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1.
Artigo em Inglês | MEDLINE | ID: mdl-38954330

RESUMO

Animal farming wastewater is one of the most important sources of ammonia nitrogen (NH4+-N) emissions. Electro-oxidation can be a viable solution for removing NH4+-N in wastewater. Compared with other treatment methods, electro-oxidation has the advantages of i) high removal efficiency, ii) smaller size of treatment facilities, and iii) complete removal of contaminant. In this study, a previously prepared DSA (W, Ti-doped IrO2) was used for electro-oxidation of synthetic mariculture and livestock wastewater. The DSA was tested for chlorine evolution reaction (CER) activity, and the reaction kinetics was investigated. CER current efficiency reaches 60-80% in mariculture wastewater and less than 20% in livestock wastewater. In the absence of NH4+-N, the generation of active chlorine follows zero-order kinetics and its consumption follows first-order kinetics, with cathodic reduction being its main consumption pathway, rather than escape or conversion to ClO3-. Cyclic voltammetry experiments show that NH4+-N in the form of NH3 can be oxidized directly on the anode surface. In addition, the generated active chlorine combines with NH4+-N at a fast rate near the anode, rather than in the bulk solution. In electrolysis experiments, the NH4+-N removal rate in synthetic mariculture wastewater (30-40 mg/L NH4+-N) and livestock wastewater (~ 450 mg/L NH4+-N) is 112.9 g NH4+-N/(m2·d) and 186.5 g NH4+-N/(m2·d), respectively, which is much more efficient than biological treatment. The specific energy consumption (SEC) in synthetic mariculture wastewater is 31.5 kWh/kg NH4+-N, comparable to other modified electro-catalysts reported in the literature. However, in synthetic livestock wastewater, the SEC is as high as 260 kWh/kg NH4+-N, mainly due to the suppression of active chlorine generation by HCO3- and the generation of NO3- as a by-product. Therefore, we conclude that electro-oxidation is suitable for mariculture wastewater treatment, but is not recommended for livestock wastewater. Electrolysis prior to urea hydrolysis may enhance the treatment efficiency in livestock wastewater.

2.
Int J Biol Macromol ; : 133361, 2024 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-38960245

RESUMO

Diabetic wound healing poses a substantial challenge owing to bacterial infections, insufficient angiogenesis, and excessive exudates. Currently, most of the clinical dressings used for diabetic wounds are still conventional dressings such as gauze. In this study, a three-layer Janus dressing was developed via continuous electrostatic spinning. The top-layer was composed of polylactic acid-glycolic acid and hydroxyapatite doped with silver ions and silicate. The hydrophobic top-layer prevented the adhesion of foreign bacteria. The mid-layer was composed of polyethylene glycol, polylactic acid-glycolic acid and hydroxyapatite doped with silver ions and silicate facilitated exudate absorption and bioactive ion release. The modified sub-layer containing polylactic acid-glycolic acid, hydroxyapatite doped with silver ions and silicate and sodium alginate microspheres enabled both the transport of wound exudate from the wound bed to dressing and the backflow of bioactive silver ions and silicate to the wound bed, thereby reducing infection and stimulating angiogenesis. Through in vivo and in vivo experiments, the Janus dressing showed to have antimicrobial, angiogenic, and exudate-control properties that accelerate healing in diabetic wounds. As a novel dressing, the multifunctional, self-pumping Janus wound dressing with bi-directional biofluidic transport offers a new approach to diabetic wound healing.

3.
Cancer Lett ; 597: 217043, 2024 Jun 12.
Artigo em Inglês | MEDLINE | ID: mdl-38876386

RESUMO

HER2-positive cancer is a prevalent subtype of malignancy with poor prognosis, yet current targeted therapies, like Trastuzumab and pyrotinib, have resulted in remission in patients with HER2-positive cancer. This study provides a novel approach for immunotherapy based on a hydroxyapatite (HA) gene delivery system producing a bispecific antibody for HER2-positive cancer treatment. An HA nanocarrier has been synthesized by the classical hydrothermal method. Particularly, the HA-nanoneedle system was able to mediate stable gene expression of minicircle DNA (MC) encoding a humanized anti-CD3/anti-HER2 bispecific antibody (BsAbHER2) in vivo. The produced BsAbs exhibited a potent killing effect not only in HER2-positive cancer cells but also in patient-derived organoids in vitro. This HA-nanoneedle gene delivery system features simple large-scale preparation and clinical applicability. Hence, the HA-nanoneedle gene delivery system combined with minicircle DNA vector encoding BsAbHER2 reported here provides a potential immunotherapy strategy for HER2-positive tumors.

4.
Poult Sci ; 103(8): 103877, 2024 May 17.
Artigo em Inglês | MEDLINE | ID: mdl-38843563

RESUMO

This study aims to provide new insight on the association between the development of wooden breast myopathy and mitochondrial and glycolytic activity under oxidative stress. Myopathic muscle had higher oxidative stress together with altered glycolytic metabolism and tricarboxylic acid (TCA) cycle. This was evidenced by significantly elevated antioxidant enzyme activities (catalase, superoxide dismutase, and glutathione peroxidase), decreased citrate synthase activity and postmortem glycolytic potential with increasing wooden breast severity. In addition, affected muscles also exhibited higher initial and ultimate pH values as well as reduced total glucose and lactate contents. Citrate synthase activity was negatively correlated to antioxidant enzyme activities. Taken together, we propose that the development of the wooden breast lesion is a chronic process that may be related to the failure of muscle fibers to defend against the excessively generated oxidative products promoted by mitochondrial damage accompanied by impaired TCA cycle. Furthermore, there was a positive correlation between citrate synthase activity and glycolytic potential, which suggests that the wooden breast condition is linked to the overall altered energy metabolism of the muscle, including the oxidative phosphorylation and glycolytic pathways.

5.
Oncol Res ; 32(6): 1129-1139, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38827325

RESUMO

Circular RNAs (circRNAs) have been recognized as pivotal regulators in tumorigenesis, yet the biological functions as well as molecular mechanisms of the majority of circRNAs in hepatocellular carcinoma (HCC) remain elusive. We sought to unveil the expression profile and biological role of circMYBL2 in HCC. Initial microarray analyses were conducted to probe the expression profile of circMYBL2 in HCC cells, and qRT‒PCR analysis was then performed in HCC cell lines and tissues, revealing significant upregulation of circMYBL2. Subsequent experiments were conducted to evaluate the biological function of circMYBL2 in HCC progression. Furthermore, bioinformatics analysis, qRT‒PCR analysis, luciferase reporter assays, and western blot analysis were employed to investigate the interplay among circMYBL2, miR-1205, and E2F1. CircMYBL2 was found to exhibit marked upregulation in tumor tissues as well as HCC cell lines. Elevated expression of circMYBL2 increased the proliferation and migration of HCC cells, whereas circMYBL2 knockdown elicited contrasting effects. Mechanistically, our results indicated that circMYBL2 promoted E2F1 expression and facilitated HCC progression by sponging miR-1205. Our findings revealed that circMYBL2 contributed to HCC progression through the circMYBL2/miR-1205/E2F1 axis, suggesting the potential of circMYBL2 as a novel target for HCC treatment or a prognostic biomarker for HCC.


Assuntos
Carcinoma Hepatocelular , Movimento Celular , Proliferação de Células , Progressão da Doença , Fator de Transcrição E2F1 , Regulação Neoplásica da Expressão Gênica , Neoplasias Hepáticas , MicroRNAs , RNA Circular , Humanos , Carcinoma Hepatocelular/patologia , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/metabolismo , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/metabolismo , Fator de Transcrição E2F1/genética , Fator de Transcrição E2F1/metabolismo , RNA Circular/genética , Proliferação de Células/genética , Linhagem Celular Tumoral , MicroRNAs/genética , Movimento Celular/genética , Camundongos , Prognóstico
6.
Sci Rep ; 14(1): 12800, 2024 06 04.
Artigo em Inglês | MEDLINE | ID: mdl-38834591

RESUMO

This study aims to observe the hemostatic and anti-inflammatory effects of intravenous administration of tranexamic acid (TXA) in dual segment posterior lumbar interbody fusion (PLIF). The data of 53 patients with lumbar disease treated with double-segment PLIF were included in this study. The observation group was received a single-dose intravenous of TXA (1 g/100 mL) 15 min before skin incision after general anesthesia. The control group was not received TXA. The observation indicators included postoperative activated partial prothrombin time (APTT), thrombin time (PT), thrombin time (TT), fibrinogen (FIB), platelets (PLT), and postoperative deep vein thrombosis in the lower limbs, surgical time, intraoperative bleeding volume, postoperative drainage volume, transfusion rate, postoperative hospital stay, red blood cell (RBC), hemoglobin (HB), hematocrit (HCT), C-reactive protein (CRP), and erythrocyte sedimentation rate (ESR) on the 1st, 4th, 7th, and last tested day after surgery. All patients successfully completed the operation, and there was no deep vein thrombosis after operation. There was no statistically significant difference in postoperative APTT, PT, TT, FIB, PLT, surgical time, and postoperative hospital stay between the two groups (p > 0.05). The intraoperative bleeding volume, postoperative drainage volume, and transfusion rate in the observation group were lower than those in the control group, and the differences were statistically significant (p < 0.05). There was no statistically significant difference in RBC, HB, HCT, CRP, and ESR between the two groups on the 1st, 4th, 7th, and last tested day after surgery (p > 0.05). Intravenous administration of TXA in dual segment PLIF does not affect coagulation function and can reduce bleeding volume, postoperative drainage volume, and transfusion rate. Moreover, it does not affect the postoperative inflammatory response.


Assuntos
Fusão Vertebral , Ácido Tranexâmico , Humanos , Ácido Tranexâmico/administração & dosagem , Feminino , Masculino , Pessoa de Meia-Idade , Fusão Vertebral/métodos , Fusão Vertebral/efeitos adversos , Estudos de Casos e Controles , Idoso , Vértebras Lombares/cirurgia , Administração Intravenosa , Anti-Inflamatórios/administração & dosagem , Anti-Inflamatórios/farmacologia , Hemostáticos/administração & dosagem , Hemostáticos/farmacologia , Adulto , Perda Sanguínea Cirúrgica/prevenção & controle , Antifibrinolíticos/administração & dosagem , Antifibrinolíticos/uso terapêutico
7.
Curr Biol ; 2024 Jun 17.
Artigo em Inglês | MEDLINE | ID: mdl-38906143

RESUMO

Protected areas conserve biodiversity and ecosystem functions but might impede local economic growth. Understanding the global patterns and predictors of different relationships between protected area effectiveness and neighboring community economic growth can inform better implementation of the Kunming-Montreal Global Biodiversity Framework. We assessed 10,143 protected areas globally with matched samples to address the non-random location of protected areas. Our results show that protected areas resist human-induced land cover changes and do not limit nightlight increases in neighboring settlements. This result is robust, using different matching techniques, parameter settings, and selection of covariates. We identify four types of relationships between land cover changes and nightlight changes for each protected area: "synergy," "retreat," and two tradeoff relationships. About half of the protected areas (47.5%) retain their natural land cover and do so despite an increase of nightlights in the neighboring communities. This synergy relationship is the most common globally but varies between biomes and continents. Synergy is less frequent in the Amazon, Southeast Asia, and some developing areas, where most biodiversity resides and which suffer more from poverty. Smaller protected areas and those with better access to cities, moderate road density, and better baseline economic conditions have a higher probability of reaching synergy. Our results are promising, as the expansion of protected areas and increased species protection will rely more on conserving the human-modified landscape with smaller protected areas. Future interventions should address local development and biodiversity conservation together to achieve more co-benefits.

8.
Curr Biol ; 34(9): R379-R387, 2024 05 06.
Artigo em Inglês | MEDLINE | ID: mdl-38714169

RESUMO

For decades, China has implemented restoration programs on a large scale, thanks to its capacity to set policy and mobilize funding resources. An understanding of China's restoration achievements and remaining challenges will help to guide future efforts to restore 30% of its diverse ecosystems under the Kunming-Montreal Global Biodiversity Framework. Here we summarize the major transitions in China's approach to ecosystem restoration since the 1970s, with a focus on the underlying motivations for restoration, approaches to ecosystem management, and financing mechanisms. Whereas China's restoration efforts were predominantly guided by the delivery of certain ecosystem functions and services in earlier decades, more recently it has come to emphasize the restoration of biodiversity and ecosystem integrity. Accordingly, the focal ecosystems, approaches, and financing mechanisms of restoration have also been considerably diversified. This evolution is largely guided by the accumulation of scientific evidence and past experiences. We highlight the key challenges facing China's restoration efforts and propose future directions to improve restoration effectiveness, with regard to goal setting, monitoring, stakeholder involvement, adaptive management, resilience under climate change, and financing.


Assuntos
Biodiversidade , Mudança Climática , Conservação dos Recursos Naturais , Ecossistema , China , Conservação dos Recursos Naturais/métodos , Recuperação e Remediação Ambiental/métodos
9.
Sci Rep ; 14(1): 10997, 2024 05 14.
Artigo em Inglês | MEDLINE | ID: mdl-38744855

RESUMO

Intravenous application of tranexamic acid (TXA) in posterior lumbar interbody fusion (PLIF) can effectively reduce blood loss without affecting coagulation function. However, it has not been reported whether preoperative use of anticoagulants may affect the efficacy of TXA in PLIF. The purpose of this study is to observe the effect of preoperative use of anticoagulants on coagulation indicators and blood loss after PLIF receiving intravenous unit dose TXA. A retrospective analysis was conducted on data from 53 patients with PLIF between 2020.11 and 2022.9, who received intravenous application of a unit dose of TXA (1 g/100 mL) 15 min before the skin incision after general anesthesia. Those who used anticoagulants within one week before surgery were recorded as the observation group, while those who did not use anticoagulants were recorded as the control group. The main observation indicators include surgical time, intraoperative blood loss, postoperative drainage volume, blood transfusion, and red blood cell (RBC), hemoglobin (HB), and hematocrit (HCT) measured on the 1st, 4th, 7th, and last-test postoperative days. Secondary observation indicators included postoperative incision healing, deep vein thrombosis of lower limbs, postoperative hospital stay, and activated partial thrombin time (APTT), prothrombin time (PT), thrombin time (TT), fibrinogen (FIB), and platelets (PLT) on the 1st and 4th days after surgery. The operation was successfully completed in both groups, the incision healed well after operation, and no lower limb deep vein thrombosis occurred. There was no significant difference in surgical time, intraoperative blood loss, postoperative drainage volume, and blood transfusion between the two groups (p > 0.05). There was no significant difference in the RBC, HB, and HCT measured on the 1st, 4th, 7th, and last-test postoperative days between the two groups (p > 0.05). There was no statistically significant difference in APTT, PT, TT, FIB and PLT between the two groups on the 1st and 4th postoperative days (p > 0.05). There was no significant difference in postoperative hospital stay between the two groups (p > 0.05). The use of anticoagulants within one week before surgery does not affect the hemostatic effect of intravenous unit dose TXA in PLIF.


Assuntos
Anticoagulantes , Perda Sanguínea Cirúrgica , Ácido Tranexâmico , Humanos , Ácido Tranexâmico/administração & dosagem , Ácido Tranexâmico/uso terapêutico , Feminino , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Estudos de Casos e Controles , Anticoagulantes/administração & dosagem , Anticoagulantes/uso terapêutico , Anticoagulantes/farmacologia , Perda Sanguínea Cirúrgica/prevenção & controle , Idoso , Administração Intravenosa , Fusão Vertebral/métodos , Cuidados Pré-Operatórios/métodos , Antifibrinolíticos/administração & dosagem , Antifibrinolíticos/uso terapêutico , Coagulação Sanguínea/efeitos dos fármacos
10.
Small Methods ; : e2301506, 2024 May 16.
Artigo em Inglês | MEDLINE | ID: mdl-38752313

RESUMO

A cost-effective and scalable approach for the fabrication of heterostructured microsupercapacitors (MSCs) employing screen-printing followed by sequential electrochemical and microspray deposition techniques has been demonstrated. The microsupercapacitor electrode (MSC) that composed of stacked layers of mesoporous carbon, polyaniline (PANI), and MXene hold significant promise for wearable electronics. By adjusting the deposition and spray cycles, the MSC can be readily coated with PANI and MXene. The sequentially stacked two layers of MXene and PANI on the mesoporous carbon spheres (PMPM-MSC) yielded a specific capacitance of 1003 mF cm-2 at 0.5 mA cm-2, surpassing the performance of PANI/mesoporous carbon electrode by 1.6 times (771 mF cm-2). After 10,000 cycles of charge and discharge, PMPM-MSCs retained more than 86% of their initial capacitance. In-situ Raman spectroscopy confirmed the synergistic effects between MXene and PANI within the heterostructured stacked PMPM-MSC electrodes, including enhanced electronic conductivity and improved electrolyte ion dissociation, which aligned with the electrochemical measurement results, such as fast charge/discharge rates and reduced internal and mass transport resistance. This study demonstrates the potential of screen-printed heterostructured MSC stacks with maximum electrochemical synergy for portable and wearable energy storage devices.

11.
Front Med (Lausanne) ; 11: 1358046, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38716420

RESUMO

Purpose: To evaluate the effect of 0.01% atropine combined with orthokeratology (OK) lens on axial elongation in schoolchildren with myopia. Methods: Sixty children aged 8-12 years with spherical equivalent refraction (SER) from -1.00D to -4.00D in both eyes were enrolled in this randomized, double-masked, placebo-controlled, cross-over trial. Children who had been wearing OK lenses for 2 months were randomly assigned into combination group (combination of OK lens and 0.01% atropine) for 1 year followed by control group (combination of OK lens and placebo) for another 1 year or vice versa. This trial was registered in the Chinese Clinical Trial Registry (Number: ChiCTR2000033904, 16/06/2020). The primary outcome was changes in axial length (AL). Data of right eyes were analyzed. Results: There were statistically significant differences in the changes in AL between combination and control groups after generalized estimating equation model adjusting for age and baseline SER (p = 0.001). The mean axial elongation difference between combination and control groups was 0.10 mm in the first year (0.10 ± 0.13 mm vs. 0.20 ±0.15 mm; p = 0.01), and 0.09 mm in the second year (0.22 ± 0.10 mm vs. 0.13 ± 0.14 mm; p = 0.01), respectively. The mean axial elongation difference of two groups in the first year was similar to that in the second year during the cross-over treatment. Conclusion: In central Mainland China in myopic children, the treatment of combination therapy is more effective than single OK lens in controlling axial elongation.

12.
Nanoscale ; 16(21): 10448-10457, 2024 May 30.
Artigo em Inglês | MEDLINE | ID: mdl-38752569

RESUMO

With continuous advances in medical technology, non-invasive embolization has emerged as a minimally invasive treatment, offering new possibilities in cancer therapy. Fluorescent labeling can achieve visualization of therapeutic agents in vivo, providing technical support for precise treatment. This paper introduces a novel in situ non-invasive embolization composite material, Au NPs@(mPEG-PLGTs), created through the electrostatic combination of L-cysteine-modified gold nanoparticles (Au NPs) and methoxy polyethylene glycol amine-poly[(L-glutamic acid)-(L-tyrosine)] (mPEG-PLGTs). Experiments were undertaken to confirm the biocompatibility, degradability, stability and performance of this tumor therapy. The research results demonstrated a reduction in tumor size as early as the fifth day after the initial injection, with a significant 90% shrinkage in tumor volume observed after a 20-day treatment cycle, successfully inhibiting tumor growth and exhibiting excellent anti-tumor effects. Utilizing near-infrared in vivo imaging, Au NPs@(mPEG-PLGTs) displayed effective fluorescence tracking within the bodies of nude BALB-c mice. This study provides a novel direction for the further development and innovation of in situ non-invasive embolization in the field, highlighting its potential for rapid, significant therapeutic effects with minimal invasiveness and enhanced safety.


Assuntos
Ouro , Nanopartículas Metálicas , Camundongos Endogâmicos BALB C , Camundongos Nus , Polietilenoglicóis , Ouro/química , Animais , Nanopartículas Metálicas/química , Nanopartículas Metálicas/uso terapêutico , Camundongos , Polietilenoglicóis/química , Linhagem Celular Tumoral , Humanos , Concentração de Íons de Hidrogênio , Embolização Terapêutica , Ácido Poliglutâmico/química , Ácido Poliglutâmico/análogos & derivados
13.
Front Immunol ; 15: 1382520, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38698857

RESUMO

Background: The Y-box-binding proteins (YBX) act as a multifunctional role in tumor progression, metastasis, drug resistance by regulating the transcription and translation process. Nevertheless, their functions in a pan-cancer setting remain unclear. Methods: This study examined the clinical features expression, prognostic value, mutations, along with methylation patterns of three genes from the YBX family (YBX1, YBX2, and YBX3) in 28 different types of cancer. Data used for analysis were obtained from Cancer Genome Atlas (TCGA) and Genotype-Tissue Expression (GTEx) databases. A novel YBXs score was created using the ssGSEA algorithm for the single sample gene set enrichment analysis. Additionally, we explored the YBXs score's association with the tumor microenvironment (TME), response to various treatments, and drug resistance. Results: Our analysis revealed that YBX family genes contribute to tumor progression and are indicative of prognosis in diverse cancer types. We determined that the YBXs score correlates significantly with numerous malignant pathways in pan-cancer. Moreover, this score is also linked with multiple immune-related characteristics. The YBXs score proved to be an effective predictor for the efficacy of a range of treatments in various cancers, particularly immunotherapy. To summarize, the involvement of YBX family genes is vital in pan-cancer and exhibits a significant association with TME. An elevated YBXs score indicates an immune-activated TME and responsiveness to diverse therapies, highlighting its potential as a biomarker in individuals with tumors. Finally, experimental validations were conducted to explore that YBX2 might be a potential biomarker in liver cancer. Conclusion: The creation of YBXs score in our study offered new insights into further studies. Besides, YBX2 was found as a potential therapeutic target, significantly contributing to the improvement of HCC diagnosis and treatment strategies.


Assuntos
Biomarcadores Tumorais , Regulação Neoplásica da Expressão Gênica , Neoplasias Hepáticas , Microambiente Tumoral , Humanos , Biomarcadores Tumorais/genética , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/diagnóstico , Microambiente Tumoral/genética , Microambiente Tumoral/imunologia , Prognóstico , Proteína 1 de Ligação a Y-Box/genética , Proteína 1 de Ligação a Y-Box/metabolismo , Mutação , Resistencia a Medicamentos Antineoplásicos/genética , Perfilação da Expressão Gênica , Linhagem Celular Tumoral , Metilação de DNA
14.
J Food Sci ; 89(5): 2921-2932, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38591324

RESUMO

It is crucial to clarify the stability of Kombucha in the manufacture and storage stages due to the extensive study on the fermented products of Kombucha and the increase in the use of bacterial cellulose (BC). This study aimed to evaluate the stability of Kombucha in different manufacturing and storage temperatures within a certain time period. The stability of microorganisms and BC in Kombucha was investigated through regular replacement with the tea media at 28 and 25°C for manufacture, and the storage temperature of Kombucha was at 25, 4, and -20°C. Morphological observations of the BC in Kombucha ended at 28 and 25°C for manufacture and storage were performed using atomic force microscopy (AFM) before inoculation. The viable cell counts and AFM results showed that the stability of Kombucha during manufacture was better at 28°C than at 25°C, with higher microbial viability and BC productivity in the former at the time of manufacture, whereas 25°C was more favorable for the stability of Kombucha during storage. At the same temperature of 25°C, the manufacturing practice improved the microbial viability and BC stability compared with storage; the pH value of Kombucha was lower, and the dry weight of BC was higher during storage compared with manufacture. The maximum BC water holding capacity (97.16%) was maintained by storage at 4°C on day 63, and the maximum BC swelling rate (56.92%) was observed after storage at -20°C on day 7. The research was conducted to provide reference information for applying Kombucha and its BC in food and development in other industries.


Assuntos
Celulose , Fermentação , Temperatura , Celulose/química , Armazenamento de Alimentos/métodos , Microbiologia de Alimentos , Chá de Kombucha/microbiologia , Concentração de Íons de Hidrogênio , Viabilidade Microbiana , Acetobacteraceae/metabolismo , Manipulação de Alimentos/métodos
15.
Brain Behav ; 14(5): e3412, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38664915

RESUMO

PURPOSE: Obsessive-compulsive disorder (OCD) is a complex psychiatric disorder. Genetic and broad environmental factors are common risk factors for OCD. The purpose of this study is to explore the molecular mechanism of OCD and to find new molecular targets for the diagnosis and management of OCD. METHODS: All data were downloaded from public dataset. Key modules and candidate key mRNAs were identified based on weighted gene co-expression network analysis (WGCNA). The "limma" R package was used for differential expression analysis of mRNAs. Subsequently, functional enrichment analysis of differentially expressed mRNAs (DEmRNAs) was also carried out. In addition, a diagnostic model was constructed. Finally, the infiltration level of immune cells in OCD and its correlation with multicentric key DEmRNAs were analyzed. RESULTS: Green and red modules were selected as the hub modules. A total of 447 mRNAs were considered candidate key mRNAs according to GS > 0.2 and MM > 0.3. A total of 26 DEmRNAs in the same direction were identified in the GSE60190 and GSE78104 datasets. A total of 26 DEmRNAs were intersected with candidate key mRNAs in WGCNA to obtain 10 intersection DEmRNAs (HSPB1, ITPK1, CBX7, PPP1R10, TAOK1, PISD, MKNK2, RWDD1, PPA1, and RELN). However, only four DEmRNAs (HSPB1, TAOK1, MKNK2, and PPA1) predicted related drugs. Subsequently, receiver operating characteristic analysis shows that the diagnostic model has high diagnostic value. Moreover, six multicentric key DEmRNAs (SNRPF, SNRNP70, PRPF8, NOP56, EPRS, and CCT2) were screened by UpSet package. Finally, six multicentric key DEmRNAs were found to be associated with immune cells. CONCLUSION: The key molecules obtained in this study lay a foundation for further research on the molecular mechanism of OCD.


Assuntos
Redes Reguladoras de Genes , Transtorno Obsessivo-Compulsivo , RNA Mensageiro , Transdução de Sinais , Humanos , Transtorno Obsessivo-Compulsivo/genética , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Transdução de Sinais/genética , Perfilação da Expressão Gênica
16.
J Hepatol ; 80(6): 892-903, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38458319

RESUMO

BACKGROUND & AIMS: Cholangiocarcinoma (CCA) is a poorly immunogenic malignancy associated with limited survival. Syngeneic immunocompetent mouse models of CCA are an essential tool to elucidate the tumor immune microenvironment (TIME), understand mechanisms of tumor immune evasion, and test novel immunotherapeutic strategies. The scope of this study was to develop and characterize immunocompetent CCA models with distinct genetic drivers, and correlate tumor genomics, immunobiology, and therapeutic response. METHODS: A multifaceted approach including scRNA-seq, CITE-seq, whole exome and bulk RNA sequencing was employed. FDA-approved PD-1/PD-L1 antibodies were tested in humanized PD-1/PD-L1 mice (HuPD-H1). RESULTS: A genetic mouse model of intrahepatic CCA (iCCA) driven by intrabiliary transduction of Fbxw7ΔF/Akt that mimics human iCCA was generated. From the Fbxw7ΔF/Akt tumors, a murine cell line (FAC) and syngeneic model with genetic and phenotypic characteristics of human iCCA were developed. Established SB1 (YAPS127A/Akt) and KPPC (KrasG12Dp53L/L) models were compared to the FAC model. Although the models had transcriptomic similarities, they had substantial differences as well. Mutation patterns of FAC, SB1, and KPPC cells matched different mutational signatures in Western and Japanese CCA patient cohorts. KPPC tumors had a high tumor mutation burden. FAC tumors had a T cell-infiltrated TIME, while SB1 tumors had a preponderance of suppressive myeloid cells. FAC, SB1, and KPPC tumors matched different immune signatures in human iCCA cohorts. Moreover, FAC, SB1, and KPPC tumor-bearing HuPD-H1 mice displayed differential responses to nivolumab or durvalumab. CONCLUSIONS: Syngeneic iCCA models display a correlation between tumor genotype and TIME phenotype, with differential responses to FDA-approved immunotherapies. This study underscores the importance of leveraging multiple preclinical models to understand responses to immunotherapy in different genetic subsets of human CCA. IMPACT AND IMPLICATIONS: Understanding the relationship between tumor genotype and the phenotype of the immune microenvironment is an unmet need in cholangiocarcinoma (CCA). Herein, we use syngeneic murine models of intrahepatic CCA with different genetic drivers to demonstrate a correlation between tumor genotype and immune microenvironment phenotype in murine models, which is associated with differential responses to FDA-approved immunotherapies. This information will help guide other preclinical studies. Additionally, it emphasizes that immune checkpoint inhibition in patients with CCA is not a "one-size-fits-all" approach. Our observations suggest that, as for targeted therapies, patients should be stratified and selected for treatment according to their tumor genetics.


Assuntos
Neoplasias dos Ductos Biliares , Colangiocarcinoma , Modelos Animais de Doenças , Microambiente Tumoral , Animais , Colangiocarcinoma/imunologia , Colangiocarcinoma/genética , Camundongos , Microambiente Tumoral/imunologia , Humanos , Neoplasias dos Ductos Biliares/imunologia , Neoplasias dos Ductos Biliares/genética , Proteína 7 com Repetições F-Box-WD/genética , Linhagem Celular Tumoral
17.
Zhen Ci Yan Jiu ; 49(3): 274-282, 2024 Mar 25.
Artigo em Inglês, Chinês | MEDLINE | ID: mdl-38500324

RESUMO

OBJECTIVES: To observe the effect of electroacupuncture (EA) on the changes of behavior and hippocampal inflammatory factors in rats with chronic fatigue syndrome (CFS), so as to explore its possible mechanisms in the treatment of CFS. METHODS: Twenty-seven SD rats were randomly divided into control, model and electroacupuncture (EA) groups (n=9 rats in each group). The CFS model was established by multi-factor compound stress stimulation method. Rats of the EA group received EA (10 Hz) at "Shenting" (GV24) penetrating "Baihui" (GV20), "Dazhui" (GV14) for 15 min, twice a day for 14 days. The general conditions, Morris water maze test, open field test, the exhausted running platform were conducted for determining the rats' locomotor and learning-memory activities. H.E. staining was used to observe the morphological structure of neurons in hippocampal CA1 region. The contents of interleukin (IL)-10, IL-17 and transforming growth factor (TGF) ß1 in hippocampus and serum of rats were detected by ELISA, and the positive expressions of IL-10, IL-17 and TGF-ß1 in hippocampal CA1 region were detected by immunofluorescence staining. RESULTS: Compared with the control group, the score of general condition was increased (P<0.05), the escape latency was prolonged (P<0.05), the number of crossing the original platform was decreased (P<0.05), the numbers of crossing the grid and entering the central area were increased (P<0.05), and the exhaustive treadmill time was shortened (P<0.05) in the model group. The contents of IL-10 in the hippocampus and serum were decreased (P<0.05), while IL-17 and TGF-ß1 contents were increased (P<0.05). The immunofluorescence intensity of IL-10 in the hippocampus was decreased (P<0.05), while the intensity of IL-17 and TGF-ß1 were increased (P<0.05). After treatment, compared with the model group, the score of general condition was decreased (P<0.05), the escape latency was shortened (P<0.05), the number of crossing the original platform was increased (P<0.05), the numbers of crossing the grid and entering the central area were decreased (P<0.05), and the exhaustive treadmill time was prolonged (P<0.05) in the EA group. The contents of IL-10 in the hippocampus and serum were increased (P<0.05), while IL-17 and TGF-ß1 levels were decreased (P<0.05). The immunofluorescence intensity of IL-10 in the hippocampus was increased (P<0.05), while the intensity of IL-17 and TGF-ß1 were decreased (P<0.05). H.E. staining showed that in the model group, the number of neurons in the hippocampus decreased, with disordered arrangement and loose structure, and a small numbers of neuronal nuclei were missing. The degree of tissue damage of the EA group was milder than that of the model group. CONCLUSIONS: EA can alleviate fatigue and spatial learning and memory impairment in CFS rats, which may be related to the regulation of peripheral and central inflammation.


Assuntos
Eletroacupuntura , Síndrome de Fadiga Crônica , Ratos , Animais , Ratos Sprague-Dawley , Interleucina-10 , Síndrome de Fadiga Crônica/terapia , Interleucina-17/genética , Fator de Crescimento Transformador beta1/genética , Hipocampo
18.
J Dent Sci ; 19(1): 130-138, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38303804

RESUMO

Background/purpose: Lymphoepithelial sialadenitis (LESA), Sjögren's syndrome (SS), and salivary MALT lymphoma are diseases characterized by lymphoepithelial lesions, and the differential diagnosis between them in the salivary glands is challenging. This study aimed to explore clinicopathological and genetic characteristics of the three diseases. Materials and methods: We retrospectively analyzed the clinical features, the histomorphology, immunohistochemistry, and genetic profiling by polymerase chain reaction (PCR) and next-generation sequencing (NGS). Results: There included 68 LESAs, 25 SSs, and 62 MALT lymphomas. Ten cases relapsed in total, and 3 of MALT lymphomas died due to high-level transformation. Immunohistochemical double staining showed FCRL4 cells co-expressed Pax-5 and Ki-67, suggesting FCRL4 cells were proliferative B-cells. The expression level of the FCRL4 was significantly higher in MALT lymphoma than LESA and SS. The detection rates of clonal IGH, IGK, and IGL gene rearrangements in MALT lymphoma with a sensitivity of 83.33%. Monoclonal immunoglobulin gene rearrangements were confirmed in five suspected patients by NGS (100%). Conclusion: FCRL4 B cells might play an important role in the formation of lymphoepithelial lesions and might be as a diagnostic positive marker of salivary MALT lymphoma. The application of multiple detection methods could significantly improve the diagnostic accuracy for MALT lymphomas from LESA and SS.

19.
Food Chem X ; 21: 101148, 2024 Mar 30.
Artigo em Inglês | MEDLINE | ID: mdl-38304043

RESUMO

Cellulase can increase the soluble dietary fiber (SDF) content in Rosa roxburghii Tratt (RRT), but the effects on polyphenol content, bioactivity, and flavor are unknown. This study analyzed the changes in SDF content, total phenolic content, antioxidant activity and flavor before and after cellulase treatment. Cellulase treatment increased the SDF and total phenolic content of RRT by 13 % (P < 0.05) and 25.68 % (P < 0.05), respectively, and increased the antioxidant activity. HS-GC-IMS identified a total of 42 volatile compounds present, and ROAV analysis revealed that the characteristic aroma compounds of RRT were mainly aldehydes, alcohols, and ethers. The electronic nose and tongue results were consistent with the HS-GC-IMS analysis, indicating the positive effect of cellulase on the quality of RRT. Cellulase treatment significantly improved the oxidative activity and flavor performance of RRT. These results of RRT, providing practical guidance for improving the flavor and product quality.

20.
Heliyon ; 10(2): e24873, 2024 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-38304779

RESUMO

Background: Warthin-like Mucoepidermoid carcinoma (MEC) is a new and rare morphological variant of MEC, with only a few case reports in the literature. The clinicopathological, molecular features and bio-behaviors of Warthin-like MEC has not been studied extensively. We reappraisal all Warthin-like MEC patients diagnosed and treated at our hospital. Methods: Patient characteristics including clinicopathological features, genetic aberrations, treatment, and prognostic information were assessed and evaluated. Results: Twenty-nine Warthin-like MEC patients were identified, 19 patients were female (65.5 %), and 10 were male (34.5 %). The patients' age varied widely from 8 to 68 years (mean 42.3 years). Genetic aberrations of MAML2 rearrangement were detected in all Warthin-like MEC patients, which suggesting this genetic event is the unique feature of Warthin-like MEC. Twenty-five patients (86.2 %) were assessed as having a low-stage disease (I/II), and four (13.8 %) as having high-clinical stage disease (III/IV). More than half of the patients (16/29) underwent only partial sialoadenectomy; 2 patients underwent extended sialoadenectomy, and 11 patients underwent extended sialoadenectomy with cervical lymph node dissection. After a median follow-up time of 73 months (5-128 months), Twenty-eight patients were alive without recurrence at the end of the follow-up period, one patient died 1 year after surgery due to lung metastasis. Conclusion: Our data suggested that most Warthin-like MEC exhibited mild clinicopathological course and less aggressive bio-behavior, and an aggressive bio-behavior seemed to be very rare. In addition, in the salivary gland, MAML2 rearrangement seems to be a unique molecular feature of salivary Warthin-like MEC.

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