Palladium(0) and Brønsted Acid Co-catalyzed Enantioselective Hydro-Cyclization of 2,4-Dienyl Hydrazones and Oximes.

The transition metal-catalyzed asymmetric hydro-functionalization of 1,3-dienes has been well explored, but most reactions focus on electron-neutral substrates in an intermolecular manner. Here we first demonstrate that readily available 2,4-dienyl hydrazones and oximes can be efficiently utilized in the hydro-cyclization reaction under co-catalysis of a Brønsted acid and a chiral palladium complex, furnishing multifunctional dihydropyrazones and dihydroisoxazoles, respectively. Diverse substitution patterns for both types of electron-deficient diene compounds are tolerated, and corresponding heterocycles were generally constructed with moderate to excellent enantioselectivity, which can be elaborated to access products with higher molecular complexity and diversity. Control experiments and density functional theory calculations support that α-regioselective protonation of dienyl substrates by acid and concurrent π-Lewis base activation of Pd0 complex is energetically favoured in the formation of active π-allylpalladium intermediates, and an outer-sphere allylic amination or etherification mode is adopted to deliver the observed cyclized products enantioselectively.

TMAO Impairs Mouse Aortic Vasodilation by Inhibiting TRPV4 Channels in Endothelial Cells.

Trimethylamine oxide (TMAO) is an intestinal flora metabolite associated with risk of cardiovascular diseases. Transient receptor potential vanilloid 4 (TRPV4) is a Ca2+-permeable ion channel that is essential for vasodilation and endothelial function. Currently, there are few studies on the effect of TMAO on TRPV4 channels. In the present study, Ca2+ imaging of vascular tissue showed that TMAO inhibited TRPV4-mediated Ca2+ influx into aortic endothelial cells in a dose-dependent manner. Furthermore, a whole-cell patch clamp assay showed that TMAO blocked TRPV4-mediated cation currents. Notably, results of aortic vascular tension measurement showed that TMAO impaired endothelium-dependent vasodilation in mouse aortic vessels through the TRPV4-NO pathway. Our results indicated that TMAO inhibited Ca2+ entry in endothelial cells and impaired vasodilation through the TRPV4-NO pathway in mice. These results provide scientific evidence for novel pathogenic mechanisms underlying the role of TMAO in cardiovascular disease.

Efficient recovery of gold from solution with a thiocyanate-modified Zr-MOF: adsorption properties and DFT calculations.

The design and development of new large-capacity and selective materials for extracting rare precious metals via electronic waste is practically essential. In this paper, a new efficient UiO-66-NCS has been obtained as a consequence of the modification of the classical Zr-MOF (UiO-66-NH2), and its ability to recover gold has been investigated. These batch results adequately illustrated that UiO-66-NCS exhibited good adsorption capacity (675.5 mg g-1) and exceptional selectivity. In addition, UiO-66-NCS achieved faster adsorption equilibrium times of about 120 min. Adsorption kinetics and isotherms demonstrated that the pseudo-second-order adsorption scheme and a Langmuir-type procedure were shown by the adsorption of Au(III) on UiO-66-NCS. Characterized by pH effect experiments, TEM, XRD, and XPS, the adsorption of UiO-66-NCS with Au(III) relies on coordination, which further results in reduction, and the generated Au(0) is uniformly dispersed in the MOF. The adsorbent has considerable advantages for cyclic regeneration. Finally, DFT fitting results showed that the adsorption binding energy of UiO-66-NCS with [AuCl4]- was -8.63 kcal mol-1 for the adsorption process. UiO-66-NCS is likely to be an ideal substance for gold recovery.

Research Progress on Micro(nano)plastic-Induced Programmed Cell Death Associated with Disease Risks.

Due to their robust migration capabilities, slow degradation, and propensity for adsorbing environmental pollutants, micro(nano)plastics (MNPs) are pervasive across diverse ecosystems. They infiltrate various organisms within different food chains through multiple pathways including inhalation and dermal contact, and pose a significant environmental challenge in the 21st century. Research indicates that MNPs pose health threats to a broad range of organisms, including humans. Currently, extensive detection data and studies using experimental animals and in vitro cell culture indicate that MNPs can trigger various forms of programmed cell death (PCD) and can induce various diseases. This review provides a comprehensive and systematic analysis of different MNP-induced PCD processes, including pyroptosis, ferroptosis, autophagy, necroptosis, and apoptosis, based on recent research findings and focuses on elucidating the links between PCD and diseases. Additionally, targeted therapeutic interventions for these diseases are described. This review provides original insights into the opportunities and challenges posed by current research findings. This review evaluates ways to mitigate various diseases resulting from cell death patterns. Moreover, this paper enhances the understanding of the biohazards associated with MNPs by providing a systematic reference for subsequent toxicological research and health risk mitigation efforts.

Interaction of microplastics with perfluoroalkyl and polyfluoroalkyl substances in water: A review of the fate, mechanisms and toxicity.

It is well known that microplastics can act as vectors of pollutants in the environment and are widely spread in freshwater and marine environments. PFAS (perfluoroalkyl and polyfluoroalkyl substances) can remain in the aqueous environment for long periods due to their wide application and good stability. The coexistence of microplastics and PFAS in the aqueous environment creates conditions for their interaction and combined toxicity. Studies on adsorption experiments between them and combined toxicity have been documented in the literature but have not been critically summarized and reviewed. Therefore, in this review, we focused on the interaction mechanisms, influencing factors, and combined toxicity between microplastics and PFAS. It was found that surface complexation may be a new interaction mechanism between microplastics and PFAS. In addition, aged microplastics reduce the adsorption of PFAS due to the presence of oxygenated groups on the surface compared to virgin microplastics. Attached biofilms can increase the adsorption capacity and create conditions for biodegradation. And, the interaction of microplastics and PFAS affects their spatial and temporal distribution in the environment. This review can provide insights into the fate of microplastics and PFAS in the global aquatic environment, fill knowledge gaps on the interactions between microplastics and PFAS, and provide a basic reference for assessing their combined toxicity.

Hepatic IL22RA1 deficiency promotes hepatic steatosis by modulating oxysterol in the liver.

BACKGROUND AND AIMS: An imbalance in lipid metabolism is the main cause of NAFLD. While the pathogenesis of lipid accumulation mediated by extrahepatic regulators has been extensively studied, the intrahepatic regulators modulating lipid homeostasis remain unclear. Previous studies have shown that systemic administration of IL-22 protects against NAFLD; however, the role of IL-22/IL22RA1 signaling in modulating hepatic lipid metabolism remains uncertain. APPROACH AND RESULTS: This study shows that hepatic IL22RA1 is vital in hepatic lipid regulation. IL22RA1 is downregulated in palmitic acid-treated mouse primary hepatocytes, as well as in the livers of NAFLD model mice and patients. Hepatocyte-specific Il22ra1 knockout mice display diet-induced hepatic steatosis, insulin resistance, impaired glucose tolerance, increased inflammation, and fibrosis compared with flox/flox mice. This is attributed to increased lipogenesis mediated by the accumulation of hepatic oxysterols, particularly 3 beta-hydroxy-5-cholestenoic acid (3ß HCA). Mechanistically, hepatic IL22RA1 deficiency facilitates 3ß HCA deposition through the activating transcription factor 3/oxysterol 7 alpha-hydroxylase axis. Notably, 3ß HCA facilitates lipogenesis in mouse primary hepatocytes and human liver organoids by activating liver X receptor-alpha signaling, but IL-22 treatment attenuates this effect. Additionally, restoring oxysterol 7 alpha-hydroxylase or silencing hepatic activating transcription factor 3 reduces both hepatic 3ß HCA and lipid contents in hepatocyte-specific Il22ra1 knockout mice. CONCLUSIONS: These findings indicate that IL22RA1 plays a crucial role in maintaining hepatic lipid homeostasis in an activating transcription factor 3/oxysterol 7 alpha-hydroxylase-dependent manner and establish a link between 3ß HCA and hepatic lipid homeostasis.

TBN as Organic Redox Cocatalyst for Oxidative Tiffeneau-Demjanov-Type Rearrangement Using O2 as Sole Oxidant.

The Tiffeneau-Demjanov-type rearrangement is a ring-expansion reaction involving the cationic rearrangement of cyclic alcohols. The carbocation intermediates can be generated in situ via various means, including Wacker oxidation. In near recent reports on the reinvestiagtions by Wahl et al. (Sietmann, J.; Tenberge, M.; Wahl, J. M. Wacker Oxidation of Methylenecyclobutanes: Scope and Selectivity in an Unusual Setting. Angew. Chem., Int. Ed. 2023, 62, e202215381) and Zhu et al. (Feng, Q.; Wang, Q.; Zhu, J.-P. Oxidative Rearrangement of 1,1-Disubstituted Alkenes to Ketones. Science 2023, 379, 1363-1368), stoichiometric oxidants were involved. In this work, we report the Tiffeneau-Demjanov-type rearrangement can be smoothly promoted by the Pd-TBN cocatalyzed aerobic Wacker oxidation using molecular oxygen as the sole oxidant. tert-Butanol is essential for achieving high yields. Since the first report by Grigg et al. in 1977 (Boontanonda, P.; Grigg, R. J. Palladium (II)-Catalysed Ring Expansion of Methylenecyclobutanes and Related Systems. J. Chem. Soc. Chem. Commun. 1977, 17, 583-584), the five-decade journey of Pd-catalyzed Tiffeneau-Demjanov-type rearrangement returns to the aerobic again.

Study on flow field characteristics of gas-liquid hydrocyclone separation under vibration conditions.

The complex vibration phenomenon occurs in the downhole environment of the gas-liquid hydrocyclone, which affects the flow field in the hydrocyclone. In order to study the influence of vibration on hydrocyclone separation, the characteristics of the flow field in the downhole gas-liquid hydrocyclone were analyzed and studied under the condition of vibration coupling. Based on Computational Fluid Dynamics (CFD), Computational Solid Mechanics Method (CSM) and fluid-solid coupling method, a fluid-solid coupling mechanical model of a gas-liquid cyclone is established. It is found that under the condition of vibration coupling, the velocity components in the three directions of the hydrocyclone flow field change obviously. The peak values of tangential velocity and axial velocity decrease, and the asymmetry of radial velocity increases. The distribution regularity of vorticity and turbulence intensity in the overflow pipe becomes worse. Among them, the vorticity intensity of the overflow pipe is obviously enhanced, and the higher turbulence intensity near the wall occupies more area distribution range. The gas-liquid separation efficiency of the hydrocyclone will decrease with the increase of the rotational speed of the screw pump, and the degree of reduction can reach more than 10%. However, this effect will decrease with the increase of the rotational speed of the screw pump, so the excitation effect caused by the rotational speed has a maximum limit on the flow field.

Two-dimensional bilayer ice in coexistence with three-dimensional ice without confinement.

Icing plays an important role in various physical-chemical process. Although the formation of two-dimensional ice requires nanoscale confinement, two-dimensional bilayer ice in coexistence with three-dimensional ice without confinement remains poorly understood. Here, a critical value of a surface energy parameter is identified to characterize the liquid-solid interface interaction, above which two-dimensional and three-dimensional coexisting ice can surprisingly form on the surface. The two-dimensional ice growth mechanisms could be revealed by capturing the growth and merged of the metastable edge structures. The phase diagram about temperature and pressure vs energy parameters is predicted to distinguish liquid water, two-dimensional ice and three-dimensional ice. Furthermore, the deicing characteristics of coexisting ice demonstrate that the ice adhesion strength is linearly related to the ratio of ice-surface interaction energy to ice temperature. In addition, for gas-solid phase transition, the phase diagram about temperature and energy parameters is predicted to distinguish gas, liquid water, two-dimensional ice and three-dimensional ice. This work gives a perspective for studying the singular structure and dynamics of ice in nanoscale and provides a guide for future experimental realization of the coexisting ice.

Catalytic effects of graphene structures on Pt/graphene catalysts.

Pt/C catalysts have been considered the ideal cathodic catalyst for proton exchange membrane fuel cells (PEMFCs) due to their superior oxygen reduction reaction (ORR) catalytic activity at low temperatures. However, oxidation and corrosion of the carbon black support at the cathode result in the agglomeration of Pt particles, which reduces the active sites in the Pt/C catalyst. Graphene supports have shown great promise to address this issue, and therefore, finding out the main structural features of the graphene support is of great significance for guiding the rational construction of graphene-based Pt (Pt/graphene) catalysts for optimized ORR catalysts. In order to systematically study the influence of the structural features of the graphene support on the electro-catalytic properties of Pt/graphene catalysts, we prepared porous nitrogen-doped reduced graphene oxide (P-NRGO), nitrogen-doped reduced graphene oxide (NRGO), treated P-NRGO (TP-NRGO) and reduced graphene oxide (RGO) with different nitrogen species contents (7.76, 7.54, 3.24, and 0.14 at%), oxygen species contents (18.68, 18.12, 6.34 and 21.12 at%), specific surface areas (370.4, 70.6, 347.7 and 276.2 m2 g-1) and pore volumes (1.366, 0.1424, 1.3299 and 1.0414 cm3 g-1). The ORR activity of the four Pt/graphene catalysts when listed in the order of their half-wave potentials (E 1/2) and peak power densities was found to be as Pt/P-NRGO > Pt/NRGO > Pt/TP-NRGO > Pt/RGO. The long-term durability of Pt/P-NRGO for the operation of H2-air PEMFCs is better than that of commercial Pt/C catalysts. The excellent ORR catalytic performance of Pt/P-NRGO compared to that of the other three Pt/graphene catalysts is ascribed to the high nitrogen species content of P-NRGO that can facilitate the uniform dispersion of Pt particles and provide accessible active sites for ORR. The results indicate that the specific surface area (SSA) and heteroatom dopants have strong influence on the Pt particle size, and that the nitrogen species of graphene supports play a more important role than the oxygen species, specific surface area and pore volume for the Pt/graphene catalysts in providing accessible active sites.

Long-term exposure to ionic liquid [C8mim]Br induces the potential risk of anxiety and memory deterioration through disturbing neurotransmitter systems.

1-octyl-3-methylimidazolium bromide ([C8mim]Br), one of the ionic liquids (ILs), has been used in various fields as an alternative green solvent of conventional organic solvents. Increased application and stabilization of imidazole ring structure lead to its release into the aquatic environment and long-term retention. Structure-activity relationship consideration suggested that ILs may be acetylcholinesterase inhibitors; however, neurotoxicity in vivo, especially the underlying mechanisms is rarely studied. In this study, the zebrafish were exposed to 2.5-10 mg/L [C8mim]Br for 28 days to comprehensively evaluate the neurotoxicity of ILs on adult zebrafish from the behavioral profiles and neurotransmitter systems for the first time. The results indicate that zebrafish exhibit suppressed spatial working memory and anxious behaviors. To assess the potential neurotoxic mechanisms underlying the behavioral responses of zebrafish, we measured the levels of neurotransmitters and precursors, key enzyme activities, and expression levels of relevant genes. Nissl staining showed significant neural cell death in zebrafish after 28-day [C8mim]Br exposure, with corresponding decreases in the levels of neurotransmitters (acetylcholine, glutamate, 5-hydroxytryptophan, gamma-aminobutyric acid, dopamine, and norepinephrine). Furthermore, these results were associated with mRNA expression levels of the disrupted neurotransmitter key genes (th, tph2, mao, slc6a3, ache, gad67). Overall, our study determined that [C8mim]Br caused potential mental disorders like anxiety and memory deterioration in zebrafish by impairing neurotransmitter systems, providing recommendations for the industrial production and application of [C8mim]Br.

Surgical treatment of liver cancer and pancreatic cancer under the China Healthcare Security Diagnosis Related Groups payment system.

BACKGROUND: Data from the World Health Organization's International Agency for Research on Cancer reported that China had the highest prevalence of cancer and cancer deaths in 2022. Liver and pancreatic cancers accounted for the highest number of new cases. Real-world data (RWD) is now widely preferred to traditional clinical trials in various fields of medicine and healthcare, as the traditional research approach often involves highly selected populations and interventions and controls that are strictly regulated. Additionally, research results from the RWD match global reality better than those from traditional clinical trials. AIM: To analyze the cost disparity between surgical treatments for liver and pancreatic cancer under various factors. METHODS: This study analyzed RWD 1137 cases within the HB1 group (patients who underwent pancreatectomy, hepatectomy, and/or shunt surgery) in 2023. It distinguished different expenditure categories, including medical, nursing, technical, management, drug, and consumable costs. Additionally, it assessed the contribution of each expenditure category to total hospital costs and performed cross-group comparisons using the non-parametric Kruskal-Wallis test. This study used the Steel-Dwass test for post-hoc multiple comparisons and the Spearman correlation coefficient to examine the relationships between variables. RESULTS: The study found that in HB11 and HB13, the total hospitalization costs were significantly higher for pancreaticoduodenectomy than for pancreatectomy and hepatectomy. Although no significant difference was observed in the length of hospital stay between patients who underwent pancreaticoduodenectomy and pancreatectomy, both were significantly longer than those who underwent liver resection. In HB15, no significant difference was observed in the total cost of hospitalization between pancreaticoduodenectomy and pancreatectomy; however, both were significantly higher than those in hepatectomy. Additionally, the length of hospital stay was significantly longer for patients who underwent pancreaticoduodenectomy than for those who underwent pancreatectomy or liver resection. CONCLUSION: China Healthcare Security Diagnosis Related Groups payment system positively impacts liver and pancreatic cancer surgeries by improving medical quality and controlling costs. Further research could refine this grouping system and ensure continuous effectiveness and sustainability.

Low levels of supercoiled mitochondrial DNA are involved in heart failure induced by transverse aortic constriction in mice via an inflammatory response mediated by ZBP1.

BACKGROUND: Inflammation in the myocardium plays a critical role in cardiac remodeling and the pathophysiology of heart failure (HF). Previous studies have shown that mitochondrial DNA (mtDNA) can exist in different topological forms. However, the specific influence of the ratio of supercoiled/relaxed mtDNA on the inflammatory response in cardiomyocytes remains poorly understood. The aim of this study was to elucidate the differential effects of different mtDNA types on cardiomyocyte inflammation through regulation of ZBP1. MATERIALS AND METHODS: A mouse model of HF was established by transverse aortic constriction (TAC) or doxorubicin (Doxo) induction. Histopathological changes were assessed by HE staining. ELISA was used to measure cytokine levels (IL-1ß and IL-6). Southern blot analysis was performed to examine the different topology of mtDNA. Pearson correlation analysis was used to determine the correlation between the ratio of supercoiled/relaxed mtDNA and inflammatory cytokines. Reverse transcription quantitative PCR (RT-qPCR) was used to measure the mRNA expression levels of cytokines (IL-1ß, IL-6) and Dloop, as an mtDNA marker. RESULTS: The ratio of supercoiled to relaxed mtDNA was significantly increased in the myocardium of Doxo-induced mice, whereas no significant changes were observed in TAC-induced mice. The levels of IL-1ß and IL-6 were positively correlated with the cytoplasmic mtDNA supercoiled/relaxed circle ratio. Different mtDNA topology has different effects on inflammatory pathways. Low supercoiled mtDNA primarily activates the NF-κB (Ser536) pathway via ZBP1, whereas high supercoiled mtDNA significantly affects the STAT1 and STAT2 pathways. The RIPK3-NF-κB pathway, as a downstream target of ZBP1, mediates the inflammatory response induced by low supercoiled mtDNA. Knockdown of TLR9 enhances the expression of ZBP1, p-NF-κB, and RIPK3 in cardiomyocytes treated with low supercoiled mtDNA, indicating the involvement of TLR9 in the anti-inflammatory role of ZBP1 in low supercoiled mtDNA-induced inflammation. CONCLUSION: Different ratios of supercoiled to relaxed mtDNA influence the inflammatory response of cardiomyocytes and contribute to HF through the involvement of ZBP1. ZBP1, together with its downstream inflammatory mechanisms, mediates the inflammatory response induced by a low ratio of supercoiled mtDNA.

Deep learning-based automatic ASPECTS calculation can improve diagnosis efficiency in patients with acute ischemic stroke: a multicenter study.

OBJECTIVES: The Alberta Stroke Program Early CT Score (ASPECTS), a systematic method for assessing ischemic changes in acute ischemic stroke using non-contrast computed tomography (NCCT), is often interpreted relying on expert experience and can vary between readers. This study aimed to develop a clinically applicable automatic ASPECTS system employing deep learning (DL). METHODS: This study enrolled 1987 NCCT scans that were retrospectively collected from four centers between January 2017 and October 2021. A DL-based system for automated ASPECTS assessment was trained on a development cohort (N = 1767) and validated on an independent test cohort (N = 220). The consensus of experienced physicians was regarded as a reference standard. The validity and reliability of the proposed system were assessed against physicians' readings. A real-world prospective application study with 13,399 patients was used for system validation in clinical contexts. RESULTS: The DL-based system achieved an area under the receiver operating characteristic curve (AUC) of 84.97% and an intraclass correlation coefficient (ICC) of 0.84 for overall-level analysis on the test cohort. The system's diagnostic sensitivity was 94.61% for patients with dichotomized ASPECTS at a threshold of ≥ 6, with substantial agreement (ICC = 0.65) with expert ratings. Combining the system with physicians improved AUC from 67.43 to 89.76%, reducing diagnosis time from 130.6 ± 66.3 s to 33.3 ± 8.3 s (p < 0.001). During the application in clinical contexts, 94.0% (12,591) of scans successfully processed by the system were utilized by clinicians, and 96% of physicians acknowledged significant improvement in work efficiency. CONCLUSION: The proposed DL-based system could accurately and rapidly determine ASPECTS, which might facilitate clinical workflow for early intervention. CLINICAL RELEVANCE STATEMENT: The deep learning-based automated ASPECTS evaluation system can accurately and rapidly determine ASPECTS for early intervention in clinical workflows, reducing processing time for physicians by 74.8%, but still requires validation by physicians when in clinical applications. KEY POINTS: The deep learning-based system for ASPECTS quantification has been shown to be non-inferior to expert-rated ASPECTS. This system improved the consistency of ASPECTS evaluation and reduced processing time to 33.3 seconds per scan. 94.0% of scans successfully processed by the system were utilized by clinicians during the prospective clinical application.

Piloting an intraoral pH device to track gastroesophageal reflux in adults.

This study evaluated in vivo, an intraoral device against the gold standard esophageal device for gastroesophageal reflux disease (GERD) monitoring. Subjects scheduled for a catheter-based esophageal pH/impedance testing at a gastroenterology clinic were recruited. They were screened using the GerdQ questionnaire, demographics and dental conditions recorded. A prototype intraoral device, consisting of a Bravo™ capsule embedded in an Essix-style retainer fabricated for each subject, monitored intraoral pH. Concurrently, subjects underwent 24-h esophageal pH-impedance monitoring. A self-administered survey elicited the comfort and acceptance of both devices. The study recruited ten adult subjects (23 to 60-years-old) with a median GerdQ score of 9.5 corresponding to a 79% likelihood of GERD. Subjects with severe dental erosion had significantly (p < 0.05) higher acid exposure time and more non-meal reflux events. No adverse events were associated with the intraoral device while one was recorded for the esophageal device. The intraoral device was significantly more comfortable to place, more comfortable to wear, and interfered less with daily routine compared to the esophageal device. Accuracy of the intraoral device ranged between 86.15% and 37.82%. Being more tolerable than traditional esophageal pH monitoring, intraoral pH monitoring may be a useful adjunct for the diagnosis and management of GERD.

[Discussion on reference sample research of traditional Chinese medicine compound preparations developed from catalogued ancient classical prescriptions].

The concept of reference sample was put forward in the Guidance on CMC of Traditional Chinese Medicine Compound Preparations Developed from Catalogued Ancient Classical Prescriptions(Interim). The research on reference sample is a key link in the research and development of traditional Chinese medicine(TCM) compound prescriptions from catalogued ancient classical prescriptions(known as Category 3.1 TCM). This paper discusses the content of research on reference sample by analyzing the characteristics of Category 3.1 TCM and the purpose of research on reference sample. Furthermore, suggestions on the research of reference sample are proposed according to the development and evaluation practice of Category 3.1 TCM and research achievements of TCM regulatory science, aiming to provide reference for colleagues in this industry.

Concurrently boosted oxygen reduction/evolution electrocatalysis over highly loaded CoNi/onion-like carbon hybrid nanosheets.

Balancing the bicatalytic activities and stabilities between oxygen reduction reaction (ORR) and oxygen evolution reaction (OER) is a critical yet challenging task for exploring advanced rechargeable Zinc-air batteries (ZABs). Herein, a hybrid nanosheet catalyst with highly dispersed and densified metallic species is developed to boost the kinetics and stabilities of both ORR and OER concurrently. Through a progressive coordination and pyrolysis approach, we directly prepared highly conductive onion-like carbon (OLC) accommodating dense ORR-active CoNC species and enveloping high-loading OER-active CoNi-synergic structures within a porous lamellar architecture. The resultant CoNi/OLC nanosheet catalyst delivers better ORR and OER activities showcasing a smaller reversible oxygen electrode index (ΔE = Ej10 - E1/2) of 0.71 V, compared to state-of-the-art Pt/C-RuO2 catalysts (0.75 V), Co/amorphous carbon polyhedrons (0.80 V), NiO nanoparticles with higher Ni loading (1.00 V), and most CoNi-based bifunctional catalysts reported so far. The rechargeable ZAB assembled with the developed catalyst achieves a remarkable peak power density of 270.3 mW cm-2 (172 % of that achieved by Pt/C + RuO2) and ultrahigh cycling stability with a negligible increase in voltage gap after 800 h (110 mV increase after 200 h for a Pt/C + RuO2-based battery), standing the top level of those ever reported.

Activation of PPAR-α attenuates myocardial ischemia/reperfusion injury by inhibiting ferroptosis and mitochondrial injury via upregulating 14-3-3η.

This study aimed to explore the effects of peroxisome proliferator-activated receptor α (PPAR-α), a known inhibitor of ferroptosis, in Myocardial ischemia/reperfusion injury (MIRI) and its related mechanisms. In vivo and in vitro MIRI models were established. Our results showed that activation of PPAR-α decreased the size of the myocardial infarct, maintained cardiac function, and decreased the serum contents of creatine kinase-MB (CK-MB), lactate dehydrogenase (LDH), and Fe2+ in ischemia/reperfusion (I/R)-treated mice. Additionally, the results of H&E staining, DHE staining, TUNEL staining, and transmission electron microscopy demonstrated that activation of PPAR-α inhibited MIRI-induced heart tissue and mitochondrial damage. It was also found that activation of PPAR-α attenuated MIRI-induced ferroptosis as shown by a reduction in malondialdehyde, total iron, and reactive oxygen species (ROS). In vitro experiments showed that intracellular contents of malondialdehyde, total iron, LDH, reactive oxygen species (ROS), lipid ROS, oxidized glutathione disulphide (GSSG), and Fe2+ were reduced by the activation of PPAR-α in H9c2 cells treated with anoxia/reoxygenation (A/R), while the cell viability and GSH were increased after PPAR-α activation. Additionally, changes in protein levels of the ferroptosis marker further confirmed the beneficial effects of PPAR-α activation on MIRI-induced ferroptosis. Moreover, the results of immunofluorescence and dual-luciferase reporter assay revealed that PPAR-α achieved its activity via binding to the 14-3-3η promoter, promoting its expression level. Moreover, the cardioprotective effects of PPAR-α could be canceled by pAd/14-3-3η-shRNA or Compound C11 (14-3-3η inhibitor). In conclusion, our results indicated that ferroptosis plays a key role in aggravating MIRI, and PPAR-α/14-3-3η pathway-mediated ferroptosis and mitochondrial injury might be an effective therapeutic target against MIRI.

Genetic variation mining of the Chinese mitten crab (Eriocheir sinensis) based on transcriptome data from public databases.

At present, public databases house an extensive repository of transcriptome data, with the volume continuing to grow at an accelerated pace. Utilizing these data effectively is a shared interest within the scientific community. In this study, we introduced a novel strategy that harnesses SNPs and InDels identified from transcriptome data, combined with sample metadata from databases, to effectively screen for molecular markers correlated with traits. We utilized 228 transcriptome datasets of Eriocheir sinensis from the NCBI database and employed the Genome Analysis Toolkit software to identify 96 388 SNPs and 20 645 InDels. Employing the genome-wide association study analysis, in conjunction with the gender information from databases, we identified 3456 sex-biased SNPs and 639 sex-biased InDels. The KOG and KEGG annotations of the sex-biased SNPs and InDels revealed that these genes were primarily involved in the metabolic processes of E. sinensis. Combined with SnpEff annotation and PCR experimental validation, a highly sex-biased SNP located in the Kelch domain containing 4 (Klhdc4) gene, CHR67-6415071, was found to alter the splicing sites of Klhdc4, generating two splice variants, Klhdc4_a and Klhdc4_b. Additionally, Klhdc4 exhibited robust expression across the ovaries, testes, and accessory glands. The sex-biased SNPs and InDels identified in this study are conducive to the development of unisexual cultivation methods for E. sinensis, and the alternative splicing event caused by the sex-biased SNP in Klhdc4 may serve as a potential mechanism for sex regulation in E. sinensis. The analysis strategy employed in this study represents a new direction for the rational exploitation and utilization of transcriptome data in public databases.

Risk factors associated with intraoperative persistent hypotension in pancreaticoduodenectomy.

BACKGROUND: Intraoperative persistent hypotension (IPH) during pancreaticoduodenectomy (PD) is linked to adverse postoperative outcomes, yet its risk factors remain unclear. AIM: To clarify the risk factors associated with IPH during PD, ensuring patient safety in the perioperative period. METHODS: A retrospective analysis of patient records from January 2018 to December 2022 at the First Affiliated Hospital of Nanjing Medical University identified factors associated with IPH in PD. These factors included age, gender, body mass index, American Society of Anesthesiologists classification, comorbidities, medication history, operation duration, fluid balance, blood loss, urine output, and blood gas parameters. IPH was defined as sustained mean arterial pressure < 65 mmHg, requiring prolonged deoxyepinephrine infusion for > 30 min despite additional deoxyepinephrine and fluid treatments. RESULTS: Among 1596 PD patients, 661 (41.42%) experienced IPH. Multivariate logistic regression identified key risk factors: increased age [odds ratio (OR): 1.20 per decade, 95% confidence interval (CI): 1.08-1.33] (P < 0.001), longer surgery duration (OR: 1.15 per additional hour, 95%CI: 1.05-1.26) (P < 0.01), and greater blood loss (OR: 1.18 per 250-mL increment, 95%CI: 1.06-1.32) (P < 0.01). A novel finding was the association of arterial blood Ca2+ < 1.05 mmol/L with IPH (OR: 2.03, 95%CI: 1.65-2.50) (P < 0.001). CONCLUSION: IPH during PD is independently associated with older age, prolonged surgery, increased blood loss, and lower plasma Ca2+.