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1.
Huan Jing Ke Xue ; 45(2): 700-708, 2024 Feb 08.
Artigo em Chinês | MEDLINE | ID: mdl-38471910

RESUMO

Organic acids in atmospheric particulate matter are widely involved in various physical and chemical reactions in the atmosphere and contribute greatly to the formation of secondary organic aerosols and haze pollutions. Therefore, the concentration distribution characteristics, sources, and secondary formation of organic acids in particulate matter are of great significance for further investigation of organic aerosols and their secondary transformation. Fine particulate matter (PM2.5) samples were collected in Zhengzhou, and three types of organic acids, including dicarboxylic acids, fatty acids, and resin acids, were analyzed to explore their species distribution, seasonal variations, source contribution, and secondary generation. Malonic acid (di-C3) and succinate acid (di-C4) were the most abundant in the identified dicarboxylic acids, which showed obvious seasonal variations in the order of summer > autumn > winter > spring. Fatty acids had the highest concentration in winter and the lowest concentration in spring, showing obvious bimodal advantages, with the most abundant compounds being palmitic acid and stearic acid (C18). Principal component analysis and multiple linear regression (MLR) were used to analyze the source of organic acids in PM2.5 in Zhengzhou; the results showed that 35% of the organic acids came from combustion and traffic sources, 24% from cooking sources, 23% from secondary formation, and 17% from natural sources. The ratios of the selected marker species (i.e., di-C3 / di-C4, F/M, and C18:1 / C18) were used as tracers for the secondary formation of the organic aerosol and its aging process. The results showed that the photochemical reaction was intense in summer, and the proportion of organic aerosol aging or secondary production was high, whereas the photochemical reaction was weak in winter, and the aging degree of organic aerosol was low. Correlation analysis and MLR were used in combination to quantify the relative contribution of gas-phase oxidation and liquid-phase oxidation to dicarboxylic acid formation, and the results showed that gas-phase oxidation played a dominant role in the sampling period (accounting for 58%), especially in summer (61%).

2.
FASEB J ; 38(6): e23573, 2024 Mar 31.
Artigo em Inglês | MEDLINE | ID: mdl-38526846

RESUMO

Familial hypercholesterolemia (FH) is one of the most prevalent monogenetic disorders leading to cardiovascular disease (CVD) worldwide. Mutations in Ldlr, encoding a membrane-spanning protein, account for the majority of FH cases. No effective and safe clinical treatments are available for FH. Adenine base editor (ABE)-mediated molecular therapy is a promising therapeutic strategy to treat genetic diseases caused by point mutations, with evidence of successful treatment in mouse disease models. However, due to the differences in the genomes between mice and humans, ABE with specific sgRNA, a key gene correction component, cannot be directly used to treat FH patients. Thus, we generated a knock-in mouse model harboring the partial patient-specific fragment and including the Ldlr W490X mutation. LdlrW490X/W490X mice recapitulated cholesterol metabolic disorder and clinical manifestations of atherosclerosis associated with FH patients, including high plasma low-density lipoprotein cholesterol levels and lipid deposition in aortic vessels. Additionally, we showed that the mutant Ldlr gene could be repaired using ABE with the cellular model. Taken together, these results pave the way for ABE-mediated molecular therapy for FH.


Assuntos
Hipercolesterolemia , Hiperlipoproteinemia Tipo II , Humanos , Camundongos , Animais , RNA Guia de Sistemas CRISPR-Cas , Hiperlipoproteinemia Tipo II/genética , Hiperlipoproteinemia Tipo II/terapia , Mutação , Hipercolesterolemia/genética , Colesterol , Receptores de LDL/genética , Receptores de LDL/metabolismo
3.
Front Pharmacol ; 15: 1337150, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38523645

RESUMO

Pain is a clinical condition that is currently of great concern and is often caused by tissue or nerve damage or occurs as a concomitant symptom of a variety of diseases such as cancer. Severe pain seriously affects the functional status of the body. However, existing pain management programs are not fully satisfactory. Therefore, there is a need to delve deeper into the pathological mechanisms underlying pain generation and to find new targets for drug therapy. Sphingolipids (SLs), as a major component of the bilayer structure of eukaryotic cell membranes, also have powerful signal transduction functions. Sphingolipids are abundant, and their intracellular metabolism constitutes a huge network. Sphingolipids and their various metabolites play significant roles in cell proliferation, differentiation, apoptosis, etc., and have powerful biological activities. The molecules related to sphingolipid metabolism, mainly the core molecule ceramide and the downstream metabolism molecule sphingosine-1-phosphate (S1P), are involved in the specific mechanisms of neurological disorders as well as the onset and progression of various types of pain, and are closely related to a variety of pain-related diseases. Therefore, sphingolipid metabolism can be the focus of research on pain regulation and provide new drug targets and ideas for pain.

4.
J Colloid Interface Sci ; 664: 319-328, 2024 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-38479268

RESUMO

Rational construction of efficient and robust bifunctional oxygen electrocatalysts is key but challenging for the widespread application of rechargeable zinc-air batteries (ZABs). Herein, bifunctional ligand Co metal-organic frameworks were first explored to fabricate a hybrid of heterostructured CoOx/Co nanoparticles anchored on a carbon substrate rich in CoNx sites (CoOx/Co@CoNC) via a one-step pyrolysis method. Such a unique heterostructure provides abundant CoNx and CoOx/Co active sites to drive oxygen reduction reaction (ORR) and oxygen evolution reaction (OER), respectively. Besides, their positive synergies facilitate electron transfer and optimize charge/mass transportation. Consequently, the obtained CoOx/Co@CoNC exhibits a superior ORR activity with a higher half-wave potential of 0.88 V than Pt/C (0.83 V vs. RHE), and a comparable OER performance with an overpotential of 346 mV at 10 mA cm-2 to the commercial RuO2. The assembled ZAB using CoOx/Co@CoNC as a cathode catalyst displays a maximum power density of 168.4 mW cm-2, and excellent charge-discharge cyclability over 250 h at 5 mA cm-2. This work highlights the great potential of heterostructures in oxygen electrocatalysis and provides a new pathway for designing efficient bifunctional oxygen catalysts toward rechargeable ZABs.

5.
Angew Chem Int Ed Engl ; 63(19): e202400122, 2024 May 06.
Artigo em Inglês | MEDLINE | ID: mdl-38494445

RESUMO

Electrochemical acetylene reduction (EAR) employing Cu catalysts represents an environmentally friendly and cost-effective method for ethylene production and purification. However, Cu-based catalysts encounter product selectivity issues stemming from carbon-carbon coupling and other side reactions. We explored the use of secondary metals to modify Cu-based catalysts and identified Cd decoration as particular effective. Cd decoration demonstrated a high ethylene Faradaic efficiency (FE) of 98.38 % with well-inhibited carbon-carbon coupling reactions (0.06 % for butadiene FE at -0.5 V versus reversible hydrogen electrode) in a 5 vol % acetylene gas feed. Notably, ethylene selectivity of 99.99 % was achieved in the crude ethylene feed during prolonged stability tests. Theoretical calculations revealed that Cd metal accelerates the water dissociation on neighboring Cu surfaces allowing more H* to participate in the acetylene semi-hydrogenation, while increasing the energy barrier for carbon-carbon coupling, thereby contributing to a high ethylene semi-hydrogenation efficiency and significant inhibition of carbon-carbon coupling. This study provides a paradigm for a deeper understanding of secondary metals in regulating the product selectivity of EAR electrocatalysts.

6.
ACS Appl Mater Interfaces ; 16(5): 5522-5535, 2024 Feb 07.
Artigo em Inglês | MEDLINE | ID: mdl-38266749

RESUMO

Multidrug-resistant (MDR) pathogens pose a serious threat to the health and life of humans, necessitating the development of new antimicrobial agents. Herein, we develop and characterize a panel of nine amino acid peptides with a cation end motif. Bioactivity analysis revealed that the short peptide containing "RWWWR" as a central motif harboring mirror structure "KXR" unit displayed not only high activity against MDR planktonic bacteria but also a clearance rate of 92.33% ± 0.58% against mature biofilm. Mechanically, the target peptide (KLR) killed pathogens by excessively accumulating reactive oxygen species and physically disrupting membranes, thereby enhancing its robustness for controlling drug resistance. In the animal model of sepsis infection by MDR bacteria, the peptide KLR exhibited strong therapeutic effects. Collectively, this study provided the dominant structure of short antimicrobial peptides (AMPs) to replenish our arsenals for combating bacterial infections and illustrated what could be harnessed as a new agent for fighting MDR bacteria.


Assuntos
Anti-Infecciosos , Infecções Bacterianas , Humanos , Animais , Peptídeos Catiônicos Antimicrobianos/farmacologia , Peptídeos Catiônicos Antimicrobianos/química , Farmacorresistência Bacteriana Múltipla , Anti-Infecciosos/farmacologia , Infecções Bacterianas/tratamento farmacológico , Testes de Sensibilidade Microbiana , Bactérias , Antibacterianos/farmacologia , Antibacterianos/química
7.
Adv Mater ; 36(9): e2309251, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-37897297

RESUMO

The construction of platinum (Pt) atomic layers is an effective strategy to improve the utilization efficiency of Pt atoms in electrocatalysis, thus is important for reducing the capital costs of a wide range of energy storage and conversion devices. However, the substrates used to grow Pt atomic layers are largely limited to noble metals and their alloys, which is not conducive to reducing catalyst costs. Herein, low-cost chromium nitride (CrN) is utilized as a support for the loading of epitaxial ultrathin Pt atomic layers via a simple thermal ammonolysis method. Owing to the strong anchoring and electronic regulation of Pt atomic layers by CrN, the obtained Pt atomic layers catalyst (containing electron-deficient Pt sites) exhibits excellent activity and endurance for the formic acid oxidation reaction, with a mass activity of 5.17 A mgPt -1 that is 13.6 times higher than that of commercial Pt/C catalyst. This novel strategy demonstrates that CrN can replace noble metals as a low-cost substrate for constructing Pt atomic layers catalysts.

8.
ACS Nano ; 17(20): 19514-19525, 2023 Oct 24.
Artigo em Inglês | MEDLINE | ID: mdl-37812403

RESUMO

Single-atom catalysts (SACs) are regarded as promising non-noble-metal alternatives for the oxygen reduction reaction (ORR) in proton exchange membrane fuel cells due to their high atom utilization efficiency and excellent catalytic properties. However, the insufficient long-term stability issues of SACs under the working conditions seriously hinder their practical application. In this perspective, the recent progress of SACs with optimized ORR catalytic activity is first reviewed. Then, the possible degradation mechanisms of SACs in the ORR process and effective strategies for improving their ORR durability are summarized. Finally, some challenges and opportunities are proposed to develop stable single-atom-based ORR electrocatalysts in the future.

9.
Sci Bull (Beijing) ; 68(22): 2862-2875, 2023 Nov 30.
Artigo em Inglês | MEDLINE | ID: mdl-37884426

RESUMO

Rechargeable zinc-air batteries (ZABs) with high energy density and low pollutant emissions are regarded as the promising energy storage and conversion devices. However, the sluggish kinetics and complex four-electron processes of oxygen reduction reaction and oxygen evolution reaction occurring at air electrodes in rechargeable ZABs pose significant challenges for their large-scale application. Carbon-supported single-atom catalysts (SACs) exhibit great potential in oxygen electrocatalysis, but needs to further improve their bifunctional electrocatalytic performance, which is highly related to the coordination environment of the active sites. As an extension of SACs, dual-sites SACs with wide combination of two active sites provide limitless opportunities to tailor coordination environment at the atomic level and improve catalytic performance. The review systematically summarizes recent achievements in the fabrication of dual-site SACs as bifunctional oxygen electrocatalysts, starting by illustrating the design fundament of the electrocatalysts according to their catalytic mechanisms. Subsequently, metal-nonmetal-atom synergies and dual-metal-atom synergies to synthesize dual-sites SACs toward enhancing rechargeable ZABs performance are overviewed. Finally, the perspectives and challenges for the development of dual-sites SACs are proposed, shedding light on the rational design of efficient bifunctional oxygen electrocatalysts for practical rechargeable ZABs.

10.
Eur J Pharmacol ; 955: 175859, 2023 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-37429517

RESUMO

Pain is a ubiquitous and highly concerned clinical symptom, usually caused by peripheral or central nervous injury, tissue damage, or other diseases. The long-term existence of pain can seriously affect daily physical function and quality of life and produce great torture on the physiological and psychological levels. However, the complex pathogenesis of pain involving molecular mechanisms and signaling pathways has not been fully elucidated, and managing pain remains highly challenging. As a result, finding new targets to pursue effective and long-term pain treatment strategies is required and urgent. Autophagy is an intracellular degradation and recycling process that maintains tissue homeostasis and energy supply, which can be cytoprotective and is vital in maintaining neural plasticity and proper nervous system function. Much evidence has shown that autophagy dysregulation is linked to the emergence of neuropathic pain, such as postherpetic neuralgia and cancer-related pain. Autophagy has also been connected to pain caused by osteoarthritis and lumbar disc degeneration. It is worth noting that in recent years, studies on traditional Chinese medicine have also proved that several traditional Chinese medicine monomers involve autophagy in the mechanism of pain relief. Therefore, autophagy can serve as a potential regulatory target to provide new ideas and inspiration for pain management.


Assuntos
Dor do Câncer , Neuralgia Pós-Herpética , Neuralgia , Humanos , Qualidade de Vida , Neuralgia/tratamento farmacológico , Neuralgia Pós-Herpética/tratamento farmacológico , Autofagia
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