Enhancing H2O2 Electrosynthesis at Industrial-Relevant Current in Acidic Media on Diatomic Cobalt Sites.

Electrocatalytic synthesis of hydrogen peroxide (H2O2) in acidic media is an efficient and eco-friendly approach to produce inherently stable H2O2, but limited by the lack of selective and stable catalysts under industrial-relevant current densities. Herein, we report a diatomic cobalt catalyst for two-electron oxygen reduction to efficiently produce H2O2 at 50-400 mA cm-2 in acid. Electrode kinetics study shows a >95% selectivity for two-electron oxygen reduction on the diatomic cobalt sites. In a flow cell device, a record-high production rate of 11.72 mol gcat-1 h-1 and exceptional long-term stability (100 h) are realized under high current densities. In situ spectroscopic studies and theoretical calculations reveal that introducing a second metal into the coordination sphere of the cobalt site can optimize the binding strength of key H2O2 intermediates due to the downshifted d-band center of cobalt. We also demonstrate the feasibility of processing municipal plastic wastes through decentralized H2O2 production.

General Synthesis of a Diatomic Catalyst Library via a Macrocyclic Precursor-Mediated Approach.

Heterogeneous catalysts containing diatomic sites are often hypothesized to have distinctive reactivity due to synergistic effects, but there are limited approaches that enable the convenient production of diatomic catalysts (DACs) with diverse metal combinations. Here, we present a general synthetic strategy for constructing a DAC library across a wide spectrum of homonuclear (Fe2, Co2, Ni2, Cu2, Mn2, and Pd2) and heteronuclear (Fe-Cu, Fe-Ni, Cu-Mn, and Cu-Co) bimetal centers. This strategy is based on an encapsulation-pyrolysis approach, wherein a porous material-encapsulated macrocyclic complex mediates the structure of DACs by preserving the main body of the molecular framework during pyrolysis. We take the oxygen reduction reaction (ORR) as an example to show that this DAC library can provide great opportunities for electrocatalyst development by unlocking an unconventional reaction pathway. Among all investigated sites, Fe-Cu diatomic sites possess exceptional high durability for ORR because the Fe-Cu pairs can steer elementary steps in the catalytic cycle and suppress the troublesome Fenton-like reactions.

A new GLP-1 analogue with prolonged glucose-lowering activity in vivo via backbone-based modification at the N-terminus.

Glucagon-like peptide-1 (GLP-1) is an endogenous insulinotropic hormone with wonderful glucose-lowering activity. However, its clinical use in type II diabetes is limited due to its rapid degradation at the N-terminus by dipeptidyl peptidase IV (DPP-IV). Among the N-terminal modifications of GLP-1, backbone-based modification was rarely reported. Herein, we employed two backbone-based strategies to modify the N-terminus of tGLP-1. Firstly, the amide N-methylated analogues 2-6 were designed and synthesized to make a full screening of the N-terminal amide bonds, and the loss of GLP-1 receptor (GLP-1R) activation indicated the importance of amide H-bonds. Secondly, with retaining the N-terminal amide H-bonds, the ß-peptide replacement strategy was used and analogues 7-13 were synthesized. By two rounds of screening, analogue 10 was identified. Analogue 10 greatly improved the DPP-IV resistance with maintaining good GLP-1R activation in vitro, and showed approximately a 4-fold prolonged blood glucose-lowering activity in vivo in comparison with tGLP-1. This modification strategy will benefit the development of GLP-1-based anti-diabetic drugs.

Opportunities and challenges for plastic depolymerization by biomimetic catalysis.

Plastic waste has imposed significant burdens on the environment. Chemical recycling allows for repeated regeneration of plastics without deterioration in quality, but often requires harsh reaction conditions, thus being environmentally unfriendly. Enzymatic catalysis offers a promising solution for recycling under mild conditions, but it faces inherent limitations such as poor stability, high cost, and narrow substrate applicability. Biomimetic catalysis may provide a new avenue by combining high enzyme-like activity with the stability of inorganic materials. Biomimetic catalysis has demonstrated great potential in biomass conversion and has recently shown promising progress in plastic degradation. This perspective discusses biomimetic catalysis for plastic degradation from two perspectives: the imitation of the active centers and the imitation of the substrate-binding clefts. Given the chemical similarity between biomass and plastics, relevant work is also included in the discussion to draw inspiration. We conclude this perspective by highlighting the challenges and opportunities in achieving sustainable plastic recycling via a biomimetic approach.

PET recycling under mild conditions via substituent-modulated intramolecular hydrolysis.

Catalytic depolymerization represents a promising approach for the closed-loop recycling of plastic wastes. Here, we report a knowledge-driven catalyst development for poly(ethylene terephthalate) (PET) recycling, which not only achieves more than 23-fold enhancement in specific activity but also reduces the alkali concentration by an order of magnitude compared with the conventional hydrolysis. Substituted binuclear zinc catalysts are developed to regulate biomimetic intramolecular PET hydrolysis. Hammett studies and density functional theory (DFT) calculations indicate that the substituents modify the charge densities of the active centers, and an optimal substituent should slightly increase the electron richness of the zinc sites to facilitate the formation of a six-membered ring intermediate. The understanding of the structure-activity relationship leads to an advanced catalyst with a specific activity of 778 ± 40 gPET h-1 gcatal-1 in 0.1 M NaOH, far outcompeting the conventional hydrolysis using caustic bases (<33.3 gPET h-1 gcatal-1 in 1-5 M NaOH). This work opens new avenues for environmentally benign PET recycling.

Ascending aortic volume: A feasible indicator for ascending aortic aneurysm elective surgery?

Diameter-based criterion have been widely adopted for preventive surgery of ascending thoracic aortic aneurysm (ATAA). However, recent and growing evidence has shown that diameter-based methods may not be sufficient for identifying patients who are at risk of an ATAA. In this study, fluid-structure interaction (FSI) analysis was performed on one-hundred ATAA geometries reconstructed from clinical data to examine the relationship between hemodynamic conditions, ascending aortic volume (AAV), ascending aortic curvature, and aortic ratios measured from the reconstructed 3D models. The simulated hemodynamic and biomechanical parameters were compared among different groups of ATAA geometries classified based on AAV. The ATAAs with enlarged AAV showed significantly compromised hemodynamic conditions and higher mechanical wall stress. The maximum oscillatory shear index (OSI), particle residence time (PRT) and wall stress (WS) were significantly higher in enlarged ATAAs compared with controls (0.498 [0.497, 0.499] vs 0.499 [0.498, 0.499], p = 0.002, 312.847 [207.445, 519.391] vs 996.047 [640.644, 1573.140], p < 0.001, 769.680 [668.745, 879.795] vs 1072.000 [873.060, 1280.000] kPa, p < 0.001, respectively). Values were reported as median with interquartile range (IQR). AAV was also found to be more strongly correlated with these parameters compared to maximum diameter. The correlation coefficient between AAV and average WS was as high as 0.92 (p < 0.004), suggesting that AAV might be a feasible risk identifier for ATAAs. STATEMENT OF SIGNIFICANCE: Ascending thoracic aortic aneurysm is associated with the risk of dissection or rupture, creating life-threatening conditions. Current surgical intervention guidelines are mostly diameter based. Recently, many studies proposed to incorporate other morphological parameters into the current clinical guidelines to better prevent severe adverse aortic events like rupture or dissection. The purpose of this study is to gain a better understanding of the relationship between morphological parameters and hemodynamic parameters in ascending aortic aneurysms using fluid-solid-interaction analysis on patient-specific geometries. Our results suggest that ascending aortic volume may be a better indicator for surgical intervention as it shows a stronger association with pathogenic hemodynamic conditions.

Cuproptosis and Immune-Related Gene Signature Predicts Immunotherapy Response and Prognosis in Lung Adenocarcinoma.

Cuproptosis and associated immune-related genes (IRG) have been implicated in tumorigenesis and tumor progression. However, their effects on lung adenocarcinoma (LUAD) have not been elucidated. Therefore, we investigated the impact of cuproptosis-associated IRGs on the immunotherapy response and prognosis of LUAD using a bioinformatical approach and in vitro experiments analyzing clinical samples. Using the cuproptosis-associated IRG signature, we classified LUAD into two subtypes, cluster 1 and cluster 2, and identified three key cuproptosis-associated IRGs, NRAS, TRAV38-2DV8, and SORT1. These three genes were employed to establish a risk model and nomogram, and to classify the LUAD cohort into low- and high-risk subgroups. Biofunctional annotation revealed that cluster 2, remarkably downregulating epigenetic, stemness, and proliferation pathways activity, had a higher overall survival (OS) and immunoinfiltration abundance compared to cluster 1. Real-time quantitative PCR (RT-qPCR) validated the differential expression of these three genes in both subgroups. scRNA-seq demonstrated elevated expression of NRAS and SORT1 in macrophages. Immunity and oncogenic and stromal activation pathways were dramatically enriched in the low-risk subgroup, and patients in this subgroup responded better to immunotherapy. Our data suggest that the cuproptosis-associated IRG signature can be used to effectively predict the immunotherapy response and prognosis in LUAD. Our work provides enlightenment for immunotherapy response assessment, prognosis prediction, and the development of potential prognostic biomarkers for LUAD patients.

Natural history of isolated abdominal aortic dissection: A prospective cohort study.

Objectives: Isolated abdominal aortic dissection (IAAD) is extremely rare, with its optimal treatment and intervention timing remaining poorly understood. We aimed to study the natural history of IAAD and facilitate better clinical decision. Methods: Consecutive patients admitted to our institution from January 2016 to April 2021 were enrolled and followed up prospectively. All-cause death was taken as the primary endpoint. Results: A total of 68 patients with IAAD were included. The mean age at presentation was 61.2 ± 14.8 (Range: 26.0, 93.0) years and 55 (80.9%) were male. A total of 38 (55.9%) patients were treated conservatively, 27 (39.7%) received endovascular aneurysm repair (EVAR), and 3 (4.4%) underwent open surgery. After a mean follow-up of 2.4 years (Range: 0.1, 5.5), 9 (13.2%) patients died, 8 of whom (21.0%) were treated conservatively and 1 EVAR (3.7%). Compared with EVAR/open surgery, patient treated conservatively had a much worse survival (p = 0.043). There was no significant difference between different IAAD aortic sizes regarding mortality (p = 0.220). Patients with completely thrombosed false lumen fared improved survival rate, followed by partial thrombosis and patency, respectively, although not significantly (p = 0.190). No significant difference was observed between male and female concerning survival rate (p = 0.970). Patients without symptoms had a significantly improved survival (p = 0.048). Conclusion: On the basis of patients' preference and surgeons' experience, a more aggressive treatment regimen for IAAD should be considered, with EVAR being the first choice, especially for those with persistent symptoms and patent false lumen, regardless of sex, age, or aortic size.

Diatomic iron nanozyme with lipoxidase-like activity for efficient inactivation of enveloped virus.

Enveloped viruses encased within a lipid bilayer membrane are highly contagious and can cause many infectious diseases like influenza and COVID-19, thus calling for effective prevention and inactivation strategies. Here, we develop a diatomic iron nanozyme with lipoxidase-like (LOX-like) activity for the inactivation of enveloped virus. The diatomic iron sites can destruct the viral envelope via lipid peroxidation, thus displaying non-specific virucidal property. In contrast, natural LOX exhibits low antiviral performance, manifesting the advantage of nanozyme over the natural enzyme. Theoretical studies suggest that the Fe-O-Fe motif can match well the energy levels of Fe2 minority ß-spin d orbitals and pentadiene moiety π* orbitals, and thus significantly lower the activation barrier of cis,cis-1,4-pentadiene moiety in the vesicle membrane. We showcase that the diatomic iron nanozyme can be incorporated into air purifier to disinfect airborne flu virus. The present strategy promises a future application in comprehensive biosecurity control.

Design and rationale of the ATTRACTIVE trial: a randomised trial of intrAThrombus Thrombolysis versus aspiRAtion thrombeCTomy during prImary percutaneous coronary interVEntion in ST-segment elevation myocardial infarction patients with high thrombus burden.

INTRODUCTION: ST-segment elevation myocardial infarction (STEMI) with high thrombus burden is associated with a poor prognosis. Manual aspiration thrombectomy reduces coronary vessel distal embolisation, improves microvascular perfusion and reduces cardiovascular deaths, but it promotes more strokes and transient ischaemic attacks in the subgroup with high thrombus burden. Intrathrombus thrombolysis (ie, the local delivery of thrombolytics into the coronary thrombus) is a recently proposed treatment approach that theoretically reduces thrombus volume and the risk of microvascular dysfunction. However, the safety and efficacy of intrathrombus thrombolysis lack sufficient clinical evidence. METHODS AND ANALYSIS: The intrAThrombus Thrombolysis versus aspiRAtion thrombeCTomy during prImary percutaneous coronary interVEntion trial is a multicentre, prospective, open-label, randomised controlled trial with the blinded assessment of outcomes. A total of 2500 STEMI patients with high thrombus burden who undergo primary percutaneous coronary intervention will be randomised 1:1 to intrathrombus thrombolysis with a pierced balloon or upfront routine manual aspiration thrombectomy. The primary outcome will be the composite of cardiovascular death, recurrent myocardial infarction, cardiogenic shock, heart failure readmission, stent thrombosis and target-vessel revascularisation up to 180 days. ETHICS AND DISSEMINATION: The trial was approved by Ethics Committees of China-Japan Friendship Hospital (2022-KY-013) and all other participating study centres. The results of this trial will be published in peer-reviewed journals. TRIAL REGISTRATION NUMBER: NCT05554588.

Depression of caregivers is significantly associated with depression and hospitalization of hemodialysis patients.

INTRODUCTION: The current study aims to elucidate the relationships of depression of caregivers with depression of hemodialysis patients and determine predictors of hospitalization of hemodialysis patients. METHODS: The single-center, cross-sectional study consisted of 200 pairs of eligible hemodialysis patients and caregivers from January 2019 to January 2020. Depression was evaluated using Hospital Anxiety and Depression Scale (HADS) questionnaire. FINDINGS: There were 89 hemodialysis patients with depression (44.5%) and 74 caregivers with depression (37.0%). In multi-variable logistic regression analysis, the hemodialysis patients with depressed caregivers were at increased risk of depression after adjusting for potential confounders (OR = 2.36, p = 0.04). Depression of hemodialysis patients (ß = 0.51, p = 0.00) and depression of caregivers (ß = 0.36, p = 0.04) were predictors of hospitalization of hemodialysis patients. DISCUSSION: Depression was prevalent among hemodialysis patients and their caregivers. Depression of caregivers was a risk factor for depression and hospitalization of hemodialysis patients. Implementation of appropriate screening programs and specific interventions for depression of hemodialysis patients and their caregivers is required.

Chinese contribution to NEJM, Lancet, JAMA, and BMJ from 2011 to 2020: a 10-year bibliometric study.

Background: New England Journal of Medicine (NEJM), Lancet, Journal of the American Medical Association (JAMA), and British Medical Journal (BMJ) are collectively known as "the Top Four Medical Journals (TFMJ)" in China. Through the analysis of Chinese scholars' publications in the TFMJ in the recent 10 years, this study aimed to clarify the current situation of high-quality medical research conducted by Chinese scholars and institutions. Methods: Data were retrieved and downloaded manually from PubMed (2011-2020). Information on the publication year, journal, author, affiliation, and citation, etc. were extracted and analyzed using R software. Results: A total of 761 articles were involved in the final analysis. The number of articles published by Chinese scholars in the TFMJ was 135/29,942 (0.45%) in BMJ, 124/14,033 (0.88%) in JAMA, 314/16,117 (1.94%) in Lancet, and 188/15,242 (1.23%) in NEJM (P<0.001). Besides, the letter was the main research type, which was up to 44.54%, and the original research only accounted for 17.47%. The most popular subspecialty and subject were infectious diseases and COVID-19, respectively. The most productive researcher was Chen Wang, and Bin Cao was the most cited Chinese scholar. The most productive institute was Chinese Academy of Medical Sciences and Peking Union Medical College. The most cited study was "Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China". Conclusions: The presence of Chinese scholars in the TFMJ has grown, but there is still much room to improve. A Matthew effect in China's high-level scientific research was demonstrated.

Rational design and synthesis of potent aminoglycoside antibiotics against resistant bacterial strains.

Based on the structural information of biomacromolecule-aminoglycoside complexes, a series of kanamycin B analogues were rationally designed and synthesized. A convenient approach to the construction of kanamycin derivatives, in which the C4'-position on ring I of neamine moiety was modified, was developed. Most synthetic analogues exhibited good to excellent antibiotic activity against some typical drug-resistant bacteria. The disclosed results suggested that the C4'-position of aminoglycosides such as kanamycin may be an ideal site for modification to gain new modifying enzyme-resistant aminoglycoside antibiotics.

Synthesis and biological evaluation of bergenin derivatives as new immunosuppressants.

Bergenin, which is isolated from Bergenia species, exhibits various pharmacological properties. In the search for new types of immunosuppressants, a series of bergenin derivatives were designed and synthesized, and their immunosuppressive effects were evaluated by the CCK-8 assay. The experimental data demonstrated that compounds 7 and 13 showed the strongest inhibition effects on mouse splenocyte proliferation (IC50 = 3.52 and 5.39 µM, respectively). Further studies revealed that the inhibitory effect may come from the suppression of both IFN-γ and IL-4 cytokines. Alkylated derivatives of bergenin with n-hexyl and n-heptyl on the two phenolic hydroxyl groups showed better inhibitory activities. The hydrophobicity of bergenin derivatives, the configuration of the 4-OH in bergenin, and the ability to form hydrogen bonds of the substituents on the C-4 position are important to the immunosuppressive activity. This work proved that the modifications of bergenin may represent a new route to the discovery of a new class of immunosuppressive agents.

Correlation of Serum Adropin Levels with Risk Factors of Cardiovascular Disease in Hemodialysis Patients.

Background: Many preclinical studies have shown that adropin has physiological effects such as regulating glucose, lipid, and energy metabolism, protecting endothelial cells and antiatherosclerosis. Our aim is to explore whether adropin is correlated with risk factors of cardiovascular disease (CVD) in hemodialysis (HD) patients. Methods: We recruited 170 HD patients and 120 healthy controls. The serum adropin concentration and clinical characteristics were measured. Results: The serum adropin concentration in HD patients was significantly lower than that in healthy controls and which in HD patients with CVD or diabetes mellitus (DM) was significantly lower than that in patients without CVD or DM. The correlation analysis showed that serum adropin levels were correlated negatively with Age, CVD history, DM history, C-reactive protein, type B natriuretic peptide, phosphorus, intact parathyroid hormone, carotid artery plaque amount and carotid intima-media thickness (CIMT), left ventricular septal thickness (LVSTd), and left ventricular posterior wall thickness, whereas it was correlated positively with albumin, hemoglobin, serum creatinine and Kt/V, and ejection fraction value. Partial correlation analysis verified that serum adropin levels were correlated negatively with CIMT, and multiple linear regression analysis revealed that low serum adropin levels may be one independent predictors of CIMT. However, the partial correlation analysis and multiple linear regression analysis did not identify the significant correlation between serum adropin levels and LVSTd. Conclusions: Our study revealed that serum adropin level is significantly correlated with risk factors of CVD and low serum adropin levels may be a potential predictor of CVD in HD patients.

Salidroside shows anticonvulsant and neuroprotective effects by activating the Nrf2-ARE pathway in a pentylenetetrazol-kindling epileptic model.

Evidence points towards oxidative stress and neuroinflammation being major processes associated with brain dysfunction in epilepsy. Salidroside reportedly possesses anti-oxidative activity and neuroprotective potential, in addition to exerting an anti-neuroinflammatory response. This study was designed to evaluate the anticonvulsant and neuroprotective role of salidroside in rats with pentylenetetrazole (PTZ) kindling and to explore the underlying mechanism. Male Wistar rats were administered a sub-convulsive dose of PTZ (35 mg/kg) every other day for 15 injections, and salidroside (50 mg/kg) was injected intraperitoneally along with alternate-day PTZ. The seizure degree, cognitive function, and number of hippocampal neurons were investigated. The expression of nuclear factor erythroid 2-related factor- antioxidant response element (Nrf2-ARE) signaling pathways, oxidative stress parameters and inflammatory cytokines were also observed. Our study showed that salidroside treatment suppressed the kindling acquisition process, ameliorated cognitive impairment, and rescued the number of pyramidal neurons in the CA3 regions. Salidroside treatment could activate the Nrf2-ARE signal pathway, and suppressed oxidative stress and neuroinflammation. Our findings demonstrated that salidroside exerted anticonvulsant and neuroprotective effects in epileptic rats by activating the Nrf2-ARE signal pathway.

Novel carbohydrate-triazole derivatives as potential α-glucosidase inhibitors.

A series of novel pyrano[2, 3-d]trizaole compounds were synthesized and their α-glucosidase inhibitory activities were evaluated by in vitro enzyme assay. The experimental data demonstrated that compound 10f showed up to 10-fold higher inhibition (IC5074.0 ± 1.3 µmol·L-1) than acarbose. The molecular docking revealed that compound 10f could bind to α-glucosidase via the hydrophobic, π-π stacking, and hydrogen bonding interactions. The results may benefit further structural modifications to find new and potent α-glucosidase inhibitors.

Multicolor tunable highly luminescent carbon dots for remote force measurement and white light emitting diodes.

Multicolor tunable carbon dots (CDs) are obtained by only altering the reaction solvents in solvothermal treatment. The red CDs (R-CDs) have a quantum yield of 50.8%, the highest reported for nitrogen and sulfur co-doped R-CDs so far. These CDs are developed into fluorescent hydrogels for precise remote force measurement and WLEDs with the CIE color coordinate of (0.31, 0.32).

A small molecule, Lys-Ala-7-amido-4-methylcoumarin, facilitates RNA dimer maturation of a stem-loop 1 transcript in vitro: structure-activity relationship of the activator.

The type 1 human immunodeficiency virus (HIV-1), like all retroviruses, contains two copies of the RNA genome as a dimer. A dimer initially forms via a self-complementary sequence in the dimer initiation site (DIS) of the genomic RNA, but that dimer is converted to a mature dimer in a process generally promoted by the viral nucleocapsid (NC) protein. Formation of the mature dimer is correlated with infectivity. Study of genomic dimerization has been facilitated by discovery of short RNA transcripts containing the DIS stem-loop 1 (SL1), which can dimerize spontaneously without any protein factors in vitro as well as via the NC protein. On the basis of the palindromic nature of the apical loop of SL1, a kissing loop model has been proposed. First, a metastable kissing dimer is formed via a loop-loop interaction and then converted into a more stable extended dimer by the NC protein. This dimerization process in vitro is believed to mimic the in vivo RNA maturation. During experimental screening of potential inhibitors, we discovered a small molecule, Lys-Ala-7-amido-4-methylcoumarin (KA-AMC), which facilitates the in vitro conversion from kissing dimer to extended dimer. Here we report the structure-activity relationship for KA-AMC for promoting dimer maturation. Guanidino groups and increasing positive charge on the side chain enhance activity. For activity, the charged side chain is preferred on the benzene ring, and O 1 in the coumarin scaffold is essential. NMR studies show that the coumarin derivatives stack with aromatic bases of the RNA. The coumarin derivatives may aid in the investigation of some aspects of dimer maturation and serve as a scaffold for design of maturation inhibitors or of activators of premature maturation, either of which can lead to a potential HIV therapeutic.

Rational Design of Dimeric Lysine N-Alkylamides as Potent and Broad-Spectrum Antibacterial Agents.

Antibiotic resistance is one of the biggest threats to public health, and new antibacterial agents hence are in an urgent need to combat infectious diseases caused by multidrug-resistant (MDR) pathogens. Utilizing dimerization strategy, we rationally designed and efficiently synthesized a new series of small molecule dimeric lysine alkylamides as mimics of AMPs. Evaluation of these mimics against a panel of Gram-positive and Gram-negative bacteria including MDR strains was performed, and a broad-spectrum and potent compound 3d was identified. This compound displayed high specificity toward bacteria over mammalian cell. Time-kill kinetics and mechanistic studies suggest that compound 3d quickly eliminated bacteria in a bactericidal mode by disrupting bacterial cell membrane. In addition, lead compound 3d could inhibit biofilm formation and did not develop drug resistance in S. aureus and E. coli over 14 passages. These results suggested that dimeric lysine nonylamide has immense potential as a new type of novel small molecular agent to combat antibiotic resistance.