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1.
J Colloid Interface Sci ; 678(Pt A): 908-919, 2024 Aug 28.
Artículo en Inglés | MEDLINE | ID: mdl-39222610

RESUMEN

Atopic dermatitis is a chronic, inflammation skin disease that remains a major public health challenge. The current drug-loading hydrogel dressings offer numerous benefits with enhanced loading capacity and a moist-rich environment. However, their development is still limited by the accessibility of a suitable driven source outside the clinical environment for precise control over transdermal delivery kinetics. Here, we prepare a sulfonated poly(3,4-ethylenedioxythiophene) (PEDOT) polyelectrolyte hydrogel drug reservoir that responds to different stimuli-both endogenous cue (body temperature) and exogenous cue (electrical stimulation), for wearable on-demand transdermal delivery with enhanced efficacy. Functioned as both the drug reservoir and cathode in a Zn battery-powered iontophoresis patch, this dual-responsive hydrogel achieves high drug release efficiency (68.4 %) at 37 °C. Evaluation in hairless mouse skin demonstrates the efficacy of this technology by facilitating transdermal transport of 12.2 µg cm-2 dexamethasone phosphate when discharged with a 103 Ω external resistor for 3 h. The Zn battery-driven iontophoresis results in an effective treatment of atopic dermatitis, displaying reductions in epidermal thickness, mast cell infiltration inhibition, and a decrease in IgE levels. This work provides a new treatment modality for chronic epidermal diseases that require precise drug delivery in a non-invasive way.

2.
Nucleic Acids Res ; 2024 Sep 13.
Artículo en Inglés | MEDLINE | ID: mdl-39271120

RESUMEN

Cytidine base editors (CBEs) hold significant potential in genetic disease treatment and in breeding superior traits into animals. However, their large protein sizes limit their delivery by adeno-associated virus (AAV), given its packing capacity of <4.7 kb. To overcome this, we employed a web-based fast generic discovery (WFG) strategy, identifying several small ssDNA deaminases (Sdds) and constructing multiple Sdd-CBE 1.0 versions. SflSdd-CBE 1.0 demonstrated high C-to-T editing efficiency, comparable to AncBE4max, while SviSdd-CBE 1.0 exhibited moderate C-to-T editing efficiency with a narrow editing window (C3 to C5). Utilizing AlphaFold2, we devised a one-step miniaturization strategy, reducing the size of Sdds while preserving their efficiency. Notably, we administered AAV8 expressing PCSK9 targeted sgRNA and SflSdd-CBEs (nSaCas9) 2.0 into mice, leading to gene-editing events (with editing efficiency up to 15%) and reduced serum cholesterol levels, underscoring the potential of Sdds in gene therapy. These findings offer new single-stranded editing tools for the treatment of rare genetic diseases.

3.
Int J Biol Macromol ; 278(Pt 1): 134673, 2024 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-39142491

RESUMEN

Charcot-Marie-Tooth type 2A (CMT2A) is a single-gene motor sensory neuropathy caused by Mfn2 mutation. It is generally believed that CMT2A involves mitochondrial fusion disruption. However, how Mfn2 mutation mediates the mitochondrial membrane fusion loss and its further pathogenic mechanisms remain unclear. Here, in vivo and in vitro mouse models harboring the Mfn2R364W, Mfn2G176S and Mfn2H165R mutations were constructed. Mitochondrial membrane fusion and fission proteins analysis showed that Mfn2R364W, Mfn2G176S, and Mfn2H165R/+ mutations maintain the expression of Mfn2, but promote Drp1 upregulation and Opa1 hydrolytic cleavage. In Mfn2H165R/H165R mutation, Mfn2, Drp1, and Opa1 all play a role in inducing mitochondrial fragmentation, and the mitochondrial aggregation is affected by Mfn2 loss. Further research into the pathogenesis of CMT2A showed these three mutations all induce mitochondria-mediated apoptosis, and mitochondrial oxidative phosphorylation damage. Overall, loss of overall fusion activity affects mitochondrial DNA (mtDNA) stability and causes mitochondrial loss and dysfunction, ultimately leading to CMT2A disease. Interestingly, the differences in the pathogenesis of CMT2A between Mfn2R364W, Mfn2G176S, Mfn2H165R/+ and Mfn2H165R/H165R mutations, including the distribution of Mfn2 and mitochondria, the expression of mitochondrial outer membrane-associated proteins (Bax, VDAC1 and AIF), and the enzyme activity of mitochondrial complex I, are related to the expression of Mfn2.


Asunto(s)
Apoptosis , Enfermedad de Charcot-Marie-Tooth , GTP Fosfohidrolasas , Mitocondrias , Mutación , Fosforilación Oxidativa , Enfermedad de Charcot-Marie-Tooth/genética , Enfermedad de Charcot-Marie-Tooth/metabolismo , Enfermedad de Charcot-Marie-Tooth/patología , GTP Fosfohidrolasas/genética , GTP Fosfohidrolasas/metabolismo , Animales , Mitocondrias/metabolismo , Mitocondrias/genética , Ratones , Apoptosis/genética , Proteínas Mitocondriales/genética , Proteínas Mitocondriales/metabolismo , Dinámicas Mitocondriales/genética , Humanos , Modelos Animales de Enfermedad
4.
Zool Res ; 45(4): 833-844, 2024 07 18.
Artículo en Inglés | MEDLINE | ID: mdl-39004861

RESUMEN

Porcine reproductive and respiratory syndrome (PRRS) is a globally prevalent contagious disease caused by the positive-strand RNA PRRS virus (PRRSV), resulting in substantial economic losses in the swine industry. Modifying the CD163 SRCR5 domain, either through deletion or substitution, can eff1ectively confer resistance to PRRSV infection in pigs. However, large fragment modifications in pigs inevitably raise concerns about potential adverse effects on growth performance. Reducing the impact of genetic modifications on normal physiological functions is a promising direction for developing PRRSV-resistant pigs. In the current study, we identified a specific functional amino acid in CD163 that influences PRRSV proliferation. Viral infection experiments conducted on Marc145 and PK-15 CD163 cells illustrated that the mE535G or corresponding pE529G mutations markedly inhibited highly pathogenic PRRSV (HP-PRRSV) proliferation by preventing viral binding and entry. Furthermore, individual viral challenge tests revealed that pigs with the E529G mutation had viral loads two orders of magnitude lower than wild-type (WT) pigs, confirming effective resistance to HP-PRRSV. Examination of the physiological indicators and scavenger function of CD163 verified no significant differences between the WT and E529G pigs. These findings suggest that E529G pigs can be used for breeding PRRSV-resistant pigs, providing novel insights into controlling future PRRSV outbreaks.


Asunto(s)
Antígenos CD , Antígenos de Diferenciación Mielomonocítica , Mutación Puntual , Síndrome Respiratorio y de la Reproducción Porcina , Virus del Síndrome Respiratorio y Reproductivo Porcino , Receptores de Superficie Celular , Animales , Porcinos , Síndrome Respiratorio y de la Reproducción Porcina/genética , Síndrome Respiratorio y de la Reproducción Porcina/virología , Virus del Síndrome Respiratorio y Reproductivo Porcino/fisiología , Virus del Síndrome Respiratorio y Reproductivo Porcino/genética , Antígenos de Diferenciación Mielomonocítica/genética , Antígenos de Diferenciación Mielomonocítica/metabolismo , Antígenos CD/genética , Antígenos CD/metabolismo , Receptores de Superficie Celular/genética , Receptores de Superficie Celular/metabolismo , Animales Modificados Genéticamente/genética , Línea Celular
5.
J Environ Manage ; 366: 121723, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-39003897

RESUMEN

The inefficiency of catalysts in sulfate radical-based advanced oxidation processes (SR-AOPs) is primarily attributed to the sluggish circulation of redox couples. Herein, a carbon defects-enriched NBC-C3N5@CoMn (NCC) was synthesized through a self-assembly approach. The carbon defects within the NCC induce the electron trap effect, thereby facilitating the efficient cycling of redox couples in photo-Fenton-like processes during contaminant degradation. This effect enables the self-regeneration of the NCC catalyst. The reductive redox couples (Co (II) and Mn (II)) are continuously regenerated following the degradation process. Within the NCC, CoMn layered double hydroxides (LDHs) act as primary active sites, promoting the generation of hydroxyl radicals (•OH), sulfate radicals (SO4•-) and singlet oxygen (1O2) through continuous electron gain and loss. Additionally, the internal electric field established within the NCC further accelerates electron transfer. Density Functional Theory (DFT) calculations confirm that the carbon defects-enriched NCC exhibits lower adsorption energies and higher electron transfer efficiencies than carbon defect-deficient NCC. This study introduces a novel photocatalyst with self-regenerating capabilities, presenting an innovative approach to regulate redox couples in SR-AOPs for sustainable degradation.


Asunto(s)
Carbono , Oxidación-Reducción , Carbono/química , Catálisis , Radical Hidroxilo/química
6.
Open Biol ; 14(6): 230427, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38862020

RESUMEN

Hypertrophic cardiomyopathy (HCM) is a monogenic cardiac disorder commonly induced by sarcomere gene mutations. However, the mechanism for HCM is not well defined. Here, we generated transgenic MYH7 R453C and MYH6 R453C piglets and found both developed typical cardiac hypertrophy. Unexpectedly, we found serious fibrosis and cardiomyocyte loss in the ventricular of MYH7 R453C, not MYH6 R453C piglets, similar to HCM patients. Then, RNA-seq analysis and western blotting identified the activation of ERK1/2 and PI3K-Akt pathways in MYH7 R453C. Moreover, we observed an increased expression of fetal genes and an excess of reactive oxygen species (ROS) in MYH7 R453C piglet models, which was produced by Nox4 and subsequently induced inflammatory response. Additionally, the phosphorylation levels of Smad2/3, ERK1/2 and NF-kB p65 proteins were elevated in cardiomyocytes with the MYH7 R453C mutation. Furthermore, epigallocatechin gallate, a natural bioactive compound, could be used as a drug to reduce cell death by adjusting significant downregulation of the protein expression of Bax and upregulated Bcl-2 levels in the H9C2 models with MYH7 R453C mutation. In conclusion, our study illustrated that TGF-ß/Smad2/3, ERK1/2 and Nox4/ROS pathways have synergistic effects on cardiac remodelling and inflammation in MYH7 R453C mutation.


Asunto(s)
Cadenas Pesadas de Miosina , NADPH Oxidasa 4 , FN-kappa B , Especies Reactivas de Oxígeno , Transducción de Señal , Factor de Crecimiento Transformador beta , Animales , Cadenas Pesadas de Miosina/metabolismo , Cadenas Pesadas de Miosina/genética , Factor de Crecimiento Transformador beta/metabolismo , NADPH Oxidasa 4/metabolismo , NADPH Oxidasa 4/genética , Especies Reactivas de Oxígeno/metabolismo , FN-kappa B/metabolismo , Porcinos , Miocitos Cardíacos/metabolismo , Humanos , Miosinas Cardíacas/metabolismo , Miosinas Cardíacas/genética , Modelos Animales de Enfermedad , Sistema de Señalización de MAP Quinasas , Animales Modificados Genéticamente , Proteína Smad2/metabolismo , Proteína Smad2/genética , Mutación , Proteína smad3/metabolismo , Proteína smad3/genética , Remodelación Ventricular , Cardiomiopatía Hipertrófica/metabolismo , Cardiomiopatía Hipertrófica/genética , Cardiomiopatía Hipertrófica/patología , Ratas
7.
RSC Adv ; 14(22): 15408-15412, 2024 May 10.
Artículo en Inglés | MEDLINE | ID: mdl-38741971

RESUMEN

Iron-based electrochemical catalysts used to modify electrodes for biosensing have received more attention from biosensor manufacturers because of their excellent biocompatibility and low cost. In this work, a fast-ion conductor potassium ferrite (K2Fe4O7) modified glassy carbon electrode (GCE) was prepared for detecting epinephrine (EP) by electrochemical techniques. The obtained K2Fe4O7/GCE electrode exhibited not only a wide linear range over EP concentration from 2 µM to 260 µM with a detection limit of 0.27 µM (S/N = 3) but also high selectivity toward EP in the presence of common interferents ascorbic acid (AA) and uric acid (UA), as well as good reproducibility and stability.

8.
Front Microbiol ; 15: 1347821, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38601935

RESUMEN

The impact of climate warming on soil microbial communities can significantly influence the global carbon cycle. Coastal wetlands, in particular, are susceptible to changes in soil microbial community structure due to climate warming and the presence of invasive plant species. However, there is limited knowledge about how native and invasive plant wetland soil microbes differ in their response to warming. In this study, we investigated the temporal dynamics of soil microbes (prokaryotes and fungi) under experimental warming in two coastal wetlands dominated by native Phragmites australis (P. australis) and invasive Spartina alterniflora (S. alterniflora). Our research indicated that short-term warming had minimal effects on microbial abundance, diversity, and composition. However, it did accelerate the succession of soil microbial communities, with potentially greater impacts on fungi than prokaryotes. Furthermore, in the S. alterniflora wetland, experimental warming notably increased the complexity and connectivity of the microbial networks. While in the P. australis wetland, it decreased these factors. Analysis of robustness showed that experimental warming stabilized the co-occurrence network of the microbial community in the P. australis wetland, but destabilized it in the S. alterniflora wetland. Additionally, the functional prediction analysis using the Faprotax and FunGuild databases revealed that the S. alterniflora wetland had a higher proportion of saprotrophic fungi and prokaryotic OTUs involved in carbon degradation (p < 0.05). With warming treatments, there was an increasing trend in the proportion of prokaryotic OTUs involved in carbon degradation, particularly in the S. alterniflora wetland. Therefore, it is crucial to protect native P. australis wetlands from S. alterniflora invasion to mitigate carbon emissions and preserve the health of coastal wetland ecosystems under future climate warming in China.

9.
Environ Sci Pollut Res Int ; 31(17): 25202-25215, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38466381

RESUMEN

Laccase immobilized and cross-linked on Fe3S4/earthworm-like mesoporous SiO2 (Fe3S4/EW-mSiO2) was used to degrade methoxychlor (MXC) in aqueous environments. The effects of various parameters on the degradation of MXC were determined using free and immobilized laccase. Immobilization improved the thermal stability and reuse of laccase significantly. Under the conditions of pH 4.5, temperature 40 °C, and reaction time 8 h, the degradation rate of MXC by immobilized laccase reached a maximum value of 40.99% and remained at 1/3 of the original after six cycles. The excellent degradation performance of Fe3S4/EW-mSiO2 was attributable to the pyrite (FeS2) impurity in Fe3S4, which could act as an electron donor in reductive dehalogenation. Sulfide groups and Fe2+ reduced the activation energy of the system resulting in pyrite-assisted degradation of MXC. The degradation mechanism of MXC in aqueous environments by laccase immobilized on Fe3S4/EW-mSiO2 was determined via mass spectroscopy of the degradation products. This study is a new attempt to use pyrite to support immobilized laccase degradation.


Asunto(s)
Hierro , Metoxicloro , Oligoquetos , Animales , Metoxicloro/química , Enzimas Inmovilizadas/química , Lacasa/metabolismo , Dióxido de Silicio/química , Oligoquetos/metabolismo , Sulfuros
10.
Water Sci Technol ; 89(1): 170-186, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-38214993

RESUMEN

In this study, we synthesized Fe3O4 using the co-precipitation method and then prepared magnetic carrier LDHs@Fe3O4 by immobilizing layered double hydroxide on Fe3O4 by in situ growth method. Cellulase was immobilized on this magnetic carrier by using glutaraldehyde as a coupling agent, which can be used for degrading Methoxychlor (MXC). The results demonstrated the maximum MXC removal efficiency of 73.4% at 45 °C and pH = 6.0 with excellent reusability. Through kinetic analysis, it was found that the degradation reaction conforms to the Langmuir-Hinshelwood model and is a first-order reaction. Finally, according to the EPR analysis, the active radicals in the system were found to be OH· and the degradation mechanism was proposed in combination with LC-MS. This study provides a feasible method for degrading organochlorine pesticides, which can be used for groundwater purification.


Asunto(s)
Celulasa , Hidróxidos , Nanocompuestos , Metoxicloro , Cinética
11.
Environ Res ; 248: 118312, 2024 May 01.
Artículo en Inglés | MEDLINE | ID: mdl-38295971

RESUMEN

Overuse of chlorinated disinfectants leads to a significant accumulation of disinfection by-products. Trichloroacetic acid (TCA) is a typical carcinogenic disinfection by-product. The efficacy of the conventional degradation process is reduced by the complex nature of its structure, causing a yearly increase in its prevalence within the ecological environment and consequent infliction of significant harm. In this paper, TCA was chosen as the research subject, Fe/Ni bimetallic nanoparticles were employed as the reducing catalyst, ZIF-8@HMON as the catalytic carrier combined with Fe/Ni nanoparticles, and peroxymonosulfate (PMS) was introduced to construct the reducing-advanced oxidation synergistic system and investigated the effect of this system on the degradation performance and degradation pathway of TCA. Various characterization techniques, including TEM, SEM, XRD, FT-IR, XPS, BET, were employed to investigate the morphology, element composition and structure of composite materials analysis. Moreover, the conditions for TCA degradation can be optimized by changing the experimental environment. The results showed that 25 mg of composite catalyst (mole ratio Fe: Ni = 1:1) and 10 mg of PMS effectively degraded TCA within 20-80 mg/L range at pH = 3 and 55 °C, achieving maximum degradation within 20 min. Finally, the potential pathways of TCA degradation were analyzed using EPR and LC-MS, and the corresponding reaction mechanisms were proposed.


Asunto(s)
Nanopartículas , Ácido Tricloroacético , Espectroscopía Infrarroja por Transformada de Fourier , Peróxidos/química , Nanopartículas/química
12.
Int J Biol Macromol ; 253(Pt 7): 127418, 2023 Dec 31.
Artículo en Inglés | MEDLINE | ID: mdl-37848112

RESUMEN

Adenine base editors, enabling targeted A-to-G conversion in genomic DNA, have enormous potential in therapeutic applications. However, the currently used adenine base editors are limited by wide editing windows and off-target effects in genetic therapy. Here, we report human e18 protein, a RING type E3 ubiquitin ligase variant, fusing with adenine base editors can significantly improve the preciseness and narrow the editing windows compared with ABEmax and ABE8e by diminishing the abundance of base editor protein. As a proof of concept, ABEmax-e18 and ABE8e-e18 dramatically decrease Cas9-dependent and Cas9-independent off-target effects than traditional adenine base editors. Moreover, we utilized ABEmax-e18 to establish syndactyly mouse models and achieve accurate base conversion at human PCSK9 locus in HepG2 cells which exhibited its potential in genetic therapy. Furthermore, a truncated version of base editors-RING (ABEmax-RING or AncBE4max-RING), which fusing the 63 amino acids of e18 protein RING domain to the C terminal of ABEmax or AncBE4max, exhibited similar effect compared to ABEmax-e18 or AncBE4max-e18.In summary, the e18 or RING protein fused with base editors strengthens the precise toolbox in gene modification and maybe works well with various base editing tools with a more applicable to precise genetic therapies in the future.


Asunto(s)
Sistemas CRISPR-Cas , Proproteína Convertasa 9 , Animales , Ratones , Humanos , Proproteína Convertasa 9/metabolismo , Sistemas CRISPR-Cas/genética , Adenina/metabolismo , Edición Génica , ADN/genética , Ubiquitina-Proteína Ligasas/metabolismo
13.
Huan Jing Ke Xue ; 44(9): 5046-5054, 2023 Sep 08.
Artículo en Chino | MEDLINE | ID: mdl-37699822

RESUMEN

Estuarine habitats are a critical zone of the Earth with strong land-sea interactions, that are strongly influenced by human activities. Microplastics (MPs) pollution in the Yellow River Delta (YRD) wetland, a typical young warm-temperate estuarine wetland, has not been comprehensively studied. The morphology, abundance, particle size, and polymer composition of MPs in the surface sediments of the YRD wetland were determined, and the pollution status and ecological risk in the study area were evaluated using the pollution load index (PLI) and potential pollution risk index (PRI). The results showed that the abundance of MPs in the YRD wetland was 20-520 n·kg-1, with a median value of 150 n·kg-1. The MPs were primarily fibers in shape and black in color, with particle size over 1 mm. The polymer components were primarily rayon, polyethylene, polyester, and polyethylene terephthalate. The PLI and PRI values of the MPs in the area were between 0.04-0.96 and 0.00-171.60, respectively, indicating that the pollution of MPs in the YRD wetland was at a slightly polluted level with low ecological risk.

14.
Ying Yong Sheng Tai Xue Bao ; 34(7): 1825-1833, 2023 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-37694466

RESUMEN

Coastal wetlands are highly efficient in blue carbon sequestration. The impacts of climate warming on photosynthetic rates and light response characteristics of wetland plants would change the magnitude of carbon sequestration in coastal wetlands. We constructed warming observation stations in Phragmites australis (Phragmites) wetlands located in the Yellow River Delta in Dongying with dry climate, and in Yancheng by the Yellow Sea with wet climate. By using a Li-6800 photosynthesis system, we investigated the responses of simulated warming on photosynthetic characteristics of Phragmites in both wetlands, and compared the difference between months (June and August) in Dongying wetland. The results showed the photosynthetic rates of Phragmites were higher in June than in August. Warming increased net photosynthetic rate (Pn), transpiration rate (Tr), stomatal conductance (gs) and intercellular carbon dioxide concentration (Ci) in the two months, but the variability of Pn to warming was lower in August. The Pn and water use efficiency (WUE) of Phragmites in the Yancheng wetland were higher than Dongying wetland, and the maximum net photosynthetic rate (Pn max), light saturation point (LSP), apparent quantum efficiency (AQY), and dark respiration rate (Rd) of the former responded more positively to warming. The values of AQY, LSP and Pn max of Phragmites in the Yancheng wetlands were increased by 16.7%, 53.6% and 30.3%, respectively, in the warming plots. Our results suggested that warming could improve the utilization efficiency of weak light, the adaptability to strong light and photosynthetic potential of Phragmites under rainy and humid conditions. This study is of importance for accurately quantifying carbon sequestration of coastal wetlands at the regional and seasonal scales in the context of climate warming.


Asunto(s)
Poaceae , Humedales , China , Transporte Biológico , Fotosíntesis
15.
Gene ; 883: 147684, 2023 Oct 20.
Artículo en Inglés | MEDLINE | ID: mdl-37536398

RESUMEN

Dominant genetic variants in the mitofusin 2 (MFN2) gene lead to Charcot-Marie-Tooth type 2A (CMT2A), a neurodegenerative disease caused by genetic defects that directly damage axons. In this study, we reported a proband with a pathogenic variant in the GTPase domain of MFN2, c.494A > G (p.His165Arg). To date, at least 184 distinct MFN2 variants identified in 944 independent probands have been reported in 131 references. However, the field of medical genetics has long been challenged by how genetic variation in the MFN2 gene is associated with disease phenotypes. Here, by collating the MFN2 variant data and patient clinical information from Leiden Open Variant Database 3.0, NCBI clinvar database, and available related references in PubMed, we determined the mutation frequency, age of onset, sex ratio, and geographical distribution. Furthermore, the results of an analysis examining the relationship between variants and phenotypes from multiple genetic perspectives indicated that insertion and deletions (indels), copy number variants (CNVs), duplication variants, and nonsense mutations in single nucleotide variants (SNVs) tend to be pathogenic, and the results emphasized the importance of the GTPase domain to the structure and function of MFN2. Overall, three reliable classification methods of MFN2 genotype-phenotype associations provide insights into the prediction of CMT2A disease severity. Of course, there are still many MFN2 variants that have not been given clear clinical significance, which requires clinicians to make more accurate clinical diagnoses.


Asunto(s)
Enfermedad de Charcot-Marie-Tooth , Enfermedades Neurodegenerativas , Humanos , Mutación , Enfermedad de Charcot-Marie-Tooth/genética , Enfermedad de Charcot-Marie-Tooth/patología , GTP Fosfohidrolasas/genética , Estudios de Asociación Genética , Proteínas Mitocondriales/genética , Proteínas Mitocondriales/química
16.
Research (Wash D C) ; 6: 0203, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37496633

RESUMEN

Familial hypercholesterolemia (FH) is a frequently occurring genetic disorder that is linked to early-onset cardiovascular disease. If left untreated, patients with this condition can develop severe cardiovascular complications. Unfortunately, many patients remain undiagnosed, and even when diagnosed, the treatment is often not optimal. Although mutations in the LDLR gene are the primary cause of FH, predicting whether novel variants are pathogenic is not a straightforward task. Understanding the functionality of LDLR variants is crucial in uncovering the genetic basis of FH. Our study utilized CRISPR/Cas9 cytosine base editors in pooled screens to establish a novel approach for functionally assessing tens of thousands of LDLR variants on a large scale. A total of more than 100 single guide RNAs (sgRNAs) targeting LDLR pathogenic mutations were successfully screened with relatively high accuracy. Out of these, 5 sgRNAs were further subjected to functional verification studies, including 1 in the promoter, 1 in the antisense RNA, 1 in the exon, and 2 in the intron. Except for the variant caused by the sgRNA located at intron 16, the functionalities of the other LDLR variants were all downregulated. The high similarity of LDLR intron sequences may lead to some false positives. Overall, these results confirm the reliability of the large-scale screening strategy for functional analysis of LDLR variants, and the screened candidate pathogenic mutations could be used as an auxiliary means of clinical gene detection to prevent FH-induced heart disease.

17.
Viruses ; 15(2)2023 01 27.
Artículo en Inglés | MEDLINE | ID: mdl-36851573

RESUMEN

Transmissible gastroenteritis virus (TGEV) is a member of the alphacoronavirus genus, which has caused huge threats and losses to pig husbandry with a 100% mortality in infected piglets. TGEV is observed to be recombining and evolving unstoppably in recent years, with some of these recombinant strains spreading across species, which makes the detection and prevention of TGEV more complex. This paper reviews and discusses the basic biological properties of TGEV, factors affecting virulence, viral receptors, and the latest research advances in TGEV infection-induced apoptosis and autophagy to improve understanding of the current status of TGEV and related research processes. We also highlight a possible risk of TGEV being zoonotic, which could be evidenced by the detection of CCoV-HuPn-2018 in humans.


Asunto(s)
Alphacoronavirus , Virus de la Gastroenteritis Transmisible , Humanos , Animales , Porcinos , Apoptosis , Autofagia , Receptores Virales
18.
Environ Sci Pollut Res Int ; 30(17): 49577-49590, 2023 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-36781672

RESUMEN

The "trinitrogen" [ammonia nitrogen (NH4+ - N), nitrate nitrogen (NO3- - N), and nitrite nitrogen (NO2- - N)] from industrial or domestic wastewater can lead to eutrophication of water bodies. When ammonia nitrogen is converted into nitrate nitrogen, it will cause high nitrogen oxygen demand, which will also lead to hyperammonemia. High nitrite content in water bodies will increase the risk of human cancer. In this paper, Fe-Ce bimetallic-doped composites (Fe-Ce/SiO2 and Fe-Ce-SiO2/TiO2) were synthesized using SiO2 aerogel as a carrier for the adsorption and degradation of "three nitrogen."SiO2/TiO2 was prepared by dipping method, and Fe and Ce bimetals were loaded on the surface of SiO2/TiO2 material, and the effect of photo-Fenton oxidation on the degradation rate of three nitrogen under different materials was explored. The results showed that when the dosage of catalyst was 0.01 g, pH value was 11.0, and the concentration of H2O2 was 80 mmol/L, the photocatalytic efficiency was the best, and the degradation efficiency of three nitrogen remained above 70%.


Asunto(s)
Nitratos , Nitritos , Humanos , Nitritos/química , Nitratos/química , Amoníaco/química , Dióxido de Silicio/química , Peróxido de Hidrógeno/química , Titanio/química , Agua , Nitrógeno , Catálisis
20.
Environ Sci Pollut Res Int ; 30(7): 18843-18860, 2023 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-36219297

RESUMEN

Studies of heavy metal pollution are essential for the protection of coastal environments. In this study, positive matrix factorization (PMF) and a GeoDetector model were used to evaluate the sources of heavy metal contamination and associated ecological risks along the Yancheng Coastal Wetland. The distribution of heavy metals was shown to be greatly affected by clay content, except for Cr in shoal. Components from 6.5 to 9φ have the strongest ability to absorb heavy metals, where the effects of Cd and Zn sequestration in the wetlands were most apparent. The abilities of various wetland environments to sequester heavy metals were shown to be Spartina alterniflora wetland > woodland > Phragmites australis wetland > aquaculture pond > shoal > paddy > meadow > dry land. The sources of the heavy metals included parent soil material (59%), agriculture (15%), and industrial pollutants (26%). According to the single-factor pollution index, there was no evidence of pollution except Cr and Pb. In general, the heavy metal pollution was insignificant. The order of pollution loading index was shoal > paddy field > dry land > Spartina Alterniflora wetland > aquaculture ponds > woodland > meadow > Phragmites australis wetland. The ecological harm of heavy metal exposure was slight except for Cd and Hg, where vehicle emissions appeared to be the main cause of heavy metal pollution.


Asunto(s)
Metales Pesados , Contaminantes del Suelo , Ecosistema , Suelo , Cadmio , Contaminantes del Suelo/análisis , Monitoreo del Ambiente , Medición de Riesgo , Metales Pesados/análisis , Poaceae , China
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