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1.
JAMA Netw Open ; 4(4): e215302, 2021 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-33835173

RESUMO

Importance: The World Health Organization End TB (Tuberculosis) Strategy aims to decrease the global incidence and mortality of TB by 90% and 95%, respectively, as of 2035. Objective: To characterize the recent epidemiological trend of pulmonary TB (PTB) in mainland China based on the national surveillance data. Design, Setting, and Participants: This cross-sectional study collected demographic and clinical data of all patients reported in the national Tuberculosis Information Management System of China from January 1, 2005, to November 21, 2016. Data were analyzed from December 1, 2019, to July 31, 2020. Exposures: Pulmonary TB was defined as bacteriologically confirmed or clinically diagnosed TB in the lung parenchyma or the tracheobronchial tree. Main Outcomes and Measures: Temporal and spatial variation of annual incidence and demographic features of PTB in mainland China. Results: In total, 10 582 903 patients with PTB were reported in mainland China from 2005 to 2016. The median age of patients with PTB was 46 (interquartile range [IQR], 30-61) years, and 28.53% were 60 years or older. Most patients with PTB were male (69.8%) and farmers or herders (70.0%). The mean (SD) incidence of PTB was 66.61 (8.09) per 100 000 population. The annual incidence decreased from 72.95 per 100 000 population in 2005 to 52.18 per 100 000 population in 2016, and the reduction was greater in the eastern and central regions (31.6%; from 69.43 to 47.48 per 100 000 population) than in the western region (21.0%; from 82.06 to 64.82 per 100 000 population). Xinjiang Uygur Autonomous Region (135.03 per 100 000 population), Guizhou Province (115.98 per 100 000 population), and the Tibet Autonomous Region (101.98 per 100 000 population) had the highest mean annual incidences. The median time from onset of illness to diagnosis decreased from 36 (IQR, 16-92) days from 2005 to 2007 to 31 (IQR, 15-63) days in 2008 and later (P < .001) and was longer in the western region than in the eastern and central regions (41 [IQR, 20-91] vs 30 [IQR, 13-61] days; P < .001). Conclusions and Relevance: Although this study found that the incidence of PTB in mainland China showed a downward trend from 2005 to 2016, to achieve the World Health Organization 2035 goal, innovative and more efficient prevention and control strategies are needed, particularly among the most susceptible population, that is, farmers and herders in western China.

2.
J Zhejiang Univ Sci B ; 22(4): 305-309, 2021 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-33835764

RESUMO

Staphylococcal enterotoxin A (SEA) synthesized by Staphylococcus aureus is a foodborne and heat-stable toxin, which is a great threat to human health (Pexaraet al., 2010). Highly sensitive antibodies are a key factor in the immunological detection of SEA, which is one of the most effective ways to detect SEA because of its accuracy, agility, and efficiency (Nouri et al., 2018). In this study, we constructed a tetravalent anti-SEA antibody gene by linking the tetramerization domain of human p53 to the C-terminus of the anti-SEA single-chain variable fragment (scFv), which was then transformed into Escherichia coli BL21 (DE3) for the production of a SEA-specific tetravalent antibody. Successful expression of the tetravalent antibody was determined by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) and western blot. An indirect non-competitive enzyme-linked immunosorbent assay (ELISA) revealed that the tetravalent antibody exhibited SEA-specific binding activity. A sandwich ELISA demonstrated that compared to the scFv monomer, the tetravalent antibody was more sensitive in detecting SEA. Molecular docking analysis revealed that the SEA interacted with the scFv mainly on the opposite side of the residue linked to p53. Thus, this study indicated that genetically engineered tetramerization is a potential way to improve the sensitivity of SEA-specific scFv.

3.
J Integr Plant Biol ; 2021 Mar 03.
Artigo em Inglês | MEDLINE | ID: mdl-33656245

RESUMO

The alternative splicing of select genes is an important mechanism to regulate responses to endogenous and environmental signals in plants. However, the role of alternative splicing in regulating fruit ripening remains unclear. Here, we discovered that MaMYB16L, an R1-type MYB transcription factor, undergoes alternative splicing and generates two transcripts, the full-length isoform MaMYB16L and a truncated form MaMYB16S, in banana fruit. During banana fruit ripening, the alternative splicing process intensifies with downregulated MaMYB16L and upregulated MaMYB16S. Moreover, MaMYB16L is a transcriptional repressor that directly binds with the promoters of many genes associated with starch degradation and MaDREB2, a positive ripening regulator, and represses their expression. In contrast, MaMBY16S lacks a DNA-binding domain but competitively combines and forms nonfunctional heterodimers with functional MaMYB16L. MaMYB16L-MaMYB16S heterodimers decrease the binding capacity and transrepression activity of MaMYB16L. The downregulation of MaMYB16L and the upregulation of MaMYB16S, i.e., a decreased ratio of active to nonactive isoforms, facilitates the activation of ripening-related genes and thereby promotes fruit ripening. Furthermore, the transient overexpression of MaMYB16S promotes banana fruit ripening, whereas the overexpression of MaMYB16L delays this process. Therefore, the alternative splicing of MaMYB16L might generate a self-controlled regulatory loop to regulate banana fruit ripening. This article is protected by copyright. All rights reserved.

4.
Front Immunol ; 12: 620365, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33717119

RESUMO

Background and Aims: Acute-on-chronic liver failure (ACLF) is characterized by systemic inflammation accompanied by defective anti-bacterial immunity. The role of neutrophils in immune derangement of ACLF has not been fully elucidated. This study is aimed to characterize the role of circulating neutrophils in HBV-related ACLF patients. Methods: Quantitative, phenotypic, transcriptomic, and functional alterations of circulating neutrophils were compared in ACLF and non-ACLF subjects and analyzed for associations with short-term outcomes. Interventional experiments were performed to test the impact on ACLF-patient neutrophil function in vitro. Results: Circulating absolute neutrophil count was significantly increased in patients with ACLF and was an independent risk factor for 28-day mortality. ACLF-patient neutrophils differentially expressed a panel of surface markers (include TLR-1, TLR-2, TLR-4, CEACAM-1 and FPR1), as well as a distinct transcriptomic signature. ACLF-neutrophils displayed significantly impaired phagocytosis but an increased capacity to form neutrophil extracellular traps (NETs), which was more pronounced in patients with poor outcome. Healthy neutrophils mimicked functional characteristics of ACLF counterpart after co-cultured with plasma from ACLF patients. The oxidative burst and cytokine production capacities remained unchanged. Plasma GM-CSF, IL-6, IL-8, IL-10, and IP-10 levels, as well as lipopolysaccharide (LPS) concentration, were markedly elevated in ACLF patients but not DAMP molecules HMGB-1 and HSP70. Finally, a glycolysis inhibitor, 2-deoxy-glucose, reduced NET formation of ACLF patients' neutrophils. Conclusions: Circulating ACLF-patient neutrophils exhibit alterations in number, phenotype, gene expression and function, which was associated with poor outcome and shaped by the ACLF circulatory environment. Inhibiting glycolysis can reverse neutrophil dysfunction in ACLF patients.

5.
Comput Biol Med ; 131: 104272, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33636420

RESUMO

Computer-aided detection (CADe) of pulmonary nodules is an effective approach for early detection of lung cancer. However, due to the low contrast of lung computed tomography (CT) images, the interference of blood vessels and classifications, CADe has the problems of low detection rate and high false-positive rate (FPR). To solve these problems, a novel method using Hessian information and multi-scale reverse Laplacian of Gaussian (LoG) (Hessian-MRLoG) is proposed and developed in this work. Also, since the intensity distribution of the LoG operator and the lung nodule in CT images are inconsistent, and their shapes are mismatched, a multi-scale reverse Laplacian of Gaussian (MRLoG) is constructed. In addition, in order to enhance the effectiveness of target detection, the second-order partial derivatives of MRLoG are partially adjusted by introducing an adjustment factor. On this basis, the Hessian-MRLoG model is developed, and a novel elliptic filter is designed. Ultimately, in this study, the method of Hessian-MRLoG filtering is proposed and developed for pulmonary nodule detection. To verify its effectiveness and accuracy, the proposed method was used to analyze the LUNA16 dataset. The experimental results revealed that the proposed method had an accuracy of 93.6% and produced 1.0 false positives per scan (FPs/scan), indicating that the proposed method can improve the detection rate and significantly reduce the FPR. Therefore, the proposed method has the potential for application in the detection, localization and labeling of other lesion areas.

6.
Artigo em Inglês | MEDLINE | ID: mdl-33579831

RESUMO

BACKGROUND: Shenfu injection (SFI) is a traditional Chinese herbal medicine which has been clinically used for treatment of septic shock and cardiac shock. The aim of this study was to clarify effects of SFI on cerebral microcirculation and brain injury after hemorrhagic shock (HS). METHODS: Twenty-one domestic male Beijing Landrace pigs were randomly divided into three groups: SFI group (SFI, n = 8), saline group (SA, n = 8) or sham operation group (SO, n = 5). In the SFI group, animals were induced to HS by rapid bleeding to a mean arterial pressure of 40 mmHg within 10 minutes and maintained at 40±3 mmHg for 60 minutes. Volume resuscitation (shed blood and crystalloid) and SFI were given after 1 hour of HS. In the SA group, animals received the same dose of saline instead of SFI. In the SO group, the same surgical procedure was performed but without inducing HS and volume resuscitation. The cerebral microvascular flow index (MFI), nitric oxide synthase (NOS) expression, aquaporin-4 expression, interleukin-6, tumor necrosis factor-α (TNF-α) and ultrastructural of microvascular endothelia were measured. RESULTS: Compared with the SA group, SFI significantly improved cerebral MFI after HS. SFI up regulated cerebral endothelial NOS expression, but down regulated interleukin-6, TNF-α, inducible NOS and aquaporin-4 expression compared with the SA group. The cerebral microvascular endothelial injury and interstitial edema in the SFI group were lighter than those in the SA group. CONCLUSIONS: Combined application of SFI with volume resuscitation after HS can improve cerebral microcirculation and reduce brain injury.

7.
Clin Transplant ; : e14238, 2021 Feb 02.
Artigo em Inglês | MEDLINE | ID: mdl-33527545

RESUMO

OBJECTIVE: The objective of this study was to assess how pre-transplant dialysis duration affects transplant outcomes after simultaneous pancreas-kidney transplant (SPK) in patients with type 1 diabetes mellitus (T1DM). METHODS: Data of 6887 T1DM patients who underwent SPK transplantation between 2008 and 2018 were obtained from the Scientific Registry of Transplant Recipients database. According to pre-transplant dialysis duration, the patients were divided into the preemptive SPK, 0-2 years, 2-5 years, and >5 years dialysis groups. Kaplan-Meier survival analysis was performed to compare patient and graft survival among the groups. Univariate and multivariate Cox regression analyses were used to identify predictors of transplant outcomes. RESULTS: The mean follow-up period was 56.7 ± 34.7 months. Compared with no dialysis or preemptive SPK, dialysis for 0-2 years was not significantly associated with patient or kidney graft survival, while long-term dialysis of 2-5 years and >5 years was significantly associated with increased risk of death and kidney graft failure. However, the duration of dialysis was not associated with pancreas graft survival. CONCLUSION: Long-term dialysis duration before SPK transplant is an independent predictor of patient death and kidney graft failure in T1DM patients.

8.
Eur J Ophthalmol ; : 1120672121996641, 2021 Feb 24.
Artigo em Inglês | MEDLINE | ID: mdl-33626917

RESUMO

OBJECTIVES: To determine the biomechanical changes of porcine corneas after the application of hydrogen peroxide(H2O2) solution. METHODS: Fifty-five porcine eyeballs with similar sizes were divided into 11 groups based on the H2O2 application. The eyeballs were treated with the following concentrations of H2O2 solution: 1 mol/L, 500 mmol/L, 250 mmol/L, 125 mmol/L, 62.5 mmol/L, 31.25 mmol/L, 15.63 mmol/L, 7.81 mmol/L, 3.91 mmol/L, 0.9% saline, or blank. The eyeballs were immersed into the solution for 30 min. The biomechanics of each cornea in the different groups was determined soon after the indentation and tensile tests. We calculated the average Young's modulus of the different groups to determine the effects of H2O2 solution on porcine corneas. The comparison between the groups was conducted using ANOVA analysis. Moreover, the safety of each concentration of H2O2 solution on the corneal tissues was determined by histopathological examination. RESULTS: The Young's modulus was significantly different among all the groups (p = 0.003). The modulus was the highest in the group treated with 3.91 mmol/L H2O2 and it was significantly different from that in the group treated with 0.9% saline or the blank group, for both the indentation and tensile tests. Histopathological examination showed that H2O2 at a concentration of ⩾62.5 mmol/L damaged the epithelium, stroma, or both, while H2O2 at a concentration ⩽31.25 mmol/L did not change the morphology of the epithelium or stroma. CONCLUSIONS: Treatment with 3.91 mmol/L H2O2 solution can safely and effectively increase the biomechanical strength of the cornea.

9.
Plant Sci ; 304: 110797, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33568296

RESUMO

Maize is one of the most broadly cultivated crops throughout the world, and flowering time is a major adaptive trait for its diffusion. The biggest challenge in understanding maize flowering genetic architecture is that the trait is confounded with population structure. To eliminate the effect, we revisited the flower time genetic network by using a tropical maize population Pop32, which was under mass selection for adaptation to early flowering time in China for six generations from tropical to temperate regions. The days to anthesis (DTA) of the initial (Pop32C0), intermedia (Pop32C3), and final population (Pop32C5) was 90.77, 84.63, and 79.72 days on average, respectively. To examine the genetic mechanism and identify the genetic loci underlying this rapid change in flowering time of Pop32, we bulked 30 individuals from C0, C3, and C5 to conduct the whole genome sequencing. And we finally identified 4,973,810 high-quality single nucleotide polymorphisms (SNPs) and 6,517 genes with allele frequency significantly changed during the artificial improvement process. We speculate that these genes might participate in the adaptive improvement process and control flowering time. To identify the candidate genes for flowering time from the gene set with allele frequency changed, we carried out weighted gene co-expression network analysis (WGCNA), and identified four co-expression modules that highly associated with the flowering time development, as well as constructed the co-expression network of key flowering time genes. Gene Ontology (GO) enrichment analysis revealed that the GO terms photosynthesis/light reaction, carbohydrate binding, auxin mediated signaling pathway, response to temperature stimulus that are closely connected with flowering time. Furthermore, targeted GWAS revealed the genes are significantly connected with the flowering time. qRT-PCR of four candidate genes GRMZM2G019879, GRMZM2G055905, GRMZM2G058158, and GRMZM2G171365 showed that their expression level is similar to the flowering time genes, which playing a key role in maize flowering time transition. This study revealed that the changes of flowering time in mass selection process may be strongly associated with the variations of allele frequency changes, and we identified some important candidate genes for flowering time, which will provide a new insight for the rapid improvement of maize important agronomic traits and promote the gene cloning of maize flowering time.

10.
J Int Med Res ; 49(2): 300060520987059, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33626941

RESUMO

OBJECTIVE: Length of hospital stay is a sensitive indicator of short-term prognosis. In this retrospective study, we investigated how pancreas preservation time affects length of hospital stay after pancreas transplantation. METHODS: Patients receiving pancreas transplantation (1998.7-2018.6) were identified from the Scientific Registry of Transplant Recipients database and grouped according to pancreas preservation time. We analyzed the relationship of pancreas preservation time with graft and patient survival and prolonged length of stay (PLOS; i.e., hospital stay ≥20 days). RESULTS: We included 18,099 pancreas transplants in the survival analysis. Pancreas preservation time >20 hours had a significantly higher risk of graft failure than 8 to 12 hours. Pancreas preservation time was not significantly associated with patient survival. We included 17,567 pancreas transplants in the analysis for PLOS. Compared with 8 to 12 hours, pancreas preservation time >12 hours had a significantly higher PLOS risk, which increased with increased pancreas preservation time. In simultaneous pancreas-kidney transplantation, we also found that pancreas preservation time was positively associated with PLOS risk with pancreas preservation time >12 hours. CONCLUSION: Pancreas preservation time is a sensitive predictor of PLOS. Transplant centers should minimize pancreas preservation time to optimize patient outcomes.

11.
ACS Nano ; 15(2): 2611-2623, 2021 02 23.
Artigo em Inglês | MEDLINE | ID: mdl-33533242

RESUMO

Long-distance walking with heavy loads is often needed when going hiking or for field rescue, which is prone to cumulative fatigue. There is also a great need for labor-saving and biomechanical energy harvesting in daily life for extended security and communication needs. Here, we report a load-suspended backpack for harvesting the wasted energy of human motion based on a triboelectric nanogenerator (TENG). Two elastomers are incorporated into the backpack to decouple the synchronous movement of the load and the human body, which results in little or no extra accelerative force. With such a design, through theoretical analysis and field experiments, the backpack can realize a reduction of 28.75 % in the vertical oscillation of the load and 21.08 % in the vertical force on the wearer, respectively. Meanwhile, the mechanical-to-electric energy conversion efficiency is modeled and calculated to be 14.02 % under normal walking conditions. The designed backpack has the merits of labor-saving and shock absorption as well as electricity generation, which has the promising potential to be a power source for small-scale wearable and portable electronics, GPS systems, and other self-powered health care sensors.

12.
Arch Virol ; 166(2): 389-402, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33385245

RESUMO

Recombination is an important phenomenon that accelerates evolution and enriches the genetic diversity of porcine reproductive and respiratory syndrome virus (PRRSV). Recombinant PRRSV isolates sometimes have different genetic backgrounds. In this study, we report a recombinant PRRSV (SD-YL1712) isolated from a pig farm. The genome of SD-YL1712 is 15,014 nucleotides in length, and its nucleotide and amino acid sequence conservation is higher than that of PRRSV strain JXA1 except within the NSP2 region. The NSP2 region of SDYL1712 shares the highest nucleotide (85.9%) and amino acid (84.1%) sequence identity with PRRSV strain NADC30. SD-YL1712 was found to contain a characteristic 131-amino-acid deletion in the NSP2 region. Two recombination breakpoints were detected at nt 2134 and nt 3958 within the NSP2 region, which revealed that SD-YL1712 originated from a recombination event between NADC30-like and HP-PRRSV-derived MLV-like strains. Interestingly, SD-YL1712 had an additional deletion at position 586, similar to that found in strain TJnh1501. Moreover, the pathogenicity of strain SD-YL1712 was found to be similar to that of HP-PRRSV JXA1, which was higher than that of the CH1a strain. Further analysis indicated that SD-YL1712 might be a transitional intermediate in the evolution of TJbd1401 to TJnh1501.


Assuntos
Genoma Viral/genética , Síndrome Respiratória e Reprodutiva Suína/virologia , Vírus da Síndrome Respiratória e Reprodutiva Suína/genética , Recombinação Genética/genética , Sequência de Aminoácidos , Animais , China , Evolução Molecular , Fazendas , Variação Genética/genética , Genômica , Filogenia , Análise de Sequência de DNA/métodos , Suínos , Proteínas não Estruturais Virais/genética , Virulência/genética
13.
Org Lett ; 2021 Jan 13.
Artigo em Inglês | MEDLINE | ID: mdl-33438394

RESUMO

A visible-light photoredox catalyzed radical cascade cyclization of simple ethers with cyanamides is developed at room temperature. This strategy involves sequential inert Csp3-H/Csp2-H functionalizations through intermolecular addition reaction of oxyalkyl radicals to N-cyano groups followed by radical cyclization of iminyl radicals in situ generated with C-2 aryl rings. This method allows for efficient synthesis of tetracyclic benzo[4,5]imidazo[1,2-c]quinazolines. Importantly, this is the first example of an intermolecular-intramolecular radical cascade cyclization reaction of cyanamides.

14.
Artigo em Inglês | MEDLINE | ID: mdl-33393190

RESUMO

Approaches to achieve stable perovskite nanocrystals (PNCs) of interest, in particular those with large structural anisotropy, through protective coating of the inorganic shell at a single-nanocrystal (NC) level are comparatively few and limited in scope. Reported here is a robust amphiphilic-diblock-copolymer-enabled strategy for crafting highly-stable anisotropic CsPbBr3 nanosheets (NSs) by in situ formation of a uniform inorganic shell (1st shielding) that is intimately ligated with hydrophobic polymers (2nd shielding). The dual-protected NSs display an array of remarkable stabilities (i.e., thermal, photostability, moisture, polar solvent, aliphatic amine, etc.) and find application in white-light-emitting diodes. In principle, by anchoring other multidentate amphiphilic polymer ligands on the surface of PNCs, followed by templated-growth of shell materials of interest, a rich variety of dual-shelled, multifunctional PNCs with markedly improved stabilities can be created for use in optics, optoelectronics, and sensory devices.

15.
J Hazard Mater ; 412: 125200, 2021 Jan 22.
Artigo em Inglês | MEDLINE | ID: mdl-33517061

RESUMO

The introduction of heavy metal-free biomass into the sewage sludge (SS) pyrolysis can effectively improve the biochar properties and reduce the bioavailability and toxicity of heavy metals (HMs) in blended biochar. Herein, this study aimed to understand the biochar properties and associated environmental risks of HMs, by comparing the residual contents from the co-pyrolysis of SS with various organic fractions of municipal solid waste (OFMSW) at 550 °C and pyrolysis alone at different temperatures between 350 and 750 °C. The results indicated that, compared with SS pyrolysis alone, co-pyrolysis of SS with various OFMSW (except PVC) lead to lower biochar yields but with higher pH values (increased between 21.80% and 31.70%) and carbon contents (raised between 33.45% and 48.22%) in blended biochars, and the chemical speciation analysis suggested that co-pyrolysis further promoted the HMs transformation into more stable forms which significantly reduce the associated environmental risk of HMs in the blended biochars (the values of RI lower than 55.80). The addition of PVC, however, impeded biochar properties and compromised HMs immobilization during SS pyrolysis.

16.
Adv Mater ; : e2006367, 2020 Dec 09.
Artigo em Inglês | MEDLINE | ID: mdl-33296108

RESUMO

Photothermal actuators have attracted increasing attention due to their ability to convert light energy into mechanical deformation and locomotion. This work reports a freestanding, multidirectional photothermal robot that can walk along a predesigned pathway by modulating laser polarization and on-off switching. Magnetic-plasmonic hybrid Fe3 O4 /Ag nanorods are synthesized using an unconventional templating approach. The coupled magnetic and plasmonic anisotropy allows control of the rod orientation, plasmonic excitation, and photothermal conversion by simply applying a magnetic field. Once the rods are fixed with desirable orientations in a bimorph actuator by magnetic-field-assisted lithography, the bending of the actuator can be controlled by switching the laser polarization. A bipedal robot is created by coupling the rod orientation with the alternating actuation of its two legs. Irradiating the robot by a laser with alternating or fixed polarization synergistically results in basic movement (backward and forward) and turning (including left-, right-, and U-turn), respectively. A complex walk along predesigned pathways can be potentially programmed by combining the movement and turning modes of the robots. This strategy provides an alternative driving mechanism for preparing functional soft robots, thus breaking through the limitations in the existing systems in terms of light sources and actuation manners.

17.
Circulation ; 2020 Dec 11.
Artigo em Inglês | MEDLINE | ID: mdl-33305586

RESUMO

Background: Immunoglobulin E (IgE) belongs to a class of immunoglobulins involved in immune response to specific allergens. However, the roles of IgE and IgE receptor (FcεR1) in pathological cardiac remodeling and heart failure (HF) are unknown. Methods: Serum IgE levels and cardiac IgE receptor (FcεR1) expression were assessed in diseased hearts from human and mouse. The role of FcεR1 signaling in pathological cardiac remodeling was explored in vivo by FcεR1 genetic depletion, anti-IgE antibodies, and bone-marrow (BM) transplantation. The roles of IgE-FcεR1 pathway were further evaluated in vitro in primary cultured rat cardiomyocytes (CMs) and cardiac fibroblasts (CFs). RNA-seq and bioinformatic analyses were used to identify biochemical changes and signaling pathways that are regulated by IgE/FcεR1. Results: Serum IgE levels were significantly elevated in patients with HF as well as in two mouse cardiac disease models induced by chronic pressure overload via transverse aortic contraction (TAC) and chronic angiotensin II (Ang II) infusion. Interestingly, FcεR1 expression levels were also significantly up-regulated in failing hearts from human and mouse. Blockade of the IgE-FcεR1 pathway by FcεR1 knockout alleviated TAC- or Ang II-induced pathological cardiac remodeling and/or dysfunction. Anti-IgE antibodies (including the clinical drug, omalizumab) also significantly alleviated Ang II-induced cardiac remodeling. BM transplantation experiments indicated that IgE-induced cardiac remodeling was mediated through non-BM-derived cells. FcεR1 was found to be expressed in both CMs and CFs. In cultured rat CMs, IgE-induced CM hypertrophy and hypertrophic marker expression were abolished by depleting FcεR1. In cultured rat CFs, IgE-induced CF activation and matrix protein production were also blocked by FcεR1 deficiency. RNA-seq and signaling pathway analyses revealed that transforming growth factor-ß (TGF-ß) may be a critical mediator and blocking TGF-ß indeed alleviated IgE-induced cardiomyocyte hypertrophy and cardiac fibroblast activation in vitro. Conclusions: Our findings suggest that IgE induction plays a causative role in pathological cardiac remodeling, at least partially via the activation of IgE-FcεR1 signaling in CMs and CFs. Therapeutic strategies targeting the IgE-FcεR1 axis may be effective for managing IgE-mediated cardiac remodeling.

19.
Eur Radiol ; 2020 Nov 27.
Artigo em Inglês | MEDLINE | ID: mdl-33247343

RESUMO

OBJECTIVE: To determine the value of a maximum-intensity projection (MIP) image derived from abbreviated breast MRI for excluding occult nipple-areolar complex (NAC) involvement in patients with breast cancer. METHODS: This prospective study included breast cancer patients with clinically normal NACs between April 2016 and May 2019. Abbreviated breast MRI was performed, and an MIP image was generated for each patient. MIP images were examined for the following features: asymmetric nipple enhancement, tumor-nipple distance (TND), tumor diameter, lesion type, location, and multifocality. Independent predictive MIP features for occult NAC involvement were identified by univariable and multivariable logistic regression analyses. Models based on independent predictive MIP features were developed, and their diagnostic performances were evaluated using ROC analysis. The utility of an MIP image for excluding occult NAC involvement was assessed by considering NPVs across patient subgroups. RESULTS: Eight hundred forty-three patients (67 NAC-positive and 776 NAC-negative) were enrolled. On MIP images, asymmetric nipple enhancement (odds ratio, 6.098; p < 0.001) and TND (odds ratio, 0.564; p = 0.003) were independent predictors of occult NAC involvement. A parallel test model of "asymmetric nipple enhancement or TND ≤ 15 mm" yielded the highest AUC value (0.838) among prediction models. The NPV of MIP images for excluding occult NAC involvement was 99.5%, which was applicable across various patient subgroups. CONCLUSIONS: A single MIP image derived from abbreviated breast MRI has utility for excluding occult NAC involvement in breast cancer patients and reducing the number of unnecessary sub-nipple biopsies in nipple-sparing mastectomy. KEY POINTS: • On MIP images derived from abbreviated breast MRI, asymmetric nipple enhancement and tumor-nipple distance were independent predictors for occult nipple involvement in patients with breast cancer. • Negative findings on MIP image can help select patients at minimal risk of occult nipple involvement, for whom unnecessary intraoperative sub-nipple biopsies in nipple-sparing mastectomy can be omitted.

20.
Nucleic Acids Res ; 2020 Nov 22.
Artigo em Inglês | MEDLINE | ID: mdl-33221906

RESUMO

Long non-coding RNAs (lncRNAs) play important functional roles in many diverse biological processes. However, not all expressed lncRNAs are functional. Thus, it is necessary to manually collect all experimentally validated functional lncRNAs (EVlncRNA) with their sequences, structures, and functions annotated in a central database. The first release of such a database (EVLncRNAs) was made using the literature prior to 1 May 2016. Since then (till 15 May 2020), 19 245 articles related to lncRNAs have been published. In EVLncRNAs 2.0, these articles were manually examined for a major expansion of the data collected. Specifically, the number of annotated EVlncRNAs, associated diseases, lncRNA-disease associations, and interaction records were increased by 260%, 320%, 484% and 537%, respectively. Moreover, the database has added several new categories: 8 lncRNA structures, 33 exosomal lncRNAs, 188 circular RNAs, and 1079 drug-resistant, chemoresistant, and stress-resistant lncRNAs. All records have checked against known retraction and fake articles. This release also comes with a highly interactive visual interaction network that facilitates users to track the underlying relations among lncRNAs, miRNAs, proteins, genes and other functional elements. Furthermore, it provides links to four new bioinformatics tools with improved data browsing and searching functionality. EVLncRNAs 2.0 is freely available at https://www.sdklab-biophysics-dzu.net/EVLncRNAs2/.

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