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1.
Plant Commun ; : 100944, 2024 May 09.
Artigo em Inglês | MEDLINE | ID: mdl-38733080

RESUMO

The Caesalpinioideae subfamily contains many well-known trees that are important for the sustainability of the economy and human health, but the lack of genomic resources hindered the breeding and utilization of these plants. Here, we present chromosome-level reference genomes for two food and industrial trees Gleditsia sinensis (921 Mb) and Biancaea sappan (872 Mb), three shade and ornamental trees Albizia julibrissin (705 Mb), Delonix regia (580 Mb) and Acacia confusa (566 Mb), as well as two pioneer and hedgerow trees Leucaena leucocephala (1,338 Mb) and Mimosa bimucronata (641 Mb). Phylogeny inference showed that the mimosoid clade has a much higher evolution rate than the other clades of Caesalpinioideae. Macrosynteny comparison showed that the fusion and broken of an unstable chromosome was responsible for the difference in the basic chromosome number 13 and 14 for Caesalpinioideae. After the ancient whole genome duplication shared by all Caesalpinioideae species (CWGD, ∼72.0 MYA), we found two recent successive WGD events LWGD-1 (16.2-19.5 MYA) and LWGD-2 (7.1-9.5 MYA) in L. leucocephala. Then, ∼40% gene loss and genome size contraction occurred during the diploidization process in L. leucocephala. For the secondary metabolites, we identified all the gene copies involved in mimosine metabolism for these species and revealed that the abundance of mimosine biosynthesis genes in L. leucocephala largely explains its high mimosine production. Moreover, we identified all the potential genes involved in triterpenoid saponin biosynthesis in G. sinensis, which is more complete than the previous transcriptome-derived unigenes. Our analyzing results and the genomic resources will facilitate the biological studies of Caesalpinioideae and promote the utilization of valuable secondary metabolites.

2.
Environ Int ; 187: 108722, 2024 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-38733765

RESUMO

Chinese children are exposed to broad environmental risks ranging from well-known hazards, such as pesticides and heavy metals, to emerging threats including many new man-made chemicals. Although anecdotal evidence suggests that the exposure levels in Chinese children are substantially higher than those of children in developed countries, a systematic assessment is lacking. Further, while these exposures have been linked to a variety of childhood diseases, such as respiratory, endocrine, neurological, behavioral, and malignant disorders, the magnitude of the associations is often unclear. This review provides a current epidemiologic overview of commonly reported environmental contaminants and their potential impact on children's health in China. We found that despite a large volume of studies on various topics, there is a need for more high-quality research and better-coordinated regional and national data collection. Moreover, prevention of such diseases will depend not only on training of environmental health professionals and enhanced research programs, but also on public education, legislation, and networking.

3.
Methods ; 226: 164-175, 2024 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-38702021

RESUMO

Ensuring the safety and efficacy of chemical compounds is crucial in small-molecule drug development. In the later stages of drug development, toxic compounds pose a significant challenge, losing valuable resources and time. Early and accurate prediction of compound toxicity using deep learning models offers a promising solution to mitigate these risks during drug discovery. In this study, we present the development of several deep-learning models aimed at evaluating different types of compound toxicity, including acute toxicity, carcinogenicity, hERG_cardiotoxicity (the human ether-a-go-go related gene caused cardiotoxicity), hepatotoxicity, and mutagenicity. To address the inherent variations in data size, label type, and distribution across different types of toxicity, we employed diverse training strategies. Our first approach involved utilizing a graph convolutional network (GCN) regression model to predict acute toxicity, which achieved notable performance with Pearson R 0.76, 0.74, and 0.65 for intraperitoneal, intravenous, and oral administration routes, respectively. Furthermore, we trained multiple GCN binary classification models, each tailored to a specific type of toxicity. These models exhibited high area under the curve (AUC) scores, with an impressive AUC of 0.69, 0.77, 0.88, and 0.79 for predicting carcinogenicity, hERG_cardiotoxicity, mutagenicity, and hepatotoxicity, respectively. Additionally, we have used the approved drug dataset to determine the appropriate threshold value for the prediction score in model usage. We integrated these models into a virtual screening pipeline to assess their effectiveness in identifying potential low-toxicity drug candidates. Our findings indicate that this deep learning approach has the potential to significantly reduce the cost and risk associated with drug development by expediting the selection of compounds with low toxicity profiles. Therefore, the models developed in this study hold promise as critical tools for early drug candidate screening and selection.

4.
Environ Pollut ; : 124095, 2024 May 02.
Artigo em Inglês | MEDLINE | ID: mdl-38703984

RESUMO

Elevated CO2 levels and methylmercury (MeHg) pollution are important environmental issues faced across the globe. However, the impact of elevated CO2 on MeHg production and its biological utilization remains to be fully understood, particularly in realistic complex systems with biotic interactions. Here, a complete paddy wetland microcosm, namely, the rice-fish-snail co-culture system, was constructed to investigate the impacts of elevated CO2 (600 ppm) on MeHg formation, bioaccumulation, and possible health risks, in multiple environmental and biological media. The results revealed that elevated CO2 significantly increased MeHg concentrations in the overlying water, periphyton, snails and fish, by 135.5%, 66.9%, 45.5%, and 52.1%, respectively. A high MeHg concentration in periphyton, the main diet of snails and fish, was the key factor influencing the enhanced MeHg in aquatic products. Furthermore, elevated CO2 alleviated the carbon limitation in the overlying water and proliferated green algae, with subsequent changes in physico-chemical properties and nutrient concentrations in the overlying water. More algal-derived organic matter promoted an enriched abundance of Archaea-hgcA and Deltaproteobacteria-hgcA genes. This consequently increased the MeHg in the overlying water and food chain. However, MeHg concentrations in rice and soil did not increase under elevated CO2, nor did hgcA gene abundance in soil. The results reveal that elevated CO2 exacerbated the risk of MeHg intake from aquatic products in paddy wetland, indicating an intensified MeHg threat under future elevated CO2 levels.

5.
Front Oncol ; 14: 1370009, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38665957

RESUMO

Objective: Currently, there are no studies showing which neoadjuvant therapy modality can provide better prognosis for patients after pancreatic cancer surgery. This study explores the optimal neoadjuvant therapy model by comparing the survival differences between patients with non-metastatic pancreatic cancer (cT1-4N0-1M0) who received neoadjuvant chemotherapy (NACT) and neoadjuvant chemoradiotherapy (NARCT). Methods: We retrospectively analyzed the clinical data of 723 patients with cT1-4N0-1M0 pancreatic cancer who received neoadjuvant therapy before surgery from the Surveillance, Epidemiology, and End Results (SEER) database. After propensity score matching (PSM), we compared the effects of NACT and NARCT on overall survival (OS) and cancer-specific survival (CSS) in patients with non-metastatic pancreatic cancer, and then performed subgroup analyze. Finally, we used univariate and multivariate Cox regression analysis to explore potential risk factors for OS and CSS in patients with non-metastatic pancreatic cancer treated with preoperative neoadjuvant therapy. Result: Before PSM, mOS (30.0 months VS 26.0 months, P=0.122) and mCSS (30.0 months VS 26.0 months, P=0.117) were better in patients with non-metastatic pancreatic cancer treated with NACT compared with NARCT, but this was not statistically significant (P>0.05). After PSM, mOS (30.0 months VS 25.0 months, P=0.032) and mCSS (33.0 months VS 26.0 months, P=0.028) were better in patients with non-metastatic pancreatic cancer treated with NACT compared with NARCT, and this difference was statistically significant (P<0.05). Multivariate Cox regression analysis results showed that age, lymph node positivity, and NARCT were independent adverse prognostic factors for OS and CSS in patients with non-metastatic pancreatic cancer. Conclusion: The study results show that compared with NARCT, NACT is the best preoperative neoadjuvant therapy mode for patients with non-metastatic pancreatic cancer. This result still needs to be confirmed by more prospective randomized controlled trials.

6.
Front Immunol ; 15: 1309739, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38655264

RESUMO

Introduction: Macrophage-mediated inflammatory response may have crucial roles in the pathogenesis of a variety of human diseases. Growth differentiation factor 15 (GDF15) is a cytokine of the transforming growth factor-ß superfamily, with potential anti-inflammatory activities. Previous studies observed in human lungs some macrophages which expressed a high level of GDF15. Methods: In the present study, we employed multiple techniques, including immunofluorescence, flow cytometry, and single-cell RNA sequencing, in order to further clarify the identity of such GDF15high macrophages. Results: We demonstrated that macrophages derived from human peripheral blood mononuclear cells and rat bone marrow mononuclear cells by in vitro differentiation with granulocyte-macrophage colony stimulating factor contained a minor population (~1%) of GDF15high cells. GDF15high macrophages did not exhibit a typical M1 or M2 phenotype, but had a unique molecular signature as revealed by single-cell RNA sequencing. Functionally, the in vitro derived GDF15high macrophages were associated with reduced responsiveness to pro-inflammatory activation; furthermore, these GDF15high macrophages could inhibit the pro-inflammatory functions of other macrophages via a paracrine mechanism. We further confirmed that GDF15 per se was a key mediator of the anti-inflammatory effects of GDF15high macrophage. Also, we provided evidence showing that GDF15high macrophages were present in other macrophage-residing human tissues in addition to the lungs. Further scRNA-seq analysis in rat lung macrophages confirmed the presence of a GDF15high sub-population. However, these data indicated that GDF15high macrophages in the body were not a uniform population based on their molecular signatures. More importantly, as compared to the in vitro derived GDF15high macrophage, whether the tissue resident GDF15high counterpart is also associated with anti-inflammatory functions remains to be determined. We cannot exclude the possibility that the in vitro priming/induction protocol used in our study has a determinant role in inducing the anti-inflammatory phenotype in the resulting GDF15high macrophage cells. Conclusion: In summary, our results suggest that the GDF15high macrophage cells obtained by in vitro induction may represent a distinct cluster with intrinsic anti-inflammatory functions. The (patho)physiological importance of these cells in vivo warrants further investigation.


Assuntos
Diferenciação Celular , Fator 15 de Diferenciação de Crescimento , Macrófagos , Fator 15 de Diferenciação de Crescimento/metabolismo , Fator 15 de Diferenciação de Crescimento/genética , Animais , Humanos , Macrófagos/imunologia , Macrófagos/metabolismo , Ratos , Células Cultivadas , Masculino , Inflamação/imunologia
7.
Lab Chip ; 24(10): 2712-2720, 2024 May 14.
Artigo em Inglês | MEDLINE | ID: mdl-38655620

RESUMO

A colorimetric biosensor was elaboratively designed for fast, sensitive and multiplex bacterial detection on a single microfluidic chip using immune magnetic nanobeads for specific bacterial separation, immune gold@platinum palladium nanoparticles for specific bacterial labeling, a finger-actuated mixer for efficient immunoreaction and two coaxial rotatable magnetic fields for magnetic nanobead capture (outer one) and magnet-actuated valve control (inner one). First, preloaded bacteria, nanobeads and nanozymes were mixed through a finger actuator to form nanobead-bacteria-nanozyme conjugates, which were captured by the outer magnetic field. After the inner magnetic field was rotated to successively wash the conjugates and push the H2O2-TMB substrate for resuspending these conjugates, colorless TMB was catalyzed into blue TMBox products, followed by color analysis using ImageJ software for bacterial determination. This simple biosensor enabled multiplex Salmonella detection as low as 9 CFU per sample in 45 min.


Assuntos
Técnicas Biossensoriais , Dispositivos Lab-On-A-Chip , Salmonella , Técnicas Biossensoriais/instrumentação , Salmonella/isolamento & purificação , Colorimetria/instrumentação , Ouro/química , Técnicas Analíticas Microfluídicas/instrumentação , Paládio/química , Nanopartículas Metálicas/química , Platina/química
8.
Clin Cosmet Investig Dermatol ; 17: 891-900, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38660588

RESUMO

Purpose: The purpose of this study was to investigate the comprehensive impact of family history of psoriasis, lesion size, disease severity, and the possibility of joint involvement on patients' quality of life(QoL). Patients and Methods: Data from 5961 patients with psoriasis recruited from 440 hospitals throughout China were analyzed. The effects of family history of psoriasis, Body Surface Area(BSA), Psoriasis Area and Severity Index(PASI), and Psoriasis Epidemiology Screening Tool(PEST) on their Dermatology Life Quality Index(DLQI) were studied using a moderated chained mediated effects test. Results: A total of 912 patients (15.30%) had a family history of psoriasis, and 5071 patients (85.10%) had plaque psoriasis. In patients with plaque psoriasis, the variables of family history, PASI, PEST, and DLQI were positively correlated with each other. Additionally, in patients with other types of psoriasis, PASI was positively correlated with PEST and DLQI. Age was positively correlated with PASI and PEST and negatively correlated with DLQI in patients with plaque psoriasis; their Body Mass Index(BMI) and disease duration were in positive correlation with PASI and PEST. The mediation effect of PASI and PEST between family history and DLQI was remarkable in patients with plaque psoriasis and not in those with other types of psoriasis. BSA moderated the association between family history and PASI in patients with plaque psoriasis. Conclusion: PASI and PEST play a chain mediating role in the relationship between family history and DLQI in patients with plaque psoriasis, and high levels of BSA increase the ability of family history to positively predict PASI in plaque psoriasis, thereby affecting the patient's QoL.

9.
EClinicalMedicine ; 71: 102580, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38618206

RESUMO

Background: The pathological examination of lymph node metastasis (LNM) is crucial for treating prostate cancer (PCa). However, the limitations with naked-eye detection and pathologist workload contribute to a high missed-diagnosis rate for nodal micrometastasis. We aimed to develop an artificial intelligence (AI)-based, time-efficient, and high-precision PCa LNM detector (ProCaLNMD) and evaluate its clinical application value. Methods: In this multicentre, retrospective, diagnostic study, consecutive patients with PCa who underwent radical prostatectomy and pelvic lymph node dissection at five centres between Sep 2, 2013 and Apr 28, 2023 were included, and histopathological slides of resected lymph nodes were collected and digitised as whole-slide images for model development and validation. ProCaLNMD was trained at a dataset from a single centre (the Sun Yat-sen Memorial Hospital of Sun Yat-sen University [SYSMH]), and externally validated in the other four centres. A bladder cancer dataset from SYSMH was used to further validate ProCaLNMD, and an additional validation (human-AI comparison and collaboration study) containing consecutive patients with PCa from SYSMH was implemented to evaluate the application value of integrating ProCaLNMD into the clinical workflow. The primary endpoint was the area under the receiver operating characteristic curve (AUROC) of ProCaLNMD. In addition, the performance measures for pathologists with ProCaLNMD assistance was also assessed. Findings: In total, 8225 slides from 1297 patients with PCa were collected and digitised. Overall, 8158 slides (18,761 lymph nodes) from 1297 patients with PCa (median age 68 years [interquartile range 64-73]; 331 [26%] with LNM) were used to train and validate ProCaLNMD. The AUROC of ProCaLNMD ranged from 0.975 (95% confidence interval 0.953-0.998) to 0.992 (0.982-1.000) in the training and validation datasets, with sensitivities > 0.955 and specificities > 0.921. ProCaLNMD also demonstrated an AUROC of 0.979 in the cross-cancer dataset. ProCaLNMD use triggered true reclassification in 43 (4.3%) slides in which micrometastatic tumour regions were initially missed by pathologists, thereby correcting 28 (8.5%) missed-diagnosed cases of previous routine pathological reports. In the human-AI comparison and collaboration study, the sensitivity of ProCaLNMD (0.983 [0.908-1.000]) surpassed that of two junior pathologists (0.862 [0.746-0.939], P = 0.023; 0.879 [0.767-0.950], P = 0.041) by 10-12% and showed no difference to that of two senior pathologists (both 0.983 [0.908-1.000], both P > 0.99). Furthermore, ProCaLNMD significantly boosted the diagnostic sensitivity of two junior pathologists (both P = 0.041) to the level of senior pathologists (both P > 0.99), and substantially reduced the four pathologists' slide reviewing time (-31%, P < 0.0001; -34%, P < 0.0001; -29%, P < 0.0001; and -27%, P = 0.00031). Interpretation: ProCaLNMD demonstrated high diagnostic capabilities for identifying LNM in prostate cancer, reducing the likelihood of missed diagnoses by pathologists and decreasing the slide reviewing time, highlighting its potential for clinical application. Funding: National Natural Science Foundation of China, the Science and Technology Planning Project of Guangdong Province, the National Key Research and Development Programme of China, the Guangdong Provincial Clinical Research Centre for Urological Diseases, and the Science and Technology Projects in Guangzhou.

10.
PLoS One ; 19(4): e0301660, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38626146

RESUMO

BACKGROUND: Ulcerative colitis (UC) is an inflammatory disease of the digestive tract. Rauwolfia polysaccharide (Rau) has therapeutic effects on colitis in mice, but its mechanism of action needs to be further clarified. In the study, we explored the effect of Rau on the UC cell model induced by Lipopolysaccharide (LPS). METHODS: We constructed a UC cell model by stimulating HT-29 cells with LPS. Dextran sodium sulfate (DSS) was used to induce mice to construct an animal model of UC. Subsequently, we performed Rau administration on the UC cell model. Then, the therapeutic effect of Rau on UC cell model and was validated through methods such as Cell Counting Kit-8 (CCK8), Muse, Quantitative real­time polymerase chain reaction (RT-qPCR), Western blotting, and Enzyme-linked immunosorbent assay (ELISA). RESULTS: The results showed that Rau can promote the proliferation and inhibit the apoptosis of the HT-29 cells-induced by LPS. Moreover, we observed that Rau can inhibit the expression of NOS2/JAK2/STAT3 in LPS-induced HT-29 cells. To further explore the role of NOS2 in UC progression, we used siRNA technology to knock down NOS2 and search for its mechanism in UC. The results illustrated that NOS2 knockdown can promote proliferation and inhibit the apoptosis of LPS-induced HT-29 cells by JAK2/STAT3 pathway. In addition, in vitro and in vivo experiments, we observed that the activation of the JAK2/STAT3 pathway can inhibit the effect of Rau on DSS-induced UC model. CONCLUSION: In short, Rauwolfia polysaccharide can inhibit the progress of ulcerative colitis through NOS2-mediated JAK2/STAT3 pathway. This study provides a theoretical clue for the treatment of UC by Rau.


Assuntos
Alcaloides , Colite Ulcerativa , Colite , Rauwolfia , Animais , Camundongos , Alcaloides/farmacologia , Colite/metabolismo , Colite Ulcerativa/induzido quimicamente , Colite Ulcerativa/tratamento farmacológico , Colite Ulcerativa/genética , Sulfato de Dextrana/toxicidade , Modelos Animais de Doenças , Lipopolissacarídeos/farmacologia , Polissacarídeos/metabolismo
11.
Artigo em Inglês | MEDLINE | ID: mdl-38581322

RESUMO

Objective: This study aimed to evaluate the efficacy of adjunct low-frequency pulse electrical stimulation alongside dexamethasone in the treatment of facial nerve paralysis and its subsequent effects on facial nerve function and electromyographic parameters. With the aim of addressing a knowledge gap in the field, this research provides valuable insights into the potential benefits of combining these treatments and their impact on clinical outcomes, facial nerve functionality, and electromyographic dynamics. Methods: A cohort of 66 patients with facial nerve paralysis treated at our institution between April 2018 and November 2021 were randomly assigned to either an observation (n=33) or an experimental group (n=33). The observation group received standard pharmacotherapy, including Western medications and Daqinjiao decoction, along with dexamethasone. The experimental group was administered low-frequency pulse electrical stimulation in addition to the observation group's regimen. Outcomes assessed were clinical efficacy, facial nerve paralysis scoring, facial nerve functional scoring and indices, electromyographic latency, amplitude ratios between affected and unaffected sides, as well as any adverse events. Results: The experimental group demonstrated a significant improvement over the observation group in clinical treatment outcomes, facial nerve paralysis scores, and facial nerve function scores (P < .05 for all). Furthermore, electromyographic analysis revealed shorter latency periods and greater amplitude ratios in the experimental group's facial muscles post-treatment (P < .05). No significant difference was observed in the incidence of adverse reactions between the two groups (P > .05). Conclusion: The integration of low-frequency pulse electrical stimulation with dexamethasone therapy significantly ameliorates the severity of facial nerve paralysis, enhances facial nerve function, and improves electromyographic signals in facial muscles without increasing adverse effects. These findings support the clinical value and safety of this combined treatment approach for facial nerve paralysis, suggesting its suitability for broader clinical application. These results suggest that this combined treatment approach holds promise for broader clinical application, potentially providing a more effective and safer therapeutic option for patients with facial nerve paralysis. Implementing this approach in clinical practice may lead to improved treatment outcomes, better functional recovery, and enhanced quality of life for affected individuals.

12.
EClinicalMedicine ; 71: 102566, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38686219

RESUMO

Background: Urine cytology is an important non-invasive examination for urothelial carcinoma (UC) diagnosis and follow-up. We aimed to explore whether artificial intelligence (AI) can enhance the sensitivity of urine cytology and help avoid unnecessary endoscopy. Methods: In this multicentre diagnostic study, consecutive patients who underwent liquid-based urine cytology examinations at four hospitals in China were included for model development and validation. Patients who declined surgery and lacked associated histopathology results, those diagnosed with rare subtype tumours of the urinary tract, or had low-quality images were excluded from the study. All liquid-based cytology slides were scanned into whole-slide images (WSIs) at 40 × magnification and the WSI-labels were derived from the corresponding histopathology results. The Precision Urine Cytology AI Solution (PUCAS) was composed of three distinct stages (patch extraction, features extraction, and classification diagnosis) and was trained to identify important WSI features associated with UC diagnosis. The diagnostic sensitivity was mainly used to validate the performance of PUCAS in retrospective and prospective validation cohorts. This study is registered with the ChiCTR, ChiCTR2300073192. Findings: Between January 1, 2018 and October 31, 2022, 2641 patients were retrospectively recruited in the training cohort, and 2335 in retrospective validation cohorts; 400 eligible patients were enrolled in the prospective validation cohort between July 7, 2023 and September 15, 2023. The sensitivity of PUCAS ranged from 0.922 (95% CI: 0.811-0.978) to 1.000 (0.782-1.000) in retrospective validation cohorts, and was 0.896 (0.837-0.939) in prospective validation cohort. The PUCAS model also exhibited a good performance in detecting malignancy within atypical urothelial cells cases, with a sensitivity of over 0.84. In the recurrence detection scenario, PUCAS could reduce 57.5% of endoscopy use with a negative predictive value of 96.4%. Interpretation: PUCAS may help to improve the sensitivity of urine cytology, reduce misdiagnoses of UC, avoid unnecessary endoscopy, and reduce the clinical burden in resource-limited areas. The further validation in other countries is needed. Funding: National Natural Science Foundation of China; Key Program of the National Natural Science Foundation of China; the National Science Foundation for Distinguished Young Scholars; the Science and Technology Planning Project of Guangdong Province; the National Key Research and Development Programme of China; Guangdong Provincial Clinical Research Centre for Urological Diseases.

13.
Front Oncol ; 14: 1371342, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38595825

RESUMO

Background: Our earlier research revealed that the secreted lysyl oxidase-like 4 (LOXL4) that is highly elevated in triple-negative breast cancer (TNBC) acts as a catalyst to lock annexin A2 on the cell membrane surface, which accelerates invasive outgrowth of the cancer through the binding of integrin-ß1 on the cell surface. However, whether this machinery is subject to the LOXL4-mediated intrusive regulation remains uncertain. Methods: Cell invasion was assessed using a transwell-based assay, protein-protein interactions by an immunoprecipitation-Western blotting technique and immunocytochemistry, and plasmin activity in the cell membrane by gelatin zymography. Results: We revealed that cell surface annexin A2 acts as a receptor of plasminogen via interaction with S100A10, a key cell surface annexin A2-binding factor, and S100A11. We found that the cell surface annexin A2/S100A11 complex leads to mature active plasmin from bound plasminogen, which actively stimulates gelatin digestion, followed by increased invasion. Conclusion: We have refined our understanding of the role of LOXL4 in TNBC cell invasion: namely, LOXL4 mediates the upregulation of annexin A2 at the cell surface, the upregulated annexin 2 binds S100A11 and S100A10, and the resulting annexin A2/S100A11 complex acts as a receptor of plasminogen, readily converting it into active-form plasmin and thereby enhancing invasion.

14.
Mol Biomed ; 5(1): 15, 2024 Apr 29.
Artigo em Inglês | MEDLINE | ID: mdl-38679629

RESUMO

Tuberculosis (TB) is an infectious disease that significantly threatens human health. However, the differential diagnosis of latent tuberculosis infection (LTBI) and active tuberculosis (ATB) remains a challenge for clinicians in early detection and preventive intervention. In this study, we developed a novel biomarker named HP16118P, utilizing 16 helper T lymphocyte (HTL) epitopes, 11 cytotoxic T lymphocyte (CTL) epitopes, and 8 B cell epitopes identified from 15 antigens associated with LTBI-RD using the IEDB database. We analyzed the physicochemical properties, spatial structure, and immunological characteristics of HP16118P using various tools, which indicated that it is a hydrophilic and relatively stable alkaline protein. Furthermore, HP16118P exhibited good antigenicity and immunogenicity, while being non-toxic and non-allergenic, with the potential to induce immune responses. We observed that HP16118P can stimulate the production of high levels of IFN-γ+ T lymphocytes in individuals with ATB, LTBI, and health controls. IL-5 induced by HP16118P demonstrated potential in distinguishing LTBI individuals and ATB patients (p=0.0372, AUC=0.8214, 95% CI [0.5843 to 1.000]) with a sensitivity of 100% and specificity of 71.43%. Furthermore, we incorporated the GM-CSF, IL-23, IL-5, and MCP-3 induced by HP16118P into 15 machine learning algorithms to construct a model. It was found that the Quadratic discriminant analysis model exhibited the best diagnostic performance for discriminating between LTBI and ATB, with a sensitivity of 1.00, specificity of 0.86, and accuracy of 0.93. In summary, HP16118P has demonstrated strong antigenicity and immunogenicity, with the induction of GM-CSF, IL-23, IL-5, and MCP-3, suggesting their potential for the differential diagnosis of LTBI and ATB.


Assuntos
Biomarcadores , Tuberculose Latente , Mycobacterium tuberculosis , Humanos , Antígenos de Bactérias/imunologia , Proteínas de Bactérias/imunologia , Biomarcadores/sangue , Diagnóstico Diferencial , Epitopos de Linfócito B/imunologia , Epitopos de Linfócito T/imunologia , Tuberculose Latente/diagnóstico , Tuberculose Latente/imunologia , Mycobacterium tuberculosis/imunologia
15.
J Org Chem ; 89(9): 6494-6505, 2024 May 03.
Artigo em Inglês | MEDLINE | ID: mdl-38634729

RESUMO

Herein, a novel and practical methodology for the photoinduced decarboxylative difluoroalkylation and perfluoroalkylation of α-fluoroacrylic acids is reported. A wide range of α-fluoroacrylic acids can be used as applicable feedstocks, allowing for rapid access to structurally important difluoroalkylated and polyfluoroalkylated monofluoroalkenes with high Z-stereoselectivity under mild conditions. The protocol demonstrates excellent functional group compatibility and provides a platform for modifying complex biologically active molecules.

16.
Artigo em Inglês | MEDLINE | ID: mdl-38551426

RESUMO

Context: Mortality from severe sepsis has been declining in recent years but remains a challenge worldwide because it remains the most frequent cause of death in ICUs. High-quality nursing care during a patient's CBP can play an important role in promoting a patient's physical condition. Objective: The study intended to explore the effects of nursing based on a humanistic care concept on continuous blood purification (CBP) treatment for patients with severe sepsis in an intensive care unit (ICU). Design: The research team performed a prospective randomized controlled study. Setting: The study took place at Minhang Hospital at Fudan University in Shanghai, China. Participants: Participants were 80 patients with severe sepsis who had been admitted to the ICU of the hospital and who were receiving CBP between April 2021 and December 2022. Intervention: The research team randomly divided participants into two groups according to their admission sequence, with 40 participants in each group: (1) an intervention group, the humanistic care group, who received CBP under humanistic care, and (2) a control group who received CBP under routine nursing. Outcome Measures: At baseline and postintervention, the research team: (1) measured participants' negative emotions using the Self-rating Anxiety Scale (SAS) and the Self-rating Depression scale (SDS), (2) assessed participants' hope levels using the Herth Hope Index (HHI), and (3) evaluated participants' health statuses using the Acute Physiology and Chronic Health Evaluation (APACHE-II). The team also measured the complication rate and determined participants' treatment compliance. Results: Postintervention compared to the control group, the humanistic care group's: (1) SAS and SDS scores were significantly lower, with P < .001 and P < .001, respectively; (2) HHI score was significantly higher, with P < .001; (3) APACHE-II scores and complication rate were significantly lower, with P < .001 and < .001, respectively; and (4) treatment compliance was significantly higher, with P = .0186. Conclusions: Nursing based on a humanistic care concept in ICUs can effectively alleviate the negative mood of patients with severe sepsis receiving CBP, enhance their hope levels and the treatment effect, improve their health statuses and treatment compliance, and reduce the occurrence of complications.

17.
Int J Surg ; 2024 Mar 28.
Artigo em Inglês | MEDLINE | ID: mdl-38537084

RESUMO

INTRODUCTION: Music interventions can alleviate patient anxiety and improve post-surgical satisfaction. However, it remains uncertain whether music personal preferences affect efficacy. We tested whether personal music intervention with patient-selected songs played ad libitum is more effective than standard therapist-designed treatment with classical music. METHODS: A prospective, parallel-group, single-blinded, randomized controlled trial with 229 participants (aged 18 to 60 y) previously scheduled for elective surgery. Data analyses followed a modified intention-to-treat principle. The patients were randomized into three groups: Standard care without music (Control), therapist-designed classic music treatment (TT), or personal music intervention with patient-selected songs played ad libitum by the patient (PI). All patients received standard post-anesthesia care, and music intervention was started upon arrival at the post-anesthesia care unit. Primary outcomes were anxiety and overall satisfaction at discharge. In contrast, secondary outcomes were systolic blood pressure during music intervention, the sleep quality of the night after surgery, and the occurrence of postoperative nausea and vomiting within the first 24 hours after surgery. RESULTS: Compared with therapist-designed music treatment, personal intervention decreased systolic blood pressure (T 0 : 124.3±13.7, 95%CI:121-127.7; T 20min : 117.6±10.4, 95%CI:115-120.1; T 30min : 116.9±10.6, 95%CI:114.3-119.4), prevented postoperative nausea and vomiting (Control: 55.9%, TT: 64.6%, PI: 77.6%), including severe postoperative nausea (VAS score>4; Control:44.1%; TT:33.8%; PI:20.9%) and severe emesis (Frequency≥3, Control:13.2%; TT:7.7%; PI:4.5%). None of the treatments affected sleep quality at night after surgery (Median, Q1-Q3, Control:3,1-3; TT:3,1-4; PI:3,1-3.5). Personal, but not therapist, music intervention significantly prevented anxiety (Control: 36.4±5.9, 95% CI:35.0-37.9; TT: 36.2±7.1, 95%CI: 34.4-37.9; PI: 33.8±5.6, 95%CI: 32.4-35.2) and emesis (Control:23.9%; TT:23.4%; PI:13.2%) and improved patient satisfaction (Median, Q1-Q3, C:8, 6-8; TT:8,7-9; PI:8,7-9). CONCLUSIONS: Personal music intervention improved postoperative systolic blood pressure, anxiety, nausea, emesis, and overall satisfaction, but not sleep quality, as compared to therapist-designed classic intervention.

18.
Hum Brain Mapp ; 45(5): e26672, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38549429

RESUMO

Mother-child interaction is highly dynamic and reciprocal. Switching roles in these back-and-forth interactions serves as a crucial feature of reciprocal behaviors while the underlying neural entrainment is still not well-studied. Here, we designed a role-controlled cooperative task with dual EEG recording to explore how differently two brains interact when mothers and children hold different roles. When children were actors and mothers were observers, mother-child interbrain synchrony emerged primarily within the theta oscillations and the frontal lobe, which highly correlated with children's attachment to their mothers (self-reported by mothers). When their roles were reversed, this synchrony was shifted to the alpha oscillations and the central area and associated with mothers' perception of their relationship with their children. The results suggested an observer-actor neural alignment within the actor's oscillations, which was related to the actor-toward-observer emotional bonding. Our findings contribute to the understanding of how interbrain synchrony is established and dynamically changed during mother-child reciprocal interaction.


Assuntos
Encéfalo , Mães , Feminino , Humanos , Mães/psicologia , Encéfalo/diagnóstico por imagem , Lobo Frontal , Relações Mãe-Filho/psicologia , Diencéfalo
19.
Cereb Cortex ; 34(2)2024 01 31.
Artigo em Inglês | MEDLINE | ID: mdl-38425214

RESUMO

Volitional control of local field potential oscillations in low gamma band via brain machine interface can not only uncover the relationship between low gamma oscillation and neural synchrony but also suggest a therapeutic potential to reverse abnormal local field potential oscillation in neurocognitive disorders. In nonhuman primates, the volitional control of low gamma oscillations has been demonstrated by brain machine interface techniques in the primary motor and visual cortex. However, it is not clear whether this holds in other brain regions and other species, for which gamma rhythms might involve in highly different neural processes. Here, we established a closed-loop brain-machine interface and succeeded in training mice to volitionally elevate low gamma power of local field potential in the primary motor and visual cortex. We found that the mice accomplished the task in a goal-directed manner and spiking activity exhibited phase-locking to the oscillation in local field potential in both areas. Moreover, long-term training made the power enhancement specific to direct and adjacent channel, and increased the transcriptional levels of NMDA receptors as well as that of hypoxia-inducible factor relevant to metabolism. Our results suggest that volitionally generated low gamma rhythms in different brain regions share similar mechanisms and pave the way for employing brain machine interface in therapy of neurocognitive disorders.


Assuntos
Ritmo Gama , Córtex Visual , Camundongos , Animais , Encéfalo
20.
Food Chem ; 448: 139086, 2024 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-38520990

RESUMO

Amanita exitialis, a deadly mushroom found in eastern Asia, causes the highest death rates among all poisonous mushrooms in China. The aim of the present study was to develop an efficient, accurate, and user-friendly PCR-based method for identifying A. exitialis that could facilitate the prevention, diagnosis, and treatment of associated food poisoning. A. exitialis-specific primers and probes were designed based on the internal transcribed spacer region variations of 27 mushroom species. Specificity was confirmed using conventional and real-time PCR for 23 non-target mushroom species, including morphologically similar and closely related species. Compared to conventional PCR, real-time PCR was more sensitive (detectable DNA concentration: 1.36 × 10-2 ng/µL vs. 1.36 × 10-3) and efficient (analysis time: 1 h vs. 40 min). Furthermore, the real-time PCR results could be immediately visualized using amplification curve analysis. The results present two robust PCR-based methods for A. exitialis identification that can facilitate food safety.


Assuntos
Amanita , DNA Fúngico , Reação em Cadeia da Polimerase em Tempo Real , Amanita/genética , Amanita/química , Amanita/classificação , DNA Fúngico/genética , Primers do DNA/genética , Reação em Cadeia da Polimerase , China , Intoxicação Alimentar por Cogumelos/diagnóstico
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