Cobalt-electrocatalytic HAT for functionalization of unsaturated C-C bonds.

The study and application of transition metal hydrides (TMHs) has been an active area of chemical research since the early 1960s1, for energy storage, through the reduction of protons to generate hydrogen2,3, and for organic synthesis, for the functionalization of unsaturated C-C, C-O and C-N bonds4,5. In the former instance, electrochemical means for driving such reactivity has been common place since the 1950s6 but the use of stoichiometric exogenous organic- and metal-based reductants to harness the power of TMHs in synthetic chemistry remains the norm. In particular, cobalt-based TMHs have found widespread use for the derivatization of olefins and alkynes in complex molecule construction, often by a net hydrogen atom transfer (HAT)7. Here we show how an electrocatalytic approach inspired by decades of energy storage research can be made use of in the context of modern organic synthesis. This strategy not only offers benefits in terms of sustainability and efficiency but also enables enhanced chemoselectivity and distinct, tunable reactivity. Ten different reaction manifolds across dozens of substrates are exemplified, along with detailed mechanistic insights into this scalable electrochemical entry into Co-H generation that takes place through a low-valent intermediate.

Origins of enhanced oxygen reduction activity of transition metal nitrides.

Transition metal nitride (TMN-) based materials have recently emerged as promising non-precious-metal-containing electrocatalysts for the oxygen reduction reaction (ORR) in alkaline media. However, the lack of fundamental understanding of the oxide surface has limited insights into structure-(re)activity relationships and rational catalyst design. Here we demonstrate how a well-defined TMN can dictate/control the as-formed oxide surface and the resulting ORR electrocatalytic activity. Structural characterization of MnN nanocuboids revealed that an electrocatalytically active Mn3O4 shell grew epitaxially on the MnN core, with an expansive strain along the [010] direction to the surface Mn3O4. The strained Mn3O4 shell on the MnN core exhibited an intrinsic activity that was over 300% higher than that of pure Mn3O4. A combined electrochemical and computational investigation indicated/suggested that the enhancement probably originates from a more hydroxylated oxide surface resulting from the expansive strain. This work establishes a clear and definitive atomistic picture of the nitride/oxide interface and provides a comprehensive mechanistic understanding of the structure-reactivity relationship in TMNs, critical for other catalytic interfaces for different electrochemical processes.

Heterozygous Variants in KCNJ10 Cause Paroxysmal Kinesigenic Dyskinesia Via Haploinsufficiency.

OBJECTIVE: Most paroxysmal kinesigenic dyskinesia (PKD) cases are hereditary, yet approximately 60% of patients remain genetically undiagnosed. We undertook the present study to uncover the genetic basis for undiagnosed PKD patients. METHODS: Whole-exome sequencing was performed for 106 PRRT2-negative PKD probands. The functional impact of the genetic variants was investigated in HEK293T cells and Drosophila. RESULTS: Heterozygous variants in KCNJ10 were identified in 11 individuals from 8 unrelated families, which accounted for 7.5% (8/106) of the PRRT2-negative probands. Both co-segregation of the identified variants and the significantly higher frequency of rare KCNJ10 variants in PKD cases supported impacts from the detected KCNJ10 heterozygous variants on PKD pathogenesis. Moreover, a KCNJ10 mutation-carrying father from a typical EAST/SeSAME family was identified as a PKD patient. All patients manifested dystonia attacks triggered by sudden movement with a short episodic duration. Patch-clamp recordings in HEK293T cells revealed apparent reductions in K+ currents of the patient-derived variants, indicating a loss-of-function. In Drosophila, milder hyperexcitability phenotypes were observed in heterozygous Irk2 knock-in flies compared to homozygotes, supporting haploinsufficiency as the mechanism for the detected heterozygous variants. Electrophysiological recordings showed that excitatory neurons in Irk2 haploinsufficiency flies exhibited increased excitability, and glia-specific complementation with human Kir4.1 rescued the Irk2 mutant phenotypes. INTERPRETATION: Our study established haploinsufficiency resulting from heterozygous variants in KCNJ10 can be understood as a previously unrecognized genetic cause for PKD and provided evidence of glial involvement in the pathophysiology of PKD. ANN NEUROL 2024.

Construction of a cross-species cell landscape at single-cell level.

Individual cells are basic units of life. Despite extensive efforts to characterize the cellular heterogeneity of different organisms, cross-species comparisons of landscape dynamics have not been achieved. Here, we applied single-cell RNA sequencing (scRNA-seq) to map organism-level cell landscapes at multiple life stages for mice, zebrafish and Drosophila. By integrating the comprehensive dataset of > 2.6 million single cells, we constructed a cross-species cell landscape and identified signatures and common pathways that changed throughout the life span. We identified structural inflammation and mitochondrial dysfunction as the most common hallmarks of organism aging, and found that pharmacological activation of mitochondrial metabolism alleviated aging phenotypes in mice. The cross-species cell landscape with other published datasets were stored in an integrated online portal-Cell Landscape. Our work provides a valuable resource for studying lineage development, maturation and aging.

How many cell types are there in nature? How do they change during the life cycle? These are two fundamental questions that researchers have been trying to understand in the area of biology. In this study, single-cell mRNA sequencing data were used to profile over 2.6 million individual cells from mice, zebrafish and Drosophila at different life stages, 1.3 million of which were newly collected. The comprehensive datasets allow investigators to construct a cross-species cell landscape that helps to reveal the conservation and diversity of cell taxonomies at genetic and regulatory levels. The resources in this study are assembled into a publicly available website at http://bis.zju.edu.cn/cellatlas/.

Atomically Dispersed Zn/Co-N-C as ORR Electrocatalysts for Alkaline Fuel Cells.

Hydrogen fuel cells have drawn increasing attention as one of the most promising next-generation power sources for future automotive transportation. Developing efficient, durable, and low-cost electrocatalysts, to accelerate the sluggish oxygen reduction reaction (ORR) kinetics, is urgently needed to advance fuel cell technologies. Herein, we report on metal-organic frameworks-derived nonprecious dual metal single-atom catalysts (SACs) (Zn/Co-N-C), consisting of Co-N4 and Zn-N4 local structures. These catalysts exhibited superior ORR activity with a half-wave potential (E1/2) of 0.938 V versus RHE (reversible hydrogen electrode) and robust stability (ΔE1/2 = -8.5 mV) after 50k electrochemical cycles. Moreover, this remarkable performance was validated under realistic fuel cell working conditions, achieving a record-high peak power density of ∼1 W cm-2 among the reported SACs for alkaline fuel cells. Operando X-ray absorption spectroscopy was conducted to identify the active sites and reveal catalytic mechanistic insights. The results indicated that the Co atom in the Co-N4 structure was the main catalytically active center, where one axial oxygenated species binds to form an Oads-Co-N4 moiety during the ORR. In addition, theoretical studies, based on a potential-dependent microkinetic model and core-level shift calculations, showed good agreement with the experimental results and provided insights into the bonding of oxygen species on Co-N4 centers during the ORR. This work provides a comprehensive mechanistic understanding of the active sites in the Zn/Co-N-C catalysts and will pave the way for the future design and advancement of high-performance single-site electrocatalysts for fuel cells and other energy applications.

The Electrochemical Peroxydisulfate-Oxalate Autocatalytic Reaction.

Aqueous solutions containing both the strong oxidant, peroxydisulfate (S2O82-), and the strong reductant, oxalate (C2O42-), are thermodynamically unstable due to the highly exothermic homogeneous redox reaction: S2O82- + C2O42- → 2 SO42- + 2 CO2 (ΔG0 = -490 kJ/mol). However, at room temperature, this reaction does not occur to a significant extent over the time scale of a day due to its inherently slow kinetics. We demonstrate that the S2O82-/C2O42- redox reaction occurs rapidly, once initiated by the Ru(NH3)62+-mediated 1e- reduction of S2O82- to form S2O83•-, which rapidly undergoes bond cleavage to form SO42- and the highly oxidizing radical SO4•-. Theoretically, the mediated electrochemical generation of a single molecule of S2O83•- can initiate an autocatalytic cycle that consumes both S2O82- and C2O42- in bulk solution. Several experimental demonstrations of S2O82-/C2O42- autocatalysis are presented. Differential electrochemical mass spectrometry measurements demonstrate that CO2 is generated in solution for at least 10 min following a 30-s initiation step. Quantitative bulk electrolysis of S2O82- in solutions containing excess C2O42- is initiated by electrogeneration of immeasurably small quantities of S2O83•-. Capture of CO2 as BaCO3 during electrolysis additionally confirms the autocatalytic generation of CO2. First-principles density functional theory calculations, ab initio molecular dynamics simulations, and finite difference simulations of cyclic voltammetric responses are presented that support and provide additional insights into the initiation and mechanism of S2O82-/C2O42- autocatalysis. Preliminary evidence indicates that autocatalysis also results in a chemical traveling reaction front that propagates into the solution normal to the planar electrode surface.

A Photo-induced Cross-Linking Enhanced A and B Combined Multi-Functional Spray Hydrogel Instantly Protects and Promotes of Irregular Dynamic Wound Healing.

Wounds in harsh environments can face long-term inflammation and persistent infection, which can slow healing. Wound spray is a product that can be rapidly applied to large and irregularly dynamic wounds, and can quickly form a protective film in situ to inhibit external environmental infection. In this study, a biodegradable A and B combined multi-functional spray hydrogel is developed with methacrylate-modified chitosan (CSMA1st) and ferulic acid (FA) as type A raw materials and oxidized Bletilla striata polysaccharide (OBSP) as type B raw materials. The precursor CSMA1st-FA/OBSP (CSOB-FA1st) hydrogel is formed by the self-cross-linking of dynamic Schiff base bonds, the CSMA-FA/OBSP (CSOB-FA) hydrogel is formed quickly after UV-vis light, so that the hydrogel fits with the wound. Rapid spraying and curing provide sufficient flexibility and rapidity for wounds and the hydrogel has good injectability, adhesive, and mechanical strength. In rats and miniature pigs, the A and B combined spray hydrogel can shrink wounds and promote healing of infected wounds, and promote the enrichment of fibrocyte populations. Therefore, the multifunctional spray hydrogel combined with A and B can protect irregular dynamic wounds, prevent wound infection and secondary injury, and be used for safe and effective wound treatment, which has a good prospect for development.

CLOSE protocol versus lower ablation index value for paroxysmal atrial fibrillation: A randomized noninferior clinical trial.

INTRODUCTION: The optimized ablation index (AI) value for catheter ablation of atrial fibrillation (AF) remains to be defined. We aimed to compare the efficacy and safety of CLOSE protocol and lower AI protocol in paroxysmal AF. METHODS AND RESULTS: Patients with symptomatic, drug-resistant paroxysmal AF for first ablation were prospectively enrolled from September 2020 to January 2022. The patients were randomly divided into CLOSE group (AI ≥ 550 for anterior/roof segments and ≥400 for posterior/inferior segments) and lower AI group (AI ≥ 450 for anterior/roof segments and ≥350 for posterior/inferior segments). First-pass isolation, acute pulmonary vein (PV) reconnections, 1-year arrhythmia recurrence, and major complications were assessed. Of the 270 enrolled patients, 238 completed 1-year follow-up (118 in CLOSE group and 120 in lower AI group). First-pass isolation in left PVs was higher in CLOSE group (71.2% vs. 53.3%, p = .005). Acute PV reconnections were comparable between groups (9.3% vs. 14.2%, p = .246). At 1 year, 86.4% in CLOSE group versus 81.7% in lower AI group were free from atrial arrhythmia (log rank p = .334). The proportion difference was -4.8% (95% CI: -14.1% to 4.6%), and p = .475 for noninferiority. Stroke occurred in four patients of lower AI group, and no cardiac tamponade, atrioesophageal fistula, major bleeding or death occurred post procedure. CONCLUSION: For patients with paroxysmal AF and treated by AI-guided PV ablation, lower AI is not noninferior to CLOSE protocol.

Independent and joint relationships of cardiorespiratory fitness and body mass index with liver fat content.

AIMS: To investigate the relationship between cardiorespiratory fitness (CRF) and liver fat content (LFC) in community-based participants and highlight their relationship in people with different body mass indices (BMIs). MATERIALS AND METHODS: Using UK Biobank data, CRF was estimated with bicycle ergometer fitness testing and was evaluated based on physical work capacity at 75% maximum heart rate (PWC75%). LFC was quantified through liver proton density fat fraction (PDFF) on magnetic resonance imaging. Multivariate linear regression models were used to analyse the associations of CRF and BMI with absolute reduction and percentage change in PDFF (%). RESULTS: In total, 5765 participants with a mean age of 55.57 years and a median (range) follow-up of 10.7 (4.0-17.7) years were included. Compared with the lowest PWC75% tertile, the absolute reduction and percentage change in PDFF in the highest PWC75% tertile were -0.450 (95% confidence interval [CI] -0.699 to -0.192) and -4.152 (95% CI -6.044 to -2.104), respectively. These associations were independent of BMI, and individuals with obesity and normal weight had the largest absolute reduction and percentage change in LFC, respectively (p for interaction <0.001). Joint analysis showed that PWC75% and BMI had a negative dose-response relationship with PDFF. These associations were consistent in different sex and age subgroups (p for interaction >0.05). CONCLUSIONS: There was a significant negative association between CRF and LFC, and this association was independent of BMI. The results of this study strongly recommend improving CRF to mitigate LFC.

Amyloid A and lactic acid as a predictor in patients with sepsis in patients with liver cirrhosis.

BACKGROUND: Sepsis is triggered by pathogenic microorganisms, resulting in a systemic inflammatory response. Liver cirrhosis and sepsis create a vicious cycle: cirrhosis weakens immune function, raising infection risk and hindering pathogen clearance. Optimal treatment outcomes depend on understanding liver cirrhosis patients' sepsis risk factors. Thus, preventing sepsis involves addressing these risk factors. Therefore, early identification and understanding of clinical characteristics in liver cirrhosis patients with sepsis are crucial for selecting appropriate antibiotics. A case-control study using logistic regression was conducted to examine the prognostic value of amyloid A/lactate level monitoring in identifying sepsis risk factors in liver cirrhosis patients. METHODS: From March 2020 to March 2022, 136 liver cirrhosis patients treated at our hospital were divided into a sepsis group (n = 35) and a non-sepsis group (n = 101) based on sepsis complications. General clinical data were collected. Univariate analysis screened for liver cirrhosis patients' sepsis risk factors. Multivariate logistic analysis was subsequently employed to evaluate the risk factors. Sepsis patients were followed up for a month. Based on prognosis, patients were categorized into a poor prognosis group (n = 16) and a good prognosis group (n = 19). Serum amyloid A (SAA) and blood lactic acid (BLA) levels were compared between the two groups. The receiver operating characteristic (ROC) curve was used to evaluate the prognostic value of both individual and combined SAA/BLA monitoring. RESULTS: Patient data, including age, diabetes history, liver cancer, hepatic artery embolization, recent antibiotic use, invasive procedures within two weeks, APACHE II Scoring, ALB and SAA and BLA levels, were compared between the sepsis and non-sepsis groups, showing significant differences (P < 0.05). Logistic regression identified factors such as age ≥ 70, recent antibiotic use, recent invasive procedures, history of liver cancer, hepatic artery embolization history, high APACHE II scores, decreased albumin, and elevated SAA and BLA levels as independent sepsis risk factors in liver cirrhosis patients (P < 0.05). Among the 35 sepsis patients, 16 had a poor prognosis, representing an incidence rate of 45.71%. Serum SAA and BLA levels were significantly higher in the poor prognosis group than in the good prognosis group (P < 0.05). The AUC for serum SAA and BLA was 0.831 (95%CI: 0.738-0.924), 0.720 (95%CI: 0.600-0.840), and 0.909 (95%CI: 0.847-0.972), respectively. The combined diagnostic AUC was significantly higher than that of single factor predictions (P < 0.05). The predictive value ranked as follows: joint detection > SAA > BLA. CONCLUSION: In treating liver cirrhosis, prioritize patients with advanced age, a history of hepatic artery embolization, recent invasive operations, history of liver cancer, recent antibiotic exposure, high APACHE II scores and low albumin. Closely monitoring serum SAA and BLA levels in these patients can offer valuable insights for early clinical prevention and treatment.