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1.
Waste Manag ; 181: 188-198, 2024 May 30.
Artigo em Inglês | MEDLINE | ID: mdl-38615501

RESUMO

The sharp increase in food waste poses a serious threat to food security and environmental sustainability. However, most existing studies have investigated the determinants of food waste behaviors in a separate behavioral process without considering the potential impacts of different factors in an integrated process. To narrow this gap, a comprehensive action determination model (CADM), which integrates network embeddedness and incentive measures, was constructed to explore the impact of various determinants in different processes on food waste behaviors, using data collected from 913 residents in eastern China via an online survey. The empirical results showed that environmental concern was the largest positive factor in predicting personal norms (ß = 0.80, p < 0.001), followed by network embeddedness. With the habitual process considered, residents with ingrained waste habits were more likely to waste food (ß = 0.38, p < 0.001). Moreover, the normative process alleviates behavioral decisions via intentions to reduce food waste. This study confirmed the differences in the situational process and suggested that menu tips increase food waste behaviors, while incentive measures reinforce the influence of intentions on behavior. We therefore address the insufficient ingredients on the effects of different processes on behavior and provide a new perspective for formulating behavioral intervention policies.


Assuntos
Modelos Teóricos , China , Humanos , Inquéritos e Questionários , Alimentos , Gerenciamento de Resíduos/métodos , Feminino , Perda e Desperdício de Alimentos
2.
J Dermatol Sci ; 113(3): 93-102, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38383230

RESUMO

BACKGROUND: Aberrant keratinocytes differentiation has been demonstrated to be associated with a number of skin diseases. The roles of lncRNAs in keratinocytes differentiation remain to be largely unknown. OBJECTIVE: Here we aim to investigate the role of lnc-DC in regulating epidermal keratinocytes differentiation. METHODS: Expression of lnc-DC in the skin was queried in AnnoLnc and verified by FISH. The lncRNA expression profiles during keratinocytes differentiation were reanalyzed and verified by qPCR and FISH. Gene knock-down and over-expression were used to explore the role of lnc-DC in keratinocytes differentiation. The downstream target of lnc-DC was screened by whole transcriptome sequencing. CUT&RUN assay and siRNAs transfection was used to reveal the regulatory effect of GRHL3 on lnc-DC. The mechanism of lnc-DC regulating ZNF750 was revealed by RIP assay and RNA stability assay. RESULTS: Lnc-DC was biasedly expressed in skin and up-regulated during epidermal keratinocytes differentiation. Knockdown lnc-DC repressed epidermal keratinocytes differentiation while over-express lnc-DC showed the opposite effect. GRHL3, a well-known transcription factor regulating keratinocytes differentiation, could bind to the promoter of lnc-DC and regulate its expression. By whole transcriptome sequencing, we identified that ZNF750 was a downstream target of lnc-DC during keratinocytes differentiation. Mechanistically, lnc-DC interacted with RNA binding protein IGF2BP2 to stabilize ZNF750 mRNA and up- regulated its downstream targets TINCR and KLF4. CONCLUSION: Our study revealed the novel role of GRHL3/lnc-DC/ZNF750 axis in regulating epidermal keratinocytes differentiation, which may provide new therapeutic targets of aberrant keratinocytes differentiation related skin diseases.


Assuntos
RNA Longo não Codificante , Dermatopatias , Humanos , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , Fatores de Transcrição/metabolismo , Queratinócitos/metabolismo , Pele/metabolismo , Dermatopatias/metabolismo , Proteínas de Ligação a DNA/genética , Proteínas de Ligação a DNA/metabolismo , Proteínas de Ligação a RNA/metabolismo , Proteínas Supressoras de Tumor/metabolismo
3.
Ecotoxicol Environ Saf ; 273: 116121, 2024 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-38402792

RESUMO

In recent years, nanoplastics (NPs) and triclosan (TCS, a pharmaceutical and personal care product) have emerged as environmental pollution issues, and their combined presence has raised widespread concern regarding potential risks to organisms. However, the combined toxicity and mechanisms of NPs and TCS remain unclear. In this study, we investigated the toxic effects of polystyrene NPs and TCS and their mechanisms on KGN cells, a human ovarian granulosa cell line. We exposed KGN cells to NPs (150 µg/mL) and TCS (15 µM) alone or together for 24 hours. Co-exposure significantly reduced cell viability. Compared with exposure to NPs or TCS alone, co-exposure increased reactive oxygen species (ROS) production. Interestingly, co-exposure to NPs and TCS produced synergistic effects. We examined the activity of superoxide dismutase (SOD) and catalase (CAT), two antioxidant enzymes; it was significantly decreased after co-exposure. We also noted an increase in the lipid oxidation product malondialdehyde (MDA) after co-exposure. Furthermore, co-exposure to NPs and TCS had a more detrimental effect on mitochondrial function than the individual treatments. Co-exposure activated the NRF2-KEAP1-HO-1 antioxidant stress pathway. Surprisingly, the expression of SESTRIN2, an antioxidant protein, was inhibited by co-exposure treatments. Co-exposure to NPs and TCS significantly increased the autophagy-related proteins LC3B-II and LC3B-Ⅰ and decreased P62. Moreover, co-exposure enhanced CASPASE-3 expression and inhibited the BCL-2/BAX ratio. In summary, our study revealed the synergistic toxic effects of NPs and TCS in vitro exposure. Our findings provide insight into the toxic mechanisms associated with co-exposure to NPs and TCS to KGN cells by inducing oxidative stress, activations of the NRF2-KEAP1-HO-1 pathway, autophagy, and apoptosis.


Assuntos
Triclosan , Feminino , Humanos , Espécies Reativas de Oxigênio/metabolismo , Triclosan/toxicidade , Triclosan/metabolismo , Antioxidantes/metabolismo , Proteína 1 Associada a ECH Semelhante a Kelch/metabolismo , Microplásticos/metabolismo , Poliestirenos/toxicidade , Poliestirenos/metabolismo , Fator 2 Relacionado a NF-E2/metabolismo , Estresse Oxidativo , Células da Granulosa/metabolismo
4.
Waste Manag Res ; : 734242X231221082, 2024 Jan 09.
Artigo em Inglês | MEDLINE | ID: mdl-38193464

RESUMO

Residents' food waste is a key part of environmental sustainability and food security. This study investigates influencing factors in reducing food waste by constructing a conceptual model examining the relationship between network embeddedness (NE) and food waste behaviour (FWB), using questionnaire data from 853 urban residents in eastern China, as well as the moderating role of incentive measures (IMs). We find that NE consists of three dimensions: structural embeddedness, relational embeddedness and functional embeddedness. There is an inverted-U-shaped relationship between structural embeddedness and food waste reduction behaviour, whereas relational embeddedness and functional embeddedness positively correlate with food waste reduction behaviour. Furthermore, IMs significantly strengthen the inverted-U-shaped relationship between NE and food waste reduction behaviour. This article reveals the significance of NE and IMs in influencing FWB, expands the application fields of NE and provides valuable guidance for policymakers to better utilize policy interventions.

5.
J Inflamm Res ; 16: 4271-4285, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37791116

RESUMO

Background: Rheumatoid arthritis (RA) patients are prone to developing different metabolic complications. Traditional Chinese Medicine attributes this uncertainty to varied syndrome types. Methods and Results: We retrospectively analyzed some serological indicators of active RA patients and healthy individuals. Randomly selected RA patients were divided into three groups according to NAMPT and SIRT1 expression levels in white blood cells (WBCs). Their disease severity and metabolic status were compared. Representative blood samples were subjected to a UPLC-MS/MS-based metabolomics analysis. Different human WBCs were treated with oleic acid and palmitic acid in vitro. The results indicated that blood glucose and lipid levels were decreased in RA patients, but their decrease was not in accordance with disease severity. Nutrients in the patients highly expressing SIRT1 were well preserved, with the lowest levels of RF and ß-CTX and the highest levels of adiponectin and resistin. Most of them exhibited cold symptoms. When SIRT1 deficiency was obvious, lipid depletion became evident, irrespective of expression levels of NAMPT. Simultaneous high-expression of SIRT1 and NAMPT coincided with the increase in production of lactic acid and the prevalence of hot symptoms. Despite the low levels of IL-6, joint injuries were severe. The corresponding WBCs were especially sensitive to fatty acids anti-inflammatory treatments. The levels of CCL27, CCL11, CCL5, AKP, CRP and ESR were similar among all the groups. Conclusion: NAMPT overexpression is a risk factor for joint injuries and nutrient depletion in RA. Supplementation with lipids would exert beneficial effects on these RA patients. Its aftermath would cause even severe inflammation. Contrarily, SIRT1 up-regulation restrains inflammation and lipid depletion.

6.
Zhongguo Dang Dai Er Ke Za Zhi ; 25(9): 915-922, 2023.
Artigo em Chinês | MEDLINE | ID: mdl-37718396

RESUMO

OBJECTIVES: To identify risk factors associated with early-onset sepsis (EOS) in very preterm infants and develop a nomogram model for predicting the risk of EOS. METHODS: A retrospective analysis was conducted on 344 very preterm infants delivered at the First Affiliated Hospital of Zhengzhou University and admitted to the Department of Neonatology between January 2020 and December 2022. These infants were randomly divided into a training set (241 infants) and a validating set (103 infants) in a 7:3 ratio. The training set was further divided into two groups based on the presence or absence of EOS: EOS (n=64) and non-EOS (n=177). Multivariate logistic regression analysis was performed to identify risk factors for EOS in the very preterm infants. The nomogram model was developed using R language and validated using the validating set. The discriminative ability, calibration, and clinical utility of the model were assessed using receiver operating characteristic (ROC) curve analysis, calibration curve analysis, and decision curve analysis, respectively. RESULTS: The multivariate logistic regression analysis revealed that gestational age, need for tracheal intubation in the delivery room, meconium-stained amniotic fluid, serum albumin level on the first day of life, and chorioamnionitis were risk factors for EOS in very preterm infants (P<0.05). The area under the ROC curve for the training set was 0.925 (95%CI: 0.888-0.963), and that for the validating set was 0.796 (95%CI: 0.694-0.898), confirming the model's good discrimination. The Hosmer-Lemeshow goodness-of-fit test suggested that the model was well-fitting (P=0.621). The calibration curve analysis and decision curve analysis demonstrated that the model had high predictive efficacy and clinical applicability. CONCLUSIONS: Gestational age, need for tracheal intubation in the delivery room, meconium-stained amniotic fluid, serum albumin level on the first day of life, and chorioamnionitis are significantly associated with the development of EOS in very preterm infants.The nomogram model for predicting the risk of EOS in very preterm infants, constructed based on these factors, has high predictive efficacy and clinical applicability.

7.
Zhongguo Zhong Yao Za Zhi ; 48(12): 3215-3223, 2023 Jun.
Artigo em Chinês | MEDLINE | ID: mdl-37382005

RESUMO

This study aimed to investigate the relationship between coagulating cold and blood stasis syndrome and glycolysis, and observe the intervention effect of Liangfang Wenjing Decoction(LFWJD) on the expression of key glycolytic enzymes in the uterus and ovaries of rats with coagulating cold and blood stasis. The rat model of coagulating cold and blood stasis syndrome was established by ice-water bath. After modeling, the quantitative scoring of symptoms were performed, and according to the scoring results, the rats were randomly divided into a model group and LFWJD low-, medium-and high-dose groups(4.7, 9.4, 18.8 g·kg~(-1)·d~(-1)), with 10 in each group. Another 10 rats were selected as the blank group. After 4 weeks of continuous administration by gavage, the quantitative scoring of symptoms was repeated. Laser speckle flowgraphy was used to detect the changes of microcirculation in the ears and uterus of rats in each group. Hematoxylin-eosin(HE) staining was used to observe the pathological morphology of uterus and ovaries of rats in each group. The mRNA and protein expressions of pyruvate dehydrogenase kinase 1(PDK1), hexokinase 2(HK2) and lactate dehydrogenase A(LDHA) in the uterus and ovaries of rats were examined by real-time quantitative polymerase chain reaction(RT-qPCR) and Western blot, respectively. The rats in the model group showed signs of coagulating cold and blood stasis syndrome, such as curl-up, less movement, thickened veins under the tongue, and reduced blood perfusion in the microcirculation of the ears and uterus, and HE staining revealed a thinning of the endometrium with disorganized arrangement of epithelial cells and a decrease in the number of ovarian follicles. Compared with the model group, the treatment groups had alleviated coagulating cold and blood stasis, which was manifested as red tongue, reduced nail swelling, no blood stasis at the tail end as well as increased blood perfusion of the microcirculation in the ears and uterus(P<0.05 or P<0.01). Among the groups, the LFWJD medium-and high-dose groups had the most significant improvement in coagulating cold and blood stasis, with neatly arranged columnar epithelial cells in uterus, and the number of ovarian follicles was higher than that in the model group, especially mature follicles. The mRNA and protein expressions of PDK1, HK2, LDHA in uterus and ovaries were up-regulated in the model group(P<0.05 or P<0.01), while down-regulated in LFWJD medium-and high-dose groups(P<0.05 or P<0.01). The LFWJD low-dose group presented a decrease in the mRNA expressions of PDK1, HK2 and LDHA in uterus and ovaries as well as in the protein expressions of HK2 and LDHA in uterus and HK2 and PDK1 in ovaries(P<0.05 or P<0.01). The therapeutic mechanism of LFWJD against coagulating cold and blood stasis syndrome is related to the down-regulation of key glycolytic enzymes PDK1, HK2 and LDHA, and the inhibition of glycolytic activities in uterus and ovaries.


Assuntos
Ovário , Útero , Feminino , Animais , Ratos , Folículo Ovariano , Lactato Desidrogenase 5 , Glicólise
8.
Data Brief ; 48: 109291, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-37383732

RESUMO

Plant factories are an advanced form of facility agriculture that enable efficient plant cultivation through controllable environmental conditions, making them highly suitable for the automation and intelligent application of machinery. Tomato cultivation in plant factories has significant economic and agricultural value and can be utilized for various applications such as seedling cultivation, breeding, and genetic engineering. However, manual completion is still required for operations such as detection, counting, and classification of tomato fruits, and the application of machine detection is currently inefficient. Furthermore, research on the automation of tomato harvesting in plant factory environments is limited due to the lack of a suitable dataset. To address this issue, a tomato fruit dataset was constructed for plant factory environments, named as TomatoPlantfactoryDataset, which can be quickly applied to multiple tasks, including the detection of control systems, harvesting robots, yield estimation, and rapid classification and statistics. This dataset features a micro tomato variety and was captured under different artificial lighting conditions, including changes in tomato fruit, complex lighting environment changes, distance changes, occlusion, and blurring. By facilitating the intelligent application of plant factories and the widespread adoption of tomato planting machinery, this dataset can contribute to the detection of intelligent control systems, operation robots, and fruit maturity and yield estimation. The dataset is publicly available for free and can be utilized for research and communication purposes.

9.
Br J Pharmacol ; 180(15): 1899-1929, 2023 08.
Artigo em Inglês | MEDLINE | ID: mdl-37197802

RESUMO

Antimalarial drug discovery has until recently been driven by high-throughput phenotypic cellular screening, allowing millions of compounds to be assayed and delivering clinical drug candidates. In this review, we will focus on target-based approaches, describing recent advances in our understanding of druggable targets in the malaria parasite. Targeting multiple stages of the Plasmodium lifecycle, rather than just the clinically symptomatic asexual blood stage, has become a requirement for new antimalarial medicines, and we link pharmacological data clearly to the parasite stages to which it applies. Finally, we highlight the IUPHAR/MMV Guide to MALARIA PHARMACOLOGY, a web resource developed for the malaria research community that provides open and optimized access to published data on malaria pharmacology.


Assuntos
Antimaláricos , Malária , Humanos , Malária/tratamento farmacológico , Antimaláricos/farmacologia , Antimaláricos/uso terapêutico , Descoberta de Drogas , Ensaios de Triagem em Larga Escala
10.
Chin J Integr Med ; 29(11): 989-997, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37171548

RESUMO

OBJECTIVE: To explore the underlying mechanism of inhibition by Jinkui Shenqi Pills (JKSQP) on glucocorticoid-enhanced axial length elongation in experimental lens-induced myopia (LIM) guinea pigs. METHODS: Sixty 2-week old male guinea pigs were randomly divided into 4 groups with 15 guinea pigs in each group, according to the random numbers generated by SPSS software: control, LIM, saline and JKSQP groups. The control group includes animals with no treatment, while the guinea pigs in the other 3 groups received lens-induced myopization on the right eyes throughout the experiment (for 8 weeks). The saline and JKSQP groups were given daily intraperitoneal injections of 10 mg/kg hydrocortisone for 2 consecutive weeks at the same time, and then orally administered either saline or JKSQP [13.5 g/(kg•d) for 6 consecutive weeks. Body weight, anal temperature and animal appearance were observed and recorded to evaluate the GC-associated symptoms. The ocular parameters, including refraction and axial length, were measured by streak retinoscopy and A-scan ultrasonography, respectively. The levels of plasma hormones associated with the hypothalamic-pituitary-adrenal axis (HPAA), including free triiodothyronine, free thyroxine, estradiol and testosterone, were measured by radioimmunoassay, and cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate were measured by enzyme-linked immunosorbent assay. In addition, the mRNA and protein expressions of retinal amphiregulin (AREG) was measured by quantitative real-time polymerase chain reaction and Western blotting, respectively. RESULTS: JKSQP effectively increased body weight and anal temperature, improved animal appearance and suppressed axial length elongation in glucocorticoid-enhanced myopic guinea pigs with normalization of 4 HPAA-associated plasma hormones (all P<0.05). The plasma level of cAMP was significantly increased, whereas the plasma level of cGMP and the mRNA and protein expressions of retinal AREG were decreased after treatment with JKSQP (all P<0.05). CONCLUSION: JKSQP exhibited a significant inhibitory effect on axial length elongation with decreased expression of AREG in the retina, and normalized 4 HPAA-associated plasma hormones and the expression of cAMP and cGMP in GC-enhanced myopic guinea pigs.


Assuntos
Glucocorticoides , Miopia , Cobaias , Masculino , Animais , Sistema Hipotálamo-Hipofisário , Sistema Hipófise-Suprarrenal , Miopia/tratamento farmacológico , Miopia/metabolismo , Peso Corporal , RNA Mensageiro , Modelos Animais de Doenças
11.
Front Psychol ; 14: 1129752, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36925591

RESUMO

The widespread adoption of electric vehicles (EVs) largely depends on the acceptance of the public. Previous studies pay more attention to the factors affecting EV adoption from the customer perspective but lack the perspective of the interaction between sellers and customers. Based on a survey of 1,014 respondents in China, this work developed a research model analyzing the effect of interaction on the intention to purchase EVs and using experience value (EPV) as the mediating variable. The results showed that the functional experience value (FEV) was positively affected by the environment-customer interaction (ECI). The FEV, emotional experience value (EEV), and social experience value (SEV) were all positively affected by salesman-customer interaction (SCI). In addition, they all had positive impacts on purchasing intention (PI). We further analyzed the differences in the interaction between the different business models. Compared with multi-business model car companies, the ECI for single-business model car companies had a more positive impact on the PI. However, the impact of ECI for single-business model companies on PI was negative. The SCI of single-business model car companies positively impacted the PI, whereas the SCI of multi-business model car companies had no significant impact on the PI. These findings provide insight into further understanding the mechanism of interactions affecting EV adoption and help perfect future promotion strategies.

12.
Kaohsiung J Med Sci ; 39(5): 511-521, 2023 May.
Artigo em Inglês | MEDLINE | ID: mdl-36744836

RESUMO

Chronic wounds seriously affect the quality of life of the elderly, obese people, and diabetic patients. The excessive inflammatory response is a key driver of delayed chronic wound healing. Although lavender essential oil (EO [lav]) has been proven to have anti-inflammatory and accelerate wound curative effects, the specific molecular mechanism involved is still ambiguous. The results showed that the wounds treated with lipopolysaccharide (LPS) not only had delayed healing, but also the expression levels of pro-inflammatory cytokines, such as tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), interleukin-1ß (IL-1ß), and the inflammatory mediator protein, high-mobility group box 1 protein (HMGB-1), in the wound tissues were significantly increased. However, treatment of LPS-induced chronic wounds with EO (lav) accelerated wound healing and decreased IL-1ß and HMGB-1 expression levels. It was further found that LPS induced macrophage pyroptosis to produce IL-1ß. After treatment with EO (lav), the expression level of macrophage pyroptosis marker Gasdermin D (GSDMD) and pyroptosis-related cytotoxic effects were significantly reduced. Immunofluorescence results also directly indicate that EO (lav) can protect macrophages from LPS-induced pyroptosis. Moreover, EO (lav) can down-regulate expression levels of IL-1ß, GSDMD, and nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3) in the caspase-11-related pyroptotic signaling pathway. This study demonstrates that EO (lav) can reduce proinflammatory factor production and ameliorate inflammatory response by inhibiting macrophage pyroptosis, which accelerates LPS-induced chronic wound healing.


Assuntos
Caspases , Lipopolissacarídeos , Humanos , Idoso , Lipopolissacarídeos/farmacologia , Caspases/metabolismo , Caspases/farmacologia , Piroptose , Qualidade de Vida , Macrófagos/metabolismo , Proteínas de Transporte/metabolismo , Proteínas HMGB/metabolismo , Proteínas HMGB/farmacologia
13.
Bioorg Chem ; 133: 106402, 2023 04.
Artigo em Inglês | MEDLINE | ID: mdl-36791618

RESUMO

As an ideal anti-inflammatory target, cyclin-dependent kinase 8 (CDK8) has gradually attracted the attention of researchers. CDK8 inhibition up-regulates Interleukin-10 (IL-10) expression by enhancing the transcriptional activity of activator protein-1 (AP-1), and augmenting IL-10 abundance is a viable strategy for the treatment of inflammatory bowel disease (IBD). In this research, through structure-based drug design and dominant fragment hybridization, a series of poly-substituted pyridine derivatives were designed and synthesized as CDK8 inhibitors. Ultimately, compound CR16 was identified as the best one, which exhibited good inhibitory activity against CDK8 (IC50 = 74.4 nM). In vitro and in vivo studies indicated that CR16 could enhance the transcriptional activity of AP-1, augment the abundance of IL-10, and affect CDK8-related signaling pathways including TLR7/NF-κB/MAPK and IL-10-JAK1-STAT3 pathways. In addition, CR16 showed potent therapeutic effect in an animal model of IBD.


Assuntos
Interleucina-10 , Inibidores de Proteínas Quinases , Animais , Quinase 8 Dependente de Ciclina/antagonistas & inibidores , Interleucina-10/metabolismo , Inibidores de Proteínas Quinases/química , Inibidores de Proteínas Quinases/farmacologia , Piridinas/farmacologia , Transdução de Sinais , Fator de Transcrição AP-1
14.
J Magn Reson Imaging ; 57(5): 1352-1364, 2023 05.
Artigo em Inglês | MEDLINE | ID: mdl-36222324

RESUMO

BACKGROUND: The high level of expertise required for accurate interpretation of prostate MRI. PURPOSE: To develop and test an artificial intelligence (AI) system for diagnosis of clinically significant prostate cancer (CsPC) with MRI. STUDY TYPE: Retrospective. SUBJECTS: One thousand two hundred thirty patients from derivation cohort between Jan 2012 and Oct 2019, and 169 patients from a publicly available data (U-Net: 423 for training/validation and 49 for test and TrumpeNet: 820 for training/validation and 579 for test). FIELD STRENGTH/SEQUENCE: 3.0T/scanners, T2 -weighted imaging (T2 WI), diffusion-weighted imaging, and apparent diffusion coefficient map. ASSESSMENT: Close-loop AI system was trained with an Unet for prostate segmentation and a TrumpetNet for CsPC detection. Performance of AI was tested in 410 internal and 169 external sets against 24 radiologists categorizing into junior, general and subspecialist group. Gleason score >6 was identified as CsPC at pathology. STATISTICAL TESTS: Area under the receiver operating characteristic curve (AUC-ROC); Delong test; Meta-regression I2 analysis. RESULTS: In average, for internal test, AI had lower AUC-ROC than subspecialists (0.85 vs. 0.92, P < 0.05), and was comparable to junior (0.84, P = 0.76) and general group (0.86, P = 0.35). For external test, both AI (0.86) and subspecialist (0.86) had higher AUC than junior (0.80, P < 0.05) and general reader (0.83, P < 0.05). In individual, it revealed moderate diagnostic heterogeneity in 24 readers (Mantel-Haenszel I2  = 56.8%, P < 0.01), and AI outperformed 54.2% (13/24) of readers in summary ROC analysis. In multivariate test, Gleason score, zonal location, PI-RADS score and lesion size significantly impacted the accuracy of AI; while effect of data source, MR device and parameter settings on AI performance is insignificant (P > 0.05). DATA CONCLUSION: Our AI system can match and to some case exceed clinicians for the diagnosis of CsPC with prostate MRI. EVIDENCE LEVEL: 3 TECHNICAL EFFICACY: Stage 2.


Assuntos
Imageamento por Ressonância Magnética , Neoplasias da Próstata , Masculino , Humanos , Imageamento por Ressonância Magnética/métodos , Neoplasias da Próstata/patologia , Inteligência Artificial , Estudos Retrospectivos , Imagem de Difusão por Ressonância Magnética/métodos
15.
Brain ; 146(1): 278-294, 2023 01 05.
Artigo em Inglês | MEDLINE | ID: mdl-35867854

RESUMO

Spinal bulbar muscular atrophy (SBMA), the first identified CAG-repeat expansion disorder, is an X-linked neuromuscular disorder involving CAG-repeat-expansion mutations in the androgen receptor (AR) gene. We utilized CRISPR-Cas9 gene editing to engineer novel isogenic human induced pluripotent stem cell (hiPSC) models, consisting of isogenic AR knockout, control and disease lines expressing mutant AR with distinct repeat lengths, as well as control and disease lines expressing FLAG-tagged wild-type and mutant AR, respectively. Adapting a small-molecule cocktail-directed approach, we differentiate the isogenic hiPSC models into motor neuron-like cells with a highly enriched population to uncover cell-type-specific mechanisms underlying SBMA and to distinguish gain- from loss-of-function properties of mutant AR in disease motor neurons. We demonstrate that ligand-free mutant AR causes drastic mitochondrial dysfunction in neurites of differentiated disease motor neurons due to gain-of-function mechanisms and such cytotoxicity can be amplified upon ligand (androgens) treatment. We further show that aberrant interaction between ligand-free, mitochondria-localized mutant AR and F-ATP synthase is associated with compromised mitochondrial respiration and multiple other mitochondrial impairments. These findings counter the established notion that androgens are requisite for mutant AR-induced cytotoxicity in SBMA, reveal a compelling mechanistic link between ligand-free mutant AR, F-ATP synthase and mitochondrial dysfunction, and provide innovative insights into motor neuron-specific therapeutic interventions for SBMA.


Assuntos
Células-Tronco Pluripotentes Induzidas , Atrofia Muscular Espinal , Humanos , Receptores Androgênicos/genética , Receptores Androgênicos/metabolismo , Células-Tronco Pluripotentes Induzidas/metabolismo , Atrofia Muscular Espinal/genética , Atrofia Muscular Espinal/metabolismo , Atrofia Muscular , Mitocôndrias/metabolismo , Trifosfato de Adenosina/metabolismo
16.
Zhongguo Dang Dai Er Ke Za Zhi ; 24(11): 1207-1212, 2022 Nov 15.
Artigo em Chinês | MEDLINE | ID: mdl-36398545

RESUMO

OBJECTIVES: To investigate the efficacy of intravitreal anti-vascular endothelial growth factor (anti-VEGF) injection in the treatment of retinopathy of prematurity (ROP) and the risk factors for recurrence. METHODS: A retrospective analysis was performed on the medical data of 159 infants with ROP who were born in the First Affiliated Hospital of Zhengzhou University and underwent anti-VEGF treatment from January 2016 to December 2021. According to the presence or absence of recurrence within the follow-up period after initial anti-VEGF treatment, they were divided into a recurrence group with 24 infants and a non-recurrence group with 135 infants. The medical data were compared between the two groups, and a multivariate logistic regression analysis was used to investigate the risk factors for the recurrence of ROP after anti-VEGF treatment. RESULTS: After one-time anti-VEGF treatment, all 159 infants showed regression of plus disease. Recurrence was observed in 24 infants (15.1%) after anti-VEGF treatment, with a mean interval of (8.4±2.6) weeks from treatment to recurrence. The multivariate logistic regression analysis showed that preoperative fundus hemorrhage and prolonged total oxygen supply time were risk factors for the recurrence of ROP (P<0.05), while gestational hypertension was a protective factor (P<0.05). CONCLUSIONS: Intravitreal anti-VEGF injection is effective for ROP. Preoperative fundus hemorrhage and long duration of oxygen therapy may increase the risk of ROP recurrence, and further studies are needed to investigate the influence of gestational hypertension on the recurrence of ROP.


Assuntos
Hipertensão Induzida pela Gravidez , Retinopatia da Prematuridade , Feminino , Humanos , Lactente , Recém-Nascido , Gravidez , Inibidores da Angiogênese/efeitos adversos , Inibidores da Angiogênese/uso terapêutico , Fatores de Crescimento Endotelial/uso terapêutico , Hemorragia , Oxigênio/uso terapêutico , Retinopatia da Prematuridade/tratamento farmacológico , Estudos Retrospectivos , Fatores de Risco , Fator A de Crescimento do Endotélio Vascular
17.
Comput Math Methods Med ; 2022: 6517965, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36245838

RESUMO

Obstructive sleep apnea (OSA) is caused by repeated blockage of the upper respiratory airways during sleep. The traditional evaluation methods for OSA severity are yet limited. This study aimed to screen gene signatures to effectively evaluate OSA severity. Expression profiles of peripheral blood mononuclear cells in the different severities of OSA patients were accessed from Gene Expression Omnibus (GEO) database. A total of 446 differentially expressed genes (DEGs) were screened among the varying severities of OSA samples by analysis of variance (ANOVA) test. A total of 1,152 DEGs were screened between the pre- and post-treatment OSA samples by using t test. Overlap of the two groups of DEGs was selected (88 DEGs) for Metascape enrichment analysis. Afterwards, Mfuzz package was used to perform soft clustering analysis on these 88 genes, by which 6 clusters were obtained. It was observed that the gene expression condition of the cluster 3 was positively associated with OSA severity degree; also, the gene expression condition in cluster 4 was negatively correlated with OSA severity. A total of 10 gene markers related to OSA progression were selected from cluster 3 and cluster 4. Their expression levels and correlation were analyzed. The marker genes in cluster 3 and cluster 4 were examined, finding that most genes were significantly correlated with apnea hypopnea index (AHI). An accurate and objective assessment of the severity of OSA is of great significance for formulating follow-up treatment strategies for patients with OSA. In this paper, a set of marker genes that can detect the severity of OSA were screened by bioinformatics methods, which could be jointly used with the traditional OSA diagnostic index to achieve a more reliable OSA severity evaluation.


Assuntos
Leucócitos Mononucleares , Apneia Obstrutiva do Sono , Análise por Conglomerados , Marcadores Genéticos , Humanos , Polissonografia , Sono , Apneia Obstrutiva do Sono/diagnóstico , Apneia Obstrutiva do Sono/genética
18.
Front Pediatr ; 10: 985878, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36034570

RESUMO

Objective: To explore the potential of walking alone milestone combined reading-frame rule to improve the early diagnosis of Duchenne muscular dystrophy (DMD). Method: To retrospectively describe the genotype and phenotype of Duchenne and Becker muscular dystrophies (BMD) patients with deletions and duplicates in the dystrophin gene. The sensitivity and specificity of the reading frame rule were calculated and compared to that of the combined reading frame rule and walking alone milestone. The diagnostic coincidence rate of two different methods was analyzed. Result: One hundred sixty-nine male DMD/BMD patients were enrolled, including 17 cases of BMD and 152 cases of DMD. The diagnostic coincidence rate, diagnostic sensitivity, and specificity of the reading-frame rule for DMD/BMD were 85.2, 86.8, and 70.59%, respectively. The sensitivity and specificity of the reading frame principle combined with the walking alone milestone for DMD/BMD were 96.05 and 70.59%, respectively. The diagnostic coincidence rate increased to 93.49%, significantly different from that predicted by reading- frame rule (P < 0.05). Conclusion: The reading-frame rule combined with the walking alone milestone significantly improved the early diagnosis rate of DMD.

19.
Biomed Pharmacother ; 150: 113067, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35658235

RESUMO

Methotrexate (MTX) is a first line anti-rheumatic drug. This study was designed to investigate the impact of rheumatoid arthritis (RA) conditions on its oral absorption, and clarify the relevance with changes of MTX absorption-related transporters in rheumatic models. MTX was orally administered to healthy, collagen-induced arthritis (CIA), and adjuvant-induced arthritis (AIA) rats. MTX plasma concentrations were determined by a validated liquid chromatography-mass spectrometry method. We found that intestinal MTX absorption was significantly increased in CIA/AIA rats versus healthy controls. This finding was supported by small intestine-based MTX uptake assay in vitro. Meanwhile, intestinal expression of both reduced folate carrier 1 (RCF1) and proton-coupled folate transporter (PCFT) remained unchanged. The everted intestinal sac assay confirms RFC1 is the key transporter accounting for intestinal MTX absorption, as its antagonist salicylazosulfapyridine showed potent capacity in reducing MTX uptake. No correlation between RA-related cytokines and RCF1 expression was observed in clinical samples. We further revealed that when cultured with AIA rat or RA patient serum, lactate and adenosine triphosphate (ATP) production as well as MTX uptake in MDCKII cells were significantly increased, and this increase was completely abrogated by ATP production-related metabolic inhibitors. Thanks to its inhibitory effects on MTX bioavailability, the glycolysis inhibitor shikonin diminished MTX-induced injuries of kidney and liver in AIA rats. These data demonstrate that glycolysis-driven high energy metabolism increases MTX absorption in rheumatic subjects, leading to the exacerbated toxicity. These findings will have important implications in optimizing MTX regimens for RA treatment with better efficacy and lower toxicity.


Assuntos
Antirreumáticos , Artrite Experimental , Artrite Reumatoide , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos , Trifosfato de Adenosina/metabolismo , Animais , Antirreumáticos/uso terapêutico , Antirreumáticos/toxicidade , Artrite Experimental/tratamento farmacológico , Artrite Reumatoide/tratamento farmacológico , Artrite Reumatoide/metabolismo , Glicólise , Humanos , Absorção Intestinal , Metotrexato/farmacologia , Ratos
20.
Int J Biol Macromol ; 214: 290-300, 2022 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-35716788

RESUMO

AHL (AT-HOOK MOTIF NUCLEAR LOCALIZED) protein is an important transcription factor in plants that regulates a wide range of biological process. It is considered to have evolved from an independent PPC domain in prokaryotes to a complete protein in modern plants. AT-hook motif and PPC conserved domains are the main functional domains of AHL. Since the discovery of AHL, their evolution and function have been continuously studied. The AHL gene family has been identified in multiple species and the functions of several members of the gene family have been studied. Here, we summarize the evolution and structural characteristics of AHL genes, and emphasize their biological functions. This review will provide a basis for further functional study and crop breeding.


Assuntos
Motivos AT-Hook , Proteínas de Arabidopsis , Motivos AT-Hook/genética , Proteínas de Arabidopsis/genética , Núcleo Celular/genética , Núcleo Celular/metabolismo , Melhoramento Vegetal , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo
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