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Lithium (Li) metal batteries (LMBs) are among the most promising candidates for future battery technology due to their high theoretical capacity and energy density. However, the formation of dendritic Li, characterized by needle-like structures, poses serious safety issues. To address this, numerous methods are developed to prevent Li dendrite formation. Another significant challenge in LMBs is the formation of inactive Li, known as dead Li, which significantly impacts their Coulombic efficiency and overall performance. This review explores the issues surrounding dead Li in LMBs, specifically focusing on electrically isolated Li metal and the repeatedly generated solid electrolyte interphase (SEI). Advanced techniques for characterizing inactive Li are discussed, alongside various strategies designed to activate or suppress dead Li, thus restoring battery capacity. The review summarizes recent advancements in research related to the activation, reuse, and prevention of dead Li, offering valuable insights for enhancing the efficiency and safety of LMBs. This comprehensive overview provides fundamental guidance for the practical application of Li metal anodes and similar metal batteries.
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Rosacea is a complex chronic inflammatory skin disorder with high morbidity. Pyroptosis is known as a regulated inflammatory cell death. While its association with immune response to various inflammatory disorders is well established, little is known about its functional relevance of rosacea. So, we aimed to explore and enrich the pathogenesis involved in pyroptosis-related rosacea aggravations. In this study, we evaluated the pyroptosis-related patterns of rosacea by consensus clustering analysis of 45 ferroptosis-related genes (FRGs), with multiple immune cell infiltration analysis to identify the pyroptosis-mediated immune response in rosacea using GSE65914 dataset. The co-co-work between PRGs and WGCNA-revealed hub genes has established using PPI network. FRG signature was highlighted in rosacea using multi-transcriptomic and experiment analysis. Based on this, three distinct pyroptosis-related rosacea patterns (non/moderate/high) were identified, and the notably enriched pathways have revealed through GO, KEGG and GSEA analysis, especially immune-related pathways. Also, the XCell/MCPcount/ssGSEA/Cibersort underlined the immune-related signalling (NK cells, Monocyte, Neutrophil, Th2 cells, Macrophage), whose hub genes were identified through WGCNA (NOD2, MYD88, STAT1, HSPA4, CXCL8). Finally, we established a pyroptosis-immune co-work during the rosacea aggravations. FRGs may affect the progression of rosacea by regulating the immune cell infiltrations. In all, pyroptosis with its mediated immune cell infiltration is a critical factor during the development of rosacea.
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Piroptosis , Rosácea , Humanos , Piroptosis/genética , Rosácea/genética , Piel , Proteínas Adaptadoras Transductoras de Señales , Perfilación de la Expresión GénicaRESUMEN
Prussian white (PW) is considered a promising cathode material for sodium-ion batteries. However, challenges, such as lattice defects and poor conductivity limit its application. Herein, the composite materials of manganese-iron based Prussian white and reduced graphene oxide (PW/rGO) were synthesized via a one-step in situ synthesis method with sodium citrate, which was employed both as a chelating agent to control the reaction rate during the coprecipitation process of PW synthesis and as a reducing agent for GO. The low precipitation speed helps minimize lattice defects, while rGO enhances electrical conductivity. Furthermore, the one-step in situ synthesis method is simpler and more efficient than the traditional synthesis method. Compared with pure PW, the PW/rGO composites exhibit significantly improved electrochemical properties. Cycling performance tests indicated that the PW/rGO-10 sample exhibited the highest initial discharge capacity and the best cyclic stability. The PW/rGO-10 has an initial discharge capacity of 128 mAh g-1 at 0.1 C (1 C = 170 mA g-1), and retains 49.53% capacity retention after 100 cycles, while the PW only delivers 112 mAh g-1 with a capacity retention of 17.79% after 100 cycles. Moreover, PW/rGO-10 also shows better rate performance and higher sodium ion diffusion coefficient (DNa+) than the PW sample. Therefore, the incorporation of rGO not only enhances the electrical conductivity but also promotes the rapid diffusion of sodium ions, effectively improving the electrochemical performance of the composite as a cathode material for sodium-ion batteries.
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A Pd-catalyzed thiocarbonylative cyclization of N-(o-iodoaryl)acrylamides with easily accessible thioformates has been developed. The reaction has a wide substrate scope with good yields and represents a powerful route to the synthesis of thioester-functionalized oxindoles. Both S-aryl and alkyl thioformates as the thioester sources were well tolerated. The active Pd-CO intermediate may play an important role in the transformation process.
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A palladium-catalyzed cascade reaction of α,ß-unsaturated N-tosylhydrazones with iodoarene derivatives containing a nucleophilic group has been developed, which provides facile access to 2H-chromenes and 2H-quinolines, respectively. Additionally, the double Pd-carbene migratory insertion/nucleophilic substitution processes for the synthesis of a ternary heterocyclic skeleton were possible in the developed catalytic system.
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BACKGROUND: Accumulating evidence shows that free fatty acids (FFA) are associated with gestational diabetes mellitus (GDM). However, most of the studies focus on a few specific types of FFA, such as α-linolenic acid (C18:3n3) and Arachidonic acid (C20:4n6) or a total level of FFA. OBJECTIVE: This study aimed to test the association between a variety of FFAs during the first trimester and the risk of GDM. METHODS: The participants came from the Zhoushan Pregnant Women Cohort (ZWPC). A 1:2 nested case-control study was conducted: fifty mothers with GDM were matched with 100 mothers without GDM by age, pre-pregnancy body mass index (BMI), month of oral glucose tolerance test (OGTT) and parity. Thirty-seven FFAs (including 17 saturated fatty acids (SFA), 8 monounsaturated fatty acids (MUFA), 10 polyunsaturated fatty acids (PUFA) and 2 trans fatty acids (TFA)) in maternal plasma during the first trimester were tested by Gas Chromatography-Mass Spectrometry (GC-MS). Conditional logistic regression models were performed to assess the associations of FFA with the risk of GDM. RESULTS: Nine FFAs were respectively associated with an increased risk of GDM (P < 0.05), and four FFAs were respectively associated with a decreased risk of GDM (P < 0.05). SFA risk score was associated with a greater risk of GDM (OR = 1.34, 95% CI: 1.12-1.60), as well as UFA risk score (OR = 1.26, 95% CI: 1.11-1.44), MUFA risk score (OR = 1.70, 95%CI: 1.27-2.26), PUFA risk score (OR = 1.32, 95%CI: 1.09-1.59) and TFA risk score (OR = 2.51, 95%CI: 1.23-5.13). Moreover, joint effects between different types of FFA risk scores on GDM were detected. For instance, compared with those with low risk scores of SFA and UFA, women with high risk scores of SFA and UFA had the highest risk of GDM (OR = 8.53, 95%CI: 2.41-30.24), while the Odds ratio in those with a low risk score of SFA and high risk score of UFA and those with a high risk score of SFA and low risk score of UFA was 6.37 (95%CI:1.33- 30.53) and 4.25 (95%CI: 0.97-18.70), respectively. CONCLUSION: Maternal FFAs during the first trimester were positively associated with the risk of GDM. Additionally, there were joint effects between FFAs on GDM risk. CONDENSATION: Elevated FFA levels in the first trimester increased the risk of GDM.
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Diabetes Gestacional , Ácidos Grasos no Esterificados , Primer Trimestre del Embarazo , Humanos , Femenino , Diabetes Gestacional/epidemiología , Diabetes Gestacional/sangre , Embarazo , Estudios de Casos y Controles , Adulto , Ácidos Grasos no Esterificados/sangre , Primer Trimestre del Embarazo/sangre , Factores de Riesgo , Biomarcadores/sangreRESUMEN
The syntheses of atomically precise silver (Ag) clusters stabilized by multidentate lacunary polyoxometalate (POM) ligands have been emerging as a promising but challenging research direction, the combination of redox-active POM ligands and silver clusters will render them unexpected geometric structures and catalytic properties. Herein, we report the successful construction of two structurally-new lacunary POM-stabilized Ag clusters, TBA6 H14 Ag14 (DPPB)4 (CH3 CN)9 [Ag24 (Si2 W18 O66 )3 ] â 10CH3 CN â 9H2 O ({Ag24 (Si2 W18 O66 )3 }, TBA=tetra-n-butylammonium, DPPB=1,4-Bis(diphenylphosphino)butane) and TBA14 H6 Ag9 Na2 (H2 O)9 [Ag27 (Si2 W18 O66 )3 ] â 8CH3 CN â 10H2 O ({Ag27 (Si2 W18 O66 )3 }), using a facile one-pot solvothermal approach. Under otherwise identical synthetic conditions, the molecular structures of two POM-stabilized Ag clusters could be readily tuned by the addition of different organic ligands. In both compounds, the central trefoil-propeller-shaped {Ag24 }14+ and {Ag27 }17+ clusters bearing 10 delocalized valence electrons are stabilized by three C-shaped {Si2 W18 O66 } units. The femtosecond/nanosecond transient absorption spectroscopy revealed the rapid charge transfer between {Ag24 }14+ core and {Si2 W18 O66 } ligands. Both compounds have been pioneeringly investigated as catalysts for photocatalytic CO2 reduction to HCOOH with a high selectivity.
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BACKGROUND: We aimed to evaluate whether extracellular vesicles (EV)-derived microRNAs (miRNAs) can be used as biomarkers for advanced adenoma (AA) and colorectal cancer (CRC). METHODS: We detected the changes in the plasma EV-delivered miRNA profiles in healthy donor (HD), AA patient, and I-II stage CRC patient groups using miRNA deep sequencing assay. We performed the TaqMan miRNA assay using 173 plasma samples (two independent cohorts) from HDs, AA patients, and CRC patients to identify the candidate miRNA(s). The accuracy of candidate miRNA(s) in diagnosing AA and CRC was determined using the area under the receiver-operating characteristic curve (AUC) values. Logistic regression analysis was performed to evaluate the association of candidate miRNA(s) as an independent factor for the diagnosis of AA and CRC. The role of candidate miRNA(s) in the malignant progression of CRC was explored using functional assays. RESULTS: We screened and identified four prospective EV-delivered miRNAs, including miR-185-5p, which were significantly upregulated or downregulated in AA vs. HD and CRC vs. AA groups. In two independent cohorts, miR-185-5p was the best potential biomarker with the AUCs of 0.737 (Cohort I) and 0.720 (Cohort II) for AA vs. HD diagnosis, 0.887 (Cohort I) and 0.803 (Cohort II) for CRC vs. HD diagnosis, and 0.700 (Cohort I) and 0.631 (Cohort II) for CRC vs. AA diagnosis. Finally, we demonstrated that the upregulated expression of miR-185-5p promoted the malignant progression of CRC. CONCLUSION: EV-delivered miR-185-5p in the plasma of patients is a promising diagnostic biomarker for colorectal AA and CRC. Trial registration The study protocol was approved by the Ethics Committee of Changzheng Hospital, Naval Medical University, China (Ethics No. 2022SL005, Registration No. of China Clinical Trial Registration Center: ChiCTR220061592).
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Adenoma , Neoplasias Colorrectales , Vesículas Extracelulares , MicroARNs , Humanos , Estudios Prospectivos , MicroARNs/genética , Adenoma/diagnóstico , Adenoma/genética , Neoplasias Colorrectales/diagnóstico , Neoplasias Colorrectales/genéticaRESUMEN
Immunogenic cell death (ICD), one of cell-death types through release of damage-associated molecular patterns from dying tumor cells, activates tumor-specific immune response and elicits anti-tumor immunity by traditional radiotherapy and chemotherapy. However, whether natural products could induce ICD in leukemia is not elucidated. Here, we report dietary γ-mangostin eradicates murine primary leukemic cells and prolongs the survival of leukemic mice. As well, it restrains primary leukemic cells and CD34+ leukemic progenitor cells from leukemia patients. Strikingly, γ-mangostin attenuates leukemic cells by inducing ICD as characterized by expression of HSP90B1, ANXA1 and IL1B. Additionally, γ-mangostin accelerates cytoplasmic chromatin fragments generation, promoting DNA damage response, and enhances cGAS activation, leading to up-regulation of chemokines. Meanwhile, it induces HDAC4 degradation and acetylated histone H3 accumulation, which promotes chemokines transcription. Ultimately, CD8+ T cell is activated and recruited by γ-mangostin-induced chemokines in the microenvironment. Our study identifies γ-mangostin triggers ICD and activates cGAS signaling through DNA damage response and epigenetic modification. Therefore, dietary γ-mangostin would act as a potential agent to provoke anti-tumor immunity in the prevention and treatment of leukemia.
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Muerte Celular Inmunogénica , Leucemia Mieloide Aguda , Humanos , Animales , Ratones , Leucemia Mieloide Aguda/tratamiento farmacológico , Dieta , Quimiocinas , Microambiente TumoralRESUMEN
We report herein a concise method for the construction of phosphinonyl-azaindoline and -azaoxindole derivatives via a palladium-catalyzed cascade cyclization with P(O)H compounds. Various H-phosphonates, H-phosphinates, and aromatic secondary phosphine oxides are all tolerated under the reaction conditions. Furthermore, the phosphinonyl-azaindoline isomer families such as 7-, 5-, and 4-azaindolines could be synthesized in moderate to good yields.
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A palladium-catalyzed cyclization coupling of iodoarene-tethered alkynes with cyclobutanone-derived N-tosylhydrazones is reported, providing a convenient and efficient approach to benzofuran-3-cyclobutylidenes. On this basis, spirocyclobutanes can be generated smoothly in an efficient cascade manner by the addition of dienophiles. Good yields and scalability are demonstrated. Sequential intramolecular carbopalladation, palladium-carbene migratory insertion, δ-hydride elimination, and cycloaddition processes are involved.
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The purpose of this study is to implement point prevalence survey (PPS), assess antimicrobial prescribing and resistance in general hospitals and clinical specialties in China, and compare them with similar data from other parts of the world. Twenty general hospitals in China were surveyed in October or November, 2019. A standardized surveillance protocol was used to collect data on patient demographics, diagnosis of infection, the prevalence and intensity of antimicrobial use, prescribing quality, bacterium type and resistance spectrum, and the prevalence and type of healthcare-associated infections (HAIs). Overall, 10,881 beds and 10,209 inpatients were investigated. The overall prevalence of antibiotic use was 37.00%, the use of antibiotic prophylaxis in surgical patients was high (74.97%). The intensity of antimicrobial use was 61.25 DDDs/100 patient days. Only 11.62% of antimicrobial prescriptions recorded the reason for prescribing. Intravenous or combination treatments comprised 92.02% and 38.07%, respectively, and only 30.65% of prescriptions referred to a microbiological or biomarker tests. The incidence of HAIs in all patients was 3.79%. The main associated factors for HAIs included more frequent invasive procedures (27.34%), longer hospital stay (> 1-week stay accounting for 51.47%), and low use of alcohol hand rubs (only 29.79% placed it bedside). Most of the resistant bacteria declined; only carbapenem-resistant Enterobacter is higher than previously reported. The prevalence of antibiotic use in general hospitals fell significantly, the overall bacterial resistance declined, and the incidence of HAI was low. However, the low quality of antimicrobial use requires urgent attention.
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Antiinfecciosos , Infecciones Bacterianas , Infección Hospitalaria , Humanos , Prevalencia , Hospitales Generales , Antiinfecciosos/uso terapéutico , Antibacterianos/farmacología , Antibacterianos/uso terapéutico , Infección Hospitalaria/tratamiento farmacológico , Infección Hospitalaria/epidemiología , Infección Hospitalaria/microbiología , Infecciones Bacterianas/tratamiento farmacológico , Infecciones Bacterianas/epidemiología , Bacterias , Atención a la SaludRESUMEN
BACKGROUND: COVID-19 is a global pandemic. Understanding the immune responses in pregnant women recovering from COVID-19 may suggest new therapeutic approaches. METHODS: We performed a cross-sectional study between March 1, 2020, and September 1, 2020. Participants were assigned into the convalescent COVID-19 group if they had a previous COVID-19 infection during pregnancy or the healthy control group. RNA-Seq was performed on human umbilical cord mesenchymal stem cells (hUMSCs) and human amniotic mesenchymal stem cells (hAMSCs). Immunohistochemical staining, cytokine testing, lymphocyte subset analysis, RNA-Seq, and functional analyses were performed on the placental and umbilical cord blood (UCB) and compared between the two groups. RESULTS: A total of 40 pregnant women were enrolled, with 13 in the convalescent group and 27 in the control group. There were 1024, 46, and 32 differentially expressed genes (DEGs) identified in the placental tissue, hUMSCs, and hAMSCs between the convalescent and control groups, respectively. Enrichment analysis showed those DEGs were associated with immune homeostasis, antiviral activity, cell proliferation, and tissue repair. Levels of IL-6, TNF-α, total lymphocyte counts, B lymphocytes, Tregs percentages, and IFN-γ expressing CD4+ and CD8+ T cells were statistically different between two groups (p ≤ 0.05). ACE2 and TMPRSS2 expressed on the placenta were not different between the two groups (p > 0.05). CONCLUSION: Multiple changes in immune responses occurred in the placental tissue, hUMSCs, and hAMSCs after maternal recovery from COVID-19, which might imply their protective roles against COVID-19 infection.
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COVID-19 , Citocinas , Embarazo , Femenino , Humanos , Linfocitos T CD8-positivos , Estudios Transversales , Mujeres Embarazadas , Placenta , ARNRESUMEN
Psychological stress increases the susceptibility to herpes simplex virus type 1 (HSV-1) infection. There is no effective intervention due to the unknown pathogenesis mechanisms. In this study we explored the molecular mechanisms underlying stress-induced HSV-1 susceptibility and the antiviral effect of a natural compound rosmarinic acid (RA) in vivo and in vitro. Mice were administered RA (11.7, 23.4 mg·kg-1·d-1, i.g.) or acyclovir (ACV, 206 mg·kg-1·d-1, i.g.) for 23 days. The mice were subjected to restraint stress for 7 days followed by intranasal infection with HSV-1 on D7. At the end of RA or ACV treatment, mouse plasma samples and brain tissues were collected for analysis. We showed that both RA and ACV treatment significantly decreased stress-augmented mortality and alleviated eye swelling and neurological symptoms in HSV-1-infected mice. In SH-SY5Y cells and PC12 cells exposed to the stress hormone corticosterone (CORT) plus HSV-1, RA (100 µM) significantly increased the cell viability, and inhibited CORT-induced elevation in the expression of viral proteins and genes. We demonstrated that CORT (50 µM) triggered lipoxygenase 15 (ALOX15)-mediated redox imbalance in the neuronal cells, increasing the level of 4-HNE-conjugated STING, which impaired STING translocation from the endoplasmic reticulum to Golgi; the abnormality of STING-mediated innate immunity led to HSV-1 susceptibility. We revealed that RA was an inhibitor of lipid peroxidation by directly targeting ALOX15, thus RA could rescue stress-weakened neuronal innate immune response, thereby reducing HSV-1 susceptibility in vivo and in vitro. This study illustrates the critical role of lipid peroxidation in stress-induced HSV-1 susceptibility and reveals the potential for developing RA as an effective intervention in anti-HSV-1 therapy.
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Herpes Simple , Herpesvirus Humano 1 , Neuroblastoma , Humanos , Animales , Ratones , Herpesvirus Humano 1/genética , Peroxidación de Lípido , Aciclovir/farmacología , Aciclovir/uso terapéutico , Herpes Simple/tratamiento farmacológicoRESUMEN
The correct duplication and transfer of genetic material to daughter cells is the major event of cell division. Dysfunction of DNA replication or chromosome segregation presents challenges in cancer initiation and development as well as opportunities for cancer treatment. Cyclic GMP-AMP synthase (cGAS) of the innate immune system detects cytoplasmic DNA and mediates downstream immune responses through the molecule stimulator of interferon genes (STING). However, how cytosolic DNA sensor cGAS participates in guaranteeing accurate cell division and preventing tumorigenesis is still unclear. Recent evidence indicates malfunction of cGAS/STING pathway in cancer progression. Cell cycle-targeted therapy synergizes with immunotherapy via cGAS/STING activation, leading to promising therapeutic benefit. Here, we review the interactions between cell cycle regulation and cGAS/STING signaling, thus enabling us to understand the role of cGAS/STING in cancer initiation, development, and treatment.
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Proteínas de la Membrana , Neoplasias , Ciclo Celular/genética , División Celular , ADN/metabolismo , Humanos , Inmunidad Innata , Inmunoterapia , Proteínas de la Membrana/metabolismo , Neoplasias/genética , Neoplasias/terapia , Nucleotidiltransferasas/genética , Nucleotidiltransferasas/metabolismoRESUMEN
BACKGROUND: The ratio of gamma-glutamyltransferase to high-density lipoprotein cholesterol (GGT/HDL-C) has been highlighted in nonalcoholic fatty liver disease (NAFLD) by previous studies. However, there have been fewer investigations into the correlation between the GGT/HDL-C ratio and type 2 diabetes mellitus (T2DM) incidence. Our secondary analysis used published data from a Japanese population and aimed to investigate the role of the GGT/HDL-C ratio in the incidence of T2DM. METHODS: The research was a longitudinal cohort study completed by Okamura, Takuro et al. We obtained the data from the DATADRYAD website and used it for secondary analysis only. The participants recruited from a medical program called the NAGALA database received regular medical examinations and standardized questionnaires to obtain the baseline variables. Abdominal ultrasound was used to diagnose fatty liver disease. The participants were followed up, and the duration and occurrence of T2DM were documented. The GGT/HDL-C ratio evaluated at baseline served as the independent variable, while the occurrence of diabetes served as the dependent variable. RESULTS: A total of 15,453 cases (8,419 men and 7,034 women) were included in our study. After adjusting for age, sex, BMI, DBP, SBP, ALT, AST, TG, TC, HbA1C, FPG, drinking status, smoking status, exercise status, and fatty liver, we observed that the GGT/HDL-C ratio was positively associated with the incidence of T2DM (hazard ratio = 1.005, 95% confidence interval: 1.000 to 1.010, P = 0.0667). The results were consistent when the GGT/HDL-C quartile was used as a categorical variable (P for trend < 0.00396). A curvilinear relationship with a threshold effect was identified between the GGT/HDL-C ratio and the risk of incident T2DM. On the left of the point, a one-unit increase in the GGT/HDL-C ratio was associated with a 1.5-fold increase in the risk of incident T2DM (hazard ratio 2.57, 95% confidence interval 1.20 to 5.49). On the right of the point, when GGT/HDL-C was greater than 6.53, their relationship became saturated. CONCLUSION: The GGT/HDL-C ratio correlated with the incidence of T2DM in a curvilinear form with a threshold effect. Their positive relationship could be observed when GGT/HDL-C was less than 6.53.
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Diabetes Mellitus Tipo 2 , Enfermedad del Hígado Graso no Alcohólico , Masculino , Humanos , Femenino , Diabetes Mellitus Tipo 2/epidemiología , Diabetes Mellitus Tipo 2/diagnóstico , HDL-Colesterol , Estudios Longitudinales , gamma-Glutamiltransferasa , Japón/epidemiología , Factores de RiesgoRESUMEN
Background: Sepsis, which could cause a systemic inflammatory response, is a life-threatening disease with a high morbidity and mortality rate. There is evidence that brain injury may be related to severe systemic infection induced by sepsis. The brain injury caused by sepsis could increase the risk of mortality in septic patients, which seriously affects the septic patient's prognosis of survival. Although there remains a focus on sepsis research, clinical measures to prevent and treat brain injury in sepsis are not yet available, and the high mortality rate is still a big health burden. Therefore, it is necessary to investigate the new molecules or regulated pathways that can effectively inhibit the progress of sepsis. Objective: NLR family pyrin domain-containing 3 (NLRP3) increased in the procession of sepsis and functioned as the key regulator of pyroptosis. Heat shock factor 1 (HSF1) can protect organs from multiorgan dysfunction syndrome induced by lipopolysaccharides in mice, and NLRP3 could be inhibited by HSF1 in many organs. However, whether HSF1 regulated NLRP3 in sepsis-induced brain injury, as well as the detailed mechanism of HSF1 in brain injury, remains unknown in the sepsis model. In this research, we try to explore the relationship between HSF1 and NLRP3 in a sepsis model and try to reveal the mechanism of HSF1 inhibiting the process of brain injury. Methods: In this study, we used wild-type mice and hsf1 -/- mice for in vivo research and PC12 cells for in vitro research. Real-time PCR and Western blot were used to analyze the expression of HSF1, NLRP3, cytokines, and pyrolytic proteins. EthD-III staining was chosen to detect the pyroptosis of the hippocampus and PC12 cells. Results: The results showed that HSF1 is negatively related to pyroptosis. The pyroptosis in cells of brain tissue was significantly increased in the hsf1 -/- mouse model compared to hsf1 +/+ mice. In PC12 cells, hsf1 siRNA can upregulate pyroptosis while HSF1-transfected plasmid could inhibit the pyroptosis. HSF1 could negatively regulate the NLRP3 pathway in PC12 cells, while hsf1 siRNA enhanced the pyroptosis in PC12 cells, which could be reversed by nlrp3 siRNA. Conclusion: These results imply that HSF1 could alleviate sepsis-induced brain injury by inhibiting pyroptosis through the NLRP3-dependent pathway in brain tissue and PC12 cells, suggesting HSF1 as a potential molecular target for treating brain injury in sepsis clinical studies.
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Lesiones Encefálicas , Factores de Transcripción del Choque Térmico , Proteína con Dominio Pirina 3 de la Familia NLR , Sepsis , Animales , Ratones , Ratas , Factores de Transcripción del Choque Térmico/farmacología , Inflamasomas/metabolismo , Proteína con Dominio Pirina 3 de la Familia NLR/metabolismo , Piroptosis , ARN Interferente Pequeño , Sepsis/metabolismoRESUMEN
PURPOSE: Two clinical trials were conducted to investigate the oral and perioral irritation and sensitization potential of a tooth whitening leave-on-gel alone and in combination with a whitening toothpaste, each containing 1.0% of the active ingredient potassium monopersulfate (MPS). METHODS: Both clinical trials were Institutional Review Board (IRB) approved, double-blind, randomized, and parallel group designed studies. For the MPS leave-on gel study, 200 qualifying and consented subjects were randomly assigned to two groups: (1) 0.1% hydrogen peroxide (H2O2) gel pen (34 subjects); and (2) 0.1% H2O2 + 1.0% MPS gel pen (166 subjects). Subjects used the assigned products according to instructions provided and returned on Days 22 and 36 for oral and perioral tissue examination (pre-challenge). At the Day 36 visit, the subject applied the assigned gel on site (challenge) and received oral and perioral tissue examinations 1 and 24 hours following the application to detect any post-challenge tissue reactions. For the MPS toothpaste/MPS gel pen study, 200 qualifying and consented subjects were randomly assigned to three groups: (1) Placebo toothpaste + placebo gel pen (66 subjects); (2) 1.0% MPS toothpaste + 1.0% MPS gel pen (67 subjects); and (3) 1.0% MPS toothpaste + placebo gel pen (67 subjects). The study design and procedures were the same as those for the MPS gel pen study described above. RESULTS: For the MPS gel pen study, 192 subjects completed the study. None of the eight dropouts was related to the product use. The demographic data were comparable between the two groups. No evidence of tissue irritation and sensitization was detected in any subjects at any visit, and the findings were comparable between the groups. The detected and self-reported tissue issues were minimal and minor, and they were comparable between the two groups. For the MPS toothpaste/MPS gel pen study, 200 subjects were enrolled with 12 dropped from the study, resulting in an overall dropout rate of 6%. Of the 12 that did not complete the study, none were due to product-related use. The demographic data were comparable among the three groups. The detected and self-reported tissue issues were minimal and minor, and they were comparable among the three groups. CLINICAL SIGNIFICANCE: Potassium monopersulfate (MPS) at the active concentration of 1.0% in the tooth whitening leave-on-gel and the toothpaste plus the gel did not cause oral/perioral irritation nor sensitization.
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Blanqueamiento de Dientes , Decoloración de Dientes , Humanos , Pastas de Dientes/uso terapéutico , Peróxido de Hidrógeno/efectos adversos , Resultado del Tratamiento , Blanqueamiento de Dientes/efectos adversos , Blanqueamiento de Dientes/métodos , Método Doble Ciego , Decoloración de Dientes/tratamiento farmacológicoRESUMEN
A structurally-new, carbon-free hexadecanuclear Ni-containing silicotungstate, [Ni16(H2O)15(OH)9(PO4)4(SiW9O34)3]19-, has been facilely synthesized using a one-pot, solution-based synthetic method systematically characterized by single-crystal X-ray diffraction and several other techniques. The resulting complex works as a noble-metal-free catalyst for visible-light-driven catalytic generation of hydrogen, by coupling with a [Ir(coumarin)2(dtbbpy)][PF6] photosensitizer and a triethanolamine (TEOA) sacrificial electron donor. Under minimally optimized conditions, a turnover number (TON) of 842 was achieved for TBA-Ni16P4(SiW9)3-catalyzed hydrogen evolution system. The structural stability of TBA-Ni16P4(SiW9)3 catalyst under photocatalytic conditions was evaluated by the mercury-poisoning test, FT-IR, and DLS measurements. The photocatalytic mechanism was elucidated by both time-solved luminescence decay and static emission quenching measurements.
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The toxicity of boron nitride nanotubes (BNNTs) has been the subject of conflicting reports, likely due to differences in the residuals and impurities that can make up to 30-60% of the material produced based on the manufacturing processes and purification employed. Four BNNTs manufactured by induction thermal plasma process with a gradient of BNNT purity levels achieved through sequential gas purification, water and solvent washing, allowed assessing the influence of these residuals/impurities on the toxicity profile of BNNTs. Extensive characterization including infrared and X-ray spectroscopy, thermogravimetric analysis, size, charge, surface area, and density captured the alteration in physicochemical properties as the material went through sequential purification. The material from each step is screened using acellular and in vitro assays for evaluating general toxicity, mechanisms of toxicity, and macrophage function. As the material increased in purity, there are more high-aspect-ratio particulates and a corresponding distinct increase in cytotoxicity, nuclear factor-κB transcription, and inflammasome activation. There is no alteration in macrophage function after BNNT exposure with all purity grades. The cytotoxicity and mechanism of screening clustered with the purity grade of BNNTs, illustrating that greater purity of BNNT corresponds to greater toxicity.