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1.
Eye (Lond) ; 2024 May 13.
Artigo em Inglês | MEDLINE | ID: mdl-38740961

RESUMO

PURPOSE: To further explore the influence of genotype, including mutation type and structural domain, on the severity of macular atrophy, we measured the central retinal thickness (CRT) in patients with ABCA4-related retinopathy. METHODS: A total of 66 patients were included in the cohort. This was a retrospective investigation. The patients were tested using whole exon sequencing and ophthalmic exams, including slip lamp exams, best-corrected visual acuity, optical coherence tomography, fundus photo, and fundus autofluorescence. RESULTS: In this study, we discovered that mutations on nucleotide binding domains (NBD) lead to less CRT (45.00 ± 25.25µm, 95% CI: 31.54-58.46) had significantly less CRT than the others (89.75 ± 71.17µm, 95% CI: 30.25-149.25, p = 0.032), and could accelerate the rate of CRT decrease. CONCLUSIONS: Our study provides new perspectives in the understanding of ABCA4-related retinopathy.

2.
Artigo em Inglês | MEDLINE | ID: mdl-38663991

RESUMO

BACKGROUND AND PURPOSE: Acute mountain sickness is a series of brain-centered symptoms that occur when rapidly ascending to high altitude. Predicting acute mountain sickness before high-altitude exposure is crucial for protecting susceptible individuals. The present study aimed to evaluate the feasibility of predicting acute mountain sickness after high-altitude exposure by using multimodal brain MR imaging features measured at sea level. MATERIALS AND METHODS: We recruited 45 healthy sea-level residents who flew to the Qinghai-Tibet Plateau (3650 m). We conducted T1-weighted structural MR imaging, resting-state fMRI, and arterial spin-labeling perfusion MR imaging both at sea level and high altitude. Acute mountain sickness was diagnosed for 5 days using Lake Louise Scoring. Logistic regression with Least Absolute Shrinkage and Selection Operator logistic regression was performed for predicting acute mountain sickness using sea-level MR imaging features. We also validated the predictors by using MR images obtained at high altitude. RESULTS: The incidence rate of acute mountain sickness was 80.0%. The model achieved an area under the receiver operating characteristic curve of 86.4% (sensitivity = 77.8%, specificity = 100.0%, and P < .001) in predicting acute mountain sickness At sea level, valid predictors included fractional amplitude of low-frequency fluctuations (fALFF) and degree centrality from resting-state fMRI, mainly distributed in the somatomotor network. We further learned that the acute mountain sickness group had lower levels of fALFF in the somatomotor network at high altitude, associated with smaller changes in CSF volume and higher Lake Louise Scoring, specifically relating to fatigue and clinical function. CONCLUSIONS: Our study found that the somatomotor network function detected by sea-level resting-state fMRI was a crucial predictor for acute mountain sickness and further validated its pathophysiologic impact at high altitude. These findings show promise for pre-exposure prediction, particularly for individuals in need of rapid ascent, and they offer insight into the potential mechanism of acute mountain sickness.

3.
Chemosphere ; 358: 142152, 2024 Apr 26.
Artigo em Inglês | MEDLINE | ID: mdl-38679178

RESUMO

In recent years, filamentous algae blooms and microplastics (MPs) pollution have become two major ecological and environmental problems in urban water systems. In order to solve these two problems at the same time, this study explored the loading capacity of MPs on fresh filamentous algae, and successfully synthesized magnetic filamentous algae biochar loading with Fe3O4 by hydrothermal method, with the purpose of removing MPs from water. The magnetic filamentous algal biochar was characterized by scanning electron microscopy (SEM), Fourier transform infrared (FTIR), X-ray photoelectron spectroscopy (XPS), X-ray diffraction (XRD), and so on. Experiments on adsorption kinetics, adsorption isotherms and optimum pH were carried out to explore the adsorption mechanism of MPs on magnetic filamentous algal biochar. The adsorption kinetics and adsorption isotherm models were evaluated, and the selection criterion for the appropriate model was determined by using the residual sum of squares (RSS) and Bayesian information criterion (BIC). Microscope images revealed that fresh filamentous algae could interact with MPs in the form of entanglement, adhesion and encapsulation. The average load of MPs in filamentous algae samples was 14.1 ± 5 items/g dry weight. The theoretical maximum adsorption capacities of polystyrene MPs (PS-MPs) by raw biochar (A500) and magnetic biochar with Fe3O4 (M2A500) were 176.99 mg/g and 215.58 mg/g, respectively. The adsorbent materials gave better reusability because they could be reused up to five times. Overall, these findings have provided new insights into the use of filamentous algae for in situ remediation of fluvial MPs pollution, as well as feasible strategies for the recycling of algal waste.

4.
Psychooncology ; 33(3): e6314, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38459736

RESUMO

OBJECTIVE: Psychological distress is prevalent in couples facing breast cancer. Couples often deal with breast cancer as a unit instead of as individuals. Couple's dyadic coping is important for their adjustment to breast cancer; however, little is known about how couple's coping congruence influences their distress. This study examined how common dyadic coping (CDC) and coping congruence impact psychological distress in couples facing breast cancer. METHODS: Baseline data were analyzed from 343 women with recently diagnosed early-stage breast cancer and their partners who participated in a randomized clinical trial. Psychological distress was indicated by depressed mood and state anxiety. Common dyadic coping was measured by a self-report scale. Coping congruence was assessed by the absolute difference between a woman's and her partner's CDC scores. RESULTS: Higher CDC scores were associated with lower psychological distress in both women and partners. In the CDC subscales, women who suffered less scored higher on open communication, sharing a positive outlook, and lower on avoidance coping. Partners who suffered less scored higher on open communication, sharing a positive outlook, spending time talking, and lower on avoidance coping. Greater congruence in CDC was associated with lower psychological distress in women and their partners. Congruence in sharing a positive outlook benefited both members of the dyad; congruence in avoidance coping significantly benefited patients; congruence in open communication significantly benefited partners. CONCLUSIONS: CDC and its congruence in specific areas have potential benefit to couple's psychological distress when facing breast cancer. Health care providers could consider enhancing couple's CDC and coping congruence to improve their adjustment.


Assuntos
Neoplasias da Mama , Angústia Psicológica , Humanos , Feminino , Adaptação Psicológica , Neoplasias da Mama/psicologia , Cônjuges/psicologia , Capacidades de Enfrentamento
5.
Math Biosci Eng ; 21(2): 2646-2670, 2024 Jan 19.
Artigo em Inglês | MEDLINE | ID: mdl-38454700

RESUMO

Research on functional changes in the brain of inflammatory bowel disease (IBD) patients is emerging around the world, which brings new perspectives to medical research. In this paper, the methods of canonical correlation analysis (CCA), kernel canonical correlation analysis (KCCA), and sparsity preserving canonical correlation analysis (SPCCA) were applied to the fusion of simultaneous EEG-fMRI data from 25 IBD patients and 15 healthy individuals. The CCA, KCCA and SPCCA fusion methods were used for data processing to compare the results obtained by the three methods. The results clearly show that there is a significant difference in the activation intensity between IBD and healthy control (HC), not only in the frontal lobe (p < 0.01) and temporal lobe (p < 0.01) regions, but also in the posterior cingulate gyrus (p < 0.01), gyrus rectus (p < 0.01), and amygdala (p < 0.01) regions, which are usually neglected. The mean difference in the SPCCA activation intensity was 60.1. However, the mean difference in activation intensity was only 36.9 and 49.8 by using CCA and KCCA. In addition, the correlation of the relevant components selected during the SPCCA calculation was high, with correlation components of up to 0.955; alternatively, the correlations obtained from CCA and KCCA calculations were only 0.917 and 0.926, respectively. It can be seen that SPCCA is indeed superior to CCA and KCCA in processing high-dimensional multimodal data. This work reveals the process of analyzing the brain activation state in IBD disease, provides a further perspective for the study of brain function, and opens up a new avenue for studying the SPCCA method and the change in the intensity of brain activation in IBD disease.


Assuntos
Análise de Correlação Canônica , Imageamento por Ressonância Magnética , Humanos , Imageamento por Ressonância Magnética/métodos , Encéfalo/diagnóstico por imagem , Eletroencefalografia , Mapeamento Encefálico/métodos
6.
Behav Neurol ; 2024: 1551807, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38323301

RESUMO

Objective: The aim of this study was to explore the resting-state functional connectivity (rsFC) of amygdala subregions in healthy controls (HCs) and in patients with Crohn's disease (CD) both with and without anxiety or depression. Materials and Methods: A total of 33 patients with CD and with anxiety or depression (CDad group), 31 patients with CD but without anxiety or depression (CDnad group), and 29 age-, sex-, and education level-matched HCs underwent functional magnetic resonance imaging. rsFC analysis was used to analyze the FC between the amygdala subregions and other areas of the brain. Results: Compared with the HC group, the CDad group demonstrated decreased rsFC between the right laterobasal subregion and the left hippocampus (P < .001) and right middle frontal gyrus (P < .001) and between the left superficial subregion and the left insula (P < .001). Compared with the HC group, the CDnad group demonstrated decreased rsFC between the left centromedial subregion and the left insula (P < .001). Compared with the CDnad group, the CDad group demonstrated decreased rsFC between the left centromedial subregion and the right precuneus (P < .001) and postcentral gyrus (P < .001), between the right laterobasal subregion and the left hippocampus (P < .001), and between the left superficial subregion and the right middle frontal gyrus (P < .001). Conclusions: There are significant FC changes in the amygdala subregions in patients with CD. These changes may be related to the disease itself or to the symptoms of anxiety and depression.


Assuntos
Doença de Crohn , Depressão , Humanos , Tonsila do Cerebelo , Encéfalo , Ansiedade , Imageamento por Ressonância Magnética
7.
Sci Adv ; 10(8): eadl2238, 2024 Feb 23.
Artigo em Inglês | MEDLINE | ID: mdl-38394209

RESUMO

Skeletal stem cells (SSCs) that are capable of self-renewal and multipotent differentiation contribute to bone development and homeostasis. Several populations of SSCs at different skeletal sites have been reported. Here, we identify a metaphyseal SSC (mpSSC) population whose transcriptional landscape is distinct from other bone mesenchymal stromal cells (BMSCs). These mpSSCs are marked by Sstr2 or Pdgfrb+Kitl-, located just underneath the growth plate, and exclusively derived from hypertrophic chondrocytes (HCs). These HC-derived mpSSCs have properties of self-renewal and multipotency in vitro and in vivo, producing most HC offspring postnatally. HC-specific deletion of Hgs, a component of the endosomal sorting complex required for transport, impairs the HC-to-mpSSC conversion and compromises trabecular bone formation. Thus, mpSSC is the major source of BMSCs and osteoblasts in bone marrow, supporting the postnatal trabecular bone formation.


Assuntos
Osso Esponjoso , Células-Tronco Mesenquimais , Células-Tronco , Osso e Ossos , Diferenciação Celular , Osteoblastos , Osteogênese/genética
8.
Biomedicines ; 12(2)2024 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-38397945

RESUMO

In the healthcare system, lower leg fractures remain relevant, incurring costs related to surgical treatment, hospitalization, and rehabilitation. The duration of treatment may vary depending on the individual case and its severity. Casting as a post-surgical fracture treatment is a common method in human and experimental veterinary medicine. Despite the high importance of sheep in preclinical testing materials for osteosynthesis, there is no standardised cast system ensuring proper stabilisation and functionality of hind limbs during the healing of tibia fractures or defects. Existing treatment approaches for tibial osteosynthesis in laboratory animal science include sling hanging, external fixators, or former Achilles tendon incision. These methods restrict animal movement for 4-6 weeks, limit species-typical behaviour, and impact social interactions. Our pilot study introduces a Standardised Walking Cast (SWC) for sheep, enabling immediate physiological movement post surgery. Seven Rhone sheep (female, 63.5 kg ± 6.45 kg) each with a single tibia defect (6 mm mechanical drilled defect) underwent SWC application for 4 weeks after plate osteosynthesis. The animals bore weight on their operated leg from day one, exhibiting slight lameness (grade 1-2 out of 5). Individual step lengths showed good uniformity (average deviation: 0.89 cm). Group housing successfully started on day three after surgery. Weekly X-rays and cast changes ensured proper placement, depicting the healing process. This study demonstrates the feasibility of using an SWC for up to 72 kg of body weight without sling hanging via ceiling mounting or external fixation techniques. Allowing species-typical movement and social behaviour can significantly improve the physiological behaviour of sheep in experiments, contributing to refinement.

9.
PLoS One ; 19(2): e0297942, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38329986

RESUMO

Machine perfusion (MP) is often referred to as one of the most promising advancements in liver transplantation research of the last few decades, with various techniques and modalities being evaluated in preclinical studies using animal models. However, low scientific rigor and subpar reporting standards lead to limited reproducibility and translational potential, hindering progress. This pre-registered systematic review (PROSPERO: CRD42021234667) aimed to provide a thematic overview of the preclinical research landscape on MP in liver transplantation using in vivo transplantation models and to explore methodological and reporting standards, using the ARRIVE (Animal Research: Reporting of In Vivo Experiments) score. In total 56 articles were included. Studies were evenly distributed across Asia, Europe, and the Americas. Porcine models were used in 57.1% of the studies, followed by rats (39.3%) and dogs (3.6%). In terms of graft type, 55.4% of the studies used donation after cardiac death grafts, while donation after brain death grafts accounted for 37.5%. Regarding MP modalities, the distribution was as follows: 41.5% of articles utilized hypothermic MP, 21.5% normothermic MP, 13.8% subnormothermic MP, and 16.9% utilized hypothermic oxygenated MP. The stringent documentation of ARRIVE elements concerning precise experimental execution, group size and selection, the choice of statistical methods, as well as adherence to the principles of the 3Rs, was notably lacking in the majority of publications, with less than 30% providing comprehensive details. Postoperative analgesia and antibiotics treatment were not documented in 82.1% of all included studies. None of the analyzed studies fully adhered to the ARRIVE Guidelines. In conclusion, the present study emphasizes the importance of adhering to reporting standards to promote reproducibility and adequate animal welfare in preclinical studies in machine perfusion. At the same time, it highlights a clear deficiency in this field, underscoring the need for further investigations into animal welfare-related topics.


Assuntos
Transplante de Fígado , Preservação de Órgãos , Suínos , Animais , Cães , Ratos , Reprodutibilidade dos Testes , Preservação de Órgãos/métodos , Fígado , Perfusão/métodos , Transplante de Fígado/métodos
10.
J Psychosoc Oncol ; : 1-18, 2024 Jan 19.
Artigo em Inglês | MEDLINE | ID: mdl-38240291

RESUMO

OBJECTIVE: Couples' joint coping is important in managing the impact of breast cancer. However, measures assessing couples' communication as a way of coping are insufficient. This study aimed to generate a self-report valid and reliable measure of couples' coping with a particular focus on communication. METHOD: We used baseline data of 343 couple dyads who participated in a randomized clinical trial targeting marital communication. Women were diagnosed with early-stage breast cancer in the past eight months; couples were married or in an intimate relationship for at least six months, could read and write English, and lived within 100 miles of the study center. An expert panel selected items with conceptual fit from the Mutuality and Interpersonal Sensitivity Scale (MIS) that was originally designed to evaluate marital communication about breast cancer. RESULTS: Exploratory and confirmatory factor analyses supported a 12-item measurement model with four factors: Keeping the communication open with each other about breast cancer (4 items), Sharing a positive outlook on breast cancer (2 items), Avoiding discussion of negative thoughts and feelings about breast cancer (3 items), and Spending sufficient time together talking about breast cancer (3 items). Reliability ranged from 0.76 to 0.87 for women and 0.70 to 0.83 for spouses. CONCLUSION: This new measure has potential application in clinical practice and future research to assess couple's joint coping efforts especially through communication.

11.
Retina ; 44(1): 166-174, 2024 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-37695977

RESUMO

PURPOSE: To investigate the possible correlation factors of choroidal thickness in ABCA4 -related retinopathy. METHODS: A total of 66 patients were included in the cohort. It is a retrospective, cross-sectional laboratory investigation. The patients were tested using whole-exon sequencing and ophthalmic examinations, including slit-lamp examinations, best-corrected visual acuity, spectral-domain optical coherence tomography, fundus photograph, and fundus autofluorescence. RESULTS: Besides demographic characteristics (age, onset age, duration), we selected genetic factors and ocular characteristics on spectral-domain optical coherence tomography as the candidates related to choroidal thickness. Mutation type (inframe mutation or premature termination codon), epiretinal membrane, retinal pigment epithelium- Bruch membrane integrity, and macular curvature changes were identified as related factors to choroidal thickness in ABCA4 -related retinopathy after the adjustment of Logistic LASSO regression. CONCLUSION: Mutation type, epiretinal membrane, retinal pigment epithelium-Bruch membrane integrity, and macular curvature changes are related factors to choroidal thinning. These findings could provide us a further understanding for the pathological process and clinical features of ABCA4 mutation.


Assuntos
Membrana Epirretiniana , Doenças Retinianas , Humanos , Estudos Retrospectivos , Tomografia de Coerência Óptica/métodos , Estudos Transversais , Doenças Retinianas/diagnóstico , Doenças Retinianas/genética , Doenças Retinianas/patologia , Transportadores de Cassetes de Ligação de ATP/genética
12.
Eye (Lond) ; 38(2): 328-334, 2024 02.
Artigo em Inglês | MEDLINE | ID: mdl-37553355

RESUMO

BACKGROUND: To investigate the prevalence of outer retinal tubulation (ORT) and its correlations with optical coherence tomography (OCT) parameters in Chinese population with inherited retinal diseases (IRDs). METHODS: This retrospective study enrolled consecutive patients identified with IRDs and referred for genetic testing between February 2016 and April 2021. Clinical characteristics from medical records and features of cross-sectional B-scans were reviewed and analysed. The associations of patient-specific and ocular features with the presence of ORT were evaluated using univariate and multivariate analyses. RESULTS: Two hundred and three patients (401 eyes) with a mean age of 49.7 ± 16.7 years were enrolled. ORT was observed in 41 eyes (10.2%), including 26 of 28 eyes (92.9%) with Bietti crystalline corneoretinal dystrophy (BCD), 14 of 338 eyes (4.1%) with retinitis pigmentosa (RP), and 1 of 26 eyes (3.8%) in eyes with cone-rod dystrophy. Eyes with ORT showed significantly worse visual acuity than those without ORT (P = 0.002). Multivariate analysis indicated that the presence of ORT was positively correlated with choroidal atrophy and inner nuclear layer (INL) cysts (P < 0.01). ORTs were detected more frequently in eyes with BCD than RP (P = 0.024), most of which located exclusively within the extrafoveal area. Large choroidal vessels were detected underneath the corresponding ORTs in both patients with BCD and RP. CONCLUSIONS: The prevalence of ORT varies among different IRDs phenotypes, with the highest prevalence in BCD. The presence of choroidal atrophy and INL cysts may be associated with an increased risk of ORT formation in patients with IRD.


Assuntos
Distrofias Hereditárias da Córnea , Cistos , Doenças Retinianas , Retinose Pigmentar , Humanos , Adulto , Pessoa de Meia-Idade , Idoso , Tomografia de Coerência Óptica/métodos , Estudos Retrospectivos , Prevalência , Estudos Transversais , Doenças Retinianas/epidemiologia , Retinose Pigmentar/genética , China/epidemiologia , Atrofia
13.
Oral Oncol ; 148: 106632, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38039875

RESUMO

OBJECTIVES: The efficacy of immune checkpoint inhibitors (ICIs) is unclear in patients aged ≥ 75 years with head and neck squamous cell carcinoma (HNSCC). We conducted a systematic review and meta-analysis of randomized trials that compared ICIs with standard-of-care (SOC) therapy for recurrent/metastatic HNSCC. MATERIALS AND METHODS: PubMed, EMBASE, Web of Science, and ClinicalTrials.gov were searched for eligible trials. We evaluated the overall survival (OS) benefit of ICIs versus SOC according to patient age (<75 versus ≥ 75 years). The OS benefit was evaluated and compared between the age subgroups using hazard ratios (HRs). Data were pooled using a random-effects model. RESULTS: Five phase 3 trials involving 3437 patients were included. In patients aged ≥ 75 years (n = 207), ICIs did not improve OS compared to SOC (HR = 1.30, 95 % confidence interval [CI]: 0.93-1.81, P = 0.127). However, an improvement in OS was observed in patients aged < 75 years (n = 3230, HR = 0.90, 95 % CI: 0.83-0.99, P = 0.025). There is a significant difference in OS benefit between patients aged < 75 and ≥ 75 years (ratio of HR = 0.69, 95 % CI: 0.49-0.98, P = 0.036). Subgroup, meta-regression, and sensitivity analyses supported the reliability of the results. CONCLUSIONS: Given the small sample size, our findings showing no improvement in OS suggest a lack of evidence to support the use of ICIs in patients with recurrent/metastatic HNSCC aged ≥ 75 years. Therefore, prospective studies are needed to clarify their efficacy among this age group.


Assuntos
Carcinoma , Neoplasias de Cabeça e Pescoço , Humanos , Carcinoma de Células Escamosas de Cabeça e Pescoço/tratamento farmacológico , Inibidores de Checkpoint Imunológico/farmacologia , Inibidores de Checkpoint Imunológico/uso terapêutico , Reprodutibilidade dos Testes , Recidiva Local de Neoplasia/tratamento farmacológico , Recidiva Local de Neoplasia/patologia , Neoplasias de Cabeça e Pescoço/tratamento farmacológico
14.
Mar Genomics ; 72: 101074, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38008534

RESUMO

Aestuariibaculum lutulentum L182T (= KCTC 92530T = MCCC 1K08065T) was isolated from the tidal sediment collected in Beihai, People's Republic of China. The genome was sequenced and consisted of a single chromosome with the size of 3,782,725 bp and DNA G + C content of 35.1%. Genomic annotations demonstrated that it encoded 12 rRNA genes, 56 tRNA genes and 3210 ORFs. The percentages of ORFs assigned to CAZy, COG, and KEGG databases were 5.5, 86.2 and 45.5%, respectively. Comparative genomic analysis indicated that the pan- and core-genomes of the genus Aestuariibaculum consisted of 4826 and 2257 orthologous genes, respectively. Carbohydrate-active enzyme annotations of the genus Aestuariibaculum genomes revealed that they shared three polysaccharide lyase (PL) families including PL1, PL22 and PL42. Meanwhile, one carotenoid biosynthetic gene cluster related to biosynthesizing flexixanthin was found in the genus Aestuariibaculum. Furthermore, the core-genome of the genus Aestuariibaculum showed that this genus played a role in cleaving pectate, degrading ulvan, and biosynthesizing carotenoids. This study is a complete genomic report of the genus Aestuariibaculum and broadens understandings of its ecological roles and biotechnological applications.


Assuntos
Flavobacteriaceae , Água do Mar , Humanos , Ácidos Graxos , DNA Bacteriano/genética , Genômica , Carotenoides , Análise de Sequência de DNA , Flavobacteriaceae/genética , Filogenia , RNA Ribossômico 16S
16.
World J Surg Oncol ; 21(1): 334, 2023 Oct 26.
Artigo em Inglês | MEDLINE | ID: mdl-37880766

RESUMO

Lung cancer is a highly prevalent malignancy characterized by significant metabolic alterations. Understanding the metabolic rewiring in lung cancer is crucial for the development of effective therapeutic strategies. The hexosamine biosynthesis pathway (HBP) is a metabolic pathway that plays a vital role in cellular metabolism and has been implicated in various cancers, including lung cancer. Abnormal activation of HBP is involved in the proliferation, progression, metastasis, and drug resistance of tumor cells. In this review, we will discuss the function and regulation of metabolic enzymes related to HBP in lung cancer. Furthermore, the implications of targeting the HBP for lung cancer treatment are also discussed, along with the challenges and future directions in this field. This review provides a comprehensive understanding of the role and intervention of HBP in lung cancer. Future research focusing on the HBP in lung cancer is essential to uncover novel treatment strategies and improve patient outcomes.


Assuntos
Neoplasias Pulmonares , Humanos , Neoplasias Pulmonares/tratamento farmacológico , Hexosaminas/metabolismo , Vias Biossintéticas
17.
Environ Sci Technol ; 57(44): 16906-16917, 2023 11 07.
Artigo em Inglês | MEDLINE | ID: mdl-37897806

RESUMO

In silico models for predicting physicochemical properties and environmental fate parameters are necessary for the sound management of chemicals. This study employed graph attention network (GAT) algorithms to construct such models on 15 end points. The results showed that the GAT models outperformed the previous state-of-the-art models, and their performance was not influenced by the presence or absence of compounds with certain structures. Molecular similarity density (ρs) was found to be a key metrics characterizing data set modelability, in addition to the proportion of compounds at activity cliffs. By introducing molecular graph (MG) contrastive learning, MG-based ρs and molecular inconsistency in activities (IA) were calculated and employed for characterizing the structure-activity landscape (SAL)-based applicability domain ADSAL{ρs, IA}. The GAT models coupled with ADSAL{ρs, IA} significantly improved the prediction coefficient of determination (R2) on all the end points by an average of 14.4% and enabled all the end points to have R2 > 0.9, which could hardly be achieved previously. The models were employed to screen persistent, mobile, and/or bioaccumulative chemicals from inventories consisting of about 106 chemicals. Given the current state-of-the-art model performance and coverage of the various environmental end points, the constructed models with ADSAL{ρs, IA} may serve as benchmarks for future efforts to improve modeling efficacy.


Assuntos
Algoritmos , Benchmarking , Simulação por Computador
18.
Eur J Pharmacol ; 960: 176122, 2023 Dec 05.
Artigo em Inglês | MEDLINE | ID: mdl-37863414

RESUMO

Ulcerative colitis is an inflammatory bowel disease with increasing prevalence and incidence. Current treatments for ulcerative colitis are not generally applicative and are often accompanied by side effects. IGF2 is an endogenous protein that plays roles in anti-inflammation and stemness maintenance, but little is known about its mechanism and function in the progression of ulcerative colitis. In this study, mouse recombinant IGF2 was used in a mouse model of ulcerative colitis established by DSS. IGF2 expression was reduced in colon tissues but not plasma of DSS-induced colitis mice. IGF2R expression was also decreased in colitis colons, which was then elevated by recombinant IGF2. Recombinant IGF2 alleviated colon injury in colitis, which was evaluated by colon shortening, body weight loss and DAI score. IGF2 treatment also relieved the inflammatory response in colitis, which was assessed by the spleen weight index, MPO activity and proinflammatory cytokine expression and was also detected in LPS-stimulated RAW264.7 cells in vitro. Moreover, IGF2R was predicted and further verified to interact with the Sting protein, and the cGAS-Sting pathway as a key pathway for stemness regulation, was upregulated in colonic colons, which was blocked by IGF2 treatment. Additionally, IGF2 treatment can maintain colonic stemness and further repair colonic tight junction function in DSS-induced colitis. In conclusion, IGF2/IGF2R downregulated the cGAS-Sting pathway to sustain colonic stemness and barrier integrity to protect against ulcerative colitis induced by DSS.


Assuntos
Colite Ulcerativa , Colite , Camundongos , Animais , Colite Ulcerativa/induzido quimicamente , Colite Ulcerativa/tratamento farmacológico , Colite Ulcerativa/metabolismo , Colo , Colite/induzido quimicamente , Colite/tratamento farmacológico , Colite/metabolismo , Transdução de Sinais , Nucleotidiltransferases/metabolismo , Sulfato de Dextrana/efeitos adversos , Modelos Animais de Doenças , Camundongos Endogâmicos C57BL
19.
Nano Lett ; 23(20): 9618-9625, 2023 10 25.
Artigo em Inglês | MEDLINE | ID: mdl-37793647

RESUMO

Understanding liver tissue mechanics, particularly in the context of liver pathologies like fibrosis, cirrhosis, and carcinoma, holds pivotal significance for assessing disease severity and prognosis. Although the static mechanical properties of livers have been gradually studied, the intricacies of their dynamic mechanics remain enigmatic. Here, we characterize the dynamic creep responses of healthy, fibrotic, and mesenchymal stem cells (MSCs)-treated fibrotic lives. Strikingly, we unearth a ubiquitous two-stage power-law rheology of livers across different time scales with the exponents and their distribution profiles highly correlated to liver status. Moreover, our self-similar hierarchical theory effectively captures the delicate changes in the dynamical mechanics of livers. Notably, the viscoelastic multiscale mechanical indexes (i.e., power-law exponents and elastic stiffnesses of different hierarchies) and their distribution characteristics prominently vary with liver fibrosis and MSCs therapy. This study unveils the viscoelastic characteristics of livers and underscores the potential of proposed mechanical criteria for assessing disease evolution and prognosis.


Assuntos
Cirrose Hepática , Fígado , Humanos , Cirrose Hepática/terapia , Fígado/patologia , Reologia , Resultado do Tratamento , Viscosidade
20.
Heliyon ; 9(8): e18956, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-37609406

RESUMO

Background: Since the poor prognosis of uveal melanoma with distant metastasis, we intended to screen out possible biomarkers for uveal melanoma metastasis risk and establish a nomogram model for predicting the risk of uveal melanoma (UVM) metastasis. Methods: Two datasets of UVM (GSE84976, GSE22138) were selected. Data was analyzed by R language, CTD database and GEPIA. Results: The co-upregulated genes of two datasets, HTR2B, CHAC1, AHNAK2, and PTP4A3 were identified using a Venn diagram. These biomarkers are combined with clinical characteristics, and Lasso regression was conducted to filter the metastasis-related biomarkers. HTR2B, CHAC1, AHNAK2, PTP4A3, tumor thickness, and retinal detachment (RD) were selected to establish the nomogram. Conclusion: Our study provides a comprehensive predictive model and personalized risk estimation tool for assessment of 3-year metastasis risk of UVM with a better accuracy.

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