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1.
Eur. j. psychiatry ; 37(1): 15-23, enero 2023.
Artigo em Inglês | IBECS | ID: ibc-213937

RESUMO

Background and objectives: Despite the growing pieces of evidence on the relationship between the altered expression level of miRNAs and major depressive disorder (MDD), few studies have focused on the relationship between the altered expression of miRNAs and the severity of depressive symptoms. This study aimed to investigate the relationship between the expression level of miRNA-4485 and the severity of depressive symptoms in major depressive disorder (MDD) patients.MethodsEighty MDD patients without antidepressants and 45 healthy controls were placed and tested for the expression level of miRNA-4485 using quantitative RT‒PCR. At the same time, the Hamilton Depression Scale (HAMD) was used to assess depression symptoms for MDD patients. Twenty-nine out of 80 MDD patients were selected for miRNA expression level testing and symptomatology assessments before and after three weeks of treatment.ResultsThe expression level of miRNA-4485 in the MDD group was significantly overexpressed compared to that in healthy controls (P < 0.05), and the expression level of miRNA-4485 in the higher HAMD group was also much higher than that in the lower HAMD group and healthy controls (P < 0.05). The expression level of miRNA-4485 in MDD patients was negatively correlated with HAMD total score, anxiety/somatization, and bodyweight factor score (P < 0.05), accounting for 9.4%, 12.4% and 5.7%, respectively. MiRNA-4485 significantly predicted MDD and the severity of depressive symptoms (P < 0.05). Compared with that before treatment, the expression level of miRNA-4485 was significantly downregulated after treatment, while the patient's depressive symptoms were improved (p < 0.05). The improvement in depressive symptoms was positively correlated with the downregulation of miRNA-4485, which could significantly predict the effects of antidepressant treatment on MDD (P < 0.05). (AU)


Assuntos
Humanos , Transtorno Depressivo Maior , MicroRNAs , Depressão , Ansiedade , Terapêutica
2.
Biochem Pharmacol ; 208: 115404, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36592709

RESUMO

Developing novel drugs for gastric cancer (GC) is greatly needed, and a reactive oxygen species (ROS)-modulating strategy has been demonstrated to be useful for cancer treatment. However, no organic arsenical-derived ROS-modulating drug has been developed in GC. Here, we constructed ACZ2 and investigated its efficacy and potential mechanism for GC in vitro and in vivo. Our data showed that ACZ2 could inhibit GC proliferation and cause G2/M phase arrest. Moreover, ACZ2 induced ROS accumulation by depleting glutathione (GSH) and TrxR1, triggering a subsequent ER stress response by activating the PERK/EIF2/ATF4/CHOP signalling pathways, which is a crucial step for ACZ2-mediated apoptosis and autophagy. Vitally, ROS scavenger (NAC) and ER stress inhibitor (4PBA) reversed ACZ2/ROS/ER stress-mediated apoptosis and autophagy. Our in vivo results clearly demonstrated that ACZ2 suppressed tumour growth in a GC xenograft model. Collectively, our data indicated that ACZ2 is a potential agent against GC.


Assuntos
Neoplasias Gástricas , Humanos , Neoplasias Gástricas/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Linhagem Celular Tumoral , Apoptose , Autofagia , Tiorredoxinas , Estresse do Retículo Endoplasmático
3.
Insect Mol Biol ; 2023 Jan 13.
Artigo em Inglês | MEDLINE | ID: mdl-36636859

RESUMO

Animal behaviour regulation is a complex process involving many factors, and the nervous system is an essential factor in this process. In many species, pathogens can alter host behaviour by affecting the host's nervous system. An interesting example is that the silkworm shows enhanced locomotor behaviour after being infected with the nucleopolyhedrosis virus. In this study, we analysed the transcriptome of the silkworm brain at different time points after infection and found that various genes related to behaviour regulation changed after infection. In-depth analysis showed that the tyrosine hydroxylase gene might be a key candidate gene, and the content of dopamine, its downstream metabolite, increased significantly in the brain of silkworms infected with the virus. After the injection of tyrosine hydroxylase inhibitor into the infected silkworm, the dopamine content in the silkworm brain decreased and the locomotor behaviour caused by the virus was blocked successfully. These results confirm that tyrosine hydroxylase is involved in regulating enhanced locomotor behaviour after virus infection in silkworms. Furthermore, the tyrosine hydroxylase gene was specifically overexpressed in the brain of the silkworm, and the transgenic silkworm was enhanced in locomotor behaviour and foraging behaviour. These results suggest that the tyrosine hydroxylase gene plays a vital role in regulating insect behaviour.

4.
Org Lett ; 25(3): 517-521, 2023 Jan 27.
Artigo em Inglês | MEDLINE | ID: mdl-36649602

RESUMO

An oxidative dehydrogenative coupling of thiols with alkanes via direct C(sp3)-H bond functionalization to form a new C-S bond and S═O double bond was developed. The present reaction features the use of readily available reagents and high step- and atom-efficiency, thus providing an efficient access to sulfoxides. A possible mechanism is proposed.

5.
J Enzyme Inhib Med Chem ; 38(1): 2169282, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36656085

RESUMO

To explore the potential use of CDK inhibitors in pancreatic ductal adenocarcinoma (PDAC) therapy, a series of novel 2-((4-sulfamoylphenyl)amino)-pyrrolo[2,3-d]pyrimidine derivatives was designed, synthesised, and investigated for inhibition on both CDK kinase activity and cellular proliferation of pancreatic cancer. Most of new sulphonamide-containing derivatives demonstrated strong inhibitory activity on CDK9 and obvious anti-proliferative activity in cell culture. Moreover, two new compounds suppressed cell proliferation of multiple human pancreatic cancer cell lines. The most potent compound 2g inhibited cancer cell proliferation by blocking Rb phosphorylation and induced apoptosis via downregulation of CDK9 downstream proteins Mcl-1 and c-Myc in MIA PaCa-2 cells. CDK9 knockdown experiment suggests its anti-proliferative activity is mainly mediated by CDK9. Additionally, 2g displayed moderate tumour inhibition effect in AsPC-1 derived xenograft mice model. Altogether, this study provided a new start for further optimisation to develop potential CDK inhibitor candidates for PDAC treatment by alone or combination use.


Assuntos
Antineoplásicos , Neoplasias Pancreáticas , Humanos , Camundongos , Animais , Linhagem Celular Tumoral , Antineoplásicos/farmacologia , Pontos de Checagem do Ciclo Celular , Neoplasias Pancreáticas/tratamento farmacológico , Inibidores de Proteínas Quinases/farmacologia , Proliferação de Células , Apoptose , Pirimidinas/farmacologia
6.
Chemosphere ; 317: 137888, 2023 Jan 16.
Artigo em Inglês | MEDLINE | ID: mdl-36657568

RESUMO

Intimately coupled photocatalysis and biodegradation (ICPB) is a promising technology to remove refractory contaminants from water. The key to successful ICPB is a carrier capable of accumulating biofilm and adhering photocatalyst firmly. Herein, BC/g-C3N4 was prepared into a three dimensional porous hydrogel and used as a carrier in ICPB system for the first time. Degradation experiments revealed that the removal rate of tetracycline hydrochloride (TCH) in water by the ICPB system was 96.0% after 10 h, which was significantly higher than that by the photocatalysis (PC, 76.3%), biodegradation (B, 32.5%), adsorption (AD, 17.2%), and photolysis (P, 5.0%) systems. Photo-electrochemical tests confirmed that ICPB system had superior electron transfer ability between photocatalysts and microorganisms. The removal efficiency of COD proved that microorganisms played an important role in the mineralization process of TCH by the ICPB system. After the ICPB degradation experiment, microorganisms maintained high activity and Pseudomonas, Burkholderiaceae and Flavobacterium which had TCH degradation or electron transport ability, were enriched. In conclusion, the novel ICPB carrier overcame shortcomings of the traditional ICPB carrier and the novel ICPB system had superior degradation performance for TCH. This study provided a possible method to promote the practical application of ICPB technology.

7.
J Chromatogr A ; 1689: 463759, 2023 Jan 25.
Artigo em Inglês | MEDLINE | ID: mdl-36599193

RESUMO

Schiff base networks (SNWs) were introduced as a new stir bar coating, and a method of SNWs- coated stir bar sorptive extraction (SBSE) coupled to high performance liquid chromatography-ultraviolet detector (HPLC-UV) was developed for determination of pyrethroid pesticide residues in tobacco. The prepared amorphous SNWs polymer from melamine and 3,5-dihydroxybenzaldehyde riches in triazine rings, hydroxyl groups and amino groups, and the SNWs/polydimethylsiloxane (PDMS) stir bar prepared by sol-gel method can extract weakly polar pyrethroid pesticides through hydrophobic, π-π and hydrogen bonding. The SNWs/PDMS stir bar exhibited high extraction efficiency toward pyrethroid pesticides (70-76%) and good mechanical stability with reused time more than 50 times. Under the optimal experimental conditions, the limits of detection were 0.20 - 0.66 µg/L with relative standard deviation varying in the range of 2.3-8.2%, which meets the requirements of trace analysis of pesticide residues in the tobacco industry. The method was applied to the determination of six pyrethroid pesticides in cigarette samples, and the recovery for the spiked samples ranged from 82 to 117%, showing a great applicability for the analysis of pesticide residues in real samples with a complex sample matrix.


Assuntos
Resíduos de Praguicidas , Praguicidas , Piretrinas , Tabaco , Limite de Detecção , Bases de Schiff , Cromatografia Líquida de Alta Pressão/métodos , Reprodutibilidade dos Testes
8.
Phytomedicine ; 110: 154607, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36610352

RESUMO

BACKGROUND: Sambucus williamsii Hance (SWH) has effectively been adopted to treat joint and bone disorders. Diabetes-induced osteopenia (DOP) is caused primarily by impaired bone formation as a result of hyperglycemia. We had previously demonstrated that SWH extract accelerated fracture healing and promoted osteoblastic MC3T3-E1 cell proliferation and osteogenic differentiation. This study assessed the impacts of SWH extract on diabetes-induced bone loss and explored the mechanisms underlying its osteoprotective effects. METHODS: This work employed MC3T3-E1 cell line for evaluating how SWH extract affected osteogenesis, oxidative stress (OS), and the underlying mechanism in vitro. Streptozotocin-induced osteopenia mouse model was applied with the purpose of assessing SWH extract's osteoprotection on bone homeostasis in vivo. RESULTS: The increased OS of MC3T3-E1 cells exposed to high glucose (HG) was largely because of the upregulation of pro-oxidant genes and the downregulation of antioxidant genes, whereas SWH extract reduced the OS by modulating NADPH oxidase-4 and thioredoxin-related genes by activating cyclic guanosine monophosphate (cGMP) production and increasing the level of cGMP-mediated protein kinase G type-2 (PKG2). The oral administration of SWH extract maintained bone homeostasis in type 1 diabetes mellitus (T1DM) mice by enhancing osteogenesis while decreasing OS. In bones from hyperglycemia-induced osteopenia mice and HG-treated MC3T3-E1 cells, the SWH extract achieved the osteoprotective effects through activating the cGMP/PKG2 signaling pathway, upregulating the level of antioxidant genes, as well as downregulating the level of pro-oxidant genes. CONCLUSION: SWH extract exerts osteoprotective effects on hyperglycemia-induced osteopenia by reversing OS via cGMP/PKG signal transduction and is a potential therapy for DOP.


Assuntos
Doenças Ósseas Metabólicas , Hiperglicemia , Sambucus , Camundongos , Animais , Osteogênese , Sambucus/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Antioxidantes/farmacologia , Antioxidantes/metabolismo , Osteoblastos , Transdução de Sinais , Doenças Ósseas Metabólicas/tratamento farmacológico , Doenças Ósseas Metabólicas/etiologia , Doenças Ósseas Metabólicas/metabolismo , Hiperglicemia/tratamento farmacológico , Hiperglicemia/metabolismo , Homeostase , Estresse Oxidativo
9.
J Clin Med ; 12(2)2023 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-36675377

RESUMO

Objective: To identify and describe the certainty of evidence of gynecology and obstetrics systematic reviews (SRs) using the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) approach. Method: Database searches of SRs using GRADE, published between 1 January 2016 to 31 December 2020, in the 10 "gynecology and obstetrics" journals with the highest impact factor, according to the Journal Citation Report 2019. Selected studies included those SRs using the GRADE approach, used to determine the certainty of evidence. Results: Out of 952 SRs, ninety-six SRs of randomized control trials (RCTs) and/or nonrandomized studies (NRSs) used GRADE. Sixty-seven SRs (7.04%) rated the certainty of evidence for specific outcomes. In total, we identified 946 certainty of evidence outcome ratings (n = 614 RCT ratings), ranging from very-low (42.28%) to low (28.44%), moderate (17.65%), and high (11.63%). High and very low certainty of evidence ratings accounted for 2.16% and 71.60% in the SRs of NRSs, respectively, compared with 16.78% and 26.55% in the SRs of RCTs. In the SRs of RCTs and NRSs, certainty of evidence was mainly downgraded due to imprecision and bias risks. Conclusions: More attention needs to be paid to strengthening GRADE acceptance and building knowledge of GRADE methods in gynecology and obstetrics evidence synthesis.

10.
Molecules ; 28(2)2023 Jan 09.
Artigo em Inglês | MEDLINE | ID: mdl-36677721

RESUMO

As consumers' interest in nature-sourced additives has increased, zein has been treated hydrothermally under alkaline conditions to prepare a nature-sourced emulsifier. The effects of mild hydrothermal-alkaline treatment with different temperatures or alkaline concentrations on the emulsifying properties of zein were investigated. The emulsification activity and stability index of zein hydrolysates increased by 39% and 164%, respectively. The optimal simple stabilized emulsion was uniform and stable against heat treatment up to 90 °C, sodium chloride up to 200 mmol/L, and pH values ranging from 6 to 9. Moreover, it presented excellent storage stability compared to commonly used food emulsifiers. The surface hydrophobicity caused the depolymerization of the tertiary structure of zein and the dissociation of subunits along with exposure of hydrophilic groups. The amino acid composition and circular dichroism results reveal that the treatment dissociated protein subunits and transformed α-helices into anti-parallel ß-sheets and random coil. In conclusion, mild hydrothermal-alkaline treatment may well contribute to the extended functional properties of zein as a nature-sourced emulsifier.


Assuntos
Zea mays , Zeína , Zea mays/química , Zeína/química , Emulsificantes/química , Emulsões , Interações Hidrofóbicas e Hidrofílicas
11.
Sci Adv ; 9(4): eabq5095, 2023 Jan 25.
Artigo em Inglês | MEDLINE | ID: mdl-36696492

RESUMO

We aimed to identify markers in blood (serum) to predict clinically relevant knee osteoarthritis (OA) progression defined as the combination of both joint structure and pain worsening over 48 months. A set of 15 serum proteomic markers corresponding to 13 total proteins reached an area under the receiver operating characteristic curve (AUC) of 73% for distinguishing progressors from nonprogressors in a cohort of 596 individuals with knee OA. Prediction based on these blood markers was far better than traditional prediction based on baseline structural OA and pain severity (59%) or the current "best-in-class" biomarker for predicting OA progression, urinary carboxyl-terminal cross-linked telopeptide of type II collagen (58%). The generalizability of the marker set was confirmed in a second cohort of 86 individuals that yielded an AUC of 70% for distinguishing joint structural progressors. Blood is a readily accessible biospecimen whose analysis for these biomarkers could facilitate identification of individuals for clinical trial enrollment and those most in need of treatment.


Assuntos
Osteoartrite do Joelho , Humanos , Osteoartrite do Joelho/diagnóstico , Osteoartrite do Joelho/metabolismo , Proteômica , Progressão da Doença , Biomarcadores , Dor
12.
Psychol Trauma ; 2023 Jan 26.
Artigo em Inglês | MEDLINE | ID: mdl-36701540

RESUMO

OBJECTIVE: We provide an overview of regression-based causal mediation analysis in the field of traumatic stress and guidance on how to conduct mediation analysis using our R package regmedint. METHOD: We discuss the causal interpretations of the quantities that causal mediation analysis estimates, including total, direct, and indirect effects, especially when the interaction between exposure and mediator is permitted. We discuss the assumptions that must be fulfilled for mediation analyses to validly estimate these causal quantities, discuss suitable study designs for assessing mediation, and describe how causal mediation analysis differs from traditional methods of mediation. To illustrate how to conduct and interpret mediation analysis using our R package regmedint, we use data from a published longitudinal study to assess the extent to which children's externalizing behavior mediates changes in parental negative feelings during the COVID-19 lockdown. We compare the results to those obtained using traditional methods, thus illustrating the importance of accounting for exposure-mediator interaction when an interaction may be present. RESULTS: When the exposure and the mediator interact, traditional methods can provide estimates of direct and indirect effects that differ from those provided by more flexible causal mediation methods. When the exposure and the mediator do not interact, traditional methods and causal mediation method may estimate similar direct and indirect effects depending on the model specification. CONCLUSIONS: In contrast to traditional methods of mediation analysis, regression-based causal mediation methods seek to estimate specific interventional quantities, not mere associations, and the causal methods explicitly allow for exposure-mediator interactions. We recommend using these methods by default rather than using more restrictive traditional methods. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

13.
EBioMedicine ; 88: 104443, 2023 Jan 24.
Artigo em Inglês | MEDLINE | ID: mdl-36701900

RESUMO

BACKGROUND: A reliable risk prediction model is critically important for identifying individuals with high risk of developing lung cancer as candidates for low-dose chest computed tomography (LDCT) screening. Leveraging a cutting-edge machine learning technique that accommodates a wide list of questionnaire-based predictors, we sought to optimize and validate a lung cancer prediction model. METHODS: We developed an Optimized early Warning model for Lung cancer risk (OWL) using the XGBoost algorithm with 323,344 participants from the England area in UK Biobank (training set), and independently validated it with 93,227 participants from UKB Scotland and Wales area (validation set 1), as well as 70,605 and 66,231 participants in the Prostate, Lung, Colorectal, and Ovarian cancer screening trial (PLCO) control and intervention subpopulations, respectively (validation sets 2 & 3) and 23,138 and 18,669 participants in the United States National Lung Screening Trial (NLST) control and intervention subpopulations, respectively (validation sets 4 & 5). By comparing with three competitive prediction models, i.e., PLCO modified 2012 (PLCOm2012), PLCO modified 2014 (PLCOall2014), and the Liverpool Lung cancer Project risk model version 3 (LLPv3), we assessed the discrimination of OWL by the area under receiver operating characteristic curve (AUC) at the designed time point. We further evaluated the calibration using relative improvement in the ratio of expected to observed lung cancer cases (RIEO), and illustrated the clinical utility by the decision curve analysis. FINDINGS: For general population, with validation set 1, OWL (AUC = 0.855, 95% CI: 0.829-0.880) presented a better discriminative capability than PLCOall2014 (AUC = 0.821, 95% CI: 0.794-0.848) (p < 0.001); with validation sets 2 & 3, AUC of OWL was comparable to PLCOall2014 (AUCPLCOall2014-AUCOWL < 1%). For ever-smokers, OWL outperformed PLCOm2012 and PLCOall2014 among ever-smokers in validation set 1 (AUCOWL = 0.842, 95% CI: 0.814-0.871; AUCPLCOm2012 = 0.792, 95% CI: 0.760-0.823; AUCPLCOall2014 = 0.791, 95% CI: 0.760-0.822, all p < 0.001). OWL remained comparable to PLCOm2012 and PLCOall2014 in discrimination (AUC difference from -0.014 to 0.008) among the ever-smokers in validation sets 2 to 5. In all the validation sets, OWL outperformed LLPv3 among the general population and the ever-smokers. Of note, OWL showed significantly better calibration than PLCOm2012, PLCOall2014 (RIEO from 43.1% to 92.3%, all p < 0.001), and LLPv3 (RIEO from 41.4% to 98.7%, all p < 0.001) in most cases. For clinical utility, OWL exhibited significant improvement in average net benefits (NB) over PLCOall2014 in validation set 1 (NB improvement: 32, p < 0.001); among ever smokers of validation set 1, OWL (average NB = 289) retained significant improvement over PLCOm2012 (average NB = 213) (p < 0.001). OWL had equivalent NBs with PLCOm2012 and PLCOall2014 in PLCO and NLST populations, while outperforming LLPv3 in the three populations. INTERPRETATION: OWL, with a high degree of predictive accuracy and robustness, is a general framework with scientific justifications and clinical utility that can aid in screening individuals with high risks of lung cancer. FUNDING: National Natural Science Foundation of China, the US NIH.

14.
Arthritis Rheumatol ; 2023 Jan 27.
Artigo em Inglês | MEDLINE | ID: mdl-36704903

RESUMO

OBJECTIVE: To evaluate the association of Dipeptidyl-peptidase 4 (DPP4, also known as CD26) with cellular senescence of human cartilage and knee osteoarthritis (OA) progression. METHODS: Articular cartilage sections and chondrocytes were acquired from 35 individuals undergoing total knee replacement for OA to evaluate: (1) the association between OA severity and established senescence markers (SA-ß-gal activity and p16) quantified by immunohistochemistry and flow cytometry (n=19); (2) the co-expression of DPP4 with established senescence markers by flow cytometry, and (3) expression levels of anabolic and catabolic genes, senescence related genes and senescence-associated secretory phenotypes (SASPs) in DPP4+ and DPP4- cells, isolated by fluorescence-activated cell sorting vs magnetic-activated cell sorting (n=16). The concentration of soluble DPP4 was measured in synovial fluid (SF) and plasma of the Prediction of Osteoarthritis Progression cohort, and evaluated for its association with knee radiographic OA (rOA) severity at baseline (n=65) and structural rOA progression (n=57) over three years. RESULTS: DPP4 expression was associated with higher SA-ß-gal, p16 expression, senescence-related gene and catabolic gene (ADAMTS5, MMP13, IL6, and IL8) expression, higher SASPs secretion, and lower anabolic gene (COL2A1 and ACAN) expression in primary chondrocytes. SF DPP4 was associated with rOA progression (Odds ratio=105.32, p=0.015), proteases (SF MMP-1 and -3), aggrecan degradation (SF sGAG), indicators of activated macrophages (SF CD14 and CD163) and inflammation (SF IL-6). CONCLUSION: Our study identifies DPP4 as a key surface marker of senescent chondrocytes, and a predictor of rOA progression.

15.
J Hazard Mater ; 446: 130716, 2023 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-36610339

RESUMO

Multimedia contamination by neonicotinoid (NEO) residues has attracted global attention. However, data regarding the multimedia polluted status under certain typical cropping scenarios and the associated risks are scarce. Here, the multimedia occurrence, spatiotemporal distribution, driving factors, transport, and ecological risks of NEOs from tropical rice-vegetable rotation fields were characterized. The heavy NEOs resided in multiple media, and imidacloprid and acetamiprid were the prevailing NEOs, with concentration contributions of 65-80%. The pollution levels of the NEOs, rather than their compositions, exhibited significant spatiotemporal heterogeneity and were highly correlated with the collective (agricultural practices and climate conditions) and differential (e.g., media properties) factors identified using an auto linear regression model. Furthermore, the multimedia transport of NEOs was largely similar but non-negligibly different during the rainy and dry seasons. A new multimedia ecological risk assessment revealed that 50.6% sites were at high risk, and the risk hotspots occurred in the central areas and the winter planting period. The risks were largely contributed by imidacloprid and thiamethoxam, indicating that there were non-ignorable ecological risks. Our results highlight the differential pollution patterns (distribution, transport, and driving factors) of the prevailing NEOs under tropical agricultural scenarios, and the fact that special attention should be paid to the risks posed by NEOs.


Assuntos
Inseticidas , Oryza , Inseticidas/análise , Verduras , Multimídia , Neonicotinoides , China
16.
Environ Res ; 221: 115242, 2023 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-36634891

RESUMO

Low-head dams are one of the most common hydraulic facilities, yet they often fragment rivers, leading to profound changes in aquatic biodiversity and river eutrophication levels. Systematic assessments of river ecosystem structure and functions, and their contribution to eutrophication, are however lacking, especially for urban rivers where low-head dams prevail. In this study, we address this gap with a field survey on microbial community structure and ecosystem function, in combination with hydrological, environmental and ecological factors. Our findings revealed that microbial communities showed significant differences among the cascade impoundments, which may be due to the environment heterogeneity resulting from the cascade low-head dams. The alternating lentic-lotic flow environment created by the low-head dams caused nutrient accumulation in the cascade impoundments, enhancing environmental sorting and interspecific competition relationships, and thus possibly contributing to the reduction in sediment denitrification function. Decreased denitrification led to excessive accumulation of nutrients, which may have aggravated river eutrophication. In addition, structural equation model analysis showed that flow velocity may be the key controlling factor for river eutrophication. Therefore, in the construction of river flood control and water storage systems, the location, type and water storage capacity of low-head dams should be fully considered to optimize the hydrodynamic conditions of rivers. To summarize, our findings revealed the cumulative effects of cascade low-head dams in an urban river, and provided new insights into the trade-off between construction and decommissioning of low-head dams in urban river systems.

17.
BMC Ophthalmol ; 23(1): 28, 2023 Jan 23.
Artigo em Inglês | MEDLINE | ID: mdl-36690959

RESUMO

OBJECTIVE: To develop and validate a nomogram model for predicting chronic ocular graft-versus-host disease (coGVHD) in patients after allogenic haematopoietic stem cell transplantation (allo-HSCT). METHODS: This study included 61 patients who survived at least 100 days after allo-HSCT. Risk factors for coGVHD were screened using LASSO regression, then the variables selected were subjected to logistic regression. Nomogram was established to further confirm the risk factors for coGVHD. Receiver operating characteristic (ROC) curves were constructed to assess the performance of the predictive model with the training and test sets. Odds ratios and 95% confidence intervals (95% CIs) were calculated by using logistic regression analysis. RESULTS: Among the 61 patients, 38 were diagnosed with coGVHD. We selected five texture features: lymphocytes (LYM) (OR = 2.26), plasma thromboplastin antecedent (PTA) (OR = 1.19), CD3 + CD25 + cells (OR = 1.38), CD3 + HLA-DR + cells (OR = 0.95), and the ocular surface disease index (OSDI) (OR = 1.44). The areas under the ROC curve (AUCs) of the nomogram with the training and test sets were 0.979 (95% CI, 0.895-1.000) and 0.969 (95% CI, 0.846-1.000), respectively.And the Hosmer-Lemeshow test was nonsignificant with the training (p = 0.9949) and test sets (p = 0.9691). CONCLUSION: We constructed a nomogram that can assess the risk of coGVHD in patients after allo-HSCT and help minimize the irreversible loss of vision caused by the disease in high-risk populations.


Assuntos
Doença Enxerto-Hospedeiro , Transplante de Células-Tronco Hematopoéticas , Humanos , Nomogramas , Transplante Homólogo/efeitos adversos , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Doença Enxerto-Hospedeiro/etiologia , Fatores de Risco
18.
J Thromb Haemost ; 21(1): 117-132, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36695375

RESUMO

BACKGROUND: Trimethylamine N-oxide (TMAO), a gut microbe-generated metabolite, elicits thrombotic events by enhancing platelet reactivity; however, no studies have reported the effects of TMAO on the metabolism of and response to clopidogrel. OBJECTIVES: To determine whether choline and TMAO could significantly impair metabolic activation of and platelet response to clopidogrel in choline- or TMAO-fed mice and the mechanisms involved. METHODS: Male mice were fed with vehicle control (Ctrl), TMAO, choline alone or in combination with 3,3-dimethyl-1-butanol, N-acetyl-L-cysteine, or ML385 for 14 days and then treated with Ctrl or a single oral dose of clopidogrel. Plasma TMAO, protein levels of clopidogrel-metabolizing enzymes in the liver, plasma concentrations of clopidogrel and its metabolites, and adenosine diphosphate-induced platelet aggregation and activation were measured. In addition, HepG2 cells were treated with Ctrl or TMAO alone or in combination with N-acetyl-L-cysteine, ML385, or apocynin, and CES1, reactive oxygen species (ROS), and Nrf2 protein levels were measured, respectively. RESULTS: TMAO significantly increased Ces1 protein expression and activity and clopidogrel hydrolysis in the liver as well as intracellular ROS and CES1 levels and Nrf2 nucleus translocation in HepG2 cells but decreased the formation of clopidogrel active metabolite and impaired platelet response to clopidogrel. Furthermore, concomitant use of 3,3-dimethyl-1-butanol, N-acetyl-L-cysteine, or ML385 effectively reversed choline- or TMAO-induced impairment of inhibition of platelet aggregation by clopidogrel in mice, respectively. CONCLUSIONS: Choline and TMAO impair the metabolic activation of and platelet response to clopidogrel through the activation of the NOX-dependent ROS/Nrf2/CES1 pathway, suggesting novel strategies for overcoming clopidogrel resistance from bench to bedside.


Assuntos
Colina , Fator 2 Relacionado a NF-E2 , Masculino , Animais , Camundongos , Colina/metabolismo , Clopidogrel , Fator 2 Relacionado a NF-E2/metabolismo , Espécies Reativas de Oxigênio , Ativação Metabólica , Acetilcisteína/farmacologia , Acetilcisteína/metabolismo
19.
J Am Chem Soc ; 2023 Jan 26.
Artigo em Inglês | MEDLINE | ID: mdl-36700656

RESUMO

Supramolecular host-guest ferroelectrics based on solution processing are highly desirable because they are generally created with intrinsic piezoelectricity/ferroelectricity and do not need further poling. Poly(vinylidene fluoride) (PVDF) in the electric-active beta phase after stretching/annealing still shows no piezoelectric response unless poled. Although many supramolecular host-guest ferroelectrics have been discovered, their piezoelectricity is relatively small. Based on H/F substitution, we reported a supramolecular host-guest compound [(CF3-C6H4-NH3)(18-crown-6)][TFSA] (CF3-C6H4-NH3 = 4-trifluoromethylanilinium, TFSA = bis(trifluoromethanesulfonyl)ammonium) with a remarkable piezoelectric response of 42 pC/N under no poling condition. The introduction of F atoms increases phase transition temperature, polar axes, second harmonic generation (SHG) intensity, and piezoelectric coefficient d33. To our knowledge, such a large piezoelectric performance of [(CF3-C6H4-NH3)(18-crown-6)][TFSA] makes its d33, piezoelectric voltage coefficient g33, and mechanical quality factor Qm the highest among the reported supramolecular host-guest ferroelectric compounds and even larger than the values of PVDF. This work provides inspiration for optimizing piezoelectricity on molecular materials.

20.
Cell Discov ; 9(1): 1, 2023 Jan 03.
Artigo em Inglês | MEDLINE | ID: mdl-36596774

RESUMO

Unraveling cell fate plasticity during tissue homeostasis and repair can reveal actionable insights for stem cell biology and regenerative medicine. In the pancreas, it remains controversial whether lineage transdifferentiation among the exocrine cells occur under pathophysiological conditions. Here, to address this question, we used a dual recombinase-mediated genetic system that enables simultaneous tracing of pancreatic acinar and ductal cells using two distinct genetic reporters, avoiding the "ectopic" labeling by Cre-loxP recombination system. We found that acinar-to-ductal transdifferentiation occurs after pancreatic duct ligation or during caerulein-induced pancreatitis, but not during homeostasis or after partial pancreatectomy. On the other hand, pancreatic ductal cells contribute to new acinar cells after significant acinar cell loss. By genetic tracing of cell proliferation, we also quantify the cell proliferation dynamics and deduce the turnover rate of pancreatic exocrine lineages during homeostasis. Together, these results suggest that the lineage transdifferentiation happens between acinar cells and ductal cells in the pancreatic exocrine glands under specific conditions.

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