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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.
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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.
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Contactinas , Epilepsia Generalizada , Epistasia Genética , Redes Reguladoras de Genes , Predisposição Genética para Doença , Adolescente , Adulto , Criança , Feminino , Humanos , Masculino , Adulto Jovem , Estudos de Casos e Controles , Contactinas/genética , Epilepsia Generalizada/genética , Sequenciamento do Exoma , Frequência do GeneRESUMO
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.
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Artemisininas , Disfunção Cognitiva , Diabetes Mellitus Tipo 2 , Ferroptose , Animais , Camundongos , Fator 2 Relacionado a NF-E2 , Espécies Reativas de Oxigênio , Disfunção Cognitiva/tratamento farmacológico , Disfunção Cognitiva/etiologia , Hipocampo , Artemisininas/farmacologia , Artemisininas/uso terapêutico , NeurôniosRESUMO
Chronic obstructive pulmonary disease (COPD) is a leading aging related cause of global mortality. Small airway narrowing is recognized as an early and significant factor for COPD development. Senescent fibroblasts were observed to accumulate in lung of COPD patients and promote COPD progression through aberrant extracellular matrix (ECM) deposition and senescence-associated secretory phenotype (SASP). On the basis of our previous study, we further investigated the the causes for the increased levels of miR-377-3p in the blood of COPD patients, as well as its regulatory function in the pathological progression of COPD. We found that the majority of up-regulated miR-377-3p was localized in lung fibroblasts. Inhibition of miR-377-3p improved chronic smoking-induced COPD in mice. Mechanistically, miR-377-3p promoted senescence of lung fibroblasts, while knockdown of miR-377-3p attenuated bleomycin-induced senescence in lung fibroblasts. We also identified ZFP36L1 as a direct target for miR-377-3p that likely mediated its pro senescence activity in lung fibroblasts. Our data reveal that miR-377-3p is crucial for COPD pathogenesis, and may serve as a potential target for COPD therapy.
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Fator 1 de Resposta a Butirato , MicroRNAs , Doença Pulmonar Obstrutiva Crônica , Animais , Humanos , Camundongos , Envelhecimento , Fator 1 de Resposta a Butirato/metabolismo , Senescência Celular/genética , Fibroblastos/metabolismo , Pulmão/metabolismo , MicroRNAs/metabolismo , Doença Pulmonar Obstrutiva Crônica/metabolismoRESUMO
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.
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Quimiocina CCL3 , Mucosa Gástrica , Infecções por Helicobacter , Helicobacter pylori , Macrófagos , Helicobacter pylori/fisiologia , Quimiocina CCL3/metabolismo , Quimiocina CCL3/genética , Animais , Mucosa Gástrica/metabolismo , Mucosa Gástrica/patologia , Mucosa Gástrica/microbiologia , Macrófagos/metabolismo , Macrófagos/microbiologia , Camundongos , Infecções por Helicobacter/metabolismo , Infecções por Helicobacter/patologia , Homeostase , Camundongos Endogâmicos C57BL , Humanos , Apoptose , Proliferação de Células , Masculino , Células RAW 264.7RESUMO
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.
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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.
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Transplante de Rim , Insuficiência Renal Crônica , Humanos , Transplante de Rim/efeitos adversos , Contagem de Plaquetas , Estudos Retrospectivos , Subpopulações de Linfócitos T/metabolismo , Proteína C-Reativa/metabolismoRESUMO
Five new cembrane-type diterpenes, lobocalines A-E (1-5), and four new steroids, lobocaloids A-D (9-12), along with six known related compounds (6-8 and 13-15) were isolated from the Yalong Bay soft coral Lobophytum catalai Tixier-Durivault. The structures of the new compounds were elucidated by extensive spectroscopic analysis, NMR calculation with DP4+ analysis, time-dependent density functional theory-electronic circular dichroism (TDDFT-ECD) calculations, X-ray diffraction analyses and comparison with the reported spectroscopic data of known compounds. Further, with the aid of X-ray diffraction analysis, the structure of lobocrasol B (15) was firmly revised as 15a. In in vitro bioassays, compound 2 showed moderate antibacterial activities against fish pathogenic bacteria Streptococcus parauberis KSP28 and Phoyobacterium damselae FP2244 with minimum inhibitory concentration (MIC) values of 8.7 and 17.3 µg/mL, respectively. All the steroids exhibited antibacterial activities against the S. parauberis KSP28 with MIC values ranging from 12.3 to 53.6 µg/mL. Compounds 2, 7 and 14 have remarkable inhibitory effects on the hemolysin production of Staphylococcus aureus, while compounds 8-12 have medium inhibitory effects on the pyocyanin production in Pseudomonas aeruginosa.
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Antozoários , Diterpenos , Animais , Esteroides/farmacologia , Antibacterianos/farmacologia , Espectroscopia de Ressonância Magnética , Antozoários/química , Diterpenos/química , China , Estrutura MolecularRESUMO
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.
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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.
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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.
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OBJECTIVE: To explore the expression of microRNA-3162-3p in different clinical stages of childhood primary immune thrombocytopenia (ITP) and its significance. METHODS: Ninety-six children with ITP were enrolled and divided into new diagnosis group (n=40), persistent group (n=30) and chronic group (n=26) according to the course of disease. 80 healthy children were selected as the control group. Peripheral blood mononuclear cells (PBMNC) of ITP children and healthy children were isolated and cultured, and the expression of microRNA-3162-3p in PBMNC of subjects was detected by real-time fluorescence quantitative PCR. The contents of IL-17, IL-23, IL-10 and TGF-ß in PBMNC of subjects were determined by ELISA. The correlation between microRNA-3162-3p and platelet count, IL-17, IL-23, IL-10 and TGF-ß was analyzed. RESULTS: Compared with the control group, the expression of microRNA-3162-3p and IL-10 in PBMNC and platelet count of ITP children were significantly decreasedï¼P < 0.05ï¼, while IL-17, IL-23 and TGF-ß were significantly increased (P < 0.05). With the prolongation of the disease course, the expressions of microRNA-3162-3p and IL-10 in PBMNC and platelet count were significantly decreasedï¼P < 0.05ï¼, while the expressions of IL-17, IL-23 and TGF-ß were significantly increased (P < 0.05). The expression of microRNA-3162-3p in PBMNC was positively correlated with platelet count and IL-10 (r =0.716, 0.667), and negatively correlated with IL-17, IL-23, and TGF-ß (r =-0.540, -0.641, -0.560). CONCLUSION: MicroRNA-3162-3p expression is significantly reduced in PBMNC of children with ITP, and is involved in the regulation of Th17/Treg imbalance, which can be used as a potential therapeutic target of ITP.
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MicroRNAs , Púrpura Trombocitopênica Idiopática , Criança , Humanos , Púrpura Trombocitopênica Idiopática/genética , Interleucina-10 , Interleucina-17 , Leucócitos Mononucleares , Fator de Crescimento Transformador beta , Interleucina-23RESUMO
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.
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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.
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Transtorno Bipolar , Transtorno Depressivo Maior , Humanos , Transtorno Depressivo Maior/diagnóstico , Transtorno Bipolar/diagnóstico , Algoritmos , Máquina de Vetores de Suporte , BiomarcadoresRESUMO
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.
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Inflamação , Lipopolissacarídeos , Miométrio , NF-kappa B , Transdução de Sinais , Receptor 4 Toll-Like , Feminino , Animais , Miométrio/patologia , Miométrio/metabolismo , Ratos , Receptor 4 Toll-Like/metabolismo , Receptor 4 Toll-Like/genética , Inflamação/patologia , Inflamação/metabolismo , Inflamação/induzido quimicamente , NF-kappa B/metabolismo , Humanos , Gravidez , Ratos Sprague-Dawley , Citocinas/metabolismo , Contração Uterina/efeitos dos fármacos , Miócitos de Músculo Liso/metabolismo , Miócitos de Músculo Liso/patologia , Modelos Animais de Doenças , Útero/patologia , Útero/metabolismoRESUMO
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.
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Antozoários , Sesquiterpenos , Antozoários/química , Sesquiterpenos/química , Sesquiterpenos/farmacologia , Sesquiterpenos/isolamento & purificação , Animais , Camundongos , Estrutura Molecular , Antibacterianos/farmacologia , Antibacterianos/química , Antibacterianos/isolamento & purificação , China , Células RAW 264.7 , Testes de Sensibilidade Microbiana , Lipopolissacarídeos/farmacologia , Lipopolissacarídeos/antagonistas & inibidores , Relação Estrutura-Atividade , Humanos , Antineoplásicos/farmacologia , Antineoplásicos/química , Antineoplásicos/isolamento & purificação , Teoria da Densidade Funcional , Relação Dose-Resposta a DrogaRESUMO
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.
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Hyperactivation of ribosome biosynthesis (RiBi) is a hallmark of cancer, and targeting ribosome biogenesis has emerged as a potential therapeutic strategy. The depletion of TAF1B, a major component of selectivity factor 1 (SL1), disrupts the pre-initiation complex, preventing RNA polymerase I from binding ribosomal DNA and inhibiting the hyperactivation of RiBi. Here, we investigate the role of TAF1B, in regulating RiBi and proliferation in stomach adenocarcinoma (STAD). We disclosed that the overexpression of TAF1B correlates with poor prognosis in STAD, and found that knocking down TAF1B effectively inhibits STAD cell proliferation and survival in vitro and in vivo. TAF1B knockdown may also induce nucleolar stress, and promote c-MYC degradation in STAD cells. Furthermore, we demonstrate that TAF1B depletion impairs rRNA gene transcription and processing, leading to reduced ribosome biogenesis. Collectively, our findings suggest that TAF1B may serve as a potential therapeutic target for STAD and highlight the importance of RiBi in cancer progression.
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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.
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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.