Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 401
Filtrar
1.
Nat Commun ; 15(1): 7861, 2024 Sep 09.
Artículo en Inglés | MEDLINE | ID: mdl-39251585

RESUMEN

Simultaneously improving the activity and stability of catalysts for anodic oxygen evolution reaction (OER) in proton exchange membrane water electrolysis (PEMWE) remains a notable challenge. Here, we report a chromium-doped ruthenium dioxide with oxygen vacancies, termed Cr0.2Ru0.8O2-x, that drives OER with an overpotential of 170 mV at 10 mA cm-2 and operates stably over 2000 h in acidic media. Experimental and theoretical studies show that the synergy of Cr dopant and oxygen vacancy induces an unconventional dopant-mediated hydroxyl spillover mechanism. Such dynamic hydroxyl spillover from Cr dopant to Ru active site changes the rate-determining step from OOH* formation to O2 formation and thus greatly improves the OER performance. Moreover, the Cr dopant and oxygen vacancy also play a crucial role in stabilizing surface Ru and lattice oxygen in the Ru-O-Cr structural motif. When assembled into the anode of a practical PEMWE device, Cr0.2Ru0.8O2-x enables long-term durability of over 200 h at an ampere-level current density and 60 degrees centigrade.

2.
JACS Au ; 4(9): 3413-3420, 2024 Sep 23.
Artículo en Inglés | MEDLINE | ID: mdl-39328756

RESUMEN

The formation of a hexagonal diamond represents one of the most intriguing questions in materials science. Under shock conditions, the graphite basal plane tends to slide and pucker to form diamond. However, how the shock strength determines the phase selectivity remains unclear. In this work, using a DFT-trained carbon global neural network model, we studied the shock-induced graphite transition. The poor sliding caused by scarce sliding time under high-strength shock leads to metastable hexagonal diamond with an orientation relationship of (001)G//(100)HD+[010]G//[010]HD, while under low-strength shock due to long sliding distance cubic diamond forms with the orientation (001)G//(111)CD+[100]G//[110]CD, unveiling the strength-dependent graphite transition mechanism. We for the first time provide computational evidence of the strength-dependent graphite transition from first-principles, clarifying the long-term unresolved shock-induced hexagonal diamond formation mechanism and the structural source of the strength-dependent trend, which facilitates the hexagonal diamond synthesis via controlled experiment.

3.
Heliyon ; 10(16): e36017, 2024 Aug 30.
Artículo en Inglés | MEDLINE | ID: mdl-39229496

RESUMEN

Background: Colorectal cancer is a predominant contributor to global cancer-related morbidity and mortality. The oncogene PTOV1 has been linked to various human malignancies, yet its specific role in CRC pathogenesis requires further elucidation. Methods: Our study used a comprehensive array of authoritative bioinformatics tools, such as TIMER, UCSC Xena, GEO, Human Protein Atlas, UALCAN, CIBERSORTx and others which used to investigate the complex effects of PTOV1 on gene expression profiles, diagnostic and prognostic biomarkers, tumor immunology, signaling pathways, epigenetic alterations, and genetic mutations. Gene expression validation was conducted using Western blot and qRT-PCR. The in vitro proliferative and migratory potentials of CRC cells were evaluated using CCK-8 assays, colony formation, and transwell migration assays, respectively. MSP was applied to assess the methylation status of the PTOV1 promoter region. Results: Our results reveal a significant association between increased PTOV1 expression, driven by promoter hypomethylation, and poor patient prognosis in CRC. Elevated PTOV1 levels were positively correlated with the enrichment of diverse immune cell subsets and immune-related molecules within the tumor microenvironment. In vitro assays demonstrated that PTOV1 knockdown markedly reduced CRC cell proliferation, colony formation, and migration, while ectopic PTOV1 expression had the opposite effect. Importantly, PTOV1 was shown to regulate the PI3K-AKT signaling pathway, significantly influencing the phosphorylation of AKT1 and the expression of cell cycle regulators P21 and P27. The pharmacological inhibition of AKT1 phosphorylation using MK2206 effectively counteracted the proliferative effects induced by PTOV1 overexpression. Conclusion: The ability of PTOV1 to enhance CRC cell proliferation via modulation of the AKT1 signaling pathway establishes it as a potential therapeutic target and a promising biomarker for prognostic stratification in CRC.

4.
ACS Appl Mater Interfaces ; 16(34): 44767-44779, 2024 Aug 28.
Artículo en Inglés | MEDLINE | ID: mdl-39143897

RESUMEN

Solid-state lithium-sulfur batteries (SSLSBs) have attracted a great deal of attention because of their high theoretical energy density and intrinsic safety. However, their practical applications are severely impeded by slow redox kinetics and poor cycling stability. Herein, we revealed the detrimental effect of aggregation of lithium polysulfides (LiPSs) on the redox kinetics and reversibility of SSLSBs. As a paradigm, we introduced a multifunctional hyperbranched ionic conducting (HIC) polymer serving as a solid polymer electrolyte (SPE) and cathode binder for constructing SSLSBs featuring high electrochemical activity and high cycling stability. It is demonstrated that the unique structure of the HIC polymer with numerous flexible ether oxygen dangling chains and fast segmental relaxation enables the dissociation of LiPS clusters, facilitates the conversion kinetics of LiPSs, and improves the battery's performance. A Li|HIC SPE|HIC-S battery, in which the HIC polymer acts as an SPE and cathode binder, exhibits an initial capacity of 910.1 mA h gS-1 at 0.1C and 40 °C, a capacity retention of 73.7% at the end of 200 cycles, and an average Coulombic efficiency of approximately 99.0%, demonstrating high potential for application in SSLSBs. This work provides insights into the electrochemistry performance of SSLSBs and provides a guideline for SPE design for SSLSBs with high specific energy and high safety.

5.
Hortic Res ; 11(8): uhae166, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-39108585

RESUMEN

Sinojackia Hu represents the first woody genus described by Chinese botanists, with all species classified as endangered ornamental plants endemic to China. Their characteristic spindle-shaped fruits confer high ornamental value to the plants, making them favored in gardens and parks. Nevertheless, the fruits likely pose a germination obstacle, contributing to the endangered status of this lineage. Here we report the chromosome-scale genome of S. xylocarpa, and explore the mechanisms underlying its endangered status, as well as its population dynamics throughout evolution. Population genomic analysis has indicated that S. xylocarpa experienced a bottleneck effect following the recent glacial period, leading to a continuous population reduction. Examination of the pericarp composition across six stages of fruit development revealed a consistent increase in the accumulation of lignin and fiber content, responsible for the sturdiness of mature fruits' pericarps. At molecular level, enhanced gene expression in the biosynthesis of lignin, cellulose and hemicellulose was detected in pericarps. Therefore, we conclude that the highly lignified and fibrotic pericarps of S. xylocarpa, which inhibit its seed germination, should be its threatening mechanism, thus proposing corresponding strategies for improved conservation and restoration. This study serves as a seminal contribution to conservation biology, offering valuable insights for the study of other endangered ornamental plants.

6.
Heliyon ; 10(15): e35715, 2024 Aug 15.
Artículo en Inglés | MEDLINE | ID: mdl-39170204

RESUMEN

Smoking is by far one of the greatest public health threats and is recognized as an important predisposing factor for osteoporosis. Exposure to cigarette smoke (CS) has been reported to be associated with inflammation-associated diseases through the induction of pyroptosis. Nevertheless, the correlation between pyroptosis and bone loss induced by CS remains uninvestigated. Here, a mouse model of mainstream smoke exposure-induced osteoporosis was established. µCT, biomechanical testing, and immunohistochemical staining of bone tissue were used to assess the deleterious effects of CS on bone metabolism. In vitro, the effects of cigarette smoke extracts (CSE) on mouse primary bone marrow-derived mesenchymal stem cells (BMSCs) were tested by cell viability assays, gene and protein expression assays, and alizarin red staining. The utilization of the pyroptosis inhibitor MCC950 served to confirm the critical role of BMSCs pyroptosis in CS-induced osteoporosis. Our results indicated that exposure to mainstream smoke led to a notable decrease in the quantity of osteoblasts and hindered the process of osteogenic differentiation in mice. Additionally, there was a significant increase in the expression of pyroptosis-related proteins in the bone marrow. The inhibitory effects of CSE on cell viability and osteogenic differentiation of BMSCs were found to be dose-dependent in vitro. However, the presence of the pyroptosis inhibitor MCC950 significantly improved the impaired osteogenic differentiation and bone mineralization caused by CSE. These results highlight the crucial involvement of BMSCs pyroptosis in the development of bone loss induced by CS. In summary, the findings of this study provide novel evidence that CS exerts a detrimental effect on the process of osteogenesis in BMSCs through the induction of pyroptosis, ultimately leading to bone loss. Inhibition of pyroptosis effectively attenuated the toxicological effects of CS on BMSCs, providing a new target for preventing inflammatory osteoporosis.

7.
Phys Chem Chem Phys ; 26(33): 22182-22188, 2024 Aug 22.
Artículo en Inglés | MEDLINE | ID: mdl-39129444

RESUMEN

In this study, we report a novel monoclinic phase of carbon that contains 4+5+6+7+8 member rings in P21/m symmetry, identified by applying the stochastic surface walking method combined with high dimensional neural network potentials. We demonstrate that this phase possesses lower energy than graphite above 21.5 GPa. The phonon spectra show that this structure is stable under ambient pressure. This phase is a super hard material with a shear hardness as high as 81.9 GPa while it possesses an indirect band gap of 3.16 eV. The energy barrier of graphite to the Y phase is 0.27 eV, slightly higher than that of the hexagonal diamond (0.21 eV) in a similar phase transition mechanism. Two types of thermodynamically stable interfaces can be formed with the hexagonal diamond (HD), namely (001)Y//(100)HD, [100]Y//[010]HD and (001)Y//(001)HD, [010]Y//[001]HD. Although the discrete bulk Y phase is hard to synthesize, a faulted structure between HD is possible because of the well-matched interface between Y and HD. Our work shows that the Y phase may be formed in some special conditions and enhances our understanding of the formation of novel carbon allotropes.

8.
Cell Biochem Biophys ; 82(3): 2957-2975, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-39014186

RESUMEN

Podocyte damage plays a crucial role in the occurrence and development of diabetic nephropathy (DN). Accumulating evidence suggests that dysregulation of transcription factors plays a crucial role in podocyte damage in DN. However, the biological functions and underlying mechanisms of most transcription factors in hyperglycemia-induced podocytes damage remain largely unknown. Through integrated analysis of data mining, bioinformatics, and RT-qPCR validation, we identified a critical transcription factor forkhead box F1 (FOXF1) implicated in DN progression. Moreover, we discovered that FOXF1 was extensively down-regulated in renal tissue and serum from DN patients as well as in high glucose (HG)-induced podocyte damage. Meanwhile, our findings showed that FOXF1 might be a viable diagnostic marker for DN patients. Functional experiments demonstrated that overexpression of FOXF1 strikingly enhanced proliferation, outstandingly suppressed apoptosis, and dramatically reduced inflammation and fibrosis in HG-induced podocytes damage. Mechanistically, we found that the downregulation of FOXF1 in HG-induced podocyte damage was caused by DNMT1 directly binding to FOXF1 promoter and mediating DNA hypermethylation to block FOXF1 transcriptional activity. Furthermore, we found that FOXF1 inhibited the transcriptional expression of miR-342-3p by binding to the promoter of miR-342, resulting in reduced sponge adsorption of miR-342-3p to E2F1, promoting the expression of E2F1, and thereby inhibiting HG-induced podocytes damage. In conclusion, our findings showed that blocking the FOXF1/miR-342-3p/E2F1 axis greatly alleviated HG-induced podocyte damage, which provided a fresh perspective on the pathogenesis and therapeutic strategies for DN patients.


Asunto(s)
ADN (Citosina-5-)-Metiltransferasa 1 , Nefropatías Diabéticas , Regulación hacia Abajo , Factor de Transcripción E2F1 , Factores de Transcripción Forkhead , Glucosa , MicroARNs , Podocitos , Podocitos/metabolismo , Podocitos/patología , MicroARNs/genética , MicroARNs/metabolismo , Factores de Transcripción Forkhead/metabolismo , Factores de Transcripción Forkhead/genética , Humanos , Factor de Transcripción E2F1/metabolismo , Factor de Transcripción E2F1/genética , Nefropatías Diabéticas/metabolismo , Nefropatías Diabéticas/patología , Nefropatías Diabéticas/genética , Glucosa/farmacología , Glucosa/metabolismo , ADN (Citosina-5-)-Metiltransferasa 1/metabolismo , ADN (Citosina-5-)-Metiltransferasa 1/genética , Animales , Apoptosis/efectos de los fármacos , Metilación de ADN , Regiones Promotoras Genéticas , Ratones , Proliferación Celular
9.
J Am Chem Soc ; 146(29): 20193-20204, 2024 Jul 24.
Artículo en Inglés | MEDLINE | ID: mdl-39004825

RESUMEN

High-entropy intermetallic (HEI) nanocrystals, composed of multiple elements with an ordered structure, are of immense interest in heterogeneous catalysis due to their unique geometric and electronic structures and the cocktail effect. Despite tremendous efforts dedicated to regulating the metal composition and structures with advanced synthetic methodologies to improve the performance, the surface structure, and local chemical order of HEI and their correlation with activity at the atomic level remain obscure yet challenging. Herein, by determining the three-dimensional (3D) atomic structure of quinary PdFeCoNiCu (PdM) HEI using atomic-resolution electron tomography, we reveal that the local chemical order of HEI regulates the surface electronic structures, which further mediates the alkyl-substitution-dependent alkyne semihydrogenation. The 3D structures of HEI PdM nanocrystals feature an ordered (intermetallic) core enclosed by a disordered (solid-solution) shell rather than an ordered surface. The lattice mismatch between the core and shell results in apparent near-surface distortion. The chemical order of the intermetallic core increases with annealing temperature, driving the electron redistribution between Pd and M at the surface, but the surface geometrical (chemically disordered) configurations and compositions are essentially unchanged. We investigate the catalytic performance of HEI PdM with different local chemical orders toward semihydrogenation across a broad range of alkynes, finding that the electron density of surface Pd and the hindrance effect of alkyl substitutions on alkynes are two key factors regulating selective semihydrogenation. We anticipate that these findings on surface atomic structure will clarify the controversy regarding the geometric and/or electronic effects of HEI catalysts and inspire future studies on tuning local chemical order and surface engineering toward enhanced catalysts.

10.
Neurol Ther ; 13(4): 1259-1271, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-38914793

RESUMEN

INTRODUCTION: Intracerebral hemorrhage (ICH) is a severe manifestation of stroke, demonstrating notably elevated global mortality and morbidity. Thus far, effective therapeutic strategies for ICH have proven elusive. Currently, minimally invasive techniques are widely employed for ICH management, particularly using endoscopic hematoma evacuation in cases of deep ICH. Exploration of strategies to achieve meticulous surgery and diminish iatrogenic harm, especially to the corticospinal tract, with the objective of enhancing the neurological prognosis of patients, needs further efforts. METHODS: We comprehensively collected detailed demographic, clinical, radiographic, surgical, and postoperative treatment and recovery data for patients who underwent endoscopic hematoma removal. This thorough inclusion of data intends to offer a comprehensive overview of our technical experience in this study. RESULTS: One hundred fifty-four eligible patients with deep supratentorial intracerebral hemorrhage who underwent endoscopic hematoma removal were included in this study. The mean hematoma volume was 42 ml, with 74 instances of left-sided hematoma and 80 cases of right-sided hematoma. The median Glasgow Coma Scale (GCS) score at admission was 10 (range from 4 to 15), and the median time from symptom onset to surgery was 18 (range 2 to 96) h. The mean hematoma clearance rate was 89%. The rebleeding and mortality rates within 1 month after surgery were 3.2% and 7.8%, respectively. At the 6-month mark, the proportion of patients with modified Rankin Scale (mRS) scores of 0-3 was 58.4%. CONCLUSION: Both the reduction of surgery-related injury and the protection of the residual corticospinal tract through endoscopic hematoma removal may potentially enhance neurological functional outcomes in patients with deep ICH, warranting validation in a forthcoming multicenter clinical study.

11.
Curr Med Sci ; 44(3): 633-641, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38789820

RESUMEN

OBJECTIVE: The latest perspective suggests that elevated levels of inflammation and cytokines are implicated in atonic postpartum hemorrhage. Lipopolysaccharide (LPS) has been widely used to induce inflammation in animal models. Therefore, this study aimed to induce uterine inflammation using LPS to investigate whether local inflammation triggers dysfunction and atrophy in the myometrium, as well as the potential underlying molecular mechanisms involved. METHODS: In vivo, an animal model was established by intraperitoneal injection of 300 µg/ kg LPS in rats on gestational day 21. Hematoxylin-eosin (H&E) staining and Masson staining were employed to determine morphological changes in the rat uterine smooth muscle. Enzyme-linked immunosorbent assay (ELISA) was used to detect inflammatory cytokines. Immunohistochemistry, tissue fluorescence, and Western blotting were conducted to assess the expression levels of the uterine contraction-related proteins Toll-like receptor 4 (TLR4) and the nuclear factor kappa-B (NF-κB) signaling pathway. In vitro, human uterine smooth muscle cells (HUtSMCs) were exposed to 2 µg/mL LPS to further elucidate the involvement of the TLR4/NF-κB signaling pathway in LPS-mediated inflammation. RESULTS: In this study, LPS induced uterine myometrial dysfunction in rats, leading to a disorganized arrangement, a significant increase in collagen fiber deposition, and widespread infiltration of inflammatory cells. In both in vivo animal models and in vitro HUtSMCs, LPS elevated IL-6, IL-1ß, and TNF-α levels while concurrently suppressing the expression of connexin 43 (Cx43) and oxytocin receptor (OXTR). Mechanistically, the LPS-treated group exhibited TLR4 activation, and the phosphorylation levels of p65 and IκBα were notably increased. CONCLUSION: LPS triggered the TLR4/NF-κB signaling pathway, inducing an inflammatory response in the myometrium and leading to uterine myometrial dysfunction and uterine atony.


Asunto(s)
Inflamación , Lipopolisacáridos , Miometrio , FN-kappa B , Transducción de Señal , Receptor Toll-Like 4 , Femenino , Animales , Miometrio/patología , Miometrio/metabolismo , Ratas , Receptor Toll-Like 4/metabolismo , Receptor Toll-Like 4/genética , Inflamación/patología , Inflamación/metabolismo , Inflamación/inducido químicamente , FN-kappa B/metabolismo , Humanos , Embarazo , Ratas Sprague-Dawley , Citocinas/metabolismo , Contracción Uterina/efectos de los fármacos , Miocitos del Músculo Liso/metabolismo , Miocitos del Músculo Liso/patología , Modelos Animales de Enfermedad , Útero/patología , Útero/metabolismo
12.
Cell Commun Signal ; 22(1): 263, 2024 May 10.
Artículo en Inglés | MEDLINE | ID: mdl-38730482

RESUMEN

BACKGROUND: Helicobacter pylori (H. pylori) is the predominant etiological agent of gastritis and disrupts the integrity of the gastric mucosal barrier through various pathogenic mechanisms. After H. pylori invades the gastric mucosa, it interacts with immune cells in the lamina propria. Macrophages are central players in the inflammatory response, and H. pylori stimulates them to secrete a variety of inflammatory factors, leading to the chronic damage of the gastric mucosa. Therefore, the study aims to explore the mechanism of gastric mucosal injury caused by inflammatory factors secreted by macrophages, which may provide a new mechanism for the development of H. pylori-related gastritis. METHODS: The expression and secretion of CCL3 from H. pylori infected macrophages were detected by RT-qPCR, Western blot and ELISA. The effect of H. pylori-infected macrophage culture medium and CCL3 on gastric epithelial cells tight junctions were analyzed by Western blot, immunofluorescence and transepithelial electrical resistance. EdU and apoptotic flow cytometry assays were used to detect cell proliferation and apoptosis levels. Dual-luciferase reporter assays and chromatin immunoprecipitation assays were used to study CCL3 transcription factors. Finally, gastric mucosal tissue inflammation and CCL3 expression were analyzed by hematoxylin and eosin staining and immunohistochemistry. RESULTS: After H. pylori infection, CCL3 expressed and secreted from macrophages were increased. H. pylori-infected macrophage culture medium and CCL3 disrupted gastric epithelial cells tight junctions, while CCL3 neutralizing antibody and receptor inhibitor of CCL3 improved the disruption of tight junctions between cells. In addition, H. pylori-infected macrophage culture medium and CCL3 recombinant proteins stimulated P38 phosphorylation, and P38 phosphorylation inhibitor improved the disruption of tight junctions between cells. Besides, it was identified that STAT1 was a transcription factor of CCL3 and H. pylori stimulated macrophage to secret CCL3 through the JAK1-STAT1 pathway. Finally, after mice were injected with murine CCL3 recombinant protein, the gastric mucosal injury and inflammation were aggravated, and the phosphorylation level of P38 was increased. CONCLUSIONS: In summary, our findings demonstrate that H. pylori infection stimulates macrophages to secrete CCL3 via the JAK1-STAT1 pathway. Subsequently, CCL3 damages gastric epithelial tight junctions through the phosphorylation of P38. This may be a novel mechanism of gastric mucosal injury in H. pylori-associated gastritis.


Asunto(s)
Quimiocina CCL3 , Mucosa Gástrica , Infecciones por Helicobacter , Helicobacter pylori , Macrófagos , Helicobacter pylori/fisiología , Quimiocina CCL3/metabolismo , Quimiocina CCL3/genética , Animales , Mucosa Gástrica/metabolismo , Mucosa Gástrica/patología , Mucosa Gástrica/microbiología , Macrófagos/metabolismo , Macrófagos/microbiología , Ratones , Infecciones por Helicobacter/metabolismo , Infecciones por Helicobacter/patología , Homeostasis , Ratones Endogámicos C57BL , Humanos , Apoptosis , Proliferación Celular , Masculino , Células RAW 264.7
13.
Phytochemistry ; 222: 114110, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38663824

RESUMEN

Molecular networking strategy-based prioritization of the isolation of the rarely studied soft coral Sinularia tumulosa yielded 14 sesquiterpenes. These isolated constituents consisted of nine different types of carbon frameworks, namely asteriscane, humulane, capillosane, seco-asteriscane, guaiane, dumortane, cadinane, farnesane, and benzofarnesane. Among them, situmulosaols A-C (1, 3 and 4) were previously undescribed ones, whose structures with absolute configurations were established by the combination of extensive spectral data analyses, quantum mechanical-nuclear magnetic resonance and time-dependent density functional theory electronic circular dichroism calculations, the Snatzke's method, and the modified Mosher's method. Notably, situmulosaol C (4) was the second member of capillosane-type sesquiterpenes. The plausible biogenetic relationships of these skeletally different sesquiterpenes were proposed. All sesquiterpenoids were evaluated for their antibacterial, cytotoxic and anti-inflammatory effects. The bioassay results showed compound 14 exhibited significant antibacterial activities against a variety of fish and human pathogenic bacteria with MIC90 values ranging from 3.6 to 33.8 µg/mL. Moreover, moderate cytotoxic effects against HEL cells for components 13 and 14 and moderate inhibitory effect on lipopolysaccharide-induced inflammatory responses in RAW264.7 cells for substance 13 were also observed.


Asunto(s)
Antozoos , Sesquiterpenos , Antozoos/química , Sesquiterpenos/química , Sesquiterpenos/farmacología , Sesquiterpenos/aislamiento & purificación , Animales , Ratones , Estructura Molecular , Antibacterianos/farmacología , Antibacterianos/química , Antibacterianos/aislamiento & purificación , China , Células RAW 264.7 , Pruebas de Sensibilidad Microbiana , Lipopolisacáridos/farmacología , Lipopolisacáridos/antagonistas & inhibidores , Relación Estructura-Actividad , Humanos , Antineoplásicos/farmacología , Antineoplásicos/química , Antineoplásicos/aislamiento & purificación , Teoría Funcional de la Densidad , Relación Dosis-Respuesta a Droga
14.
Neurogenetics ; 25(2): 131-139, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38460076

RESUMEN

Twin and family studies have established the genetic contribution to idiopathic generalized epilepsy (IGE). The genetic architecture of IGE is generally complex and heterogeneous, and the majority of the genetic burden in IGE remains unsolved. We hypothesize that gene-gene interactions contribute to the complex inheritance of IGE. CNTN2 (OMIM* 615,400) variants have been identified in cases with familial adult myoclonic epilepsy and other epilepsies. To explore the gene-gene interaction network in IGE, we took the CNTN2 gene as an example and investigated its co-occurrent genetic variants in IGE cases. We performed whole-exome sequencing in 114 unrelated IGE cases and 296 healthy controls. Variants were qualified with sequencing quality, minor allele frequency, in silico prediction, genetic phenotype, and recurrent case numbers. The STRING_TOP25 gene interaction network analysis was introduced with the bait gene CNTN2 (denoted as A). The gene-gene interaction pair mode was presumed to be A + c, A + d, A + e, with a leading gene A, or A + B + f, A + B + g, A + B + h, with a double-gene A + B, or other combinations. We compared the number of gene interaction pairs between the case and control groups. We identified three pairs in the case group, CNTN2 + PTPN18, CNTN2 + CNTN1 + ANK2 + ANK3 + SNTG2, and CNTN2 + PTPRZ1, while we did not discover any pairs in the control group. The number of gene interaction pairs in the case group was much more than in the control group (p = 0.021). Taking together the genetic bioinformatics, reported epilepsy cases, and statistical evidence in the study, we supposed CNTN2 as a candidate pathogenic gene for IGE. The gene interaction network analysis might help screen candidate genes for IGE or other complex genetic disorders.


Asunto(s)
Contactinas , Epilepsia Generalizada , Epistasis Genética , Redes Reguladoras de Genes , Predisposición Genética a la Enfermedad , Adolescente , Adulto , Niño , Femenino , Humanos , Masculino , Adulto Joven , Estudios de Casos y Controles , Contactinas/genética , Epilepsia Generalizada/genética , Secuenciación del Exoma , Frecuencia de los Genes
15.
Toxics ; 12(3)2024 Mar 01.
Artículo en Inglés | MEDLINE | ID: mdl-38535928

RESUMEN

As a replacement for polybrominated diphenyl ethers (PBDEs), organophosphorus flame retardants (OPFRs) have been widely used and detected in different indoor environments all over the world. This paper comprehensively describes the concentration levels and distribution information of 11 kinds of OPFRs from 33 indoor dust and 10 air environments, from which TBOEP, TCIPP, and TDCIPP were observed to have higher concentrations in indoor environments. The ΣOPFRs displayed higher concentrations in indoor dust than in indoor air due to the higher molecular weight and vapor pressure of ΣOPFRs in building decoration materials, specifically for TCIPP and TDCIPP compounds. Considering that it is inevitable that people will be exposed to these chemicals in the indoor environments in which they work and live, we estimated their potential health risks through three human exposure pathways and found that the ingestion exposure to TBOEP for toddlers in Japan may reach up to 1270.80 ng/kg/day, which comprises a significant pathway compared to dermal contact and indoor air inhalation. Specifically, the combined total exposure to OPFRs by air inhalation, dust ingestion, and dermal contact was generally below the RfD values for both adults and toddlers, with a few notable higher exposures of some typical OPFRs.

16.
Med Sci Monit ; 30: e942324, 2024 Mar 18.
Artículo en Inglés | MEDLINE | ID: mdl-38494662

RESUMEN

BACKGROUND Infection and chronic rejection remain major issues for kidney transplant recipients (KTRs). The present study aimed to explore the association of CD4+/CD8+ T cell ratio (CD4+/CD8+) and platelet/lymphocyte ratio (PLR) with long-term infection and chronic renal insufficiency in KTRs. MATERIAL AND METHODS KTRs admitted to a single hospital from June 2014 to December 2021 were divided into infected (164) and non-infected (107) groups based on clinical data. The levels of CD4+/CD8+, PLR, neutrophil/lymphocyte ratio (NLR), and C-reactive Protein (CRP) in KTRs with long-term infection, and their correlation with chronic kidney insufficiency, were analyzed. Survival analysis was used to evaluate the risk factors for long-term infection and chronic kidney insufficiency. RESULTS Spearman correlation analysis showed that chronic kidney insufficiency was positively correlated with PLR, and negatively correlated with CRP and CD4+/CD8+ (P<0.05). PLR was positively correlated with CRP, procalcitonin, erythrocyte sedimentation rate, and NLR, but negatively with CD4+/CD8+. CD4+/CD8+ was correlated with CRP, NLR, and PLR (P<0.05). Survival analysis and survival curves showed that PLR and CD4+/CD8+ were risk factors for long-term infection and chronic kidney insufficiency in KTRs (P<0.05). CONCLUSIONS CD4+/CD8+ and PLR were associated with long-term complications, and were risk factors for long-term infection and chronic kidney insufficiency in KTRs.


Asunto(s)
Trasplante de Riñón , Insuficiencia Renal Crónica , Humanos , Trasplante de Riñón/efectos adversos , Recuento de Plaquetas , Estudios Retrospectivos , Subgrupos de Linfocitos T/metabolismo , Proteína C-Reactiva/metabolismo
17.
ACS Appl Mater Interfaces ; 16(11): 13795-13805, 2024 Mar 20.
Artículo en Inglés | MEDLINE | ID: mdl-38449335

RESUMEN

Designing a stable and highly active catalyst for hydrogen evolution and oxygen evolution reactions (HER/OER) is essential for the industrialization of hydrogen energy but remains a major challenge. This work reports a simple approach to fabricating coupled Co2P/Fe2P nanorod array catalyst for overall water decomposition, demonstrating the source of excellent activity in the catalytic process. Under alkaline conditions, Co2P/Fe2P heterostructures exhibit an overpotential of 96 and 220 mV for HER and OER, respectively, at 10 mA cm-2. For total water splitting, a low voltage of 1.56 V is required to provide a current density of 10 mA cm-2. And the catalyst exhibits long-term durability for 30 h at a high current density of 250 mA cm-2. The analysis of the results revealed that the presence of interfacial oxygen vacancies and the strong interaction between Co2P/Fe2P provided the catalyst with more electrochemically active sites and a faster charge transfer capability, which improved the hydrolysis dissociation process. Electrochemically active metal (oxygen) hydroxide phases were produced after OER stability testing. The results of this study prove its great potential in practical industrial electrolysis and provide a reasonable and feasible strategy for the design of nonprecious metal phosphide electrocatalysts.

18.
Mol Med ; 30(1): 35, 2024 Mar 07.
Artículo en Inglés | MEDLINE | ID: mdl-38454322

RESUMEN

BACKGROUND: Neuronal ferroptosis plays a critical role in the pathogenesis of cognitive deficits. The present study explored whether artemisinin protected type 2 diabetes mellitus (T2DM) mice from cognitive impairments by attenuating neuronal ferroptosis in the hippocampal CA1 region. METHODS: STZ-induced T2DM mice were treated with artemisinin (40 mg/kg, i.p.), or cotreated with artemisinin and Nrf2 inhibitor MEL385 or ferroptosis inducer erastin for 4 weeks. Cognitive performance was determined by the Morris water maze and Y maze tests. Hippocampal ROS, MDA, GSH, and Fe2+ contents were detected by assay kits. Nrf2, p-Nrf2, HO-1, and GPX4 proteins in hippocampal CA1 were assessed by Western blotting. Hippocampal neuron injury and mitochondrial morphology were observed using H&E staining and a transmission electron microscope, respectively. RESULTS: Artemisinin reversed diabetic cognitive impairments, decreased the concentrations of ROS, MDA and Fe2+, and increased the levels of p-Nr2, HO-1, GPX4 and GSH. Moreover, artemisinin alleviated neuronal loss and ferroptosis in the hippocampal CA1 region. However, these neuroprotective effects of artemisinin were abolished by Nrf2 inhibitor ML385 and ferroptosis inducer erastin. CONCLUSION: Artemisinin effectively ameliorates neuropathological changes and learning and memory decline in T2DM mice; the underlying mechanism involves the activation of Nrf2 to inhibit neuronal ferroptosis in the hippocampus.


Asunto(s)
Artemisininas , Disfunción Cognitiva , Diabetes Mellitus Tipo 2 , Ferroptosis , Animales , Ratones , Factor 2 Relacionado con NF-E2 , Especies Reactivas de Oxígeno , Disfunción Cognitiva/tratamiento farmacológico , Disfunción Cognitiva/etiología , Hipocampo , Artemisininas/farmacología , Artemisininas/uso terapéutico , Neuronas
19.
Chin J Integr Med ; 30(3): 195-202, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38374490

RESUMEN

OBJECTIVE: To evaluate the effect and safety of foot baths with Tangbi Waixi Decoction (TW) in treating patients with diabetic peripheral neuropathy (DPN). METHODS: It is a multicenter double-blinded randomized controlled trial. Participants with DPN were recruited between November 18, 2016 and May 30, 2018 from 8 hospitals in China. All patients received basic treatments for glycemic management. Patients received foot baths with TW herbal granules either 66.9 g (intervention group) or 6.69 g (control group) for 30 min once a day for 2 weeks and followed by a 2-week rest, as a therapeutic course. If the Toronto Clinical Scoring System total score (TCSS-TS) ⩾6 points, the patients received a total of 3 therapeutic courses (for 12 weeks) and were followed up for 12 weeks. The primary outcome was change in TCSS-TS score at 12 and 24 weeks. Secondary outcomes included changes in bilateral motor nerve conduction velocity (MNCV) and sensory nerve conduction velocity (SNCV) of the median and common peroneal nerve. Safety was also assessed. RESULTS: Totally 632 patients were enrolled, and 317 and 315 were randomized to the intervention and control groups, respectively. After the 12-week intervention, patients in both groups showed significant declines in TCSSTS scores, and significant increases in MNCV and SNCV of the median and common peroneal nerves compared with pre-treatment (P<0.05). The reduction of TCSS-TS score at 12 weeks and the increase of SNCV of median nerve at 24 weeks in the control group were greater than those in the intervention group (P<0.05). The number of adverse events did not differ significantly between groups (P>0.05), and no serious adverse event was related with treatment. CONCLUSION: Treatment of TW foot baths was safe and significantly benefitted patients with DPN. A low dose of TW appeared to be more effective than a high dose. (Registry No. ChiCTR-IOR-16009331).


Asunto(s)
Diabetes Mellitus , Neuropatías Diabéticas , Plantas Medicinales , Humanos , Neuropatías Diabéticas/tratamiento farmacológico , Baños , Método Doble Ciego , Extractos Vegetales/uso terapéutico
20.
Transl Psychiatry ; 14(1): 110, 2024 Feb 23.
Artículo en Inglés | MEDLINE | ID: mdl-38395985

RESUMEN

Early detection of bipolar depression (BPD) and major depressive disorder (MDD) has been challenging due to the lack of reliable and easily measurable biological markers. This study aimed to investigate the accuracy of discriminating patients with mood disorders from healthy controls based on task state skin potential characteristics and their correlation with individual indicators of oxidative stress. A total of 77 patients with BPD, 53 patients with MDD, and 79 healthy controls were recruited. A custom-made device, previously shown to be sufficiently accurate, was used to collect skin potential data during six emotion-inducing tasks involving video, pictorial, or textual stimuli. Blood indicators reflecting individual levels of oxidative stress were collected. A discriminant model based on the support vector machine (SVM) algorithm was constructed for discriminant analysis. MDD and BPD patients were found to have abnormal skin potential characteristics on most tasks. The accuracy of the SVM model built with SP features to discriminate MDD patients from healthy controls was 78% (sensitivity 78%, specificity 82%). The SVM model gave an accuracy of 59% (sensitivity 59%, specificity 79%) in classifying BPD patients, MDD patients, and healthy controls into three groups. Significant correlations were also found between oxidative stress indicators in the blood of patients and certain SP features. Patients with depression and bipolar depression have abnormalities in task-state skin potential that partially reflect the pathological mechanism of the illness, and the abnormalities are potential biological markers of affective disorders.


Asunto(s)
Trastorno Bipolar , Trastorno Depresivo Mayor , Humanos , Trastorno Depresivo Mayor/diagnóstico , Trastorno Bipolar/diagnóstico , Algoritmos , Máquina de Vectores de Soporte , Biomarcadores
SELECCIÓN DE REFERENCIAS
DETALLE DE LA BÚSQUEDA