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1.
J Diabetes Investig ; 2020 Oct 16.
Artigo em Inglês | MEDLINE | ID: mdl-33064926

RESUMO

AIM: Psychological therapies showed benefits on both glycemic control and psychological outcomes in people with diabetes. However, the effects of mindfulness-based intervention (MBI) on glycemic control and psychological outcomes are inconsistent across studies and the evidence for MBI has not been summarized. We aim to identify the effects of MBI on glycemic control and psychological outcomes in people with diabetes by conducting a systematic review and meta-analysis. METHODS: Six databases (Pubmed, Embase, CINAHL, Cochrane, Web of science, and PsycINFO) were searched from inception to October 2019. Randomized controlled trials of MBI for people with type 1 and type 2 diabetes were included. Two authors independently extracted relevant data and assessed risk of bias, with a third reviewer as arbitrator. Sub-group analyses and sensitivity analyses were also performed. RESULTS: Eight studies with 841 participants met eligibility criteria. Meta-analysis demonstrated that MBI can slightly improve glycosylated hemoglobin (HbA1c) (-0.25%, 95% CI -0.43 to -0.07) and diabetes-related distress (MD -5.81; 95% CI -10.10 to -1.52), contribute to moderate effect size in reducing depression (SMD -0.56; 95% CI -0.82 to -0.30) and stress (SMD -0.53; CI -0.75 to -0.31). Subgroup analyses demonstrated greater HbA1c reductions in subgroups with baseline HbA1c level < 8% and follow-up duration > 6 months. Mixed effects were observed for anxiety. CONCLUSIONS: MBI appears to have benefits on HbA1c, depression, stress, and diabetes-related distress in people with diabetes. More rigorous studies with longer follow-up duration are warranted to establish the full potential of MBI.

2.
Phys Med Biol ; 2020 Oct 21.
Artigo em Inglês | MEDLINE | ID: mdl-33086205

RESUMO

Deep learning (DL) based auto-segmentation has the potential for accurate organ delineation in radiotherapy applications but requires large amounts of clean labeled data to train a robust model. However, annotating medical images is extremely time-consuming and requires clinical expertise, especially for segmentation that demands voxel-wise labels. On the other hand, medical images without annotations are abundant and highly accessible. To alleviate the influence of the limited number of clean labels, we propose a weakly-supervised DL training approach using deformable image registration (DIR)-based annotations, leveraging the abundance of unlabeled data. We generate pseudo-contours by utilizing DIR to propagate atlas contours onto abundant unlabeled images and train a robust DL-based segmentation model. With 10 labeled TCIA dataset and 50 unlabeled CT scans from our institution, our model achieved Dice similarity coefficient of 87.9%, 73.4%, 73.4%, 63.2% and 61.0% on mandible, left & right parotid glands and left & right submandibular glands of TCIA test set and competitive performance on our institutional clinical dataset and a third party (PDDCA) dataset. Experimental results demonstrated the proposed method outperformed traditional multi-atlas DIR methods and fully-supervised limited data training and is promising for DL-based medical image segmentation application with limited annotated data.

3.
Fitoterapia ; 147: 104756, 2020 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-33069836

RESUMO

Male infertility has affected many families around the world. However, due to the mechanism underlying male reproductive system dysfunction are not completely elucidated, the use of drugs for male reproductive system dysfunction treatment only insignificant higher pregnancy outcomes, low-quality evidence suggests that clinical pregnancy rates may increase. Therefore, the focus in the future will be on developing more viable treatment options to prevent or treatment of male reproductive system dysfunction and achieve the purpose of improving fertility. Interestingly, natural products, as the potential inhibitors for the treatment of male reproductive system dysfunction, have shown a good therapeutic effect. Among many natural products, flavonoids have been extensively investigated for the treatment of male reproductive system dysfunction, such as testicular structural disruption, spermatogenesis disturbance and sperm quality decline. Flavonoids have been reported to have antioxidant, anti-inflammatory, immune stimulating, anti-apoptotic, anticarcinogenic, anti-allergic and antiviral activities, investigating for the treatment of male reproductive system dysfunction. In this review, we evaluate the therapeutic effects of flavonoids on male reproductive system dysfunction under different cellular scenarios and summarize the therapeutic strategies of flavonoids based on the aforementioned retrospective analysis. In the end, we describe some perspective research areas relevant to the application of flavonoids in the treatment of male reproductive system dysfunction.

4.
Mol Cancer Res ; 2020 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-33004623

RESUMO

Reactivated telomerase is a crucial event in the development and progression of a variety of tumors. However, how telomerase is activated in gastric carcinogenesis has not been fully uncovered yet. Here, we identified a key role of NF-κB/Lin28A/let-7a axis to promote human telomerase reverse transcriptase (hTERT) expression for gastric cancer initiation. Mechanistically, Lin28A expression was upregulated by H. pylori induced NF-κB activation. And Lin28A in turn suppressed Let-7a expression, forming the NF-κB/Lin28A/let-7a axis to regulate gene expression upon H. pylori infection. Of note, we first discovered hTERT as a direct target of let-7a which inhibited hTERT expression by binding to its 3'UTR of mRNA. Therefore H. pylori triggered let-7a downregulation enhanced hTERT protein translation, resulting in telomerase reactivation. Furthermore, hTERT enhanced Lin28A expression, forming the positive feedback regulation between hTERT and NF-κB/Lin28A/let-7a axis to maintain the sustained overexpression of hTERT in GC. Implications: NF-κB/Lin28A/Let-7a axis was crucial for the overexpression of hTERT upon H. pylori infection during GC development and may serve as a potential target to suppress hTERT expression for GC prevention and treatment.

5.
Phys Med Biol ; 2020 Oct 14.
Artigo em Inglês | MEDLINE | ID: mdl-33053515

RESUMO

We developed a fluence map prediction method that directly generates fluence maps for a given desired dose distribution without optimization for volumetric modulated arc therapy (VMAT) planning. The prediction consists of two steps. First, projections of the desired dose are calculated and then inversely mapped to fluence maps in the phantom geometry by a deep neural network (DNN). Second, a plan scaling technique is applied to scale fluence maps from phantom to patient geometry. We evaluated the performance of the proposed fluence map prediction method for 102 head and neck (H&N) and 14 prostate cancer VMAT plans by comparing the patient doses calculated from the predicted fluence maps with the given desired dose distributions. The mean dose differences were 1.42%±0.37%, 1.53%±0.44% and 1.25%±0.44% for the planning target volume (PTV), the region from the PTV boundary to the 50% isodose line, and the region from the 50% to the 20% isodose line, respectively. The gamma passing rate was 98.06%±2.64% with the 3 mm/3% criterion. The prediction time for a single VMAT plan was less than one second. In conclusion, we developed an inverse mapping-based method that predicts fluence maps for desired dose distributions with high accuracy. Our method is effectively an optimization-free inverse planning approach, which was orders of magnitude faster than fluence map optimization (FMO). Combining the proposed method with leaf sequencing has the potential to dramatically speed up VMAT treatment planning.

6.
Neoplasma ; 2020 Oct 08.
Artigo em Inglês | MEDLINE | ID: mdl-33038905

RESUMO

Ovarian cancer is the most lethal gynecological cancer. In spite of recent advances, clinical outcomes remain poor, urgently needing novel therapeutic approaches. Growing evidence indicates that microRNAs play crucial roles in ovarian carcinogenesis and progression and that ferroptosis serves as a novel tumor suppressor. However, the molecular mechanisms of miRNA-mediated ferroptosis regulation in ovarian cancer are still largely unknown. In the present study, we show that miR-424-5p negatively regulates ferroptosis by directly targeting ACSL4 in ovarian cancer cells. Upregulation of miR-424-5p suppressed ACSL4 by directly binding to its 3'-UTR, which subsequently reduced erastin- and RSL3-induced ferroptosis. Meanwhile, knockdown of miR-424-5p increased the sensitivity of ovarian cancer cells to erastin and RSL3. Furthermore, ACSL4 was upregulated in ovarian cancer tissues, and high ACSL4 expression predicted worse prognosis and sensitized ovarian cancer cells to erastin- and RSL3-induced ferroptosis. Importantly, decreases in lipid peroxides and ferroptotic cell death mediated by miR-424-5p could be abrogated by ACSL4 overexpression. Taken together, our findings demonstrate that miR-424-5p regulates ferroptosis by targeting ACSL4 in ovarian cancer cells and suggest a potential therapeutic approach for ovarian cancer.

7.
Cell Mol Biol (Noisy-le-grand) ; 66(5): 66-72, 2020 Jul 31.
Artigo em Inglês | MEDLINE | ID: mdl-33040816

RESUMO

Cardiomyopathy is a group of heterogeneous diseases that negatively affect cardiac function. Twenty-five years ago, clinical researchers began to realize that cardiomyopathy is an important and fairly common heart disease. Although many aspects of the pathogenesis of cardiomyopathy have been explored by biologists, the molecular mechanisms remain elusive. This study modularized the pathogenesis of non-ischemic cardiomyopathy and ischemic cardiomyopathy and finally explored their common core pathogenic driver genes. First, based on the normal expression profile data of patients with non-ischemic cardiomyopathy and ischemic cardiomyopathy, differential expression analysis was used to screen differentially expressed genes. Secondly, the co-expression analysis of differentially expressed genes was performed to obtain a co-expression module of genes. Thirdly, the enrichment analysis of GO functions and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway was conducted on the module genes. Finally, based on hypergeometric tests, non-coding RNA (ncRNA) and transcription factors with significant regulatory effects were predicted. In summary, we obtained 8 co-expression modules, of which HN1, PRDX3 genes had significant differences in expression in patients with cardiomyopathy, and had a positive regulatory role in the dysfunction module, so they were recognized as non-ischemic and key genes for non-ischemic diseases and ischemic cardiomyopathy. The enrichment results showed that the module genes were significant in the biological processes of neutrophil activation involved in immunoreaction, neutrophil-mediated immunity, neutrophil activation, and neutrophil degranulation, and significantly regulate the signal pathways such as vibrio cholerae infection. Finally, significant regulatory dysfunction modules of pivot ncRNAs (including MALAT1, miR-133a-3p, and miR-133b) and pivot TFs (including NFKB1, PML, and RELA, etc.) were identified. In summary, our work decodes a co-expression network involving the regulation of key genes in non-ischemic and ischemic cardiomyopathy. It helps to discover core dysfunction modules and potential regulatory factors, drive disease genes, and improve our understanding of its pathogenesis.

8.
Neoplasma ; 2020 Oct 07.
Artigo em Inglês | MEDLINE | ID: mdl-33030956

RESUMO

Ovarian cancer is the most lethal gynecological cancer. In spite of recent advances, clinical outcomes remain poor, urgently needing novel therapeutic approaches. Growing evidence indicates that microRNAs play crucial roles in ovarian carcinogenesis and progression and that ferroptosis serves as a novel tumor suppressor. However, the molecular mechanisms of miRNA-mediated ferroptosis regulation in ovarian cancer are still largely unknown. In the present study, we show that miR-424-5p negatively regulates ferroptosis by directly targeting ACSL4 in ovarian cancer cells. Upregulation of miR-424-5p suppressed ACSL4 by directly binding to its 3'-UTR, which subsequently reduced erastin- and RSL3-induced ferroptosis. Meanwhile, knockdown of miR-424-5p increased the sensitivity of ovarian cancer cells to erastin and RSL3. Furthermore, ACSL4 was upregulated in ovarian cancer tissues, and high ACSL4 expression predicted worse prognosis and sensitized ovarian cancer cells to erastin- and RSL3-induced ferroptosis. Importantly, decreases in lipid peroxides and ferroptotic cell death mediated by miR-424-5p could be abrogated by ACSL4 overexpression. Taken together, our findings demonstrate that miR-424-5p regulates ferroptosis by targeting ACSL4 in ovarian cancer cells and suggest a potential therapeutic approach for ovarian cancer.

10.
Molecules ; 25(17)2020 Sep 03.
Artigo em Inglês | MEDLINE | ID: mdl-32899251

RESUMO

Cerebrosides (Crb; including glucosylceramide and galactosylceramide) and lactosylceramide (LacCer) are structurally complex lipids found in many eukaryotic cell membranes, where they play important roles in cell growth, apoptosis, cell recognition and signaling. They are also found in mammalian milk as part of the milk fat globule membrane (MFGM), making milk an important dietary component for the rapidly growing infant. This study reports the development of a robust analytical method for the identification and characterization of 44 Crb and 23 LacCer molecular species in milk, using high performance liquid chromatography-tandem mass spectrometry in data-dependent acquisition mode. For the first time, it also compares the distributions of these species in human and bovine milks, a commercial MFGM-enriched dairy ingredient (MFGM Lipid 100) and commercial standards purified from bovine milk. A method for quantifying Crb and LacCer in milk using mass spectrometry in neutral loss scan mode was developed and validated for human milk, bovine milk and MFGM Lipid 100. Human milk was found to contain approximately 9.9-17.4 µg Crb/mL and 1.3-3.0 µg LacCer/mL, whereas bovine milk (pooled milk from a Friesian herd) contained 9.8-12.0 and 14.3-16.2 µg/mL of these lipids, respectively. The process used to produce MFGM Lipid 100 was shown to have enriched these components to 448 and 1036 µg/g, respectively. No significant changes in the concentrations of both Crb and LacCer were observed during lactation.

11.
J Cardiothorac Surg ; 15(1): 253, 2020 Sep 12.
Artigo em Inglês | MEDLINE | ID: mdl-32919470

RESUMO

We report a case who is a 33-year-old man admitted to our Emergency room for chest trauma caused by the factory's mechanical arm. Despite the endotracheal tube, the patient's respiratory state was poor and the oxygen saturation did not improve and the subcutaneous emphysema progressed. To improve distressed breathing, we first proposed the concept "mechanical ventilation with dual ventilator" to maintain oxygen saturation of the patient. This is, to our knowledge, the first report of using a special mechanical ventilation method in emergency surgery.

12.
Mil Med Res ; 7(1): 41, 2020 09 04.
Artigo em Inglês | MEDLINE | ID: mdl-32887670

RESUMO

The novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the cause of a rapidly spreading illness, coronavirus disease 2019 (COVID-19), affecting more than seventeen million people around the world. Diagnosis and treatment guidelines for clinicians caring for patients are needed. In the early stage, we have issued "A rapid advice guideline for the diagnosis and treatment of 2019 novel coronavirus (2019-nCoV) infected pneumonia (standard version)"; now there are many direct evidences emerged and may change some of previous recommendations and it is ripe for develop an evidence-based guideline. We formed a working group of clinical experts and methodologists. The steering group members proposed 29 questions that are relevant to the management of COVID-19 covering the following areas: chemoprophylaxis, diagnosis, treatments, and discharge management. We searched the literature for direct evidence on the management of COVID-19, and assessed its certainty generated recommendations using the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) approach. Recommendations were either strong or weak, or in the form of ungraded consensus-based statement. Finally, we issued 34 statements. Among them, 6 were strong recommendations for, 14 were weak recommendations for, 3 were weak recommendations against and 11 were ungraded consensus-based statement. They covered topics of chemoprophylaxis (including agents and Traditional Chinese Medicine (TCM) agents), diagnosis (including clinical manifestations, reverse transcription-polymerase chain reaction (RT-PCR), respiratory tract specimens, IgM and IgG antibody tests, chest computed tomography, chest x-ray, and CT features of asymptomatic infections), treatments (including lopinavir-ritonavir, umifenovir, favipiravir, interferon, remdesivir, combination of antiviral drugs, hydroxychloroquine/chloroquine, interleukin-6 inhibitors, interleukin-1 inhibitors, glucocorticoid, qingfei paidu decoction, lianhua qingwen granules/capsules, convalescent plasma, lung transplantation, invasive or noninvasive ventilation, and extracorporeal membrane oxygenation (ECMO)), and discharge management (including discharge criteria and management plan in patients whose RT-PCR retesting shows SARS-CoV-2 positive after discharge). We also created two figures of these recommendations for the implementation purpose. We hope these recommendations can help support healthcare workers caring for COVID-19 patients.


Assuntos
Quimioprevenção/métodos , Técnicas de Laboratório Clínico/métodos , Infecções por Coronavirus/tratamento farmacológico , Pneumonia Viral/tratamento farmacológico , Adulto , Betacoronavirus , Infecções por Coronavirus/diagnóstico , Infecções por Coronavirus/prevenção & controle , Medicina Baseada em Evidências , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Pandemias/prevenção & controle , Alta do Paciente/normas , Pneumonia Viral/diagnóstico , Pneumonia Viral/prevenção & controle , Guias de Prática Clínica como Assunto
13.
Artigo em Inglês | MEDLINE | ID: mdl-32960763

RESUMO

Improving the aesthetic quality of images is challenging and eager for the public. To address this problem, most existing algorithms are based on supervised learning methods to learn an automatic photo enhancer for paired data, which consists of low-quality photos and corresponding expert-retouched versions. However, the style and characteristics of photos retouched by experts may not meet the needs or preferences of general users. In this paper, we present an unsupervised image enhancement generative adversarial network (UEGAN), which learns the corresponding image-to-image mapping from a set of images with desired characteristics in an unsupervised manner, rather than learning on a large number of paired images. The proposed model is based on single deep GAN which embeds the modulation and attention mechanisms to capture richer global and local features. Based on the proposed model, we introduce two losses to deal with the unsupervised image enhancement: (1) fidelity loss, which is defined as a l2 regularization in the feature domain of a pre-trained VGG network to ensure the content between the enhanced image and the input image is the same, and (2) quality loss that is formulated as a relativistic hinge adversarial loss to endow the input image the desired characteristics. Both quantitative and qualitative results show that the proposed model effectively improves the aesthetic quality of images.

14.
J Musculoskelet Neuronal Interact ; 20(3): 429-436, 2020 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-32877980

RESUMO

OBJECTIVE: To investigate the expression of micro ribonucleic acid (miR)-214 in the bone tissue and blood of patients with fragility fracture. METHODS: The expression of miR-214 was detected via quantitative reverse transcription-polymerase chain reaction. The effect of miR-214 on proliferation and apoptosis of osteoblasts were detected via methyl thiazolyl tetrazolium assay and terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling staining. RESULTS: The expression of miR-214 in the bone tissue and blood of patients with fragility fracture significantly declined. miR-214 could promote the proliferation of osteoblasts and inhibited the apoptosis of osteoblasts. miR-214 is involved in fracture healing through inhibiting Sox4 and promoting phosphorylation of PI3K/AKT pathway. The expression of BSP in cells treated with miR-214 mimics was significantly increased to 2.5-fold (p=0.0168), while the expression of BSP in cells treated with miR-214 AMO was significantly decreased, reduced to 0.3 times (p=0.0397). The expression of BMP2 in cells treated with miR-214 mimics was significantly increased to 2.5-fold (p=0.003), while the expression of BMP2 was significantly decreased in cells treated with miR-214 AMO, reduced to 0.3 times (p=0.0002). miR-214 can regulate the expression of Sox2, PI3K and AKT proteins. CONCLUSION: MiR-214 regulates the proliferation, apoptosis, bone formation of osteoblasts and participate in the fracture healing process by inhibiting the expression of Sox4, which provided new ideas for clinical treatment of fracture healing.

15.
Sci Total Environ ; 751: 141813, 2020 Aug 20.
Artigo em Inglês | MEDLINE | ID: mdl-32898747

RESUMO

Conventional interpolation methods, such as spatial averaging, nearest neighbor, inverse distance weight and ordinary Kriging (OK); for estimating the spatial distribution of ground-level particulate matter (PM) data, do not account for the wind direction for estimating the spatial distribution of PM2.5. In this work, an interpolation algorithm, Win-OK accounting for the wind direction, is developed. In contrast to ordinary Kriging where all locations (irrespective of the wind direction) in the vicinity of a site is considered, the new algorithm (Win-OK) predicts the value at a certain location based on the measured values at locations upwind as determined by the wind direction. This new methodology, Win-OK is validated by applying it to analyze the hourly spatial distribution of ground-level PM2.5 concentrations during Chinese New Year and Chinese National Day in 2017 in Xinxiang city, China. The performance of OK and Win-OK are compared by using them to build PM2.5 concentration heat-maps. A "leave-one-out" cross validation methodology is used to calculate the root-mean-square error (RMSE) and standard deviation for evaluating both algorithms. The results show that OK sometimes gives an extremely high RMSE value using a Gaussian semi-variance model, and the standard deviation significantly deviates from the measured values. Win-OK was found to more accurately predict the PM2.5 spatial distribution in a specific sector. The performance of Win-OK is more stable than OK as established by comparing the calculated RMSE and standard deviation from predictions of both algorithms. Win-OK with a spherical semi-variance model is the most accurate method investigated here for deriving the spatial distribution of ground-level PM2.5. The new algorithm developed here could improve the prediction accuracy of PM2.5 spatial distribution by considering the effect of wind direction.

16.
Health Qual Life Outcomes ; 18(1): 298, 2020 Sep 04.
Artigo em Inglês | MEDLINE | ID: mdl-32887630

RESUMO

BACKGROUND: Many previous studies have reported factors that contribute to health-related quality of life (HRQoL) for a single skin disease. However, little is known about generalized factors associated with HRQoL across skin diseases. The objective of this study was to investigate overall HRQoL, and to identify factors related to severely impaired HRQoL among patients with 16 different skin diseases. METHODS: A cross-sectional study of 9845 patients with skin disease was conducted in 9 hospitals in China. HRQoL was assessed with the Chinese version of the Skindex-29 which measures dermatology-specific health along three domains (symptoms, emotions and functioning). With the published Skindex-29 cut-off scores for severely impaired HRQoL, logistic regression models assessed the relationship between severely impaired HRQoL and demographic/clinical characteristics, with adjustments for different skin diseases. To guarantee the models' convergence, 16 skin diseases with frequencies of at least 100 were included, and the sample size was 8789. RESULTS: Emotions was the most impaired aspect of HRQoL. Co-existing chronic diseases, 3 years or longer duration, and more severity were identified as associated factors for severely impaired HRQoL for each Skindex-29 domain, and for the aggregate. Being female, under 45 years old, and consuming alcohol were associated with a severely impaired emotion domain; Lack of exercise and smoking were associated with severely impaired symptoms and function domains, respectively. CONCLUSIONS: Skin diseases can affect many facets of HRQoL, but the emotional impairment deserves more attention. In addition to skin disease severity, this study shows that other chronic diseases and long duration are correlated with severely impaired HRQoL for patients with 16 clinical common skin diseases. This suggests the need for increased awareness in treating skin disease as a chronic disease. It also suggests that disease management decisions should consider HRQoL improvement, especially emotional conditions, when making management decisions.

17.
Artigo em Inglês | MEDLINE | ID: mdl-32909911

RESUMO

Pig production systems in China are shifting from small to industrial scale. Significant variation in housing ammonia (NH3) emissions can exist due to differences in diet, housing design, and management practices. However, there is a knowledge gap regarding the impacts of farm-scale in China, which may be critical in identifying hotspots and mitigation targets. Here, continuous in-situ NH3 concentration measurements were made at pig farms of different scales for sows and fattening pigs over periods of 3-6 days during two different seasons (summer vs. winter). For the sow farms, NH3 emission rates were greater at the small farm (summer: 0.52 g pig-1 hr-1; winter: 0.21 g pig-1 hr-1) than at the large farm (summer: 0.34 g pig-1 hr-1; winter: 0.12 g pig-1 hr-1). For the fattening pig farms, NH3 emission rates were greater at the large farm (summer: 0.22 g pig-1 hr-1; winter: 0.16 g pig-1 hr-1) than at the small farm (summer: 0.19 g pig-1 hr-1; winter: 0.07 g pig-1 hr-1). Regardless of farm scale, the NH3 emission rates measured in summer were greater than those in winter; the NH3 emission rates were greater in the daytime than at the nighttime; a positive relationship (R2=0.06-0.68) was established between temperature and NH3 emission rate whereas a negative relationship (R2=0.10-0.47) was found between relative humidity and NH3 emission rate. The effect of farm-scale on indoor NH3 concentration could mostly be explained by the differences in ventilation rates between farms. The diurnal variation in NH3 concentration could be partly explained by ventilation rate (R2=0.48-0.78) in the small traditional farms and by emission rate (R2=0.26-0.85) in the large industrial farms, except for the large fattening pig farm in summer. Overall, mitigation of NH3 emissions from sow farms should be a top priority in the North China Plain. IMPLICATION The present study firstly examined the farm-scale effect of ammonia emissions in the North China Plain. Of all farms, the sow farm was identified as the greatest source of ammonia emission. Regardless of farm scale, ammonia emission rates were observed to be higher in summer. Ammonia concentrations were mostly higher in the large industrial farms partly due to lower ventilation rates than in the small traditional farms.

18.
Histopathology ; 2020 Sep 14.
Artigo em Inglês | MEDLINE | ID: mdl-32926596

RESUMO

AIMS: Coronavirus Disease 2019 (COVID-19) caused by Severe Acute Respiratory Syndrome Coronavirus -2 (SARS-CoV-2) infection has been deemed as a global pandemic by World Health Organization. While diffuse alveolar damage (DAD) is recognized to be the primary manifestation COVID-19 pneumonia, there has been little emphasis on the progression to the fibrosing phase of DAD. This topic is of great interest due to growing concerns regarding the potential long-term complications in prolonged survivors. METHODS: Here we report a detailed histopathologic study of thirty autopsy cases with COVID-19 virus infection, based on minimally invasive autopsies performed between February to March, 2020. RESULTS: The mean age was 69 years, with twenty (67%) males and 10 (33%) females and frequent (70.0%) underlying comorbidities. The duration of illness ranged from 16 to 82 (median=42) days. Histologically, the most common manifestation was diffuse alveolar damage (DAD) in 28 (93.3%) cases which showed predominantly acute (32%), organizing (25%), and/or fibrosing (43%) patterns. Patients with fibrosing DAD were one decade younger (p=0.034) and they had a longer duration of illness (p=0.033), hospitalization (p=0.037) and mechanical ventilation (p=0.014) compared to those with acute DAD. Patients with organizing DAD had a longer duration of illness (p=0.032) and hospitalization (p=0.023) compared to those with acute DAD. CONCLUSIONS: COVID-19 pneumonia patients who develop DAD can progress to the fibrosing pattern. While we observed fibrosing DAD in fatal cases, whether surviving patients are at risk for developing pulmonary fibrosis and the frequency of this complication will require further clinical and radiologic follow-up studies.

19.
Stem Cells ; 2020 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-32930470

RESUMO

Allogeneic immune rejection is a major barrier for the application of human pluripotent stem cells (hPSCs) in regenerative medicine. A broad spectrum of immune cells, including T cells, natural killer (NK) cells, and antigen-presenting cells, which either cause direct cell killing or constitute an immunogenic environment, are involved in allograft immune rejection. A strategy to protect donor cells from cytotoxicity while decreasing the secretion of inflammatory cytokines of lymphocytes is still lacking. Here, we engineered hPSCs with no surface expression of classical human leukocyte antigen (HLA) class I proteins via beta-2 microglobulin (B2M) knockout or biallelic knockin of HLA-G1 within the frame of endogenous B2M loci. Elimination of the surface expression of HLA class I proteins protected the engineered hPSCs from cytotoxicity mediated by T cells. However, this lack of surface expression also resulted in missing-self response and NK cell activation, which were largely compromised by expression of ß2m-HLA-G1 fusion proteins. We also proved that the engineered ß2m-HLA-G5 fusion proteins were soluble, secretable, and capable of safeguarding low immunogenic environments by lowering inflammatory cytokines secretion in allografts. Our current study reveals a novel strategy that may offer unique advantages to construct hypoimmunogenic hPSCs via the expression of membrane-bound and secreted ß2m-HLA-G fusion proteins. These engineered hPSCs are expected to serve as an unlimited cell source for generating universally compatible "off-the-shelf" cell grafts in the future.

20.
Mol Plant ; 2020 Sep 05.
Artigo em Inglês | MEDLINE | ID: mdl-32896642

RESUMO

Controlled pedigrees and the multi-decade timescale of national crop plant breeding programs offer a unique experimental context for examining how selection affects plant genomes. More than 3000 wheat cultivars have been registered, released, and documented since 1949 in China. In this study, a set of 145 elite cultivars selected from historical points of wheat breeding in China were re-sequenced. A total of 43.75 Tb of sequence data were generated with an average read depth of 17.94× for each cultivar, and more than 60.92 million SNPs and 2.54 million InDels were captured, based on the Chinese Spring RefSeq genome v1.0. Seventy years of breeder-driven selection led to dramatic changes in grain yield and related phenotypes, with distinct genomic regions and phenotypes targeted by different breeders across the decades. There are very clear instances illustrating how introduced Italian and other foreign germplasm was integrated into Chinese wheat programs and reshaped the genomic landscape of local modern cultivars. Importantly, the resequencing data also highlighted significant asymmetric breeding selection among the three sub-genomes: this was evident in both the collinear blocks for homeologous chromosomes and among sets of three homeologous genes. Accumulation of more newly assembled genes in newer cultivars implied the potential value of these genes in breeding. Conserved and extended sharing of linkage disequilibrium (LD) blocks was highlighted among pedigree-related cultivars, in which fewer haplotype differences were detected. Fixation or replacement of haplotypes from founder genotypes after generations of breeding was related to their breeding value. Based on the haplotype frequency changes in LD blocks of pedigree-related cultivars, we propose a strategy for evaluating the breeding value of any given line on the basis of the accumulation (pyramiding) of beneficial haplotypes. Collectively, our study demonstrates the influence of "founder genotypes" on the output of breeding efforts over many decades and also suggests that founder genotype perspectives are in fact more dynamic when applied in the context of modern genomics-informed breeding.

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