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1.
Genome Biol ; 23(1): 2, 2022 Jan 03.
Artigo em Inglês | MEDLINE | ID: mdl-34980216

RESUMO

BACKGROUND: Reproducible detection of inherited variants with whole genome sequencing (WGS) is vital for the implementation of precision medicine and is a complicated process in which each step affects variant call quality. Systematically assessing reproducibility of inherited variants with WGS and impact of each step in the process is needed for understanding and improving quality of inherited variants from WGS. RESULTS: To dissect the impact of factors involved in detection of inherited variants with WGS, we sequence triplicates of eight DNA samples representing two populations on three short-read sequencing platforms using three library kits in six labs and call variants with 56 combinations of aligners and callers. We find that bioinformatics pipelines (callers and aligners) have a larger impact on variant reproducibility than WGS platform or library preparation. Single-nucleotide variants (SNVs), particularly outside difficult-to-map regions, are more reproducible than small insertions and deletions (indels), which are least reproducible when > 5 bp. Increasing sequencing coverage improves indel reproducibility but has limited impact on SNVs above 30×. CONCLUSIONS: Our findings highlight sources of variability in variant detection and the need for improvement of bioinformatics pipelines in the era of precision medicine with WGS.

2.
J Hematol Oncol ; 15(1): 2, 2022 Jan 06.
Artigo em Inglês | MEDLINE | ID: mdl-34991659

RESUMO

Tumor-associated macrophages (TAMs) are major components of the tumor microenvironment (TME) which are closely associated with the tumor malignant progression. However, the regulatory mechanisms by which TAMs influence the progression of triple-negative breast cancer (TNBC) remain unclear. Here, we report that hepatic leukemia factor (HLF) acts as a novel oncoprotein in TNBC. We found that HLF was regulated by transforming growth factor-beta1 (TGF-ß1) that is secreted by TAMs. Then, HLF transactivated gamma-glutamyltransferase 1 (GGT1) to promote the ferroptosis resistance, thus driving TNBC cell proliferation, metastasis and cisplatin resistance. Reciprocally, IL-6 produced by TNBC cells activated the JAK2/STAT3 axis to induce TGF-ß1 secretion by TAMs, thus constituted a feed-forward circuit. The accuracy of TNBC patient prognosis could be improved by employing a combination of HLF and GGT1 values. Thus, our findings document that the interactive dialogue between TNBC cells and TAMs promotes sustained activation of HLF in tumor cells through the IL-6-TGF-ß1 axis. Subsequently, HLF promotes the ferroptosis resistance in TNBC cells via GGT1 and ultimately facilitates the malignant tumor progression. Our study provides a potential target for the treatment of TNBC.

3.
Fish Shellfish Immunol ; 120: 441-450, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34933090

RESUMO

Interleukin-8 (IL-8 or C-X-C motif chemokine ligand 8, CXCL8) is a cytokine secreted by numerous cell types and is best known for its functional roles in inflammatory response by binding to specific receptors (the interleukin-8 receptors, IL-8Rs). From the transcriptomic data of largemouth bass (Micropterus salmoides), we identified an IL-8R that is highly homologous to the functionally validated teleost IL-8Rs. The M. salmoides IL-8 receptor (MsCXCR2) was further compared with the C-X-C motif chemokine receptor 2 subfamily by phylogenetic analysis. Briefly, the full-length CDS sequence of MsCXCR2 was cloned into the pEGFP-N1 plasmid, and the membrane localization of fusion expressing MsCXCR2-EGFP was revealed in HEK293 cells. To determine the functional interaction between IL-8 and MsCXCR2, secretory expressed Larimichthys crocea IL-8 (LcIL-8) was used to stimulate MsCXCR2 expressing cells. MsCXCR2 was demonstrated to be activated by LcIL-8, leading to receptor internalization, which was further revealed by the detection of extracellular regulated protein kinase (ERK) phosphorylation. Quantitative real-time PCR was used to evaluate the expressional distribution and variation of MsCXCR2 in healthy and Nocardia seriolae infected fish. Based on our findings, MsCXCR2 was constitutively expressed in all examined tissues, despite at different levels. Furthermore, gene expression was found to be significantly upregulated in the liver and head kidney of diseased fish. Collectively, our findings reveal the molecular activity of MsCXCR2 and indicate the functional involvement of this IL-8R in the immune response induced by N. seriolae in M. salmoides.

4.
Adv Exp Med Biol ; 1354: 207-236, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-34807444

RESUMO

Carbohydrate, which is the most abundant nutrient in plant-sourced feedstuffs, is an economically indispensable component in commercial compound feeds for fish. This nutrient can enhance the physical quality of diets and allow for pellet expansion during extrusion. There is compelling evidence that an excess dietary intake of starch causes hepatic disorders, thereby further reducing the overall food consumption and growth performance of fish species. Among the severe metabolic disturbances are glycogenic hepatopathy (hepatomegaly caused by the excessive accumulation of glycogen in hepatocytes) and hepatic steatosis (the accumulation of large vacuoles of triacylglycerols in hepatocytes). The development of those disorders is mainly due to the limited ability of fish to oxidize glucose and control blood glucose concentration. The prolonged elevations of blood glucose increase glucose intake by the liver, and excess glucose is stored either as glycogen through glycogenesis in hepatocytes or as triglycerides via lipogenesis in tissues, depending on the species. In some fish species (e.g., largemouth bass), the liver has a low ability to regulate glycolysis, gluconeogenesis, and glycogen breakdown in response to high starch intake. For most species of fish, the liver size increases with lipid or glycogen accumulation when they have a high starch intake. It is a challenge to develop the same set of diagnostic criteria for all fish species as their physiology or metabolic patterns differ. Although glycogenic hepatopathy appears to be a common disease in carnivorous fish, it has been under-recognized in many studies. As a result, understanding these diseases and their pathogeneses in different fish species is crucial for manufacturing cost-effective pellet diets to promote the health, growth, survival, and feed efficiency of fish in future.


Assuntos
Bass , Glucose , Animais , Carboidratos da Dieta , Glicogênio , Fígado
5.
Clin Imaging ; 82: 237-243, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-34915318

RESUMO

PURPOSE: To explore the value of MRI conventional features and apparent diffusion coefficient (ADC) on the differential diagnosis of atypical meningioma (AtM) and anaplastic meningioma (AnM). MATERIALS AND METHODS: This retrospective study analyzed the preoperative clinical data, MRI conventional features, and DWI data of 55 AtM and 25 AnM confirmed by pathology in our hospital. The clinical features, MRI conventional features, ADCmean, ADCmin, and relative ADC (rADC) values were compared between the two tumors by Chi-square test or an independent sample t-test. Receiver operating characteristic curve (ROC) and binary logistic regression analysis were used to evaluate the diagnostic efficacy of each parameter to differentiate between these tumors. RESULTS: The MRI conventional features had a certain ability to distinguish AnM and AtM, with an area under the curve value (AUC) of 0.824 (95% CI, 0.723-0.900). The ADCmean, ADCmin, and rADC values were significantly higher in AtM compared to AnM (all P < 0.05). ADCmean had the best identification effect with an AUC of 0.867 (95% CI, 0.772-0.933) among them, at an cut-off of 0.817 × 10-3 mm2/s, the sensitivity and specificity of distinguishing AtM from AnM were 78.18% and 88.00%, respectively. A combination of ADCmean and MRI conventional features showed the optimum discrimination ability for the two tumors, the AUC, sensitivity, specificity, and accuracy were 0.918 (95% CI, 0.835-0.967), 80.00%, 94.55%, and 90.00%, respectively. CONCLUSION: MRI conventional features combined with ADCmean, as a non-invasive method, has potential clinical value in the preoperative diagnosis of AtM and AnM.


Assuntos
Neoplasias Meníngeas , Meningioma , Diagnóstico Diferencial , Imagem de Difusão por Ressonância Magnética , Humanos , Neoplasias Meníngeas/diagnóstico por imagem , Meningioma/diagnóstico por imagem , Estudos Retrospectivos , Sensibilidade e Especificidade
6.
Inorg Chem ; 61(1): 706-712, 2022 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-34935373

RESUMO

A quaternary nonlinear-optical (NLO) zinc germanate, Rb2ZnGe2O6 (RZGO), was prepared from its stoichiometric melts, which belongs to the noncentrosymmetric space group C2221 (No. 20) and features a 3D framework formed by GeO4 tetrahedra, ZnO4 tetrahedra, and Rb+ cations filling into the void space. RZGO displays a good phase-matchable second-harmonic-generation (SHG) intensity similar to that of KH2PO4. The UV cutoff edge for RZGO was found to be approximately 0.37 µm with a broad optical band gap of 3.22 eV, indicating a large laser-induced damage threshold. Further characterizations suggested that this compound displays an excellent thermal stability (1014 °C) and melts congruently. Besides, theoretical analysis was also implemented to investigate the electronic structures and effective NLO coefficients as well as the origin of the observed SHG response for RZGO. The present study can enrich the diversity of acentric germanate structures and pave the way for the synthesis of new NLO compounds.

7.
PLoS One ; 16(12): e0260512, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34871309

RESUMO

This research proposes a new multi-membrane search algorithm (MSA) based on cell biological behavior. Cell secretion protein behavior and cell division and fusion strategy are the main inspirations for the algorithm. In order to verify the performance of the algorithm, we used 19 benchmark functions to compare the MSA test results with MVO, GWO, MFO and ALO. The number of iterations of each algorithm on each benchmark function is 100, the population number is 10, and the running is repeated 50 times, and the average and standard deviation of the results are recorded. Tests show that the MSA is competitive in unimodal benchmark functions and multi-modal benchmark functions, and the results in composite benchmark functions are all superior to MVO, MFO, ALO, and GWO algorithms. This paper also uses MSA to solve two classic engineering problems: welded beam design and pressure vessel design. The result of welded beam design is 1.7252, and the result of pressure vessel design is 5887.7052, which is better than other comparison algorithms. Statistical experiments show that MSA is a high-performance algorithm that is competitive in unimodal and multimodal functions, and its performance in compound functions is significantly better than MVO, MFO, ALO, and GWO algorithms.

8.
Materials (Basel) ; 14(23)2021 Dec 05.
Artigo em Inglês | MEDLINE | ID: mdl-34885618

RESUMO

The process optimization and structural safety improvement of the in-service repair welding of the X80 pipeline are very important. In this paper, the temperature, microstructure, and stress distribution were analyzed using the combination of TMM (thermal-metallurgical-mechanical) simulations and the corresponding verification experiments. The effects of the sleeve material strength and the fillet weld size were discussed. The results showed that the fillet weld zone was mainly composed of ferrite and bainite when the material of the sleeve pipe was Q345B. Furthermore, the sleeve pipe's HAZ (heat affected zone) was dominated by lath martensite, lath bainite, and granular bainite. Moreover, granular bainite and a small amount of ferrite were found in the HAZ of the X80 pipe. It was found that, as the fillet weld size increased, the welding residual stress distribution became more uniform. The hoop stress at weld toe reduced from ~860 MPa of case A to ~680 MPa of case E, and the axial stress at weld toe reduced from ~440 MPa of case A to ~380 MPa of case E. From the viewpoint of welding residual stress, fillet weld size was suggested to be larger than 1.4T. The stress concentration and the stress distribution showed a correlation with the cracking behavior. Weld re-solidification ripples on the weld surface and weld ripples between welding passes or near the weld toe could cause stress concentration and the corresponding crack initiation. Furthermore, when the material of the sleeve pipe changed from Q345B to X80, the high-level tensile stress zone was found to be enlarged. The hoop stress at weld toe increased from ~750 to ~800 MPa, and the axial stress at weld toe increased from ~500 to ~600 MPa. After implementing the new sleeve repair welding process where X80 replaces the material of sleeve pipe, the cracking risk in sleeve pipe will improve. From the perspective of the welding residual stress, it was concluded that the fillet weld size reduction and the sleeve material strength improvement are harmful to in-service welded structures' safety and integrity.

9.
Ultrason Sonochem ; 82: 105882, 2021 Dec 20.
Artigo em Inglês | MEDLINE | ID: mdl-34969003

RESUMO

Stable cavitation (SC) has shown great potential for novel therapeutic applications. The spatiotemporal distribution of the SC activity of microbubbles circulating in a target region is not only correlated with the uniformity of treatment, but also with some undesirable effects. Therefore, it is important to achieve controllable and desirable SC activity in target regions for improved therapeutic efficiency and biosafety. This study proposes a closed-loop feedback controller based on pulse length (PL) regulation to improve the temporal stability of SC activity. Microbubbles circulating in a physiological flowing phantom were exposed to a 1 MHz focused transducer. The SC signals produced were initially received by another 7.5 MHz plane transducer, followed by high-speed signal acquisition and real-time processing. Based on the real-time-measured SC intensity excited by the current acoustic pulse, the proposed closed-loop feedback controller used three proportional coefficients to regulate the peak negative pressure (PNP) and PL of the next acoustic pulse during the acceleration and stable stages, respectively. The results show that the rise time and the temporal stability of the SC intensity of the microbubbles circulating in these two stages were improved significantly by the optimized proportional coefficients used in the proposed controller. Importantly, when compared with the traditional closed-loop feedback controller based on PNP regulation, the proposed closed-loop feedback controller based on PL regulation reduced the probability of a transition between stable and inertial cavitation, thus avoiding the risk of disadvantageous bioeffects in practical applications. These results demonstrate the effectiveness of the proposed PL-based closed-loop feedback controller and provide a feasible strategy for realization of controllable cavitation activity in applications.

10.
Biomed Res Int ; 2021: 6388492, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34901275

RESUMO

Breast cancer is one of the common malignant tumors, and liquid biopsy has become a hot spot for clinical testing. To clarify the detection effect of liquid biopsy in breast cancer, we collected peripheral blood of HER2-positive (human epidermal growth factor receptor 2-positive) patients. Circulating tumor cells (CTCs) were isolated and analyzed. HER2 expression on CTCs was detected. The results showed that in the 198 HER2-positive samples, the CTC detection rate was 79.8% (158/198), and the mean number of CTCs was 21, ranging from 1 to 63/7.5 mL peripheral blood. Only 41.1% (65/158) of patients had histology and CTC HER2 status consistent with the remaining 58.9% (93/158) of patients, although their histological HER2 was positive, and CTC HER2 was negative. Our study confirmed the value of CTC HER2 real-time status testing in HER2-positive breast cancer patients. The inconsistency in HER2 status between CTCs and histology may be related to the time interval between CTCs and histological HER2 detection, suggesting that real-time HER2 detection is necessary for histological HER2-positive patients.

11.
Cell Death Dis ; 12(12): 1156, 2021 12 14.
Artigo em Inglês | MEDLINE | ID: mdl-34907160

RESUMO

Lots of cell death initiator and effector molecules, signalling pathways and subcellular sites have been identified as key mediators in both cell death processes in cancer. The XDeathDB visualization platform provides a comprehensive cell death and their crosstalk resource for deciphering the signaling network organization of interactions among different cell death modes associated with 1461 cancer types and COVID-19, with an aim to understand the molecular mechanisms of physiological cell death in disease and facilitate systems-oriented novel drug discovery in inducing cell deaths properly. Apoptosis, autosis, efferocytosis, ferroptosis, immunogenic cell death, intrinsic apoptosis, lysosomal cell death, mitotic cell death, mitochondrial permeability transition, necroptosis, parthanatos, and pyroptosis related to 12 cell deaths and their crosstalk can be observed systematically by the platform. Big data for cell death gene-disease associations, gene-cell death pathway associations, pathway-cell death mode associations, and cell death-cell death associations is collected by literature review articles and public database from iRefIndex, STRING, BioGRID, Reactom, Pathway's commons, DisGeNET, DrugBank, and Therapeutic Target Database (TTD). An interactive webtool, XDeathDB, is built by web applications with R-Shiny, JavaScript (JS) and Shiny Server Iso. With this platform, users can search specific interactions from vast interdependent networks that occur in the realm of cell death. A multilayer spectral graph clustering method that performs convex layer aggregation to identify crosstalk function among cell death modes for a specific cancer. 147 hallmark genes of cell death could be observed in detail in these networks. These potential druggable targets are displayed systematically and tailoring networks to visualize specified relations is available to fulfil user-specific needs. Users can access XDeathDB for free at https://pcm2019.shinyapps.io/XDeathDB/ .


Assuntos
Morte Celular/fisiologia , Morte Celular Regulada/fisiologia , Transdução de Sinais/fisiologia , Animais , COVID-19/metabolismo , COVID-19/fisiopatologia , Análise por Conglomerados , Bases de Dados Factuais , Humanos , Necroptose , Neoplasias/metabolismo , Neoplasias/fisiopatologia , Fagocitose , SARS-CoV-2/metabolismo , SARS-CoV-2/fisiologia , Transdução de Sinais/efeitos dos fármacos , Software
12.
BMC Infect Dis ; 21(1): 1273, 2021 Dec 20.
Artigo em Inglês | MEDLINE | ID: mdl-34930163

RESUMO

BACKGROUND: The manifestations and prognoses of acute-on-chronic liver failure (ACLF) with different precipitating events remain heterogeneous. We aimed to investigate the characteristics and prognosis of patients with hepatotropic viral insult (HVI)-induced hepatitis B-related ACLF (HBV-ACLF). METHODS: 452 patients with confirmed diagnosis of ACLF were screened in three medical centers in China, and 203 HBV-ACLF patients with definite acute precipitating events were retrospectively analyzed. According to the precipitating events, HBV-ACLF patients induced by HBV reactivation and super-infection with HAV were classified as the hepatotropic viral insult group and those induced by other factors, as the non-virus insult (NVI) group. The clinical characteristics, predictive scoring model, and prognosis of the two groups were compared. RESULTS: Hepatitis B virus reactivation accounted for the largest proportion (39.9%) among all precipitating events. Exacerbation time frame of the HVI group was significantly longer than that of the NVI group (20 days vs. 10 days, P < 0.001). Comparison of intergroup prognosis showed that there was no significant difference in the 28 day mortality (20.9 vs. 13.7%, P = 0.125), while the 90 day and 1 year mortality in the HVI group were higher than those in the NVI group (36.3 vs. 24.4%, P = 0.014; 39.5% vs. 27.5%, P = 0.020, respectively). In the HVI group, the lactic acid-free APASL-ACLF Research Consortium (AARC) had better predictive value for 90 day mortality (0.741). CONCLUSIONS: The 90 day and 1 year survival rate was lower in HBV-ACLF patients induced by HVI than by NVI. The lactate-free AARC score was a better predictor of short- and long-term prognosis in patients with HVI-induced HBV-ACLF.


Assuntos
Insuficiência Hepática Crônica Agudizada , Hepatite B , China/epidemiologia , Hepatite B/complicações , Humanos , Prognóstico , Estudos Retrospectivos
13.
Artigo em Inglês | MEDLINE | ID: mdl-34962861

RESUMO

Most existing deep neural networks are static, which means they can only do inference at a fixed complexity. But the resource budget can vary substantially across different devices. Even on a single device, the affordable budget can change with different scenarios, and repeatedly training networks for each required budget would be incredibly expensive. Therefore, in this work, we propose a general method called MutualNet to train a single network that can run at a diverse set of resource constraints. Our method trains a cohort of model configurations with various network widths and input resolutions. This mutual learning scheme not only allows the model to run at different width-resolution configurations but also transfers the unique knowledge among these configurations, helping the model to learn stronger representations overall. MutualNet is a general training methodology that can be applied to various network structures (e.g., 2D networks: MobileNets, ResNet, 3D networks: SlowFast, X3D) and various tasks (e.g., image classification, object detection, segmentation, and action recognition), and is demonstrated to achieve consistent improvements on a variety of datasets. Since we only train the model once, it also greatly reduces the training cost compared to independently training several models.

14.
Sci Rep ; 11(1): 22959, 2021 Nov 25.
Artigo em Inglês | MEDLINE | ID: mdl-34824300

RESUMO

Quercetin has demonstrated antioxidant, anti-inflammatory, hypoglycemic, and hypolipidemic activities, suggesting therapeutic potential against type 2 diabetes mellitus (T2DM) and Alzheimer's disease (AD). In this study, potential molecular targets of quercetin were first identified using the Swiss Target Prediction platform and pathogenic targets of T2DM and AD were identified using online Mendelian inheritance in man (OMIM), DisGeNET, TTD, DrugBank, and GeneCards databases. The 95 targets shared among quercetin, T2DM, and AD were used to establish a protein-protein interaction (PPI) network, top 25 core genes, and protein functional modules using MCODE. Metascape was then used for gene ontology and kyoto encyclopedia of genes and genomes (KEGG) pathway enrichment analysis. A protein functional module with best score was obtained from the PPI network using CytoHubba, and 6 high-probability quercetin targets (AKT1, JUN, MAPK, TNF, VEGFA, and EGFR) were confirmed by docking simulations. Molecular dynamics simulation was carried out according to the molecular docking results. KEGG pathway enrichment analysis suggested that the major shared mechanisms for T2DM and AD include "AGE-RAGE signaling pathway in diabetic complications," "pathways in cancer," and "MAPK signaling pathway" (the key pathway). We speculate that quercetin may have therapeutic applications in T2DM and AD by targeting MAPK signaling, providing a theoretical foundation for future clinical research.

15.
Arch Virol ; 2021 Nov 26.
Artigo em Inglês | MEDLINE | ID: mdl-34826001

RESUMO

Paper mulberry vein banding virus (PMVBV), a member of the genus Badnavirus in the family Caulimoviridae, infects paper mulberry (Broussonetia papyrifera), a dicotyledonous plant. Putative promoter regions in the PMVBV genome were tested using recombinant plant expression vectors, revealing that the promoter activity of three genome fragments was about 1.5-fold higher than that of the 35S promoter of cauliflower mosaic virus in Nicotiana benthamiana. In transformed transgenic Arabidopsis thaliana plants, these promoter constructs showed constitutive expression. Based on the activity and gene expression patterns of these three promoter constructs, a fragment of 384 bp (named PmVP) was deduced to contain the full-length promoter of the PMVBV genome. The results suggest that the PMVBV-derived promoter can be used for the constitutive expression of transgenes in dicotyledonous plants.

16.
J Hepatol ; 2021 Nov 13.
Artigo em Inglês | MEDLINE | ID: mdl-34785325

RESUMO

BACKGROUND & AIMS: The association between sarcopenia and prognosis in patients with cirrhosis remains to be determined. In this study, we aimed to quantify the association between sarcopenia and the risk of mortality in patients with cirrhosis, by sex, underlying liver disease etiology, and severity of hepatic dysfunction. METHODS: PubMed, Web of Science, EMBASE, and major scientific conference sessions were searched without language restriction through 13 January 2021 with additional manual search of bibliographies of relevant articles. Cohort studies of ≥100 patients with cirrhosis and ≥12 months of follow-up that evaluated the association between sarcopenia, muscle mass and the risk of mortality were included. RESULTS: 22 studies with 6965 patients with cirrhosis were included. The pooled prevalence of sarcopenia in patients with cirrhosis was 37.5% overall (95% CI 32.4%-42.8%), higher in male patients, patients with alcohol associated liver disease (ALD), patients with CTP grade C, and when sarcopenia was defined in patients by lumbar 3- skeletal muscle index (L3-SMI). Sarcopenia was associated with the increased risk of mortality in patients with cirrhosis (adjusted-hazard ratio [aHR] 2.30, 95% CI 2.01-2.63), with similar findings in sensitivity analysis of cirrhosis patients without HCC (aHR 2.35, 95% CI 1.95-2.83) and in subgroup analysis by sex, liver disease etiology, and severity of hepatic dysfunction. The association between quantitative muscle mass index and mortality further supports the poor prognosis for patients with sarcopenia (aHR 0.95, 95% CI 0.93-0.98). There was no significant heterogeneity in all analyses. CONCLUSIONS: Sarcopenia was highly and independently associated with higher risk of mortality in patients with cirrhosis. LAY SUMMARY: The prevalence of sarcopenia and its association with death in patients with cirrhosis remain unclear. This meta-analysis indicated that sarcopenia affected about one-third of patients with cirrhosis and up to 50% in patients with ALD or Child's class C cirrhosis. Sarcopenia was independently associated with about 2-fold higher risk of mortality in patients with cirrhosis. The mortality rate increased with greater severity or longer period of having sarcopenia. Increasing awareness about the importance of sarcopenia in patients with cirrhosis among stakeholders must be prioritized.

17.
J Gastrointest Oncol ; 12(5): 2287-2309, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34790393

RESUMO

Background: Cholangiocarcinoma (CCA) is a malignant tumor of the digestive system, with occult onset in the early stage, a high degree of malignancy in the late stage, and poor prognosis. At present, the pathogenesis of CCA is not clear, and there is a lack of effective immunotherapy. The purpose of this study was to identify the potential regulatory mechanism of CCA and analyze the possibility of its related immunotherapy. Methods: The circular RNAs (circRNAs) expression profile data of CCA was downloaded from the Gene Expression Omnibus (GEO) database; the miRNA and mRNA expression profile data of CCA were downloaded from The Cancer Genome Atlas (TCGA) database. Prognostic factors were screened by univariate Cox regression analysis, and the competing endogenous RNA (ceRNA) network was constructed via survival analysis. Multivariate Cox analysis was used to screen the independent prognostic factors and construct a prognostic correlation subnetwork. Analyzing the tumor microenvironment of CCA and survival analysis were performed according to the score of the microenvironment, and the distribution of tumor infiltrating immune cells (TICs) in CCA was calculated using the CIBERSORT algorithm. We explored the expression pattern of the target genes in pan-cancer, and the correlation between the key genes in the ceRNA subnetwork, TICs and immune checkpoints was analyzed using an online database. Finally, the expression levels of target genes were validated based on the Human Protein Atlas (HPA) databases. Results: We screened four circRNAs, 10 miRNAs, and 17 mRNAs with significant differences, and constructed the ceRNA network. Independent prognostic factors were screened by multivariate Cox regression analysis, and a subnetwork containing five nodes (hsa_circ_0002073→hsa-mir-4524a-3p→SLC16A3/SLC35E4/DDX4) was constructed. Further analysis showed that SLC16A3 was not only an independent posterior factor of CCA, but was also closely correlated with immune cells, immune checkpoints, and immunotherapy, and had a certain regulatory effect on the tumor microenvironment. Conclusions: Our study identified a novel prognostic marker of CCA, SLC16A3, and revealed the regulatory role of SLC16A3 in the tumor microenvironment, which is expected to provide new insights for the early diagnosis, prognosis, and targeted therapy of CCA.

18.
World J Clin Cases ; 9(28): 8587-8594, 2021 Oct 06.
Artigo em Inglês | MEDLINE | ID: mdl-34754872

RESUMO

BACKGROUND: A patient with advanced tuberculosis of the hip joint combined with Crowe type IV developmental dysplasia of the hip (DDH) and a drainage sinus is a rare condition. There are no previous reports of this condition, and it is a complex challenge for surgeons to develop a treatment scheme. CASE SUMMARY: We report a 73-year-old male patient with severe hip pain and drainage sinus of the left hip for one month. Approximately 40 years ago, a drainage sinus occurred at the lateral left hip was healed at the local hospital with anti-infectious therapy. After the sinus healed, gradual pain occurred in the left hip for 40 years. Approximately one month prior, hip pain was sharply aggravated, and a drainage sinus reoccurred in the left hip. The X-ray and computed tomography examinations showed destruction of the head and neck of the left femur, as well as an acetabular deformity. The results of Mycobacterium tuberculosis antibody and Xpert were positive. Therefore, the patient was diagnosed with advanced TH combined with Crowe type IV DDH. After 22 d of treatment with anti-tuberculosis chemotherapy, the sinus healed, and the patient underwent one-stage total hip arthroplasty (THA) surgery consisting of debridement, osteotomy, and joint replacement. After surgery, the patient received anti-tuberculosis chemotherapy drugs for nine months, with no recurrent infection. After one year of follow-up, the Harris score of the patient increased from 21 pre-THA to 86. CONCLUSION: Although drainage sinuses are a contraindication to one-stage THA, one-stage THA is still an effective and safe surgical method after the sinus heals.

19.
J Hazard Mater ; 424(Pt C): 127589, 2021 Oct 24.
Artigo em Inglês | MEDLINE | ID: mdl-34740155

RESUMO

Knowledge on the interaction between microplastics (MPs) and zinc oxide nanoparticles (ZnO NPs) is limited. Here, we investigated effects of embryo-larvae exposure to 500 µg/L polystyrene MPs (5 µm), 1200 µg/L ZnO NPs (< 100 nm), 500 µg/L dissolved Zn2+ from ZnSO4, and the mixtures of MPs and ZnO NPs or ZnSO4 on exposed F0 larvae and unexposed F1 larvae. Consequently, ZnO particles adhered to MPs surfaces rather than Zn2+, and increased Zn transport into larvae. Growth inhibition, oxidative stress, apoptosis, and disturbance of growth hormone and insulin-like growth factor (GH/IGF) axis were induced by MPs and ZnO NPs alone, which were further aggravated by their co-exposure in F0 larvae. MPs + ZnO increased apoptotic cells in the gill and esophagus compared with MPs and ZnO NPs alone. Reduced growth and antioxidant capacity and down-regulated GH/IGF axis were merely observed in F1 larvae from F0 parents exposed to MPs + ZnO. Contrary to ZnO NPs, dissolved Zn2+ reversed MPs toxicity, suggesting the protective role of Zn2+ may be not enough to ameliorate thfie negative effects of ZnO particles. To summarize, we found that particles rather than released Zn2+ from ZnO nanoparticles amplified MPs toxicity in early stages of exposed zebrafish and their unexposed offspring.

20.
BMC Plant Biol ; 21(1): 529, 2021 Nov 11.
Artigo em Inglês | MEDLINE | ID: mdl-34763662

RESUMO

BACKGROUND: Natural hybridization can influence the adaptive response to selection and accelerate species diversification. Understanding the composition and structure of hybrid zones may elucidate patterns of hybridization processes that are important to the formation and maintenance of species, especially for taxa that have experienced rapidly adaptive radiation. Here, we used morphological traits, ddRAD-seq and plastid DNA sequence data to investigate the structure of a Rhododendron hybrid zone and uncover the hybridization patterns among three sympatric and closely related species. RESULTS: Our results show that the hybrid zone is complex, where bi-directional hybridization takes place among the three sympatric parental species: R. spinuliferum, R. scabrifolium, and R. spiciferum. Hybrids between R. spinuliferum and R. spiciferum (R. ×duclouxii) comprise multiple hybrid classes and a high proportion of F1 generation hybrids, while a novel hybrid taxon between R. spinuliferum and R. scabrifolium dominated the F2 generation, but no backcross individuals were detected. The hybrid zone showed basically coincident patterns of population structure between genomic and morphological data. CONCLUSIONS: Natural hybridization exists among the three Rhododendron species in the hybrid zone, although patterns of hybrid formation vary between hybrid taxa, which may result in different evolutionary outcomes. This study represents a unique opportunity to dissect the ecological and evolutionary mechanisms associated with adaptive radiation of Rhododendron species in a biodiversity hotspot.

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