials of merely 1.300 and -0.112 V versus RHE at 100 mA cm-2 for the EGOR and HER, respectively, also attaining an ultralow cell bias of 1.300 V at 10 mA cm-2 for EG oxidation assisted-water splitting. DFT and characterization results validate that the as-formed built-in electric fields in the Co2P-Ni2P heterointerface can accelerate electrons transfer and deepen structural self-reconstruction, thereby boosting effectively water dissociation and ethylene glycol (EG) dehydrogenation. Impressively, coupling HER with PET-derived EG-to-formate in a flow-cell electrolyzer assembled with Co2P-Ni2P/CC pair achieves an intriguing formate Faradaic efficiency of 90.6% and an extraordinary stable operation of over 70 h at 100 mA cm-2. The work exemplifies a facile and effective strategy for synthesizing metal phosphides electrocatalysts with extraordinary performance toward H2 generation of water splitting and recycling of PET.

Modulating Silver Performance in Electrocatalytic Oxidation of HCHO via SMSI between Ag-Co3O4 Interfaces.

The replacement of oxygen evolution reactions with organic molecule oxidation reactions to enable energy-efficient hydrogen production has been a subject of interest. However, further reducing reaction energy consumption and releasing hydrogen from organic molecules continue to pose significant challenges. Herein, a strategy is proposed to produce hydrogen and formic acid from formaldehyde using Ag/Co3O4 interface catalysts at the anode. The key to improving the performance of Ag-based catalysts for formaldehyde oxidation lies in the strong SMSI achieved through the well-designed "spontaneous redox reaction" between Ag and Co3O4 precursors. Nano-sized Ag particles are uniformly dispersed on Co3O4 nanosheets, and electron-deficient Agδ+ are formed by the SMSI between Ag and Co3O4. Ag/Co3O4 demonstrates exceptional formaldehyde oxidation activity at low potentials of 0.32 V versus RHE and 0.65 V versus RHE, achieving current densities of 10 and 100 mA cm-2, respectively. The electrolyzer "Ag/Co3O4||20% Pt/C" achieves over 195% hydrogen efficiency and over 98% formic acid selectivity, maintaining stable operation for 60 hours. This work not only presents a novel approach to precisely modulate Ag particle size and interface electronic structure via SMSI, but also provides a promising approach to efficient and energy-saving hydrogen production and the transformation of harmful formaldehyde.

Impact of Hepatic Pedicle Clamping on Long-Term Survival Following Hepatectomy for Hepatocellular Carcinoma: Stratified Analysis Based on Intraoperative Blood Transfusion Status.

BACKGROUND: Hepatic pedicle clamping (HPC) is frequently utilized during hepatectomy to reduce intraoperative bleeding and diminish the need for intraoperative blood transfusion (IBT). The long-term prognostic implications of HPC following hepatectomy for hepatocellular carcinoma (HCC) remain under debate. This study aims to elucidate the association between HPC and oncologic outcomes after HCC resection, stratified by whether IBT was administered. PATIENTS AND METHODS: Prospectively collected data on patients with HCC who underwent curative resection from a multicenter database was studied. Patients were stratified into two cohorts on the basis of whether IBT was administered. The impact of HPC on long-term overall survival (OS) and recurrence-free survival (RFS) between the two cohorts was assessed by univariable and multivariable Cox regression analyses. RESULTS: Of 3362 patients, 535 received IBT. In the IBT cohort, using or not using HPC showed no significant difference in OS and RFS outcomes (5-year OS and RFS rates 27.9% vs. 24.6% and 13.8% vs. 12.0%, P = 0.810 and 0.530). However, in the non-IBT cohort of 2827 patients, the HPC subgroup demonstrated significantly decreased OS (5-year 45.9% vs. 56.5%, P < 0.001) and RFS (5-year 24.7% vs. 33.3%, P < 0.001) when compared with the subgroup without HPC. Multivariable Cox regression analysis identified HPC as an independent risk factor of OS and RFS [hazard ratios (HR) 1.16 and 1.12, P = 0.024 and 0.044, respectively] among patients who did not receive IBT. CONCLUSIONS: The impact of HPC on the oncological outcomes following hepatectomy for patients with HCC differed significantly whether IBT was administered, and HPC adversely impacted on long-term survival for patients without receiving IBT during hepatectomy.

Quma Tongluo Prescription in the Treatment of Chronic Oxaliplatin Related Peripheral Neuropathy: A Single-Center, Open, Randomized Controlled Study.

Objective: To observe the effect of oral Quma Tongluo decoction on oxaliplatin-related chronic peripheral neuropathy. Methods: A total of 64 patients who met the inclusion criteria were randomly divided into an experimental group and a control group, with 32 cases in each group. The experimental group took Quma Tongluo decoction granules orally (2 times a day, 1 package each time, morning and evening after meals), and the control group took mecobalamin tablets orally (1 tablet each time, 3 times a day, after meals). After 4 weeks of treatment, the quantitative score of chronic peripheral neuropathy severity, a quantitative score of numbness, a quantitative score of pain, a chemotherapeutic peripheral neurotoxicity score, comprehensive neuropathy score, peripheral neurotoxicity grade, KPS score, and neuropathy area range score were compared between the two groups before and after treatment. Results: Before treatment, there were no significant differences between the two groups in the quantitative score of chronic peripheral neuropathy severity, quantitative score of numbness, chemotherapeutic peripheral neurotoxicity score, total neuropathy score, peripheral neurotoxicity grade, and chronic OIPN symptom range score (P > .05). After 4 weeks of treatment, there were significant differences in the quantitative score of chronic peripheral neuropathy severity, quantitative score of numbness, chemotherapeutic peripheral neurotoxicity score, total neuropathy score, peripheral neurotoxicity grade, and chronic OIPN symptom range score between the two groups (P < .05). There was no significant difference in pain quantification score and KPS score between the two groups before and after treatment (P > .05). The total effective rate of Quma Tongluo decoction in the treatment of oxaliplatin-related chronic peripheral neuropathy was higher than that of mecobalamin (87.1% > 20.6%), and no obvious adverse reactions such as Gastrointestinal reactions and allergic reactions were observed.One patient in the experimental group had diarrhea, the incidence of adverse reactions was about 3.2%, and the control group had no adverse reactions. Conclusions: Quma Tongluo decoction can effectively treat oxaliplatin-related chronic peripheral neuropathy, reduce the symptoms while reducing the scope of symptoms, and has no obvious adverse reactions in clinical practice, with good safety.

Enabling Efficient Anchoring-Conversion Interface by Fabricating Double-Layer Functionalized Separator for Suppressing Shuttle Effect.

Lithium-sulfur batteries (LiSBs) with high energy density still face challenges on sluggish conversion kinetics, severe shuttle effects of lithium polysulfides (LiPSs), and low blocking feature of ordinary separators to LiPSs. To tackle these, a novel double-layer strategy to functionalize separators is proposed, which consists of Co with atomically dispersed CoN4 decorated on Ketjen black (Co/CoN4@KB) layer and an ultrathin 2D Ti3C2Tx MXene layer. The theoretical calculations and experimental results jointly demonstrate metallic Co sites provide efficient adsorption and catalytic capability for long-chain LiPSs, while CoN4 active sites facilitate the absorption of short-chain LiPSs and promote the conversion to Li2S. The stacking MXene layer serves as a microscopic barrier to further physically block and chemically anchor leaked LiPSs from the pores and gaps of the Co/CoN4@KB layer, thus preserving LiPSs within efficient anchoring-conversion reaction interfaces to balance the accumulation of "dead S" and Li2S. Consequently, with an ultralight loading of Co/CoN4@KB-MXene, the LiSBs exhibit amazing electrochemical performance even under high sulfur loading and lean electrolyte, and the outperforming performance for lithium-selenium batteries (LiSeBs) can also be achieved. This work exploits a universal and effective strategy of a double-layer functionalized separator to regulate the equilibrium adsorption-catalytic interface, enabling high-energy and long-cycle LiSBs/LiSeBs.

Re-Dispersion of Platinum From CNTs Substrate to α-MoC1 - x to Boost the Hydrogen Evolution Reaction.

Developing high-performance electrocatalysts toward hydrogen evolution reaction (HER) is important for clean and sustainable hydrogen energy, yet still challenging. Herein, an α-MoC1 - x induced redispersing strategy to construct a superior HER electrocatalyst (Pt/CNTs-N + α-MoC1 - x ) by mechanical mixing of α-MoC1 - x with Pt/CNTs-N followed by thermal reduction is reported. It is found that thermo-activation treatment enables partial Pt atoms to redisperse on α-MoC1 - x substrate from carbon nanotubes, which creates dual active interfaces of Pt species dispersed over carbon nanotubes and α-MoC1 - x . Benefiting from the strong electronic interaction between the Pt atom and α-MoC1 - x , the utilization efficiency of the Pt atom and the zero-valence state of Pt is evidently enhanced. Consequently, Pt/CNTs-N + α-MoC1 - x catalyst exhibits excellent HER activity with low overpotentials of 17 and 34 mV to achieve a current density of 10 mA cm-2 in acidic and alkaline electrolytes, respectively. Density functional theory calculations further reveal that the synergistic effect between Pt and α-MoC1 - x makes it accessible for the dissociation of water molecules and subsequent desorption of hydrogen atoms. This work reveals the crucial roles of α-MoC1 - x additives, providing practical solutions to enhance platinum dispersion, and thereby enhance the catalytic activity in HER.

Association of Concurrent Metabolic Syndrome with Long-term Oncological Prognosis Following Liver Resection for Hepatocellular Carcinoma Among Patients with Chronic Hepatitis B Virus Infection: A Multicenter Study of 1753 Patients.

BACKGROUND: Although hepatitis B virus (HBV) infection remains the main cause of hepatocellular carcinoma (HCC) worldwide, metabolic syndrome, with its increase in prevalence, has become an important and significant risk factor for HCC. This study was designed to investigate the association of concurrent metabolic syndrome with long-term prognosis following liver resection for patients with HBV-related HCC. METHODS: From a Chinese, multicenter database, HBV-infected patients who underwent curative resection for HCC between 2010 and 2020 were identified. Long-term oncological prognosis, including overall survival (OS), recurrence-free survival (RFS), and early (≤2 years of surgery) and late (>2 years) recurrences were compared between patients with versus those without concurrent metabolic syndrome. RESULTS: Of 1753 patients, 163 (9.3%) patients had concurrent metabolic syndrome. Compared with patients without metabolic syndrome, patients with metabolic syndrome had poorer 5-year OS (47.5% vs. 61.0%; P = 0.010) and RFS (28.3% vs. 44.2%; P = 0.003) rates and a higher 5-year overall recurrence rate (67.3% vs. 53.3%; P = 0.024). Multivariate analysis revealed that concurrent metabolic syndrome was independently associated with poorer OS (hazard ratio: 1.300; 95% confidence interval: 1.018-1.660; P = 0.036) and RFS (1.314; 1.062-1.627; P = 0.012) rates, and increased rates of late recurrence (hazard ratio: 1.470; 95% confidence interval: 1.004-2.151; P = 0.047). CONCLUSIONS: In HBV-infected patients with HCC, concurrent metabolic syndrome was associated with poorer postoperative long-term oncologic survival outcomes. These results suggested that patients with metabolic syndrome should undergo enhanced surveillance for tumor recurrence even after 2 years of surgery to early detect late HCC recurrence. Whether improving metabolic syndrome can reduce postoperative recurrence of HCC deserves further exploration.

Prognostic implications of alpha-fetoprotein and C-reactive protein elevation in hepatocellular carcinoma following resection (PACE): a large cohort study of 2770 patients.

BACKGROUND: Routine clinical staging for hepatocellular carcinoma (HCC) incorporates liver function, general health, and tumor morphology. Further refinement of prognostic assessments and treatment decisions may benefit from the inclusion of tumor biological marker alpha-fetoprotein (AFP) and systemic inflammation indicator C-reactive protein (CRP). METHODS: Data from a multicenter cohort of 2770 HCC patients undergoing hepatectomy were analyzed. We developed the PACE risk score (Prognostic implications of AFP and CRP Elevation) after initially assessing preoperative AFP and CRP's prognostic value. Subgroup analyzes were performed in BCLC cohorts A and B using multivariable Cox analysis to evaluate the prognostic stratification ability of the PACE risk score and its complementary utility for BCLC staging. RESULTS: Preoperative AFP ≥ 400ng/mL and CRP ≥ 10 mg/L emerged as independent predictors of poorer prognosis in HCC patients who underwent hepatectomy, leading to the creation of the PACE risk score. PACE risk score stratified patients into low, intermediate, and high-risk groups with cumulative 5-year overall (OS) and recurrence-free survival (RFS) rates of 59.6%/44.9%, 43.9%/38.4%, and 20.6%/18.0% respectively (all P < 0.001). Increased PACE risk scores correlated significantly with early recurrence and extrahepatic metastases frequency (all P < 0.001). The multivariable analysis identified intermediate and high-risk PACE scores as independently correlating with poor postoperative OS and RFS. Furthermore, the PACE risk score proficiently stratified the prognosis of BCLC stages A and B patients, with multivariable analyses demonstrating it as an independent prognostic determinant for both stages. CONCLUSION: The PACE risk score serves as an effective tool for postoperative risk stratification, potentially supplementing the BCLC staging system.

Linc-ROR drive adriamycin resistance by targeting AP-2α/Wnt/ß-catenin axis in hepatocellular carcinoma.

Adriamycin is widely used as a chemotherapeutic strategy for advanced hepatocellular carcinoma (HCC). However, the clinical response was disappointing because of the acquired drug resistance with long-term usage. Revealing the underlying mechanism could provide promising therapeutics for the drug-resistant patients. The recently identified linc-ROR (long intergenic non-protein-coding RNA, regulator of reprogramming) has been found to be an oncogene in various cancers, and it also demonstrated to mediate drug resistance and metastasis. We thereby wonder whether this lincRNA could mediate adriamycin chemoresistance in HCC. In this study, linc-ROR was found to be upregulated in adriamycin-resistant HCC cells. And its overexpression accelerated epithelial-mesenchymal transition (EMT) program and adriamycin resistance. Conversely, its silence suppressed EMT and made HCC cells sensitize to adriamycin in vitro and in vivo. Further investigation revealed that linc-ROR physically interacted with AP-2α, mediated its stability by a post-translational modification manner, and sequentially activated Wnt/ß-catenin pathway. Furthermore, linc-ROR expression was positively associated with ß-catenin expression in human clinical specimens. Taken together, linc-ROR promoted tumorigenesis and adriamycin resistance in HCC via a linc-ROR/AP-2α/Wnt/ß-catenin axis, which could be developed as a potential therapeutic target for the adriamycin-resistant patients.

Low-temperature hydrogen production from water and methanol using Pt/α-MoC catalysts.

Polymer electrolyte membrane fuel cells (PEMFCs) running on hydrogen are attractive alternative power supplies for a range of applications, with in situ release of the required hydrogen from a stable liquid offering one way of ensuring its safe storage and transportation before use. The use of methanol is particularly interesting in this regard, because it is inexpensive and can reform itself with water to release hydrogen with a high gravimetric density of 18.8 per cent by weight. But traditional reforming of methanol steam operates at relatively high temperatures (200-350 degrees Celsius), so the focus for vehicle and portable PEMFC applications has been on aqueous-phase reforming of methanol (APRM). This method requires less energy, and the simpler and more compact device design allows direct integration into PEMFC stacks. There remains, however, the need for an efficient APRM catalyst. Here we report that platinum (Pt) atomically dispersed on α-molybdenum carbide (α-MoC) enables low-temperature (150-190 degrees Celsius), base-free hydrogen production through APRM, with an average turnover frequency reaching 18,046 moles of hydrogen per mole of platinum per hour. We attribute this exceptional hydrogen production-which far exceeds that of previously reported low-temperature APRM catalysts-to the outstanding ability of α-MoC to induce water dissociation, and to the fact that platinum and α-MoC act in synergy to activate methanol and then to reform it.

Initial attitudes toward a drug predict medication adherence in first-episode patients with schizophrenia: a 1-year prospective study in China.

BACKGROUND: Patients' attitudes toward medication have been shown to be a predictor of nonadherence to antipsychotic treatment. However, most previous studies that explored this relationship used a cross-sectional design. It is important to explore the association of attitudes toward drugs with discontinuation at different time points during antipsychotic treatment. In this study, we investigated the association of attitudes toward drugs (measured by the Drug Attitude Inventory (DAI-10)) with adherence at seven time points (baseline, 4 weeks, 8 weeks, 12 weeks, 26 weeks, 39 weeks, and 52 weeks) during 1 year of treatment. Factors that were potentially associated with attitudes toward drugs at the time point of interest were also studied. METHODS: Demographic characteristics, psychopathology, social functioning, and attitudes toward drugs (measured by the DAI-10) were collected at baseline, 4 weeks, 8 weeks, 12 weeks, 26 weeks, 39 weeks and 52 weeks. The association of attitudes toward drugs (measured by DAI-10) with adherence at the seven time points was calculated using the Mann‒Whitney U test. The optimal cutoff point for the DAI-10 was then determined using receiver operating characteristic (ROC) analysis. Cox regression analysis was conducted to further investigate the association of DAI-10 scores with discontinuation, controlling for potential confounding variables. We used multiple regression analysis to identify the factors associated with DAI-10 scores. RESULTS: Among the six time points, only baseline DAI-10 total scores were significantly different between the completed and discontinued groups (p = 0.004). Female sex and a baseline DAI-10 total score greater than - 1 were found to be independent protective factors against discontinuation of antipsychotic drug treatments during the 1-year follow-up. At baseline, the severity of the disease (CGI-s) and insight regarding the disease were shown to be associated with DAI-10 total scores. CONCLUSION: Attitudes toward antipsychotic drugs at baseline were shown to play a crucial role in predicting treatment discontinuation. TRIAL REGISTRATION: The data were collected from a clinical trial and the clinical trials.gov ID of the study is NCT01057849.

The association of sleep quality and burnout among Chinese medical residents under standardized residency training in a tertiary hospital.

PURPOSE: To investigate the impact of sleep quality and chronotype on job burnout among medical residents under standardized residency training (SRT) in a tertiary hospital in Beijing, China. METHODS: Medical residents in the Department of Internal Medicine of Peking Union Medical College Hospital were assessed by Morning and Evening Questionaire-5 (MEQ-5), Pittsburgh sleep quality index (PSQI), and Maslach Burnout Inventory-General Survey (MBI-GS). Factors associated with burnout were analyzed. RESULTS: A total of 142 respondents returned completed questionnaires. Burnout was present in 85 (60%) residents. Prevalence of high emotional exhaustion, high depersonalization, and low personal accomplishment were 51%, 28%, and 18%, respectively. The global PSQI score of residents was 5.9 ± 2.4, and the self-reported sleep duration was 6.2 ± 0.8 h/day. The MEQ-5 distribution skewed towards morningness, with a median score of 14.5 [13.0, 16.3]. Poor daytime function significantly predicted emotional exhaustion and depersonalization. Chronotypes were not associated with any of the burnout components. CONCLUSION: Sleep-related daytime dysfunction was strongly related to burnout. Strategies protecting the sleep of residents should be incorporated into the SRT programs for both efficiency and sustainability considerations.

A Stable and Scalable Digital Composite Neurocognitive Test for Early Dementia Screening Based on Machine Learning: Model Development and Validation Study.

BACKGROUND: Dementia has become a major public health concern due to its heavy disease burden. Mild cognitive impairment (MCI) is a transitional stage between healthy aging and dementia. Early identification of MCI is an essential step in dementia prevention. OBJECTIVE: Based on machine learning (ML) methods, this study aimed to develop and validate a stable and scalable panel of cognitive tests for the early detection of MCI and dementia based on the Chinese Neuropsychological Consensus Battery (CNCB) in the Chinese Neuropsychological Normative Project (CN-NORM) cohort. METHODS: CN-NORM was a nationwide, multicenter study conducted in China with 871 participants, including an MCI group (n=327, 37.5%), a dementia group (n=186, 21.4%), and a cognitively normal (CN) group (n=358, 41.1%). We used the following 4 algorithms to select candidate variables: the F-score according to the SelectKBest method, the area under the curve (AUC) from logistic regression (LR), P values from the logit method, and backward stepwise elimination. Different models were constructed after considering the administration duration and complexity of combinations of various tests. Receiver operating characteristic curve and AUC metrics were used to evaluate the discriminative ability of the models via stratified sampling cross-validation and LR and support vector classification (SVC) algorithms. This model was further validated in the Alzheimer's Disease Neuroimaging Initiative phase 3 (ADNI-3) cohort (N=743), which included 416 (56%) CN subjects, 237 (31.9%) patients with MCI, and 90 (12.1%) patients with dementia. RESULTS: Except for social cognition, all other domains in the CNCB differed between the MCI and CN groups (P<.008). In feature selection results regarding discrimination between the MCI and CN groups, the Hopkins Verbal Learning Test-5 minutes Recall had the best performance, with the highest mean AUC of up to 0.80 (SD 0.02) and an F-score of up to 258.70. The scalability of model 5 (Hopkins Verbal Learning Test-5 minutes Recall and Trail Making Test-B) was the lowest. Model 5 achieved a higher level of discrimination than the Hong Kong Brief Cognitive test score in distinguishing between the MCI and CN groups (P<.05). Model 5 also provided the highest sensitivity of up to 0.82 (range 0.72-0.92) and 0.83 (range 0.75-0.91) according to LR and SVC, respectively. This model yielded a similar robust discriminative performance in the ADNI-3 cohort regarding differentiation between the MCI and CN groups, with a mean AUC of up to 0.81 (SD 0) according to both LR and SVC algorithms. CONCLUSIONS: We developed a stable and scalable composite neurocognitive test based on ML that could differentiate not only between patients with MCI and controls but also between patients with different stages of cognitive impairment. This composite neurocognitive test is a feasible and practical digital biomarker that can potentially be used in large-scale cognitive screening and intervention studies.

The Analgesic Efficacy of Intraperitoneal Ropivacaine Versus Bupivacaine for Laparoscopic Cholecystectomy: a Meta-Analysis.

INTRODUCTION: This meta-analysis aimed to compare the analgesic efficacy of intraperitoneal ropivacaine versus bupivacaine for laparoscopic cholecystectomy. METHODS: We searched PubMed, EMbase, Web of Science, EBSCO, and Cochrane Library databases from inception through January 2020 and included randomized controlled trials (RCTs) evaluating the analgesic efficacy of ropivacaine versus bupivacaine for laparoscopic cholecystectomy. RESULTS: Five RCTs are included in the meta-analysis. In patients with laparoscopic cholecystectomy, ropivacaine and bupivacaine demonstrated comparable pain scores at 2 h (SMD = -0.22; 95% CI = -0.54 to 0.10; p = 0.18), 4 h (SMD = -0.16; 95% CI = -0.42 to 0.10; p = 0.22), 8 h (SMD = -0.60; 95% CI = -1.19 to -0.01; p = 0.05), and 24 h (SMD = 0.33; 95% CI = -1.19 to 1.84; p = 0.67), as well as time to first analgesic requirement (SMD = 0.10; 95% CI = -0.23 to 0.42; p = 0.56). CONCLUSIONS: Intraperitoneal ropivacaine and bupivacaine have a similar analgesic efficacy for laparoscopic cholecystectomy.

Engineering the Local Coordination Environment and Density of FeN4 Sites by Mn Cooperation for Electrocatalytic Oxygen Reduction.

Single atom sites (SAS) of FeN4 are clarified as one of the most active components for the oxygen reduction reaction (ORR). Effective strategies by engineering the local coordination environment and site density of FeN4 sites are crucial to further enhance the electrocatalytic ORR performance. Herein, the integration of a second metal of Mn with Fe to construct Fe&Mn/N-C catalysts with enhanced density of FeN4 active sites and modulated electronic structure is reported. The formation of MnN4 centers modulates the local environment of FeN4 sites and reserves more FeN4 embedded in carbon substrate by forming the possible FeN4 -O-MnN4 configurations. Density functional theory calculations demonstrate that the overall energy barrier of ORR is decreased over the FeN4 -O-MnN4 moieties. Therefore, the Fe&Mn/N-C catalyst exhibits enhanced ORR performance both in alkaline and acidic solution (half-wave potentials are 0.904 and 0.781 V). This work provides an effective strategy by modulating the local electronic structure and density of FeN4 active sites to improve the ORR activity and stability through Mn cooperation.

Icariside II suppressed tumorigenesis by epigenetically regulating the circß-catenin-Wnt/ß-catenin axis in colorectal cancer.

Icariside II, a flavonol glycoside, one of the major components of Traditional Chinese Medicine Herba epimedii. In the present study, we found that Icariside II suppressed the proliferation of CRC by inducing cell cycle arrest and apoptosis in vitro and inhibited tumor growth in vivo. The further mechanism investigation showed that Icariside II suppressed the expression of ß-catenin and led to the functional inactivation of Wnt/ß-catenin signaling. Circß-catenin was considered as a promising candidate for mediating the tumorigenesis and the activation of Wnt/ß-catenin signaling in CRC cells. Furthermore, Icariside II has been proven to suppress the biogenesis of circß-catenin via epigenetically targeting DNA methyltransferases (DNMTs) to decrease global DNA methylation levels in CRC cells. Taken together, our results indicated that Icariside II suppressed tumorigenesis by epigenetically silencing the activation of circß-catenin-Wnt/ß-catenin axis in colorectal cancer. More importantly, the information gained from this study suggest that Icariside II may have great potential to be developed as a therapeutic drug for CRC patients.

Impact of parathyroidectomy among nondiabetic hemodialysis patients with severe hyperparathyroidism.

BACKGROUND: Parathyroidectomy (PTX) is a treatment for hyperparathyroidism (HPT) and has uncertain risks and benefits. The aim of this study was to evaluate the effect of PTX versus nonoperative treatment among nondiabetic hemodialysis patients. METHODS: A retrospective matched cohort study was performed. Each PTX patient was matched with one patient who had severe HPT but rejected PTX. The patients were matched by sex, birth date, date of first dialysis, nondiabetic status, and left ventricular ejection fraction. The serum markers, survival, main adverse cardiovascular and cerebrovascular event (MACCE) rates, and hospitalization were compared between the PTX patients and matched non-PTX patients. RESULTS: There were 1143 patients at our center in the Chinese National Renal Data System (CNRDS) between 2010 and 2020. Of these, 75 PTX patients were matched with 75 non-PTX patients. Rapid decreases in the mean intact parathyroid hormone, calcium and phosphorus concentrations, and a gradual increase in hemoglobin concentration were observed in the PTX group. The mortality was 2.9 per 100 patient-years in the PTX group and 10.9 per 100 patient-years in the non-PTX group (p < 0.001). Compared with non-PTX patients, PTX patients had an adjusted HR for death of 0.236 (95% CI 0.108-0.518). The cumulative MACCE rates were 6.7 per 100 patient-years in the PTX group and 15.2 per 100 patient-years in the non-PTX group (p < 0.001). The adjusted HR of the occurrence of first MACCE for PTX patients compared with non-PTX patients was 0.524 (95% CI 0.279-0.982). The cumulative hospitalization rates were 50.3 per 100 patient-years in the PTX group and 66.5 per 100 patient-years in the matched non-PTX group (p < 0.001). CONCLUSIONS: Compared with non-PTX patients, PTX was associated with an improvement in the biochemical measures and patient-level outcomes in nondiabetic hemodialysis patients with severe HPT.