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1.
Medicine (Baltimore) ; 100(9): e24829, 2021 Mar 05.
Artigo em Inglês | MEDLINE | ID: mdl-33655944

RESUMO

ABSTRACT: An increasing number of studies focus on the effectiveness of Massive Open Online Courses (MOOC)-based blended learning, whereas none have yet studied using it for teaching fundamental nursing skills at an undergraduate level.To evaluate the effectiveness of MOOC-based blended learning versus face-to-face classroom teaching techniques within the fundamental nursing course at the Faculty of Nursing, University of Xiang Nan, China.This cluster randomized controlled trial enrolled 181 students and assigned them into either an MOOC-based blended or a face-to-face classroom teaching group, both involving the Fundamental Nursing course for undergraduate nursing students. The analyzed outcomes included test scores, critical thinking ability, and feedback received from the students on the Fundamental Nursing course.MOOC-based blended techniques versus face-to-face classroom teaching methods demonstrated higher daily performance (P = .014), operational performance (P = .001), theoretical achievements (P < .001), and final grades (P < .001) in Fundamental Nursing.Moreover, the mean change in the participants' critical thinking ability items between groups were, mostly, statistically significant. The items focusing on the feedback from the students demonstrated significant differences between the groups in terms of their satisfaction with the teaching they received (P < .001) and the overall learning effects (P = .030).This study confirmed that receiving MOOC-based blended learning was superior when compared against face-to-face classroom teaching techniques for learning within the Fundamental Nursing course.

2.
Exp Cell Res ; 400(2): 112509, 2021 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-33529711

RESUMO

Here, we assessed the effects of varying concentrations of gelatin coating on Receptor Activator of Nuclear Factor κ-B Ligand (RANKL)-induced RAW264.7 murine macrophage differentiation into osteoclast (OC) via osteoclastogenesis. The microstructures of coating surfaces with different concentrations of gelatin were examined by scanning electron microscopy and atomic force microscopy. Increased gelatin coating concentrations led to decreased gel rigidity but increased surface adhesion force attenuated OC differentiation and the decreased actin ring formation in RANKL-induced osteoclastogenesis. The decreased actin ring formation is associated with decreased lysosomal-associated membrane protein 1 (LAMP1) activity and bone resorption in the differentiated OCs with different gelatin coating concentrations as compared to the cells differentiated without gelatin coatings. In addition, increasing concentrations of gelatin coating attenuated the medium TGF-ß1 protein levels and the expression levels of TGF-ß and type-I (R1) and type-II (R2) TGF-ß receptors in OCs, suggesting the gelatin-induced suppression of TGF-ß signaling for the regulation of RNAKL-induced OC differentiation. Taken together, these findings showed that changes in gelatin coating concentrations, which were associated with altered gel thickness and substrate rigidity, might attenuate TGF-ß signaling events to modulate OC differentiation and concomitant actin ring formation and bone matrix resorption in RANKL-induced osteoclastogenesis.

3.
Cell Host Microbe ; 2021 Jan 29.
Artigo em Inglês | MEDLINE | ID: mdl-33548198

RESUMO

The SARS-CoV-2 virus, the causative agent of COVID-19, is undergoing constant mutation. Here, we utilized an integrative approach combining epidemiology, virus genome sequencing, clinical phenotyping, and experimental validation to locate mutations of clinical importance. We identified 35 recurrent variants, some of which are associated with clinical phenotypes related to severity. One variant, containing a deletion in the Nsp1-coding region (Δ500-532), was found in more than 20% of our sequenced samples and associates with higher RT-PCR cycle thresholds and lower serum IFN-ß levels of infected patients. Deletion variants in this locus were found in 37 countries worldwide, and viruses isolated from clinical samples or engineered by reverse genetics with related deletions in Nsp1 also induce lower IFN-ß responses in infected Calu-3 cells. Taken together, our virologic surveillance characterizes recurrent genetic diversity and identified mutations in Nsp1 of biological and clinical importance, which collectively may aid molecular diagnostics and drug design.

4.
Environ Pollut ; 274: 116524, 2021 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-33548667

RESUMO

Increasing attention has been brought to microplastics pollution recently, while emerging evidences indicate that nano-plastics degraded from microplastics are more of research significance owing to stronger toxicity. However, there is little study focused on the prevention of nano-plastics induced toxicity until now. Canidin-3-glucoside (C3G), a natural anthocyanin proved to possess multiple functions like antioxidant and intestinal tissue protection. Thus, we proposed whether C3G could act as a molecular weapon against nano-plastics induced toxicity. In Caco2 cell and Caenorhabditis elegans (C. elegans) models, we found that polystyrene (PS) nano-plastics exposure resulted in physiological toxicity and oxidative damage, which could be restored by C3G. More significantly in Caco2 cells, we observed that autophagy was activated via Sirt1-Foxo1 signaling pathway to attenuate PS induced toxicity after C3G intervention and further verified by adding autophagy inhibitor 3-Methyladenine (3-MA). Meanwhile, PS co-localization with lysosomes was observed, indicating the encapsulation and degradation of PS. In C. elegans, by detecting LGG-1/LC3 expression in GFP-targeted LGG-1 report gene (LGG-1:GFP) labeled transgenic DA2123 strain, the co-localization of LGG-1:GFP with PS was found as well, means that autophagy is involved in C3G's beneficial effects. Furthermore, we were surprised to find that C3G could promote the discharge of PS from N2 nematodes, which reduces PS toxicity more directly.


Assuntos
Caenorhabditis elegans , Plásticos , Animais , Autofagia , Células CACO-2 , Glucosídeos/toxicidade , Humanos , Microplásticos
5.
J Stud Alcohol Drugs ; 82(1): 152-157, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33573733

RESUMO

OBJECTIVE: The present study investigated the extent to which individual and school characteristics may differentially affect parental consent and child assent in the enrollment of a school-based substance use prevention study in Taiwan. METHOD: This study linked field notes on response and consent status during enrollment of the school-based prevention study with administrative survey data reported by the targeted students when they were in fourth grade (age 10-11) (N = 2,560; 53% male, 97.8% matched). The outcome variables, defined by the combined status of parental consent/child assent, were nonresponse and negative, discordant, and positive consent. Individual characteristics included family (parental education, employment) and child (psychological/behavioral, substance use) factors. Aggregate school-level substance use and percentage of aboriginal students and nonnative parents served as school-level factors. Multilevel multinomial regression analyses were performed. RESULTS: Successful consent was obtained from only 820 students (32%). Male gender and feeling neglected by families were associated with failing to respond (adjusted odds ratio = 1.78 and 1.71, respectively). Higher parental educational attainment reduced the odds of negative consent by 30%, whereas having unemployed parents increased the odds of discordant consent by 326%. Children attending schools with a higher percentage of indigenous students were two times more likely to have nonresponse, negative consent, and discordant consent. CONCLUSIONS: Nonresponse to the consent request or negative consent appeared to be associated with disadvantaged background and unfavorable parent-child interaction. This suggests complex pathways underlying ascertainment and a need to modify the consent practices in school-based prevention studies involving minors, especially in schools with higher ethnic minority composition.

6.
PLoS One ; 16(2): e0246166, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33529262

RESUMO

This study was to compare the efficacy and safety of combined glycoprotein IIb/IIIa inhibitor (GPI) and ticagrelor versus ticagrelor in patients with acute coronary syndrome (ACS). An observational study was conducted using the Improving Care for Cardiovascular Disease in China-ACS project. Totally, 13,264 patients with ACS and received combination therapy or ticagrelor therapy were analyzed. The primary outcome was the composite of major cardiovascular events (MACE: all-cause mortality, myocardial infarction [MI], stent thrombosis, cardiogenic shock, and ischemic stroke), and secondary outcomes included all-cause mortality, MI, stent thrombosis, cardiogenic shock, and ischemic stroke. The multivariable adjusted analysis indicated that combination therapy was associated with an increased risk of major cardiovascular events (MACE) (P = 0.001), any bleeding (P<0.001), and major bleeding (P = 0.005). Moreover, the multivariable adjusted for propensity score-matched (PSM) analysis suggested that combination therapy produced additional risk of MACE (P = 0.014), any bleeding (P<0.001), and major bleeding (P = 0.005). Moreover, PSM analysis suggested that combination therapy was associated with greater risk of stent thrombosis (P = 0.012) and intracranial bleeding (P = 0.020). Combined GPI and ticagrelor therapies did not have any beneficial effects on MACE, stent thrombosis, intracranial bleeding, any bleeding, or major bleeding.

7.
Ecotoxicol Environ Saf ; 212: 111989, 2021 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-33524913

RESUMO

Drinking water exposure to microcystin-leucine-arginine (MC-LR), the most widely occurring cyanotoxins, poses a highly potential risk for human health. However, the health risk of MC-LR exposure at current guideline value in drinking water has not yet entirely evaluated. In the current study, we used 1H NMR-based metabolomics combined with targeted metabolic profiling by GC/LC-MS to explore the toxic effects of MC-LR exposure at environmentally relevant concentrations via drinking water in rats. The results revealed that multiple biological consequences of MC-LR exposure on host metabolism in rats. Both relatively low and high doses of MC-LR used here induced hepatic lipogenesis and inflammation. While only relatively high dose MC-LR (10 µg/L) in drinking water caused more metabolic disorders including inhibition of gluconeogenesis and promotion of ß-oxidation of fatty acid. Although the dose of 1.0 µg/L MC-LR is extremely low for rats, alterations of metabolic profiles were unexpectedly found in rat liver and serum, alarming potential health risk of MC-LR at the WHO guideline level.

8.
Invest Ophthalmol Vis Sci ; 62(2): 35, 2021 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-33620373

RESUMO

Purpose: To investigate environmental factors associated with corneal morphologic changes. Methods: A cross-sectional study was conducted, which enrolled adults of the Han ethnicity aged 18 to 44 years from 20 cities. The cornea-related morphology was measured using an ocular anterior segment analysis system. The geographic indexes of each city and meteorological indexes of daily city-level data from the past 40 years (1980-2019) were obtained. Correlation analyses at the city level and multilevel model analyses at the eye level were performed. Results: In total, 114,067 eyes were used for analysis. In the correlation analyses at the city level, the corneal thickness was positively correlated with the mean values of precipitation (highest r [correlation coefficient]: >0.700), temperature, and relative humidity (RH), as well as the amount of annual variation in precipitation (r: 0.548 to 0.721), and negatively correlated with the mean daily difference in the temperature (DIF T), duration of sunshine, and variance in RH (r: -0.694 to 0.495). In contrast, the anterior chamber (AC) volume was negatively correlated with the mean values of precipitation, temperature, RH, and the amount of annual variation in precipitation (r: -0.672 to -0.448), and positively associated with the mean DIF T (r = 0.570) and variance in temperature (r = 0.507). In total 19,988 eyes were analyzed at the eye level. After adjusting for age, precipitation was the major explanatory factor among the environmental factors for the variability in corneal thickness and AC volume. Conclusions: Individuals who were raised in warm and wet environments had thicker corneas and smaller AC volumes than those from cold and dry ambient environments. Our findings demonstrate the role of local environmental factors in corneal-related morphology.

9.
In Vivo ; 35(2): 1083-1089, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33622905

RESUMO

BACKGROUND/AIM: To investigate the prognostic values of fat invasion (FI) and renal vein invasion (RVI) in pT3a renal cell carcinoma (RCC), as single factors or concomitant presence. PATIENTS AND METHODS: We retrospectively reviewed the data of 173 patients who underwent radical or partial nephrectomy for RCC in our Institution. RESULTS: At a median follow-up time of 48 months, patients with RVI showed significantly increased risk of disease recurrence and worse cancer-specific survival (CSS) when compared to those with FI (p=0.007, p=0.022, respectively). Having combined RVI and FI did not show inferior prognosis compared to those with RVI only. In multivariable analysis, RVI was an independent factor for disease recurrence (HR=2.06, 95% CI=1.10-3.87, p=0.024) and CSS (HR=2.46, 95% CI=1.01-6.0, p=0.048). CONCLUSION: For patients with T3a renal tumors, RVI was associated with inferior prognosis compared to those with FI.

10.
Medicine (Baltimore) ; 100(5): e24007, 2021 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-33592857

RESUMO

RATIONALE: This study aimed to investigate the genetic mutation characteristics of congenital idiopathic hypogonadotropic hypogonadism (IHH) through the clinical features and genetic analysis of 2 patients with IHH in 1 pedigree. PATIENT CONCERNS: A 23-year-old girl presented with primary amenorrhea, sparse pubic hair, lack of breast development, and delayed sexual development. DIAGNOSES: Combined with the clinical characteristics, auxiliary examinations, and molecular genetic analysis, the patient was diagnosed as IHH. INTERVENTIONS: Whole exome and Sanger sequencing were performed to validate the mutation in family members. OUTCOMES: A novel homozygous missense mutation c.521A > G (p.Q174R) in the GNRHR gene was identified in the 2 affected sisters. Familial segregation showed that the homozygous variant was inherited from their parents respectively and the eldest sister was the carrier without correlative symptom. LESSONS: We reported a novel GNRHR mutation in a pedigree with congenital idiopathic hypogonadotropic hypogonadism. Glutamine at amino acid position 174 was highly conserved among various species. The molecular structure of GNRHR protein showed that p.Q174R mutation brought in a new stable hydrogen bond between position 174 and 215, may impede conformational mobility of the TMD4 and TMD5. It suggests that the missense mutation c.521A > G related to congenital idiopathic hypogonadotropic hypogonadism was probably a causative factor for both sisters. Through high-throughput sequencing and experimental verification, we had basically determined the patient's pathogenic mutation and inheritance, which could better guide doctors for treatment.


Assuntos
Hipogonadismo , Receptores LHRH/genética , Feminino , Predisposição Genética para Doença , Testes Genéticos/métodos , Homozigoto , Humanos , Hipogonadismo/congênito , Hipogonadismo/genética , Hipogonadismo/fisiopatologia , Mutação de Sentido Incorreto , Linhagem , Irmãos , Adulto Jovem
11.
World Neurosurg ; 2021 Feb 22.
Artigo em Inglês | MEDLINE | ID: mdl-33631388

RESUMO

OBJECTIVE: To investigate the effect of superficial temporal artery-posterior cerebral artery (STA-PCA) bypass (STA-PCA bypass) on chronic basilar artery occlusion (CBAO) METHODS: A total of 4 patients who underwent STA-PCA bypass between January 2018 and October 2019 were enrolled in this study. Cerebral blood perfusion, ischemic events, STA diameter and blood flow changes, modified Rankin scale score (mRS) and National Institutes of Health Stroke Scale (NHISS score changes were recorded before and after bypass surgery. RESULTS: The average time from basilar artery occlusion (confirmed by cerebral angiography or CT angiography) to operation was 76±38.89 days (30-120 days). Average scores on the NIHSS were 6.8±1.26(5-8) and 5.2±2.06(3-7) before and after treatment, respectively. mRS scores averaged 1.8±0.5(1-2) and 1.5±0.58(1-2) points, respectively. There were no obvious complications or further stroke during the follow-up. The STA diameter and flow rate were significantly increased at 12 months after operation (p <0.05). CONCLUSION: STA-PCA bypass can improve cerebral blood flow perfusion in CBAO patients. The diameter and flow of the superficial temporal artery can be increased to meet the demand of blood supply.

12.
Int J Biol Sci ; 17(1): 151-162, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33390840

RESUMO

As a systemic syndrome characterized by age-associated degenerative skeletal muscle atrophy, sarcopenia leads to a risk of adverse outcomes in the elderly. Age-related iron accumulation is found in the muscles of sarcopenia animal models and patients, but the role of iron in sarcopenia remains poorly understood. It has been recently found that iron overload in several diseases is involved in ferroptosis, an iron- dependent form of programmed cell death. However, whether this excess iron can result in ferroptosis in muscles is still unclear. In our present study, we found that ferric citrate induced ferroptosis in C2C12 cells, as well as impaired their differentiation from myoblasts to myotubes. Due to the decreased muscle mass and fiber size, 40-week-old senescence accelerated mouse prone 8 (SAMP8) mice were used as a sarcopenia model, in whose muscles the iron content and markers of ferroptosis were found to increase, compared to 8-week- old SAMP8 controls. Moreover, our results showed that iron overload upregulated the expression of P53, which subsequently repressed the protein level of Slc7a11 (solute carrier family 7, member 11), a known ferroptosis-related gene. The downregulation of Slc7a11 then induced the ferroptosis of muscle cells through the accumulation of lipid peroxidation products, which may be one of the causes of sarcopenia. The findings in this study indicate that iron plays a key role in triggering P53- Slc7a11-mediated ferroptosis in muscles, and suggest that targeting iron accumulation and ferroptosis might be a therapeutic strategy for treating sarcopenia.

13.
Mol Neurobiol ; 2021 Jan 09.
Artigo em Inglês | MEDLINE | ID: mdl-33421017

RESUMO

Proper development of neuronal cells is important for brain functions, and impairment of neuronal development may lead to neuronal disorders, implying that improvement in neuronal development may be a therapeutic direction for these diseases. Huntington's disease (HD) is a neurodegenerative disease characterized by impairment of neuronal structures, ultimately leading to neuronal death and dysfunctions of the central nervous system. Based on previous studies, fibroblast growth factor 9 (FGF9) may provide neuroprotective functions in HD, and FGFs may enhance neuronal development and neurite outgrowth. However, whether FGF9 can provide neuronal protective functions through improvement of neuronal morphology in HD is still unclear. Here, we study the effects of FGF9 on neuronal length in HD and attempt to understand the related working mechanisms. Taking advantage of striatal cell lines from HD knock-in mice, we found that FGF9 increases total neuronal length and upregulates several structural and synaptic proteins under HD conditions. In addition, activation of nuclear factor kappa B (NF-kB) signaling by FGF9 was observed to be significant in HD cells, and blockage of NF-kB leads to suppression of these structural and synaptic proteins induced by FGF9, suggesting the involvement of NF-kB signaling in these effects of FGF9. Taken these results together, FGF9 may enhance total neuronal length through upregulation of NF-kB signaling, and this mechanism could serve as an important mechanism for neuroprotective functions of FGF9 in HD.

14.
Cell Death Dis ; 12(1): 65, 2021 Jan 11.
Artigo em Inglês | MEDLINE | ID: mdl-33431801

RESUMO

Legumain is required for maintenance of normal kidney homeostasis. However, its role in acute kidney injury (AKI) is still unclear. Here, we induced AKI by bilateral ischemia-reperfusion injury (IRI) of renal arteries or folic acid in lgmnWT and lgmnKO mice. We assessed serum creatinine, blood urea nitrogen, histological indexes of tubular injury, and expression of KIM-1 and NGAL. Inflammatory infiltration was evaluated by immunohistological staining of CD3 and F4/80, and expression of TNF-α, CCL-2, IL-33, and IL-1α. Ferroptosis was evaluated by Acsl4, Cox-2, reactive oxygen species (ROS) indexes H2DCFDA and DHE, MDA and glutathione peroxidase 4 (GPX4). We induced ferroptosis by hypoxia or erastin in primary mouse renal tubular epithelial cells (mRTECs). Cellular survival, Acsl4, Cox-2, LDH release, ROS, and MDA levels were measured. We analyzed the degradation of GPX4 through inhibition of proteasomes or autophagy. Lysosomal GPX4 was assessed to determine GPX4 degradation pathway. Immunoprecipitation (IP) was used to determine the interactions between legumain, GPX4, HSC70, and HSP90. For tentative treatment, RR-11a was administrated intraperitoneally to a mouse model of IRI-induced AKI. Our results showed that legumain deficiency attenuated acute tubular injury, inflammation, and ferroptosis in either IRI or folic acid-induced AKI model. Ferroptosis induced by hypoxia or erastin was dampened in lgmnKO mRTECs compared with lgmnWT control. Deficiency of legumain prevented chaperone-mediated autophagy of GPX4. Results of IP suggested interactions between legumain, HSC70, HSP90, and GPX4. Administration of RR-11a ameliorated ferroptosis and renal injury in the AKI model. Together, our data indicate that legumain promotes chaperone-mediated autophagy of GPX4 therefore facilitates tubular ferroptosis in AKI.

15.
Molecules ; 26(3)2021 Jan 20.
Artigo em Inglês | MEDLINE | ID: mdl-33498575

RESUMO

Starting from the enantiopure precursors, a pair of chiral macrocyclic arenes named helic[1]triptycene[3]arenes were conveniently synthesized. The circular dichroism (CD) spectra of the enantiomeric macrocyclic arenes exhibited mirror images, and the X-ray single crystal structures confirmed their absolute conformations as well. Moreover, the macrocyclic arenes showed strong complexation with secondary ammonium and primary ammonium salts containing aminoindan groups. In particular, the chiral macrocyclic arenes exhibited enantioselective recognition ability towards the chiral secondary ammonium salts containing aminoindan groups with an enantioselective ratio up to 3.89.

16.
Int J Mol Sci ; 22(1)2021 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-33466434

RESUMO

The maternal-to-zygotic transition (MZT), which controls maternal signaling to synthesize zygotic gene products, promotes the preimplantation development of mouse zygotes to the two-cell stage. Our previous study reported that mouse granzyme g (Gzmg), a serine-type protease, is required for the MZT. In this study, we further identified the maternal factors that regulate the Gzmg promoter activity in the zygote to the two-cell stage of mouse embryos. A full-length Gzmg promoter from mouse genomic DNA, FL-pGzmg (-1696~+28 nt), was cloned, and four deletion constructs of this Gzmg promoter, Δ1-pGzmg (-1369~+28 nt), Δ2-pGzmg (-939~+28 nt), Δ3-pGzmg (-711~+28 nt) and Δ4-pGzmg (-417~+28 nt), were subsequently generated. Different-sized Gzmg promoters were used to perform promoter assays of mouse zygotes and two-cell stage embryos. The results showed that Δ4-pGzmg promoted the highest expression level of the enhanced green fluorescent protein (EGFP) reporter in the zygotes and two-cell embryos. The data suggested that time-specific transcription factors upregulated Gzmg by binding cis-elements in the -417~+28-nt Gzmg promoter region. According to the results of the promoter assay, the transcription factor binding sites were predicted and analyzed with the JASPAR database, and two transcription factors, signal transducer and activator of transcription 3 (STAT3) and GA-binding protein alpha (GABPα), were identified. Furthermore, STAT3 and GABPα are expressed and located in zygote pronuclei and two-cell nuclei were confirmed by immunofluorescence staining; however, only STAT3 was recruited to the mouse zygote pronuclei and two-cell nuclei injected with the Δ4-pGzmg reporter construct. These data indicated that STAT3 is a maternal transcription factor and may upregulate Gzmg to promote the MZT. Furthermore, treatment with a STAT3 inhibitor, S3I-201, caused mouse embryonic arrest at the zygote and two-cell stages. These results suggest that STAT3, a maternal protein, is a critical transcription factor and regulates Gzmg transcription activity in preimplantation mouse embryos. It plays an important role in the maternal-to-zygotic transition during early embryonic development.

17.
Lancet Digit Health ; 3(2): e88-e97, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33509389

RESUMO

BACKGROUND: Ocular changes are traditionally associated with only a few hepatobiliary diseases. These changes are non-specific and have a low detection rate, limiting their potential use as clinically independent diagnostic features. Therefore, we aimed to engineer deep learning models to establish associations between ocular features and major hepatobiliary diseases and to advance automated screening and identification of hepatobiliary diseases from ocular images. METHODS: We did a multicentre, prospective study to develop models using slit-lamp or retinal fundus images from participants in three hepatobiliary departments and two medical examination centres. Included participants were older than 18 years and had complete clinical information; participants diagnosed with acute hepatobiliary diseases were excluded. We trained seven slit-lamp models and seven fundus models (with or without hepatobiliary disease [screening model] or one specific disease type within six categories [identifying model]) using a development dataset, and we tested the models with an external test dataset. Additionally, we did a visual explanation and occlusion test. Model performances were evaluated using the area under the receiver operating characteristic curve (AUROC), sensitivity, specificity, and F1* score. FINDINGS: Between Dec 16, 2018, and July 31, 2019, we collected data from 1252 participants (from the Department of Hepatobiliary Surgery of the Third Affiliated Hospital of Sun Yat-sen University, the Department of Infectious Diseases of the Affiliated Huadu Hospital of Southern Medical University, and the Nantian Medical Centre of Aikang Health Care [Guangzhou, China]) for the development dataset; between Aug 14, 2019, and Jan 31, 2020, we collected data from 537 participants (from the Department of Infectious Diseases of the Third Affiliated Hospital of Sun Yat-sen University and the Huanshidong Medical Centre of Aikang Health Care [Guangzhou, China]) for the test dataset. The AUROC for screening for hepatobiliary diseases of the slit-lamp model was 0·74 (95% CI 0·71-0·76), whereas that of the fundus model was 0·68 (0·65-0·71). For the identification of hepatobiliary diseases, the AUROCs were 0·93 (0·91-0·94; slit-lamp) and 0·84 (0·81-0·86; fundus) for liver cancer, 0·90 (0·88-0·91; slit-lamp) and 0·83 (0·81-0·86; fundus) for liver cirrhosis, and ranged 0·58-0·69 (0·55-0·71; slit-lamp) and 0·62-0·70 (0·58-0·73; fundus) for other hepatobiliary diseases, including chronic viral hepatitis, non-alcoholic fatty liver disease, cholelithiasis, and hepatic cyst. In addition to the conjunctiva and sclera, our deep learning model revealed that the structures of the iris and fundus also contributed to the classification. INTERPRETATION: Our study established qualitative associations between ocular features and major hepatobiliary diseases, providing a non-invasive, convenient, and complementary method for hepatobiliary disease screening and identification, which could be applied as an opportunistic screening tool. FUNDING: Science and Technology Planning Projects of Guangdong Province; National Key R&D Program of China; Guangzhou Key Laboratory Project; National Natural Science Foundation of China.

18.
Chemosphere ; 263: 128130, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33297118

RESUMO

In the present study, we exposed Procambarus clarkii to different doses (0, 1, and 10 mg/L) of diclofenac (DCF). Meanwhile, we investigated the effects of exposure to DCF on intestinal histology, antioxidant defense, and microbial communities in P. clarkii. The results showed DCF caused histological changes in the intestines. Additionally, DCF induced significant changes in the expression of antioxidant genes including Mn-sod, cat, gst, and gpx. High-throughput sequencing of 16 S rRNA gene revealed DCF changed the diversity, richness, and composition of intestinal microbial communities. The relative abundances of the predominant phyla Proteobacteria, Firmicutes, Bacteroidetes, and Actinobacteria showed significant changes at the phylum level after treatment with DCF. At the genus level, the most predominant genera with marked differences in abundance were Lucibacterium, Shewanella, Bacteroides, Anaerorhabdus, Aeromonas, Acinetobacter, Clostridium XlVb, Arcobacter, Bosea, and so on. To conclude, treatment with DCF could cause intestinal histological damage, induce significant changes of the expression of intestinal antioxidant genes, and impact the composition of intestinal microbiota in P. clarkii. This research will provide novel insights into the toxic effects of DCF on aquatic crustaceans.


Assuntos
Astacoidea , Microbiota , Animais , Antioxidantes , Diclofenaco/toxicidade , Água Doce , Intestinos
19.
J Hazard Mater ; 403: 123569, 2021 02 05.
Artigo em Inglês | MEDLINE | ID: mdl-32798793

RESUMO

Identification of microorganisms that contribute to the whole microbial community is important. In this study, dynamic changes in bioaugmentation process in diesel-polluted seawater collected from two different sites were assessed via simulation experiments. Ultraviolet spectrophotometry and analysis using the molecular operating environment software revealed that the degradation rate of diesel due to bioaugmentation was higher than 70 % after 45 days because of the formation of hydrogen bonds among biosurfactants and diesel components. Community structure and functional genes were analysed via high-throughput sequencing. Results showed that community diversity recovered during bioaugmentation. Principal coordinate analysis showed that the difference in microbial community between the two sites was considerably smaller than that when diesel was added and bioaugmentation was conducted. After bioaugmentation, the main families playing key roles in degradation that became dominant were Alcanivoracaceae, Rhodobiaceae, and Rhodospirillaceae. Moreover, the abundance of functional genes remarkably increased at two different sites.

20.
Life Sci ; 267: 118952, 2021 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-33383048

RESUMO

AIMS: Huntington's disease (HD) is a neurodegenerative disease that causes deficits in neurite outgrowth, which suggests that enhancement of neurite outgrowth is a potential direction by which to improve HD. Our previous publications showed that fibroblast growth factor 9 (FGF9) provides anti-apoptosis and anti-oxidative functions in striatal cell models of HD through the extracellular signal-regulated kinases (ERK) pathway, and FGF9 also stimulates cytoskeletons to enhance neurite outgrowth via nuclear factor kappa B (NF-kB) signaling. In this study, we further demonstrate the importance of the ERK pathway for the neurite outgrowth induced by FGF9 in HD striatal models. MATERIALS AND METHODS: FGF9 was treated with ERK (U0126) or NF-kB (BAY11-7082) inhibitors in STHdhQ7/Q7 and STHdhQ111/Q111 striatal knock-in cell lines to examine neurite outgrowth, cytoskeletal markers, and synaptic proteins via immunofluorescence staining and Western blotting. NF-kB activity was analyzed by NF-kB promoter reporter assay. KEY FINDINGS: Here, we show that suppression of ERK signaling significantly inhibits FGF9-induced neurite outgrowth, cytoskeletal markers, and synaptic proteins in HD striatal cells. In addition, we also show suppression of ERK signaling significantly decreases FGF9-induced NF-kB activation, whereas suppression of NF-kB does not decrease FGF9-induced ERK signaling. These results suggest that FGF9 activates ERK signaling first, stimulates NF-kB upregulation, and then enhances neurite outgrowth in HD striatal cells. SIGNIFICANCE: We elucidate the more detailed mechanisms of neurite outgrowth enhanced by FGF9 in these HD striatal cells. This study may provide insights into targeting neurite outgrowth for HD therapy.


Assuntos
Fator 9 de Crescimento de Fibroblastos/metabolismo , Fator 9 de Crescimento de Fibroblastos/farmacologia , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Neuritos/metabolismo , Animais , Butadienos/farmacologia , Linhagem Celular , Células Cultivadas , Corpo Estriado/metabolismo , Inibidores Enzimáticos/farmacologia , Fator 9 de Crescimento de Fibroblastos/antagonistas & inibidores , Humanos , Proteína Huntingtina/genética , Proteína Huntingtina/metabolismo , Doença de Huntington/metabolismo , Camundongos , Camundongos Transgênicos , NF-kappa B/antagonistas & inibidores , NF-kappa B/metabolismo , Neuritos/efeitos dos fármacos , Crescimento Neuronal/fisiologia , Nitrilos/farmacologia , Proteínas Nucleares/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Proteínas Recombinantes/farmacologia , Transdução de Sinais , Sulfonas/farmacologia
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