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The capability of traditional ligand in countering rapid passivation on nanoscale zero-valent iron (nZVI) surface is inadequate, and the precise electron transfer mechanism remains elusive. In this study, we reported that myo-inositol hexakisphosphate (IHP), a redox-inactive organophosphorus in soil, could highly enhance Cr(VI) reduction and immobilization in comparison with typical ligands (TPP, EDTA, oxalate and phosphate). And the effects of IHP concentration, Cr(VI) concentration and initial pH were systematically investigated. Cr K-edge XANES and XPS analysis revealed that Cr(III) was the exclusive form in solid products regardless of IHP existence. Results of ATR-FTIR and FESEM inferred that IHP was adsorbed on nZVI surface via inner-sphere complexation, thus averting encapsulation of [Fe, Cr](OH)3 coprecipitate and impeding solid particles agglomeration. Additionally, IHP expedited the production of surface-bound Fe(II), primarily attributable to the interaction between nZVI and oxygen. These surface-bound Fe(II) species played a pivotal role in Cr(VI) reduction. Electrochemical analysis unveiled that IHP lowered redox potential of Fe(III)/Fe(II), thereby facilitating reaction between Fe(II) and Cr(VI), whereas inhibited direct electron transfer from nZVI core to Cr(VI). Our findings proposed a novel potential ligand for alleviating nZVI passivation in Cr(VI) removal and deepened our understanding in the process of electron transfer.
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Cromo , Ferro , Cromo/química , Ferro/química , Ácido Fítico/química , Oxirredução , Modelos Químicos , Transporte de Elétrons , Poluentes do Solo/química , AdsorçãoRESUMO
AIM: This paper aims to investigate the humanistic care ability among surgical nurses in China and identify its statistically significant influencing factors. DESIGN: A cross-sectional, descriptive and correlational design was used. METHODS: A total of 210 surgical nurses were recruited from a tertiary public hospital in Wuhu, Anhui Province. Four with incomplete responses were excluded, leaving 206 participants for data analysis. Variables were measured using the general questionnaire, caring ability inventory (CAI), and General Self-Efficacy Scale (GSES). Multivariate linear regression analyses were performed to identify the statistically significant influencing factors of participants' humanistic caring ability. RESULTS: The overall average score of the CAI was 190.14 (SD = 19.24), and the average scores for the three dimensions of cognitive, courage, and patience were 70.46 (SD = 7.77), 62.12 (SD = 8.47) and 57.56 (SD = 6.02), respectively. The overall average score of the GSES was 26.05 (SD = 5.77). Professional attitude, perceived care from the department head nurse, perceived care from colleagues and self-efficacy were the statistically significant factors influencing the humanistic care ability of surgical nurses (R2 = 0.45, adjusted R2 = 0.44, F = 40.64, p < 0.001).
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Humanismo , Humanos , Estudos Transversais , China , Feminino , Adulto , Inquéritos e Questionários , Masculino , Autoeficácia , Atitude do Pessoal de Saúde , Enfermagem Perioperatória , Pessoa de Meia-Idade , Recursos Humanos de Enfermagem Hospitalar/psicologia , Recursos Humanos de Enfermagem Hospitalar/estatística & dados numéricos , Enfermeiras e Enfermeiros/psicologia , Enfermeiras e Enfermeiros/estatística & dados numéricos , População do Leste AsiáticoRESUMO
Aedes-borne diseases infect millions of people each year. In the last decade several arbovirus outbreaks have been reported in Ethiopia. Arbovirus diagnosis and surveillance is lacking and the true burden is unknown. In this study we conducted a seroprevalence survey using a commercially available test kit that that tests for immunological responses to IgM and IgG for dengue (DENV), Zika (ZIKV), and chikungunya (CHIKV) viruses in Dire Dawa city, eastern Ethiopia. We found a high IgG seroprevalence for DENV (76%), CHIKV (44%), and ZIKV (38%), and <20% IgM seropositivity across all viruses. As a comparison, we conducted serosurveillance in Addis Ababa, the national capital with no reported history of arbovirus outbreaks. The highest seropositivity we found was to IgM for DENGV at approximately 3%. Our results suggest both past and recent widespread exposure to these arboviruses, underscoring the need for improved surveillance and public health interventions in Ethiopia.
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BACKGROUND: Thioester-containing protein 1 (TEP1) is a crucial component of mosquitoes' natural resistance to parasites. To effectively combat malaria, there is a need to better understand how TEP1 polymorphism affects phenotypic traits during infections. Therefore, the purpose of this study was to determine the Tep1 genotype frequency in malaria vector populations from south-western Ethiopia and investigate its effect on Plasmodium oocyst development in Anopheles arabiensis populations. METHODS: Using standard dippers, Anopheles mosquito larvae were collected from aquatic habitats in Asendabo, Arjo Dedessa, and Gambella in 2019 and 2020. Collected larvae were reared to adults and identified morphologically. Female An. gambiae s.l. were allowed to feed on infected blood containing the same number of gametocytes obtained from P. falciparum and P. vivax gametocyte-positive individuals using indirect membrane feeding methods. Polymerase Chain Reaction (PCR) was used to identify An. gambiae s.l. sibling species. Three hundred thirty An. gambiae s.l. were genotyped using Restricted Fragment Length Polymorphism (RFLP) PCR and sub samples were sequenced to validate the TEP1 genotyping. RESULTS: Among the 330 samples genotyped, two TEP1 alleles, TEP1*S1 (82% frequency) and TEP1*R1 (18% frequency), were identified. Three equivalent genotypes, TEP1*S1/S1, TEP1*R1/R1, and TEP1*S1/R1, had mean frequencies of 65.15%, 2.12%, and 32.73%, respectively. The nucleotide diversity was ranging from 0.36554 to 0. 46751 while haplotype diversity ranged from 0.48871 to 0.63161, across all loci. All sample sites had positive Tajima's D and Fu's Fs values. There was a significant difference in the TEP1 allele frequency and genotype frequency among mosquito populations (p < 0.05), except populations of Anopheles arabiensis from Asendabo and Gambella (p > 0.05). In addition, mosquitoes with the TEP1 *RR genotype were susceptible and produced fewer Plasmodium oocysts than mosquitoes with the TEP1 *SR and TEP1 *SS genotypes. CONCLUSION: The alleles identified in populations of An. arabiensis were TEP1*R1 and TEP1*S1. There was no significant variation in TEP1*R1 allele frequency between the high and low transmission areas. Furthermore, An. arabiensis carrying the TEP1*R1 allele was susceptible to Plasmodium infection. Further studies on vector-parasite interactions, particularly on the TEP1 gene, are required for vector control techniques.
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Anopheles , Frequência do Gene , Genótipo , Proteínas de Insetos , Mosquitos Vetores , Oocistos , Animais , Anopheles/parasitologia , Anopheles/genética , Etiópia , Mosquitos Vetores/parasitologia , Mosquitos Vetores/genética , Proteínas de Insetos/genética , Proteínas de Insetos/metabolismo , Feminino , Plasmodium falciparum/genética , Plasmodium vivax/genética , Malária/parasitologia , Malária/transmissão , Plasmodium/genéticaRESUMO
Glutamine (GLN) is considered an immunomodulatory nutrient, while caspase recruitment domain 11 (CARD11) is a susceptibility locus for atopic dermatitis (AD). T-cell antigen receptor (TCR)-stimulated GLN uptake requires CARD11. However, the specific pathogenesis of AD via GLN uptake remains unclear. This study aimed to elucidate the association between dietary GLN supplementation and the CARD11 pathway in the pathogenesis of AD, focusing on T helper type 1 (Th1) and Th17 cell expression in AD. Herein, wild-type (WT) mice with house dust mite epidermal-sensitized skin exhibited increased expression of interferon-gamma (IFN-gamma) and interleukin (IL)-17, whereas CARD11 deficiency impaired Th1 and Th17 responses at the same site. CARD11 is a key mediator of Th1 and Th17 expression in AD. Additionally, we suppressed mammalian target of rapamycin complex 1 (mTORC1) signaling, downstream of CARD11, to underscore the critical role of CARD11 in mediating Th1 and Th17 expression in AD. Further, dietary supplementation of GLN to CARD11-/- mice restored Th1 and Th17 responses, whereas inflammatory expression was reduced in WT mice, and p-CARD11 expression and mTORC1 signaling activity were increased in JPM50.6 cells and CARD11-/- mice. Upon inhibiting the GLN transporter, alanine-serine-cysteine transporter carrier 2 (ASCT2), we observed that the Th1 and Th17 response in AD was reduced. Conclusively, ASCT2-mediated GLN uptake improves the expression of Th1 and Th17 cells via CARD11-mTORC1 signaling pathway in AD, suggesting the potential of glutamine supplementation for AD treatment.
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Understanding the nature of a transition-metal-catalyzed process, including catalyst evolution and the real active species, is rather challenging yet of great importance for the rational design and development of novel catalysts, and this is even more difficult for a bimetallic catalytic system. Pd(0)/carboxylic acid combined system-catalyzed allylic alkylation reaction of alkynes has been used as an atom-economical protocol for the synthesis of allylic products. However, the asymmetric version of this reaction is still rather limited, and the in-depth understanding of the nature of active Pd species is still elusive. Herein we report an enantioselective coupling between readily available aldimine esters and alkynes using a synergistic Cu/Pd catalyst system, affording a diverse set of α-quaternary allyl amino ester derivatives in good yields with excellent enantioselectivities. Mechanistic studies indicated that it is most likely a synergistic asymmetric molecular Cu catalysis with Pd nanoparticle catalysis. The Pd catalyst precursor is transformed to soluble Pd nanoparticles in situ, which are responsible for activating the alkyne to an electrophilic allylic Pd intermediate, while the chiral Cu complex of the aldimine ester enolate provides chiral induction and works in synergy with the Pd nanoparticles.
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OBJECTIVE: Precise root torque adjustment of anterior teeth is indispensable for optimizing dental esthetics and occlusal stability in orthodontics. The efficiency of traditional rectangular archwire manipulation within bracket slots seems to be limited. The crimpable gate spring, a novel device, has emerged as a promising alternative. Yet, there is a paucity of guidelines for its optimal clinical application. This study used finite element analysis (FEA) to investigate the biomechanical impact of the gate spring on torque adjustment of individual anterior teeth and to elucidate the most effective application strategy. METHODS: A FEA model was constructed by a maxillary central incisor affixed with an edgewise bracket featuring a 0.022â¯× 0.028â¯inch (in) slot. A range of stainless steel rectangular archwires, in conjunction with a gate spring, were modeled and simulated within the bracket slots. A control group utilized a conventional rectangular wire devoid of a gate spring. Palatal root moments were standardized to 9, 18, and 36â¯Nmm for both experimental and control groups. RESULTS: The gate spring significantly amplified palatal root movement, notably with the 0.019â¯× 0.025â¯in archwire. However, this was accompanied by an increase in stress on the tooth and periodontal ligament, particularly in the cervical regions. The synergistic use of a 0.019â¯× 0.025â¯in rectangular archwire with a gate spring in a 0.022â¯× 0.028â¯in bracket slot was identified as most efficacious for torque control of individual anterior teeth. CONCLUSIONS: The gate spring is a viable auxiliary device for enhancing torque adjustment on individual teeth. However, caution is advised as excessive initial stress may concentrate in the cervical and apical regions of the periodontal ligament and tooth.
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Biallelic loss of cyclin-dependent kinase 12 (CDK12) defines a metastatic castration-resistant prostate cancer (mCRPC) subtype. It remains unclear, however, whether CDK12 loss drives prostate cancer (PCa) development or uncovers pharmacologic vulnerabilities. Here, we show Cdk12 ablation in murine prostate epithelium is sufficient to induce preneoplastic lesions with lymphocytic infiltration. In allograft-based CRISPR screening, Cdk12 loss associates positively with Trp53 inactivation but negatively with Pten inactivation. Moreover, concurrent Cdk12/Trp53 ablation promotes proliferation of prostate-derived organoids, while Cdk12 knockout in Pten-null mice abrogates prostate tumor growth. In syngeneic systems, Cdk12/Trp53-null allografts exhibit luminal morphology and immune checkpoint blockade sensitivity. Mechanistically, Cdk12 inactivation mediates genomic instability by inducing transcription-replication conflicts. Strikingly, CDK12-mutant organoids and patient-derived xenografts are sensitive to inhibition or degradation of the paralog kinase, CDK13. We therein establish CDK12 as a bona fide tumor suppressor, mechanistically define how CDK12 inactivation causes genomic instability, and advance a therapeutic strategy for CDK12-mutant mCRPC.
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Quinases Ciclina-Dependentes , Neoplasias da Próstata , Mutações Sintéticas Letais , Masculino , Animais , Humanos , Quinases Ciclina-Dependentes/metabolismo , Quinases Ciclina-Dependentes/genética , Camundongos , Mutações Sintéticas Letais/genética , Neoplasias da Próstata/patologia , Neoplasias da Próstata/genética , Neoplasias da Próstata/metabolismo , Proteína Supressora de Tumor p53/metabolismo , Proteína Supressora de Tumor p53/genética , Progressão da Doença , PTEN Fosfo-Hidrolase/metabolismo , PTEN Fosfo-Hidrolase/genética , Instabilidade Genômica , Transcrição Gênica , Organoides/patologia , Organoides/metabolismo , Neoplasias de Próstata Resistentes à Castração/patologia , Neoplasias de Próstata Resistentes à Castração/genética , Neoplasias de Próstata Resistentes à Castração/metabolismo , Proliferação de Células/genética , Replicação do DNA/genética , Camundongos Knockout , Linhagem Celular Tumoral , Camundongos Endogâmicos C57BL , Proteína Quinase CDC2RESUMO
Oxidative stress frequently contributes to intestinal barrier injury in animals and humans. It was reported that both Selenomethionine (SeMet) and allicin exhibit protective effects against a range of diseases caused by oxidative stress. This study aimed to investigate the synergistic antioxidant effects and underlying mechanisms of SeMet and allicin on a H2O2-induced intestinal barrier injury model using IPEC-J2 cells and mice. The results showed that H2O2 induced severe oxidative stress, including a decrease in cell viability, antioxidant level, migration capacity, and cell integrity. SeMet and allicin exhibited significant synergistic anti-oxidative effects on intestinal epithelial cells. The combined use of SeMet and allicin increased SOD activity, GSH content, and GSH/GSSG ratio while decreasing MDA, NO, and ROS content levels. Furthermore, we found that SeMet and allicin synergistically activated the nuclear factor erythroid-related factor 2 (Nrf2)-NAD(P)H dehydrogenase [quinone] 1 (NQO1) signaling pathway and down-regulated endoplasmic reticulum stress (ER stress)-related proteins. However, the synergistic antioxidative and intestinal barrier protective effects of SeMet and allicin were abolished by Nrf2 inhibitor ML385 in vitro and in vivo. In conclusion, SeMet and allicin synergistically attenuate intestinal barrier injury induced by excessively oxidative stress through the activation of the Nrf2 signaling pathway and inhibition ER stress. These findings support that the combined use of SeMet and allicin could enhance antioxidative properties and alleviate intestinal injury in further clinical practice.
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Hysterothylacium aduncum is one of six pathogens responsible for human anisakiasis. Infection with H. aduncum can cause acute abdominal symptoms and allergic reactions and is prone to misdiagnosis in clinical practice. This study aims to enhance the efficiency and accuracy of detecting H. aduncum in food ingredients. We targeted the internal transcribed spacer 1 (ITS 1) regions of Anisakis to develop a visual screening method for detecting H. aduncum using recombinase polymerase amplification (RPA) combined with the CRISPR/Cas12a system. By comparing the ITS 1 region sequences of eight nematode species, we designed specific primers and CRISPR RNA (crRNA). The specificity of RPA primers was screened and evaluated, and the CRISPR system was optimized. We assessed its specificity and sensitivity and performed testing on commercial samples. The results indicated that the alternative primer ADU 1 was the most effective. The final optimized concentrations were 250 nM for Cas12a, 500 nM for crRNA, and 500 nM for ssDNA. The complete test procedure was achievable within 45 min at 37 °C, with a limit of detection (LOD) of 1.27 pg/µL. The amplified product could be directly observed using a fluorescence microscope or ultraviolet lamp. Detection results for 15 Anisakis samples were entirely consistent with those obtained via Sanger sequencing, demonstrating the higher efficacy of this method for detecting and identifying H. aduncum. This visual detection method, characterized by simple operation, visual results, high sensitivity, and specificity, meets the requirements for food safety testing and enhances monitoring efficiency.
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Anisakis , Sistemas CRISPR-Cas , Animais , Anisakis/genética , Anisakis/isolamento & purificação , Limite de Detecção , Técnicas de Amplificação de Ácido Nucleico/métodos , Sensibilidade e Especificidade , Endodesoxirribonucleases/genética , Endodesoxirribonucleases/metabolismo , Recombinases/metabolismo , Humanos , Proteínas de Bactérias , Proteínas Associadas a CRISPRRESUMO
ETHNOPHARMACOLOGICAL RELEVANCE: Inflammatory bowel disease (IBD) is a globally increasing disease. Despite continuous efforts, the clinical application of treatment drugs has not achieved satisfactory success and faces limitations such as adverse drug reactions. Numerous investigations have found that the pathogenesis of IBD is connected with disturbances in bile acid circulation and metabolism. Traditional Chinese medicine targeting bile acids (BAs) has shown significant therapeutic effects and advantages in treating inflammatory bowel disease. AIM OF THIS REVIEW: IThis article reviews the role of bile acids and their receptors in IBD, as well as research progress on IBD therapeutic drugs based on bile acids. It explores bile acid metabolism and its interaction with the intestinal microbiota, summarizes clinical drugs for treating IBD including single herbal medicine, traditional herbal prescriptions, and analyzes the mechanisms of action in treating IBD. MATERIALS AND METHODS: IThe electronic databases such as PubMed, Web of Science, and China National Knowledge Infrastructure (CNKI) have been utilized to retrieve relevant literature up to January 2024, using keywords "bile acid", "bile acid receptor", "inflammatory bowel disease", "intestinal microbiota" and "targeted drugs". RESULTS: IImbalance in bile acid levels can lead to intestinal inflammation, while IBD can disrupt the balance of microbes, result in alterations in the bile acid pool's composition and amount. This change can damage of intestinal mucosa healing ability. Bile acids are vital for keeping the gut barrier function intact, regulating gene expression, managing metabolic equilibrium, and influencing the properties and roles of the gut's microbial community. Consequently, focusing on bile acids could offer a potential treatment strategy for IBD. CONCLUSION: IIBD can induce intestinal homeostasis imbalance and changes in BA pool, leading to fluctuations in levels of relevant metabolic enzymes, transporters, and nuclear receptors. Therefore, by regulating the balance of BA and key signaling molecules of bile acids, we can treat IBD. Traditional Chinese medicine has great potential and promising prospects in treating IBD. We should focus on the characteristics and advantages of Chinese medicine, promote the development and clinical application of innovative Chinese medicine, and ultimately make Chinese medicine targeting bile acids the mainstream treatment for IBD.
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Dietary restriction-influenced biological performance is found in many animal species. Pardosa pseudoannulata is a dominant spider species in agricultural fields and is important for controlling pests. In this study, three groups - a control group (CK group), a re-feeding group (RF group), and a dietary restriction group (RT group) - were used to explore development, mating, reproduction, and the expression levels of Vg (vitellogenin) and VgR (vitellogenin receptor) genes in the spider. The findings indicated that when subjected to dietary restriction, the carapace size, weight of the spiderlings, and weight of the adults exhibited a decrease. Furthermore, the preoviposition period and egg stage were observed to be prolonged, while the number of spiderlings decreased. It was also observed that re-feeding reduced cannibalism rates and extended the preoviposition period. Dietary restriction also affected the expression of the Vg-3 gene in the spider. These results will contribute to the understanding of the impact of dietary restriction in predators of pest control, as well as provide a theoretical foundation for the artificial rearing and utilisation of the dominant spider in the field.
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To investigate the safety of pancreatic body suspension (PBS) technique in laparoscopic splenectomy combined with pericardial devascularization for patients. A retrospective study inclusive of 16 patients who underwent laparoscopic splenectomy combined with pericardial devascularization from 2017 to 2022 was performed. A total of 5 patients underwent PBS technique and 11 underwent the traditional technique. There was no significant difference in age, sex, body mass index (BMI), preoperative serum white cell count (WBC), platelets (PLT), hemoglobin (HB), albumin (ALB), prothrombin time (PT), total bilirubin (TBIL), or spleen size between the 2 groups (Pâ >â .05). In the PBS group, the operation time was 280 minutes. The estimated intraoperative blood loss (EBL) was 250 mL. The mean postoperative hospitalization length was 11.2 days. There was no conversion to an open procedure or postoperative bleeding. In the traditional method group, the mean operation time was 240.91 minutes. The EBL was 290.91 mL. There were 2 cases of conversion to open, 3 cases of postoperative bleeding, and 1 reoperation. The incidence of postoperative short-term complications (postoperative bleeding, reoperation) was significantly higher in the traditional method group than in the PBS group (36.36% vs 0%, Pâ =â .034). PBS technique improved the safety of laparoscopic splenectomy combined with pericardial dissection and is worthy of clinical promotion.
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Laparoscopia , Duração da Cirurgia , Pericárdio , Esplenectomia , Humanos , Esplenectomia/métodos , Esplenectomia/efeitos adversos , Masculino , Feminino , Laparoscopia/métodos , Laparoscopia/efeitos adversos , Estudos Retrospectivos , Pessoa de Meia-Idade , Adulto , Pericárdio/transplante , Pericárdio/cirurgia , Perda Sanguínea Cirúrgica/estatística & dados numéricos , Pâncreas/cirurgia , Pâncreas/irrigação sanguínea , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Hemorragia Pós-Operatória/epidemiologia , Hemorragia Pós-Operatória/etiologia , Tempo de Internação/estatística & dados numéricosRESUMO
The invasion of Anopheles stephensi into Africa poses a potential threat to malaria control and elimination on the continent. However, it is not clear if the recent malaria resurgence in Ethiopia has linked to the expansion of An. stephensi. We obtained the clinical malaria case reports and malaria intervention data from the Ethiopian Ministry of Health (MoH) for the period 2001-2022. We analyzed clinical malaria hotspots and investigated the potential role of An. stephensi in the 2022 malaria outbreaks. Clinical malaria cases in Ethiopia decreased by 80%, from 5.2 million cases in 2004 to 1.0 million cases in 2018; however, cases increased steadily to 2.6 million confirmed cases in 2022. Plasmodium vivax cases and proportion have increased significantly in the past 5 years. Clinical malaria hotspots are concentrated along the western Ethiopian border areas and have grown significantly from 2017 to 2022. Major malaria outbreaks in 2022/2023 were detected in multiple sites across Ethiopia, and An. stephensi was the predominant vector in some of these sites, however, it was absence from many of the outbreak sites. The causes of recent upsurge in malaria in Ethiopia may be multi-factorial and it is a subject of further investigation.
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Leaching of per- and polyfluoroalkyl substances (PFAS) during the post-consumer disposal of food contact materials (FCMs) poses a potential environmental threat but has seldom been evaluated. This study characterized the leaching behavior of PFAS and unidentified precursors from six common FCMs and assessed the impact of environmental conditions on PFAS release during disposal. The total concentration of 21 PFAS ranged from 3.2 to 377 ng/g in FCMs, with PFAS leachability into water varying between 1.1-42.8 %. Increasing temperature promoted PFAS leaching, with leached nine primary PFAS (∑9PFAS) reaching 46.3, 70.4, and 102 ng/L at 35, 45, and 55 â, respectively. Thermodynamic analysis (∆G>0, ∆H>0, and ∆S<0) indicated hydrophobic interactions control PFAS leaching. The presence of dissolved organic matter in synthetic leachate increased the leached ∑9PFAS from 47.1 to 103 ng/L but decreased PFBS, PFOS, and 6:2 FTS leaching. The total release of seven perfluorocarboxylic acids (∑7PFCAs) from takeaway food packaging waste was estimated to be 0.3-8.2 kg/y to landfill leachate and 0.6-15.4 kg/y to incineration plant leachate, contributing 0.2-4.8 % and 0.1-3.2 % of total ∑7PFCAs in each leachate type. While the study presents a refined methodology for estimating PFAS release during disposal, future research is needed on the indirect contribution from precursors.
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Fluorocarbonos , Embalagem de Alimentos , Poluentes Químicos da Água , Fluorocarbonos/análise , Fluorocarbonos/química , Poluentes Químicos da Água/análise , Poluentes Químicos da Água/química , Eliminação de Resíduos , Contaminação de Alimentos/análiseRESUMO
Viral encephalitis is characterized by inflammation of the brain parenchyma caused by a variety of viruses, among which the Japanese encephalitis (JE) virus (JEV) is a typical representative arbovirus. Neuronal death, neuroinflammation, and breakdown of the blood brain barrier (BBB) constitute vicious circles of JE progression. Currently, there is no effective therapy to prevent this damage. Growth arrest specific gene 6 (GAS6) is a secreted growth factor that binds to the TYRO3, AXL, and MERTK (TAM) family of receptor tyrosine kinases and has been demonstrated to participate in neuroprotection and suppression of inflammation in many central nervous system (CNS) diseases which has great potential for JE intervention. In this study, we found that GAS6 expression in the brain was decreased and was reversely correlated with viral load and neuronal loss. Mice with GAS6/TAM signalling deficiency showed higher mortality and accelerated neuroinflammation during peripheral JEV infection, accompanied by BBB breakdown. GAS6 directly promoted the expression of tight junction proteins in bEnd.3 cells and strengthened BBB integrity, partly via AXL. Mice administered GAS6 were more resistant to JEV infection due to increased BBB integrity, as well as decreased viral load and neuroinflammation. Thus, targeted GAS6 delivery may represent a strategy for the prevention and treatment of JE especially in patients with impaired BBB.
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Encefalite Japonesa , Peptídeos e Proteínas de Sinalização Intercelular , Doenças Neuroinflamatórias , Animais , Camundongos , Receptor Tirosina Quinase Axl , Barreira Hematoencefálica/metabolismo , Barreira Hematoencefálica/patologia , Modelos Animais de Doenças , Encefalite Japonesa/metabolismo , Peptídeos e Proteínas de Sinalização Intercelular/genética , Peptídeos e Proteínas de Sinalização Intercelular/metabolismo , Camundongos Endogâmicos C57BL , Camundongos Knockout , Doenças Neuroinflamatórias/metabolismo , Receptores Proteína Tirosina Quinases/metabolismo , Receptores Proteína Tirosina Quinases/genéticaRESUMO
BACKGROUNDFrailty significantly affects morbidity and mortality rates in the older population (age >65 years). Age-related degenerative diseases are influenced by the intestinal microbiota. However, limited research exists on alterations in the intestinal microbiota in frail older individuals, and the effectiveness of prebiotic intervention for treating frailty remains uncertain.OBJECTIVEWe sought to examine the biological characteristics of the intestinal microbiome in frail older individuals and assess changes in both frailty status and gut microbiota following intervention with a prebiotic blend consisting of inulin and oligofructose.METHODSThe study consisted of 3 components: an observational analysis with a sample size of 1,693, a cross-sectional analysis (n = 300), and a multicenter double-blind, randomized, placebo-controlled trial (n = 200). Body composition, commonly used scales, biochemical markers, intestinal microbiota, and metabolites were examined in 3 groups of older individuals (nonfrail, prefrail, and frail). Subsequently, changes in these indicators were reevaluated after a 3-month intervention using the prebiotic mixture for the prefrail and frail groups.RESULTSThe intervention utilizing a combination of prebiotics significantly improved frailty and renal function among the older population, leading to notable increases in protein levels, body fat percentage, walking speed, and grip strength. Additionally, it stimulated an elevation in gut probiotic count and induced alterations in microbial metabolite expression levels as well as corresponding metabolic pathways.CONCLUSIONSThe findings suggest a potential link between changes in the gut microbiota and frailty in older adults. Prebiotics have the potential to modify the gut microbiota and metabolome, resulting in improved frailty status and prevention of its occurrence.TRIAL REGISTRATIONClinicalTrials.gov NCT03995342.
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Idoso Fragilizado , Fragilidade , Microbioma Gastrointestinal , Prebióticos , Humanos , Prebióticos/administração & dosagem , Idoso , Masculino , Método Duplo-Cego , Feminino , Idoso de 80 Anos ou mais , Vida Independente , Oligossacarídeos/administração & dosagem , Inulina/administração & dosagem , Estudos TransversaisRESUMO
The efficiency of silicon solar cells is still lower than theoretical values, partly due to their inability to utilize the ultraviolet and infrared portions of the solar spectrum. Herein, a novel method using a KCa2Mg2(VO4)3 phosphor with a down-shift effect to improve the photovoltaic performance of silicon solar cells and enhance the utilization of UV light in standard p-type silicon solar cells is proposed. The synthesized phosphors were mixed with an ethylene vinyl acetate (EVA) copolymer and pressed into a film, which was subsequently encapsulated in monocrystalline silicon solar cells. The results show that the addition of this film notably enhanced the photovoltaic performance of the silicon solar cells; the current density was increased by 2.89% (from 33.20 to 34.16 mA cm-2), and the photovoltaic conversion efficiency was improved by 5.69% (from 15.11% to 15.97%) at the optimal concentration compared to bare cells.
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Herein, we synthesized and characterized gadolinium-based hyperbranched polymers, POADGd and PODGd, through RAFT polymerization as magnetic resonance imaging (MRI) contrast agents for detecting fibrosis. POADGd and PODGd contain biocompatible short-chain OEGMA to prolong blood circulation, and they can be decomposed in response to ROS after MRI examination to prevent potential accumulation. The relaxivities of POADGd and PODGd are 9.81 mM-1 s-1 and 9.58 mM-1 s-1 respectively, which are significantly higher than that of DTPA-Gd, a clinically used agent (3.74 mM-1 s-1). In comparison with PODGd, POADGd can specifically target allysine in fibrosis tissues through its oxyamine groups. Therefore, it displays a sharp spatial resolution and a high signal-to-noise ratio in the liver and lung fibrosis tissue at a field strength of 3.0 T or 7.0 T, and the morphology of these fibrosis tissues is accurately delineated. Our MRI diagnosis results based on POADGd are highly aligned with those from pathological examinations, while MRI diagnosis could avoid invasive biopsy. In addition, POADGd shows excellent biosafety and low toxicity. Therefore, POADGd could be applied to non-invasively and accurately diagnose liver and lung fibrosis diseases.
Assuntos
Meios de Contraste , Gadolínio , Imageamento por Ressonância Magnética , Polímeros , Imageamento por Ressonância Magnética/métodos , Animais , Meios de Contraste/química , Polímeros/química , Gadolínio/química , Gadolínio/administração & dosagem , Humanos , Fibrose , Fibrose Pulmonar/diagnóstico por imagem , Camundongos , Cirrose Hepática/diagnóstico por imagem , Masculino , Fígado/diagnóstico por imagem , Fígado/metabolismo , Fígado/patologiaRESUMO
INTRODUCTION: Cisplatin-based chemotherapy is one of the fundamental therapeutic modalities for gastric cancer (GC). Chemoresistance to cisplatin is a great clinical challenge, and its underlying mechanisms remain poorly understood. Circular RNAs (circRNAs) are involved in the pathophysiology of multiple human malignancies. METHODS: High-throughput sequencing was performed to determine the differentially expressed profile of circRNA in GC tissues and cisplatin-resistant GC cells. Quantitative real-time polymerase chain reaction and Fluorescence in situ hybridization was utilized to confirm the dysregulation of circ_0008315 in GC tissues. To evaluate the prognostic significance of circ_0008315 in GC, we used Kaplan-Meier plot. The self-renewal ability of drug-resistant GC cell was verified through tumor sphere formation assay. GC organoids were constructed to simulate the tumor microenvironment and verified the function of circ_0008315 in cisplatin resistance of gastric cancer. In vivo evaluation was conducted using patient-derived xenograft models. Dual-luciferase reporter gene, RNA immunoprecipitation and miRNA pull-down assays were employed to investigate the molecular mechanisms of circ_0008315 in GC. RESULTS: We revealed that a novel circRNA hsa_circ_0008315 was upregulated in GC and cisplatin-resistant GC cells. Elevated circ_0008315 was also observed in cisplatin-resistant GC organoid model. High circ_0008315 expression predicted unfavorable survival outcome in GC patients. Downregulation of circ_0008315 expression inhibited proliferation, mobility, and epithelial-mesenchymal transition of GC cells in vitro and in vivo. Reducing circ_0008315 expression in cisplatin-resistant GC organoid model reversed cisplatin resistance. Mechanistically, circ_0008315 modulated the stem cell properties of GC through the miR-3666/CPEB4 signaling pathway, thereby promoting cisplatin resistance and GC malignant progression. Furthermore, we developed PLGA-PEG nanoparticles targeting circ_0008315, and the nanoparticles could effectively inhibit GC proliferation and cisplatin resistance. CONCLUSION: Circ_0008315 exacerbates GC progression and cisplatin resistance, and can be used as a prognostic predictor. Circ_0008315 may function as a promising nanotherapeutic target for GC treatment.