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A recent study demonstrated near-ambient superconductivity in nitrogen-doped lutetium hydride1. This stimulated a worldwide interest in exploring room-temperature superconductivity at low pressures. Here, by using a high-pressure and high-temperature synthesis technique, we have obtained nitrogen-doped lutetium hydride (LuH2±xNy), which has a dark-blue colour and a structure with the space group [Formula: see text] as evidenced by X-ray diffraction. This structure is the same as that reported in ref. 1, with a slight difference in lattice constant. Raman spectroscopy of our samples also showed patterns similar to those observed in ref. 1. Energy-dispersive X-ray spectroscopy confirmed the presence of nitrogen in the samples. We observed a metallic behaviour from 350 K to 2 K at ambient pressure. On applying pressures from 2.1 GPa to 41 GPa, we observed a gradual colour change from dark blue to violet to pink-red. By measuring the resistance at pressures ranging from 0.4 GPa to 40.1 GPa, we observed a progressively improved metallic behaviour; however, superconductivity was not observed above 2 K. Temperature dependence of magnetization at high pressure shows a very weak positive signal between 100 K and 320 K, and the magnetization increases with an increase in magnetic field at 100 K. All of these are not expected for superconductivity above 100 K. Thus, we conclude the absence of near-ambient superconductivity in this nitrogen-doped lutetium hydride at pressures below 40.1 GPa.
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OBJECTIVE: The objective of this study is to provide a description of a group of retrospective cohort outcomes in patients with systemic lupus erythematosus (SLE) complicated with immune thrombocytopenia (ITP) receiving belimumab. METHODS: This study reports on the treatment of 10 female patients (mean age 34.3 ± 14.0 years, mean weight 58.7 ± 18.2 kg) with both SLE and ITP who received belimumab in addition to basic drug therapy. The belimumab treatment regimen consisted of a dosage of 10 mg/kg, with an initial infusion every 2 weeks for the first 3 doses, followed by an infusion every 4 weeks. RESULTS: Ten patients were included in the study. The overall response rate of thrombocytopenia was 90% after treatment. The parameters such as platelet count, lymphocyte count, erythrocyte count, hemoglobin, dsDNA, C3, and C4 were significantly improved (p < .05). The SLE Disease Activity Index (SLEDAI), British Islet lupus Assessment Group 2004 (BILAG-2004), and Physician Global assessment (PGA) scores were significantly decreased (p < .05). There were no significant differences in glutamic pyruvic transaminase (ALT), glutamic oxaloacetic transaminase (AST), and serum creatinine (Scr) before and after treatment (p > .05). CONCLUSION: Belimumab shows promising clinical outcomes in the treatment on patients with both SLE and ITP. Further studies are needed to validate these findings in larger patient populations and compare the efficacy of belimumab with other treatments for SLE complicated with ITP. Long-term response rates and adverse events associated with belimumab treatment also warrant further investigation.
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Anticorpos Monoclonais Humanizados , Lúpus Eritematoso Sistêmico , Púrpura Trombocitopênica Idiopática , Trombocitopenia , Humanos , Feminino , Adulto Jovem , Adulto , Pessoa de Meia-Idade , Lúpus Eritematoso Sistêmico/complicações , Lúpus Eritematoso Sistêmico/tratamento farmacológico , Estudos Retrospectivos , Púrpura Trombocitopênica Idiopática/tratamento farmacológico , Resultado do Tratamento , Trombocitopenia/tratamento farmacológico , Imunossupressores/efeitos adversos , Índice de Gravidade de DoençaRESUMO
The rising in situ chemical oxidation (ISCO) technologies based on polymerization reactions have advanced the removal of emerging contaminants in the aquatic environment. However, despite their promise, uncertainties persist regarding their effectiveness in eliminating structurally complex contaminants, such as sulfonamide antibiotics (SAs). This study elucidated that oligomerization, rather than mineralization, predominantly governs the removal of SAs in the carbon materials/periodate system. The amine groups in SAs played a crucial role in forming organic radicals and subsequent coupling reactions due to their high f- index and low bond orders. Moreover, the study highlighted the robust adhesion of oligomers to the catalyst surface, facilitated by enhanced van der Waals forces and hydrophobic interactions. Importantly, plant and animal toxicity assessments confirmed the nontoxic nature of oligomers deposited on the carbon material surface, affirming the efficacy of carbon material-based ISCO in treating contaminated surface water and groundwater. Additionally, a novel classification approach, Δlogâ¯k, was proposed to differentiate SAs based on their kinetic control steps, providing deeper insights into the quantitative structure-activity relationship (QSAR) and facilitating the selection of optimal descriptors during the oligomerization processes. Overall, these insights significantly enhance our understanding of SAs removal via oligomerization and demonstrate the superiority of C-ISCO based on polymerization in water decontamination.
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Antibacterianos , Carbono , Sulfonamidas , Antibacterianos/química , Carbono/química , Sulfonamidas/química , Poluentes Químicos da Água/química , Purificação da ÁguaRESUMO
PURPOSE: This paper explores the causes of paediatric inguinal hernia (PIH) recurrence after single-port laparoscopic percutaneous extraperitoneal closure (SPLPEC). METHOD: From January 2015 to December 2020, the clinical data of 3480 children with PIHs who underwent SPLPEC were retrospectively reviewed, including 644 children who underwent SPLPEC with a homemade single-hook hernia needle from January 2015 to December 2016 and 2836 children who underwent the SPLPEC with a double-hook hernia needle and hydrodissection from January 2017 to December 2020. There were 39 recurrences (including communicating hydrocele) during the 2-5 years of follow-up. The findings of redo-laparoscopy were recorded and correlated with the revised video of the first operation to analyse the causes of recurrence. RESULT: Thirty-three males and 6 females experienced recurrence, and 8 patients had a unilateral communicating hydrocele. The median time to recurrence was 7.1 months (0-38). There were 20 cases (3.11%) in the single-hook group and 19 cases (0.67%) in the double-hook group. Based on laparoscopic findings, recurrence most probably resulted from multiple factors, including uneven tension of the ligation (10 cases), missing part of the peritoneum (14 cases), loose ligation (8 cases), broken knot (5 cases), and knot reaction (2 cases). All children who underwent repeat SPLPEC were cured by double ligations or reinforcement with medial umbilical ligament. CONCLUSION: The main cause of recurrence is improper ligation. Tension-free and complete PIH ligation are critical to the success of surgery, which requires avoiding the peritoneum skip area and the subcutaneous and muscular tissues. Redo-laparoscopic surgery was suitable for the treatment of recurrent inguinal hernia (RIH). For giant hernias, direct ligation of the internal ring incorporating the medial umbilical ligament (DIRIM) may be needed.
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Hérnia Inguinal , Laparoscopia , Hidrocele Testicular , Masculino , Feminino , Criança , Humanos , Lactente , Hérnia Inguinal/etiologia , Hérnia Inguinal/cirurgia , Estudos Retrospectivos , Resultado do Tratamento , Herniorrafia/métodos , Laparoscopia/métodos , Hidrocele Testicular/cirurgia , RecidivaRESUMO
AIM: To determine whether continuous venovenous hemodiafiltration (CVVHDF) plus standard medical therapy (SMT) vs. SMT alone prevents rhabdomyolysis (RM)-induced acute kidney injury (AKI) and analyze the related health economics. METHODS: This retrospective cohort study involved 9 RM patients without AKI, coronary heart disease, or chronic kidney disease treated with CVVHDF plus SMT (CVVHDF + SMT group). Nine matched RM patients without AKI treated with SMT only served as controls (SMT group). Baseline characteristics, biochemical indexes, renal survival data, and health economic data were compared between groups. In the CVVHDF + SMT group, biochemical data were compared at different time points. RESULTS: At 2 and 7 days after admission, serum biochemical indices (e.g., myoglobin, creatine kinase, creatinine, and blood urea nitrogen) did not differ between the groups. Total (P = 0.011) and daily hospitalization costs (P = 0.002) were higher in the CVVHDF + SMT group than in the SMT group. After 53 months of follow-up, no patient developed increased serum creatinine, except for 1 CVVHDF + SMT-group patient who died of acute myocardial infarction. In the CVVHDF + SMT group, myoglobin levels significantly differed before and after the first CVVHDF treatment (P = 0.008), and serum myoglobin, serum creatinine, and blood urea nitrogen decreased significantly at different time points after CVVHDF. CONCLUSIONS: Although CVVHDF facilitated myoglobin elimination, its addition to SMT did not improve biochemical indices like serum myoglobin, serum creatine kinase, creatinine, blood urea nitrogen, and lactate dehydrogenase or the long-term renal prognosis. Despite similar hospitalization durations, both total and daily hospitalization costs were higher in the CVVHDF + SMT group.
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Injúria Renal Aguda , Terapia de Substituição Renal Contínua , Hemodiafiltração , Rabdomiólise , Humanos , Creatinina , Estudos Retrospectivos , Mioglobina , Injúria Renal Aguda/etiologia , Injúria Renal Aguda/prevenção & controle , Rabdomiólise/complicações , Creatina QuinaseRESUMO
Antarctic krill (Euphausia superba) is the world's largest resource of animal proteins and is thought to be a high-quality resource for future marine healthy foods and functional products. Therefore, Antarctic krill was degreased and separately hydrolyzed using flavourzyme, pepsin, papain, and alcalase. Protein hydrolysate (AKH) of Antarctic krill prepared by trypsin showed the highest Ca-chelating rate under the optimized chelating conditions: a pH of 8.0, reaction time of 50 min, temperature of 50 °C, and material/calcium ratio of 1:15. Subsequently, fourteen Ca-chelating peptides were isolated from APK by ultrafiltration and a series of chromatographic methods and identified as AK, EAR, AEA, VERG, VAS, GPK, SP, GPKG, APRGH, GVPG, LEPGP, LEKGA, FPPGR, and GEPG with molecular weights of 217.27, 374.40, 289.29, 459.50, 275.30, 300.36, 202.21, 357.41, 536.59, 328.37, 511.58, 516.60, 572.66, and 358.35 Da, respectively. Among fourteen Ca-chelating peptides, VERG presented the highest Ca-chelating ability. Ultraviolet spectrum (UV), Fourier Transform Infrared (FTIR), and scanning electron microscope (SEM) analysis indicated that the VERG-Ca chelate had a dense granular structure because the N-H, C=O and -COOH groups of VERG combined with Ca2+. Moreover, the VERG-Ca chelate is stable in gastrointestinal digestion and can significantly improve Ca transport in Caco-2 cell monolayer experiments, but phytate could significantly reduce the absorption of Ca derived from the VERG-Ca chelate. Therefore, Ca-chelating peptides from protein hydrolysate of Antarctic krill possess the potential to serve as a Ca supplement in developing healthy foods.
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Euphausiacea , Hidrolisados de Proteína , Animais , Humanos , Hidrolisados de Proteína/química , Euphausiacea/química , Cálcio , Células CACO-2 , Peptídeos/química , Regiões AntárticasRESUMO
OBJECTIVES: To investigate the current surgery strategies for bilateral proliferative diabetic retinopathy (PDR), as well as the surgical outcomes of patients with bilateral PDR who underwent pars plana vitrectomy (PPV). MATERIALS: Patients undergoing bilateral vitrectomy for PDR from January 2019 to December 2020 at The Eye Hospital of Wenzhou Medical University were enrolled. Clinical data were collected from the electronic medical records. Factors associated with the time interval between the surgeries on two eyes and postoperative visual outcomes were analyzed. RESULTS: In total, 152 patients with bilateral PDR who underwent bilateral PPV were included in this analysis. Mean age was 53.7 ± 11.4 years. Compared with second-surgery eyes, 60.5% of first-surgery eyes had worse preoperative best-corrected visual acuity (BCVA). The overall PPV time (median, quartile range) between first and second surgeries eye was 1.40 (0.70, 3.15) months. Multivariate analysis showed that the preoperative BCVA of the second-surgery eye had a significant effect on the inter-surgery time interval (P = 0.048). First-surgery eyes had greater vision improvement than second-surgery eyes (Difference of the logarithm of the minimum angle of resolution [LogMAR] BCVA: - 1.00 [- 1.48, - 0.12] versus 0.00 [- 1.30, 0.00], respectively, P < 0.001), especially when eyes with poorer BCVA underwent PPV first (- 1.15 [- 1.87, - 0.54] versus 0.00 [- 0.70, 0.00], respectively, P < 0.001). CONCLUSIONS: Visual acuity is a significant factor that influences surgical strategies, including both surgery order and interval, for patients with bilateral PDR. The eyes operated upon first show more vision improvement due to prompt surgery.
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Diabetes Mellitus , Retinopatia Diabética , Vitreorretinopatia Proliferativa , Humanos , Adulto , Pessoa de Meia-Idade , Idoso , Retinopatia Diabética/diagnóstico , Retinopatia Diabética/cirurgia , Retinopatia Diabética/complicações , Vitrectomia , Olho , Acuidade Visual , Estudos RetrospectivosRESUMO
The purpose of this study is to investigate whether chrysin reduces cerebral ischemia-reperfusion injury(CIRI) by inhi-biting ferroptosis in rats. Male SD rats were randomly divided into a sham group, a model group, high-, medium-, and low-dose chrysin groups(200, 100, and 50 mg·kg~(-1)), and a positive drug group(Ginaton, 21.6 mg·kg~(-1)). The CIRI model was induced in rats by transient middle cerebral artery occlusion(tMCAO). The indexes were evaluated and the samples were taken 24 h after the operation. The neurological deficit score was used to detect neurological function. The 2,3,5-triphenyl tetrazolium chloride(TTC) staining was used to detect the cerebral infarction area. Hematoxylin-eosin(HE) staining and Nissl staining were used to observe the morphological structure of brain tissues. Prussian blue staining was used to observe the iron accumulation in the brain. Total iron, lipid pero-xide, and malondialdehyde in serum and brain tissues were detected by biochemical reagents. Real-time quantitative polymerase chain reaction(RT-qPCR), immunohistochemistry, and Western blot were used to detect mRNA and protein expression of solute carrier fa-mily 7 member 11(SLC7A11), transferrin receptor 1(TFR1), glutathione peroxidase 4(GPX4), acyl-CoA synthetase long chain family member 4(ACSL4), and prostaglandin-endoperoxide synthase 2(PTGS2) in brain tissues. Compared with the model group, the groups with drug intervention showed restored neurological function, decreased cerebral infarction rate, and alleviated pathological changes. The low-dose chrysin group was selected as the optimal dosing group. Compared with the model group, the chrysin groups showed reduced content of total iron, lipid peroxide, and malondialdehyde in brain tissues and serum, increased mRNA and protein expression levels of SLC7A11 and GPX4, and decreased mRNA and protein expression levels of TFR1, PTGS2, and ACSL4. Chrysin may regulate iron metabolism via regulating the related targets of ferroptosis and inhibit neuronal ferroptosis induced by CIRI.
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Isquemia Encefálica , Ferroptose , Traumatismo por Reperfusão , Ratos , Masculino , Animais , Ratos Sprague-Dawley , Transdução de Sinais , Isquemia Encefálica/tratamento farmacológico , Isquemia Encefálica/genética , Isquemia Encefálica/metabolismo , Ciclo-Oxigenase 2/metabolismo , RNA Mensageiro , Infarto Cerebral , Traumatismo por Reperfusão/tratamento farmacológico , Traumatismo por Reperfusão/genética , Traumatismo por Reperfusão/metabolismo , Malondialdeído , Infarto da Artéria Cerebral MédiaRESUMO
PURPOSE: To identify the indications for hepatocellular carcinoma (HCC) irradiated by intensity-modulated photon radiotherapy (IMRT), proton radiotherapy (PRT) or carbon-ion radiotherapy (CIRT) by comparing of dosimetric parameters and incidences of classic radiation-induced liver disease (RILD). METHODS: In all, 40 HCCs were divided into group A (tumors located >â¯1â¯cm away from gastrointestinal [GI] tract), and group B (tumors located <â¯1â¯cm away from GI tract). The prescribed curative doses were 60â¯Gy (relative biological effectiveness [RBE]) in 10 fractions for group A, and 67.5â¯Gy (RBE) in 15 fractions for group B. IMRT, PRT and CIRT plans were separately generated to reach the curative doses and coverage. Dosimetric parameters evaluated were mean dose to normal liver (MDTNL) and the volume of normal liver receiving more than 1â¯Gy (RBE) (V1). Lyman-Kutcher-Burman model was used to determine the incidences of classic RILD, and Power model of non-linear regression, to estimate the tumor volume that could be irradiated with the curative doses within dose constraint of MDTNL. RESULTS: With comparable target doses, the MDTNL (Gy [RBE]) were 18.8⯱ 3.7, 13.5⯱ 3.1 and 12.8⯱ 2.7 in group A and 24.9⯱ 7.1, 18.2⯱ 3.7 and 17.5⯱ 3.7 in group B, respectively, for IMRT, PRT and CIRT. The classic RILD incidences (%) were 22.3⯱ 30.0 in IMRT, 2.3⯱ 4.9 in PRT and 1.2⯱ 2.4 in CIRT. V1 (%) were 89.9⯱ 8.8, 43.0⯱ 10.2 and 45.9⯱ 8.8, respectively, for IMRT, PRT and CIRT. CONCLUSIONS: PRT and CIRT could spare the liver more than IMRT. IMRT could deliver the curative doses to HCC up to a diameter of 7.9â¯cm; PRT, up to 13.2â¯cm; and CIRT, up to 14.8â¯cm.
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Carcinoma Hepatocelular , Radioterapia com Íons Pesados , Neoplasias Hepáticas , Radioterapia de Intensidade Modulada , Carcinoma Hepatocelular/radioterapia , Humanos , Neoplasias Hepáticas/radioterapia , Dosagem Radioterapêutica , Planejamento da Radioterapia Assistida por Computador , Radioterapia de Intensidade Modulada/efeitos adversosRESUMO
In recent years, the application of low-refractive-index materials in the optical field has attracted considerable attention due to it high transmittance and high optical sensitivity. In this study, we synthesized SiO2 porous hollow spheres (SPHS) with an ultralow refractive index (n = 1.05) by using a templating method. Their refractive indices could be easily controlled from 1.05 to 1.08 by tuning the thickness of shell. In addition, a droplet coatings method is proposed for SPHS colloidal crystal (CC) by controlling the temperature and humidity. The SPHS CCs displayed distinct structural colors when the incident angle was adjusted and demonstrated high angular resolution. Moreover, the iridescent color changes could be observed with the naked eye. For surface-enhanced Raman scattering application, more analyte could be absorbed by the porous shells, and metal nanoparticles were coated on the SPHSs surface to increase the hot spot density for improving the SERS intensity.
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MOFs@MOFs (metal-organic frameworks, MOFs) possess precise customized functionalities and predesigned structures that enable the implementation of structure and property regulation for specific functions in comparison to traditional single MOFs. However, the synthesis and fluorescence properties of multilayer MOFs@MOFs are still worth improving. Herein, a fluorescent raspberry-shaped MOF@MOF was constructed via optimized seed-mediated synthesis by tuning the reaction time, reaction mode, and reaction concentration, involving the initial synthesis of the UiO-66-NH2 core and then the coating of the UiO-67-bpy shell. The raspberry-shaped UiO-66@67-bpy showed stable fluorescence and desirable sensing selectivity for the Hg2+ ion under the interference of other ions; meanwhile, the raspberry-shaped UiO-66@67-bpy indicated amplified sensing performance than pure UiO-66-NH2, mechanically mixed UiO-66-NH2 + UiO-67-bpy, and UiO-66@UiO-67 counterpart due to the accumulation effect of outer UiO-67-bpy toward Hg2+. Density functional theory (DFT) calculations including adsorption energy calculations and electronic density difference analysis further showed that the enhanced fluorescence quenching was possibly attributed to the outer UiO-67-bpy enrichment promoting the charge transfer between Hg2+ and the ligands of fluorescent UiO-66@67-bpy. The synergistic effect of MOFs@MOFs unlocks more possibilities for the construction of enhanced sensors and other applications.
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This study investigated the role of calpain in Eimeria tenella-induced host cell apoptosis. Chick embryo cecal epithelial cell culture technology, flow cytometry, enzyme-linked immunosorbent assays, and fluorescence quantitative PCR were used to detect the E. tenella host cell apoptotic rate, Bax and Bid expression levels, and calpain activity. The results demonstrated that Bax, Bid, and calpain levels were upregulated and apoptosis was increased following E. tenella infection at 24-120 h. Calpain levels were reduced by pharmacological inhibition of calpain using SJA6017 or by blocking Ca2+ entry into the cell using BAPTA/AM at 24-120 h. The mRNA and protein levels of Bax and Bid, the E. tenella infection rate, and the early apoptotic and late apoptotic (necrosis) rates were decreased by using SJA6017 at 24-120 h. These results indicated that E. tenella-promoted host cell apoptosis is regulated by calpain via Bid and Bax at 24-120 h. Thus, manipulation of calpain levels could be used to manage E. tenella infection in chickens in the middle and late developmental stages.
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Coccidiose , Eimeria tenella , Doenças das Aves Domésticas , Animais , Apoptose , Calpaína/genética , Embrião de Galinha , Galinhas , Coccidiose/metabolismo , Coccidiose/veterinária , Eimeria tenella/genética , Doenças das Aves Domésticas/genética , Proteína X Associada a bcl-2/genéticaRESUMO
OBJECTIVE: We hypothesize that loss of inhibition from the cerebellum can lead to cortical activation and seizures. BACKGROUND: The traditional model for development of seizures purports that the source of seizures is increased electrical activity originating from cerebral cortical neurons. Studies have shown a decrease in inhibition results in a shift of cortical activity to a hyperexcitable state, which may lead to seizures. Interestingly, a 1978 study suggested the term "disorder of disinhibition" as a way to describe epilepsy from studies of chronic cerebellar stimulation. DESIGN/METHODS: Cases and experimental studies in which cerebellar lesions have been implicated in the development of seizures were reviewed. Cases in which cerebellar inhibition has been targeted in the treatment of seizures were also included. Twenty-six studies and case reports are presented for this report. RESULTS: The cases show cerebellar lesions can lead to cortical epileptiform activity. Purkinje cell loss is linked to the occurrence of seizures in animals. The majority of patients with cerebellar lesions were seizure free after complete resection, while less than half of patients were seizure free after partial resection. Novel treatments using deep-brain stimulation targeting cerebellar structures demonstrated therapeutic benefits for seizures. CONCLUSIONS: Although pathophysiology is not well-understood, the cerebellum likely plays an inherent role in inhibiting aberrant cortical epileptogenesis. Cerebellar lesions may cause seizures due to loss of the inhibition of cortical areas or through intrinsic epileptic activity. Treatments enhancing cerebellar stimulation have shown therapeutic benefits in treating seizures, which could potentially provide another avenue for treatment.
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Epilepsia , Comportamento Problema , Animais , Cerebelo , Córtex Cerebral , Epilepsia/complicações , Humanos , ConvulsõesRESUMO
Seven undescribed withanolides (1-7) and six artificial withanolides (8-13), along with 20 known compounds (14-33) were isolated from the aerial parts of Tubocapsicum anomalum. Their structures were confirmed by comprehensive spectroscopic analyses. The absolute configuration of compound 1 was defined by single-crystal X-ray crystallography. All isolates were evaluated for their antiproliferative effects against five human tumor cell lines (Hep3B, MDA-MB-231, SW480, HCT116 and A549), among which compound 24 (tubocapsanolide A) exhibited the highest activities against the MDA-MB-231 cells with an IC50 value of 1.89 ± 1.03 µM. Further studies showed that 24 exhibited significant damage to mitochondria in MDA-MB-231 cells, including excess reactive oxygen species, decreased mitochondrial membrane potential, and apoptosis initiation. In addition, compound 24 also inhibited cell migration. These findings show that tubocapsanolide A may be a promising molecule for triple-negative breast cancer treatment and merit further evaluation.
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Antineoplásicos Fitogênicos/farmacologia , Extratos Vegetais/farmacologia , Solanaceae/química , Vitanolídeos/farmacologia , Antineoplásicos Fitogênicos/química , Antineoplásicos Fitogênicos/isolamento & purificação , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Conformação Molecular , Extratos Vegetais/química , Extratos Vegetais/isolamento & purificação , Relação Estrutura-Atividade , Células Tumorais Cultivadas , Vitanolídeos/química , Vitanolídeos/isolamento & purificaçãoRESUMO
Sulfur mustard (SM) is a highly toxic chemical warfare agent that causes acute lung injury (ALI) and/or acute respiratory distress syndrome (ARDS). There are no effective therapeutic treatments or antidotes available currently to counteract its toxic effects. Our previous study shows that bone marrow-derived mesenchymal stromal cells (BMSCs) could exert therapeutic effects against SM-induced lung injury. In this study, we explored the therapeutic potential of BMSC-derived exosomes (BMSC-Exs) against ALI and the underlying mechanisms. ALI was induced in mice by injection of SM (30 mg/kg, sc) at their medial and dorsal surfaces. BMSC-Exs (20 µg/kg in 200 µL PBS, iv) were injected for a 5-day period after SM exposure. We showed that BMSC-Exs administration caused a protective effect against pulmonary edema. Using a lung epithelial cell barrier model, BMSC-Exs (10, 20, 40 µg) dose-dependently inhibited SM-induced cell apoptosis and promoted the recovery of epithelial barrier function by facilitating the expression and relocalization of junction proteins (E-cadherin, claudin-1, occludin, and ZO-1). We further demonstrated that BMSC-Exs protected against apoptosis and promoted the restoration of barrier function against SM through upregulating G protein-coupled receptor family C group 5 type A (GPRC5A), a retinoic acid target gene predominately expressed in the epithelial cells of the lung. Knockdown of GPRC5A reduced the antiapoptotic and barrier regeneration abilities of BMSC-Exs and diminished their therapeutic effects in vitro and in vivo. BMSC-Exs-caused upregulation of GPRC5A promoted the expression of Bcl-2 and junction proteins via regulating the YAP pathway. In summary, BMSC-Exs treatment exerts protective effects against SM-induced ALI by promoting alveolar epithelial barrier repair and may be an alternative approach to stem cell-based therapy.
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Lesão Pulmonar Aguda/terapia , Exossomos/transplante , Células-Tronco Mesenquimais/citologia , Transdução de Sinais/efeitos dos fármacos , Lesão Pulmonar Aguda/induzido quimicamente , Lesão Pulmonar Aguda/metabolismo , Animais , Apoptose/fisiologia , Linhagem Celular , Células Epiteliais/metabolismo , Técnicas de Inativação de Genes , Pulmão/metabolismo , Pulmão/patologia , Masculino , Camundongos Endogâmicos ICR , Camundongos Knockout , Gás de Mostarda , Receptores Acoplados a Proteínas G/genética , Receptores Acoplados a Proteínas G/metabolismo , Proteínas de Sinalização YAP/metabolismoRESUMO
BACKGROUND: Bronchoscopy treatments of central airway obstruction (CAO) under general anesthesia are high-risky procedures, and posing a giant challenge to the anesthesiologists. We summarized and analyzed our clinical experience in patients with CAO undergoing flexible or rigid bronchoscopy, to estimate the safety of skeletal muscle relaxants application and the traditional Low-frequency ventilation. METHODS: Clinical data of 375 patients with CAO who underwent urgent endoscopic treatments in general anesthesia from January 2016 to October 2019 were retrospectively reviewed. The use ratio of skeletal muscle relaxants, dose of skeletal muscle relaxants used, the incidence of perioperative adverse events, adequacy of ventilation and gas exchange, post-operative recovery between rigid bronchoscopy and flexible bronchoscopy therapy, and risk factors for postoperative ICU admission were evaluated. RESULTS: Of the 375 patients with CAO, 204 patients were treated with flexible bronchoscopy and 171 patients were treated with rigid bronchoscopy. Muscle relaxants were used in 362 of 375 patients (including 313 cisatracurium, 45 rocuronium, 4 atracurium, and 13 unrecorded). The usage rate of muscle relaxants (96.5% in total) was very high in patients with CAO who underwent either flexible bronchoscopy (96.6%) or rigid bronchoscopy (96.5%) therapy. The dosage of skeletal muscle relaxants (Cisatracium) used was higher in rigid bronchoscopy compared with flexible bronchoscopy therapy (10.8 ± 3.8 VS 11.6 ± 3.6 mg, respectively, p < 0.05). No patient suffered the failure of ventilation, bronchospasm and intraoperative cough either in flexible or rigid bronchoscopy therapy. Hypoxemia was occurred in 13 patients (8 in flexible, 5 in rigid bronchoscopy) during the procedure, and reintubation after extubation happened in 2 patients with flexible bronchoscopy. Sufficient ventilation was successfully established using the traditional Low-frequency ventilation with no significant carbon dioxide accumulation and hypoxemia occurred both in flexible and rigid bronchoscopy group (p > 0.05). Three patients (1 in flexible and 2 in rigid) died, during the post-operative recovery, and the higher grade of American Society of Anesthesiologists (ASA) and obvious dyspnea or orthopnea were the independent risk factors for postoperative ICU admission. CONCLUSION: The muscle relaxants and low-frequency traditional ventilation can be safely used both in flexible and rigid bronchoscopy treatments in patients with CAO. These results may provide strong clinical evidence for optimizing the anesthesia management of bronchoscopy for these patients.
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Obstrução das Vias Respiratórias/terapia , Broncoscopia/métodos , Máscaras Laríngeas , Relaxantes Musculares Centrais/administração & dosagem , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Anestesia Geral , Feminino , Humanos , Hipóxia/etiologia , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Adulto JovemRESUMO
The widespread use of herbicides has raised considerable concern with regard to their harmful consequences on plant growth, crop yield and the soil ecological environment. It has been well documented that colonization of rhizobacteria in the plant root system has a positive effect on activation of plant defenses to protect the plant from damage. Using the platform of high-throughput analysis with tandem mass spectrometry and Illumina sequencing, we identified the specific activated rhizobacteria, the key growth stimulating substances and the metabolic pathways involved in seedling stage tolerance to mefenacet stress in rice. The relative abundance of beneficial rhizospheremicrobes such as Acidobacteria and Firmicutes increased with mefenacet treatment, indicating that the rhizosphere recruited some beneficial microbes to resist mefenacet stress. Mefenacet treatment induced alterations in several interlinked metabolic pathways, many of which were related to activation of defense response signaling, especially the indole-3-pyruvate pathway. Indole-3-acetaldehyde and indole-3-ethanol from this pathway may act as flexible storage pools for indole-3-acetic acid (IAA). Our findings also suggest that a significant increase of IAA produced by the enrichment of beneficial rhizospheremicrobes, for example genus Bacillus, alleviated the dwarfing phenomenon observed in hydroponic medium following mefenacet exposure, which may be a key signaling molecule primarily for phytostimulation and phytotolerance in microbe-plant interactions.
Assuntos
Oryza , Rizosfera , Acetanilidas , Benzotiazóis , Raízes de Plantas , Microbiologia do SoloRESUMO
Six new triterpenoids (1-6) and 22 known analogues (7-28), were separated from the aerial parts of Anchusa italica Retz., a traditional Uygur medicine for treating cardiovascular and cerebrovascular diseases in the Xinjiang region, China. The possible effects of compounds 1-28 on hypoxia/reoxygenation (H/R) induced cardiomyocytes injury were assayed, and compounds 4, 6-17, 21-22 and 26-28 showed significant protective effects. Further, the representative new compound 6 significantly suppressed the levels of H/R-induced apoptosis and autophagy in neonatal rat cardiomyocytes, with the reversing of the downregulated expression of Bcl-2 and upregulated expression of Bax and Beclin-1 by compound 6 treatment in neonatal rat cardiomyocytes following H/R injury. In addition, compound 6 protected cardiomyocyte from H/R injury, and pretreatment with 6 could decrease CK and LDH levels. Compound 6 also alleviated H/R-induced phosphorylation of p38 MAPK in neonatal rat cardiomyocytes. Therefore, tripterpenoid 6 and its analogues may be the pharmacodyamic material of A. italica, and offer a promising therapeutic approach for treating cardiomyocyte injury induced by H/R.
Assuntos
Boraginaceae/química , Cardiotônicos/farmacologia , Hipóxia Celular/efeitos dos fármacos , Miócitos Cardíacos/efeitos dos fármacos , Triterpenos/farmacologia , Animais , Apoptose/efeitos dos fármacos , Cardiotônicos/química , Células Cultivadas , Hipóxia/tratamento farmacológico , Hipóxia/metabolismo , Hipóxia/patologia , Traumatismo por Reperfusão Miocárdica/tratamento farmacológico , Traumatismo por Reperfusão Miocárdica/metabolismo , Traumatismo por Reperfusão Miocárdica/patologia , Miócitos Cardíacos/metabolismo , Miócitos Cardíacos/patologia , Oxigênio/metabolismo , Ratos Sprague-Dawley , Triterpenos/químicaRESUMO
The gene PSEN2 encodes presenilin-2, a subunit of γ-secretase. Mutations in PSEN2 are not only related to Alzheimer's disease but are also involved in other diseases. The Chinese tree shrew (Tupaia belangeri chinensis) is a potential animal model for Alzheimer's disease, although little is known about its cDNA sequence, protein structure, and PSEN2 expression. To better understand PSEN2 in the tree shrew, we cloned this gene by rapid amplification of cDNA ends technology. Hence, we analyzed the sequence and molecular characteristics of PSEN2 mRNA, predicted its spatial structure, and analyzed its expression profiles. We found that tree shrew PSEN2 is 1539 base pairs in length and encodes 330 amino acids. It is homologous and genetically similar to humans (97.64% identity). The protein structure of tree shrew PSEN2 indicated similarities to human PSEN2, both being comprised of numerous transmembrane helices. However, tree shrew PSEN2 possesses seven α-helices, and thus lacks three compared with human PSEN2. Tree shrew PSEN2 mRNAs were ubiquitously detected in all tissues, with a tissue- and temporal-specific pattern. These results pave the way towards the function of tree shrew PSEN2, which will give insights into the mechanisms leading to neurodegenerative and other diseases in humans.
Assuntos
Presenilina-2/genética , Transcriptoma/genética , Tupaia/genética , Animais , DNA Complementar , Modelos Animais de Doenças , RNA MensageiroRESUMO
Acute lung injury (ALI) is served as a severe life-threatening disease. However, the pathogenesis that contributes to ALI has not been fully understood. Tumor necrosis factor receptor-associated factor 1 (TRAF1) interacts with multiple regulators, performing its diverse role in biological functions. However, the effects of TRAF1 on ALI remain unknown. In this study, we attempted to explore the role of TRAF1 in ALI progression. The findings suggested that TRAF1-knockout (KO) markedly attenuated LPS-induced severe mortality rate in murine animals. LPS-elicited histological alterations in pulmonary tissues were significantly alleviated by TRAF1-deletion. Additionally, TRAF1 knockout effectively attenuated lung injury, as evidenced by the reduced lung wet/dry (W/D) weight ratio, as well as decreased bronchoalveolar lavage fluid (BALF) protein levels and neutrophil infiltration. Meanwhile, TRAF1 deletion markedly lessened inflammation, oxidative stress and apoptosis in BALF and/or lung tissues. The levels of pro-inflammatory cytokines stimulated by LPS were down-regulated by TRAF1 ablation, along with the inactivation of nuclear factor κB (NF-κB). LPS-promoted reactive oxygen species (ROS) generation was decreased in TRAF1-KO mice, partly through the improvement of anti-oxidants. Apoptosis was also inhibited by TRAF1 deletion in lung tissues of LPS-challenged mice through the suppression of cleaved Caspase-3. Moreover, TRAF1 knockout significantly decreased c-Jun N-terminal kinase (JNK) activation and its down-streaming signal of c-Jun in pulmonary samples of LPS-induced mice. Importantly, the in vitro study suggested that promoting JNK activation markedly abrogated TRAF1 knockdown-attenuated inflammation, ROS production and apoptosis in LPS-exposed A549â¯cells. Therefore, our experimental results provided evidence that TRAF1 suppression effectively protected LPS-induced ALI against inflammation, oxidative stress and apoptosis through the suppression of JNK activity.