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1.
BMC Neurol ; 24(1): 39, 2024 Jan 23.
Artigo em Inglês | MEDLINE | ID: mdl-38263044

RESUMO

OBJECTIVE: To predict the appearance of early neurological deterioration (END) among patients with isolated acute pontine infarction (API) based on magnetic resonance imaging (MRI)-derived radiomics of the infarct site. METHODS: 544 patients with isolated API were recruited from two centers and divided into the training set (n = 344) and the verification set (n = 200). In total, 1702 radiomics characteristics were extracted from each patient. A support vector machine algorithm was used to construct a radiomics signature (rad-score). Subsequently, univariate and multivariate logistic regression (LR) analysis was adopted to filter clinical indicators and establish clinical models. Then, based on the LR algorithm, the rad-score and clinical indicators were integrated to construct the clinical-radiomics model, which was compared with other models. RESULTS: A clinical-radiomics model was established, including the 5 indicators rad-score, age, initial systolic blood pressure, initial National Institute of Health Stroke Scale, and triglyceride. A nomogram was then made based on the model. The nomogram had good predictive accuracy, with an area under the curve (AUC) of 0.966 (95% confidence interval [CI] 0.947-0.985) and 0.920 (95% [CI] 0.873-0.967) in the training and verification sets, respectively. According to the decision curve analysis, the clinical-radiomics model showed better clinical value than the other models. In addition, the calibration curves also showed that the model has excellent consistency. CONCLUSION: The clinical-radiomics model combined MRI-derived radiomics and clinical metrics and may serve as a scoring tool for early prediction of END among patients with isolated API.


Assuntos
Nomogramas , Radiômica , Humanos , China , Imageamento por Ressonância Magnética , Infarto
2.
Environ Monit Assess ; 194(5): 379, 2022 Apr 19.
Artigo em Inglês | MEDLINE | ID: mdl-35441264

RESUMO

The present study aims to monitor and assess the occurrence of veterinary antibiotics (VAs) in animal manure, compost, and fertilized soil, originating from different large-scale feedlots. The corresponding concentrations of 39 types of VAs in 8 large-scale feedlots of pig, dairy cow, and poultry were sampled in different seasons and analyzed using LC-MS. The results indicated that 17 types, 16 types, and 5 types of VAs were detected in the swine manure, compost, and fertilized soil with the concentrations of 0.003-17.82, 0.002-9.59, and 0.004-0.007 mg kg-1 (dry matter), respectively; 3 types, 2 types, and 1 type of VAs were detected in the dairy manure, compost, and fertilized soil with the concentrations of 0.003-1.94, 0.014-0.044, and 0.025 mg kg-1 (dry matter), respectively; 7 types, 5 types, and 1 type of VAs were detected in the poultry manure, compost, and fertilized soil with the concentrations of 0.035-1.06, 0.018-0.049, and 0.019 mg kg-1 (dry matter), respectively. The main antibiotic classes persisted in the animal manure and their composting product and fertilized soil were sulfonamides (SAs), macrolides (MAs), and tetracyclines (TCs). Thus, this study would help to adopt strategies in pollution control of VAs and environmental protection of agriculture.


Assuntos
Compostagem , Esterco , Agricultura , Animais , Antibacterianos/análise , Bovinos , China , Monitoramento Ambiental/métodos , Feminino , Esterco/análise , Solo , Suínos
3.
J Biochem Mol Toxicol ; 35(5): e22724, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33491845

RESUMO

Increasing studies have indicated that abnormal expressed long noncoding RNAs (lncRNAs) play a vital role in ischemic stroke. Small nucleolar RNA host gene 8 (Snhg8), a member of lncRNAs, has been found to induce neuronal apoptosis in chronic cerebral ischemia models. Here, we aim to explore the function and molecular mechanism of Snhg8 in modulating microglial inflammation as well as brain microvascular endothelial cell (BMEC) damage following ischemic injury. Our data suggested that Snhg8 was low-expressed in the brain tissues of mice that underwent middle cerebral artery occlusion (MCAO) surgery and oxygen-glucose deprivation (OGD)-treated primary microglia and BMECs. Gain- or loss-of function approaches found that Snhg8 upregulation not only attenuated ischemic induced inflammatory response in microglia but also relieved BMECs injury both in vitro and in vivo. Furthermore, we conducted a bioinformatics analysis to explore the underlying mechanism of Snhg8. The results indicated that Snhg8 served as a competitive endogenous RNA by sponging miR-425-5p, which was proved to promote microglial inflammation and BMECs injury by targeting sirtuin1 (SIRT1)-mediated nuclear factor-κB (NF-κB) pathway. Overall, these results revealed that the Snhg8/miR-425-5p/SIRT1/NF-κB axis plays a critical role in the regulation of cerebral ischemia-induced microglial inflammation and brain-blood barrier damage.


Assuntos
Barreira Hematoencefálica/metabolismo , AVC Isquêmico/metabolismo , MicroRNAs/metabolismo , Microglia/metabolismo , NF-kappa B/metabolismo , RNA Longo não Codificante/metabolismo , Transdução de Sinais , Sirtuína 1/metabolismo , Animais , Barreira Hematoencefálica/lesões , Barreira Hematoencefálica/patologia , AVC Isquêmico/patologia , Masculino , Camundongos , Microglia/patologia
4.
J Hazard Mater ; 465: 133069, 2024 03 05.
Artigo em Inglês | MEDLINE | ID: mdl-38056264

RESUMO

The occurrence of microplastics (MPs) in farmlands poses a threat to soil health and crop yield. There needs to be more research on the role of cropping patterns in the accumulation of MPs and quantizing the threat of MPs on soil health and crop yield. In this study, a field study was carried out to explore the role of cropping patterns in the accumulation of MPs in agricultural soil in Shanghai, China. Furthermore, the specific effect and importance of MPs and each soil physicochemical indicator to soil health and crop yield were clarified, and the threat of MPs in reducing soil health and crop yield was quantized. Relative lower MPs abundance was detected in Shanghai. MPs abundance in vegetable fields was significantly higher than that in orchards. The broad source of MPs, the acceleration of plastics breaking under artificial disturbance and warmer temperatures, and the block of MPs exchange could account for the quicker accumulation of MPs in vegetable fields. MPs have a negligible effect on microbial diversity and metabolic activity which plays a role in soil enzyme activity. Besides, MPs served as one of the critical factors for rice yield reduction.


Assuntos
Microplásticos , Plásticos , Fazendas , China , Solo , Verduras
5.
Int Immunopharmacol ; 128: 111497, 2024 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-38241842

RESUMO

Sepsis is recognized as a potentially fatal condition characterized by acute organ dysfunction resulting from an imbalanced immune response to infection. Acute liver injury (ALI) arises as an inflammatory outcome of immune response dysregulation associated with sepsis. Kupffer cells, which are liver-specific macrophages, are known to have a significant impact on ALI, although the precise regulatory mechanism remains unclear. Numerous studies have showcased the regulatory impact of long non-coding RNAs (lncRNAs) on the progression of diverse ailments, yet their precise regulatory mechanisms remain predominantly unexplored. In this study, a novel long non-coding RNA (lncRNA), referred to as lncRNA 220, was discovered using high-throughput sequencing. The expression of lncRNA 220 was found to be significantly elevated in the livers of mice with lipopolysaccharide (LPS)-induced endotoxemia, specifically during the 8-hour time period. Furthermore, in Kupffer cells treated with LPS, lncRNA 220 was observed to inhibit apoptosis and autophagy by activating the PI3K-AKT-mTORC1 pathway. This effect was achieved through the reduction of X-box protein 1 unspliced (Xbp1u) mRNA stability and suppression of its translation in the context of endoplasmic reticulum stress (ERS). Ultimately, this intervention mitigated the progression of LPS-induced ALI. To summarize, our study establishes lncRNA 220 as a newly identified regulator that suppresses apoptosis and autophagy in Kupffer cells subjected to LPS treatment, indicating its potential as a molecular target for ALI in endotoxemic mice.


Assuntos
Endotoxemia , RNA Longo não Codificante , Camundongos , Animais , Proteínas Proto-Oncogênicas c-akt/metabolismo , Transdução de Sinais , RNA Longo não Codificante/genética , Lipopolissacarídeos , Fosfatidilinositol 3-Quinases/metabolismo , Células de Kupffer/metabolismo , Autofagia , Apoptose
6.
Front Aging Neurosci ; 16: 1364808, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38646447

RESUMO

Background: Vascular cognitive impairment (VCI) is a major cause of cognitive impairment in the elderly and a co-factor in the development and progression of most neurodegenerative diseases. With the continuing development of neuroimaging, multiple markers can be combined to provide richer biological information, but little is known about their diagnostic value in VCI. Methods: A total of 83 subjects participated in our study, including 32 patients with vascular cognitive impairment with no dementia (VCIND), 21 patients with vascular dementia (VD), and 30 normal controls (NC). We utilized resting-state quantitative electroencephalography (qEEG) power spectra, structural magnetic resonance imaging (sMRI) for feature screening, and combined them with support vector machines to predict VCI patients at different disease stages. Results: The classification performance of sMRI outperformed qEEG when distinguishing VD from NC (AUC of 0.90 vs. 0,82), and sMRI also outperformed qEEG when distinguishing VD from VCIND (AUC of 0.8 vs. 0,0.64), but both underperformed when distinguishing VCIND from NC (AUC of 0.58 vs. 0.56). In contrast, the joint model based on qEEG and sMRI features showed relatively good classification accuracy (AUC of 0.72) to discriminate VCIND from NC, higher than that of either qEEG or sMRI alone. Conclusion: Patients at varying stages of VCI exhibit diverse levels of brain structure and neurophysiological abnormalities. EEG serves as an affordable and convenient diagnostic means to differentiate between different VCI stages. A machine learning model that utilizes EEG and sMRI as composite markers is highly valuable in distinguishing diverse VCI stages and in individually tailoring the diagnosis.

7.
PeerJ Comput Sci ; 9: e1337, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37346613

RESUMO

The traditional data-sharing model relies on a centralized third-party platform, which presents challenges such as poor transaction transparency and unsecured data security. In this article, we propose a blockchain-based traceable and secure data-sharing scheme. Firstly, we designed an attribute encryption-based method to protect data and enable fine-grained shared access. Secondly, we developed a secure data storage scheme that combines on-chain and off-chain collaboration. The InterPlanetary File System (IPFS) is used to store encrypted data off-chain, and the hash value of encrypted data is stored on the blockchain. To improve data security, elliptic curve cryptography (ECC) encryption is performed before the hash value is stored. Finally, we designed a smart contract-based log tracking mechanism. The mechanism stores data sharing records on the blockchain and displays them in a visual form to meet the identity tracking needs of both data sharing parties. Experimental results show that our scheme can effectively secure data, track the identities of both parties sharing data in real-time, and ensure high data throughput.

8.
Front Neurol ; 14: 1130748, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36741286

RESUMO

Background: Our previous study revealed that circulating levels of IgG natural antibodies (NAbs) for vascular endothelial growth factor receptor 1 (VEGFR1) were significantly decreased in patients with arteriosclerosis compared with control subjects. To enhance the sensitivity of an enzyme-linked immunosorbent assay (ELISA) developed in-house for antibody testing, the present work was designed to investigate additive signals in the in-house ELISA developed with the combination of two or more linear peptide antigens derived from target proteins of interest, including VEGFR1, oxidized low-density lipoprotein receptor 1 (LOX-1), interleukins 6 (IL6) and 8 (IL8). Methods: A total of 218 patients with ischemic stroke and 198 healthy controls were enrolled and an in-house ELISA was developed with linear peptides derived from VEGFR1, LOX-1, IL6, and IL8 to detect their IgG levels in plasma. Results: Compared with control subjects, plasma levels of IgG NAbs for the IL6-IL8 combination were significantly lower in female patients (Z = -3.149, P = 0.002), whereas male patients showed significantly lower levels of plasma anti-VEGFR IgG (Z = -3.895, P < 0.001) and anti-LOX1a IgG (Z = -4.329, P < 0.001). Because plasma levels of IgG NAbs for both the IL6-IL8-LOX1a-LOX1b combination and the VEGFR1a-VEGFR1b-LOX1a-LOX1b combination were significantly lower in the patient group than the control group, receiver operating characteristic (ROC) analysis was performed and the results showed that the VEGFR1a-VEGFR1b-LOX1a-LOX1b combination had an area under the ROC curve (AUC) of 0.70 for its IgG assay with a sensitivity of 27.1% against the specificity of 95.5% and that the IL6-IL8-LOX1a-LOX1b combination had an AUC of 0.67 for its IgG assay with a sensitivity of 21.1% against the specificity of 95.5%. Spearman correlation analysis showed that plasma IgG NAbs against the IL6-IL8 combination were positively correlated with carotid plaque size only in male patients (r = 0.270, p = 0.002). Conclusions: Circulating IgG NAbs for the target molecules studied may be potential biomarkers for a subgroup of ischemic stroke and also contribute to the gender differences in clinical presentation of the disease.

9.
Sci Total Environ ; 905: 167318, 2023 Dec 20.
Artigo em Inglês | MEDLINE | ID: mdl-37742985

RESUMO

Co-hydrothermal carbonization of sludge and food waste is a promising method for hydrochar valorization. The sulfur content and form of hydrochar are the key parameters that determine its further utilization. However, the effect of the chemical composition of food waste on sulfur redistribution remains unknown. Herein, the sulfur transformation behavior during the co-hydrothermal carbonization of sludge and model compounds (cellulose, starch, xylan, and palmitic acid) of food waste was investigated, with focus on the detailed reaction pathways from inorganic-S/organic-S media in aqueous to hydrochar. The added model compounds, particularly the starch and xylan, increased the sulfur retention ratio from 41.0 to 44.7- 49.2 % in hydrochar. Among them, starch and xylan can react with aliphatic-S in aqueous via cyclization and oxidization to form the thiophene-S/aromatic-S and sulfone-S and can react with SO42--S to form sulfone-S via sulfonate reaction. These formed organic-S can polymerize with hydrolyzed intermediates (i.e., 5 hydroxymethyl-furfural, glucose, and xylose) from model compounds to transform into hydrochar. Cellulose enhanced the formation of sulfone-S in hydrochar via the reactions between the water-insoluble partial hydrolysate and SO42- in the aqueous. Additionally, palmitic acid hydrolysate provided an acidic environment that facilitated the polymerization of thiophene-S/aromatic-S from aqueous to hydrochar. Generally, the chemical composition of food waste largely affects the redistribution behavior of sulfur during co-hydrothermal carbonization, and this occurs primarily due to the differences in the hydrolysate and degree of hydrolysis for various model compounds. The results can provide guidance for preparing sludge-based hydrochar possessing different sulfur content and species, that can be used as clean fuel or carbon material.

10.
BMC Med Genomics ; 16(1): 58, 2023 03 22.
Artigo em Inglês | MEDLINE | ID: mdl-36949429

RESUMO

BACKGROUND: Cuproptosis, a novel form of programmed cell death, plays an essential role in various cancers. However, studies of the function of cuproptosis lncRNAs (CRLs) in colorectal cancer (CRC) remain limited. Thus, this study aims to identify the cuprotosis-related lncRNAs (CRLs) in CRC and to construct the potential prognostic CRLs signature model in CRC. METHODS: First, we downloaded RNA-Seq data and clinical information of CRC patients from TCGA database and obtained the prognostic CRLs based on typical expression analysis of cuproptosis-related genes (CRGs) and univariate Cox regression. Then, we constructed a prognostic model using the Least Absolute Shrinkage and Selection Operator algorithm combined with multiple Cox regression methods (Lasso-Cox). Next, we generated Kaplan-Meier survival and receiver operating characteristic curves to estimate the performance of the prognostic model. In addition, we also analysed the relationships between risk signatures and immune infiltration, mutation, and drug sensitivity. Finally, we performed quantitative reverse transcription polymerase chain reaction (qRT -PCR) to verify the prognostic model. RESULT: Lasso-Cox analysis revealed that four CRLs, SNHG16, LENG8-AS1, LINC0225, and RPARP-AS1, were related to CRC prognosis. Receiver operating characteristic (ROC) and Kaplan-Meier analysis curves indicated that this model performs well in prognostic predictions of CRC patients. The DCA results also showed that the model included four gene signatures was better than the traditional model. In addition, GO and KEGG analyses revealed that DE-CRLs are enriched in critical signalling pathway, such as chemical carcinogenesis-DNA adducts and basal cell carcinoma. Immune infiltration analysis revealed significant differences in immune infiltration cells between the high-risk and low-risk groups. Furthermore, significant differences in somatic mutations were noted between the high-risk and low-risk groups. Finally, we also validated the expression of four CRLs in FHCs cell lines and CRC cell lines using qRT-PCR. CONCLUSION: The signature composed of SNHG16, LENG8-AS1, LINC0225, and RPARP-AS1, which has better performance in predicting colorectal cancer prognosis and are promising biomarkers for prognosis prediction of CRC.


Assuntos
Apoptose , Neoplasias Colorretais , RNA Longo não Codificante , Humanos , Algoritmos , Neoplasias Colorretais/diagnóstico , Neoplasias Colorretais/genética , Prognóstico , RNA Longo não Codificante/genética , Cobre
11.
Chemosphere ; 344: 140378, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37806332

RESUMO

Hydrothermal carbonization of biogas slurry and animal manure into hydrochar could enhance waste recycling waste and minimize ammonia (NH3) volatilization from paddy fields. In this study, cattle manure-derived hydrochar prepared in the presence of Milli-Q water (CMWH) and biogas slurry (CMBSH), and biogas slurry-based hydrochar embedded with zeolite (ZHC) were applied to rice-paddy soil. The results demonstrated that CMBSH and ZHC treatments could significantly mitigate the cumulative NH3 volatilization and yield-scale NH3 volatilization by 27.9-45.2% and 28.5-45.4%, respectively, compared to the control group (without hydrochar addition), and significantly correlated with pH and ammonium-nitrogen (NH4+-N) concentration in floodwater. Nitrogen (N) loss via NH3 volatilization in the control group accounted for 24.9% of the applied N fertilizer, whereas CMBSH- and ZHC-amended treatments accounted for 13.6-17.9% of N in applied fertilizer. The reduced N loss improved soil N retention and availability for rice; consequently, grain N content significantly increased by 6.5-14.9% and N-use efficiency increased by 6.4-16.0% (P < 0.05), respectively. Based on linear fitting results, NH3 volatilization mitigation resulted from lower pH and NH4+-N concentration in floodwater that resulted from the acidic property and specific surface area of hydrochar treatments. Moreover, NH3-oxidizing archaea abundance in hydrochar-treated soil decreased by 40.9-46.9% in response to CMBSH and ZHC treatments, potentially suppressing NH4+-N transformation into nitrate and improving soil NH4+-N retention capacity. To date, this study applied biogas slurry-based hydrochar into paddy soil for the first time and demonstrated that ZHC significantly mitigated NH3 and increased N content. Overall, this study proposes an environmental-friendly strategy to recycle the wastes, biogas slurry, to the paddy fields to mitigate NH3 volatilization and increase grain yield of rice.


Assuntos
Amônia , Oryza , Bovinos , Animais , Amônia/química , Solo/química , Esterco/análise , Biocombustíveis/análise , Volatilização , Fertilizantes/análise , Carvão Vegetal/química , Nitrogênio/análise , Oryza/química , Grão Comestível/química
12.
Plant Physiol Biochem ; 196: 197-209, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-36724704

RESUMO

Heat stress reduces plant growth and reproduction and increases agricultural risks. As a natural compound, melatonin modulates broad aspects of the responses of plants to various biotic and abiotic stresses. However, regulation of the photosynthetic electron transfer, reactive oxygen species (ROS) homeostasis and the redox state of redox-sensitive proteins in the tolerance to heat stress induced by melatonin remain largely unknown. The oxygen evolution complex activity on the electron-donating side of photosystem II (PSII) is inhibited, and the electron transfer process from QA to QB on the electron-accepting side of PSII is inhibited. In this case, heat stress decreased the chlorophyll content, carbon assimilation rate, PSII activity, and the proportion of light absorbed by tomato seedlings during electron transfer. The ROS burst led to the breakdown of the PSII core protein. However, exogenous melatonin increased the net photosynthetic rate by 11.3% compared with heat stress, substantially reducing the restriction of photosynthetic systems induced by heat stress. Additionally, melatonin reduces the oxidative damage to PSII by balancing electron transfer on the donor, reactive center, and acceptor sides. Melatonin was used under heat stress to increase the activity of the antioxidant enzyme and preserve ROS equilibrium. In addition, redox proteomics also showed that melatonin controls the redox levels of proteins involved in photosynthesis, and stress and defense processes, which enhances the expression of oxidative genes. In conclusion, melatonin via controlling the photosynthetic electron transport and antioxidant, melatonin increased tomato heat stress tolerance and aided plant growth.


Assuntos
Antioxidantes , Melatonina , Estresse Oxidativo , Fotossíntese , Solanum lycopersicum , Termotolerância , Melatonina/farmacologia , Solanum lycopersicum/efeitos dos fármacos , Solanum lycopersicum/crescimento & desenvolvimento , Termotolerância/efeitos dos fármacos , Fotossíntese/efeitos dos fármacos , Transporte de Elétrons/efeitos dos fármacos , Espécies Reativas de Oxigênio/metabolismo , Homeostase , Complexo de Proteína do Fotossistema II/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Antioxidantes/farmacologia , Clorofila/metabolismo
13.
Front Aging Neurosci ; 15: 1051177, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36815175

RESUMO

Objective: This study explored the structural imaging changes in patients with subcortical ischemic vascular disease (SIVD)-vascular cognitive impairment no dementia (VCIND) and the correlation between the changes in gray matter volume and the field of cognitive impairment to provide new targets for early diagnosis and treatment. Methods: Our study included 15 patients with SIVD-normal cognitive impairment (SIVD-NCI), 63 with SIVD-VCIND, 26 with SIVD-vascular dementia (SIVD-VD), and 14 normal controls (NC). T1-weighted images of all participants were collected, and DPABI and SPM12 software were used to process the gray matter of the four groups based on voxels. Fisher's exact test, one-way ANOVA and Kruskal-Wallis H test were used to evaluate all clinical and demographic data and compare the characteristics of diencephalic gray matter atrophy in each group. Finally, the region of interest (ROI) of the SIVD-VCIND was extracted, and Pearson correlation analysis was performed between the ROI and the results of the neuropsychological scale. Results: Compared to the NC, changes in gray matter atrophy were observed in the bilateral orbitofrontal gyrus, right middle temporal gyrus, superior temporal gyrus, and precuneus in the SIVD-VCIND. Gray matter atrophy was observed in the left cerebellar region 6, cerebellar crural region 1, bilateral thalamus, right precuneus, and calcarine in the SIVD-VD. Compared with the SIVD-VCIND, gray matter atrophy changes were observed in the bilateral thalamus in the SIVD-VD (p < 0.05, family-wise error corrected). In the SIVD-VCIND, the total gray matter volume, bilateral medial orbital superior frontal gyrus, right superior temporal gyrus, middle temporal gyrus, and precuneus were positively correlated with Boston Naming Test score, whereas the total gray matter volume, right superior temporal gyrus, and middle temporal gyrus were positively correlated with overall cognition. Conclusion: Structural magnetic resonance imaging can detect extensive and subtle structural changes in the gray matter of patients with SIVD-VCIND and SIVD-VD, providing valuable evidences to explain the pathogenesis of subcortical vascular cognitive impairment and contributing to the early diagnosis of SIVD-VCIND and early warning of SIVD-VD.

14.
ACS Chem Neurosci ; 14(17): 3226-3248, 2023 09 06.
Artigo em Inglês | MEDLINE | ID: mdl-37561893

RESUMO

Concomitant inhibition of butyrylcholinesterase (BChE) and histone deacetylase 6 (HDAC6) is supposed to be effective in the treatment of Alzheimer's disease (AD). Inspired by our previous efforts in designing BChE inhibitors, herein, selective BChE and HDAC6 dual inhibitors were successfully identified through the fusion of the core pharmacophoric moiety of BChE and HDAC6 inhibitors. After the structure-activity relationship (SAR) studies, two compounds (24g and 29a) were confirmed to have superior inhibitory activity against BChE (the IC50 against hBChE are 4.0 and 1.8 nM, respectively) and HDAC6 (the IC50 against HDAC6 are 8.9 and 71.0 nM, respectively). These two compounds showed prominently neuroprotective effects in vitro, potent reactive oxygen species (ROS) scavenging effects, and effective metal ion (Fe2+ and Cu2+) chelation. In addition, they exhibited pronounced inhibition of phosphorylated tau and a moderate immunomodulatory effect, with a lack of neurotoxicity at the cellular level. In vivo studies showed that both 24g and 29a ameliorated the cognitive impairment in an Aß1-42-induced mouse model at a low dosage (2.5 mg/kg). Our data demonstrated that BChE/HDAC6 dual inhibitors could establish the basis for a potential new symptomatic and disease-modifying strategy to treat AD.


Assuntos
Doença de Alzheimer , Butirilcolinesterase , Camundongos , Animais , Butirilcolinesterase/metabolismo , Desacetilase 6 de Histona , Inibidores da Colinesterase/farmacologia , Relação Estrutura-Atividade , Inibidores de Histona Desacetilases/farmacologia , Acetilcolinesterase/metabolismo
15.
Eur J Med Chem ; 261: 115828, 2023 Dec 05.
Artigo em Inglês | MEDLINE | ID: mdl-37778239

RESUMO

Kristen rat sarcoma (KRAS) is one of the most common oncogenes in human cancers. As a guanine nucleotide exchange factor, Son of Sevenless Homologue 1 (SOS1) represents a potential therapeutic concept for the treatment of KRAS-mutant cancers because of its activation on KRAS and downstream signaling pathways. In this review, we provide a comprehensive overview of the structure, biological function, and regulation of SOS1. We also focus on the recent advances in SOS1 inhibitors and emphasize their binding modes, structure-activity relationships and pharmacological activities. We hope that this publication can provide a comprehensive compendium on the rational design of SOS1 inhibitors.


Assuntos
Neoplasias , Proteínas Proto-Oncogênicas p21(ras) , Humanos , Proteínas Proto-Oncogênicas p21(ras)/genética , Proteínas Proto-Oncogênicas p21(ras)/metabolismo , Proteína SOS1/metabolismo , Núcleo Familiar , Transdução de Sinais
16.
MedComm (2020) ; 4(5): e398, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37829506

RESUMO

Sepsis is an often-deadly complication of infection that can lead to multiple organ failure. Previous studies have demonstrated that autophagy has a protective effect on liver injury in sepsis. Here, we report a novel long noncoding RNA (lncRNA), named lipopolysaccharide (LPS)-induced liver autophagy regulator (LILAR), which was highly induced in the liver tissues of endotoxemic mice. LILAR deficiency significantly increased the susceptibility of mice to LPS. In contrast, LILAR overexpression rescued the liver injury mediated by LILAR deficiency and increased the survival of LILAR knockout mice with endotoxemia. Autophagy-related protein 13 (Atg13) is a potential downstream target gene of LILAR. LILAR deficiency notably decreased Atg13 expression and suppressed autophagy in the livers of mice challenged with LPS. A reporter gene assay showed that LILAR competitively adsorbed miR-705 to increase the expression of Atg13 in cultured cells, indicating that LILAR participates in the regulation of the autophagy in the liver tissues of endotoxemic mice through a competitive endogenous RNA mechanism. In summary, we identified a novel lncRNA, LILAR, as a hepatic autophagy regulator, which not only promotes our understanding of liver pathophysiology but also provides a potential therapeutic target and/or diagnostic biomarker for liver injury in endotoxemia.

17.
Animals (Basel) ; 13(10)2023 May 17.
Artigo em Inglês | MEDLINE | ID: mdl-37238092

RESUMO

It is important to describe lineages before they go extinct, as we can only protect what we know. This is especially important in the case of microendemic species likely to be relict populations, such as Hynobius salamanders in southern China. Here, we unexpectedly sampled Hynobius individuals in Fujian province, China, and then worked on determining their taxonomic status. We describe Hynobius bambusicolus sp. nov. based on molecular and morphological data. The lineage is deeply divergent and clusters with the other southern Chinese Hynobius species based on the concatenated mtDNA gene fragments (>1500 bp), being the sister group to H. amjiensis based on the COI gene fragment, despite their geographic distance. In terms of morphology, the species can be identified through discrete characters enabling identification in the field by eye, an unusual convenience in Hynobius species. In addition, we noted some interesting life history traits in the species, such as vocalization and cannibalism. The species is likely to be incredibly rare, over a massively restricted distribution, fitting the definition of Critically Endangered following several lines of criteria and categories of the IUCN Red List of Threatened Species.

18.
Hum Psychopharmacol ; 27(4): 392-6, 2012 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-22778022

RESUMO

BACKGROUND: The co-occurrence of schizophrenia and type 2 diabetes mellitus (T2DM) has been well documented. Recent genome-wide association studies and meta-analyses have shown robust associations of the solute carrier family 30 member 8 (SLC30A8) gene variants with T2DM in various populations. We examined the involvement of the SLC30A8 in the susceptibility to schizophrenia in a Han Chinese population. METHODS: The SLC30A8 rs13266634 gene polymorphism was genotyped in 837 chronic schizophrenic and 1109 unrelated healthy controls by using a case control design. We also assessed clinical symptoms. RESULTS: There were no significant differences in the rs13266634 genotype (χ(2) = 1.95, df = 2, p = 0.38) and allele (χ(2) = 0.47, df = 1, p = 0.50) distributions between the patient and control groups. There was no association between rs13266634 and clinical symptoms. CONCLUSION: The SLC30A8 gene variation does not appear to contribute a genetic basis for the co-occurrence of schizophrenia and T2DM.


Assuntos
Proteínas de Transporte de Cátions/genética , Diabetes Mellitus Tipo 2/genética , Esquizofrenia/genética , Adulto , Povo Asiático/genética , Estudos de Casos e Controles , China , Feminino , Estudos de Associação Genética , Predisposição Genética para Doença , Variação Genética , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Adulto Jovem , Transportador 8 de Zinco
19.
Sci Total Environ ; 807(Pt 3): 150997, 2022 Feb 10.
Artigo em Inglês | MEDLINE | ID: mdl-34656588

RESUMO

This study reports the transformation behavior of nitrogen during the co-hydrothermal carbonization of sewage sludge and model compounds (microcrystalline cellulose, starch, lignin, and xylan) of food waste at 220 °C, with a focus on the reaction routes between starch/xylan and NH4+. Most of the nitrogen in the raw sludge was transformed into organic-N (44.6%) and NH4+ (23.3%) in the aqueous product, and only 20.3% of nitrogen was retained in the hydrochar. The added model compounds could react with organic-N (i.e., amino acids and amines) and NH4+ in aqueous products through Maillard and Mannich reactions, generating heterocyclic-N (especially pyrrole-N) which further polymerizes to form nitrogen-containing polyaromatic hydrochar. This leads to an increase in the retention rate of nitrogen to 36.8-50.9%, especially upon the addition of starch and xylan. During the hydrothermal carbonization of starch/xylan in the NH4+ solution, the polymers are first hydrolyzed into monomers, followed by their further reaction with NH4+ to generate pyrrole-N and pyridine-N in aqueous products (especially xylan), and the pyrrole-N can then polymerize with aromatic clusters to form hydrochar-N. The results show that the model compounds of food waste substantially affect the nitrogen transformation pathways during hydrothermal carbonization, mainly because of the structures of their monomers. These findings can guide the production of sludge-based hydrochar with the targeted regulation of nitrogen content and species.


Assuntos
Nitrogênio , Eliminação de Resíduos , Alimentos , Esgotos , Amido
20.
J Agric Food Chem ; 70(7): 2127-2135, 2022 Feb 23.
Artigo em Inglês | MEDLINE | ID: mdl-35138837

RESUMO

Fenobucarb (2-sec-butylphenyl methylcarbamate, BPMC) is a potent carbamate pesticide with high insecticidal activity. In this study, the enantioselective accumulation of BPMC in earthworms (Eisenia foetida) and dissipation in cabbage, Chinese cabbage, strawberry, and soils were investigated. The samples were prepared using the QuEChERS method and analyzed using fast and sensitive chiral high-performance liquid chromatography tandem mass spectrometry (HPLC-MS/MS) analysis. The stereoselective accumulation of BPMC enantiomers revealed that S-(+)-BPMC was preferentially accumulated in earthworms rather than its antipode. However, the dissipation studies showed that S-(+)-BPMC degraded faster than the R-(-)-isomer in cabbage, Chinese cabbage, strawberry, and soils. Furthermore, the cytotoxic effect of BPMC enantiomers toward PC12 and N9 neuronal, A549 lung cancer, and MRC5 lung fibroblast cell lines was evaluated using an 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. Compared with R-(-)- and rac-isomers, S-(+)-BPMC exhibited lower cytotoxicity in neuronal cells and a weaker proliferating effect on lung cancer and lung fibroblast cells. Altogether, the findings suggest the use of the pure S-(+)-enantiomer in agricultural management rather than the use of the racemate or the R-(-)-isomer, which might reduce the environmental risk.


Assuntos
Oligoquetos , Poluentes do Solo , Animais , Carbamatos/análise , Frutas/química , Solo/química , Poluentes do Solo/química , Estereoisomerismo , Espectrometria de Massas em Tandem , Verduras/química
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