Artificial Heterointerfaces with Regulated Charge Distribution of Ni Active Sites for Urea Oxidation Reaction.

In contrast to the thermodynamically unfavorable anodic oxygen evolution reaction, the electrocatalytic urea oxidation reaction (UOR) presents a more favorable thermodynamic potential. However, the practical application of UOR has been hindered by sluggish kinetics. In this study, hierarchical porous nanosheet arrays featuring abundant Ni-WO3 heterointerfaces on nickel foam (Ni-WO3/NF) is introduced as a monolith electrode, demonstrating exceptional activity and stability toward UOR. The Ni-WO3/NF catalyst exhibits unprecedentedly rapid UOR kinetics (200 mA cm-2 at 1.384 V vs. RHE) and a high turnover frequency (0.456 s-1), surpassing most previously reported Ni-based catalysts, with negligible activity decay observed during a durability test lasting 150 h. Ex situ X-ray photoelectron spectroscopy and density functional theory calculations elucidate that the WO3 interface significantly modulates the local charge distribution of Ni species, facilitating the generation of Ni3+ with optimal affinity for interacting with urea molecules and CO2 intermediates at heterointerfaces during UOR. This mechanism accelerates the interfacial electrocatalytic kinetics. Additionally, in situ Fourier transform infrared spectroscopy provides deep insights into the substantial contribution of interfacial Ni-WO3 sites to UOR electrocatalysis, unraveling the underlying molecular-level mechanisms. Finally, the study explores the application of a direct urea fuel cell to inspire future practical implementations.

Economical one-pot synthesis of isoquercetin and D-allulose from quercetin and sucrose using whole-cell biocatalyst.

Isoquercetin and D-allulose have diverse applications and significant value in antioxidant, antibacterial, antiviral, and lipid metabolism. Isoquercetin can be synthesized from quercetin, while D-allulose is converted from D-fructose. However, their production scale and overall quality are relatively low, leading to high production costs. In this study, we have devised a cost-effective one-pot method for biosynthesizing isoquercetin and D-allulose using a whole-cell biocatalyst derived from quercetin and sucrose. To achieve this, the optimized isoquercetin synthase and D-allulose-3-epimerase were initially identified through isofunctional gene screening. In order to reduce the cost of uridine diphosphate glucose (UDPG) during isoquercetin synthesis and ensure a continuous supply of UDPG, sucrose synthase is introduced to enable the self-circulation of UDPG. At the same time, the inclusion of sucrose permease was utilized to successfully facilitate the catalytic production of D-allulose in whole cells. Finally, the recombinant strain BL21/UGT-SUS+DAE-SUP, which overexpresses MiF3GTMUT, GmSUS, EcSUP, and DAEase, was obtained. This strain co-produced 41±2.4 mg/L of isoquercetin and 5.7±0.8 g/L of D-allulose using 120 mg/L of quercetin and 20 g/L of sucrose as substrates for 5 h after optimization. This is the first green synthesis method that can simultaneously produce flavonoid compounds and rare sugars. These findings provide valuable insights and potential for future industrial production, as well as practical applications in factories.

A new scoring system predicting side branch occlusion in patients undergoing left main bifurcation intervention: the LM V-RESOLVE score.

BACKGROUND: The risk of side branch (SB) occlusion is pivotal for decision-making of stenting strategies during unprotected left main (LM) bifurcation percutaneous coronary intervention (PCI). Accordingly, this study aimed to develop a scoring system for predicting SB occlusion during unprotected LM bifurcation PCI. METHODS: A total of 855 consecutive patients undergoing unprotected LM bifurcation PCI with provisional strategy at Fuwai Hospital from January 2014 to December 2016 were recruited. A prediction model was selected by all subsets logistic regression, and a multivariable risk score (LM V-RESOLVE [LM Visual Estimation for Risk Prediction of Side Branch Occlusion in Coronary Bifurcation Intervention]) was then established with incremental weights attributed to each component variable based on its estimate coefficients. SB occlusion was defined as any decrease in Thrombolysis in Myocardial Infarction (TIMI) flow grade or absence of flow in SB after main vessel (MV) stenting. RESULTS: SB occlusion occurred in 19 (2.22%) LM bifurcation lesions. In multivariable model, three variables, including MV/SB diameter ratio, MV plaque ipsilateral to SB, and baseline diameter stenosis of SB, were independent predictors for SB occlusion (model C-statistics, 0.829; 95% confidence interval [CI], 0.735-0.923, with good calibration). The risk score had a C-statistics of 0.830 (95%CI, 0.738-0.923), with good calibration. Satisfactory discriminative ability of the risk score was also preserved in external validation (C-statistics, 0.794; 95%CI, 0.691-0.896). CONCLUSIONS: The LM bifurcation-specific novel scoring system (LM V-RESOLVE), based on three simple baseline angiographic findings, could help to rapidly discriminate lesions at risk of SB occlusion during LM bifurcation PCI.

Auxin acts upstream of nitric oxide to regulate cell wall xyloglucan and its aluminium-binding capacity in Arabidopsis thaliana.

MAIN CONCLUSION: Auxin acts upstream of NO through NOA and XXT5 pathways to regulate the binding capacity of the root cell wall to Al. In our previous study, we identified an unknown mechanism by which 1-naphthaleneacetic acid (NAA) decreased the fixation of aluminum (Al) in the cell wall. Here, we observed that external application of the nitric oxide (NO) donor S-nitrosoglutathion (GSNO) increased the inhibition of Al on root elongation. Further analysis indicated that GSNO could induce Al accumulation in the roots and root cell walls, which is consistent with lower xyloglucan content. In comparison to the Columbia-0 (Col-0) wild type (WT), endogenous NO-reduced mutants noa1 (NOA pathway) and nia1nia2 (NR pathway) were more resistant to Al, with lower root Al content, higher xyloglucan content, and more Al accumulation in the root cell walls. By contrast, the xxt5 mutant with reduced xyloglucan content exhibited an Al-sensitive phenotype. Interestingly, Al treatment increased the endogenous auxin and NO levels, and the auxin levels induced under Al stress further stimulated NO production. Auxin application reduced Al retention in hemicellulose and decreased the xyloglucan content, similar to the effects observed with GSNO. In yucca and aux1-7 mutants, exogenous application of NO resulted in responses similar to those of the WT, whereas exogenous auxin had little effect on the noa1 mutant under Al stress. In addition, as auxin had similar effects on the nia1nia2 mutant and the WT, exogenous auxin and NO had little effect on the xxt5 mutant under Al stress, further confirming that auxin acts upstream of NO through NOA and XXT5 pathways to regulate the binding capacity of the root cell wall to Al.

Atranorin inhibits Zika virus infection in human glioblastoma cell line SNB-19 via targeting Zika virus envelope protein.

BACKGROUND: Zika virus (ZIKV) is a single-stranded RNA flavivirus transmitted by mosquitoes. Its infection is associated with neurological complications such as neonatal microcephaly and adult Guillain-Barré syndrome, posing a serious threat to the health of people worldwide. Therefore, there is an urgent need to develop effective anti-ZIKV drugs. Atranorin is a lichen secondary metabolite with a wide range of biological activities, including anti-inflammatory, antibacterial and antioxidant, etc. However, the antiviral activity of atranorin and underlying mechanism has not been fully elucidated. PURPOSE: We aimed to determine the anti-ZIKV activity of atranorin in human glioma cell line SNB-19 and investigate the potential mechanism from the perspective of viral life cycle and the host cell functions. METHODS: We first established ZIKV-infected human glioma cells (SNB-19) model and used Western Blot, RT-qPCR, immunofluorescence, fluorescence-activated cell sorting (FACS) and plaque assay to evaluate the anti-ZIKV activity of atranorin. Then we assessed the regulation effect of atranorin on ZIKV induced IFN signal pathway activation by RT-qPCR. Afterward, we introduced time-of-addition assay, viral adsorption assay, viral internalization assay and transferrin uptake assay to define which step of ZIKV lifecycle is influenced by atranorin. Finally, we performed virus infectivity assay, molecular docking and thermal shift assay to uncover the target protein of atranorin on ZIKV. RESULTS: Our study showed that atranorin could protect SNB-19 cells from ZIKV infection, as evidenced by inhibited viral protein expression and progeny virus yield. Meanwhile, atranorin attenuated the activation of IFN signal pathway and downstream inflammatory response that induced by ZIKV infection. The results of time-of-addition assay indicated that atranorin acted primarily by disturbing the viral entry process. After ruling out the effect of atranorin on AXL receptor tyrosine kinase (AXL) dependent virus adsorption and clathrin-mediated endocytosis, we confirmed that atranorin directly targeted the viral envelope protein and lowered ZIKV infectivity by thermal shift assay and virus infectivity assay respectively. CONCLUSION: We found atranorin inhibits ZIKV infection in SNB-19 cells via targeting ZIKV envelope protein. Our study provided an experimental basis for the further development of atranorin and a reference for antiviral drug discovery from natural resources.

Fatty acid binding protein 5 is a novel therapeutic target for hepatocellular carcinoma.

BACKGROUND: Hepatocellular carcinoma (HCC) is an aggressive subtype of liver cancer and is one of the most common cancers with high mortality worldwide. Reprogrammed lipid metabolism plays crucial roles in HCC cancer cell survival, growth, and evolution. Emerging evidence suggests the importance of fatty acid binding proteins (FABPs) in contribution to cancer progression and metastasis; however, how these FABPs are dysregulated in cancer cells, especially in HCC, and the roles of FABPs in cancer progression have not been well defined. AIM: To understand the genetic alterations and expression of FABPs and their associated cancer hallmarks and oncogenes in contributing to cancer malignancies. METHODS: We used The Cancer Genome Atlas datasets of pan cancer and liver hepatocellular carcinoma (LIHC) as well as patient cohorts with other cancer types in this study. We investigated genetic alterations of FABPs in various cancer types. mRNA expression was used to determine if FABPs are abnormally expressed in tumor tissues compared to non-tumor controls and to investigate whether their expression correlates with patient clinical outcome, enriched cancer hallmarks and oncogenes previously reported for patients with HCC. We determined the protein levels of FABP5 and its correlated genes in two HCC cell lines and assessed the potential of FABP5 inhibition in treating HCC cells. RESULTS: We discovered that a gene cluster including five FABP family members (FABP4, FABP5, FABP8, FABP9 and FABP12) is frequently co-amplified in cancer. Amplification, in fact, is the most common genetic alteration for FABPs, leading to overexpression of FABPs. FABP5 showed the greatest differential mRNA expression comparing tumor with non-tumor tissues. High FABP5 expression correlates well with worse patient outcomes (P < 0.05). FABP5 expression highly correlates with enrichment of G2M checkpoint (r = 0.33, P = 1.1e-10), TP53 signaling pathway (r = 0.22, P = 1.7e-5) and many genes in the gene sets such as CDK1 (r = 0.56, P = 0), CDK4 (r = 0.49, P = 0), and TP53 (r = 0.22, P = 1.6e-5). Furthermore, FABP5 also correlates well with two co-expressed oncogenes PLK1 and BIRC5 in pan cancer especially in LIHC patients (r = 0.58, P = 0; r = 0.58, P = 0; respectively). FABP5high Huh7 cells also expressed higher protein levels of p53, BIRC5, CDK1, CDK2, and CDK4 than FABP5low HepG2 cells. FABP5 inhibition more potently inhibited the tumor cell growth in Huh7 cells than in HepG2 cells. CONCLUSION: We discovered that FABP5 gene is frequently amplified in cancer, especially in HCC, leading to its significant elevated expression in HCC. Its high expression correlates well with worse patient outcome, enriched cancer hallmarks and oncogenes in HCC. FABP5 inhibition impaired the cell viability of FABP5high Huh7 cells. All these support that FABP5 is a novel therapeutic target for treating FABP5high HCC.

Enabling Internal Electric Field in Heterogeneous Nanosheets to Significantly Accelerate Alkaline Hydrogen Electrocatalysis.

Efficient bifunctional hydrogen electrocatalysis, encompassing both hydrogen evolution reaction (HER) and hydrogen oxidation reaction (HOR), is of paramount significance in advancing hydrogen-based societies. While non-precious-metal-based catalysts, particularly those based on nickel (Ni), are essential for alkaline HER/HOR, their intrinsic catalytic activity often falls short of expectations. Herein, an internal electric field (IEF) strategy is introduced for the engineering of heterogeneous nickel-vanadium oxide nanosheet arrays grown on porous nickel foam (Ni-V2 O3 /PNF) as bifunctional electrocatalysts for hydrogen electrocatalysis. Strikingly, the Ni-V2 O3 /PNF delivers 10 mA cm-2 at an overpotential of 54 mV for HER and a mass-specific kinetic current of 19.3 A g-1 at an overpotential of 50 mV for HOR, placing it on par with the benchmark 20% Pt/C, while exhibiting enhanced stability in alkaline electrolytes. Density functional theory calculations, in conjunction with experimental characterizations, unveil that the interface IEF effect fosters asymmetrical charge distributions, which results in more thermoneutral hydrogen adsorption Gibbs free energy on the electron-deficient Ni side, thus elevating the overall efficiency of both HER and HOR. The discoveries reported herein guidance are provided for further understanding and designing efficient non-precious-metal-based electrocatalysts through the IEF strategy.

Self-Powered Hydrogen Production with Improved Energy Efficiency via Polysulfides Redox.

In the pursuit of efficient solar-driven electrocatalytic water splitting for hydrogen production, the intrinsic challenges posed by the sluggish kinetics of anodic oxygen evolution and intermittent sunlight have prompted the need for innovative energy systems. Here, we introduce an approach by coupling the polysulfides oxidation reaction with the hydrogen evolution reaction for energy-saving H2 production, which could be powered by an aqueous zinc-polysulfides battery to construct a self-powered energy system. This unusual hybrid water electrolyzer achieves 300 mA cm-2 at a low cell voltage of 1.14 V, saving electricity consumption by 100.4% from 5.47 to 2.73 kWh per m3 H2 compared to traditional overall water splitting. Benefiting from the favorable reaction kinetics of polysulfides oxidation/reduction, the aqueous zinc-polysulfides battery exhibits an energy efficiency of approximately 89% at 1.0 mA cm-2. Specially, the zinc-polysulfide battery effectively stores intermittent solar energy as chemical energy during light reaction by solar cells. Under an unassisted light reaction, the batteries could release energy to drive H2 production through a hybrid water electrolyzer for uninterrupted hydrogen production. Therefore, the aim of simultaneously generating H2 and eliminating the restrictions of intermittent sunlight is realized by combining the merits of polysulfides redox, an aqueous metal-polysulfide battery, and solar cells. We believe that this concept and utilization of polysulfides redox will inspire further fascinating attempts for the development of sustainable energy via electrocatalytic reactions.

High-entropy alloys in electrocatalysis: from fundamentals to applications.

High-entropy alloys (HEAs) comprising five or more elements in near-equiatomic proportions have attracted ever increasing attention for their distinctive properties, such as exceptional strength, corrosion resistance, high hardness, and excellent ductility. The presence of multiple adjacent elements in HEAs provides unique opportunities for novel and adaptable active sites. By carefully selecting the element configuration and composition, these active sites can be optimized for specific purposes. Recently, HEAs have been shown to exhibit remarkable performance in electrocatalytic reactions. Further activity improvement of HEAs is necessary to determine their active sites, investigate the interactions between constituent elements, and understand the reaction mechanisms. Accordingly, a comprehensive review is imperative to capture the advancements in this burgeoning field. In this review, we provide a detailed account of the recent advances in synthetic methods, design principles, and characterization technologies for HEA-based electrocatalysts. Moreover, we discuss the diverse applications of HEAs in electrocatalytic energy conversion reactions, including the hydrogen evolution reaction, hydrogen oxidation reaction, oxygen reduction reaction, oxygen evolution reaction, carbon dioxide reduction reaction, nitrogen reduction reaction, and alcohol oxidation reaction. By comprehensively covering these topics, we aim to elucidate the intricacies of active sites, constituent element interactions, and reaction mechanisms associated with HEAs. Finally, we underscore the imminent challenges and emphasize the significance of both experimental and theoretical perspectives, as well as the potential applications of HEAs in catalysis. We anticipate that this review will encourage further exploration and development of HEAs in electrochemistry-related applications.

[Xiongcan Yishen Formula up-regulates the clock gene expressions in the testis tissue of the rats with late-onset hypogonadism].

OBJECTIVE: To investigate the effect of Xiongcan Yishen Formula (XYF) on the expressions of the clock genes in the testis tissue of the rats with late-onset hypogonadism (LOH). METHODS: Forty-eight 8-week-old male SD rats were randomly divided into 6 groups, normal control, model control, testosterone propionate (TP), and low-, medium- and high-dose XYF. The LOH model was made in the later 5 groups of rats by intraperitoneal injection of D-galactose at 480 mg/kg/d for 56 successive days, while the normal controls were injected with the same volume of normal saline. After modeling, the rats in the low-, medium- and high-dose XYF groups were treated intragastrically with XYF at 10.4, 20.8 and 41.6 g/kg/d, bid, respectively, those in the normal and model control groups with the same volume of distilled water, and those in the TP group intramuscularly with TP at 5.21 mg/kg/d, qd alt, all for 28 days. After treatment, the supernatant was obtained for measurement of the serum T level by ELISA, and the testis tissue collected for determination of the mRNA and protein expressions of BMAL1, NR1D1, PER2, CRY1, StAR and CYP11A1 by RT-qPCR and Western blot. RESULTS: Compared with the normal controls, the rats in the LOH model control group showed significantly decreased serum T and mRNA and protein expressions of BMAL1, NR1D1, PER2, CRY1, StAR and CYP11A1 (P < 0.05). In comparison with the findings in the model controls, the T level was remarkably increased in the TP and XYF groups (P < 0.05), the expressions of StAR mRNA and CYP11A1 mRNA and protein markedly up-regulated in the high-dose XYF group (P < 0.05), and so was the expression of the StAR protein in the XYF and TP groups (P < 0.05), those of BMAL1 and NR1D1 proteins and PER2 mRNA and protein in the high-dose XYF group (P < 0.05), those of BMAL1 mRNA and CRY1 protein in the medium- and high-dose XYF groups (P < 0.05), that of NR1D1 mRNA in the XYF and TP groups (P < 0.05), and that of CRY1 mRNA in the medium- and high-dose XYF and TP groups (P < 0.05). CONCLUSION: Xiongcan Yishen Formula could up-regulate the expressions of the clock genes in the testis tissue of the LOH rats and increase the serum T level as well, which may underlie the mechanisms of Xiongcan Yishen Formula acting on LOH.

Optical force conversion and conveyor belt effect with coupled graphene plasmon waveguide modes.

We propose a double-layer graphene sheets side coupling to a strip of graphene to obtain the optical pulling or pushing force. Combined with coupled mode theory and finite-difference time-domain simulations, it is found that the conveyor belt effect can be realized in conjunction with the lateral optical equilibrium effect upon the radiation loss κe equal to the intrinsic loss κo. The maximum total optical force acting on the strip in the symmetric mode (S-mode) can be up to ∼5.95 in the unit of 1/c and the anti-symmetric (AS-mode) mode reach ∼2.75 1/c. The optical trapping potential Ux and optical trapping force Fx for the S-mode have a value around -22.5 kBT/W and 240 pN/W, while for the AS-mode can up to ∼-56 kBT/W and 520 pN/W, respectively. Our work opens a new avenue for optical manipulation with potential applications in optoelectronic devices and lab-on-a-chip platforms.

Auxin is involved in cadmium accumulation in rice through controlling nitric oxide production and the ability of cell walls to bind cadmium.

Although auxin has been linked to plants' responses to cadmium (Cd) stress, the exact mechanism is yet elusive. The objective of the current investigation was to determine the role and the mechanism of auxin in controlling rice's Cd accumulation. Rice roots with Cd stress have higher endogenous auxin levels, and exogenous auxin combined Cd treatment could reduce root cell wall's hemicellulose content when compared with Cd treatment alone, which in turn reduced its fixation of Cd, as well as decreased the expression of OsCd1 (a major facilitator superfamily gene), OsNRAMP1/5 (Natural Resistance-Associated Macrophage Protein 1/5), OsZIP5/9 (Zinc Transporter 5/9), and OsHMA2 (Heavy Metal ATPase 2) that participated in Cd uptake and root to shoot translocation. Furthermore, less Cd accumulated in the shoots as a result of auxin's impact in increasing the expression of OsCAL1 (Cadmium accumulation in Leaf 1), OsABCG36/OsPDR9 (G-type ATP-binding cassette transporter/Pleiotropic drug resistance 9), and OsHMA3, which were in charge of Cd efflux and sequestering into vacuoles, respectively. Additionally, auxin decreased endogenous nitric oxide (NO) levels and antioxidant enzyme activity, while treatment of a NO scavenger-cPTIO-reduced auxin's alleviatory effects. In conclusion, the rice's ability to tolerate Cd toxicity was likely increased by the auxin-accelerated cell wall Cd exclusion mechanism, a pathway that controlled by the buildup of NO.

Efficacy and safety of combined Chinese and Western medicine in the treatment of knee osteoarthritis: a prospective, multicenter cohort study.

Purpose: To conduct a real-world evaluation of the efficacy and safety of combined Chinese and Western medicine in treating knee osteoarthritis (KOA). Methods: A multicenter, prospective cohort study design was employed, enrolling 450 KOA patients (Kellgren-Lawrence score of 3 or less). The patients were divided into a Western medicine treatment group (WM group) and a combined Western and traditional Chinese medicine treatment group (WM-CM group). A 6-week treatment plan was administered, and follow-up visits occurred at 2 weeks, 4 weeks, and 6 weeks after initiating treatment. The primary outcome indicator was the total Western Ontario and McMaster Universities Arthritis Index (WOMAC) score after 6 weeks of treatment. Secondary outcome indicators included WOMAC subscales for pain, stiffness, and joint function, visual analogue scale (VAS) score, physical component summary (PCS), mental component summary (MCS), and clinical effectiveness. The incidence of drug-related adverse events was used as a safety evaluation indicator. Results: A total of 419 patients were included in the final analysis: 98 in the WM group and 321 in the WM-CM group. The baseline characteristics of the two groups were comparable, except for the incidence of stiffness symptoms and stiffness scores. After 6 weeks of treatment, the WM-CM group exhibited superior results to the WM group in improving the total WOMAC score (24.71 ± 1.38 vs. 16.36 ± 0.62, p < 0.001). The WM-CM group also outperformed the WM group in WOMAC pain and joint function scores, VAS score, PCS score, MCS score, and clinical effectiveness (p < 0.05), which was consistent with the findings of the main evaluation index. Subgroup analysis indicated that the combined Chinese and Western medicine treatment showed more pronounced benefits in patients under 65 years of age and in those with a Kellgren-Lawrence (K-L) classification of 0-I. Throughout the study, no adverse effects were observed in either group. Conclusion: The combination of Chinese and Western medicine demonstrated superiority over Western medicine alone in relieving knee pain symptoms, improving knee function, and enhancing the quality of life for KOA patients with a K-L score of 3 or less. Moreover, the treatment exhibited a good safety profile. Clinical Trial Registration: (https://www.chictr.org.cn/), identifier (ChiCTR1900027175).

Uncovering the prominent role of satellite cells in paravertebral muscle development and aging by single-nucleus RNA sequencing.

To uncover the role of satellite cells (SCs) in paravertebral muscle development and aging, we constructed a single-nucleus transcriptomic atlas of mouse paravertebral muscle across seven timepoints spanning the embryo (day 16.5) to old (month 24) stages. Eight cell types, including SCs, fast muscle cells, and slow muscle cells, were identified. An energy metabolism-related gene set, TCA CYCLE IN SENESCENCE, was enriched in SCs. Forty-two skeletal muscle disease-related genes were highly expressed in SCs and exhibited similar expression patterns. Among them, Pdha1 was the core gene in the TCA CYCLE IN SENESCENCE; Pgam2, Sod1, and Suclg1 are transcription factors closely associated with skeletal muscle energy metabolism. Transcription factor enrichment analysis of the 42 genes revealed that Myod1 and Mef2a were also highly expressed in SCs, which regulated Pdha1 expression and were associated with skeletal muscle development. These findings hint that energy metabolism may be pivotal in SCs development and aging. Three ligand-receptor pairs of extracellular matrix (ECM)-receptor interactions, Lamc1-Dag1, Lama2-Dag1, and Hspg2-Dag1, may play a vital role in SCs interactions with slow/fast muscle cells and SCs self-renewal. Finally, we built the first database of a skeletal muscle single-cell transcriptome, the Musculoskeletal Cell Atlas (http://www.mskca.tech), which lists 630,040 skeletal muscle cells and provides interactive visualization, a useful resource for revealing skeletal muscle cellular heterogeneity during development and aging. Our study could provide new targets and ideas for developing drugs to inhibit skeletal muscle aging and treat skeletal muscle diseases.

Development and validation to predict visual acuity and keratometry two years after corneal crosslinking with progressive keratoconus by machine learning.

Purpose: To explore and validate the utility of machine learning (ML) methods using a limited sample size to predict changes in visual acuity and keratometry 2 years following corneal crosslinking (CXL) for progressive keratoconus. Methods: The study included all consecutive patients with progressive keratoconus who underwent CXL from July 2014 to December 2020, with a 2 year follow-up period before July 2022 to develop the model. Variables collected included patient demographics, visual acuity, spherical equivalence, and Pentacam parameters. Available case data were divided into training and testing data sets. Three ML models were evaluated based on their performance in predicting case corrected distance visual acuity (CDVA) and maximum keratometry (Kmax) changes compared to actual values, as indicated by average root mean squared error (RMSE) and R-squared (R2) values. Patients followed from July 2022 to December 2022 were included in the validation set. Results: A total of 277 eyes from 195 patients were included in training and testing sets and 43 eyes from 35 patients were included in the validation set. The baseline CDVA (26.7%) and the ratio of steep keratometry to flat keratometry (K2/K1; 13.8%) were closely associated with case CDVA changes. The baseline ratio of Kmax to mean keratometry (Kmax/Kmean; 20.9%) was closely associated with case Kmax changes. Using these metrics, the best-performing ML model was XGBoost, which produced predicted values closest to the actual values for both CDVA and Kmax changes in testing set (R2 = 0.9993 and 0.9888) and validation set (R2 = 0.8956 and 0.8382). Conclusion: Application of a ML approach using XGBoost, and incorporation of identifiable parameters, considerably improved variation prediction accuracy of both CDVA and Kmax 2 years after CXL for treatment of progressive keratoconus.

Paeonol repurposing for cancer therapy: From mechanism to clinical translation.

Paeonol (PAE) is a natural phenolic monomer isolated from the root bark of Paeonia suffruticosa that has been widely used in the clinical treatment of some inflammatory-related diseases and cardiovascular diseases. Much preclinical evidence has demonstrated that PAE not only exhibits a broad spectrum of anticancer effects by inhibiting cell proliferation, invasion and migration and inducing cell apoptosis and cycle arrest through multiple molecular pathways, but also shows excellent performance in improving cancer drug sensitivity, reversing chemoresistance and reducing the toxic side effects of anticancer drugs. However, studies indicate that PAE has the characteristics of poor stability, low bioavailability and short half-life, which makes the effective dose of PAE in many cancers usually high and greatly limits its clinical translation. Fortunately, nanomaterials and derivatives are being developed to ameliorate PAE's shortcomings. This review aims to systematically cover the anticancer advances of PAE in pharmacology, pharmacokinetics, nano delivery systems and derivatives, to provide researchers with the latest and comprehensive information, and to point out the limitations of current studies and areas that need to be strengthened in future studies. We believe this work will be beneficial for further exploration and repurposing of this natural compound as a new clinical anticancer drug.

Implications of bleeding on subsequent cardiovascular events in patients with atrial fibrillation after acute coronary syndrome or PCI.

INTRODUCTION: The association between bleeding and subsequent major adverse cardiac and cerebrovascular events (MACCE) remains poorly characterized. We aimed to evaluate the impact of hemorrhagic events in patients with atrial fibrillation (AF) and acute coronary syndrome (ACS) or undergoing percutaneous coronary intervention (PCI). MATERIALS AND METHODS: A total of 1877 consecutive patients with AF and ACS or undergoing PCI were prospectively recruited. The primary endpoint was MACCE, including all-cause death, myocardial infarction, ischemic stroke, systemic embolism or ischemia-driven revascularization during follow-up. Post-discharge bleeding was graded according to TIMI criteria. Associations between bleeding and subsequent MACCE were examined using time-dependent multivariate Cox regression after adjusting for baseline covariates and the time from bleeding. RESULTS: During a median follow-up of 34.2 months, 341 (18.2 %) had TIMI major or minor bleeding events, of whom 86 (25.2 %) also experienced MACCE. The risk of MACCE was significantly higher in patients with bleeding than those without (8.85 % versus 6.99 % per patient-year; HR, 1.568, 95 % CI, 1.232-1.994). In patients who had both bleeding and MACCE, 65.1 % (56 of 86) bleeding events occurred first. Temporal gradients in MACCE risk after major bleeding was highest within 30 days (HRadj, 23.877; 95 % CI, 12.810-44.506) and remained significant beyond 1 year (HRadj, 3.640; 95 % CI, 1.278-10.366). Minor bleeding was associated with increased risk of MACCE within 1 year. CONCLUSIONS: In patients with AF and ACS or PCI, major and minor bleeding were associated with subsequent MACCE with time-dependency. Our findings may aid in better defining net clinical benefit of optimal antithrombotic therapy.

Taking Advantage of Potential Coincidence Region: Advanced Self-Activated/Propelled Hydrazine-Assisted Alkaline Seawater Electrolysis and Zn-Hydrazine Battery.

Hydrazine-assisted water electrolysis presents a promising energy conversion technology for highly efficient hydrogen production. Owing to the potential coincidence region between hydrogen evolution reaction (HER) and hydrazine electro-oxidation, hydrazine oxidation reaction (HzOR) exhibits specific advantages on strategy combination, device construction, and application expansion. Herein, we report a bifunctional electrocatalyst of porous Ni foam-supported interfacial heterogeneous Ni2P/Co2P microspheres (denoted NiCoP/NF), which takes full advantage of this potential coincidence region. Thanks to the 3D microsphere structure and strong interfacial coupling effects between Ni2P and Co2P, NiCoP/NF demonstrates excellent bifunctional electrocatalytic performance, requiring ultralow overpotentials of 70 and 230 mV at 10 mA cm-2 for HER and HzOR, respectively. When using NiCoP/NF as both electrodes, HzOR-assisted water electrolysis exhibits considerably decreased potentials compared with the electro-oxidation of other chemical substrates. Furthermore, the potential coincidence region of 0.1 V makes the application of self-activated/propelled hydrazine-assisted alkaline seawater electrolysis, hydrazine-containing wastewater treatment, and Zn-hydrazine (Zn-Hz) battery realistic. The concept of potential coincidence region provided in this work has significant implications for water electrolysis and other related applications.

Heteroatom-Induced Accelerated Kinetics on Nickel Selenide for Highly Efficient Hydrazine-Assisted Water Splitting and Zn-Hydrazine Battery.

Hydrazine-assisted water electrolysis is a promising energy conversion technology for highly efficient hydrogen production. Rational design of bifunctional electrocatalysts, which can simultaneously accelerate hydrogen evolution reaction (HER)/hydrazine oxidation reaction (HzOR) kinetics, is the key step. Herein, we demonstrate the development of ultrathin P/Fe co-doped NiSe2 nanosheets supported on modified Ni foam (P/Fe-NiSe2) synthesized through a facile electrodeposition process and subsequent heat treatment. Based on electrochemical measurements, characterizations, and density functional theory calculations, a favorable "2 + 2" reaction mechanism with a two-step HER process and a two-step HzOR step was fully proved and the specific effect of P doping on HzOR kinetics was investigated. P/Fe-NiSe2 thus yields an impressive electrocatalytic performance, delivering a high current density of 100 mA cm-2 with potentials of - 168 and 200 mV for HER and HzOR, respectively. Additionally, P/Fe-NiSe2 can work efficiently for hydrazine-assisted water electrolysis and Zn-Hydrazine (Zn-Hz) battery, making it promising for practical application.

Left main bifurcation stenting: impact of residual ischaemia on cardiovascular mortality.

AIMS: The present study sought to determine the rate and prognostic implications of post-procedural physiologically significant residual ischemia according to Murray law-based quantitative flow ratio (µQFR) after left main (LM) bifurcation percutaneous coronary intervention (PCI). METHODS AND RESULTS: Consecutive patients undergoing LM bifurcation stenting at a large tertiary care center between January 2014 and December 2016 with available post-PCI µQFR were included. Physiologically significant residual ischemia was defined by post-PCI µQFR values ≤0.80 in the left anterior descending (LAD) or left circumflex artery (LCX). The primary outcome was 3-year cardiovascular death. The major secondary outcome was 3-year bifurcation-oriented composite endpoint (BOCE). Among 1170 included patients with analyzable post-PCI µQFR, 155 (13.2%) had residual ischemia in either LAD or LCX. Patients with vs. those without residual ischemia had a higher risk of 3-year cardiovascular mortality [5.4% vs. 1.3%; adjusted hazard ratio (HR) 3.20, 95% confidence interval (CI): 1.16-8.80]. The 3-year risk of BOCE was significantly higher in the residual ischemia group (17.8% vs. 5.8%; adjusted HR 2.79, 95% CI: 1.68-4.64), driven by higher incidence of the composite of cardiovascular death and target bifurcation-related myocardial infarction (14.0% vs. 3.3%; adjusted HR 4.06, 95% CI: 2.22-7.42). A significant, inverse association was observed between continuous post-PCI µQFR and the risk of clinical outcomes (per 0.1 µQFR decrease, HR of cardiovascular death 1.27, 95% CI: 1.00-1.62; HR of BOCE 1.29, 95% CI: 1.14-1.47). CONCLUSION: After angiographically successful LM bifurcation PCI, residual ischemia assessed by µQFR was identified in 13.2% of patients and was associated with higher risk of 3-year cardiovascular death, indicating the superior prognostic value of post-PCI physiological assessment.