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1.
Neural Regen Res ; 20(5): 1483-1494, 2025 May 01.
Artículo en Inglés | MEDLINE | ID: mdl-39075914

RESUMEN

JOURNAL/nrgr/04.03/01300535-202505000-00030/figure1/v/2024-07-28T173839Z/r/image-tiff Noise-induced hearing loss is the primary non-genetic factor contributing to auditory dysfunction. However, there are currently no effective pharmacological interventions for patients with noise-induced hearing loss. Here, we present evidence suggesting that the lysine-specific demethylase 1 inhibitor-tranylcypromine is an otoprotective agent that could be used to treat noise-induced hearing loss, and elucidate its underlying regulatory mechanisms. We established a mouse model of permanent threshold shift hearing loss by exposing the mice to white broadband noise at a sound pressure level of 120 dB for 4 hours. We found that tranylcypromine treatment led to the upregulation of Sestrin2 (SESN2) and activation of the autophagy markers light chain 3B and lysosome-associated membrane glycoprotein 1 in the cochleae of mice treated with tranylcypromine. The noise exposure group treated with tranylcypromine showed significantly lower average auditory brainstem response hearing thresholds at click, 4, 8, and 16 kHz frequencies compared with the noise exposure group treated with saline. These findings indicate that tranylcypromine treatment resulted in increased SESN2, light chain 3B, and lysosome-associated membrane glycoprotein 1 expression after noise exposure, leading to a reduction in levels of 4-hydroxynonenal and cleaved caspase-3, thereby reducing noise-induced hair cell loss. Additionally, immunoblot analysis demonstrated that treatment with tranylcypromine upregulated SESN2 expression via the autophagy pathway. Tranylcypromine treatment also reduced the production of NOD-like receptor family pyrin domain-containing 3 (NLRP3) production. In conclusion, our results showed that tranylcypromine treatment ameliorated cochlear inflammation by promoting the expression of SESN2, which induced autophagy, thereby restricting NLRP3-related inflammasome signaling, alleviating cochlear hair cell loss, and protecting hearing function. These findings suggest that inhibiting lysine-specific demethylase 1 is a potential therapeutic strategy for preventing hair cell loss and noise-induced hearing loss.

2.
J Med Chem ; 2024 Sep 24.
Artículo en Inglés | MEDLINE | ID: mdl-39316761

RESUMEN

Efforts to synergize hydrogen sulfide (H2S) with NSAIDs have faced challenges due to complex structural entities and independent release kinetics. This study presents a highly atom-efficient approach of using a thiocarboxylic acid (thioacid) as a novel H2S releasing precursor and successfully employs it to modify NSAIDs, which offers several critical advantages. First, thioacid-modified NSAID is active in inhibiting cyclooxygenase, sometimes with improved potency. Second, this prodrug approach avoids introducing extra structural moieties, allowing for the release of only the intended active principals. Third, the release of H2S and NSAID is concomitant, thus optimally synchronizing the concentration profiles of the two active principals. The design is based on our discovery that esterases can directly and efficiently hydrolyze thiocarboxylic acids, enabling controlled release H2S. This study demonstrates the proof of principle through synthesizing analogs, assesses release kinetics, enzyme inhibition, and pharmacological efficacy, and evaluates toxicity and gut microbiota regulation in animal models.

3.
Anal Chem ; 2024 Sep 17.
Artículo en Inglés | MEDLINE | ID: mdl-39287125

RESUMEN

In this study, we present an innovative "click-to-release" strategy for the design of highly specific H2Sn bioorthogonal probes that undergo a specific click reaction with H2Sn and release fluorophores by a following rearrangement. A library of cyclooctyne derivatives was established and successfully demonstrated the availability of the release strategy. Then, a model probe CM-CT was synthesized, which can achieve effective fluorophore release (>80%) in the presence of a H2Sn donor. To further validate the application of this class of probes, a new probe QN-RHO-CT based on Rhodamine 110 was developed. This probe showed good water solubility (>160 µM) and fast release kinetics and can achieve selective H2Sn detection in living cells. We used this probe to study the process of H2S-mediated protein S-persulfidation and demonstrated that excess H2S would directly react with protein persulfides to generate H2S2 and reduce the persulfides to thiols. Additionally, we elucidated the click-to-release mechanism in our design through a detailed mechanistic study, confirming the generation of the key intermediate α, ß-unsaturated cyclooctanethione. This bioorthogonal click-to-release reaction provides a useful tool for investigating the function of H2Sn and paves the way for biological studies on H2Sn.

4.
J Acoust Soc Am ; 156(3): 1609-1622, 2024 Sep 01.
Artículo en Inglés | MEDLINE | ID: mdl-39248559

RESUMEN

A speech intelligibility (SI) prediction model is proposed that includes an auditory preprocessing component based on the physiological anatomy and activity of the human ear, a hierarchical spiking neural network, and a decision back-end processing based on correlation analysis. The auditory preprocessing component effectively captures advanced physiological details of the auditory system, such as retrograde traveling waves, longitudinal coupling, and cochlear nonlinearity. The ability of the model to predict data from normal-hearing listeners under various additive noise conditions was considered. The predictions closely matched the experimental test data under all conditions. Furthermore, we developed a lumped mass model of a McGee stainless-steel piston with the middle-ear to study the recovery of individuals with otosclerosis. We show that the proposed SI model accurately simulates the effect of middle-ear intervention on SI. Consequently, the model establishes a model-based relationship between objective measures of human ear damage, like distortion product otoacoustic emissions, and speech perception. Moreover, the SI model can serve as a robust tool for optimizing parameters and for preoperative assessment of artificial stimuli, providing a valuable reference for clinical treatments of conductive hearing loss.


Asunto(s)
Redes Neurales de la Computación , Inteligibilidad del Habla , Percepción del Habla , Humanos , Percepción del Habla/fisiología , Estimulación Acústica , Oído Medio/fisiología , Ruido/efectos adversos , Emisiones Otoacústicas Espontáneas , Otosclerosis/fisiopatología , Otosclerosis/cirugía , Simulación por Computador , Vías Auditivas/fisiología , Cóclea/fisiología
5.
BMC Pediatr ; 24(1): 528, 2024 Aug 16.
Artículo en Inglés | MEDLINE | ID: mdl-39152427

RESUMEN

BACKGROUND: The MACF1 gene, found on chromosome 1p34.3, is vital for controlling cytoskeleton dynamics, cell movement, growth, and differentiation. It consists of 101 exons, spanning over 270 kb. The 16p13.11 microduplication syndrome results from the duplication of 16p13.11 chromosome copies and is associated with various neurodevelopmental and physiological abnormalities. Both MACF1 and 16p13.11 microduplication have significant impacts on neural development, potentially leading to nerve damage or neurological diseases. This study presents a unique case of a patient simultaneously experiencing a de novo MACF1 mutation and a hereditary 16p13.11 microduplication, which has not been reported previously. CASE PRESENTATION: In this report, we describe a Chinese preterm newborn girl exhibiting the typical characteristics of 16.13.11 microduplication syndrome. These features include developmental delay, respiratory issues, feeding problems, muscle weakness, excessive joint movement, and multiple congenital abnormalities. Through whole-exome sequencing, we identified a disease-causing mutation in the MACF1 gene (c.15266T > C / p. Met5089Thr). Additionally, after microarray analysis, we confirmed the presence of a 16p13.11 microduplication (chr16:14,916,289 - 16,315,688), which was inherited from the mother. CONCLUSIONS: The patient's clinical presentation, marked by muscle weakness and multiple birth defects, may be attributed to both the de novo MACF1 mutation and the 16p13.11 duplication, which could have further amplified her severe symptoms. Genetic testing for individuals with complex clinical manifestations can offer valuable insights for diagnosis and serve as a reference for genetic counseling for both patients and their families.


Asunto(s)
Anomalías Múltiples , Cromosomas Humanos Par 16 , Hipotonía Muscular , Humanos , Femenino , Recién Nacido , Hipotonía Muscular/genética , Cromosomas Humanos Par 16/genética , Anomalías Múltiples/genética , Recien Nacido Prematuro , Duplicación Cromosómica , Mutación , Proteínas de Microfilamentos/genética
6.
Angew Chem Int Ed Engl ; : e202412568, 2024 Aug 14.
Artículo en Inglés | MEDLINE | ID: mdl-39140424

RESUMEN

The electrochemical conversion of CO2 into valuable chemicals is a promising route for renowable energy storage and the mitigation of greenhouse gas emission, and production of multicarbon (C2+) products is highly desired. Here, we report a 1.4%Pd-Cu@CuPz2 comprising of dispersive CuOx and PdO dual nanoclusters embedded in the MOF CuPz2 (Pz = Pyrazole), which achieves a high C2+ Faradaic efficiency (FEC2+) of 81.9% and C2+ alcohol FE of 47.5% with remarkable stability when using 0.1 M KCl aqueous solution as electrolyte in a typical H-cell. Particularly, the FE of alcohol is obviously improved on 1.4%Pd-Cu@CuPz2 compared to Cu@CuPz2. Theoretical calculations have revealed that revealed that the enhanced interfacial electron transfer facilitates the adsorption of *CO intermediate and *CO-*CO dimerization on the Cu-Pd dual sites bridged by Cu nodes of CuPz2. Additionally, the oxophilicity of Pd can stabilize the key intermediate *CH2CHO and promote subsequent proton-coupled electron transfer more efficiently, confirming that the formation pathway is skew towards *C2H5OH. Consequently, the Cu-Pd dual sites play a synergistic tandem role in cooperatively improving the selectivity of alcohol and accelerating reductive conversion of CO2 to C2+.

7.
J Acoust Soc Am ; 156(2): 989-1003, 2024 Aug 01.
Artículo en Inglés | MEDLINE | ID: mdl-39136635

RESUMEN

In order to improve the prediction accuracy of the sound quality of vehicle interior noise, a novel sound quality prediction model was proposed based on the physiological response predicted metrics, i.e., loudness, sharpness, and roughness. First, a human-ear sound transmission model was constructed by combining the outer and middle ear finite element model with the cochlear transmission line model. This model converted external input noise into cochlear basilar membrane response. Second, the physiological perception models of loudness, sharpness, and roughness were constructed by transforming the basilar membrane response into sound perception related to neuronal firing. Finally, taking the calculated loudness, sharpness, and roughness of the physiological model and the subjective evaluation values of vehicle interior noise as the parameters, a sound quality prediction model was constructed by TabNet model. The results demonstrate that the loudness, sharpness, and roughness computed by the human-ear physiological model exhibit a stronger correlation with the subjective evaluation of sound quality annoyance compared to traditional psychoacoustic parameters. Furthermore, the average error percentage of sound quality prediction based on the physiological model is only 3.81%, which is lower than that based on traditional psychoacoustic parameters.


Asunto(s)
Percepción Sonora , Ruido del Transporte , Psicoacústica , Humanos , Percepción Sonora/fisiología , Estimulación Acústica/métodos , Análisis de Elementos Finitos , Modelos Biológicos , Automóviles , Membrana Basilar/fisiología , Cóclea/fisiología , Percepción Auditiva/fisiología , Ruido , Oído Medio/fisiología , Simulación por Computador
8.
Sensors (Basel) ; 24(15)2024 Jul 24.
Artículo en Inglés | MEDLINE | ID: mdl-39123850

RESUMEN

Robust object detection in complex environments, poor visual conditions, and open scenarios presents significant technical challenges in autonomous driving. These challenges necessitate the development of advanced fusion methods for millimeter-wave (mmWave) radar point cloud data and visual images. To address these issues, this paper proposes a radar-camera robust fusion network (RCRFNet), which leverages self-supervised learning and open-set recognition to effectively utilise the complementary information from both sensors. Specifically, the network uses matched radar-camera data through a frustum association approach to generate self-supervised signals, enhancing network training. The integration of global and local depth consistencies between radar point clouds and visual images, along with image features, helps construct object class confidence levels for detecting unknown targets. Additionally, these techniques are combined with a multi-layer feature extraction backbone and a multimodal feature detection head to achieve robust object detection. Experiments on the nuScenes public dataset demonstrate that RCRFNet outperforms state-of-the-art (SOTA) methods, particularly in conditions of low visual visibility and when detecting unknown class objects.

9.
Environ Technol ; : 1-11, 2024 Jul 02.
Artículo en Inglés | MEDLINE | ID: mdl-38955504

RESUMEN

As volatile organic compounds (VOCs), gaseous ethylbenzene has adverse effects on human health and ecology. Therefore, an effective degradation process is highly desirable. The Fenton process under UV 365 nm was selected as the first option to remove gaseous ethylbenzene in a bubble column reactor. The main parameters for the batch experiments were systematically studied, including H2O2 concentration, [H2O2]/[Fe2+], pH, UV wavelength, UV intensity, gaseous ethylbenzene concentration, gas flow rate, and process stability towards removal efficiency. The optimum conditions were found to be H2O2 concentration of 100 mmol·L-1, [H2O2]/[Fe2+] of 4, pH of 3.0, UV wavelength of 365 nm, UV power of 5 W, gas flow rate of 900 mL·min-1, and gaseous ethylbenzene concentration of 30 ppm, resulting in a removal efficiency of 76.3%. The study found that the Fenton process, when coupled with UV 365 nm, was highly effective in removing gaseous ethylbenzene. The degradation mechanism of gaseous ethylbenzene was proposed in the UV365/Fenton process based on EPR, radical quenching experiments, iron analysis, carbon balance, and GC-MS analysis. The results indicated that •OH played a crucial role in the process.

10.
Chem Sci ; 15(28): 10926-10934, 2024 Jul 17.
Artículo en Inglés | MEDLINE | ID: mdl-39027307

RESUMEN

Here, we report a highly effective dearomative (3 + 2) cycloaddition reaction between isoquinolinium ylides and α,ß-enamides, α,ß-γ,δ-dienamides, or an α,ß-γ,δ-ε,ζ-trienamide, which is catalyzed by a chiral π-Cu(ii) complex (1-10 mol%) and proceeds in a site-selective, exo/endo-selective, and enantioselective manner. The (3 + 2) cycloaddition involving the α,ß-enamides proceeds with high exo-selectivity and enantioselectivity. This method is applicable to various substrates including α-substituted, α,ß-disubstituted, or ß,ß-disubstituted α,ß-enamides, which are compounds with an intrinsically low reactivity. This method provides synthetic access to pyrroloisoquinoline derivatives with up to three chiral carbon centers, including those featuring fluorine and trifluoromethyl groups, as well as quaternary carbon centers. The (3 + 2) cycloaddition involving α,ß-γ,δ-dienamides proceeds with high γ,δ-site-selectivity and enantioselectivity, whereby the exo/endo-selectivity depends on the substrates and ligands. Remarkably, the (3 + 2) cycloaddition of δ-phenyl-α,ß-γ,δ-dienamide proceeds with high α,ß-site-selectivity, exo-selectivity, and enantioselectivity. In a manner similar to the reaction with the α,ß-γ,δ-dienamides, α,ß-γ,δ-ε,ζ-trienamide furnishes a (3 + 2) cycloadduct with good ε,ζ-site-selectivity, endo-selectivity, and enantioselectivity.

11.
Front Immunol ; 15: 1387811, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38911870

RESUMEN

The Nipah virus (NiV), a highly deadly bat-borne paramyxovirus, poses a substantial threat due to recurrent outbreaks in specific regions, causing severe respiratory and neurological diseases with high morbidity. Two distinct strains, NiV-Malaysia (NiV-M) and NiV-Bangladesh (NiV-B), contribute to outbreaks in different geographical areas. Currently, there are no commercially licensed vaccines or drugs available for prevention or treatment. In response to this urgent need for protection against NiV and related henipaviruses infections, we developed a novel homotypic virus-like nanoparticle (VLP) vaccine co-displaying NiV attachment glycoproteins (G) from both strains, utilizing the self-assembling properties of ferritin protein. In comparison to the NiV G subunit vaccine, our nanoparticle vaccine elicited significantly higher levels of neutralizing antibodies and provided complete protection against a lethal challenge with NiV infection in Syrian hamsters. Remarkably, the nanoparticle vaccine stimulated the production of antibodies that exhibited superior cross-reactivity to homologous or heterologous henipavirus. These findings underscore the potential utility of ferritin-based nanoparticle vaccines in providing both broad-spectrum and long-term protection against NiV and emerging zoonotic henipaviruses challenges.


Asunto(s)
Anticuerpos Neutralizantes , Anticuerpos Antivirales , Ferritinas , Infecciones por Henipavirus , Mesocricetus , Nanopartículas , Virus Nipah , Vacunas Virales , Animales , Virus Nipah/inmunología , Infecciones por Henipavirus/prevención & control , Infecciones por Henipavirus/inmunología , Ferritinas/inmunología , Anticuerpos Antivirales/inmunología , Anticuerpos Antivirales/sangre , Anticuerpos Neutralizantes/inmunología , Anticuerpos Neutralizantes/sangre , Vacunas Virales/inmunología , Vacunas Virales/administración & dosificación , Cricetinae , Vacunas de Partículas Similares a Virus/inmunología , Vacunas de Partículas Similares a Virus/administración & dosificación , Femenino , Humanos , Nanovacunas
12.
Front Chem ; 12: 1381835, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38915902

RESUMEN

Long-chain esters (LCEs) are known to affect aroma perception, but the mechanism of their effects remains unclear. In this study, ethyl palmitate (EP), an important LCE in Osmanthus fragrans flower absolute (OFFA), was selected as a target to identify its role and mechanism. The release characteristics of 10 aroma compounds from OFFA with and without EP were obtained by headspace gas chromatography mass spectrometry (HS-GC/MS) and olfactometry evaluation, respectively. The results show that EP changes the release behaviors of volatile compounds in solution, increases their olfactory detection thresholds (ODTs), and reduces the equilibrium headspace concentrations. According to Whitman's two-film model, EP was found to change the partition coefficients and mass transfer coefficients of the compounds between the liquid and gas phases. This indicates that EP plays an important role in the scent formation of a flavor product and that it is very valuable for the style design of the flavor product.

13.
Curr Neurovasc Res ; 2024 Jun 24.
Artículo en Inglés | MEDLINE | ID: mdl-38918992

RESUMEN

BACKGROUND: Adherens junction in the blood-labyrinth barrier is largely unexplored because it is traditionally thought to be less important than the tight junction. Since increasing evidence indicates that it actually functions upstream of tight junction adherens junction may potentially be a better target for ameliorating the leakage of the blood-labyrinth barrier under pathological conditions such as acoustic trauma. AIMS: This study was conducted to investigate the pathogenesis of the disruption of adherens junction after acoustic trauma and explore potential therapeutic targets. METHODS: Critical targets that regulated the disruption of adherens junction were investigated by techniques such as immunofluorescence and Western blottingin C57BL/6J mice. RESULTS: Upregulation of Vascular Endothelial Growth Factor (VEGF) and downregulation of Pigment Epithelium-derived Factor (PEDF) coactivated VEGF-PEDF/VEGF receptor 2 (VEGFR2) signaling pathway in the stria vascularis after noise exposure. Downstream effector Src kinase was then activated to degrade VE-cadherin and dissociate adherens junction which led to the leakage of the blood-labyrinth barrier. By inhibiting VEGFR2 or Src kinase VE-cadherin degradation and blood-labyrinth barrier leakage could be attenuated but Src kinase represented a better target to ameliorate blood-labyrinth barrier leakage as inhibiting it would not interfere with vascular endothelium repair neurotrophy and pericytes proliferation mediated by upstream VEGFR2. CONCLUSION: Src kinase may represent a promising target to relieve noise-induced disruption of adherens junction and hyperpermeability of the blood-labyrinth barrier.

14.
Microb Genom ; 10(5)2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38700925

RESUMEN

Paramyxoviruses are a group of single-stranded, negative-sense RNA viruses, some of which are responsible for acute human disease, including parainfluenza virus, measles virus, Nipah virus and Hendra virus. In recent years, a large number of novel paramyxoviruses, particularly members of the genus Jeilongvirus, have been discovered in wild mammals, suggesting that the diversity of paramyxoviruses may be underestimated. Here we used hemi-nested reverse transcription PCR to obtain 190 paramyxovirus sequences from 969 small mammals in Hubei Province, Central China. These newly identified paramyxoviruses were classified into four clades: genera Jeilongvirus, Morbillivirus, Henipavirus and Narmovirus, with most of them belonging to the genus Jeilongvirus. Using Illumina sequencing and Sanger sequencing, we successfully recovered six near-full-length genomes with different genomic organizations, revealing the more complex genome content of paramyxoviruses. Co-divergence analysis of jeilongviruses and their known hosts indicates that host-switching occurred more frequently in the evolutionary histories of the genus Jeilongvirus. Together, our findings demonstrate the high prevalence of paramyxoviruses in small mammals, especially jeilongviruses, and highlight the diversity of paramyxoviruses and their genome content, as well as the evolution of jeilongviruses.


Asunto(s)
Infecciones por Paramyxoviridae , Paramyxovirinae , Paramyxovirinae/genética , Infecciones por Paramyxoviridae/epidemiología , Infecciones por Paramyxoviridae/veterinaria , Mamíferos , China , Filogenia , Genoma Viral , Especificidad del Huésped
15.
Acta Otolaryngol ; 144(3): 159-167, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38742731

RESUMEN

BACKGROUND: In temporal bone specimens from long-term cochlear implant users, foreign body response within the cochlea has been demonstrated. However, how hearing changes after implantation and fibrosis progresses within the cochlea is unknown. OBJECTIVES: To investigate the short-term dynamic changes in hearing and cochlear histopathology in minipigs after electrode array insertion. MATERIAL AND METHODS: Twelve minipigs were selected for electrode array insertion (EAI) and the Control. Hearing tests were performed preoperatively and on 0, 7, 14, and 28 day(s) postoperatively, and cochlear histopathology was performed after the hearing tests on 7, 14, and 28 days after surgery. RESULTS: Electrode array insertion had a significant effect for the frequency range tested (1 kHz-20kHz). Exudation was evident one week after electrode array insertion; at four weeks postoperatively, a fibrous sheath formed around the electrode. At each time point, the endolymphatic hydrops was found; no significant changes in the morphology and packing density of the spiral ganglion neurons were observed. CONCLUSIONS AND SIGNIFICANCE: The effect of electrode array insertion on hearing and intracochlear fibrosis was significant. The process of fibrosis and endolymphatic hydrops seemed to not correlate with the degree of hearing loss, nor did it affect spiral ganglion neuron integrity in the 4-week postoperative period.


Asunto(s)
Cóclea , Implantación Coclear , Implantes Cocleares , Porcinos Enanos , Animales , Porcinos , Cóclea/patología , Implantes Cocleares/efectos adversos , Implantación Coclear/métodos , Implantación Coclear/efectos adversos , Fibrosis , Electrodos Implantados/efectos adversos
16.
Cell Discov ; 10(1): 54, 2024 May 21.
Artículo en Inglés | MEDLINE | ID: mdl-38769343

RESUMEN

A long-standing hypothesis proposes that certain RNA(s) must exhibit structural roles in microtubule assembly. Here, we identify a long noncoding RNA (TubAR) that is highly expressed in cerebellum and forms RNA-protein complex with TUBB4A and TUBA1A, two tubulins clinically linked to cerebellar and myelination defects. TubAR knockdown in mouse cerebellum causes loss of oligodendrocytes and Purkinje cells, demyelination, and decreased locomotor activity. Biochemically, we establish the roles of TubAR in promoting TUBB4A-TUBA1A heterodimer formation and microtubule assembly. Intriguingly, different from the hypomyelination-causing mutations, the non-hypomyelination-causing mutation TUBB4A-R2G confers gain-of-function for an RNA-independent interaction with TUBA1A. Experimental use of R2G/A mutations restores TUBB4A-TUBA1A heterodimer formation, and rescues the neuronal cell death phenotype caused by TubAR knockdown. Together, we uncover TubAR as the long-elusive structural RNA for microtubule assembly and demonstrate how TubAR mediates microtubule assembly specifically from αß-tubulin heterodimers, which is crucial for maintenance of cerebellar myelination and activity.

17.
Phytomedicine ; 130: 155741, 2024 Jul 25.
Artículo en Inglés | MEDLINE | ID: mdl-38772182

RESUMEN

BACKGROUND: Ulcerative colitis (UC) is a chronic recurrent intestinal disease lacking effective treatments. ß-arbutin, a glycoside extracted from the Arctostaphylos uva-ursi leaves, that can regulate many pathological processes. However, the effects of ß-arbutin on UC remain unknown. PURPOSE: In this study, we investigated the role of ß-arbutin in relieving colitis and explored its potential mechanisms in a mouse model of dextran sulfate sodium (DSS)-induced colitis. METHODS: In C75BL/6 J mice, DSS was used to induce colitis and concomitantly ß-arbutin (50 and 100 mg/kg) was taken orally to evaluate its curative effect by evaluating disease activity index (DAI) score, colon length and histopathology. Alcian blue periodic acid schiff (AB-PAS) staining, immunohistochemistry (IHC), immunofluorescence (IF) and TdT-mediated dUTP Nick-End Labeling (Tunel) staining were used to assess intestinal barrier function. Flow cytometry, double-IF and western blotting (WB) were performed to verify the regulatory mechanism of ß-arbutin on neutrophil extracellular traps (NETs) in vivo and in vitro. NETs depletion experiments were used to demonstrate the role of NETs in UC. Subsequently, the 16S rRNA gene sequencing was used to analyze the intestinal microflora of mouse. RESULTS: Our results showed that ß-arbutin can protect mice from DSS-induced colitis characterized by a lower DAI score and intestinal pathological damage. ß-arbutin reduced inflammatory factors secretion, notably regulated neutrophil functions, and inhibited NETs formation in an ErK-dependent pathway, contributing to the resistance to colitis as demonstrated by in vivo and in vitro experiments. Meanwhile, remodeled the intestinal flora structure and increased the diversity and richness of intestinal microbiota, especially the abundance of probiotics and butyric acid-producing bacteria. It further promoted the protective effect in the resistance of colitis. CONCLUSION: ß-arbutin promoted the maintenance of intestinal homeostasis by inhibiting NETs formation, maintaining mucosal-barrier integrity, and shaping gut-microbiota composition, thereby alleviating DSS-induced colitis. This study provided a scientific basis for the rational use of ß-arbutin in preventing colitis and other related diseases.


Asunto(s)
Arbutina , Sulfato de Dextran , Modelos Animales de Enfermedad , Trampas Extracelulares , Microbioma Gastrointestinal , Ratones Endogámicos C57BL , Animales , Trampas Extracelulares/efectos de los fármacos , Microbioma Gastrointestinal/efectos de los fármacos , Ratones , Arbutina/farmacología , Masculino , Colitis Ulcerosa/tratamiento farmacológico , Colitis Ulcerosa/inducido químicamente , Neutrófilos/efectos de los fármacos , Colitis/tratamiento farmacológico , Colitis/inducido químicamente , Colon/efectos de los fármacos , Colon/patología
18.
Nat Genet ; 56(6): 1257-1269, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38802564

RESUMEN

Na+ exclusion from above-ground tissues via the Na+-selective transporter HKT1;5 is a major salt-tolerance mechanism in crops. Using the expression genome-wide association study and yeast-one-hybrid screening, we identified TaSPL6-D, a transcriptional suppressor of TaHKT1;5-D in bread wheat. SPL6 also targeted HKT1;5 in rice and Brachypodium. A 47-bp insertion in the first exon of TaSPL6-D resulted in a truncated peptide, TaSPL6-DIn, disrupting TaHKT1;5-D repression exhibited by TaSPL6-DDel. Overexpressing TaSPL6-DDel, but not TaSPL6-DIn, led to inhibited TaHKT1;5-D expression and increased salt sensitivity. Knockout of TaSPL6-DDel in two wheat genotypes enhanced salinity tolerance, which was attenuated by a further TaHKT1;5-D knockdown. Spike development was preserved in Taspl6-dd mutants but not in Taspl6-aabbdd mutants. TaSPL6-DIn was mainly present in landraces, and molecular-assisted introduction of TaSPL6-DIn from a landrace into a leading wheat cultivar successfully improved yield on saline soils. The SPL6-HKT1;5 module offers a target for the molecular breeding of salt-tolerant crops.


Asunto(s)
Regulación de la Expresión Génica de las Plantas , Proteínas de Plantas , Tolerancia a la Sal , Triticum , Triticum/genética , Proteínas de Plantas/genética , Tolerancia a la Sal/genética , Proteínas de Transporte de Catión/genética , Estudio de Asociación del Genoma Completo , Oryza/genética , Simportadores/genética , Simportadores/metabolismo , Pan , Plantas Modificadas Genéticamente , Brachypodium/genética , Salinidad
19.
Chemistry ; 30(39): e202400983, 2024 Jul 11.
Artículo en Inglés | MEDLINE | ID: mdl-38747632

RESUMEN

Electrochemical CO2 reduction is a promising method for converting atmospheric CO2 into valuable low-carbon chemicals. In this study, a crystalline cadmium sulfide/amorphous cadmium hydroxide composite was successfully deposited on the carbon paper substrate surface by in-situ chemical bath deposition (named as c-CdS/a-Cd(OH)2/CP electrodes) for the efficient electrochemical CO2 reduction to produce CO. The c-CdS/a-Cd(OH)2/CP electrode exhibited high CO Faradaic efficiencies (>90 %) under a wide potential window of 1.0 V, with the highest value reaching ~100 % at the applied potential ranging from -2.16 V to -2.46 V vs. ferrocene/ferrocenium (Fc/Fc+), superior to the crystalline counterpart c-CdS/CP and c-CdS/c-Cd(OH)2@CP electrodes. Meanwhile, the CO partial current density reached up to 154.7 mA cm-2 at -2.76 V vs. Fc/Fc+ on the c-CdS/a-Cd(OH)2/CP electrode. The excellent performance of this electrode was mainly ascribed to its special three-dimensional structure and the introduction of a-Cd(OH)2. These structures could provide more active sites, accelerate the charge transfer, and enhance adsorption of *COOH intermediates, thereby improving the CO selectivity. Moreover, the electrolytes consisting of 1-butyl-3-methylimidazolium tetrafluoroborate and acetonitrile also enhanced the reaction kinetics of electrochemical CO2 reduction to CO.

20.
Gut Microbes ; 16(1): 2357177, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38781112

RESUMEN

The prevalence of eating disorders has been increasing over the last 50 years. Binge eating disorder (BED) and bulimia nervosa (BN) are two typical disabling, costly and life-threatening eating disorders that substantially compromise the physical well-being of individuals while undermining their psychological functioning. The distressing and recurrent episodes of binge eating are commonly observed in both BED and BN; however, they diverge as BN often involves the adoption of inappropriate compensatory behaviors aimed at averting weight gain. Normal eating behavior is coordinated by a well-regulated trade-off between intestinal and central ingestive mechanism. Conversely, despite the fact that the etiology of BED and BN remains incompletely resolved, emerging evidence corroborates the notion that dysbiosis of gastrointestinal microbiome and its metabolites, alteration of gut-brain axis, as well as malfunctioning central circuitry regulating motivation, execution and reward all contribute to the pathology of binge eating. In this review, we aim to outline the current state of knowledge pertaining to the potential mechanisms through which each component of the gut-brain axis participates in binge eating behaviors, and provide insight for the development of microbiome-based therapeutic interventions that hold promise in ameliorating patients afflicted with binge eating disorders.


Asunto(s)
Trastorno por Atracón , Eje Cerebro-Intestino , Encéfalo , Disbiosis , Microbioma Gastrointestinal , Microbioma Gastrointestinal/fisiología , Humanos , Trastorno por Atracón/microbiología , Trastorno por Atracón/fisiopatología , Trastorno por Atracón/metabolismo , Eje Cerebro-Intestino/fisiología , Encéfalo/microbiología , Encéfalo/fisiopatología , Animales , Disbiosis/microbiología , Conducta Alimentaria
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