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1.
Mol Biol Evol ; 41(6)2024 Jun 01.
Artículo en Inglés | MEDLINE | ID: mdl-38829799

RESUMEN

Global climate change has led to shifts in the distribution ranges of many terrestrial species, promoting their migration from lower altitudes or latitudes to higher ones. Meanwhile, successful invaders have developed genetic adaptations enabling the colonization of new environments. Over the past 40 years, Rattus tanezumi (RT) has expanded into northern China (Northwest and North China) from its southern origins. We studied the cold adaptation of RT and its potential for northward expansion by comparing it with sympatric Rattus norvegicus (RN), which is well adapted to cold regions. Through population genomic analysis, we revealed that the invading RT rats have split into three distinct populations: the North, Northwest, and Tibetan populations. The first two populations exhibited high genetic diversity, while the latter population showed remarkably low genetic diversity. These rats have developed various genetic adaptations to cold, arid, hypoxic, and high-UV conditions. Cold acclimation tests revealed divergent thermoregulation between RT and RN. Specifically, RT exhibited higher brown adipose tissue activity and metabolic rates than did RN. Transcriptome analysis highlighted changes in genes regulating triglyceride catabolic processes in RT, including Apoa1 and Apoa4, which were upregulated, under selection and associated with local adaptation. In contrast, RN showed changes in carbohydrate metabolism genes. Despite the cold adaptation of RT, we observed genotypic and phenotypic constraints that may limit its ability to cope with severe low temperatures farther north. Consequently, it is less likely that RT rats will invade and overlap with RN rats in farther northern regions.


Asunto(s)
Aclimatación , Frío , Animales , Ratas , Aclimatación/genética , China , Fenotipo , Variación Genética , Adaptación Fisiológica/genética , Regulación de la Temperatura Corporal/genética , Cambio Climático
2.
Int J Cancer ; 155(4): 697-709, 2024 Aug 15.
Artículo en Inglés | MEDLINE | ID: mdl-38577882

RESUMEN

Patient-derived organoids (PDOs) may facilitate treatment selection. This retrospective cohort study evaluated the feasibility and clinical benefit of using PDOs to guide personalized treatment in metastatic breast cancer (MBC). Patients diagnosed with MBC were recruited between January 2019 and August 2022. PDOs were established and the efficacy of customized drug panels was determined by measuring cell mortality after drug exposure. Patients receiving organoid-guided treatment (OGT) were matched 1:2 by nearest neighbor propensity scores with patients receiving treatment of physician's choice (TPC). The primary outcome was progression-free survival. Secondary outcomes included objective response rate and disease control rate. Targeted gene sequencing and pathway enrichment analysis were performed. Forty-six PDOs (46 of 51, 90.2%) were generated from 45 MBC patients. PDO drug screening showed an accuracy of 78.4% (95% CI 64.9%-91.9%) in predicting clinical responses. Thirty-six OGT patients were matched to 69 TPC patients. OGT was associated with prolonged median progression-free survival (11.0 months vs. 5.0 months; hazard ratio 0.53 [95% CI 0.33-0.85]; p = .01) and improved disease control (88.9% vs. 63.8%; odd ratio 4.26 [1.44-18.62]) compared with TPC. The objective response rate of both groups was similar. Pathway enrichment analysis in hormone receptor-positive, human epidermal growth factor receptor 2-negative patients demonstrated differentially modulated pathways implicated in DNA repair and transcriptional regulation in those with reduced response to capecitabine/gemcitabine, and pathways associated with cell cycle regulation in those with reduced response to palbociclib. Our study shows that PDO-based functional precision medicine is a feasible and effective strategy for MBC treatment optimization and customization.


Asunto(s)
Neoplasias de la Mama , Organoides , Humanos , Femenino , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/patología , Neoplasias de la Mama/genética , Organoides/patología , Organoides/efectos de los fármacos , Estudios Retrospectivos , Persona de Mediana Edad , Anciano , Adulto , Medicina de Precisión/métodos , Supervivencia sin Progresión , Metástasis de la Neoplasia , Piridinas/uso terapéutico , Piridinas/administración & dosificación , Piperazinas/uso terapéutico , Piperazinas/administración & dosificación , Resultado del Tratamiento
3.
Biochem Biophys Res Commun ; 727: 150336, 2024 Oct 01.
Artículo en Inglés | MEDLINE | ID: mdl-38959731

RESUMEN

Myocardial fibrosis involves the loss of cardiomyocytes, myocardial fibroblast proliferation, and a reduction in angiogenesis, ultimately leading to heart failure, Given its significant implications, it is crucial to explore novel therapies for myocardial fibrosis. Recently one emerging avenue has been the use of small extracellular vesicles (sEV)-carried miRNA. In this review, we summarize the regulatory role of sEV-carried miRNA in myocardial fibrosis. We explored not only the potential diagnostic value of circulating miRNA as biomarkers for heart disease but also the therapeutic implications of sEV-carried miRNA derived from various cellular sources and applications of modified sEV. This exploration is paramount for researchers striving to develop innovative, cell-free therapies as potential drug candidates for the management of myocardial fibrosis.


Asunto(s)
Vesículas Extracelulares , Fibrosis , MicroARNs , Humanos , Vesículas Extracelulares/metabolismo , Vesículas Extracelulares/genética , MicroARNs/genética , MicroARNs/metabolismo , Fibrosis/genética , Animales , Miocardio/patología , Miocardio/metabolismo , Cardiomiopatías/genética , Cardiomiopatías/patología , Cardiomiopatías/metabolismo , Biomarcadores/metabolismo , Miocitos Cardíacos/metabolismo , Miocitos Cardíacos/patología
4.
Small ; : e2311798, 2024 Mar 10.
Artículo en Inglés | MEDLINE | ID: mdl-38461518

RESUMEN

The photocatalytic environmental decontamination ability of carbon nitride (g-C3 N4 , CN) typically suffers from their inherent structural defects, causing rapid recombination of photogenerated carriers. Conjugating CN with tailored donor-acceptor (D-A) units to counteract this problem through electronic restructuring becomes a feasible strategy, where confirmation by density functional theory (DFT) calculations becomes indispensable. Herein, DFT is employed to predirect the copolymerization modification of CN by benzene derivatives, screening benzaldehyde as the optimal electron-donating candidate for the construction of reoriented intramolecular charge transfer path. Experimental characterization and testing corroborate the formation of a narrowed bandgap as well as high photoinduced carrier separation. Consequently, the optimal BzCN-2 exhibited superior photocatalytic capacity in application for tetracycline hydrochloride degradation, with 3.73 times higher than that of CN. Besides, the BzCN-2-based photocatalytic system is determined to have a toxicity-mitigating effect on TC removal via T.E.S.T and prefers the removal of dissociable TC2- species under partial alkalinity. This work provides insight into DFT guidance for the design of D-A conjugated polymer and its application scenarios in photocatalytic decontamination.

5.
Small ; : e2401970, 2024 May 21.
Artículo en Inglés | MEDLINE | ID: mdl-38770987

RESUMEN

Transition metal compounds (TMCs) have long been potential candidate catalysts in persulfate-based advanced oxidation process (PS-AOPs) due to their Fenton-like catalyze ability for radical generation. However, the mechanism involved in TMCs-catalyzed nonradical PS-AOPs remains obscure. Herein, the growth of FeO on the Fe3O4/carbon precursor is regulated by restricted pyrolysis of MIL-88A template to activate peroxymonosulfate (PMS) for tetracycline (TC) removal. The higher FeO incorporation conferred a 2.6 times higher degradation performance than that catalyzed by Fe3O4 and also a higher interference resistance to anions or natural organic matter. Unexpectedly, the quenching experiment, probe method, and electron paramagnetic resonance quantitatively revealed that the FeO reassigned high nonradical species (1O2 and FeIV═O) generation to replace original radical system created by Fe3O4. Density functional theory calculation interpreted that PMS molecular on strongly-adsorbed (200) and (220) facets of FeO enjoyed unique polarized electronic reception for surface confinement effect, thus the retained peroxide bond energetically supported the production of 1O2 and FeIV═O. This work promotes the mechanism understanding of TMCs-induced surface-catalyzed persulfate activation and enables them better perform catalytic properties in wastewater treatment.

6.
J Pharmacol Exp Ther ; 388(1): 156-170, 2024 01 02.
Artículo en Inglés | MEDLINE | ID: mdl-37918855

RESUMEN

Spleen tyrosine kinase (Syk) is an intracellular tyrosine kinase involved in the signal transduction in immune cells mainly. Its aberrant regulation is associated with diversified allergic disorders, autoimmune diseases and B cell malignancies. Therefore, inhibition of Syk is considered a reasonable approach to treat autoimmune/inflammatory diseases and B cell malignancies. Here we described the preclinical characterization of sovleplenib, a novel, highly potent and selective, oral Syk inhibitor, in several rodent autoimmune disease models. Sovleplenib potently inhibited Syk activity in a recombinant enzymatic assay and Syk-dependent cellular functions in various immune cell lines and human whole blood in vitro. Furthermore, sovleplenib, by oral administration, demonstrated strong in vivo efficacies in murine models of immune thrombocytopenia (ITP), autoimmune hemolytic anemia (AIHA), and chronic graft-versus-host disease (cGVHD), and a rat model of collagen induced arthritis (CIA) respectively, in a dose-dependent manner. Collectively, these results clearly supported sovleplenib as a therapeutic agent in the treatment of autoimmune diseases. Sovleplenib is being globally developed for ITP (Phase III, NCT05029635, Phase Ib/II, NCT03951623), wAIHA (Phase II/III, NCT05535933) and B-cell lymphoma (Phase I, NCT02857998, NCT03779113). SIGNIFICANCE STATEMENT: Syk is a key mediator of signaling pathways downstream of a wide array of receptors important for immune functions, including the B cell receptor, immunoglobulin receptors bearing Fc receptors. Inhibition of Syk could provide a novel therapeutic approach for autoimmune diseases and hematologic malignancies. The manuscript describes the preclinical pharmacology characterization of sovleplenib, a novel Syk inhibitor, in enzymatic and cellular assays in vitro and several murine autoimmune disease models in vivo.


Asunto(s)
Enfermedades Autoinmunes , Neoplasias , Ratas , Ratones , Humanos , Animales , Proteínas Tirosina Quinasas , Quinasa Syk , Transducción de Señal , Inhibidores de Proteínas Quinasas/farmacología , Enfermedades Autoinmunes/tratamiento farmacológico , Neoplasias/tratamiento farmacológico
7.
New Phytol ; 243(1): 362-380, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38730437

RESUMEN

Plants typically activate distinct defense pathways against various pathogens. Heightened resistance to one pathogen often coincides with increased susceptibility to another pathogen. However, the underlying molecular basis of this antagonistic response remains unclear. Here, we demonstrate that mutants defective in the transcription factor ETHYLENE-INSENSITIVE 3-LIKE 2 (OsEIL2) exhibited enhanced resistance to the biotrophic bacterial pathogen Xanthomonas oryzae pv oryzae and to the hemibiotrophic fungal pathogen Magnaporthe oryzae, but enhanced susceptibility to the necrotrophic fungal pathogen Rhizoctonia solani. Furthermore, necrotroph-induced OsEIL2 binds to the promoter of OsWRKY67 with high affinity, leading to the upregulation of salicylic acid (SA)/jasmonic acid (JA) pathway genes and increased SA/JA levels, ultimately resulting in enhanced resistance. However, biotroph- and hemibiotroph-induced OsEIL2 targets OsERF083, resulting in the inhibition of SA/JA pathway genes and decreased SA/JA levels, ultimately leading to reduced resistance. Our findings unveil a previously uncharacterized defense mechanism wherein two distinct transcriptional regulatory modules differentially mediate immunity against pathogens with different lifestyles through the transcriptional reprogramming of phytohormone pathway genes.


Asunto(s)
Ciclopentanos , Regulación de la Expresión Génica de las Plantas , Oryza , Oxilipinas , Enfermedades de las Plantas , Inmunidad de la Planta , Proteínas de Plantas , Rhizoctonia , Ácido Salicílico , Xanthomonas , Oxilipinas/metabolismo , Ácido Salicílico/metabolismo , Ciclopentanos/metabolismo , Oryza/microbiología , Oryza/genética , Oryza/inmunología , Enfermedades de las Plantas/microbiología , Enfermedades de las Plantas/inmunología , Xanthomonas/fisiología , Proteínas de Plantas/metabolismo , Proteínas de Plantas/genética , Rhizoctonia/fisiología , Inmunidad de la Planta/efectos de los fármacos , Mutación/genética , Resistencia a la Enfermedad/genética , Regiones Promotoras Genéticas/genética , Factores de Transcripción/metabolismo , Factores de Transcripción/genética , Unión Proteica/efectos de los fármacos
8.
Immunol Invest ; 53(3): 437-449, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38314676

RESUMEN

Cancer is an abnormal proliferation of cells that is stimulated by cyclin-dependent kinases (CDKs) and defective cell cycle regulation. The essential agent that drive the cell cycle, CDK4/6, would be activated by proliferative signals. Activated CDK4/6 results in the phosphorylation of the neuroblastoma protein (RB) and the release of the transcription factor E2F, which promotes the cell cycle progression. CDK4/6 inhibitor (CDK4/6i) has been currently a research focus, which inhibits the CDK4/6-RB-E2F axis, thereby reducing the cell cycle transition from G1 to S phase and mediating the cell cycle arrest. This action helps achieve an anti-tumor effect. Recent research has demonstrated that CDK4/6i, in addition to contributing to cell cycle arrest, is also essential for the interaction between the tumor cells and the host immune system, i.e., activating the immune system, strengthening the tumor antigen presentation, and reducing the number of regulatory T cells (Treg). Additionally, CDK4/6i would elevate the level of PD-L1, an immunosuppressive factor, in tumor cells, and CDK4/6i in combination with anti-PD-L1 therapy would more effectively reduce the tumor growth. Our results showed that CDK4/6i caused autophagy and senescence in tumor cells. Herein, the impact of CDK4/6i on the immune microenvironment of malignant tumors was mainly focused, as well as their interaction with immune checkpoint inhibitors in affecting anti-tumor immunity.


Asunto(s)
Quinasa 6 Dependiente de la Ciclina , Neoplasias , Humanos , Quinasa 4 Dependiente de la Ciclina/metabolismo , Quinasa 4 Dependiente de la Ciclina/farmacología , Quinasa 6 Dependiente de la Ciclina/metabolismo , Quinasa 6 Dependiente de la Ciclina/farmacología , Fosforilación , Puntos de Control del Ciclo Celular , Ciclo Celular , Neoplasias/metabolismo , Inhibidores de Proteínas Quinasas/farmacología , Microambiente Tumoral
9.
J Phys Chem A ; 128(6): 1074-1084, 2024 Feb 15.
Artículo en Inglés | MEDLINE | ID: mdl-38295277

RESUMEN

As one of the most important diatomic molecules in the universe, the spectroscopic characterizations of C2 have attracted wide attention in various fields, such as interstellar chemistry, planetary atmospheric chemistry, and combustion. In recent years, a systematic spectroscopic study of C2 in the vacuum ultraviolet (VUV) region has been carried out in our laboratory by using the (1VUV+1'UV) resonance-enhanced multiphoton ionization method based on the combination of a tunable VUV laser source and a time-of-flight mass spectrometer. Two new electronic transition band systems have been reported, following the pioneering work of Herzberg and co-workers in 1969. In the current study, a total of 18 vibronic transition bands of C2 from the lower a3Πu state are experimentally observed in the VUV photon energy range 72000-81000 cm-1, and 6 new upper vibronic levels of 3Δg symmetry are identified, which are assigned as the v' = 0-5 vibrational levels of the 33Δg state of C2. The term energy Te of the 33Δg state is determined to be in the range of 78425-78475 cm-1 (9.724-9.730 eV) with respect to the ground X1Σg+ state, and the molecular constants such as vibrational and rotational constants are also determined, which are in reasonable agreement with those predicted by high-level ab initio theoretical calculations. Irregular vibrational energy level spacings in the 33Δg state are observed, which is tentatively attributed to the strong perturbations between the 33Δg and 23Δg states, as previously predicted by theory.

10.
Proc Natl Acad Sci U S A ; 118(10)2021 03 09.
Artículo en Inglés | MEDLINE | ID: mdl-33649236

RESUMEN

Mechanistic Target of Rapamycin Complex 1 (mTORC1) is a central regulator of cell growth and metabolism that senses and integrates nutritional and environmental cues with cellular responses. Recent studies have revealed critical roles of mTORC1 in RNA biogenesis and processing. Here, we find that the m6A methyltransferase complex (MTC) is a downstream effector of mTORC1 during autophagy in Drosophila and human cells. Furthermore, we show that the Chaperonin Containing Tailless complex polypeptide 1 (CCT) complex, which facilitates protein folding, acts as a link between mTORC1 and MTC. The mTORC1 activates the chaperonin CCT complex to stabilize MTC, thereby increasing m6A levels on the messenger RNAs encoding autophagy-related genes, leading to their degradation and suppression of autophagy. Altogether, our study reveals an evolutionarily conserved mechanism linking mTORC1 signaling with m6A RNA methylation and demonstrates their roles in suppressing autophagy.


Asunto(s)
Autofagia , Proteínas de Drosophila/metabolismo , Diana Mecanicista del Complejo 1 de la Rapamicina/metabolismo , Metiltransferasas/metabolismo , Receptores Citoplasmáticos y Nucleares/metabolismo , Proteínas Represoras/metabolismo , Transducción de Señal , Animales , Línea Celular , Proteínas de Drosophila/genética , Drosophila melanogaster , Humanos , Diana Mecanicista del Complejo 1 de la Rapamicina/genética , Metilación , Metiltransferasas/genética , Receptores Nucleares Huérfanos , Estabilidad del ARN , Receptores Citoplasmáticos y Nucleares/genética , Proteínas Represoras/genética
11.
J Dairy Sci ; 2024 May 31.
Artículo en Inglés | MEDLINE | ID: mdl-38825137

RESUMEN

This study characterized the sleep activity, sleep mechanism, and active peptides of whey protein hydrolysates selected through behavioral analysis of fruit-flies (Drosophila melanogaster). Sleep-inducing whey protein (WP) hydrolysate was selected through fruit fly behavior analysis, and sleep activity was measured using a pentobarbital model and electroencephalographic analysis. The mechanism of action was confirmed using a γ-aminobutyric acid (GABA) receptor antagonist, and the active peptide was identified using liquid chromatography-mass spectroscopy. Whey protein hydrolysate, prepared using Alcalase and Prozyme (WP-AP), increased sleep time in a dose-dependent manner. WP-AP significantly increased not only sleep time but also slow-wave sleep and showed an insomnia-alleviating effect in a caffeine-induced insomnia mouse model. In addition, the gene and protein expression levels of GABA sub-type A (GABAA) receptors increased in the brains of mice orally administered with WP-AP. Through peptide analysis, the mixture of DIQK, VPPF peptide, and GABA contained in WP-AP was estimated to exhibit sleep activity, and due to its high content, DIQK was speculated to be the main sleep -inducing ingredient. These results indicate that WP-AP has the potential to be used as a new ingredient to improve sleep quality.

12.
Int J Mol Sci ; 25(10)2024 May 19.
Artículo en Inglés | MEDLINE | ID: mdl-38791584

RESUMEN

Autism spectrum disorder (ASD) is a complex neurodevelopmental disorder with heterogeneous and complex genetic underpinnings. Our previous microarray gene expression profiling identified significantly different neuregulin-2 gene (NRG2) expression between ASD patients and controls. Thus, we aimed to clarify whether NRG2 is a candidate gene associated with ASD. The study consisted of two stages. First, we used real-time quantitative PCR in 20 ASDs and 20 controls to confirm the microarray gene expression profiling results. The average NRG2 gene expression level in patients with ASD (3.23 ± 2.80) was significantly lower than that in the controls (9.27 ± 4.78, p < 0.001). Next, we conducted resequencing of all the exons of NRG2 in a sample of 349 individuals with ASD, aiming to identify variants of the NRG2 associated with ASD. We identified three variants, including two single nucleotide variants (SNVs), IVS3 + 13A > G (rs889022) and IVS10 + 32T > A (rs182642591), and one small deletion at exon 11 of NRG2 (delGCCCGG, rs933769137). Using data from the Taiwan Biobank as the controls, we found no significant differences in allele frequencies of rs889022 and rs182642591 between two groups. However, there is a significant difference in the genotype and allele frequency distribution of rs933769137 between ASDs and controls (p < 0.0001). The small deletion is located in the EGF-like domain at the C-terminal of the NRG2 precursor protein. Our findings suggest that NRG2 might be a susceptibility gene for ASD.


Asunto(s)
Trastorno del Espectro Autista , Predisposición Genética a la Enfermedad , Neurregulinas , Polimorfismo de Nucleótido Simple , Humanos , Trastorno del Espectro Autista/genética , Masculino , Femenino , Neurregulinas/genética , Neurregulinas/metabolismo , Frecuencia de los Genes , Estudios de Casos y Controles , Niño , Estudios de Asociación Genética , Perfilación de la Expresión Génica , Exones/genética , Adolescente , Adulto , Factores de Crecimiento Nervioso
13.
Angew Chem Int Ed Engl ; : e202407659, 2024 Jun 06.
Artículo en Inglés | MEDLINE | ID: mdl-38842476

RESUMEN

The further development of aqueous zinc (Zn)-ion batteries (AZIBs) is constrained by the high freezing points and the instability on Zn anodes. Current improvement strategies mainly focus on regulating hydrogen bond (HB) donors (H) of solvent water to disrupt HBs, while neglecting the environment of HB-acceptors (O). Herein, we propose a mechanism of chaotropic cation-regulated HB-acceptor via a "super hydrous solvated" structure. Chaotropic Ca2+ can form a solvated structure via competitively binding O atoms in H2O, effectively breaking the HBs among H2O molecules, thereby reducing the glass transition temperature of hybrid 1 mol L-1 (M) ZnCl2+4 M CaCl2 electrolyte (-113.2 °C). Meanwhile, the high hydratability of Ca2+ contributes to the water-poor solvated structure of Zn2+, suppressing side reactions and uneven Zn deposition. Benefiting from the anti-freezing electrolyte and high reversible Zn anode, the Zn||Pyrene-4,5,9,10-tetraone (PTO) batteries deliver an ultrahigh capacity of 183.9 mAh g-1 at 1.0 A g-1 over 1600-time stable cycling at -60 °C. This work presents a cheap and efficient aqueous electrolyte to simultaneously improve low-temperature performances and Zn stability, broadening the design concepts for antifreeze electrolytes.

14.
Angew Chem Int Ed Engl ; : e202410210, 2024 Jul 18.
Artículo en Inglés | MEDLINE | ID: mdl-39023074

RESUMEN

Zn metal suffers from severe zinc dendrites, anion-related side reactions, hydrogen evolution reaction (HER) and narrow electrochemical stable window (ESW). Herein, an"anions-in-colloid" hydrated deep eutectic electrolyte (ACDE-3) is designed to improve the stability of zinc anode. The ACDE-3 reconfigures the hydrogen-bond (HB) network and regulates the solvation shell. More importantly, the hydroxyl-rich ß-cyclodextrins (ß-CDs) in ACDE-3 self-assemble into micelles, in which the steric effect between the adjacent ß-CDs restricts the movement of anions. This unique "anions-in-colloid" structure enables the eutectic system with a high Zn2+ transference number (tZn2+) of 0.84.  Thus, ACDE-3 inhibits the formation of dendrite, prevents the anion-involved side reactions, suppresses the HER, and enlarges the ESW to 2.32 V. The Zn//Zn symmetric cell delivers a long lifespan of 900 hours at 0.5 mAh cm-2, and the Zn//Cu half cells have a high average columbic efficiency (ACE) of 97.9% at 0.5 mAh cm-2 with a uniform and compact zinc deposition. When matched with a poly(1,5-naphthalenediamine) cathode, the full battery with a low negative/positive capacity ratio of 2 can still cycle steadily for 200 cycles at a current density of 1.0 A g-1. Additionally, this electrolyte can operative over a wide temperature range from -40 °C to 40 °C.

15.
Clin Immunol ; 255: 109767, 2023 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-37689092

RESUMEN

RATIONALE: A persistent autoimmune and inflammatory response plays a critical role in the progression of atherosclerosis. The transcription factor forkhead box P3 (Foxp3)+CD4+ regulatory T cells (Foxp3+ Tregs) attenuate atherosclerosis. Latency-associated peptide (LAP)+CD4+ T cells are a new class of Tregs whose role in atherosclerosis is unknown. OBJECTIVE: To investigate the function of CD4+LAP+ Tregs in inhibiting inflammation and preventing atherosclerosis. METHODS AND RESULTS: Depletion of CD4+LAP+ Tregs results in aggravated inflammation and atherosclerotic lesions. Mechanistically, CD4+LAP+ Treg depletion was associated with decreased M2-like macrophages and increased Th1 and Th17 cells, characterized by increased unstable plaque promotion and decreased expression of inflammation-resolving factors in both arteries and immune organs. In contrast, adoptive transfer of CD4+LAP+ Tregs to ApoE-/- mice or CD4-/-ApoE-/- mice led to decreased atherosclerotic lesions. Compared with control animals, adoptive transfer of CD4+LAP+ Tregs induced M2-like macrophage differentiation within the atherosclerotic lesion and spleen, associated with increased collagen and α-SMA in plaques and decreased expression of MMP-2 and MMP-9. Mechanistic studies reveal that isolated CD4+LAP+ Tregs exhibit a tolerance phenotype, with increased expression of inhibitory cytokines and coinhibitory molecules. After coculture with CD4+LAP+ Tregs, monocytes/macrophages display typical features of M2 macrophages, including upregulated expression of CD206 and Arg-1 and decreased production of MCP-1, IL-6, IL-1ß and TNF-α, which was almost abrogated by transwell and partially TGF-ß1 neutralization. RNA-seq analysis showed different gene expression profiles between CD4+LAP+ Tregs and LAP-CD4+ T cells and between CD4+LAP+ Tregs of ApoE-/- mice and CD4+LAP+ Tregs of C57BL/6 mice, of which Fancd2 and IL4i1 may contribute to the powerful inhibitory properties of CD4+LAP+ Tregs. Furthermore, the number and the suppressive properties of CD4+LAP+ Tregs were impaired by oxLDL. CONCLUSIONS: Our data indicate that the remaining CD4+LAP+ Tregs play a protective role in atherosclerosis by modulating monocyte/macrophage differentiation and regulatory factors, which may partly explain the protective effect of T cells tolerance in atherosclerosis. Moreover, adoptive transfer of CD4+LAP+ Tregs constitutes a novel approach to treat atherosclerosis.

16.
Small ; 19(14): e2205902, 2023 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-36592425

RESUMEN

Recently, graphitic carbon nitride (g-C3 N4 ) has attracted increasing interest due to its visible light absorption, suitable energy band structure, and excellent stability. However, low specific surface area, finite visible light response range (<460 nm), and rapid photogenerated electron-hole (e- -h+ ) pairs recombination of the pristine g-C3 N4 limit its practical applications. The small size of quantum dots (QDs) endows the properties of abundant active sites, wide absorption spectrum, and adjustable bandgap, but inevitable aggregation. Studies have confirmed that the integration of g-C3 N4 and QDs not only overcomes these limitations of individual component, but also successfully inherits each advantage. Encouraged by these advantages, the synthetic strategies and the fundamental of QDs/g-C3 N4 composites are briefly elaborated in this review. Particularly, the synergistic effects of QDs/g-C3 N4 composites are analyzed comprehensively, including the enhancement of the photocatalytic performance and the avoidance of aggregation. Then, the photocatalytic applications of QDs/g-C3 N4 composites in the fields of environment and energy are described and further combined with DFT calculation to further reveal the reaction mechanisms. Moreover, the stability and reusability of QDs/g-C3 N4 composites are analyzed. Finally, the future development of these composites and the solution of existing problems are prospected.

17.
Int J Colorectal Dis ; 38(1): 5, 2023 Jan 09.
Artículo en Inglés | MEDLINE | ID: mdl-36622449

RESUMEN

OBJECTIVE: A pooled analysis combined with trial sequential analysis (TSA) was conducted in order to explore the effect of mechanical bowel preparation (MBP) combined with oral antibiotic bowel decontamination (OAB) versus MBP alone on patients who have undergone colorectal resection. METHODS: Comprehensive and systematic searches of PubMed, Embase, Cochrane Library, Web of Knowledge, and Clinical Trials.gov databases were conducted. The quality of literature was evaluated using Cochrane risk bias assessment tool as well as Newcastle-Ottawa Scale (NOS) score. A pooled analysis of randomized controlled trials (RCTs) and prospective studies was performed comparing patients who underwent colorectal resection and received MBP plus OAB or MBP alone. The outcome endpoints were the incidence of anastomotic leak (AL) and surgical site infection (SSI). TSA is a tool used to assess the reliability of currently available evidence to determine further clinical trial validation. RESULTS: The analysis included a total of 22 studies involving 8852 patients, including 3016 patients in the MBP + OAB group and 4415 patients exposed to MBP alone. The pooled analysis showed that the incidence of postoperative anastomotic leak was significantly lower in the group treated with MBP plus OAB compared with MBP alone (OR = 0.43, 95% CI: 0.23-0.81, P = 0.009, I2 = 73%). The incidence of postoperative surgical site infections was significantly lower in the group exposed to the combination of MBP and OAB compared with MBP alone (OR = 0.38, 95% CI: 0.32-0.46, P < 0.0001, I2 = 24%). The TSA demonstrated significant benefits of MBP plus OAB intervention in terms of AL and SSI. CONCLUSION: MBP combined with OAB significantly reduces the incidence of AL and SSI in patients after colorectal resection compared with MBP alone.


Asunto(s)
Neoplasias Colorrectales , Cirugía Colorrectal , Humanos , Fuga Anastomótica/etiología , Fuga Anastomótica/prevención & control , Fuga Anastomótica/tratamiento farmacológico , Antibacterianos/uso terapéutico , Profilaxis Antibiótica , Catárticos , Neoplasias Colorrectales/cirugía , Cirugía Colorrectal/efectos adversos , Procedimientos Quirúrgicos Electivos/efectos adversos , Cuidados Preoperatorios , Infección de la Herida Quirúrgica/etiología , Infección de la Herida Quirúrgica/prevención & control , Infección de la Herida Quirúrgica/tratamiento farmacológico , Ensayos Clínicos Controlados Aleatorios como Asunto
18.
Environ Res ; 227: 115752, 2023 06 15.
Artículo en Inglés | MEDLINE | ID: mdl-36965812

RESUMEN

The conventional Fenton process has the drawbacks of low efficiency of Fe3+/Fe2+ conversion, low utilization of H2O2, and narrow range of pH. In this paper, molybdenum sulfide (MoS2) was used as a co-catalyst to boost the nanoscale zero-valent iron (nZVI) based heterogeneous Fenton-like process for the degradation of Rhodamine B (RhB). The catalytic performance, influences of parameters, degradation mechanism, and toxicity of intermediates were explored. Compared with the conventional like-Fenton process, the existence of MoS2 accelerated the decomposition of H2O2 and the RhB degradation rate constant of MoS2/nZVI/H2O2 reached more than six times that of nZVI/H2O2. In addition, the effective pH range of MoS2/nZVI/H2O2 was broadened to 9.0 with 84.9% of RhB being removed within 15 min. The co-catalytic system of MoS2 and nZVI was stable and had high reusability according to the results of four consecutive runs. Quenching tests and electron paramagnetic resonance (EPR) demonstrated that hydroxyl radical (·OH), superoxide anions (·O2-), and singlet oxygen (1O2) were all involved in MoS2/nZVI/H2O2. Compared with nZVI/H2O2 system, MoS2 not only increased the corrosion of nZVI but also accelerated the conversion of Fe3+/Fe2+. ECOSAR analysis suggested that the overall acute and chronic toxicity of the degradation products decreased after treatment. Hence, this MoS2 co-catalytic nZVI based Fenton-like process can be used as a promising alternative for the treatment of organic wastewater.


Asunto(s)
Hierro , Contaminantes Químicos del Agua , Hierro/química , Molibdeno , Peróxido de Hidrógeno/química , Contaminantes Químicos del Agua/análisis , Catálisis
19.
Mol Ther ; 30(5): 2078-2091, 2022 05 04.
Artículo en Inglés | MEDLINE | ID: mdl-34762817

RESUMEN

Zika virus (ZIKV), a flavivirus associated with neurological disorders, constitutes a global health threat. During pregnancy, ZIKV traverses the placenta and causes congenital disease such as microcephaly and Guillain-Barré syndrome in newborns. To develop a specific antiviral therapy against ZIKV-induced microcephaly that could cross placental and blood-brain barriers, we designed targeted small extracellular vesicles (sEVs) encapsulating antiviral siRNA (small interfering RNA) to inhibit ZIKV. The neuro-specific targeting was achieved by engineering EVs membrane protein lamp2b fused with a neuron-specific rabies virus glycoprotein derived peptide (RVG). Intravenous administration of the RVG-engineered sEVs loaded with siRNA (ZIKV-specific siRNA) protected pregnant AG6 mice against vertical transmission of ZIKV. Particularly, sEVsRVG-siRNA traversed placental and blood-brain barriers and suppressed ZIKV infection in fetal brains. Moreover, sEVsRVG-siRNA alleviated the neuroinflammation and neurological damage caused by ZIKV in the fetal mouse model. In general, we developed a sEVs-based targeted system of antiviral therapy for brain and fetal brain infections.


Asunto(s)
Vesículas Extracelulares , Microcefalia , Infección por el Virus Zika , Virus Zika , Animales , Antivirales/farmacología , Encéfalo , Modelos Animales de Enfermedad , Femenino , Feto , Ratones , Microcefalia/complicaciones , Microcefalia/genética , Microcefalia/terapia , Placenta , Embarazo , ARN Interferente Pequeño/genética , ARN Interferente Pequeño/uso terapéutico , Virus Zika/genética , Infección por el Virus Zika/tratamiento farmacológico
20.
J Chem Phys ; 158(17)2023 May 07.
Artículo en Inglés | MEDLINE | ID: mdl-37125710

RESUMEN

A systematic spectroscopic study of the dicarbon molecule C2 has important applications in various research fields, such as astrochemistry and combustion. In the short vacuum ultraviolet (VUV) wavelength region, recent theoretical calculations have predicted many absorption band systems of C2, but only few of them have been verified experimentally yet. In this work, we employed a tunable VUV laser radiation source based on the two-photon resonance-enhanced four-wave mixing method and a time-of-flight mass spectrometer to investigate the absorption bands of C2 in the VUV range of 64 000-66 000 cm-1. The electronic transition 23Σg-(v')-a3Πu(v″) of C2 has been observed and identified experimentally for the first time. The term value Te for the 23Σg- state is determined to be 66 389.9 ± 0.5 cm-1 above the ground state X1Σg+, and the vibrational and rotational constants are also determined. The experimentally measured spectroscopic parameters in this study are in excellent agreement with the theoretical results based on high-level ab initio calculations.

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