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1.
Parasit Vectors ; 14(1): 186, 2021 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-33794979

RESUMO

BACKGROUND: Microsporidia are obligate intracellular parasites that can infect nearly all invertebrates and vertebrates, posing a threat to public health and causing large economic losses to animal industries such as those of honeybees, silkworms and shrimp. However, the global epidemiology of these pathogens is far from illuminated. METHODS: Publications on microsporidian infections were obtained from PubMed, Science Direct and Web of Science and filtered according to the Newcastle-Ottawa Quality Assessment Scale. Infection data about pathogens, hosts, geography and sampling dates were manually retrieved from the publications and screened for high quality. Prevalence rates and risk factors for different pathogens and hosts were analyzed by conducting a meta-analysis. The geographic distribution and seasonal prevalence of microsporidian infections were drawn and summarized according to sampling locations and date, respectively. RESULTS: Altogether, 287 out of 4129 publications up to 31 January 2020 were obtained and met the requirements, from which 385 epidemiological data records were retrieved and effective. The overall prevalence rates in humans, pigs, dogs, cats, cattle, sheep, nonhuman primates and fowl were 10.2% [2429/30,354; 95% confidence interval (CI) 9.2-11.2%], 39.3% (2709/5105; 95% CI 28.5-50.1%), 8.8% (228/2890; 95% CI 5.1-10.1%), 8.1% (112/1226; 95% CI 5.5-10.8%), 16.6% (2216/12,175; 95% CI 13.5-19.8%), 24.9% (1142/5967; 95% CI 18.6-31.1%), 18.5% (1388/7009; 95% CI 13.1-23.8%) and 7.8% (725/9243; 95% CI 6.4-9.2%), respectively. The higher prevalence in pigs suggests that routine detection of microsporidia in animals should be given more attention, considering their potential roles in zoonotic disease. The highest rate was detected in water, 58.5% (869/1351; 95% CI 41.6-75.5%), indicating that water is an important source of infections. Univariate regression analysis showed that CD4+ T cell counts and the living environment are significant risk factors for humans and nonhuman primates, respectively. Geographically, microsporidia have been widely found in 92 countries, among which Northern Europe and South Africa have the highest prevalence. In terms of seasonality, the most prevalent taxa, Enterocytozoon bieneusi and Encephalitozoon, display different prevalence trends, but no significant difference between seasons was observed. In addition to having a high prevalence, microsporidia are extremely divergent because 728 genotypes have been identified in 7 species. Although less investigated, microsporidia coinfections are more common with human immunodeficiency virus and Cryptosporidium than with other pathogens. CONCLUSIONS: This study provides the largest-scale meta-analysis to date on microsporidia prevalence in mammals, birds and water worldwide. The results suggest that microsporidia are highly divergent, widespread and prevalent in some animals and water and should be further investigated to better understand their epidemic features.

2.
Adipocyte ; 10(1): 174-188, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33825675

RESUMO

High viability and further adipogenic differentiation of adipose-derived stem cells (ADSCs) are fundamental for engraftment and growth of the transplanted adipose tissue. It has been demonstrated that extracellular matrix (ECM) regulates cell proliferation and differentiation by interacting with ERK1/2 signalling pathway. In this study, we prepared autologous decellularized extracellular matrix (d-ECM) and explored its effect on the proliferation and adipogenic ability of ADSCs in low serum culture. We found that 2% foetal bovine serum (FBS) in growth medium inhibited cell viability and DNA replication, and decreased mRNA and protein levels of PPARγ and C/EPBα compared with 10% FBS. Correspondingly, after 14-days adipogenic induction, cells cultured in 2% FBS possessed lower efficiency of adipogenesis and expressed less adipocyte differentiation markers ADIPOQ and aP2. On the contrary, the d-ECM-coated substrate continuously promoted the expression of PPARγ, and regulated the phosphorylation of ERK1/2 in different manners during differentiation. Pretreatment with ERK1/2 inhibitor PD98059 neutralized the effects of d-ECM, which suggested d-ECM might regulate the adipogenesis of ADSCs through ERK1/2-PPARγ pathway. In addition, d-ECM was revealed to regulate the transcription and expression of stemness-associated genes, such as OCT4, NANOG and SOX2, in the undifferentiated ADSCs, which might be related to the initiation of differentiation.

3.
Phys Med Biol ; 2021 Apr 06.
Artigo em Inglês | MEDLINE | ID: mdl-33823496

RESUMO

PURPOSE: This study aims to investigate the feasibility of different acquisition methods for time-resolved magnetic resonance fingerprinting (TR-MRF) in computer simulation. METHODS: Extended cardiac-torso (XCAT) phantom is used to generate abdominal T1, T2, and proton density (PD) maps for MRF simulation. The simulated MRF technique consists of an IR-FISP MRF sequence with spiral trajectory acquisition. MRF maps were simulated with different number of repetitions from 1 to 15. Three different methods were used to generate TR-MRF maps: 1) continuous acquisition without delay between MRF repetitions; 2) continuous acquisition with 5 seconds delay between MRF repetitions; 3) triggered acquisition with variable delay between MRF repetitions to allow the next acquisition to start at different respiration phase. After the generation of TR-MRF maps, the image quality indexes including absolute T1 and T2 value, signal-to-noise-ratio (SNR), tumor-to-liver contrast-to-noise ratio (CNR), error in the amplitude of diaphragm motion and tumor volume error were used to evaluate the reconstructed parameter maps. Three volunteers were recruited to test the feasibility of the selected acquisition method. RESULTS: Dynamic MR parametric maps using three different acquisition methods were estimated. The overall and liver T1 value error, liver SNR in T1 and T2 maps, and tumor SNR from T1 maps from triggered method is statistically significantly better than the other two methods (p-value < 0.05). The other image quality indexes have no significant difference between the triggered method and the other two continuous acquisition methods. All image quality indexes exhibit no significant difference between the acquisition methods with 0 second and 5 seconds delay. The triggered method was successfully performed in three healthy volunteers. CONCLUSION: TR-MRF technique was investigated using three different acquisition methods in computer simulation where the triggered method showed better performance than the other two methods. The triggered method has been tested successfully in healthy volunteers.

4.
Artigo em Inglês | MEDLINE | ID: mdl-33768336

RESUMO

Orthogonal experiments were used to simulate the enrofloxacin (ENR) elimination dynamic in deeper water of aquaculture. Two factors at values common in fishery water (temperature of 20°C, 25°C, and 30°C; pH of 5, 7, and 9) were studied. The degradation of ENR in the nine treatment groups ranged from 44.7 to 80.1%. Variance analysis indicated that pH had a strong impact on the elimination of ENR, while temperature changes showed little effect. The ENR removal rate was highest at a combination of 25°C and pH 5. The optimal conditions of eliminating ENR were performed for exploring the generation of ciprofloxacin (CIP), which indicated that higher ENR concentrations led to the production of greater amounts of CIP. The half-time of ENR was increased 2.02-times in the ENR concentrations increasing from 20 to 2000 ng/mL. This study could increase our understanding of the behaviors of ENR and CIP during the aquaculture process.

5.
Basic Res Cardiol ; 116(1): 17, 2021 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-33721106

RESUMO

The monocyte ß2-integrin Mac-1 is crucial for leukocyte-endothelium interaction, rendering it an attractive therapeutic target for acute and chronic inflammation. Using phage display, a Designed-Ankyrin-Repeat-Protein (DARPin) was selected as a novel binding protein targeting and blocking the αM I-domain, an activation-specific epitope of Mac-1. This DARPin, named F7, specifically binds to activated Mac-1 on mouse and human monocytes as determined by flow cytometry. Homology modelling and docking studies defined distinct interaction sites which were verified by mutagenesis. Intravital microscopy showed reduced leukocyte-endothelium adhesion in mice treated with this DARPin. Using mouse models of sepsis, myocarditis and ischaemia/reperfusion injury, we demonstrate therapeutic anti-inflammatory effects. Finally, the activated Mac-1-specific DARPin is established as a tool to detect monocyte activation in patients receiving extra-corporeal membrane oxygenation, as well as suffering from sepsis and ST-elevation myocardial infarction. The activated Mac-1-specific DARPin F7 binds preferentially to activated monocytes, detects inflammation in critically ill patients, and inhibits monocyte and neutrophil function as an efficient new anti-inflammatory agent.

6.
Zhongguo Gu Shang ; 34(3): 220-5, 2021 Mar 25.
Artigo em Chinês | MEDLINE | ID: mdl-33787164

RESUMO

OBJECTIVE: To measure the maximum corridor parameters of the infra acetabular screw and evaluate the feasibility of screw insertion through digital analysis of the acetabular structure. METHODS: The pelvic CT data of 100 patients who received plain pelvic CT scan from April 2013 to June 2015 were retrospectively analyzed. There were 50 males, aged 20 to 84 years, with an average age of (48.42±17.48) years, and 50 females, aged 18 to 87 years, with an average age of (55.02±19.54) years. Patients with acetabular fractures, hip dysplasia, and metal implants in the acetabulum were excluded. Import CT data into Mimics software in DICOM format to generate a three-dimensional model, and find the axialprojection of the infra-acetabular corridor in the middle of the pubis ramus in the inlet view. A virtual screw was placed in the infra-acetabular space and measure the parameters including the diameter and the length of the maximum corridor, the distance from the insertion point to the pubic symphysis, to the anterosuperior iliac spine and to the medial edge of the pelvis. Then import the pelvic model into 3- matic software, establish the pelvic model anterior pelvic plane and median sagittal plane, and measure the angle between the screw axis and the two planes. A minimum corridor diameter of at least 5 mm was defined as a cutoff for placing a 3.5 mm screw, and calculate the screw insertion rate. RESULTS: In 100 cases, 49% of patients had a infra acetabular corridor with a diameter ≥5 mm, and the rate of screw placement in men was significantly higher than that in women. The average diameter of the maximum corridor of infra-acetabular screw was (4.86±1.72) mm, the average length was (94.04±8.29) mm, the average distance from the insertion point to the pubic symphysis was (60.92±4.84) mm, to the anterosuperior iliac spine was (85.15± 6.85) mm, and to the medial edge of the pelvis was (6.12±3.32) mm. The mean angle between the axis of the screw and the median sagittal plane was (-1.38±4.74)°, and the mean angle between the axis of the screw and the anterior pelvic plane was (56.77±7.93)°. There are significant differences between male and female measured parameters, except for the angle between the screw axis and the anterior pelvic plane. There was no statistically significant difference in the maximum corridor parameters of infra-acetabular screw on both sides of the pelvis. CONCLUSION: This study shows that the insertion rate of infra-acetabular screws is low in local patients, and the feasibility of screw insertion should be fully evaluated before surgery.


Assuntos
Acetábulo , Parafusos Ósseos , Acetábulo/diagnóstico por imagem , Acetábulo/cirurgia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Viabilidade , Feminino , Fixação Interna de Fraturas , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Adulto Jovem
7.
FASEB J ; 35(5): e21445, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33774866

RESUMO

Mitochondrial Tu translation elongation factor (TUFM or EF-Tu) is part of the mitochondrial translation machinery. It is reported that TUFM expression is reduced in the brain of Alzheimer's disease (AD), suggesting that TUFM might play a role in the pathophysiology. In this study, we found that TUFM protein level was decreased in the hippocampus and cortex especially in the aged APP/PS1 mice, an animal model of AD. In HEK cells that stably express full-length human amyloid-ß precursor protein (HEK-APP), TUFM knockdown or overexpression increased or reduced the protein levels of ß-amyloid protein (Aß) and ß-amyloid converting enzyme 1 (BACE1), respectively. TUFM-mediated reduction of BACE1 was attenuated by translation inhibitor cycloheximide (CHX) or α-[2-[4-(3,4-Dichlorophenyl)-2-thiazolyl]hydrazinylidene]-2-nitro-benzenepropanoic acid (4EGI1), and in cells overexpressing BACE1 constructs deleting the 5' untranslated region (5'UTR). TUFM silencing increased the half-life of BACE1 mRNA, suggesting that RNA stability was affected by TUFM. In support, transcription inhibitor Actinomycin D (ActD) and silencing of nuclear factor κB (NFκB) failed to abolish TUFM-mediated regulation of BACE1 protein and mRNA. We further found that the mitochondria-targeted antioxidant TEMPO diminished the effects of TUFM on BACE1, suggesting that reactive oxygen species (ROS) played an important role. Indeed, cellular ROS levels were affected by TUFM knockdown or overexpression, and TUFM-mediated regulation of apoptosis and Tau phosphorylation at selective sites was attenuated by TEMPO. Collectively, TUFM protein levels were decreased in APP/PS1 mice. TUFM is involved in AD pathology by regulating BACE1 translation, apoptosis, and Tau phosphorylation, in which ROS plays an important role.

8.
Bioorg Med Chem Lett ; : 127994, 2021 Mar 25.
Artigo em Inglês | MEDLINE | ID: mdl-33775837

RESUMO

Liver fibrosis is a final result of extensive deposition of extracellular matrix (ECM) and starts with the activation and proliferation of hepatic stellate cells (HSCs). Our previous study showed that eudesmane sesquiterpenoid santamarin had cytotoxicity against hepatic stellate cell line LX2 (HSC-LX2) with IC50 values of 16.5 ± 0.7 µM. To explore the structure-activity relationships, twenty-six derivatives were synthesized by modifying the hydroxyl group, double-bond and unsaturated lactone. Cytotoxicity evaluation suggested that eight derivatives (6, 9, 13, 17, 20 and 25-27) increased activity against HSC-LX2. Especially, derivatives 17, 20 and 25 displayed obvious cytotoxicity with IC50 values of 6.4 ± 0.4, 4.6 ± 0.1, and 3.5 ± 0.1 µM, which were 3 to 5-fold higher than santamarin. Preliminary mechanisms study revealed that the active compound 20 exhibited more than 8-fold and 6-fold enhancement of inhibitory effect on the deposition of human hyaluronic acid (HA) and human laminin (HL) with IC50 values of 7.6 ± 0.6 and 3.3 ± 1.2 µM.

9.
Ecology ; : e03348, 2021 Mar 23.
Artigo em Inglês | MEDLINE | ID: mdl-33755986

RESUMO

Natural abundance of carbon (C) and nitrogen (N) stable isotope ratios (δ13 C and δ15 N) has been used to indicate ecosystem C and N status and cycling; however, use of this approach to infer plant and microbial N preference under projected ecosystem N enrichment is limited. Here, we investigated natural abundance δ13 C and δ15 N of five dominant plant species, and soil δ15 N of microbial biomass and available N forms under N addition in a meadow steppe. Additional N, applied as urea, led to decreases in δ15 N of soil NO3 - (δ15 Nnitrate , from 3.0 to 0.4‰) and increases in δ15 N of soil NH4 + (δ15 Nammonium , from -1.3 to 11‰) and dissolved organic N (δ15 NDON , from 8.5 to 15‰) that reflected increased net nitrification rates, a possible increase in NH3 volatilization, and greater availability of the three N forms. An overall increase in δ15 N of soil total N (δ15 NTN ) from 7.1 to 7.9‰ indicated accelerated and greater openness of soil N cycling that was also partially revealed by enhanced net N mineralization rates. Plant δ15 N, which ranged from -1.8 to 2.1‰, generally decreased with N addition, indicating a greater reliance on soil NO3 - under N-enrichment conditions. Nitrogen addition decreased δ15 N of microbial biomass N (from 14 to 2.8‰), possibly due to a shift in preferential N form (DON to NO3 - ), that indicated a convergence of plant and microbial preferential N forms and an increase in plant-microbial N competition. Microbes were thus more flexible than plants in the use of different forms of N. Addition of N decreased plant litter δ13 C, while plant species δ13 C remained unaffected, likely due to a shift in the abundance of dominant species with a greater proportion of biomass coming from δ13 C-depleted species. Enrichment factor (the difference in plant δ15 N relative to δ15 NTN ) of four non-legume species was negatively related to soil inorganic N availability, net nitrification rate, and net N mineralization rate, and was proven to be a good indicator of ecosystem N status. Our study highlights the importance of natural abundance of 15 N as an indicator of plant-microbial N competition and ecosystem N cycling in meadow steppe grasslands under projected ecosystem N enrichment.

10.
Med Sci Monit ; 27: e929152, 2021 Mar 19.
Artigo em Inglês | MEDLINE | ID: mdl-33737504

RESUMO

BACKGROUND Lacrimal gland pleomorphic adenoma (LGPA) is the most common clinically benign epithelial tumor of the lacrimal gland and is predominantly comprised of epithelial cells and interstitial components. At present, the exact pathogenesis of LGPA remains unclear. Previous research has indicated that the occurrence of LGPA may be related to excessive cell proliferation. MATERIAL AND METHODS This study observed the clinicopathological characteristics of LGPA and investigated the tumorigenesis mechanism of cell over-proliferation caused by the imbalance between apoptosis and proliferation. A total of 27 cases were collected from the Department of Ophthalmology of the Affiliated Hospital of Chengde Medical University and the Third Medical Center of Chinese PLA General Hospital from April 2017 to November 2019. Hematoxylin-eosin (HE) staining and immunohistochemical staining were used to observe the pathological characteristics and analyze the expression of bcl-2 and bax in the lacrimal gland. RESULTS Compared with normal lacrimal gland tissues, LGPA tumor tissues had obvious changes in pathological morphology. The expression of bcl-2 in LGPA lesion tissues was dramatically higher (P<0.001), the expression of bax was not significantly different between groups (P=0.25), but the ratio of bcl-2/bax was significantly higher in tumor tissues (P=0.01). CONCLUSIONS We found that the lacrimal gland tumor tissues had obvious excessive proliferation in pathomorphology, which revealed the necessity of complete surgical removal of the capsule from the perspective of pathological morphology and provided a theoretical basis for the hypothesis that the imbalance between apoptosis and proliferation could lead to cell hyperproliferation.

11.
Technol Cancer Res Treat ; 20: 15330338211004942, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33759637

RESUMO

Recently, immunotherapy has become the fourth pillar of cancer treatment in addition to surgery therapy, chemotherapy, and radiation therapy. The inhibitors of programed cell death protein 1 (PD-1) and its ligand PD-L1 are the new stars in immunotherapy, as they can overcome tumor immunosuppression. However, the efficacy of PD-1 inhibitors still needs to be further developed for clinical treatment. Therefore, research into treatment with anti-PD-1 drugs has emerged as a new development field. This review provides novel insights into the role and mechanism of PD-1 combination anti-tumor therapy, thereby promoting its clinical application in anti-tumor immunotherapy.

12.
Artigo em Inglês | MEDLINE | ID: mdl-33787525

RESUMO

BACKGROUND: Teleradiology has become one of the most important approaches to virtual clinical diagnosis; its importance has only grown during the coronavirus 2019 pandemic. In developing countries, asking patients to take photographs of their images using a smartphone can facilitate the process and help keep its costs down. However, the images taken by patients with smartphones often are of poor quality, and there is no regulation or standard instruction about how to use smartphones to take photographs of medical examination images effectively. These problems limit the use of smartphones in remote diagnosis and treatment. QUESTIONS/PURPOSES: To formulate a set of guidelines for the most appropriate and effective use of smartphones to capture images (radiographs, CT images, and MR images), and to determine whether these guidelines are more effectively adopted by patients of differing ages and genders. METHODS: In this prospective study, a set of step-by-step instructions was created with the goal of helping patients take better smartphone photographs of orthopaedic diagnostic images for transfer to telemedicine services. Following the advice of surgeons, experts in smartphone technology, imaging experts, and suggestions from patients, the instructions were modified based on clinical experience and finalized with the goals of simplicity, clarity, and convenience. Potentially eligible patients were older than 18 years, had no cognitive impairment, and used smart phones. Based on that, 256 participants (patients or their relatives and friends) who visited the orthopaedic department of our hospital from June to October 2020 potentially qualified for this study. A total of 11% (29) declined to participate, leaving 89% (227) for analysis here. Their mean age was 36 ± 11 years, 50% were women (113 of 227), and the patient himself/herself represented in 34% (78 of 227) of participants while relatives or friends of patients made up 66% (149 of 227) of the group. In this study, the diagnoses included spinal stenosis (47% [107 of 227]), disc herniation without spinal stenosis (31% [71 of 227]), vertebral fractures (14% [32 of 227]), and other (7% [17 of 227]). Each study participant first took photographs of their original medical images based on their own knowledge of how to use the smartphone camera function; each participant then took pictures of their original images again after receiving our instructional guidance. Three senior spine surgeons (YZ, TQL, TCM) in our hospital analyzed, in a blinded manner, the instructed and uninstructed imaging files based on image clarity (the content of the image is complete, the text information in the image is clearly visible, there is neither reflection nor shadow in the image) and image position (it is not tilted, curled, inverted, or reversed). If either of these conditions was not satisfied, the picture quality was deemed unacceptable; two of three judges' votes determined the outcome. Interobserver reliability with kappa values for the three judges were 0.89 (YZ versus TQL), 0.92 (YZ versus TCM), and 0.90 (TQL versus TCM). RESULTS: In this study, the overall proportion of smartphone medical images deemed satisfactory increased from 40% (91 of 227) for uninstructed participants to 86% (196 of 227) for instructed participants (risk ratio 2.15 [95% CI 1.82 to 2.55]; p<0.001). The proportion of acceptable-quality images in different age groups improved after instruction, except for in patients aged 51 years or older (3 of 17 uninstructed participants versus 8 of 17 instructed participants; RR 2.67 [95% CI 0.85 to 8.37]; p = 0.07). The proportion of acceptable-quality images in both genders improved after instruction, but there was no difference between the genders. CONCLUSION: We believe our guidelines for patients who wish to take smartphone photographs of their medical images will decrease image transmission cost and facilitate orthopaedic telemedicine consultations. However, it appears that patients older than 50 years are more likely to have difficulty with this approach, and if so, they may benefit from more hands-on assistance from clinic staff or younger relatives or friends. The degree to which our findings are culture-specific should be verified by other studies in other settings, but on the face of it, there is little reason to believe our findings would not generalize to a reasonable degree. Other studies in more heterogeneous populations should also evaluate factors related to levels of educational attainment and wealth differences, but in the meantime, our findings can give clinical teams an idea of which patients may need a little extra assistance. LEVEL OF EVIDENCE: Level II, therapeutic study.

13.
Nat Microbiol ; 2021 Mar 18.
Artigo em Inglês | MEDLINE | ID: mdl-33737748

RESUMO

Many enveloped animal viruses produce a variety of particle shapes, ranging from small spherical to long filamentous types. Characterization of how the shape of the virion affects infectivity has been difficult because the shape is only partially genetically encoded, and most pleomorphic virus structures have no selective advantage in vitro. Here, we apply virus fractionation using low-force sedimentation, as well as antibody neutralization coupled with RNAScope, single-particle membrane fusion experiments and stochastic simulations to evaluate the effects of differently shaped influenza A viruses and influenza viruses pseudotyped with Ebola glycoprotein on the infection of cells. Our results reveal that the shape of the virus particles determines the probability of both virus attachment and membrane fusion when viral glycoprotein activity is compromised. The larger contact interface between a cell and a larger particle offers a greater probability that several active glycoproteins are adjacent to each other and can cooperate to induce membrane merger. Particles with a length of tens of micrometres can fuse even when 95% of the glycoproteins are inactivated. We hypothesize that non-genetically encoded variable particle shapes enable pleomorphic viruses to overcome selective pressure and may enable adaptation to infection of cells by emerging viruses such as Ebola. Our results suggest that therapeutics targeting filamentous virus particles could overcome antiviral drug resistance and immune evasion in pleomorphic viruses.

14.
Artigo em Inglês | MEDLINE | ID: mdl-33689853

RESUMO

PURPOSE: To develop a deep learning-based computed tomography (CT) perfusion mapping (DL-CTPM) method that synthesizes lung perfusion images from CT images. METHODS AND MATERIALS: This paper presents a retrospective analysis of the pulmonary technetium-99m-labeled macro-aggregated albumin (MAA) single-photon emission computed tomography (SPECT)/CT scans obtained from 73 patients at xx Hospital in Hong Kong in 2019. The left and right lung scans were separated to double the size of the dataset to 146. A three-dimensional attention residual neural network (ARNN) was constructed to extract textural features from the CT images and reconstruct corresponding functional images. Eighty-four samples were randomly selected for training and cross-validation, and the remaining 62 were used for model testing in terms of voxel-wise agreement and function-wise concordance. To assess the voxel-wise agreement, the Spearman's correlation coefficient (R) and structural similarity index measure (SSIM) between the images predicted by the DL-CTPM and the corresponding SPECT perfusion images were computed to assess the statistical and perceptual image similarities, respectively. To assess the function-wise concordance, the Dice similarity coefficient (DSC) was computed to determine the similarity of the low/high functional lung volumes. RESULTS: The evaluation of the voxel-wise agreement showed a moderate-to-high voxel value correlation (0.6733 ± 0.1728) and high structural similarity (0.7635 ± 0.0697) between the SPECT and DL-CTPM predicted perfusions. The evaluation of the function-wise concordance obtained an average DSC value of 0.8183 ± 0.0752 for high-functional lungs, ranging from 0.5819 to 0.9255, and 0.6501 ± 0.1061 for low-functional lungs, ranging from 0.2405 to 0.8212. Ninety-four percent of the test cases demonstrated high concordance (DSC > 0.7) between the high functional volumes contoured from the predicted and ground-truth perfusions. CONCLUSIONS: We developed a novel DL-CTPM method for estimating perfusion-based lung functional images from the CT domain using a 3D ARNN, which yielded moderate-to-high voxel-wise approximations of lung perfusion. To further contextualize these results toward future clinical application, a multi-institutional large-cohort study is warranted.

15.
Biol Reprod ; 2021 Mar 11.
Artigo em Inglês | MEDLINE | ID: mdl-33709118

RESUMO

Zona pellucida (ZP), which is composed of at most four extracellular glycoproteins (ZP1, ZP2, ZP3, and ZP4) in mammals, shelters the oocytes and is vital in female fertility. Several studies have identified the indispensable roles of ZP1-3 in maintaining normal female fertility. However, the understanding of ZP4 is still very poor because only one study on ZP4-associated infertility performed in rabbits has been reported up to date. Here we investigated the function of mammalian Zp4 by creating a knockout (KO) rat strain (Zp4-/- rat) using CRISPR-Cas9 mediated DNA-editing method. The influence of Zp4 KO on ZP morphology and some pivotal processes of reproduction, including oogenesis, ovulation, fertilization and pup production, was studied using periodic acid-Schiff's staining, superovulation, in vitro fertilization, and natural mating. The ZP morphology in Zp4-/- rats was normal and none of these pivotal processes was affected. This study renewed the knowledge of mammalian Zp4 by suggesting that Zp4 was completely dispensable for female fertility.

16.
Ital J Pediatr ; 47(1): 49, 2021 Mar 04.
Artigo em Inglês | MEDLINE | ID: mdl-33663540

RESUMO

BACKGROUND: Phelan-McDermid syndrome (PMS), also known as 22q13.3 deletion syndrome, is a rare neurodevelopmental syndrome resulting from a deletion of the distal long arm of chromosome 22. CASE PRESENTATION: We report a case of a 21 months old Chinese girl presenting with global developmental delay, regression of language skills, unable to understand a few words or walk independently, insomnia, and autism-like behaviors. Copy number variation (CNV) analysis showed a heterozygous loss of SHANK3 gene in the 22q13 region, consistent with a diagnosis of PMS. After treatment with recombinant human growth hormone (rhGH), this patient had an improvement in motor skills and social behaviors. No side effects from rhGH therapy were reported. CONCLUSIONS: This is the first report of using rhGH to treat a Chinese girl diagnosed with PMS. We speculate rhGH could be a reasonable alternative choice for PMS treatment with similar clinical outcomes in comparison to insulin-like growth factor-1(IGF-1). However, further clinical trials are needed to confirm this hypothesis.

18.
J Gastroenterol ; 56(4): 395-405, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33742253

RESUMO

BACKGROUND: Pancreatic neuroendocrine tumors (PanNETs) are indolent pancreatic tumors derived from neuroendocrine cells in pancreatic islets. To date, reliable predictors for identifying patients at high risk for recurrence after curative cancer resection are lacking. We aimed to determine independent predictors for high-risk PanNETs and patient outcomes after surgery. METHODS: We analyzed relevant clinicopathological parameters in 319 consecutive patients of derivation cohort 1 and 106 patients of validation cohort 2 who underwent pancreatectomy and were diagnosed with PanNETs. Association of tumor characteristics with recurrence-free survival (RFS) and overall survival (OS) was evaluated using Cox regression. RESULTS: PanNET grade 3 (G3), pancreatic duct dilatation, and perineural invasion were independent prognostic factors for RFS and were significantly associated with early recurrence (within 1.5 years) of PanNETs after curative resection (P = 0.019, P < 0.001, and P < 0.001, respectively). Using these factors, we established a novel risk factor panel (R-panel), which predicted early recurrence (P < 0.001, HR = 15.02, 95% CI 5.76-39.19). Predictive accuracy of this R-panel was favorable, with a C-index of 0.853, higher than AJCC TNM staging (0.713). We further built an integrated staging system combining R-panel scoring and TNM staging, which improved predictive probability of TNM staging. Finally, we showed that adjuvant therapy with long-acting somatostatin analogs (SSAs) significantly reduced postoperative recurrence (P < 0.001) and prolonged long-term survival (P = 0.021) in patients with the above risk factors. CONCLUSION: We identified a novel risk factor panel, which includes PanNET G3, pancreatic duct dilatation, and perineural invasion; this panel predicted early recurrence of PanNETs after curative resection. Patients with these risk factors can benefit from adjuvant therapy with SSAs.

19.
Mol Biol Evol ; 2021 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-33674876

RESUMO

SARS-CoV-2 infects humans through the binding of viral S-protein (spike protein) to human ACE2 (angiotensin I converting enzyme 2). The structure of the ACE2-S-protein complex has been deciphered and we focused on the 27 ACE2 residues that bind to S-protein. From human sequence databases, we identified 9 ACE2 variants at ACE2-S-protein binding sites. We used both experimental assays and protein structure analysis to evaluate the effect of each variant on the binding affinity of ACE2 to S-protein. We found one variant causing complete binding disruption, two and three variants, respectively, strongly and mildly reducing the binding affinity, and two variants strongly enhancing the binding affinity. We then collected the ACE2 gene sequences from 57 non-human primates. Among the six apes and 20 Old World monkeys (OWMs) studied we found no new variants. In contrast, all 11 New World monkeys (NWMs) studied share four variants each causing a strong reduction in binding affinity, the Philippine tarsier also possesses three such variants, and 18 of the 19 prosimian species studied share one variant causing a strong reduction in binding affinity. Moreover, one OWM and three prosimian variants increased binding affinity by > 50%. Based on these findings we proposed that the common ancestor of primates was strongly resistant to and that of NWMs was completely resistant to SARS-CoV-2 and so is the Philippine tarsier, whereas apes and OWMs, like most humans, are susceptible. This study increases our understanding of the differences in susceptibility to SARS-CoV-2 infection among primates.

20.
PLoS Pathog ; 17(3): e1008866, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33720996

RESUMO

As an intracellular pathogen, the reproduction of the hepatitis B virus (HBV) depends on the occupancy of host metabolism machinery. Here we test a hypothesis if HBV may govern intracellular biosynthesis to achieve a productive reproduction. To test this hypothesis, we set up an affinity purification screen for host factors that interact with large viral surface antigens (LHBS). This identified pyruvate kinase isoform M2 (PKM2), a key regulator of glucose metabolism, as a binding partner of viral surface antigens. We showed that the expression of viral LHBS affected oligomerization of PKM2 in hepatocytes, thereby increasing glucose consumption and lactate production, a phenomenon known as aerobic glycolysis. Reduction of PKM2 activity was also validated in several different models, including HBV-infected HepG2-NTCP-C4 cells, adenovirus mediated HBV gene transduction and transfection with a plasmid containing complete HBV genome on HuH-7 cells. We found the recovery of PKM2 activity in hepatocytes by chemical activators, TEPP-46 or DASA-58, reduced expressions of viral surface and core antigens. In addition, reduction of glycolysis by culturing in low-glucose condition or treatment with 2-deoxyglucose also decreased expressions of viral surface antigen, without affecting general host proteins. Finally, TEPP-46 largely suppressed proliferation of LHBS-positive cells on 3-dimensional agarose plates, but showed no effect on the traditional 2-dimensional cell culture. Taken together, these results indicate that HBV-induced metabolic switch may support its own translation in hepatocytes. In addition, aerobic glycolysis is likely essential for LHBS-mediated oncogenesis. Accordingly, restriction of glucose metabolism may be considered as a novel strategy to restrain viral protein synthesis and subsequent oncogenesis during chronic HBV infection.

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