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1.
J Environ Sci (China) ; 150: 604-621, 2025 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-39306433

RESUMO

Recently, the transportation sector in China has gradually become the main source of urban air pollution and primary driver of carbon emissions growth. Considering air pollutants and greenhouse gases come from the same emission sources, it is necessary to establish an updated high-resolution emission inventory for the transportation sector in Central China, the most polluted region in China. The inventory includes on-road mobile, non-road mobile, oil storage and transportation, and covers 9 types of air pollutants and 3 types of greenhouse gases. Based on the Long-range Energy Alternatives Planning System (LEAP) model, the emissions of pollutants were predicted for the period from 2020 to 2035 in different scenarios. Results showed that in 2020, emissions of SO2, NOx, CO, PM10, PM2.5, VOCs, NH3, BC, OC, CO2, CH4, and N2O in Henan Province were 27.5, 503.2, 878.6, 20.1, 17.4, 222.1, 21.5, 9.4, 2.9, 92,077.9, 6.0, and 10.4 kilotons, respectively. Energy demand and pollutant emissions in Henan Province are simulated under four scenarios (Baseline Scenario (BS), Pollution Abatement Scenario (PA), Green Transportation Scenario (GT), and Reinforcing Low Carbon Scenario (RLC)). The collaborative emission reduction effect is most significant in the RLC scenario, followed by the GT scenario. By 2035, under the RLC scenario, energy consumption and emissions of SO2, NOx, CO, PM10, PM2.5, VOCs, NH3, CO2, CH4, and N2O are projected to decrease by 72.0%, 30.0%, 55.6%, 56.0%, 38.6%, 39.7%, 51.5%, 66.1%, 65.5%, 55.4%, and 52.8%, respectively. This study provides fundamental data support for subsequent numerical simulations.


Assuntos
Poluentes Atmosféricos , Poluição do Ar , Monitoramento Ambiental , Gases de Efeito Estufa , China , Poluentes Atmosféricos/análise , Gases de Efeito Estufa/análise , Monitoramento Ambiental/métodos , Poluição do Ar/estatística & dados numéricos , Poluição do Ar/análise , Meios de Transporte , Emissões de Veículos/análise
2.
J Environ Sci (China) ; 147: 392-403, 2025 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-39003057

RESUMO

This study used steel slag, fly ash, and metakaolin as raw materials (SFM materials) to create silica-alumina-based geopolymers that can solidify Hg2+ when activated with sodium-based water glass. The experiments began with a triangular lattice point mixing design experiment, and the results were fitted, analyzed, and predicted. The optimum SFM material mass ratio was found to be 70% steel slag, 25% fly ash, and 5% metakaolin. The optimum modulus of the activator was identified by comparing the unconfined compressive strength and solidifying impact on Hg2+of geosynthetics with different modulus. The SFM geopolymer was then applied in the form of potting to cure the granulated mercury tailings. The inclusion of 50% SFM material generated a geosynthetic that reduced mercury transport to the surface soil by roughly 90%. The mercury concentration of herbaceous plant samples was also reduced by 78%. It indicates that the SFM material can effectively attenuate the migration transformation of mercury. Finally, characterization methods such as XPS and FTIR were used to investigate the mechanism of Hg2+ solidification by geopolymers generated by SFM materials. The possible solidification mechanisms were proposed as alkaline environment-induced mercury precipitation, chemical bonding s, surface adsorption of Hg2+ and its precipitates by the geopolymer, and physical encapsulation.


Assuntos
Mercúrio , Mercúrio/química , Mercúrio/análise , Polímeros/química , Poluentes do Solo/química , Poluentes do Solo/análise , Mineração , Cinza de Carvão/química , Modelos Químicos
3.
J Environ Sci (China) ; 149: 406-418, 2025 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-39181653

RESUMO

Improving the accuracy of anthropogenic volatile organic compounds (VOCs) emission inventory is crucial for reducing atmospheric pollution and formulating control policy of air pollution. In this study, an anthropogenic speciated VOCs emission inventory was established for Central China represented by Henan Province at a 3 km × 3 km spatial resolution based on the emission factor method. The 2019 VOCs emission in Henan Province was 1003.5 Gg, while industrial process source (33.7%) was the highest emission source, Zhengzhou (17.9%) was the city with highest emission and April and August were the months with the more emissions. High VOCs emission regions were concentrated in downtown areas and industrial parks. Alkanes and aromatic hydrocarbons were the main VOCs contribution groups. The species composition, source contribution and spatial distribution were verified and evaluated through tracer ratio method (TR), Positive Matrix Factorization Model (PMF) and remote sensing inversion (RSI). Results show that both the emission results by emission inventory (EI) (15.7 Gg) and by TR method (13.6 Gg) and source contribution by EI and PMF are familiar. The spatial distribution of HCHO primary emission based on RSI is basically consistent with that of HCHO emission based on EI with a R-value of 0.73. The verification results show that the VOCs emission inventory and speciated emission inventory established in this study are relatively reliable.


Assuntos
Poluentes Atmosféricos , Poluição do Ar , Monitoramento Ambiental , Compostos Orgânicos Voláteis , Compostos Orgânicos Voláteis/análise , China , Poluentes Atmosféricos/análise , Monitoramento Ambiental/métodos , Poluição do Ar/estatística & dados numéricos , Poluição do Ar/análise
4.
Int J Biol Macromol ; 279(Pt 3): 135272, 2024 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-39226979

RESUMO

Laccase is a green catalyst that can efficiently catalyze phenolic pollutants, and its catalytic efficiency is closely related to the interaction between enzyme and substrates. To investigate the binding effects between enzyme and phenolic pollutants, phenol, p-chlorophenol, and bisphenol A were used as substrates in this study. We focused on the removal and catalytic mechanism of these pollutants in water using yellow laccase derived from Coriolopsis gallica. The enzymatic catalytic products were characterized using Ultraviolet-Visible Absorption Spectroscopy (UV-Vis), Fourier Transform Infrared Spectroscopy (FTIR), and High-Resolution Mass Spectrometry (HRMS), and the catalytic mechanism of laccase on phenolic pollutants was further explored by molecular docking. Based on the structural characterization and molecular docking results, the possible polymerization pathways of these phenolic compounds were speculated. Laccase catalyzed phenol to produce phenolic hydroxyl radicals, their para-radicals, and ortho-radicals, which polymerized to form oligomers linked by benzene­oxygen-benzene and benzene-benzene. P-chlorophenol produced phenolic hydroxyl radicals and their ortho-radicals, polymerizing to form oligomers connected by benzene­oxygen-benzene or benzene-benzene. The CC bond of the isopropyl group of bisphenol A broke to formed an intermediate product, which was further polymerized to formed a benzene­oxygen-benzene linked oligomer.

5.
Huan Jing Ke Xue ; 45(9): 5157-5167, 2024 Sep 08.
Artigo em Chinês | MEDLINE | ID: mdl-39323134

RESUMO

To clarify the pollution characteristics and sources of atmospheric VOCs in Zhengzhou City in the summer, multi-site offline sampling and laboratory analyses of atmospheric VOCs in Zhengzhou were carried out in August 2022. The observed and initial VOC volume fraction levels, OFP, SOAFP, and sources were compared. During the study period, the average values of three-site observation and initial φ(VOCs) during the study period were (31.83 ±13.51)×10-9 and (35.92 ±15.30)×10-9,respectively. Olefins (52.5 %) and aromatic hydrocarbons (29.7 %) were the components with a higher photochemical loss rate, and the spatial variations of the observed TVOCs concentration at each site were: Zhengzhou University (ZZU) > Gangli Reservoir (GLR) > Jingkaiqu (JKQ), and the concentrations of alkanes and OVOCs at each site were higher. Olefins and aromatic hydrocarbons were the components that contributed greatly to the formation of O3 and SOA. Motor vehicle sources, solvent-use sources, and industrial sources were the main contributing sources of atmospheric VOCs in Zhengzhou. Compared with the source analysis results based on the initial concentration, the contribution rates of motor vehicle sources, industrial sources, and solvent use sources were relatively high, and the contribution rates of combustion sources, plant sources, and oil and gas volatilization sources were relatively low.

6.
J Tradit Complement Med ; 14(5): 510-521, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-39262657

RESUMO

Background and aim: Muscular atrophy is one of the most common age-related conditions characterized by the deterioration of skeletal muscle structures and impaired functions. It is associated with cellular senescence and chronic inflammation, which impair the function of muscle stem cells. Bazi Bushen (BZBS) is a patent compound Chinese medicine that has been shown to have anti-aging effects in various animal models. In this study, we investigated the effects and mechanisms of BZBS on muscular atrophy in naturally aged mice. Experimental procedure: A muscular atrophy model of naturally aged mice (18 months) was employed with administration of BZBS (2 g/kg/d, 1 g/kg/d) and nicotinamide mononucleotide (NMN, 200 mg/kg/d). After six months of drug administration, muscle weight loss, muscle function and muscle histopathology were measured to evaluate the therapeutic effect of BZBS. The expression of cellular senescence, inflammatory and satellite cell-related factors were used to assess the effects of BZBS in inhibiting cellular senescence, reducing inflammation and improving muscle atrophy. Results and conclusion: Compared with age matched natural aging mice, we found that BZBS improved muscle strength, mass, and morphology by reducing senescent cells, inflammatory cytokines, and intermyofiber fibrosis in aged muscle tissues. We also found that BZBS prevented the reduction of Pax7 positive stem cells and stimulated the activation and differentiation into myocytes. Our results suggest that BZBS might be a promising intervention in senile muscular atrophy.

7.
Cell Rep Methods ; 4(9): 100842, 2024 Sep 16.
Artigo em Inglês | MEDLINE | ID: mdl-39236714

RESUMO

Gene-switch techniques hold promising applications in contemporary genetics research, particularly in disease treatment and genetic engineering. Here, we developed a compact drug-induced splicing system that maintains low background using a human ubiquitin C (hUBC) promoter and optimized drug (LMI070) binding sequences based on the Xon switch system. To ensure precise subcellular localization of the protein of interest (POI), we inserted a 2A self-cleaving peptide between the extra N-terminal peptide and POI. This streamlined and optimized switch system, named miniXon2G, effectively regulated POIs in different subcellular localizations both in vitro and in vivo. Furthermore, miniXon2G could be integrated into endogenous gene loci, resulting in precise, reversible regulation of target genes by both endogenous regulators and drugs. Overall, these findings highlight the performance of miniXon2G in controlling protein expression with great potential for general applicability to diverse biological scenarios requiring precise and delicate regulation.


Assuntos
Splicing de RNA , Humanos , Splicing de RNA/efeitos dos fármacos , Splicing de RNA/genética , Animais , Células HEK293 , Regiões Promotoras Genéticas/genética , Regiões Promotoras Genéticas/efeitos dos fármacos , Camundongos
8.
Heliyon ; 10(16): e35560, 2024 Aug 30.
Artigo em Inglês | MEDLINE | ID: mdl-39224243

RESUMO

As a common cardiovascular disease (CVD), Arrhythmia refers to any abnormality in the origin, frequency, rhythm, conduction velocity, timing, pathway, sequence, or other aspect of cardiac impulses, and it is one of the common cardiovascular diseases in clinical practice. At present, various ion channel blockers are used for treatment of arrhythmia that include Na+ ion channel blockers, K+ ion channel blockers and Ca2+ ion channel blockers. While these drugs offer benefits, they have led to a gradual increase in drug-related adverse reactions across various systems. As a result, the quest for safe and effective antiarrhythmic drugs is pressing. Recent years have seen some advancements in the treatment of ventricular arrhythmias using traditional Chinese medicine(TCM). The theory of Luobing in TCM has proposed a new drug intervention strategy of "fast and slow treatment, integrated regulation" leading to a shift in mindset from "antiarrhythmic" to "rhythm-regulating". Guided by this theory, the development of Shen Song Yang Xin Capsules (SSYX) has involved various Chinese medicinal ingredients that comprehensively regulate the myocardial electrophysiological mechanism, exerting antiarrhythmic effects on multiple ion channels and non-ion channels. Similarly, in clinical studies, evidence-based research has confirmed that SSYX combined with conventional antiarrhythmic drugs can more effectively reduce the occurrence of arrhythmias. Therefore, this article provides a comprehensive review of the composition and mechanisms of action, pharmacological components, network pharmacology analysis, and clinical applications of SSYX guided by the theory of Luobing, aiming to offer valuable insights for improved clinical management of arrhythmias and related research.

9.
Proc Natl Acad Sci U S A ; 121(34): e2403392121, 2024 Aug 20.
Artigo em Inglês | MEDLINE | ID: mdl-39141356

RESUMO

Cysteine palmitoylation or S-palmitoylation catalyzed by the ZDHHC family of acyltransferases regulates the biological function of numerous mammalian proteins as well as viral proteins. However, understanding of the role of S-palmitoylation in antiviral immunity against RNA viruses remains very limited. The adaptor protein MAVS forms functionally essential prion-like aggregates upon activation by viral RNA-sensing RIG-I-like receptors. Here, we identify that MAVS, a C-terminal tail-anchored mitochondrial outer membrane protein, is S-palmitoylated by ZDHHC7 at Cys508, a residue adjacent to the tail-anchor transmembrane helix. Using superresolution microscopy and other biochemical techniques, we found that the mitochondrial localization of MAVS at resting state mainly depends on its transmembrane tail-anchor, without regulation by Cys508 S-palmitoylation. However, upon viral infection, MAVS S-palmitoylation stabilizes its aggregation on the mitochondrial outer membrane and thus promotes subsequent propagation of antiviral signaling. We further show that inhibition of MAVS S-palmitoylation increases the host susceptibility to RNA virus infection, highlighting the importance of S-palmitoylation in the antiviral innate immunity. Also, our results indicate ZDHHC7 as a potential therapeutic target for MAVS-related autoimmune diseases.


Assuntos
Aciltransferases , Proteínas Adaptadoras de Transdução de Sinal , Imunidade Inata , Lipoilação , Membranas Mitocondriais , Humanos , Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Proteínas Adaptadoras de Transdução de Sinal/genética , Membranas Mitocondriais/metabolismo , Aciltransferases/metabolismo , Células HEK293 , Mitocôndrias/metabolismo , Animais , Cisteína/metabolismo , Transdução de Sinais/imunologia , Agregados Proteicos
10.
Bioact Mater ; 41: 440-454, 2024 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-39188381

RESUMO

Osteoporotic bone defects pose a significant challenge for bone regeneration as they exhibit impaired healing capacity and delayed healing period. To address this issue, this study introduces a hydrogel that creates a rejuvenating microenvironment, thereby facilitating efficient bone repair during the initial two weeks following bone defect surgery. The hydrogel, named GelHFS, was created through host-guest polymerization of gelatin and acrylated ß-cyclodextrin. Incorporation of the human fetal mesenchymal stem cell secretome (HFS) formed GelHFS hydrogel aimed at mimicking a rejuvenated stem cell niche. Our results demonstrated that GelHFS hydrogel promotes cell stellate spreading and osteogenic differentiation via integrin ß1-induced focal adhesion pathway. Implantation of GelHFS hydrogel in an osteoporotic bone defect rat model recruited endogenous integrin ß1-expressing cells and enhanced new bone formation and bone strength. Our findings reveal that GelHFS hydrogel provides a rejuvenating niche for endogenous MSCs and enhances bone regeneration in osteoporotic bone defect. These findings highlight the potential of GelHFS hydrogel as an effective therapeutic strategy for addressing challenging bone healing such as osteoporotic bone regeneration.

11.
Stem Cell Res ; 81: 103543, 2024 Aug 26.
Artigo em Inglês | MEDLINE | ID: mdl-39208640

RESUMO

Current methodologies for hepatocyte induction from human induced pluripotent stem cells (hiPSCs) have limited efficacy due to lack of a functional hepatocyte reporter. To address this, we developed an endogenous albumin (ALB)-sfGFP reporter system in hiPSCs using homologous directed recombination (HDR)-mediated knock-in. The hiPSCs maintained the characteristic morphology, pluripotency, and normal karyotype while demonstrating successful differentiation into all three germ layers both in vitro and in vivo. Co-expression of EGFP and ALB was observed in the derived hepatocyte-like cells (HLCs). This reporter system holds promise for functional hepatocyte induction.

12.
J Med Chem ; 67(17): 15428-15437, 2024 Sep 12.
Artigo em Inglês | MEDLINE | ID: mdl-39191393

RESUMO

Diffuse large B-cell lymphomas (DLBCLs) are heterogeneous cancers that still require better and less toxic treatments. SIRT3, a member of the sirtuin family of NAD+-dependent protein deacylase, is critical for DLBCL growth and survival. A mitochondria-targeted SIRT3 small-molecule inhibitor, YC8-02, exhibits promising activity against DLBCL. However, YC8-02 has several limitations including poor solubility. Here, we report our medicinal chemistry efforts that led to an improved mitochondria-targeted SIRT3 inhibitor, SJ-106C, achieved by using a triethylammonium group, which helps to increase both solubility and SIRT3 inhibition potency. SJ-106C, while still inhibiting SIRT1 and SIRT2, is enriched in the mitochondria to help with SIRT3 inhibition. It is more active against DLBCL than other solid tumor cells and effectively inhibits DLBCL xenograft tumor growth. The findings provide useful insights for the development of SIRT3 inhibitors and mitochondrial targeting agents and further support the notion that SIRT3 is a promising druggable target for DLBCL.


Assuntos
Antineoplásicos , Linfoma Difuso de Grandes Células B , Mitocôndrias , Sirtuína 3 , Sirtuína 3/antagonistas & inibidores , Sirtuína 3/metabolismo , Humanos , Linfoma Difuso de Grandes Células B/tratamento farmacológico , Linfoma Difuso de Grandes Células B/patologia , Linfoma Difuso de Grandes Células B/metabolismo , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/metabolismo , Animais , Antineoplásicos/farmacologia , Antineoplásicos/química , Antineoplásicos/síntese química , Linhagem Celular Tumoral , Camundongos , Ensaios Antitumorais Modelo de Xenoenxerto , Proliferação de Células/efeitos dos fármacos , Relação Estrutura-Atividade
13.
J Agric Food Chem ; 72(30): 16700-16707, 2024 Jul 31.
Artigo em Inglês | MEDLINE | ID: mdl-39037174

RESUMO

3,5-Dimethyl-8-methoxy-3,4-dihydro-1H-isochromen-6-ol (DMD) is a polyketide compound obtained from the endophytic fungus Penicillium sp. HJT-A-10 of Rhodiola tibetica. R. tibetica is a nourishing food and also used in traditional Chinese medicine and Xizang medicine. In dextran sulfate sodium (DSS)-induced ulcerative colitis (UC) mice, DMD significantly alleviated the pathological symptom of UC. Network pharmacology studies have shown that nucleotide-binding domain-like receptor family pyrin domain containing (NLRP) 3 is the primary target protein of DMD associated with anti-UC. In molecular biology studies, DMD suppressed the activation of NLRP3 and decreased the expression of downstream inflammatory proteins and pro-inflammatory cytokines in UC. The finding was further verified in knockout mice. DMD lost the effect of attenuating DSS-induced UC in NLRP3-/- mice. In conclusion, this study demonstrates that DMD reduces inflammatory response and balances the barrier integrity to attenuate UC via targeting NLRP3, and DMD is a potential natural agent or dietary supplement for attenuating UC.


Assuntos
Colite Ulcerativa , Camundongos Endogâmicos C57BL , Camundongos Knockout , Proteína 3 que Contém Domínio de Pirina da Família NLR , Animais , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Proteína 3 que Contém Domínio de Pirina da Família NLR/genética , Colite Ulcerativa/tratamento farmacológico , Colite Ulcerativa/induzido quimicamente , Colite Ulcerativa/metabolismo , Colite Ulcerativa/genética , Camundongos , Humanos , Masculino , Penicillium/química , Benzopiranos/farmacologia , Benzopiranos/química , Sulfato de Dextrana/efeitos adversos
14.
Mar Pollut Bull ; 206: 116701, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-38991612

RESUMO

This study developed an estimation method for the N2O budget using 15N stable isotope labeling techniques, a dual-layer model and a box model, which was used to elucidate the underlying dynamics of N2O accumulation in Zhanjiang Bay. The results showed that although the net input of N2O during the rainy season was 2.36 times higher than that during the dry season, the overall N2O concentration was only 66.6 % of that during the dry season due to the extended water residence time in the dry season. Our findings highlighted that water residence time was the key factor for the N2O emission, and a longer water residence time was unfavorable for the efflux of N2O through hydrodynamic processes and was more conducive to the production and accumulation of N2O within the bay. This research enhanced our comprehension of N2O dynamics and provided crucial insights for refining nitrogen management strategies and mitigation efforts.


Assuntos
Baías , Monitoramento Ambiental , Óxido Nitroso , Estações do Ano , Óxido Nitroso/análise , China , Poluentes Químicos da Água/análise , Água do Mar/química
15.
Heliyon ; 10(13): e33309, 2024 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-39040283

RESUMO

Cardiovascular diseases (CVDs) are one of the most significant diseases that pose a threat to human health. The innovative traditional Chinese medicine Tongxinluo Capsule, developed under the guidance of the theory of traditional Chinese medicine, has good clinical efficacy in various cardiovascular diseases, this medicine has effects such as blood protection, vascular protection, myocardial protection, stabilizing vulnerable plaques, and vasodilation. However, CVDs are a multifactorial disease, and their underlying mechanisms are not fully understood. Therefore, exploring the mechanism of action and clinical application of Tongxinluo Capsule in the treatment of various cardiovascular diseases is beneficial for exerting its therapeutic effect from multiple components, targets, and pathways. At the same time, it provides broader treatment ideas for other difficult to treat diseases in the cardiovascular event chain, and has significant theoretical and clinical significance for improving the treatment of cardiovascular diseases with traditional Chinese medicine.

16.
Nano Lett ; 24(31): 9743-9749, 2024 Aug 07.
Artigo em Inglês | MEDLINE | ID: mdl-39072414

RESUMO

The dynamics of ion transport at the interface is the critical factor for determining the performance of an electrochemical energy storage device. While practical applications are realized in concentrated electrolytes and nanopores, there is a limited understanding of their ion dynamic features. Herein, we studied the interfacial ion dynamics in room-temperature ionic liquids by transient single-particle imaging with microsecond-scale resolution. We observed slowed-down dynamics at lower potential while acceleration was observed at higher potential. Combined with simulation, we found that the microstructure evolution of the electric double layer (EDL) results in potential-dependent kinetics. Then, we established a correspondence between the ion dynamics and interfacial ion composition. Besides, the ordered ion orientation within EDL is also an essential factor for accelerating interfacial ion transport. These results inspire us with a new possibility to optimize electrochemical energy storage through the good control of the rational design of the interfacial ion structures.

17.
Food Chem X ; 22: 101491, 2024 Jun 30.
Artigo em Inglês | MEDLINE | ID: mdl-38840727

RESUMO

Maillard reaction products (MRPs) derived from rice protein isolate hydrolysate and D-xylose, with or without L-cysteine, were developed as a potential meat flavoring. The combined impact of temperature (80-140 °C) and cysteine on fundamental physicochemical characteristics, antioxidant activity, and flavor of MRPs were investigated through assessments of pH, color, UV-visible spectra, fluorescence spectra, free amino acids, volatile compounds, E-nose, E-tongue, and sensory evaluation. Results suggested that increasing temperature would reduce pH, deepen color, promote volatile compounds formation, and reduce the overall umami and bitterness. Cysteine addition contributed to the color inhibition, enhancement of DPPH radical-scavenging activity and reducing power, improvement in mouthfulness and continuity, reduction of bitterness, and the formation of sulfur compounds responsible for meaty flavor. Overall, MRPs prepared at 120 °C with cysteine addition could be utilized as a potential meat flavoring with the highest antioxidant activity and relatively high mouthfulness, continuity, umami, meaty aroma, and relatively low bitterness.

18.
Biotechnol Bioeng ; 2024 Jun 24.
Artigo em Inglês | MEDLINE | ID: mdl-38923503

RESUMO

Spinal muscular atrophy (SMA) is a devastating neuromuscular disease caused by mutations in the survival motor neuron 1 (SMN1) gene. Gene editing technology repairs the conversion of the 6th base T to C in exon 7 of the paralogous SMN2 gene, compensating for the SMN protein expression and promoting the survival and function of motor neurons. However, low editing efficiency and unintended off-target effects limit the application of this technology. Here, we optimized a TaC9-adenine base editor (ABE) system by combining Cas9 nickase with the transcription activator-like effector (TALE)-adenosine deaminase fusion protein to effectively and precisely edit SMN2 without detectable Cas9 dependent off-target effects in human cell lines. We also generated human SMA-induced pluripotent stem cells (SMA-iPSCs) through the mutation of the splice acceptor or deletion of the exon 7 of SMN1. TaC9-R10 induced 45% SMN2 T6 > C conversion in the SMA-iPSCs. The SMN2 T6 > C splice-corrected SMA-iPSCs were directionally differentiated into motor neurons, exhibiting SMN protein recovery and antiapoptosis ability. Therefore, the TaC9-ABE system with dual guides from the combination of Cas9 with TALE could be a potential therapeutic strategy for SMA with high efficacy and safety.

19.
Angew Chem Int Ed Engl ; 63(34): e202407303, 2024 Aug 19.
Artigo em Inglês | MEDLINE | ID: mdl-38837854

RESUMO

The Li-CO2 batteries utilizing greenhouse gas CO2 possess advantages of high energy density and environmental friendliness. However, these batteries following Li2CO3-product route typically exhibit low work voltage (<2.5 V) and energy efficiency. Herein, we have demonstrated for the first time that cobalt phthalocyanine (CoPc) as homogeneous catalyst can elevate the work plateau towards 2.98 V, which is higher than its theoretical discharge voltage without changing the Li2CO3-product route. This unprecedented discharge voltage is illustrated by mass spectrum and electrochemical analyses that CoPc has powerful adsorption capability with CO2 (-7.484 kJ mol-1) and forms discharge intermediate of C33H16CoN8O2. Besides high discharge capacity of 18724 mAh g-1 and robust cyclability over 1600 hours (1000 mAh g-1 cut-off) at a current density of 100 mA g-1, the batteries show high temperature adaptability (-30-80 °C). Our work is paving a promising avenue for the progress of high-efficiency Li-CO2 batteries.

20.
Heliyon ; 10(10): e31342, 2024 May 30.
Artigo em Inglês | MEDLINE | ID: mdl-38813233

RESUMO

Background: Breast cancer (BC), the most common cancer among women globally, has been shown by numerous studies to significantly involve non-apoptotic regulatory cell death (RCD) in its pathogenesis and progression. Methods: We obtained the RNA sequences and clinical data of BC patients from The Cancer Genome Atlas (TCGA) database for the training set, while datasets GSE96058, GSE86166, and GSE20685 from The Gene Expression Omnibus (GEO) database were utilized as validation cohorts. Initially, we performed non-negative matrix factorization (NMF) clustering analysis on the BC samples from the TCGA database to discern non-apoptotic RCD-related molecular subtypes. To identify prognostically-relevant non-apoptotic RCD genes (NRGs) and construct a prognostic model, we implemented three machine learning algorithms: lasso regression, random forest, and XGBoost analysis. The expression of selected genes was verified using real-time quantitative polymerase chain reaction (RT-qPCR), single-cell RNA-sequencing (scRNA-seq) analysis, and The Human Protein Atlas (HPA) database. The risk signature was evaluated concerning clinical characteristics and drug sensitivity. Furthermore, we developed a nomogram to predict BC patient survival. Results: The NMF method successfully compartmentalized patients from the TCGA database into three distinct non-apoptotic RCD-related subtypes, with significant variations observed in immune characteristics and prognostic stratification across these subtypes. We identified 5 differentially expressed NRGs used in establishing the risk signature. Patients with different risk groups exhibited distinct clinicopathological features, drug sensitivity, and prognostic outcomes. A nomogram was subsequently developed, incorporating the NRGs-related risk signature, age, T stage, and N stage, to aid clinical decision-making. Conclusion: We identified a novel NRGs-related risk signature, which was expected to become a potential prognostic marker in BC.

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