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1.
Artículo en Inglés | MEDLINE | ID: mdl-39259298

RESUMEN

PURPOSE: To explore the abandonment rate and factors influencing the use of rigid gas-permeable contact lenses (RGPCL) among children aged < 6 years. METHODS: This retrospective case series study included 70 children aged < 6 years who were fitted with RGPCL for visual rehabilitation between January 2016 and December 2021. We collected data on indications, discontinuation rates, and reasons for discontinuation from medical records and via telephone calls and investigated the factors influencing contact lens abandonment. RESULTS: The median age of the 70 participants was 5.0 (interquartile range: 4.0-5.9) years. Further, 36 (51.4%) children stopped wearing contact lenses; among them, 17 (47.2%) stopped within 3 months, and the median duration of lens wearing was 4.0 (interquartile range: 1.0-11.5) months. Additionally, there was a correlation between the duration of lens wearing and lens abandonment (r = -0.698, P < 0.001). A high parental education level (hazard ratio [HR] = 0.425; 95% confidence interval [CI] 0.198, 0.913; P = 0.028) was a protective factor against lens abandonment, while parental assessment indicating harder than expected practicality (HR = 4.062; 95% CI 1.204, 13.707; P = 0.024) was a risk factor for abandonment. CONCLUSION: Children aged < 6 years are susceptible to early discontinuation of RGPCL use. Since parents perform daily lens manipulation, they are crucial to the continuity of lens use in these children. To improve RGPCL use continuity, communication and supervision should be strengthened before and after RGPCL fittings.

2.
Org Lett ; 2024 Sep 06.
Artículo en Inglés | MEDLINE | ID: mdl-39240022

RESUMEN

The use of an earth-abundant and inexpensive iron complex as a catalyst, coupled with near-infrared (NIR) light as the energy source, for radical reactions with alkyl halides has been far less developed. In this study, we report NIR light-mediated iron(I) dimer-catalyzed radical cascade reactions of fluoroalkyl bromides for the synthesis of ring-fused quinazolinones bearing a difluoromethyl group. In this process, the 3-bromo-1,10-phenanthroline ligand facilitates the reactivity of [CpFe(CO)2]2, thereby improving the efficiency of the reaction.

3.
Poult Sci ; 103(12): 104253, 2024 Aug 30.
Artículo en Inglés | MEDLINE | ID: mdl-39278115

RESUMEN

Chicken egg yolk plasma (EYP), the supernatant fraction of egg yolk obtained by water dilution and centrifugation, is a rich source of various bioactive substances and a significant bearer of yolk-emulsifying properties. This study utilized proteomics to conduct a comprehensive and in-depth analysis of both common and modified EYP proteins (phosphorylated proteins and N-glycosylated proteins). Total of 208 proteins were identified in EYP, including 42 phosphorylated proteins with 137 phosphorylation sites and 150 N-glycoproteins with 332 N-glycosylation sites. Among the phosphorylation sites, tyrosine accounted for 80.6%, while the N-glycosylation sites predominantly featured "N-X-T" motifs, accounting for 58.7%. Functional enrichment analysis revealed that most proteins were involved in regulating enzyme activity and inhibition with a particular focus on modulating peptidase activity. Notably, vitellogenins-2 (30 phosphorylation sites, 9 N-glycosylation sites) and apolipoprotein B (10 phosphorylation sites, 56 N-glycosylation sites) were the 2 proteins with the most modification sites. Additionally, EYP was found to contain the highly N-glycosylated complement proteins C3 and C4. These findings provide new insights into the protein composition of EYP and its roles in chicken embryo development and immune defense, offering a theoretical foundation for the application of EYP in various fields.

4.
Transl Vis Sci Technol ; 13(9): 21, 2024 Sep 03.
Artículo en Inglés | MEDLINE | ID: mdl-39292467

RESUMEN

Purpose: Using swept-source optical coherence tomography (SS-OCT) to explore the effect of high myopia on superficial retina vascular density (SVD) of the peripheral region and the area of radial peripapillary capillaries (RPCs). Methods: In this cross-sectional study, a total of 91 volunteers (34 male subjects and 57 female subjects) were recruited and 34 individuals in the high myopic group (group A) and 57 individuals in the low myopic group (group B). Using the wide-field OCT-angiography (OCTA; 24 × 20 mm, 120 degrees angular field) compared the peripheral SVD and the area of RPC between the two groups and investigated its correlation with ocular axial length and diopter. Results: Peripheral SVD of group B around the supratemporal (SVD1), supranasal (SVD2), infratemporal (SVD3), and infranasal (SVD4) directions were significantly higher than those of group A (all P < 0.05). The RPC area of group B around the supranasal (RPC2) and infranasal (RPC4) were significantly larger than that of group A (all P < 0.01). Ocular axial length and diopter were significantly correlated with SVD2 and SVD4 (all P < 0.05), and they also have a significant correlation with the supratemporal (RPC1), RPC2, and RPC4 (all P < 0.05). Conclusions: Peripheral SVD was decreased and the RPC area was mainly reduced on the nasal side in the high myopic group. Peripheral SVD and area of RPC are significantly correlated with ocular axial length and diopter. Translational Relevance: The wide-field OCTA can be used for new detection of myopia's impact on the retinal peripheral SVD and area of peripapillary RPC, offering new insights into the progression of myopia.


Asunto(s)
Capilares , Vasos Retinianos , Tomografía de Coherencia Óptica , Humanos , Masculino , Femenino , Estudios Transversales , Tomografía de Coherencia Óptica/métodos , Adulto , Vasos Retinianos/diagnóstico por imagen , Vasos Retinianos/patología , Capilares/diagnóstico por imagen , Capilares/patología , Angiografía con Fluoresceína/métodos , Adulto Joven , Miopía/diagnóstico por imagen , Miopía/patología , Miopía/fisiopatología , Disco Óptico/irrigación sanguínea , Disco Óptico/diagnóstico por imagen , Disco Óptico/patología , Densidad Microvascular , Persona de Mediana Edad , Longitud Axial del Ojo/diagnóstico por imagen , Longitud Axial del Ojo/patología
5.
Cell Host Microbe ; 2024 Sep 13.
Artículo en Inglés | MEDLINE | ID: mdl-39293437

RESUMEN

Microbiota and feeding modes influence the susceptibility of premature newborns to necrotizing enterocolitis (NEC) through mechanisms that remain unknown. Here, we show that microbiota colonization facilitated by breastmilk feeding promotes NOD-like receptor family CARD domain containing 5 (Nlrc5) gene expression in mouse intestinal epithelial cells (IECs). Notably, inducible knockout of the Nlrc5 gene in IECs predisposes neonatal mice to NEC-like injury in the small intestine upon viral inflammation in an NK1.1+ cell-dependent manner. By contrast, formula feeding enhances neonatal gut colonization with environment-derived tilivalline-producing Klebsiella spp. Remarkably, tilivalline disrupts microbiota-activated STAT1 signaling that controls Nlrc5 gene expression in IECs through a PPAR-γ-mediated mechanism. Consequently, this dysregulation hinders the resistance of neonatal intestinal epithelium to self-NK1.1+ cell cytotoxicity upon virus infection/colonization, promoting NEC development. Together, we discover the underappreciated role of intestinal microbiota colonization in shaping a disease tolerance program to viral inflammation and elucidate the mechanisms impacting NEC development in neonates.

6.
Front Pharmacol ; 15: 1448381, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39185308

RESUMEN

Background: Artesunate (ART), a natural compound derived from Artemisia annua, has shown promising clinical potentials in the treatment of various tumors, but the exact mechanism is unclear. Choroidal melanoma (CM) is a major malignant ocular tumor in adults, known for its significant malignancy and poor prognosis, with limited efficacy in current treatments. This study explored the anti-CM effects and mechanisms of ART using a combination of network pharmacology, molecular docking and experimental validation. Methods: Potential targets of ART were screened in PubChem, Swiss Target Prediction and Traditional Chinese Medicine Systems Pharmacology (TCMSP) Database Analysis Platform databases, while target genes related to CM prognosis were selected from Online Mendelian Inheritance in Man (OMIM), GeneCards and DisGeNET databases. The intersection of these two groups of datasets yielded the target genes of ART involved in CM. Protein-protein interaction (PPI) network analysis of the intersecting targets, as well as Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses, were conducted to identify core targets and critical pathways. Molecular docking methods were performed to predict the binding interactions between ART and core targets. The effects of ART on CM were evaluated through CCK8, colony formation, transwell, as well as flow cytometry assays to detect apoptosis, cell cycle, reactive oxygen species (ROS). Western blot (WB) assays were conducted to investigate the impact of ART on key proteins and pathways associated with CM. Finally, in vivo assays were conducted to further validate the effects of ART on subcutaneous tumors in nude mice. Results: Research has shown that key pathways and core targets for ART in treating CM were identified through a network pharmacology approach. Molecular docking results verified the strong binding affinity between ART and these core targets. The analysis and predicted results indicated that ART primarily exerted its effects on CM through various tumor-related pathways like apoptosis. The assays in vitro confirmed that ART significantly inhibited the proliferation and migration of CM cells. This was achieved by promoting apoptosis through activation of the p53 signaling pathway, causing cell cycle arrest at the G0/G1 phase by inhibiting the PI3K/AKT/mTOR signaling pathway and increasing the intracellular level of ROS by activating the NRF2/HO-1 signaling pathway. Additionally, the assays in vivo further validated the significant proliferation-inhibitory effect of ART on CM. Conclusion: This study, making the initial exploration, illustrated through network pharmacology combined with molecular docking and in vitro/in vivo assays, confirmed that ART exerted potential anti-cancer effects on CM by promoting apoptosis, inducing cell cycle arrest and increasing intracellular levels of ROS. These findings suggested that ART held significant therapeutic potential for CM.

7.
Nano Lett ; 24(34): 10562-10568, 2024 Aug 28.
Artículo en Inglés | MEDLINE | ID: mdl-39159397

RESUMEN

MnBi2Te4 is a magnetic topological insulator with layered A-type antiferromagnetic order. It exhibits a rich layer- and magnetic-state dependent topological phase diagram; however, much about the coupling between spin, charge, and lattice remains to be explored. In this work, we report that MnBi2Te4 is an excellent acoustic phonon cavity by realizing phonon frequency combs using picosecond ultrasonics. With the generated acoustic phonon wavepackets, we demonstrate that the timing and phase of acoustic echoes can be used to detect the presence of stacking faults between van der Waals layers buried deep within the crystal. Furthermore, by implementing this nondestructive ultrafast optical measurement in conjunction with time-resolved magneto-optical Kerr effect experiments, we uncover that out-of-plane vibrations in MnBi2Te4 do not couple to the magnetic order, i.e. there is no appreciable magnetostriction. Our work points out how a well-developed technique can probe the structural defects and phonon pulse engineering in layered topological insulators.

8.
Front Oncol ; 14: 1441222, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39156700

RESUMEN

Genomic instability stands out as a pivotal hallmark of cancer, and PARP inhibitors (PARPi) emerging as a groundbreaking class of targeted therapy drugs meticulously crafted to inhibit the repair of DNA single-strand breaks(SSB) in tumor cells. Currently, PARPi have been approved for the treatment of ovarian cancer, pancreatic cancer, breast cancer, and prostate cancer characterized by homologous recombination(HR) repair deficiencies due to mutations in BRCA1/2 or other DNA repair associated genes and acquiring the designation of breakthrough therapy. Nonetheless, PARPi exhibit limited efficacy in the majority of HR-proficient BRCA1/2 wild-type cancers. At present, the synergistic approach of combining PARPi with agents that induce HR defects, or with chemotherapy and radiotherapy to induce substantial DNA damage, significantly enhances the efficacy of PARPi in BRCA wild-type or HR-proficient patients, supporting extension the use of PARPi in HR proficient patients. Therefore, we have summarized the effects and mechanisms of the combined use of drugs with PARPi, including the combination of PARPi with HR defect-inducing drugs such as ATRi, CHKi, HR indirectly inducing drugs like VEGFRi, CDKi, immune checkpoint inhibitors and drugs instigating DNA damage such as chemotherapy or radiotherapy. In addition, this review discusses several ongoing clinical trials aimed at analyzing the clinical application potential of these combined treatment strategies.

9.
Mol Divers ; 2024 Aug 14.
Artículo en Inglés | MEDLINE | ID: mdl-39141208

RESUMEN

A series of novel sulfonyl hydrazide based ß-carboline derivatives (SX1-SX32) were designed and synthesized, and their structures were characterized on NMR and HRMS. Their α-glucosidase inhibitory screening results found that compounds (SX1-SX32) presented potential α-glucosidase inhibitory: IC50 values being 2.12 ± 0.33-19.37 ± 1.49 µM. Compound SX29 with a para-phenyl (IC50: 2.12 ± 0.33 µM) presented the strongest activity and was confirmed as a noncompetitive inhibitor. Fluorescence spectra, CD spectra and molecular docking were conducted to describe the inhibition mechanism of SX29 against α-glucosidase. Cells cytotoxicity indicated SX29 (0-32 µM) had no cytotoxicity on 293T cells. In particular, in vivo experiments revealed that oral administration of SX29 could regulate hyperglycemia and glucose tolerance of diabetic mice. These achieved findings indicated that sulfonyl hydrazide based ß-carboline derivatives bore promising potential for discovering new α-glucosidase inhibitors with hypoglycemic activity.

10.
Am J Physiol Gastrointest Liver Physiol ; 327(4): G499-G512, 2024 Oct 01.
Artículo en Inglés | MEDLINE | ID: mdl-39104322

RESUMEN

Apoptosis, inflammation, and wound healing are critical pathophysiological events associated with various liver diseases. Currently, there is a lack of in vivo approaches to study hepatocyte apoptosis-induced liver injury and repair. To address this critical knowledge gap, we developed a unique genetically modified mouse model, namely, 3-Transgene (Tg) with inducible Hepatocyte-Specific Apoptosis Phenotype (3xTg-iHAP) in this study. The 3xTg-iHAP mice possess three transgenes including Alb-Cre, Rosa26-rtTA, and tetO-Fasl on a B6 background. These mice are phenotypically normal, viable, and fertile. After subcutaneous administration of a single dose of doxycycline (5 mg/kg, Dox) to 3xTg-iHAP mice, we observed a complete histological spectrum of sterile liver wound-healing responses: asymptomatic hepatocyte apoptosis at 8 h, necrotic liver injury and sterile inflammation at 48 h, followed by hepatocyte mitosis and regeneration within 7 days. During the injury phase, the mice exhibited an increase in the biomarkers of alanine aminotransferase (ALT), chemokine (C-X-C motif) ligand 1 (CXCL1), and IL-6 in peripheral blood, as well as α-smooth muscle actin (α-SMA) protein in liver tissues. Conversely, the mice displayed a decrease in these markers in the recovery phase. Remarkably, this model shows that the sterile liver injury following elevated hepatocyte apoptosis is associated with an increase in myeloid cells in the liver. Within 7 days post-Dox administration, the liver of Dox-treated 3xTg-iHAP mice displays a normal histological structure, indicating the completion of wound healing. Together, we established a novel mouse model of injury and regeneration induced by hepatocyte apoptosis. This tool provides a robust in vivo platform for studying the pathophysiology of sterile liver inflammation, regeneration, and new therapeutic interventions for liver diseases.NEW & NOTEWORTHY Bu et al. present a triple-transgenic mouse model, namely, 3xTg-iHAP mice that are engineered to explore hepatocyte apoptosis-triggered sterile liver injury and regeneration. This model demonstrates a full spectrum of liver wound-healing responses from asymptomatic apoptosis to injury, myeloid cell-dominant sterile inflammation, and repair after induction of hepatocyte-specific apoptosis. The robust nature of this model makes it an invaluable in vivo tool for studying sterile liver inflammation, regeneration, and new therapeutic strategies.


Asunto(s)
Apoptosis , Modelos Animales de Enfermedad , Hepatocitos , Regeneración Hepática , Ratones Transgénicos , Células Mieloides , Animales , Hepatocitos/metabolismo , Hepatocitos/patología , Ratones , Células Mieloides/metabolismo , Hígado/metabolismo , Hígado/patología , Cicatrización de Heridas , Ratones Endogámicos C57BL , Quimiocina CXCL1/metabolismo , Quimiocina CXCL1/genética
11.
Cell Host Microbe ; 32(9): 1488-1501.e5, 2024 Sep 11.
Artículo en Inglés | MEDLINE | ID: mdl-39214086

RESUMEN

The pathogenic outcome of enteric virus infections is governed by a complex interplay between the virus, intestinal microbiota, and host immune factors, with metabolites serving as a key mediator. Noroviruses bind bile acid metabolites, which are produced by the host and then modified by commensal bacteria. Paradoxically, bile acids can have both proviral and antiviral roles during norovirus infections. Working in an infant mouse model of norovirus infection, we demonstrate that microbiota and their bile acid metabolites protect from norovirus diarrhea, whereas host bile acids promote disease. We also find that maternal bile acid metabolism determines the susceptibility of newborn mice to norovirus diarrhea during breastfeeding. Finally, targeting maternal and neonatal bile acid metabolism can protect newborn mice from norovirus disease. In summary, neonatal metabolic immaturity and breastmilk bile acids are central determinants of heightened newborn vulnerability to norovirus disease.


Asunto(s)
Animales Recién Nacidos , Ácidos y Sales Biliares , Infecciones por Caliciviridae , Diarrea , Modelos Animales de Enfermedad , Microbioma Gastrointestinal , Leche Humana , Norovirus , Animales , Ratones , Ácidos y Sales Biliares/metabolismo , Infecciones por Caliciviridae/metabolismo , Infecciones por Caliciviridae/virología , Leche Humana/virología , Leche Humana/metabolismo , Diarrea/virología , Diarrea/metabolismo , Femenino , Humanos , Ratones Endogámicos C57BL
12.
Environ Res ; 259: 119576, 2024 Oct 15.
Artículo en Inglés | MEDLINE | ID: mdl-38996958

RESUMEN

The interaction between extracellular polymeric substances (EPS) in municipal sludge and antibiotics in wastewater is critical in wastewater treatment, resource recovery, and sludge management. Therefore, it is increasingly urgent to investigate the distribution coefficient (Log K) of sulfonamide antibiotics (SAs) in EPS, particularly in sludge-derived dissolved organic carbon (DOC) and aqueous phase systems. Herein, through balance experiments, the concentrations of SAs were determined using alkaline extraction EPS (AEPS) and alginate-like extracellular polymer (ALE) systems, and the Log KDOC values were determined. The results showed that the Log KDOC of AEPS was higher than that of ALE, which exhibited a negative KDOC value, indicating an inhibitory effect on dissolution. For the three SAs studied, the Log KDOC values were in the following order: sulfamethoxazole > sulfapyridine > sulfadiazine. This order can be attributed to the differing physicochemical properties, such as polarity, of the SAs. Three-dimensional excitation-emission matrix fluorescence spectra and fitting results indicated a lack of aromatic proteins dominated by tryptophan and humus-like substances in ALE. Meanwhile, the hydrophobic interaction of aromatic proteins dominated by tryptophan was the main driving force in the binding process between AEPS and SAs.


Asunto(s)
Antibacterianos , Matriz Extracelular de Sustancias Poliméricas , Aguas del Alcantarillado , Sulfonamidas , Contaminantes Químicos del Agua , Aguas del Alcantarillado/química , Antibacterianos/análisis , Antibacterianos/química , Sulfonamidas/análisis , Sulfonamidas/química , Matriz Extracelular de Sustancias Poliméricas/química , Contaminantes Químicos del Agua/análisis , Contaminantes Químicos del Agua/química , Eliminación de Residuos Líquidos/métodos
13.
Org Lett ; 26(31): 6658-6663, 2024 Aug 09.
Artículo en Inglés | MEDLINE | ID: mdl-39083395

RESUMEN

The regiocontrol in constructing benzo-fused five-membered rings by C-H cyclization remains an important challenge. We report a highly general and regioselective methodology to access such heterocycles and indenones, where under the catalysis of CoBr2/bipyridine, aryl titanates, alkynes and EX2 (E = NR, S(O), RP(O), R2Si, CO, etc.) were assembled to various heterocycles and indenones in a modular manner. Unprecedented 1,2-Co/Ti heterobimetallic arylene and benzotitanole intermediates have played crucial roles in these syntheses.

14.
Acta Histochem ; 126(5-7): 152174, 2024 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-38976933

RESUMEN

Choroidal melanoma (CM), a highly metastatic eye tumor, exhibits vasculogenic mimicry (VM) facilitated by hypoxia-induced angiogenesis. This study explored the inhibitory impact of the anti-malarial drug Artesunate (ART) on CM VM through modulation of the HIF-1α/VEGF/PDGF pathway. Immunohistochemistry (IHC) confirmed VM in CM with elevated VEGF and PDGF expression. Hypoxia promoted CM proliferation, upregulating HIF-1α, VEGF and PDGF. VEGF and PDGF enhanced CM migration, invasion and VM, with HIF-1α playing a crucial role. ART mitigated VM formation by suppressing the HIF-1α/VEGF/PDGF pathway, highlighting its potential as an anti-tumor agent in CM.


Asunto(s)
Artesunato , Neoplasias de la Coroides , Subunidad alfa del Factor 1 Inducible por Hipoxia , Melanoma , Neovascularización Patológica , Factor de Crecimiento Derivado de Plaquetas , Factor A de Crecimiento Endotelial Vascular , Subunidad alfa del Factor 1 Inducible por Hipoxia/metabolismo , Melanoma/metabolismo , Melanoma/tratamiento farmacológico , Melanoma/patología , Humanos , Neoplasias de la Coroides/tratamiento farmacológico , Neoplasias de la Coroides/metabolismo , Neoplasias de la Coroides/patología , Factor de Crecimiento Derivado de Plaquetas/metabolismo , Factor A de Crecimiento Endotelial Vascular/metabolismo , Artesunato/farmacología , Neovascularización Patológica/metabolismo , Neovascularización Patológica/tratamiento farmacológico , Neovascularización Patológica/patología , Transducción de Señal/efectos de los fármacos , Línea Celular Tumoral , Masculino , Proliferación Celular/efectos de los fármacos
15.
Sci Rep ; 14(1): 16394, 2024 Jul 16.
Artículo en Inglés | MEDLINE | ID: mdl-39014016

RESUMEN

Solid nitrogen exhibits a panoply of phenomena ranging from complex molecular crystalline configurations to polymerization and closing band gap at higher densities. Among the elemental molecular solids, nitrogen stands apart for having phases, which can only be stabilized following particular pressure-temperature pathways, indicative of metastability and kinetic barriers. Here, through the combination of Raman spectroscopy and dynamic compression techniques, we find that the appearance of the whole nitrogen phase diagram is determined by the P-T paths taken below 2 GPa. We reveal the existence of the path- and phase-dependent triple point between the ß - N 2 , δ loc - N 2 and γ - or ϵ - N 2 . We further show that the ß - N 2 towards γ - N 2 path below the triple point, that evades δ ( δ loc )- N 2 , results in the formation of γ - N 2 , which in turn becomes a dominant phase. We then demonstrate, that the ß - N 2 through δ ( δ loc )- N 2 above the triple point path leads to the formation of ϵ - N 2 and the "well-established" phase diagram. An additional pathway, which by-passes the rotationally inhibited modifications δ ( δ loc )- N 2 , via rapid compression is found to produce γ - N 2 at higher temperatures. We argue that the pathway and phase sensitive triple point and the compression rate dependent phase formation challenge our understanding of this archetypal dense molecular solid.

16.
Stem Cell Res Ther ; 15(1): 214, 2024 Jul 18.
Artículo en Inglés | MEDLINE | ID: mdl-39020385

RESUMEN

Sciatic nerve injury (SNI) is a common type of peripheral nerve injury typically resulting from trauma, such as contusion, sharp force injuries, drug injections, pelvic fractures, or hip dislocations. It leads to both sensory and motor dysfunctions, characterized by pain, numbness, loss of sensation, muscle atrophy, reduced muscle tone, and limb paralysis. These symptoms can significantly diminish a patient's quality of life. Following SNI, Wallerian degeneration occurs, which activates various signaling pathways, inflammatory factors, and epigenetic regulators. Despite the availability of several surgical and nonsurgical treatments, their effectiveness remains suboptimal. Exosomes are extracellular vesicles with diameters ranging from 30 to 150 nm, originating from the endoplasmic reticulum. They play a crucial role in facilitating intercellular communication and have emerged as highly promising vehicles for drug delivery. Increasing evidence supports the significant potential of exosomes in repairing SNI. This review delves into the pathological progression of SNI, techniques for generating exosomes, the molecular mechanisms behind SNI recovery with exosomes, the effectiveness of combining exosomes with other approaches for SNI repair, and the changes and future outlook for utilizing exosomes in SNI recovery.


Asunto(s)
Exosomas , Nervio Ciático , Exosomas/metabolismo , Exosomas/trasplante , Humanos , Animales , Nervio Ciático/lesiones , Traumatismos de los Nervios Periféricos/terapia , Traumatismos de los Nervios Periféricos/metabolismo , Regeneración Nerviosa
17.
Nat Microbiol ; 9(8): 1979-1992, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-38862603

RESUMEN

Dimethylsulfoniopropionate (DMSP) is an abundant marine organosulfur compound with roles in stress protection, chemotaxis, nutrient and sulfur cycling and climate regulation. Here we report the discovery of a bifunctional DMSP biosynthesis enzyme, DsyGD, in the transamination pathway of the rhizobacterium Gynuella sunshinyii and some filamentous cyanobacteria not previously known to produce DMSP. DsyGD produces DMSP through its N-terminal DsyG methylthiohydroxybutyrate S-methyltransferase and C-terminal DsyD dimethylsulfoniohydroxybutyrate decarboxylase domains. Phylogenetically distinct DsyG-like proteins, termed DSYE, with methylthiohydroxybutyrate S-methyltransferase activity were found in diverse and environmentally abundant algae, comprising a mix of low, high and previously unknown DMSP producers. Algae containing DSYE, particularly bloom-forming Pelagophyceae species, were globally more abundant DMSP producers than those with previously described DMSP synthesis genes. This work greatly increases the number and diversity of predicted DMSP-producing organisms and highlights the importance of Pelagophyceae and other DSYE-containing algae in global DMSP production and sulfur cycling.


Asunto(s)
Filogenia , Compuestos de Sulfonio , Compuestos de Sulfonio/metabolismo , Cianobacterias/genética , Cianobacterias/metabolismo , Cianobacterias/enzimología , Metiltransferasas/metabolismo , Metiltransferasas/genética , Proteínas Bacterianas/metabolismo , Proteínas Bacterianas/genética , Vías Biosintéticas/genética
18.
Bioresour Technol ; 406: 131044, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-38936679

RESUMEN

The recovery of biopolymers, particularly alginate-like extracellular polymers, from municipal sludge represents a promising step toward sustainable sludge treatment practices. Originating from wastewater plants in complexly polluted environments, alginate-like extracellular polymers carry potential environmental risks concerning their reuse. This study employs ultrahigh-performance liquid chromatography-tandem mass spectrometry to investigate the distribution coefficients and occurrence of alginate-like extracellular polymers and sulfamethoxazole. Results demonstrate a negative distribution coefficient, suggesting an inhibitory effect on sulfamethoxazole dissolution. The ethanol-extracted alginate-like extracellular polymers exhibits higher sulfamethoxazole levels (approximately 52%) than those obtained via dialysis extraction. Three-dimensional excitation-emission matrix analysis and adsorption studies indicate the absence of tyrosine-like substances in the alginate-like extracellular polymers, unlike in other extracellular polymeric substances. This absence diminishes hydrophobic interactions, highlighting that electrostatic interactions play a more important role. These insights are crucial for understanding the adsorption behavior of alginate-like extracellular polymers and optimizing their large-scale extraction processes.


Asunto(s)
Alginatos , Aguas del Alcantarillado , Sulfametoxazol , Alginatos/química , Aguas del Alcantarillado/química , Adsorción , Ácido Glucurónico/química , Cromatografía Líquida de Alta Presión , Matriz Extracelular de Sustancias Poliméricas/química , Matriz Extracelular de Sustancias Poliméricas/metabolismo , Polímeros/química , Espectrometría de Masas en Tándem
19.
Eur J Med Chem ; 275: 116595, 2024 Sep 05.
Artículo en Inglés | MEDLINE | ID: mdl-38875808

RESUMEN

In the quest for potent α-glucosidase inhibitors to combat diabetes, a series of novel thiosemicarbazide-based ß-carboline derivatives (CTL1∼36) were synthesized and evaluated. CTL1∼36 exhibited remarkable inhibitory effects against α-glucosidase, with IC50 values ranging from 2.81 to 12.40 µM, significantly surpassing the positive control acarbose (IC50 = 564.28 µM). Notably, CTL26 demonstrated the most potent inhibition (IC50 = 2.81 µM) and was characterized as a non-competitive inhibitor. Through a combination assay with fluorescence quenching, 3D fluorescence spectra, CD spectra, and molecular docking, we elucidated that CTL26 formed a complex with α-glucosidase via hydrogen bondings and hydrophobic interactions, leading to α-glucosidase conformation changes that impaired enzymatic activity. In vivo studies revealed that oral administration of CTL26 (25 and 50 mg/kg/d) reduced fasting blood glucose levels, enhanced glucose tolerance, and ameliorated lipid abnormalities in diabetic mice. These findings positioned CTL26 as a promising candidate for the development of α-glucosidase inhibitors with anti-diabetic potential.


Asunto(s)
Carbolinas , Diabetes Mellitus Experimental , Inhibidores de Glicósido Hidrolasas , Semicarbacidas , alfa-Glucosidasas , Inhibidores de Glicósido Hidrolasas/farmacología , Inhibidores de Glicósido Hidrolasas/síntesis química , Inhibidores de Glicósido Hidrolasas/química , Animales , alfa-Glucosidasas/metabolismo , Carbolinas/farmacología , Carbolinas/química , Carbolinas/síntesis química , Semicarbacidas/farmacología , Semicarbacidas/química , Semicarbacidas/síntesis química , Ratones , Relación Estructura-Actividad , Diabetes Mellitus Experimental/tratamiento farmacológico , Hipoglucemiantes/farmacología , Hipoglucemiantes/síntesis química , Hipoglucemiantes/química , Estructura Molecular , Simulación del Acoplamiento Molecular , Relación Dosis-Respuesta a Droga , Masculino , Glucemia/efectos de los fármacos , Glucemia/metabolismo , Glucemia/análisis , Humanos
20.
Sci Rep ; 14(1): 12718, 2024 06 03.
Artículo en Inglés | MEDLINE | ID: mdl-38830921

RESUMEN

This study evaluated retinal and choroidal microvascular changes in night shift medical workers and its correlation with melatonin level. Night shift medical workers (group A, 25 workers) and non-night shift workers (group B, 25 workers) were recruited. The images of macula and optic nerve head were obtained by swept-source OCT-angiography. Vessel density of retina, choriocapillaris (CC), choriocapillaris flow deficit (CC FD), choroidal thickness (CT) and choroidal vascularity index (CVI) were measured. 6-sulfatoxymelatonin concentration was analyzed from the morning urine. CC FD and CVI were significantly decreased and CT was significantly increased in group A (all P < 0.05). 6-sulfatoxymelatonin concentration was significantly lower in group A (P < 0.05), which was significantly positively correlated with CC FD size (r = 0.318, P = 0.024) and CVI of the most regions (maximum r-value was 0.482, P < 0.001), and was significantly negatively associated with CT of all regions (maximum r-value was - 0.477, P < 0.001). In night shift medical workers, the reduction of melatonin was significantly correlated with CT thickening, CVI reduction and CC FD reduction, which suggested that they might have a higher risk of eye diseases. CC FD could be a sensitive and accurate indicator to reflect CC perfusion.


Asunto(s)
Coroides , Melatonina , Microvasos , Vasos Retinianos , Tomografía de Coherencia Óptica , Humanos , Coroides/irrigación sanguínea , Coroides/diagnóstico por imagen , Tomografía de Coherencia Óptica/métodos , Masculino , Adulto , Femenino , Melatonina/orina , Melatonina/análogos & derivados , Microvasos/diagnóstico por imagen , Vasos Retinianos/diagnóstico por imagen , Persona de Mediana Edad , Horario de Trabajo por Turnos/efectos adversos , Angiografía/métodos , Retina/diagnóstico por imagen
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