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1.
Viruses ; 15(1)2023 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-36680208

RESUMO

Human endogenous retroviruses (HERVs) are remnants of ancestral germline infections by exogenous retroviruses. Human endogenous retroviruses W family envelope gene (HERV-W env, also called ERVWE1), located on chromosome 7q21-22, encodes an envelope glycoprotein from the HERV-W family. Mounting evidence suggests that aberrant expression of ERVWE1 involves the etiology of schizophrenia. Moreover, the genetic and morphological studies indicate that dendritic spine deficits may contribute to the onset of schizophrenia. Here, we reported that ERVWE1 changed the density and morphology of the dendritic spine through inhibiting Wingless-type (Wnt)/c-Jun N-terminal kinases (JNK) non-canonical pathway via miR-141-3p in schizophrenia. In this paper, we found elevated levels of miR-141-3p and a significant positive correlation with ERVWE1 in schizophrenia. Moreover, serum Wnt5a and actin-related protein 2 (Arp2) levels decreased and demonstrated a significant negative correlation with ERVWE1 in schizophrenia. In vitro experiments disclosed that ERVWE1 up-regulated miR-141-3p expression by interacting with transcription factor (TF) Yin Yang 1 (YY1). YY1 modulated miR-141-3p expression by binding to its promoter. The luciferase assay revealed that YY1 enhanced the promoter activity of miR-141-3p. Using the miRNA target prediction databases and luciferase reporter assays, we demonstrated that miR-141-3p targeted Wnt5a at its 3' untranslated region (3' UTR). Furthermore, ERVWE1 suppressed the expression of Arp2 through non-canonical pathway, Wnt5a/JNK signaling pathway. In addition, ERVWE1 inhibited Wnt5a/JNK/Arp2 signal pathway through miR-141-3p. Finally, functional assays showed that ERVWE1 induced the abnormalities in hippocampal neuron morphology and spine density through inhibiting Wnt/JNK non-canonical pathway via miR-141-3p in schizophrenia. Our findings indicated that miR-141-3p, Wnt5a, and Arp2 might be potential clinical blood-based biomarkers or therapeutic targets for schizophrenia. Our work also provided new insight into the role of ERVWE1 in schizophrenia pathogenesis.


Assuntos
MicroRNAs , Esquizofrenia , Humanos , Espinhas Dendríticas , Regulação da Expressão Gênica , Sistema de Sinalização das MAP Quinases , MicroRNAs/genética , Esquizofrenia/genética
2.
Neuron ; 2023 Jan 09.
Artigo em Inglês | MEDLINE | ID: mdl-36638803

RESUMO

Empathic function is essential for the well-being of social species. Empathy loss is associated with various brain disorders and represents arguably the most distressing feature of frontotemporal dementia (FTD), a leading form of presenile dementia. The neural mechanisms are unknown. We established an FTD mouse model deficient in empathy and observed that aged somatic transgenic mice expressing GGGGCC repeat expansions in C9orf72, a common genetic cause of FTD, exhibited blunted affect sharing and failed to console distressed conspecifics by affiliative contact. Distress-induced consoling behavior activated the dorsomedial prefrontal cortex (dmPFC), which developed profound pyramidal neuron hypoexcitability in aged mutant mice. Optogenetic dmPFC inhibition attenuated affect sharing and other-directed consolation in wild-type mice, whereas chemogenetically enhancing dmPFC excitability rescued empathy deficits in mutant mice, even at advanced ages when substantial cortical atrophy had occurred. These results establish cortical hypoexcitability as a pathophysiological basis of empathy loss in FTD and suggest a therapeutic strategy.

3.
Anal Chim Acta ; 1239: 340730, 2023 Jan 25.
Artigo em Inglês | MEDLINE | ID: mdl-36628773

RESUMO

In this work, we report the development of a new type of highly active and stable Bi-based electrode material, i.e., BiCu metal-organic frames (MOF) derived carbon film (CF) encapsulating BiCu alloy nanoparticles (BiCu-ANPs) for electrochemical sensing. The integration of Bi with Cu to form BiCu-ANPs can improve their electrocatalytic activity as well as the acid resistance. Meanwhile, the carbon film that encapsulates BiCu-ANPs not only guarantees the BiCu-ANPs with high electrical conductivity and fast electrochemical kinetics but also effectively alleviates the volume change during the adsorption and desorption of heavy metal (HM) ions. Therefore, the as-obtained CF encapsulating BiCu-ANPs (BiCu-ANPs@CF) exhibits fully exposed active sites, facile charge transfer, high stability and conductivity, which gives rise to enhanced sensitivity and stability for the electrochemical detection of HM ions. When integrated into a potable electrochemical sensing system for simultaneous detection of Pb2+, Cd2+ and Zn2+, the BiCu-ANPs@CF modified electrode exhibits low detection limit (i.e., 0.081 ppb for Pb2+, 0.95 ppb for Cd2+, 35 ppb for Zn2+), wide detection range (i.e., 0.5-700 ppb for Pb2+, 5-900 ppb for Cd2+, 150-600 ppb for Zn2+) and good anti-interference. Finally, the system has been used for on-site detection of multiplexed HM ions in human biological liquids and environmental water with a good spiked recovery rate, which demanstrates its promise application in the future for on-site monitoring of human health and pollutants in water quality.


Assuntos
Nanopartículas Metálicas , Metais Pesados , Humanos , Carbono , Cádmio/química , Ligas , Chumbo , Metais Pesados/química , Íons
4.
Int J Mol Sci ; 24(2)2023 Jan 06.
Artigo em Inglês | MEDLINE | ID: mdl-36674672

RESUMO

The commercial application of genetically modified plants has been seriously impeded by public concern surrounding the potential risks posed by such plants to the ecosystem and human health. Previously, we have developed a 'pollen- and seed-specific Gene Deletor' system that automatically excised all transgenes from the pollen and seeds of greenhouse-grown transgenic Nicotiana tabacum. In this study, we conducted seven field experiments over three consecutive years to evaluate the stability of transgene excision under field conditions. Our results showed that transgenes were stably excised from transgenic Nicotiana tabacum under field conditions with 100% efficiency. The stability of transgene excision was confirmed based on PCR, as well as the GUS staining patterns of various organs (roots, leaves, petiole, stem, flower, fruit, and seeds) from transgenic N. tabacum. In six transgenic lines (D4, D10, D31, D56, and D43), the transgenes were stably deleted in the T0 and T1 generations. Thus, the 'Gene Deletor' system is an efficient and reliable method to reduce pollen- and seed-mediated unintentional gene flow. This system might help to alleviate the food safety concerns associated with transgenic crops.


Assuntos
Ecossistema , Tabaco , Humanos , Plantas Geneticamente Modificadas/genética , Tabaco/genética , Transgenes , Pólen/genética , Sementes/genética
5.
Artigo em Inglês | MEDLINE | ID: mdl-36602643

RESUMO

PURPOSE: Scalpels are typical tools used for cutting in surgery, and the surgical tray is one of the locations where the scalpel is present during surgery. However, there is no known method for the classification and segmentation of multiple types of scalpels. This paper presents a dataset of multiple types of scalpels and a classification and segmentation method that can be applied as a first step for validating segmentation of scalpels and further applications can include identifying scalpels from other tools in different clinical scenarios. METHODS: The proposed scalpel dataset contains 6400 images with labeled information of 10 types of scalpels, and a classification and segmentation model for multiple types of scalpels is obtained by training the dataset based on Mask R-CNN. The article concludes with an analysis and evaluation of the network performance, verifying the feasibility of the work. RESULTS: A multi-type scalpel dataset was established, and the classification and segmentation models of multi-type scalpel were obtained by training the Mask R-CNN. The average accuracy and average recall reached 94.19% and 96.61%, respectively, in the classification task and 93.30% and 95.14%, respectively, in the segmentation task. CONCLUSION: The first scalpel dataset is created covering multiple types of scalpels. And the classification and segmentation of multiple types of scalpels are realized for the first time. This study achieves the classification and segmentation of scalpels in a surgical tray scene, providing a potential solution for scalpel recognition, localization and tracking.

6.
J Virol ; : e0194722, 2023 Jan 19.
Artigo em Inglês | MEDLINE | ID: mdl-36656013

RESUMO

Members of deltacoronavirus (DCoV) have mostly been identified in diverse avian species as natural reservoirs, though the porcine DCoV (PDCoV) is a major swine enteropathogenic virus with global spread. The important role of aminopeptidase N (APN) orthologues from various mammalian and avian species in PDCoV cellular entry and interspecies transmission has been revealed recently. In this study, comparative analysis indicated that three avian DCoVs, bulbul DCoV HKU11, munia DCoV HKU13, and sparrow DCoV HKU17 (Chinese strain), and PDCoV in the subgenera Buldecovirus are grouped together at whole-genome levels; however, the spike (S) glycoprotein and its S1 subunit of HKU17 are more closely related to night heron DCoV HKU19 in Herdecovirus. Nevertheless, the S1 protein of HKU11, HKU13, or HKU17 bound to or interacted with chicken APN (chAPN) or porcine APN (pAPN) by flow cytometry analysis of cell surface expression of APN and by coimmunoprecipitation in APN-overexpressing cells. Expression of chAPN or pAPN allowed entry of pseudotyped lentiviruses with the S proteins from HKU11, HKU13 and HKU17 into nonsusceptible cells and natural avian and porcine cells, which could be inhibited by the antibody against APN or anti-PDCoV-S1. APN knockdown by siRNA or knockout by CRISPR/Cas9 in chicken or swine cell lines significantly or almost completely blocked infection of these pseudoviruses. Hence, we demonstrate that HKU11, HKU13, and HKU17 with divergent S genes likely engage chAPN or pAPN to enter the cells, suggesting a potential interspecies transmission from wild birds to poultry and from birds to mammals by certain avian DCoVs. IMPORTANCE The receptor usage of avian deltacoronaviruses (DCoVs) has not been investigated thus far, though porcine deltacoronavirus (PDCoV) has been shown to utilize aminopeptidase N (APN) as a cell receptor. We report here that chicken or porcine APN also mediates cellular entry by three avian DCoV (HKU11, HKU13, and HKU17) spike pseudoviruses, and the S1 subunit of three avian DCoVs binds to APN in vitro and in the surface of avian and porcine cells. The results fill the gaps in knowledge about the avian DCoV receptor and elucidate important insights for the monitoring and prevention of potential interspecies transmission of certain avian DCoVs. In view of the diversity of DCoVs, whether this coronavirus genus will cause novel virus to emerge in other mammals from birds, are worthy of further surveillance and investigation.

7.
Biomaterials ; 293: 121946, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36512862

RESUMO

Sox17 is a critical regulator of arterial identity during early embryonic vascular development. However, its role in adult endothelial cells (ECs) are not fully understood. Sox17 is highly expressed in arterial ECs but not in venous ECs throughout embryonic development to adulthood suggesting that it may play a functional role in adult arteries. Here, we investigated Sox17 mediated phenotypical changes in adult ECs. To precisely control the temporal expression level of Sox17, we designed a tetracycline-inducible lentiviral gene expression system to express Sox17 selectively in cultured venous ECs. We confirmed that Sox17-induced ECs exhibit a gene profile favoring arterial and tip cell identity. Furthermore, in comparison to control ECs, Sox17-activated ECs under shear leads to greater expression of arterial markers and suppression of venous identity. These data suggest that Sox17 enables greater hemodynamic adaptability of ECs in response to fluid shear stress. Here, we also demonstrate key morphogenic behaviors of Sox17-mediated ECs. In both vasculogenic and angiogenic 3D fibrin gel studies, Sox17-mediated ECs prefer to form cohesive vessels with one another while interfering the vessel formation of the control ECs. Sox17-mediated ECs elicit hyper-sprouting behavior in the presence of pericytes but not fibroblasts, suggesting Sox17 mediated sprouting frequency is dependent on supporting cell type. Using a microfluidic chip, we also show that Sox17-mediated ECs maintain thinner diameter vessels that do not widen under interstitial flow like the control ECs. Taken together, these data showed that Sox17 mediated EC gene expression and phenotypical changes are highly modulated in the context of biomechanical stimuli, suggesting Sox17 plays a role in regulating the arterial ECs adaptability under arterial hemodynamics as well as tip cells behavior during angiogenesis and vasculogenesis. The results from this study may be valuable in improving vein graft adaptation to arterial hemodynamics and bioengineering microvasculature for tissue engineering applications.


Assuntos
Artérias , Células Endoteliais , Diferenciação Celular , Células Cultivadas , Células Endoteliais/metabolismo , Hemodinâmica , Fatores de Transcrição SOXF
8.
Obesity (Silver Spring) ; 31(1): 279-289, 2023 01.
Artigo em Inglês | MEDLINE | ID: mdl-36507560

RESUMO

OBJECTIVE: The aim of this study was to investigate the transgenerational associations between exposure to famine in early life and obesity. METHODS: This study used the longitudinal data from the China Health and Nutrition Survey from 1989 to 2015. A total of 1113 fathers and 1207 mothers (946 mother-father pairs) born in 1955 to 1966 and 1895 adult offspring were included. Offspring were classified into subgroups according to the famine exposure of their parents (unexposed, maternal exposed, paternal exposed, parental exposed) and exposure timing (during fetal development, childhood). RESULTS: Maternal exposure to famine in early life was associated with elevated levels of BMI, waist circumference, overweight, and central obesity of their children, whereas paternal exposure was inversely associated with these measurements. Compared with children of unexposed parents (P0M0), the maternal exposed group (P0M1) had higher mean BMI, by 1.3 kg/m2 (95% CI: 0.3 to 2.4); waist circumference, by 1.5 cm (-1.0 to 3.9); overweight (odds ratio [OR] [95% CI]: 3.1 [1.6 to 6.1]); and central obesity (OR [95% CI]: 1.9 [1.02 to 3.7]). No significant heterogeneity was observed in the associations by sex of offspring. CONCLUSIONS: Fetal and early childhood exposure to famine in parents may be associated with their children's risk of obesity during adulthood. A better understanding of the transgenerational associations is important for developing strategies to reduce obesity risk in future generations.


Assuntos
Efeitos Tardios da Exposição Pré-Natal , Inanição , Masculino , Feminino , Criança , Adulto , Humanos , Pré-Escolar , Idoso , Fome Epidêmica , Fatores de Risco , Sobrepeso/epidemiologia , Obesidade Abdominal , Obesidade/epidemiologia , Pais , China/epidemiologia , Inanição/epidemiologia , Efeitos Tardios da Exposição Pré-Natal/epidemiologia
10.
Biol Proced Online ; 24(1): 22, 2022 Dec 03.
Artigo em Inglês | MEDLINE | ID: mdl-36463115

RESUMO

BACKGROUND: Hepatocellular carcinoma (HCC) belongs to a representative lethality gastrointestinal malignancy, and comprehensive management of HCC remains intractable at present on account of its invasive biological feature that is easy to relapse and early metastasis. The intimate connection between platelets and tumor progression has been widely reported, and platelet-related indicators are also used in the clinical practice of carcinoma. This work is designed to investigate the significance of platelet-related genes in the prognostic prediction of patients with HCC and their potential role in the cross-talk between HCC cells and platelets in the tumor microenvironment. METHODS: By integrating the RNA-seq data and clinicopathological information of HCC patients, we extracted prognosis-associated platelet-related genes based on the univariate cox analysis and further established a relevant prognostic signature via the lasso cox regression analysis, and two independent HCC cohorts were used as external validation. Multiple bioinformatics methods were utilized to explore the underlying functional discrepancy between different risk groups classified by the risk model. And in vitro proliferation, invasion, and migration assays were conducted to investigate the effect of platelet stimulation on HCC cells' viability and motility, and flow cytometric analysis was exerted to demonstrate the influence of HCC cells on platelet activation. RESULTS: A novel platelet-related risk model was developed and patients both in the training and testing cohorts were divided into distinct risk subgroups according to the median risk score. It was observed that the high-risk status was closely associated with poor prognosis and worse clinicopathological parameters. Meanwhile, an obvious discrepancy in the constitution of the immune microenvironment also indicated that distinct immune status might be a potential determinant affecting prognosis as well as immunotherapy reactiveness. Moreover, in vitro experiments demonstrated that PRKCD could act as a molecular bridge between tumor cells and platelets, which could either participate in regulating tumor malignant phenotype or mediating platelet activation. CONCLUSIONS: In brief, this work reveals a novel platelet-related risk signature for prognostic evaluation of HCC patients and confirms that PRKCD is a key messenger in HCC cell-platelet interaction and plays a crucial role in mediating platelet-induced tumor progression.

11.
Front Nutr ; 9: 1007184, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36505248

RESUMO

Background: Muscle mass loss is common in long-standing rheumatoid arthritis (RA). The aim was to explore the prevalence and effects of RA disease characteristics in patients with early RA. Methods: This cross-sectional study was carried out based on a Chinese RA cohort and control subjects. The body composition (BC) was assessed using bioelectric impedance analysis. Myopenia was defined by an appendicular skeletal muscle mass index of ≤ 7.0 kg/m2 in men and ≤ 5.7 kg/m2 in women. Physical dysfunction was defined as a health assessment questionnaire disability index > 1. Propensity score matching was performed to balance age and gender differences among patients with early RA (disease duration ≤ 12 months) and established RA, and controls (with 1:3:3 matching). Results: In total, 2017 controls and 1,008 patients with RA were recruited for this study. Among the patients with RA, there were 190 (18.8%) patients with early RA, with a median disease duration of 7 (4, 11) months. The matched patients with early RA (n = 160) showed a higher prevalence of myopenia than the matched controls (41.3 vs. 15.8%, P < 0.0167), but no difference was found in the matched patients with established RA (41.3 vs. 50.4%, P > 0.0167). Compared with the patients with established RA, the patients with early RA exhibited higher disease activity scores [disease activity score in 28 joints with four variables including C-reactive protein (DAS28-CRP): median 4.76 vs. 3.93, P < 0.001] and a higher prevalence of physical dysfunction (26.3 vs. 19.4%, P = 0.035). In the patients with early RA, patients with myopenia showed a higher prevalence of physical dysfunction than those without myopenia (41.3 vs. 15.5%, P < 0.001), among which walking and common daily activities were the most involved subdimensions. Multivariate logistic regression analysis showed that DAS28-CRP was positively associated with myopenia [adjusted odds ratio (AOR) 1.558, 95% CI (1.138-2.132)], and myopenia [AOR 2.983, 95% CI (1.192-7.465)] was independently associated with physical dysfunction in the patients with early RA. Conclusion: Our data indicate the importance of early detection of muscle involvement in the early stage of RA and imply the significance of early aggressive control of disease activity for the prevention of myopenia and physical dysfunction in patients with early RA. Our study provides a new perspective on RA management.

12.
Front Oncol ; 12: 941454, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36505782

RESUMO

Oro-maxillo-facial metastasis from hepatocellular carcinoma (HCC) is very rare, and reports on treating maxillary metastasis from HCC are unavailable. Anti-angiogenesis therapy combined with immunotherapy represented by programmed cell death 1 (PD-1) or its ligand (PD-L1) inhibitor has become the standard treatment of advanced HCC. However, integrating chemoradiotherapy into immunotherapy-bevacizumab combination therapy has not been reported. Here, we presented a Chinese woman with maxillary metastasis from HCC who achieved a nearly complete response (CR) to a quadruple treatment scheme consisting of a PD-1 monoclonal antibody (sintilimab), bevacizumab biosimilar IBI305, hypo-fractionated intensity-modulated radiotherapy (hfIMRT), and concurrent oxaliplatin. This comprehensive treatment is an innovative and effective therapy for advanced HCC.

13.
J Gene Med ; : e3469, 2022 Dec 13.
Artigo em Inglês | MEDLINE | ID: mdl-36511295

RESUMO

BACKGROUND: Lung adenocarcinoma is one of the common causes of cancer-related deaths worldwide. Histone cluster 1 H2A family member b (HIST1H2AB) is a member of the histone H2A family. Bioinformatic analyses have revealed that HIST1H2AB is highly expressed in some cancers and might be an oncogene. However, the information on the function of HIST1H2AB in lung adenocarcinoma is limited. METHODS: The expression of HIST1H2AB was analyzed in normal lung, lung adenocarcinoma, and paracancerous tissues from The Cancer Genome Atlas (TCGA) database and immunohistochemistry staining. It was further verified in the relative cell lines using real-time quantitative polymerase chain reaction (RT-qPCR). When the adenocarcinoma cells lines (A549 and H1299 cells) were successfully transfected with shHIST1H2AB or an empty plasmid (shCtrl) packaged into a lentivirus, cell proliferation was detected using Celigo fluorescence cell-counting, colony formation, and annexin V-allophycocyanin (APC) assays. Twenty nude mice were subcutaneously injected with A549 cells transfected with shHIST1H2AB or empty plasmid; the tumor size was recorded on day 25 and then measured every 3 days thereafter. The final tumor weight was measured on day 37. Significantly differentially expressed genes were analyzed using a human gene expression array. Furthermore, the potentially relevant genes were verified using RT-qPCR and western blotting. RESULTS: HIST1H2AB was highly expressed in lung adenocarcinoma tissues from TCGA database and immunohistochemistry staining. Similar results were seen in the lung adenocarcinoma cells. When the cells were successfully transfected with shHIST1H2AB or an empty plasmid, downregulation of HIST1H2AB inhibited the growth and promoted the apoptosis of lung adenocarcinoma cells. The xenograft results suggested that HIST1H2AB downregulation delayed tumor growth and reduced tumor weight. Moreover, interferon signaling pathway and four genes (HMGB1, FOXM1, F2RL1, and SLC4A7) might be regulated by HIST1H2AB in the development of lung adenocarcinoma as indicated through gene expression array, RT-qPCR, and western blotting analyses. CONCLUSIONS: HIST1H2AB acts as an oncogenic protein and HIST1H2AB inhibition suppresses the proliferation of lung adenocarcinoma cells. It may be a novel target for lung adenocarcinoma therapy.

14.
J Hepatol ; 2022 Dec 24.
Artigo em Inglês | MEDLINE | ID: mdl-36574921

RESUMO

BACKGROUND & AIMS: Hepatitis E virus (HEV) is a globally prevalent pathogen, annually resulting in 20 million infections, 3 million cases of clinical disease, and 60,000 fatalities worldwide, significantly endangering pregnant women and immunocompromised individuals. HEV-related research has been considerably delayed, and no HEV-specific therapeutics have yet been developed. We aimed to discover efficient anti-HEV drugs through high throughput screening that could be validated in vitro and in a preclinical animal study in vivo, and elucidate the underlying antiviral mechanism. METHODS: Using appropriate cellular and rodent HEV infection models, we studied a critical pathway for host-HEV interaction and performed a preclinical study of the corresponding antivirals by targeting proteostasis of the HEV replicase. RESULTS: We found 17 inhibitors that target HEV-HSP90 interactions by an unbiased compound library screening on human hepatocytes harboring an HEV replicon. Inhibitors of HSP90 (iHSP90) markedly suppressed HEV replication with efficacy exceeding that of conventional antivirals (IFNα and ribavirin) in vitro. Mechanistically, iHSP90 treatment released the viral replicase ORF1 protein from the ORF1-HSP90 complex and triggered ORF1 for rapid ubiquitin/proteasome-mediated degradation, resulting in abrogated HEV replication. Furthermore, a preclinical trial in a Mongolian gerbil HEV infection model showed this novel anti-HEV strategy to be safe, efficient, and able to prevent HEV-induced liver damage. CONCLUSIONS: This study collectively illustrates a critical proteostasis pathway for host-HEV interaction and paves the way for translating the new understanding of the HEV life cycle into clinically promising antivirals. IMPACT AND IMPLICATIONS: Appropriate treatment options for HEV-infected pregnant women as well as immunocompromised patients are lacking, creating an urgent need for developing safe HEV-specific therapies. This study identified new antivirals (inhibitors of HSP90) that significantly decrease the HEV infection by targeting viral replicase for degradation. Moreover, these anti-HEV drugs were validated in an HEV rodent model and found to be safe and efficient for prevention of HEV-induced liver injury in preclinical experiments. Our findings substantially promote the understanding of HEV pathobiology and the pace of antiviral development.

15.
Dig Dis Sci ; 2022 Dec 30.
Artigo em Inglês | MEDLINE | ID: mdl-36583804

RESUMO

PURPOSE: To assess and compare the value of psoas muscle thickness at the level of the third lumbar (L3) vertebra (TPML) or umbilicus (TPMU) and skeletal muscle index (SMI) for diagnosing sarcopenia and predicting mortality in patients undergoing transjugular intrahepatic portosystemic shunt (TIPS). MATERIALS AND METHODS: Two hundred forty-nine patients undergoing TIPS were included in this retrospective study. The cut-offs of L3-SMI for sarcopenia were 42.0 cm2/m2 in men and 38.0 cm2/m2 in women. The cut-offs for TPML/height and TPMU/height to predict mortality was established using a receiver-operating characteristic analysis. The Kaplan-Meier and Cox regression were used for survival analyses. RESULTS: Compared with TPMU/height, TPML/height was more consistent with L3-SM for the diagnosis of sarcopenia (Kappa coefficient: 0.63 vs. 0.36 in men; 0.61 vs. 0.45 in women). The Cox analysis showed that both TPML/height and TPMU/height were independent risk factors for mortality. The optimal cut-off values of TPML/height and TPMU/height for mortality in men and women were 11.2 mm/m, 9.4 mm/m, 18.4 mm/m, 15.1 mm/m, respectively. There were 119 (47.8%), 87 (34.9%), and 82 (32.9%) patients diagnosed with sarcopenia in the TPMU/height, TPML/height, and L3-SMI models, respectively. Kaplan-Meier analysis showed that the overall survival was significantly lower in the sarcopenia group in all three models. CONCLUSION: TPMU/height and TPML/height have a similar survival prognostic value as L3-SMI. TPML/height has better consistency with L3-SMI in diagnosing sarcopenia and is a more stable alternative to L3-SMI for diagnosing sarcopenia in patients undergoing TIPS.

16.
J Vasc Interv Radiol ; 2022 Dec 28.
Artigo em Inglês | MEDLINE | ID: mdl-36586464

RESUMO

To investigate the risk factors affecting the improvement of sarcopenia after transjugular intrahepatic portosystemic shunt (TIPS) in cirrhotic patients, this study retrospectively analyzed the data of 111 cirrhotic patients with sarcopenia who had undergone TIPS in our hospital. CT-based measurement of skeletal muscle area was used to calculate skeletal muscle index (SMI) in all patients at baseline and 6 months post-TIPS. Multivariate logistic regression analysis were used to identify independent risk factors. It showed a significant increase of 6-month post-TIPS SMI compared with that of baseline in both males and females (both P < 0.001). Pre-TIPS SMI (OR: 0.93, 95%CI: 0.87-0.99, P = 0.031) and the value of change in portal pressure gradient (ΔPPG) (OR: 1.13, 95%CI: 1.03-1.24, P = 0.009) were found to be independent risk factors for experiencing substantial improvement in post-TIPS SMI.

17.
Front Endocrinol (Lausanne) ; 13: 1004112, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36506074

RESUMO

Background: While it is known that inaccurate evaluation for retroperitoneal laparoscopic adrenalectomy (RPLA) can affect the surgical results of patients, no stable and effective prediction model for the procedure exists. In this study, we aimed to develop a computed tomography (CT) -based radiological-clinical prediction model for evaluating the surgical difficulty of RPLA. Method: Data from 398 patients with adrenal tumors treated by RPLA in a single center from August 2014 to December 2020 were retrospectively analyzed and divided into sets. The influencing factors were selected by least absolute shrinkage and selection operator regression model (LASSO). Additionally, the nomogram was constructed. A receiver operating characteristic curve was used to analyze the prediction efficiency of the nomogram. The C-index and bootstrap self-sampling methods were used to verify the discrimination and consistency of the nomogram. Result: The following 11 independent influencing factors were selected by LASSO: body mass index, diabetes mellitus, scoliosis, hyperlipidemia, history of operation, tumor diameter, distance from adrenal tumor to upper pole of kidney, retro renal fat area, hyperaldosteronism, pheochromocytoma and paraganglioma, and myelolipoma. The area under the curve (AUC) of the training set was 0.787, and 0.844 in the internal validation set. Decision curve analyses indicated the model to be useful. An additional 117 patients were recruited for prospective validation, and AUC was 0.848. Conclusion: This study developed a radiological-clinical prediction model proposed for predicting the difficulty of RPLA procedures. This model was suitable, accessible, and helpful for individualized surgical preparation and reduced operational risk. Thus, this model could contribute to more patients' benefit in circumventing surgical difficulties because of accurate predictive abilities.


Assuntos
Neoplasias das Glândulas Suprarrenais , Modelos Estatísticos , Humanos , Estudos Retrospectivos , Prognóstico , Adrenalectomia , Neoplasias das Glândulas Suprarrenais/diagnóstico por imagem , Neoplasias das Glândulas Suprarrenais/cirurgia
18.
Front Plant Sci ; 13: 963377, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36388609

RESUMO

Sugarcane is one of the most crucial sugar crops globally that supplies the main raw material for sugar and ethanol production, but drought stress causes a severe decline in sugarcane yield worldwide. Enhancing sugarcane drought resistance and reducing yield and quality losses is an ongoing challenge in sugarcane genetic improvement. Here, we introduced a Tripidium arundinaceum dehydration-responsive element-binding transcription factor (TaDREB2B) behind the drought-responsible RD29A promoter into a commercial sugarcane cultivar FN95-1702 and subsequently conducted a series of drought tolerance experiments and investigation of agronomic and quality traits. Physiological analysis indicated that Prd29A: TaDREB2B transgenic sugarcane significantly confers drought tolerance in both the greenhouses and the field by enhancing water retention capacity and reducing membrane damage without compromising growth. These transgenic plants exhibit obvious improvements in yield performance and various physiological traits under the limited-irrigation condition in the field, such as increasing 41.9% yield and 44.4% the number of ratooning sugarcane seedlings. Moreover, Prd29A: TaDREB2B transgenic plants do not penalize major quality traits, including sucrose content, gravity purity, Brix, etc. Collectively, our results demonstrated that the Prd29A-TaDREB2B promoter-transgene combination will be a useful biotechnological tool for the increase of drought tolerance and the minimum of yield losses in sugarcane.

19.
J Immunol ; 2022 Nov 11.
Artigo em Inglês | MEDLINE | ID: mdl-36368721

RESUMO

Abnormally high follicle-stimulating hormone (FSH) has been reported to associate with cardiovascular diseases in prostate cancer patients with specific androgen deprivation therapy and in menopausal women. All of the cardiovascular diseases were involved in atherosclerosis. However, the pathogenic mechanism of FSH-associated atherosclerosis remains uncertain. Apolipoprotein E-deficient mice were chosen to develop atherosclerosis, of which the plaques were analyzed with administration of short- and long-term FSH imitating androgen deprivation therapy-induced and menopausal FSH elevation. The study showed that short- and long-term exposure of FSH significantly accelerated atherosclerosis progression in apolipoprotein E-deficient mice, manifested as strikingly increased plaques in the aorta and its roots, increased macrophage content, reduced fibrin, and an enlarged necrotic core, suggesting a decrease in plaque stability. Furthermore, expression profiles from the Gene Expression Omnibus GSE21545 dataset revealed that macrophage inflammation was tightly associated with FSH-induced atherosclerotic progression. The human monocyte cell line THP-1 was induced by PMA and worked as a macrophage model to detect inflammatory factors and cellular functions. FSH remarkably promoted the expression of IL-1ß in macrophages and strikingly increased the chemotactic migratory capacity of macrophages toward MCP-1, but the promigratory capacity of FSH was attenuated in foam cells. Overall, we revealed that FSH significantly promoted the inflammatory response and migration of macrophages, thereby provoking atherosclerosis development.

20.
Acc Chem Res ; 55(23): 3445-3459, 2022 Dec 06.
Artigo em Inglês | MEDLINE | ID: mdl-36368944

RESUMO

ConspectusOrganic phosphorescence is defined as a radiative transition between the different spin multiplicities of an organic molecule after excitation; here, we refer to the photoexcitation. Unlike fluorescence, it shows a long emission lifetime (∼µs), large Stokes shift, and rich excited state properties, attracting considerable attention in organic electronics during the past years. Ultralong organic phosphorescence (UOP), a type of persistent luminescence in organic phosphors, shows an emission lifetime of over 100 ms normally according to the resolution limit of the naked eye. According to the Jablonski energy diagram, two prerequisites are necessary for UOP generation and enhancement. One is to promote intersystem crossing (ISC) of the excitons from the excited singlet to triplet states by enhancing the spin-orbit coupling (SOC); the other is to suppress the nonradiative transitions of the excitons from the excited triplet states.In this Account, we will give a summary of our research on ultralong organic phosphorescence, including the design of materials, manipulation of properties, fabrication of nano/microstructures, and function applications. First, we give a brief introduction to the UOP development. Then, we discuss the constructed methods of UOP materials from the inter/intramolecular interaction types, including π-π interactions, intermolecular hydrogen bonds, halogen bonds, ionic bonds, covalent bonds, and so on. These effective interactions can build a rigid environment to restrain the nonradiative transitions from the molecular motions or external quenching by oxygen, moisture, or heat, and thus enhance the UOP performance. Next, the manipulation of UOP properties, containing excitation wavelength, emission colors, lifetimes, and quantum efficiency (QE), through molecular or crystal engineering will be summarized. Recently, the excitation wavelengths of the materials for UOP can be regulated in different regions, such as UV, visible light, and X-ray; the emission colors of UOP can cover the whole visible-light region, from deep blue to red; the phosphorescence lifetime of UOP materials can reach 2.5 s, and the quantum efficiency can be achieved up to 96.5%. Moreover, we will present the fabrication of micro/nanoscale UOP materials, including the preparation of micro/nanostructure, optical performance, and device fabrication. Afterward, we will review the potential applications of UOP materials in organic/bio-optoelectronics, such as information encryption, bioimaging, sensing, afterglow display, etc. Finally, an outlook on the development of UOP materials and applications will be proposed.


Assuntos
Citoesqueleto , Luz , Fluorescência , Eletrônica , Engenharia
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