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1.
Insects ; 15(5)2024 May 13.
Artigo em Inglês | MEDLINE | ID: mdl-38786905

RESUMO

The fall webworm (FWW), H. cunea (Drury) (Lepidoptera: Erebidae: Arctiidae), is an extremely high-risk globally invasive pest. Understanding the invasion dynamics of invasive pests and identifying the critical factors that promote their spread is essential for devising practical and efficient strategies for their control and management. The invasion dynamics of the FWW and its influencing factors were analyzed using standard deviation ellipse and spatial autocorrelation methods. The analysis was based on statistical data on the occurrence of the FWW in China. The dissemination pattern of the FWW between 1979 and 2022 followed a sequence of "invasion-occurrence-transmission-outbreak", spreading progressively from coastal to inland regions. Furthermore, areas with high nighttime light values, abundant ports, and non-forested areas with low vegetation cover at altitudes below 500 m were more likely to be inhabited by the black-headed FWW. The dynamic invasion pattern and the driving factors associated with the fall webworm (FWW) provide critical insights for future FWW management strategies. These strategies serve not only to regulate the dissemination of insects and diminish migratory tendencies but also to guarantee the implementation of efficient early detection systems and prompt response measures.

2.
Neuron ; 112(13): 2177-2196.e6, 2024 Jul 03.
Artigo em Inglês | MEDLINE | ID: mdl-38653248

RESUMO

White matter injury (WMI) causes oligodendrocyte precursor cell (OPC) differentiation arrest and functional deficits, with no effective therapies to date. Here, we report increased expression of growth hormone (GH) in the hypoxic neonatal mouse brain, a model of WMI. GH treatment during or post hypoxic exposure rescues hypoxia-induced hypomyelination and promotes functional recovery in adolescent mice. Single-cell sequencing reveals that Ghr mRNA expression is highly enriched in vascular cells. Cell-lineage labeling and tracing identify the GHR-expressing vascular cells as a subpopulation of pericytes. These cells display tip-cell-like morphology with kinetic polarized filopodia revealed by two-photon live imaging and seemingly direct blood vessel branching and bridging. Gain-of-function and loss-of-function experiments indicate that GHR signaling in pericytes is sufficient to modulate angiogenesis in neonatal brains, which enhances OPC differentiation and myelination indirectly. These findings demonstrate that targeting GHR and/or downstream effectors may represent a promising therapeutic strategy for WMI.


Assuntos
Bainha de Mielina , Neovascularização Fisiológica , Pericitos , Animais , Pericitos/metabolismo , Pericitos/efeitos dos fármacos , Camundongos , Bainha de Mielina/metabolismo , Neovascularização Fisiológica/efeitos dos fármacos , Neovascularização Fisiológica/fisiologia , Hormônio do Crescimento/metabolismo , Hormônio do Crescimento/farmacologia , Animais Recém-Nascidos , Hipóxia/metabolismo , Diferenciação Celular/efeitos dos fármacos , Camundongos Endogâmicos C57BL , Células Precursoras de Oligodendrócitos/metabolismo , Células Precursoras de Oligodendrócitos/efeitos dos fármacos , Receptores da Somatotropina/metabolismo , Receptores da Somatotropina/genética , Angiogênese
3.
Plant Phenomics ; 5: 0129, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38107768

RESUMO

Pine wilt disease (PWD) is a significantly destructive forest disease. To control the spread of PWD, an urgent need exists for a real-time and efficient method to detect infected trees. However, existing object detection models have often faced challenges in balancing lightweight design and accuracy, particularly in complex mixed forests. To address this, an improvement was made to the YOLOv5s (You Only Look Once version 5s) algorithm, resulting in a real-time and efficient model named PWD-YOLO. First, a lightweight backbone was constructed, composed of multiple connected RepVGG Blocks, significantly enhancing the model's inference speed. Second, a C2fCA module was designed to incorporate rich gradient information flow and concentrate on key features, thereby preserving more detailed characteristics of PWD-infected trees. In addition, the GSConv network was utilized instead of conventional convolutions to reduce network complexity. Last, the Bidirectional Feature Pyramid Network strategy was used to enhance the propagation and sharing of multiscale features. The results demonstrate that on a self-built dataset, PWD-YOLO surpasses existing object detection models with respective measurements of model size (2.7 MB), computational complexity (3.5 GFLOPs), parameter volume (1.09 MB), and speed (98.0 frames/s). The Precision, Recall, and F1-score on the test set are 92.5%, 95.3%, and 93.9%, respectively, which confirms the effectiveness of the proposed method. It provides reliable technical support for daily monitoring and clearing of infected trees by forestry management departments.

4.
J Biol Chem ; 299(11): 105324, 2023 11.
Artigo em Inglês | MEDLINE | ID: mdl-37806494

RESUMO

Wolf-Hirschhorn syndrome (WHS) is a developmental disorder attributed to a partial deletion on the short arm of chromosome 4. WHS patients suffer from oral manifestations including cleft lip and palate, hypodontia, and taurodontism. WHS candidate 1 (WHSC1) gene is a H3K36-specific methyltransferase that is deleted in every reported case of WHS. Mutation in this gene also results in tooth anomalies in patients. However, the correlation between genetic abnormalities and the tooth anomalies has remained controversial. In our study, we aimed to clarify the role of WHSC1 in tooth development. We profiled the Whsc1 expression pattern during mouse incisor and molar development by immunofluorescence staining and found Whsc1 expression is reduced as tooth development proceeds. Using real-time quantitative reverse transcription PCR, Western blot, chromatin immunoprecipitation, and luciferase assays, we determined that Whsc1 and Pitx2, the initial transcription factor involved in tooth development, positively and reciprocally regulate each other through their gene promoters. miRNAs are known to regulate gene expression posttranscriptionally during development. We previously reported miR-23a/b and miR-24-1/2 were highly expressed in the mature tooth germ. Interestingly, we demonstrate here that these two miRs directly target Whsc1 and repress its expression. Additionally, this miR cluster is also negatively regulated by Pitx2. We show the expression of these two miRs and Whsc1 are inversely correlated during mouse mandibular development. Taken together, our results provide new insights into the potential role of Whsc1 in regulating tooth development and a possible molecular mechanism underlying the dental defects in WHS.


Assuntos
Fenda Labial , Fissura Palatina , MicroRNAs , Síndrome de Wolf-Hirschhorn , Animais , Camundongos , MicroRNAs/genética , Fatores de Transcrição , Síndrome de Wolf-Hirschhorn/genética , Síndrome de Wolf-Hirschhorn/metabolismo , Proteína Homeobox PITX2
5.
Inorg Chem ; 62(38): 15527-15536, 2023 Sep 25.
Artigo em Inglês | MEDLINE | ID: mdl-37696003

RESUMO

Deep-ultraviolet (DUV) nonlinear optical (NLO) materials play a crucial role in cutting-edge laser technology. In order to solve the serious layered growth tendency of the sole commercial DUV NLO crystal KBe2BO3F2 (KBBF), developing alternative systems of compounds with bulk crystal habits has become an urgent task for practical applications. Herein, a novel strategy was developed by applying non-centrosymmetric (NCS) cancrinite (CAN)-type zincophosphates {Na6(OH)2(H2O)2}Cs2[ZnPO4]6 with bulk-crystal habits as the prototype to design new DUV NLO crystals. Two new anhydrous alkali zincophosphates, namely, {(Li6 -xNaxO)A2}[(ZnPO4)6] (A = Cs, Rb; x = 2-3) crystallizing in the NCS hexagonal space group P63 (no. 173) with a CAN-type framework, were successfully synthesized via a modified fluoro-solvo-hydrothermal method by applying triethylamine (TEA) and concentrated NaF solution as a co-solvent. Interestingly, the rigidity of the NCS CAN-type framework acting as the host ensures the non-centrosymmetry of the resulting new compounds. Meanwhile, the replacement of water molecules by guest cationic species in the channels or cages can greatly improve the thermal stability of the resultant crystal and tune its NLO properties. The synergetic effect of the host framework and the guest species makes the two compounds transparent down to the DUV region (<200 nm) and exhibit SHG effects. Therefore, the proposed rational design strategy of applying the known zeotype NCS frameworks as prototypes together with the modified fluoro-solvo-hydrothermal method opens a great avenue for highly effectively exploring new DUV NLO materials.

6.
Inorg Chem ; 62(35): 14431-14438, 2023 Sep 04.
Artigo em Inglês | MEDLINE | ID: mdl-37622651

RESUMO

Developing strategies to rational design noncentrosymmetric structure still attract much interest for their applications in nonlinear optical and piezoelectric materials. Two noncentrosymmetric (NCS) alkaline earth metal bismuth phosphates have been successfully achieved via partial replacement of Bi3+ with Ca2+ or Sr2+ ions. BiCa(H0.5PO4)2 (designated as CaBiPO) and BiSr(H0.5PO4)2 (designated as SrBiPO), together with their solid solution Bi(Sr1-xCax)(H0.5PO4)2 (0 < x ≤ 0.5), crystallize in the NCS space group C2. Both CaBiPO and SrBiPO exhibit ultraviolet nonlinear optical (NLO) properties, and their second-harmonic generation effects belong to type-II phase matching. Meanwhile, they could also act as photoluminescence hosts in which the Eu3+-doping samples SrBiPO:xEu3+ (x = 0.02-0.2) emit orange light. The effect of different radius ions on the derivative structures and the structure-NLO property relationship has also been discussed in detail.

7.
Clin Trials ; 20(2): 121-132, 2023 04.
Artigo em Inglês | MEDLINE | ID: mdl-36629015

RESUMO

BACKGROUND: Monitoring is essential to ensure patient safety and data integrity in clinical trials as per Good Clinical Practice. The Standard Protocol Items: Recommendations for Interventional Trials Statement and its checklist guides authors to include monitoring in their protocols. We investigated how well monitoring was reported in published 'protocol papers' for contemporary randomised controlled trials. METHODS: A systematic search was conducted in PubMed to identify eligible protocol papers published in selected journals between 1 January 2020 and 31 May 2020. Protocol papers were classified by whether they reported monitoring and, if so, by the details of monitoring. Data were summarised descriptively. RESULTS: Of 811 protocol papers for randomised controlled trials, 386 (48%; 95% CI: 44%-51%) explicitly reported some monitoring information. Of these, 20% (77/386) reported monitoring information consistent with an on-site monitoring approach, and 39% (152/386) with central monitoring, 26% (101/386) with a mixed approach, while 14% (54/386) did not provide sufficient information to specify an approach. Only 8% (30/386) of randomised controlled trials reported complete details about all of scope, frequency and organisation of monitoring; frequency of monitoring was the least reported. However, 6% (25/386) of papers used the term 'audit' to describe 'monitoring'. DISCUSSION: Monitoring information was reported in only approximately half of the protocol papers. Suboptimal reporting of monitoring hinders the clinical community from having the full information on which to judge the validity of a trial and jeopardises the value of protocol papers and the credibility of the trial itself. Greater efforts are needed to promote the transparent reporting of monitoring to journal editors and authors.


Assuntos
Lista de Checagem , Projetos de Pesquisa , Humanos , Ensaios Clínicos Controlados Aleatórios como Assunto , Revisões Sistemáticas como Assunto
8.
bioRxiv ; 2023 Dec 23.
Artigo em Inglês | MEDLINE | ID: mdl-38187542

RESUMO

While many reptiles can replace their tooth throughout life, human loss the tooth replacement capability after formation of the permanent teeth. It was thought that the difference in tooth regeneration capability depends on the persistence of a specialized dental epithelial structure, the dental lamina that contains dental epithelial stem cells (DESC). Currently, we know very little about DESC such as what genes are expressed or its chromatin accessibility profile. Multiple markers of DESC have been proposed such as Sox2 and Lgr5 . Few single cell RNA-seq experiments have been performed previously, but no obvious DESC cluster was identified in these scRNA-seq datasets, possible due to that the expression level of DESC markers such as Sox2 and Lgr5 is too low or the percentage of DESC is too low in whole tooth. We utilize a mouse line Sox2-GFP to enrich Sox2+ DESC and use Smart-Seq2 protocol and ATAC-seq protocol to generate transcriptome profile and chromatin accessibility profile of P2 Sox2+ DESC. Additionally, we generate transcriptome profile and chromatin accessibility profile of E11.5 Sox2+ dental lamina cells. With transcriptome profile and chromatin accessibility profile, we systematically identify potential key transcription factors for E11.5 Sox2+ cells and P2 Sox2+ cells. We identified transcription factors including Pitx2, Id3, Pitx1, Tbx1, Trp63, Nkx2-3, Grhl3, Dlx2, Runx1, Nfix, Zfp536 , etc potentially formed the core transcriptional regulatory networks of Sox2+ DESC in both embryonic and postnatal stages.

9.
Sensors (Basel) ; 22(22)2022 Nov 21.
Artigo em Inglês | MEDLINE | ID: mdl-36433602

RESUMO

In real-world applications of detecting faults, many factors-such as changes in working conditions, equipment wear, and environmental causes-can cause a significant mismatch between the source domain on which classifiers are trained and the target domain to which those classifiers are applied. As such, existing deep network algorithms perform poorly under different working conditions. To solve this problem, we propose a novel fault diagnosis method named Joint Adversarial Domain Adaptation (JADA) for fault detection under different working conditions. Our approach simultaneously aligns marginal distribution and conditional distribution across the source and target through a unified adversarial learning process. JADA aims to construct domain-invariant and category-discriminative feature representation that is effective and robust for substantial distribution difference caused by working conditions. We also introduce a supervision signal, namely center loss, that penalizes the distances between the deep features and their corresponding class centers. This makes the learned features better equipped with more discriminative structures and effectively prevents mode collapse. Twenty-four transfer fault diagnosis tasks based on two experimental platforms were conducted to evaluate the effectiveness of the proposed methods. Extensive experiments verified that the JADA can significantly outperform several popular methods under different transfer diagnosis tasks.


Assuntos
Aclimatação , Algoritmos
10.
Mol Ther Nucleic Acids ; 26: 1148-1158, 2021 Dec 03.
Artigo em Inglês | MEDLINE | ID: mdl-34853714

RESUMO

Anaplastic thyroid cancer (ATC) is an aggressive, highly metastatic cancer that expresses high levels of the microRNA (miR)-17-92 cluster. We employ an miR inhibitor system to study the function of the different miRs within the miR-17-92 cluster based on seed sequence homology in the ATC SW579 cell line. While three of the four miR-17-92 families were oncogenic, we uncovered a novel role for miR-17 as a tumor suppressor in vitro and in vivo. Surprisingly, miR-17 inhibition increased expression of the miR-17-92 cluster and significantly increased the levels of the miR-18a and miR-19a mature miRs. miR-17 inhibition increased expression of the cell cycle activator CCND2, associated with increased cell proliferation and tumor growth in transplanted SW579 cells in xenograft mice. miR-17 regulates MYCN and c-MYC expression in SW579 cells, and the inhibition of miR-17 increased MYCN and c-MYC expression, which increased pri-miR-17-92 transcripts. Thus, inhibition of miR-17 activated the expression of the oncogenic miRs, miR-18a and miR-19a. While many cancers express high levels of miR-17, linking it with tumorigenesis, we demonstrate that miR-17 inhibition does not inhibit thyroid tumor growth in SW579 and MDA-T32 ATC cells but increases expression of the other miR-17-92 family members and genes to induce cancer progression.

11.
Mol Ther Nucleic Acids ; 26: 307-320, 2021 Dec 03.
Artigo em Inglês | MEDLINE | ID: mdl-34513312

RESUMO

Micropeptides (microproteins) encoded by transcripts previously annotated as long noncoding RNAs (lncRNAs) are emerging as important mediators of fundamental biological processes in health and disease. Here, we applied two computational tools to identify putative micropeptides encoded by lncRNAs that are expressed in the human pancreas. We experimentally verified one such micropeptide encoded by a ß cell- and neural cell-enriched lncRNA TCL1 Upstream Neural Differentiation-Associated RNA (TUNAR, also known as TUNA, HI-LNC78, or LINC00617). We named this highly conserved 48-amino-acid micropeptide beta cell- and neural cell-regulin (BNLN). BNLN contains a single-pass transmembrane domain and localizes at the endoplasmic reticulum (ER) in pancreatic ß cells. Overexpression of BNLN lowered ER calcium levels, maintained ER homeostasis, and elevated glucose-stimulated insulin secretion in pancreatic ß cells. We further assessed the BNLN expression in islets from mice fed a high-fat diet and a regular diet and found that BNLN is suppressed by diet-induced obesity (DIO). Conversely, overexpression of BNLN enhanced insulin secretion in islets from lean and obese mice as well as from humans. Taken together, our study provides the first evidence that lncRNA-encoded micropeptides play a critical role in pancreatic ß cell functions and provides a foundation for future comprehensive analyses of micropeptide function and pathophysiological impact on diabetes.

12.
Zhongguo Zhong Yao Za Zhi ; 46(9): 2333-2343, 2021 May.
Artigo em Chinês | MEDLINE | ID: mdl-34047138

RESUMO

Network Meta-analysis was used to evaluate the efficacy and safety of different oral Chinese patent medicines combined with transcatheter arterial chemoembolization(TACE) in the treatment of primary liver cancer. Randomized controlled trials of oral Chinese patent medicines for primary liver cancer were retrieved from CNKI, Wanfang, VIP, SinoMed, PubMed, Cochrane Library and EMbase databases from inception to May 2020. According to the Cochrane recommendation standard, the quality of the included articles was evaluated, and the data were analyzed by RevMan, R software and GeMTC software. A total of 10 kinds of oral Chinese patent medicines and 68 RCTs were included. Network Meta-analysis results showed that: as compared with TACE alone, 10 kinds of oral Chinese patent medicines combined with TACE showed advantages in effective rate, 1-year survival rate, 2-year survival rate, KPS score improvement rate and reduced adverse reaction incidence. In the pairwise comparison of oral Chinese patent medicines, the results showed that Cidan Capsules were superior to Jinlong Capsules and Xihuang Pills in 1-year survival rate. According to the probabi-lity ranking results: Shenyi Capsules and Ganfule were more obvious in improving the effective rate; Cidan Capsules and Shenyi Capsules were more effective in improving the 1-year survival rate; Pingxiao Capsules and Shenyi Capsules had better efficacy in improving 2-year survival rate; Huaier Granules and Shenyi Capsules had better efficacy in improving the quality of life; Huisheng Oral Liquid and Ganfule were more effective in reducing the incidence of adverse reactions(such as nausea, vomiting and leukocytosis). The current evidence showed that oral Chinese patent medicine combined with TACE was superior to TACE alone in efficacy and safety. In terms of the effective rate, 1-year survival rate, 2-year survival rate, KPS score improvement rate and reduced adverse reaction incidence, the optimal treatment measures were Shenyi Capsules, Cidan Capsules, Pingxiao Capsules, Huaier Granules and Huisheng Oral Liquid in turn. However, due to the limitations of the research, the current level of evidence is not high, and clear conclusions and evi-dence strength still need to be further verified and improved by high-quality researches.


Assuntos
Carcinoma Hepatocelular , Quimioembolização Terapêutica , Medicamentos de Ervas Chinesas , Neoplasias Hepáticas , Carcinoma Hepatocelular/tratamento farmacológico , China , Humanos , Neoplasias Hepáticas/tratamento farmacológico , Metanálise em Rede , Medicamentos sem Prescrição , Qualidade de Vida
13.
Zhongguo Zhong Yao Za Zhi ; 46(2): 478-487, 2021 Jan.
Artigo em Chinês | MEDLINE | ID: mdl-33645137

RESUMO

To systematically evaluate the efficacy and safety of Huaier Granules in the adjuvant treatment of primary liver cancer. The databases of CNKI, Wanfang, VIP, CBMdisc, PubMed, Cochrane Library and EMbase were searched by computer to screen out the randomized controlled trial on Huaier Granules combined with Western medicine in the treatment of primary liver cancer from the establishment of the databases to January 2020. Data extraction and quality evaluation were conducted for the included literature. Meta-analysis was conducted with RevMan 5.3 software, and evidence quality evaluation was conducted for the outcomes by GRADE profiler software. A total of 24 articles were included, with a total sample size of 2 664 cases. Meta-analysis showed that as compared with Western medicine alone, Huaier Granules combined with Western medicine could improve the objective remission rate(RR=1.38, 95%CI[1.26, 1.51], P<0.000 01), disease control rate(RR=1.29, 95%CI[1.10, 1.52], P=0.002) and 6-month survival rate(RR=1.20, 95%CI[1.10, 1.32], P<0.000 1), 1-year survival rate(RR=1.39, 95%CI[1.23, 1.58], P<0.000 01), 2-year survival rate(RR=1.95, 95%CI[1.28, 2.96], P=0.002), KPS score(MD=17.15, 95%CI[6.47, 27.83], P=0.002) and the improvement rate of KPS score(RR=2.02, 95%CI[1.47, 2.77], P<0.000 1), AFP decline rate(RR=1.40, 95%CI[1.20, 1.62], P<0.000 1), CD3~+(MD=17.34, 95%CI[9.28, 25.40], P<0.000 1), CD4~+(MD=8.62, 95%CI[1.59, 15.64], P=0.02), CD8~+(MD=1.95, 95%CI[-3.93, 7.82], P=0.52), CD4~+/CD8~+(MD=0.42, 95%CI[-0.33, 1.17], P=0.27); reduce the level of AFP(MD=-71.57, 95%CI[-80.42,-62.72], P<0.000 01), recurrence rate(RR=0.76, 95%CI[0.67, 0.85], P<0.000 01), and incidence of adverse reactions(RR=0.60, 95%CI[0.41, 0.89], P=0.01) in patients with primary liver cancer. According to the GRADE system, the evidence for outcome measures was low to very low. The results show that Huaier Granules have certain efficacy and high safety in adjuvant treatment of primary liver cancer, but its effect in reducing adverse reactions and improve immunity remains to be verified. Due to the poor quality of the included studies and evidences, the conclusions still need to be further verified by multi-center, large sample, and randomized double-blind controlled studies.


Assuntos
Medicamentos de Ervas Chinesas , Neoplasias Hepáticas , Adjuvantes Farmacêuticos , Misturas Complexas , Humanos , Neoplasias Hepáticas/tratamento farmacológico , Trametes
14.
Front Neuroanat ; 15: 592772, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33716679

RESUMO

Background and Aims: Numerous studies have demonstrated thalamus-related structural, functional, and metabolic abnormalities in minimal hepatic encephalopathy (MHE). We conducted the first study to investigate thalamic structural connectivity alterations in MHE. METHODS: Diffusion tensor imaging (DTI)-based probabilistic tractography was employed to determine the structural linkage between the thalamus and cortical/subcortical regions in 52 cirrhotic patients [22 with MHE; 30 without MHE (NHE)] and 30 controls. We measured these thalamic connections, which included connectivity strength (CS), fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD), and radial diffusivity (RD), and then compared these among the three groups. Neurocognitive assessment was also performed. Correlation analysis was conducted to investigate the relationship between neurocognitive performance and the above measurements. Classification analysis was performed to determine whether thalamic connection measurements can distinguish MHE from NHE. RESULTS: The probabilistic tractography revealed thalamic structural connections, which were disrupted in cirrhotic patients (as reflected by a decrease in CS/FA and an increase in MD/AD/RD). Abnormal thalamic connections primarily involved the prefrontal cortex, sensorimotor cortex, parietal cortex, medial temporal cortex and hippocampus, and striatum. Thalamic connectivity abnormalities deteriorated from NHE to MHE, and they were correlated with patients' neurocognitive performance. The moderate classification accuracy was obtained using CS and MD as discriminating indexes. CONCLUSION: Our results demonstrated the altered thalamic structural connectivity involving both cortical and subcortical regions in MHE, which could be regarded as representative of MHE-related widespread impairments in white matter pathways. The disturbed thalamic connectivity may underlie the mechanism of cognitive deficits in MHE and may potentially be utilized as a biomarker for diagnosing MHE and in monitoring disease progression. In addition to thalamic-cortical/subcortical connections, further studies are recommended to explore the structural alterations in other white matter pathways in MHE.

15.
Autophagy ; 17(8): 1841-1855, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-32597296

RESUMO

Defective macroautophagy/autophagy and a failure to initiate the adaptive unfolded protein response (UPR) in response to the endoplasmic reticulum (ER) stress contributes to obesity-associated metabolic dysfunction. However, whether and how unresolved ER stress leads to defects in the autophagy pathway and to the progression of obesity-associated hepatic pathologies remains unclear. Obesity suppresses the expression of hepatic spliced XBP1 (X-box binding protein 1; sXBP1), the key transcription factor that promotes the adaptive UPR. Our RNA-seq analysis revealed that sXBP1 regulates genes involved in lysosomal function in the liver under fasting conditions. Chromatin immunoprecipitation (ChIP) analyzes of both primary hepatocytes and whole livers further showed that sXBP1 occupies the -743 to -523 site of the promoter of Tfeb (transcription factor EB), a master regulator of autophagy and lysosome biogenesis. Notably, this occupancy was significantly reduced in livers from patients with steatosis. In mice, hepatic deletion of Xbp1 (xbp1 LKO) suppressed the transcription of Tfeb as well as autophagy, whereas hepatic overexpression of sXbp1 enhanced Tfeb transcription and autophagy. Moreover, overexpression of Tfeb in the xbp1 LKO mouse liver ameliorated glucose intolerance and steatosis in mice with diet-induced obesity (DIO). Conversely, loss of TFEB function impaired the protective role of sXBP1 in hepatic steatosis in mice with DIO. These data indicate that sXBP1-Tfeb signaling has direct functional consequences in the context of obesity. Collectively, our data provide novel insight into how two organelle stress responses are integrated to protect against obesity-associated metabolic dysfunction.Abbreviations: AAV8: adeno-associated virus serotype 8; ACTB: actin, beta; ANOVA: analysis of variance; ATF6: activating transcription factor-6; ATG: autophagy related; BECN1: beclin 1; BMI: body mass index; ChIP: chromatin immunoprecipitation; CLEAR: coordinated lysosomal expression and regulation; Cre: cre recombinase; DIO: diet-induced obesity; EBSS: Earle's balanced salt solution; EIF2AK3/PERK: eukaryotic translation initiation factor 2 alpha kinase 3; ER: endoplasmic reticulum; ERN1/IRE1: endoplasmic reticulum (ER) to nucleus signaling 1; GAPDH: glyceraldehyde-3-phosphate dehydrogenase; GFP: green fluorescent protein; HFD: high-fat diet; h: hours; HSCs: hepatic stellate cells; INS: insulin; L/A: ammonium chloride and leupeptin; MAP1LC3B/LC3B: microtubule-associated protein 1 light chain 3 beta; mRNA: messenger RNA; NAFLD: nonalcoholic fatty liver disease; NASH: nonalcoholic steatohepatitis; RD: regular diet; RFP: red fluorescent protein; SERPINA7/TBG: serpin family A member 7; SQSTM1/p62: sequestome 1; sXbp1 LOE: liver-specific overexpression of spliced Xbp1; TFEB: transcription factor EB; TG: thapsigargin; TN: tunicamycin; UPR: unfolded protein response; wks: weeks; WT: wild type; XBP1: X-box binding protein 1; xbp1 LKO: liver-specific Xbp1 knockout.


Assuntos
Autofagia/fisiologia , Fatores de Transcrição de Zíper de Leucina e Hélice-Alça-Hélix Básicos/metabolismo , Proteína 1 de Ligação a X-Box/metabolismo , Animais , Autofagia/genética , Estresse do Retículo Endoplasmático , Humanos , Fígado/metabolismo , Lisossomos/metabolismo , Camundongos , Resposta a Proteínas não Dobradas/fisiologia
16.
International Eye Science ; (12): 304-310, 2021.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wpr-862432

RESUMO

@#AIM:To measure the macular and peripapillary choroidal thickness(CT)in primary angle-closure disease(PACD)with enhanced depth imaging optical coherence tomography(EDI-OCT). To explore the characteristics of CT in each subtypes of PACD and to evaluate its role in the pathogenesis of PACD.<p>METHODS: This was a prospective clinical study. A total of 155 PACD eyes(82 patients)were enrolled in the study, including 24 PACS eyes(24 patients), 35 APAC eyes(28 patients), 38 CPAC eyes(30 patients), 58 eyes PACG(38 patients). 87 normal eyes(87 patients)were set up as control. The EDI-OCT was used to measure the macular and peripapillary choroidal thickness in all study patients. <p>RESULTS: PACD eyes exhibited thicker choroid than the control eyes at all macular locations(<i>P</i><0.05). Choroidal thickness of PACG was thinner than other PACD eyes in area except for 3mm nasal from the fovea(<i>P</i><0.05). Subfoveal choroidal thickness(SFCT)of APAC was thickest(357.17±61.49μm), followed by PACS group(318.04±56.52μm). PACG group presented the thinnest SFCT(263.55±67.87μm). The average macular CT at 1mm centered at the fovea was thinner than SFCT(<i>P</i><0.05)in all subgroups except for CPAC. The average macular CT at 3mm as well as 1mm centered at the fovea was thinner than SFCT in all subgroups(<i>P</i><0.05). There was no statistical differences in CT at peripapillary locations between PACD and controls groups(<i>P</i>>0.05).<p>CONCLUSION: In PACD and controls groups, the CT of subfoveal location was the thickest with decreasing thickness when moving eccentrically from the fovea. The thicker CT might be another anatomic characteristic of PACD. Increased CT in macular location might be a contributing factor of acute attacks. There was no characteristic distinction in the peripapillary CT of PACD when compared with normal controls.

17.
Eur J Radiol ; 132: 109324, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-33038576

RESUMO

PURPOSE: Neurocognitive impairment is a common complication in cirrhosis and is associated with alterations in static functional network connectivity (FNC) between distinct brain systems. However, accumulating evidence suggests temporal variability in FNC even at rest. This study aimed to explore dynamic FNC (dFNC) differences and to elucidate their association with neurocognitive changes in cirrhotic patients. METHODS: Fifty-four cirrhotic patients and 42 controls underwent resting-state functional magnetic resonance imaging. Psychometric hepatic encephalopathy score (PHES) was used to assess neurocognitive function. Independent component analysis was performed to identify the components of seven intrinsic brain networks, including sensorimotor (SMN), auditory, visual, cognitive control (CCN), default mode (DMN), subcortical (SC), and cerebellar networks. Sliding window correlation approach was employed to calculate dFNC. FNC states were determined by k-means clustering method, and then functional state analysis was conducted to measure dynamic indices. RESULTS: The patients showed decreased dFNC in State 2, involving the connectivity between posterior subsystem of DMN and CCN (represented by bilateral insular cortex), and in State 3, involving the connectivity between SMN (represented by bilateral precentral gyrus) and SC (represented by bilateral putamen and caudate). The patients spent significantly longer time in State 4 that was with weakest FNC across all networks. We observed a significant correlation between PHES and fraction time/mean dwell time in State 4. CONCLUSIONS: Aberrant dFNC may be the underlying mechanism of neurocognitive impairments in cirrhosis. Dynamic FNC analysis may potentially be utilized in investigating cirrhosis-related neuropathological processes.


Assuntos
Encefalopatia Hepática , Encéfalo/diagnóstico por imagem , Mapeamento Encefálico , Encefalopatia Hepática/diagnóstico por imagem , Humanos , Cirrose Hepática/complicações , Cirrose Hepática/diagnóstico por imagem , Imageamento por Ressonância Magnética , Rede Nervosa/diagnóstico por imagem
18.
Poult Sci ; 99(4): 1813-1821, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32241461

RESUMO

Ovaries produce sex hormones, and ovariectomized animals are often used as models for ovarian dysfunction. The liver is a vital organ involved in metabolism and immunity. In the present study, we conducted experiments to investigate the effects of ovariectomy on transcription and metabolic processes in the liver in chicken. Eight Single Comb White Leghorn (SCWL) female chickens were ovariectomized at 17 wk of age, and 8 intact SCWL females served as controls. At 100 wk of age, all chickens were euthanized. High-throughput transcriptome sequencing was performed on liver RNA obtained from ovariectomized and intact females. A total of 267 differentially expressed genes (DEG) were identified in our study. After analysis using DAVID functional annotation tool, one significant Kyoto Encyclopedia of Genes and Genomes pathway, the phosphatidylinositol signaling pathway, was clustered. Gene Ontology enrichment analysis yielded 46 significant Gene Ontology terms. Among terms describing biological processes, the glycerolipid metabolic and lipid localization processes were dominant. The anabolic genes, PEPCK and GK5, and the catabolic genes, VTG1; VTG2; PLD5; DGKQ; DGKE; and FABP3, were detected in ovariectomized chickens. Differentially expressed genes such as ENSGALG00000000162, IL-1Β, SVOPL, and CA12 implied that livers in ovariectomized chickens were subjected to strong inflammatory reactions, whereas defenses against endogenous materials were compromised. A comprehensive view of gene expression in the liver of ovariectomized chickens would advance our understanding of lipid metabolism, glycometabolism, and their relationships to pathologies induced by absence of the ovary. The identified DEG indicated that ovariectomy disturbed lipid metabolism in the liver and was accompanied by an increase in hepatic gluconeogenesis and reductions in phosphatidic acid synthesis and lipid carrier capacity.


Assuntos
Galinhas/fisiologia , Fígado/fisiologia , Ovariectomia/veterinária , RNA Mensageiro/genética , Transcriptoma , Animais , Galinhas/genética , Feminino , Ovário/cirurgia , RNA Mensageiro/metabolismo
19.
Orthop Surg ; 12(1): 31-37, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-32077265

RESUMO

INTRODUCTION: The efficacy of ketorolac supplementation on pain control for knee arthroscopy remains controversial. We conduct a systematic review and meta-analysis to explore the impact of ketorolac supplementation on pain intensity after knee arthroscopy. METHODS: We search PubMed, EMbase, Web of science, EBSCO, and Cochrane library databases through September 2018 for randomized controlled trials (RCTs) assessing the effect of ketorolac supplementation vs placebo on pain management after knee arthroscopy. This meta-analysis is performed using the random-effect model. RESULTS: Ten RCTs involving 402 patients are included in the meta-analysis. Overall, compared with control group for knee arthroscopy, ketorolac supplementation is associated with notably reduced pain scores at 1 h (MD = -0.66; 95% CI = -1.12 to -0.21; P = 0.004) and 2 h (MD = -0.90; 95% CI = -1.74 to -0.07; P = 0.03), prolonged time for first analgesic requirement (MD = 1.94; 95% CI = 0.33 to 3.55; P = 0.02) and decreased number of analgesic requirement (RR = 0.41; 95% CI = 0.23 to 0.75; P = 0.003), but has no obvious impact on analgesic consumption (MD = -0.56; 95% CI = -1.14 to 0.02; P = 0.06), as well as nausea and vomiting (RR = 0.44; 95% CI = 0.12 to 0.21; P = 0.21). CONCLUSIONS: Ketorolac supplementation is effective to produce pain relief for knee arthroscopy.


Assuntos
Artroscopia , Cetorolaco/uso terapêutico , Articulação do Joelho/cirurgia , Manejo da Dor , Dor Pós-Operatória/tratamento farmacológico , Anti-Inflamatórios não Esteroides/uso terapêutico , Humanos , Ensaios Clínicos Controlados Aleatórios como Assunto
20.
Thorac Cancer ; 11(1): 72-81, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31769214

RESUMO

BACKGROUND: Localization and resection of nonvisible, nonpalpable pulmonary nodules during video-assisted thoracoscopic surgery is challenging. In this study we developed a surgical navigation puncture robot system in order to locate small pulmonary nodules before thoracoscopic surgery. METHODS: Four pigs were divided into group A and group B and underwent positioning puncture with the aid of the robotic system. The pigs in group A breathed freely during the experiment, whilst mechanical ventilation was used on the pigs in group B. RESULTS: Using the robotic system to locate nodules achieved good results. For group A, a total of nine simulated nodules were created and successfully localized. The mean positioning accuracy was 9.6 ± 4.9 mm (range, 3.2-17.4 mm), and the time required for system positioning was 7.1 ± 1.0 minutes (range, 5.6-8.2 minutes). For group B, a total of 23 simulated nodules were created and successfully localized. The mean positioning accuracy was 2.9 ± 1.5 mm (range, 0.7-5.9 mm), and the time required for system positioning was 7.8 ± 1.1 minutes (range, 6.3-9.7 minutes). CONCLUSIONS: The new method using a surgical navigation puncture robot system to locate small pulmonary nodules is feasible and safe, and its positioning accuracy is sufficient to meet clinical requirements. In addition, results indicated that breathing had a great influence on the positioning accuracy, mainly in the longitudinal direction. Our surgical navigation puncture robot system has wide future applications for accurately locating small pulmonary nodules in a clinical setting. KEY POINTS: Significant findings of the study: A new method using a surgical navigation puncture robot system was developed to locate small pulmonary nodules before thoracoscopic surgery. The results indicated that this method can provide accurate localization and permit smaller and more precise resections. WHAT THIS STUDY ADDS: A surgical navigation puncture robot system has wide future applications for accurately locating small pulmonary nodules in a clinical setting.


Assuntos
Nódulos Pulmonares Múltiplos/cirurgia , Robótica/métodos , Nódulo Pulmonar Solitário/cirurgia , Cirurgia Assistida por Computador/métodos , Cirurgia Torácica Vídeoassistida/métodos , Animais , Cuidados Intraoperatórios , Nódulos Pulmonares Múltiplos/diagnóstico por imagem , Nódulos Pulmonares Múltiplos/patologia , Punções , Nódulo Pulmonar Solitário/diagnóstico por imagem , Nódulo Pulmonar Solitário/patologia , Suínos , Tomografia Computadorizada por Raios X/métodos
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