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1.
iScience ; 27(8): 110480, 2024 Aug 16.
Artigo em Inglês | MEDLINE | ID: mdl-39156651

RESUMO

Fish cells, such as grass carp (Ctenopharyngodon idella) kidney (CIK) cells, are harder to transfect than mammalian cells. There is a need for an efficient gene delivery system for fish cells. Here, we used CIK cell line as a model to develop a strategy to enhance RNA and plasmid DNA transfection efficiency using a nanocarrier generated from α-lactalbumin (α-NC). α-NC absorbed nucleic acid cargo efficiently and exhibited low cytotoxicity. Plasmid transfection was more efficient with α-NC than with liposomal transfection reagents. We used α-NC to co-transfect Tol2 transposase mRNA and a plasmid containing Cas9 and GFP, generating a stable transgenic CIK cell line. Genome and RNA sequencing revealed that the Cas9 and GFP fragments were successfully inserted into the genome of CIK cells and efficiently transcribed. In this study, we established an efficient transfection system for fish cells using α-NC, simplifying the process of generating stable transgenic fish cell lines.

2.
Bioact Mater ; 41: 239-256, 2024 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-39149594

RESUMO

Periodontitis is a chronic inflammatory disease caused by plaque that destroys the alveolar bone tissues, resulting in tooth loss. Poor eradication of pathogenic microorganisms, persistent malignant inflammation and impaired osteo-/angiogenesis are currently the primary challenges to control disease progression and rebuild damaged alveolar bone. However, existing treatments for periodontitis fail to comprehensively address these issues. Herein, an injectable composite hydrogel (SFD/CS/ZIF-8@QCT) encapsulating quercetin-modified zeolitic imidazolate framework-8 (ZIF-8@QCT) is developed. This hydrogel possesses thermo-sensitive and adhesive properties, which can provide excellent flowability and post-injection stability, resist oral fluid washout as well as achieve effective tissue adhesion. Inspirationally, it is observed that SFD/CS/ZIF-8@QCT exhibits a rapid localized hemostatic effect following implantation, and then by virtue of the sustained release of zinc ions and quercetin exerts excellent collective functions including antibacterial, immunomodulation, pro-osteo-/angiogenesis and pro-recruitment, ultimately facilitating excellent alveolar bone regeneration. Notably, our study also demonstrates that the inhibition of osteo-/angiogenesis of PDLSCs under the periodontitis is due to the strong inhibition of energy metabolism as well as the powerful activation of oxidative stress and autophagy, whereas the synergistic effects of quercetin and zinc ions released by SFD/CS/ZIF-8@QCT are effective in reversing these biological processes. Overall, our study presents innovative insights into the advancement of biomaterials to regenerate alveolar bone in periodontitis.

3.
Molecules ; 29(15)2024 Jul 26.
Artigo em Inglês | MEDLINE | ID: mdl-39124925

RESUMO

Exploring highly active electrocatalysts as platinum (Pt) substitutes for the oxygen reduction reaction (ORR) remains a significant challenge. In this work, single Mn embedded nitrogen-doped graphene (MnN4) with and without halogen ligands (F, Cl, Br, and I) modifying were systematically investigated by density functional theory (DFT) calculations. The calculated results indicated that these ligands can transform the dyz and dxz orbitals of Mn atom in MnN4 near the Fermi-level into dz2 orbital, and shift the d-band center away from the Fermi-level to reduce the adsorption capacity for reaction intermediates, thus enhancing the ORR catalytic activity of MnN4. Notably, Br and I modified MnN4 respectively with the lowest overpotentials of 0.41 and 0.39 V, possess superior ORR catalytic activity. This work is helpful for comprehensively understanding the ligand modification mechanism of single-atom catalysts and develops highly active ORR electrocatalysts.

4.
medRxiv ; 2024 Jun 12.
Artigo em Inglês | MEDLINE | ID: mdl-38947042

RESUMO

Background: Despite the availability of HPV vaccines for over a decade, coverage across the United States (US) is varied. While some states have made concerted efforts to increase HPV vaccination coverage, most model-based analyses have estimated vaccine impact on the US. We estimated the impact of hypothetical changes in HPV vaccination coverage at the state level for three states with varying levels of HPV vaccination coverage and cervical cancer incidence (California, New York, Texas) using a mathematical model. Methods: We developed a new mathematical model of HPV transmission and cervical cancer tailored to state-level cancer incidence and mortality. We quantified the public health impact of increasing HPV vaccination coverage to 80% by 2025 or 2030 and the effect on time to elimination in the three states. Results: Increasing vaccination coverage to 80% in Texas in 10 years could reduce cervical cancer incidence by 50.9% (95%-CrI: 46.6-56.1%) by 2100. In New York and California, achieving the same coverage could reduce incidence by 27.3% (95%-CrI: 23.9-31.5%) and 24.4% (95%-CrI: 20.0-30.0%), respectively. Achieving 80% coverage in 5 years will slightly increase the reduction. If 2019 vaccination coverage continues, cervical cancer elimination would be reached in the US by 2051 (95%-Crl: 2034-2064). However, the timeline by which individual states reach elimination could vary by decades. Conclusion: Achieving an HPV vaccination coverage target of 80% by 2030 will benefit states with low vaccination coverage and high cervical cancer incidence the most. Our results highlight the value of more geographically focused analyses to inform priorities.

5.
J Hazard Mater ; 476: 135023, 2024 Sep 05.
Artigo em Inglês | MEDLINE | ID: mdl-38986406

RESUMO

This study investigates the effects of varying Cu/Ce doping ratios on the NH3-SCR denitrification efficiency using Cu-HPW/CePO4 catalysts, where CePO4 serves as the support and copper-doped phosphotungstic acid (HPW) acts as the active phase. The NH3-SCR reaction mechanism was studied by In-situ Diffuse Reflectance Infrared Fourier Transform Spectroscopy (In-situ DRIFTs) and Density Functional Theory (DFT). In-situ DRIFTs were employed to delve into the intricacies of adsorption and transformation dynamics at the surface sites of catalysts. This approach furnished a robust theoretical foundation aimed at augmenting the efficacy of low-temperature denitrification catalysts. DFT calculations were used to systematically investigate the reaction pathways, intermediates, transition states, and energy barriers over the HPW structure model to complete the NH3-SCR reaction. Empirical evidence suggests that modifying the catalysts with copper substantially enhances their denitrification efficacy and extends their operational temperature spectrum. A notable initial increase in denitrification efficiency was observed with increasing levels of copper modification, followed by a decline. Within the HPW-O15H site, the NH3-SCR reaction advances through both the E-R and L-H mechanisms, encompassing processes such as NH3 adsorption, intermediate formation and transformation, and product release.

6.
J Dent Sci ; 19(3): 1525-1532, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-39035284

RESUMO

Background/purpose: Oral lichen planus (OLP) is a chronic inflammatory disease with unknown mechanisms of pathogenesis. Keratin 17 (KRT17) is a protein that regulates numerous cellular processes. This study aimed to explore the expression of KRT17 in OLP and its correlation with the severity of OLP. Materials and methods: RNA sequencing using epithelium from 5 OLP patients and 5 health control (HC) was performed, followed by functional analysis. The validation cohort of 20 OLP and 20 HC tissues were used to investigate positive area value of KRT17 by immunohistochemical analysis. Reticular, erosive and ulcerative (REU) scores were used for measuring the severity of OLP. Results: A total of 15493 genes were detected, of which 1492 genes were significantly up-regulated in OLP and 622 were down-regulated. The mRNA expression of KRT17 was elevated by 13.09-fold in OLP compared to that in HC. Pathway analysis demonstrated high KRT17 expression was associated with multiple biological processes. The median of percentage of KRT17 positive area value was 19.30 % in OLP and 0.01 % in HC (P < 0.001). Percentage of KRT17 positive area value was higher in erosive OLP patients (27.25 %) compared to that in non-erosive patients (15.02 %, P = 0.006). REU scores were positively correlated with percentage of KRT17 positive area value (r = 0.628, P = 0.003). Conclusion: The mRNA expression of KRT17 was elevated in OLP tissues compared to that in HC. KRT17 was positively correlated with the severity of OLP, indicating KRT17 might play a vital role in the pathogenesis of OLP.

7.
Int Immunopharmacol ; 139: 112661, 2024 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-39008936

RESUMO

The therapeutic effect of 5-amino salicylic acid (5-ASA), a first-line therapeutic agent for the treatment of ulcerative colitis (UC), is limited by the modest bioavailability afforded by its oral administration. In this study, a 5-ASA oral delivery system was developed using Eudragit S100-coated iron oxide-chitosan nanocomposites (ES-IOCS/5-ASA) to address this issue. According to drug release studies in vitro, ES-IOCS/5-ASA only released a small amount of drug in simulated gastric fluid with a pH of 1.2. However, in a medium with a pH of 7.5, a relatively rapid and complete release was noted. 5-ASA-loaded iron oxide-chitosan nanocomposites (IOCS/5-ASA) could be effectively taken up by NCM460 cells and performed better anti-inflammatory effects than free 5-ASA. At the same time, IOCS/5-ASA improved barrier damage in DSS-induced NCM460 cells. In vivo models of dextran sulphate sodium (DSS)-induced colitis were used to assess the therapeutic efficacy of oral administration of ES-IOCS/5-ASA. ES-IOCS/5-ASA significantly relieved DSS-induced colitis and enhanced the integrity of the intestinal epithelial barrier. ES-IOCS/5-ASA also reduced the expression of NLRP3, ASC and IL-1ß. Additionally, iron oxide nanoparticles used as nanozymes could alleviate inflammation. In summary, this study indicates that ES-IOCS/5-ASA exert anti-inflammatory effects on DSS-induced colitis by improving intestinal barrier function and inhibiting NLRP3 inflammasome expression, presenting a viable therapeutic choice for the treatment of UC.


Assuntos
Quitosana , Colite Ulcerativa , Colo , Inflamassomos , Mesalamina , Proteína 3 que Contém Domínio de Pirina da Família NLR , Nanocompostos , Ácidos Polimetacrílicos , Quitosana/química , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Animais , Mesalamina/uso terapêutico , Mesalamina/farmacologia , Mesalamina/administração & dosagem , Mesalamina/química , Colite Ulcerativa/tratamento farmacológico , Inflamassomos/metabolismo , Nanocompostos/química , Humanos , Ácidos Polimetacrílicos/química , Colo/efeitos dos fármacos , Colo/patologia , Colo/metabolismo , Camundongos , Compostos Férricos/química , Sulfato de Dextrana , Linhagem Celular , Camundongos Endogâmicos C57BL , Mucosa Intestinal/efeitos dos fármacos , Mucosa Intestinal/metabolismo , Mucosa Intestinal/patologia , Masculino , Anti-Inflamatórios não Esteroides/administração & dosagem , Anti-Inflamatórios não Esteroides/farmacologia , Anti-Inflamatórios não Esteroides/uso terapêutico , Função da Barreira Intestinal
8.
J Am Chem Soc ; 146(31): 21903-21912, 2024 Aug 07.
Artigo em Inglês | MEDLINE | ID: mdl-39046794

RESUMO

In photoelectrochemical (PEC) cells, selective oxidation of organic substrates coupled with hydrogen evolution represents a promising approach for value-added chemical production and solar energy conversion. In this study, we report on PEC epoxidation of alkenes at a ruthenium dye-sensitized photoanode in a CH3CN/H2O mixed solvent with LiBr as a mediator and water as the oxygen source. The dye-sensitized photoanode was found to exhibit significant advantages in the simultaneous improvement of charge separation and suppression of charge recombination. First, LiBr as a redox mediator plays a critical role in charge separation, leading to an excellent excited electron injection efficiency of 95% and a high dye regeneration efficiency of 87%. Second, the predominant charge recombination pathway on the dye-sensitized photoanode is efficiently blocked by the reaction between alkene and the in situ generated bromine oxidant. As a result, the current system achieved a remarkable photocurrent density of over 4 mA cm-2 with a record-high incident photo-to-current efficiency (IPCE) of 51% and extraordinary selectivity of up to 99% for the epoxidation of a wide range of alkenes. Meanwhile, nearly 100% Faradaic efficiency for hydrogen evolution was obtained. The performance shown here exceeds that obtained by metal oxide-based semiconductor photoanodes under comparable conditions, demonstrating the great potential of dye-sensitized photoelectrodes for organic synthesis owing to their diversity and tunability.

9.
Sci Rep ; 14(1): 16885, 2024 07 23.
Artigo em Inglês | MEDLINE | ID: mdl-39043809

RESUMO

There is no reliable causal evidence for the effect of statins on diabetic nephropathy (DN) and diabetic retinopathy (DR), and the results of previous observational studies are contradictory. Genetic variants linked to low-density lipoprotein cholesterol (LDL-C) from a UK biobank genome-wide association study and located within a 100kb window around HMGCR were used to proxy statins, comparing with PCSK9 inhibitors (control). DN and DR genome-wide association study summary statistics were obtained from the FinnGen study. Secondary MR analyses and NHANES cross-sectional data were used for validation. Drug-target Mendelian randomization (MR) was applied to investigate the association between the genetically proxied inhibition of HMGCR and PCSK9 with DN and DR, p < 0.0125 was considered significant after Bonferroni Correction. To triangulate the findings, genetic variants of whole blood-derived targets gene expression (cis-eQTL) and plasma-derived protein (cis-pQTL) levels were used to perform secondary MR analyses and data from the National Health and Nutrition Examination Survey were used for cross-sectional analysis. Genetically proxied inhibition of HMGCR was associated with higher risks of DN and DR (DN: OR = 1.79, p = 0.01; DR: OR = 1.41, p = 0.004), while no such association was found for PCSK9. Secondary MR analyses confirmed these associations. Cross-sectional analysis revealed a positive link between statin use and DR incidence (OR = 1.26, p = 0.03) and a significant negative association with glomerular filtration rate (Beta = - 1.9, p = 0.03). This study provides genetic evidence that genetically proxied inhibition of HMGCR is associated with increased risks of DN/DR, and this effect may not be attributed to their LDL-C-lowering properties. For patients with diabetic dyslipidemia, PCSK9 inhibitors may be a preferable alternative.


Assuntos
Nefropatias Diabéticas , Retinopatia Diabética , Estudo de Associação Genômica Ampla , Hidroximetilglutaril-CoA Redutases , Inibidores de Hidroximetilglutaril-CoA Redutases , Análise da Randomização Mendeliana , Pró-Proteína Convertase 9 , Humanos , Nefropatias Diabéticas/genética , Nefropatias Diabéticas/tratamento farmacológico , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Retinopatia Diabética/genética , Retinopatia Diabética/tratamento farmacológico , Hidroximetilglutaril-CoA Redutases/genética , Pró-Proteína Convertase 9/genética , Estudos Transversais , Masculino , LDL-Colesterol/sangue , Polimorfismo de Nucleotídeo Único , Feminino , Pessoa de Meia-Idade
10.
Adv Mater ; : e2407315, 2024 Jul 26.
Artigo em Inglês | MEDLINE | ID: mdl-39058238

RESUMO

Liquid-like surfaces (LLSs) with dynamic repellency toward various pollutants (e.g., bacteria, oil, and ice), have shown enormous potential in the fields of biology, environment, and energy. However, most of the reported LLSs cannot meet the demands for practical applications, particularly in terms of de-wettability and durability. To solve these problems, considerable progress has been made in enhancing the de-wettability and durability of LLSs in complex environments. Therefore, this review mainly focuses on the recent progress in LLSs, encompassing designed structures and repellent capabilities, as well as their diverse applications, offering greater insights for the targeted design of desired LLSs. First, a detailed overview of the development of LLSs from the perspective of their molecular structural evolution is provided. Then highlight recent approaches for enhancing the dynamic de-wettability and durability of LLSs by optimizing their structural designs, including linear, looped, crosslinked, and hybrid structures. Later, the diverse applications and unique advantages of recently developed LLSs, including repellency (e.g., liquid anti-adhesion/transportation/condensation, anti-icing/scaling/waxing, and biofouling repellency) are summarized. Finally, Perspectives on potential innovative advancements and the promotion of technology selection to advance this exciting field are offered.

11.
Pathogens ; 13(7)2024 Jun 30.
Artigo em Inglês | MEDLINE | ID: mdl-39057779

RESUMO

In 2023, Rana dybowskii exhibiting characteristic skin ulcers were found on a farm in northeastern China. Subsequently, two dominant bacteria, Aeromonas hydrophila Rd001 and Acinetobacter johnsonii Rd002, were isolated from naturally infected R. dybowskii. Experimental infection confirmed that Rd001 was the primary pathogen responsible for the disease in R. dybowskii, with a mean lethal dose (LD50) of 6.25 × 102 CFU/g. The virulence genotype of Rd001 was identified as ser+/aha+/lip+/nuc+/hlyA+/aer+/alt+/ast+/act+. Antimicrobial susceptibility testing indicated that Rd001 was sensitive to enrofloxacin, flumequine, and neomycin. MLST analysis showed that Rd001 belonged to a new sequence type of A. hydrophila, named ST2378. This study offered the first comprehensive investigation into the pathogenicity, virulence genotypes, antimicrobial resistance, and genetic traits of A. hydrophila isolated from R. dybowskii, providing a theoretical foundation for preventing and controlling A. hydrophila infections.

12.
Nutr Metab (Lond) ; 21(1): 53, 2024 Jul 30.
Artigo em Inglês | MEDLINE | ID: mdl-39080739

RESUMO

BACKGROUND: The pathogenesis of diabetic cardiomyopathy is closely linked to abnormal glycosylation modifications. N-acetylglucosaminyltransferase V (GnT-V), which catalyzes the production of N-linked -1-6 branching of oligosaccharides, is involved in several pathophysiological mechanisms of many disorders, including cardiac hypertrophy and heart failure. However, the mechanism by which GnT-V regulates cardiac hypertrophy in diabetic cardiomyopathy is currently poorly understood. In this study, we investigated the role of GnT-V on myocardial hypertrophy in diabetic cardiomyopathy and elucidated the underlying mechanisms. MATERIAL AND METHODS: Streptozotocin (STZ) was intraperitoneally injected into mice to induce diabetic cardiomyopathy. An adeno-associated virus (AAV) carrying negative control small hairpin RNA (shNC) or GnT-V-specifc small hairpin RNA (shGnT-V) was used to manipulate GnT-V expression. In our study, forty male C57BL/6J mice were randomly divided into four groups (10 mice per group): control mice with AAV-shNC, diabetic cardiomyopathy mice with AAV-shNC, control mice with AAV-shGnT-V, and diabetic cardiomyopathy mice with AAV-shGnT-V. In addition, H9C2 cells and primary neonatal cardiac fibroblasts treated with high glucose were used as a cell model of diabetes. Analysis of cardiac hypertrophy and fibrosis, as well as functional studies, were used to investigate the underlying molecular pathways. RESULTS: AAV-mediated GnT-V silencing dramatically improved cardiac function and alleviated myocardial hypertrophy and fibrosis in diabetic mice. In vitro experiments demonstrated that GnT-V was elevated in cardiomyocytes and induced cardiomyocyte hypertrophy in response to high glucose stimulation. GnT-V knockdown significantly reduced the expression of the integrinß1 signaling pathway, as evidenced by decreased downstream ERK1/2 activity, which inhibited cardiomyocyte hypertrophy accompanied by reduced ANP, BNP, and ß-MHC expression. Furthermore, knocking down GnT-V expression lowered the TGF-ß1-Smads signaling pathway, which reduced the expression of α-SMA, collagen I, and collagen III. CONCLUSIONS: Overall, our research indicated that GnT-V may be a useful therapeutic target to treat diabetic cardiomyopathy, primarily in the inhibition of myocardial hypertrophy and fibrosis.

13.
Clin Proteomics ; 21(1): 40, 2024 Jun 08.
Artigo em Inglês | MEDLINE | ID: mdl-38849742

RESUMO

BACKGROUND: Allergen immunotherapy (AIT) is the only disease-modifying therapy that can achieve immune tolerance in patients through long-term allergen stimulation. Glycans play crucial roles in allergic disease, but no information on changes in glycosylation related to an allergic tolerance status has been reported. METHODS: Fifty-seven patients with house dust mite (HDM) allergies were enrolled. Twenty-eight patients were not treated with AIT, 19 patients had just entered the AIT maintenance treatment phase, and 10 patients had been in the AIT maintenance phase for more than 1 year. Serum protein N-glycans were analyzed by matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS), which included linkage-specific sialylation information. RESULTS: Eighty-four N-glycans were identified in all three groups. Compared with the patients treated without AIT, the patients treated with AIT for a shorter time showed downregulated expression of high-mannose glycans and upregulated expression of α2,6 sialic acid. The patients treated with AIT in the maintenance phase for over 1 year, which was considered the start of immunological tolerance, showed downregulated expression of biantennary N-glycans and upregulated expression of multibranched and complex N-glycans. Nine N-glycans were changed between allergic and allergic-tolerant patients. CONCLUSIONS: The glycan form changed from mannose to a more complex type as treatment time increased, and multibranched complex glycans have the potential to be used as a monitoring indicator of immune tolerance. This serum N-glycome analysis provided important information for a deeper understanding of AIT treatment at the molecular level.

14.
Small ; : e2403136, 2024 May 21.
Artigo em Inglês | MEDLINE | ID: mdl-38770989

RESUMO

Hollandite-type manganese dioxide (α-MnO2) is recognized as a promising cathode material upon high-performance aqueous zinc-ion batteries (ZIBs) owing to the high theoretical capacities, high working potentials, unique Zn2+/H+ co-insertion chemistry, and environmental friendliness. However, its practical applications limited by Zn2+ accommodation, where the strong coulombic interaction and sluggish kinetics cause significant lattice deformation, fast capacity degradation, insufficient rate capability, and undesired interface degradation. It remains challenging to accurately modulate H+ intercalation while suppressing Zn2+ insertion for better lattice stability and electrochemical kinetics. Herein, proton Grotthuss transfer channels are first tunneled by shielding MnO2 with hydrophilic-zincophobic heterointerface, fulfilling the H+-dominating diffusion with the state-of-the-art ZIBs performance. Local atomic structure and theoretical simulation confirm that surface-engineered α-MnO2 affords to the synergy of Mn electron t2g-eg activation, oxygen vacancy enrichment, selective H+ Grotthuss transfer, and accelerated desolvation kinetics. Consequently, fortified α-MnO2 achieves prominent low current density cycle stability (≈100% capacity retention at 1 C after 400 cycles), remarkable long-lifespan cycling performance (98% capacity retention at 20 C after 12 000 cycles), and ultrafast rate performance (up to 30 C). The study exemplifies a new approach of heterointerface engineering for regulation of H+-dominating Grotthuss transfer and lattice stabilization in α-MnO2 toward reliable ZIBs.

15.
J Environ Manage ; 360: 121145, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38788406

RESUMO

Phosphorus (P) is one of the essential nutrient elements for plant growth and development. Sludge compost products can be used as an important source of soil P to solve the shortage of soil P. The difference in the initial carbon-to-phosphorus ratio (C/P) will lead to difference in the bacterial community, which would affect the biological pathway of P conversion in composting. However, few studies have been reported on adjusting the initial C/P of composting to explore P conversion. Therefore, this study investigated the response of P component transformations, bacterial community and P availability to C/P during sludge composting by adjusting initial C/P. The results showed that increasing C/P promoted the mineralization of organic P and significantly increased the content of the labile P. High C/P also increased the relative content of available P, especially when the C/P was at 45 and 60, it reached 60.51% and 60.47%. High C/P caused differences in the community structure, and improved the binding ability of microbial network modules and the competitiveness of microbial communities. Additionally, high C/P strengthened the effect of microbial communities on the transformation of P components. Finally, the study showed that C/P was the main contributor to P content variation (64.7%) and indirectly affected P component conversion by affecting the microbial community. Therefore, adjusting the C/P is crucial to improve the P utilization rate of composting products.


Assuntos
Carbono , Compostagem , Fósforo , Esgotos , Solo , Fósforo/metabolismo , Fósforo/análise , Carbono/metabolismo , Solo/química , Microbiologia do Solo , Microbiota
16.
Biochem Pharmacol ; 225: 116329, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38821375

RESUMO

Calcium signaling abnormality in cardiomyocytes, as a key mechanism, is closely associated with developing heart failure. Fibroblast growth factor 13 (FGF13) demonstrates important regulatory roles in the heart, but its association with cardiac calcium signaling in heart failure remains unknown. This study aimed to investigate the role and mechanism of FGF13 on calcium mishandling in heart failure. Mice underwent transaortic constriction to establish a heart failure model, which showed decreased ejection fraction, fractional shortening, and contractility. FGF13 deficiency alleviated cardiac dysfunction. Heart failure reduces calcium transients in cardiomyocytes, which were alleviated by FGF13 deficiency. Meanwhile, FGF13 deficiency restored decreased Cav1.2 and Serca2α expression and activity in heart failure. Furthermore, FGF13 interacted with microtubules in the heart, and FGF13 deficiency inhibited the increase of microtubule stability during heart failure. Finally, in isoproterenol-stimulated FGF13 knockdown neonatal rat ventricular myocytes (NRVMs), wildtype FGF13 overexpression, but not FGF13 mutant, which lost the binding site of microtubules, promoted calcium transient abnormality aggravation and Cav1.2 downregulation compared with FGF13 knockdown group. Generally, FGF13 deficiency improves abnormal calcium signaling by inhibiting the increased microtubule stability in heart failure, indicating the important role of FGF13 in cardiac calcium homeostasis and providing new avenues for heart failure prevention and treatment.


Assuntos
Sinalização do Cálcio , Fatores de Crescimento de Fibroblastos , Insuficiência Cardíaca , Microtúbulos , Miócitos Cardíacos , Animais , Masculino , Camundongos , Ratos , Células Cultivadas , Fatores de Crescimento de Fibroblastos/metabolismo , Fatores de Crescimento de Fibroblastos/genética , Insuficiência Cardíaca/metabolismo , Insuficiência Cardíaca/genética , Camundongos Endogâmicos C57BL , Camundongos Knockout , Microtúbulos/metabolismo , Microtúbulos/efeitos dos fármacos , Miócitos Cardíacos/metabolismo , Miócitos Cardíacos/efeitos dos fármacos , Ratos Sprague-Dawley
17.
Nat Commun ; 15(1): 4522, 2024 May 28.
Artigo em Inglês | MEDLINE | ID: mdl-38806500

RESUMO

The wet bulb temperature (Tw) has gained considerable attention as a crucial indicator of heat-related health risks. Here we report south-to-north spatially heterogeneous trends of Tw in China over 1979-2018. We find that actual water vapor pressure (Ea) changes play a dominant role in determining the different trend of Tw in southern and northern China, which is attributed to the faster warming of high-latitude regions of East Asia as a response to climate change. This warming effect regulates large-scale atmospheric features and leads to extended impacts of the South Asia high (SAH) and the western Pacific subtropical high (WPSH) over southern China and to suppressed moisture transport. Attribution analysis using climate model simulations confirms these findings. We further find that the entire eastern China, that accommodates 94% of the country's population, is likely to experience widespread and uniform elevated thermal stress the end of this century. Our findings highlight the necessity for development of adaptation measures in eastern China to avoid adverse impacts of heat stress, suggesting similar implications for other regions as well.

18.
Plant Biotechnol J ; 2024 May 30.
Artigo em Inglês | MEDLINE | ID: mdl-38816933

RESUMO

Multiple distinct specialized regions shape the architecture of maize leaves. Among them, the fringe-like and wedge-shaped auricles alter the angle between the leaf and stalk, which is a key trait in crop plant architecture. As planting density increased, a small leaf angle (LA) was typically selected to promote crop light capture efficiency and yield. In the present study, we characterized two paralogous INDETERMINATE DOMAIN (IDD) genes, ZmIDD14 and ZmIDD15, which contain the Cys2-His2 zinc finger domain and function redundantly to regulate auricle development and LA in maize. Loss-of-function mutants showed decreased LA by reducing adaxial sclerenchyma thickness and increasing the colourless cell layers. In addition, the idd14;idd15 double mutant exhibited asymmetrically smaller auricles, which might cause by a failed maintenance of symmetric expression of the key auricle size controlling gene, LIGULELESS(LG1). The transcripts of ZmIDD14 and ZmIDD15 enriched in the ligular region, where LG1 was highly expressed, and both proteins physically interacted with ZmILI1 to promote LG1 transcription. Notably, the idd14;idd15 enhanced the grain yield of hybrids under high planting densities by shaping the plant architecture with a smaller LA. These findings demonstrate the functions of ZmIDD14 and ZmIDD15 in controlling the abaxial/adaxial development of sclerenchyma in the midrib and polar development along the medial-lateral axes of auricles and provide an available tool for high-density and high-yield breeding in maize.

19.
Artigo em Inglês | MEDLINE | ID: mdl-38818580

RESUMO

Fibroblast growth factor (FGF) isoform 13, a distinct type of FGF, boasts significant potential for therapeutic intervention in cardiovascular dysfunctions. However, its impact on regulating fibrosis remains unexplored. This study aims to elucidate the role and mechanism of FGF13 on cardiac fibrosis. Here, we show that following transverse aortic constriction (TAC) surgery, interstitial fibrosis and collagen content increase in mice, along with reduced ejection fraction and fractional shortening, augmented heart mass. However, following Fgf13 deletion, interstitial fibrosis is decreased, ejection fraction and fractional shortening are increased, and heart mass is decreased, compared with those in the TAC group. Mechanistically, incubation of cardiac fibroblasts with transforming growth factor ß (TGFß) increases the expressions of types I and III collagen proteins, as well as α-smooth muscle actin (α-SMA) proteins, and enhances fibroblast proliferation and migration. In the absence of Fgf13, the expressions of these proteins are decreased, and fibroblast proliferation and migration are suppressed, compared with those in the TGFß-stimulated group. Overexpression of FGF13, but not FGF13 mutants defective in microtubule binding and stabilization, rescues the decrease in collagen and α-SMA protein and weakens the proliferation and migration function of the Fgf13 knockdown group. Furthermore, Fgf13 knockdown decreases ROCK protein expression via microtubule disruption. Collectively, cardiac Fgf13 knockdown protects the heart from fibrosis in response to haemodynamic stress by modulating microtubule stabilization and ROCK signaling pathway.

20.
ChemSusChem ; : e202301942, 2024 May 12.
Artigo em Inglês | MEDLINE | ID: mdl-38735842

RESUMO

Aqueous zinc ion batteries (AZIBs) with metallic Zn anode have the potential for large-scale energy storage application due to their cost-effectiveness, safety, environmental-friendliness, and ease of preparation. However, the concerns regarding dendrite growth and side reactions on Zn anode surface hamper the commercialization of AZIBs. This review aims to give a comprehensive evaluation of the protective interphase construction and provide guidance to further improve the electrochemical performance of AZIBs. The failure behaviors of the Zn metal anode including dendrite growth, corrosion, and hydrogen evolution are analyzed. Then, the applications and mechanisms of the constructed interphases are introduced, which are classified by the material species. The fabrication methods of the artificial interfaces are summarized and evaluated, including the in-situ strategy and ex-situ strategy. Finally, the characterization means are discussed to give a full view for the study of Zn anode protection. Based on the analysis of this review, a stable and high-performance Zn anode could be designed by carefully choosing applied material, corresponding protective mechanism, and appropriate construction technique. Additionally, this review for Zn anode modification and construction techniques for anode protection in AZIBs may be helpful in other aqueous metal batteries with similar problems.

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