Publications by authors named "Xiaomin Yang"

111 Publications

Home blood pressure telemonitoring for improving blood pressure control in middle-aged and elderly patients with hypertension.

J Clin Hypertens (Greenwich) 2021 Sep 5;23(9):1744-1751. Epub 2021 Aug 5.

Research Institute of Hypertension, Department of Cardiovascular Medicine, The Second Affiliated Hospital of Baotou Medical College, Baotou, Inner Mongolia, P.R. China.

The blood pressure (BP) control rate among treated hypertensives in China remains low at 37.5%. The relationship between home blood pressure telemonitoring (HBPT) and BP control is controversial. The authors aimed to investigate the relationship between HBPT and BP control in middle-aged and elderly hypertensives. In total, 252 hypertension patients aged between 60 and 79 years were enrolled. The patients were given either HBPT through interactive platforms between physicians and patients (telemonitoring group, n = 126) or conventional management (routine management group, n = 126). All patients were followed-up for 15 months. BP control was defined as home systolic blood pressure < 135 mm Hg and home diastolic blood pressure < 85 mm Hg. At baseline, there were no significant differences in the baseline BP control rate (p = .083). However, after 15 months, the BP control rate improved in both groups, and the telemonitoring group (71.3%) had a significantly higher BP control than the routine management group (49.8%) (p < .001). The change of BP control rate from baseline in the routine management group increased by 26.1%, and that of the telemonitoring group increased by 35.4%. The results of the fully adjusted binary logistic regression showed that HBPT was positively associated with BP control after adjusting for confounders (OR = 4.15, 95% CI 2.05-8.39). Similar results were observed after 3, 9, and 12 months. The association of HBPT with BP control was similar in subgroups. In conclusions, HBPT is recommended for BP control in middle-aged and elderly hypertensives in the community setting.
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http://dx.doi.org/10.1111/jch.14341DOI Listing
September 2021

Genomic Insights Into the Admixture History of Mongolic- and Tungusic-Speaking Populations From Southwestern East Asia.

Front Genet 2021 22;12:685285. Epub 2021 Jun 22.

Department of Forensic Medicine, Guizhou Medical University, Guiyang, China.

As a major part of the modern Eurasian or Altaic language family, most of the Mongolic and Tungusic languages were mainly spoken in northern China, Mongolia, and southern Siberia, but some were also found in southern China. Previous genetic surveys only focused on the dissection of genetic structure of northern Altaic-speaking populations; however, the ancestral origin and genomic diversification of Mongolic and Tungusic-speaking populations from southwestern East Asia remain poorly understood because of the paucity of high-density sampling and genome-wide data. Here, we generated genome-wide data at nearly 700,000 single-nucleotide polymorphisms (SNPs) in 26 Mongolians and 55 Manchus collected from Guizhou province in southwestern China. We applied principal component analysis (PCA), ADMIXTURE, statistics, analysis, , TreeMix, Fst, and ALDER to infer the fine-scale population genetic structure and admixture history. We found significant genetic differentiation between northern and southern Mongolic and Tungusic speakers, as one specific genetic cline of Manchu and Mongolian was identified in Guizhou province. Further results from ADMIXTURE and statistics showed that the studied Guizhou Mongolians and Manchus had a strong genetic affinity with southern East Asians, especially for inland southern East Asians. The -based estimates of ancestry admixture proportion demonstrated that Guizhou Mongolians and Manchus people could be modeled as the admixtures of one northern ancestry related to northern Tungusic/Mongolic speakers or Yellow River farmers and one southern ancestry associated with Austronesian, Tai-Kadai, and Austroasiatic speakers. The -based phylogeny and neighbor-joining tree further confirmed that Guizhou Manchus and Mongolians derived approximately half of the ancestry from their northern ancestors and the other half from southern Indigenous East Asians. The estimated admixture time ranged from 600 to 1,000 years ago, which further confirmed the admixture events were mediated the Mongolians Empire expansion during the formation of the Yuan dynasty.
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http://dx.doi.org/10.3389/fgene.2021.685285DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8258170PMC
June 2021

Real-Time Environment Monitoring Using a Lightweight Image Super-Resolution Network.

Int J Environ Res Public Health 2021 05 31;18(11). Epub 2021 May 31.

College of Electronics and Information Engineering, Sichuan University, Chengdu 610064, China.

Deep-learning (DL)-based methods are of growing importance in the field of single image super-resolution (SISR). The practical application of these DL-based models is a remaining problem due to the requirement of heavy computation and huge storage resources. The powerful feature maps of hidden layers in convolutional neural networks (CNN) help the model learn useful information. However, there exists redundancy among feature maps, which can be further exploited. To address these issues, this paper proposes a lightweight efficient feature generating network (EFGN) for SISR by constructing the efficient feature generating block (EFGB). Specifically, the EFGB can conduct plain operations on the original features to produce more feature maps with parameters slightly increasing. With the help of these extra feature maps, the network can extract more useful information from low resolution (LR) images to reconstruct the desired high resolution (HR) images. Experiments conducted on the benchmark datasets demonstrate that the proposed EFGN can outperform other deep-learning based methods in most cases and possess relatively lower model complexity. Additionally, the running time measurement indicates the feasibility of real-time monitoring.
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http://dx.doi.org/10.3390/ijerph18115890DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8199203PMC
May 2021

Radiation Enhancer Effect of Platinum Nanoparticles in Breast Cancer Cell Lines: In Vitro and In Silico Analyses.

Int J Mol Sci 2021 Apr 23;22(9). Epub 2021 Apr 23.

Commissariat à l'Energie Atomique et aux Energies Alternatives (CEA), Fundamental Research Division (DRF), François Jacob Institute (IBFJ), Institute of Molecular and Cellular Radiobiology (IRCM), Laboratoire de Cancérologie Expérimentale (LCE), University Paris Saclay, Route du Panorama, CEDEX, 92265 Fontenay-aux-Roses, France.

High-Z metallic nanoparticles (NPs) are new players in the therapeutic arsenal against cancer, especially radioresistant cells. Indeed, the presence of these NPs inside malignant cells is believed to enhance the effect of ionizing radiation by locally increasing the dose deposition. In this context, the potential of platinum nanoparticles (PtNPs) as radiosensitizers was investigated in two breast cancer cell lines, T47D and MDA-MB-231, showing a different radiation sensitivity. PtNPs were internalized in the two cell lines and localized in lysosomes and multivesicular bodies. Analyses of cell responses in terms of clonogenicity, survival, mortality, cell-cycle distribution, oxidative stress, and DNA double-strand breaks did not reveal any significant enhancement effect when cells were pre-exposed to PtNPs before being irradiated, as compared to radiation alone. This result is different from that reported in a previous study performed, under the same conditions, on cervical cancer HeLa cells. This shows that the efficacy of radio-enhancement is strongly cell-type-dependent. Simulation of the early stage ionization processes, taking into account the irradiation characteristics and realistic physical parameters in the biological sample, indicated that PtNPs could weakly increase the dose deposition (by 3%) in the immediate vicinity of the nanoparticles. Some features that are potentially responsible for the biological effect could not be taken into account in the simulation. Thus, chemical and biological effects could explain this discrepancy. For instance, we showed that, in these breast cancer cell lines, PtNPs exhibited ambivalent redox properties, with an antioxidant potential which could counteract the radio-enhancement effect. This work shows that the efficacy of PtNPs for enhancing radiation effects is strongly cell-dependent and that no effect is observed in the case of the breast cancer cell lines T47D and MDA-MB-231. Thus, more extensive experiments using other relevant biological models are needed in order to evaluate such combined strategies, since several clinical trials have already demonstrated the success of combining nanoagents with radiotherapy in the treatment of a range of tumor types.
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http://dx.doi.org/10.3390/ijms22094436DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8123015PMC
April 2021

Interference of TGF-β1/Smad7 signal pathway affects myocardial fibrosis in hypertension.

Pak J Pharm Sci 2020 Nov;33(6):2625-2631

Department of Cardiology, Jiangxi Provincial People's Hospital, Nanchang, Jiangxi, China.

Hypertension can cause myocardial fibrosis, during which tumor growth factor-beta 1 (TGF-β1) can facilitate myocardial cell proliferation and transition towards myofibroblast (MFB). Smad7 is a negative regulator of TGF-β1/Smads signal pathway. This study used hypertension rat model to investigate the regulatory role of TGF-β1/Smad7 signal pathway in myocardial fibrosis. Rat renal hypertension model was established to test collagen volume fraction, myocardial hydroxyl proline content and COL1A1 expression as well as the expression of TGF-β1 and Smad7. The expressions of TGF-β1, Smad7, COLA1A1 and α-SMA at certain generations (P2, P4 and P6) were measured in cultured human cardiac fibroblast (HCF) during differentiation towards MFB differentiation. P6 generation HCF was transfected with pIRES2-EGFP-Smad7 and pIRES2-EGFP-blank followed by measuring expressions of TGF-β1, Smad7, COLA1A1 and α-SMA. Hydroxyl-proline content and collagen volume fraction were compared between Ad-NC and Ad-Smad7 injection groups. Hypertensive rats had significantly elevated collagen volume fraction, hydroxyl proline contents, and expression of COLA1 and TGF-β1 than Sham group, whilst Smad7 expression was lower. With increased cell passage, HCF showed gradually increased TGF-β1, COL1A1 and α-SMA expression, plus decreased Smad7 expression. Over-expression of Smad7 remarkably decreased COLA1 and α-SMA expression in HCF. Tail vein injection of Ad-Smad7 decreased both hydroxyl proline and collagen volume fraction. Elevated TGF-β1 expression and decreased Smad7 expression are found in fibrotic myocardial tissues of hypertensive rats. Over-expression of Smad7 inhibits differentiation of HCF towards MFB cells, thus decreasing myocardial fibrosis in hypertensive rats.
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November 2020

What is behind the fear of cancer during menopausal hormone therapy in China?

Arch Gynecol Obstet 2021 Apr 4. Epub 2021 Apr 4.

Department of Obstetrics and Gynecology, Peking Union Medical College, Chinese Academy of Medical Sciences, Peking Union Medical College Hospital, Dongcheng District, Beijing, 100730, China.

Purpose: The application of menopausal hormone therapy (MHT) is generally restricted most likely due to limited prescriptions by doctors. Fear of cancer risk may be a critical factor. We investigated the views of Chinese obstetricians and gynecologists on the relationship between hormone therapy and cancer risk.

Methods: A self-administered web-based nationwide cross-sectional questionnaire.

Results: In total, 5243 medical workers responded to the questionnaire (response rate 94.5%); 4995 were certified obstetricians and gynecologists. Most were aged 36-55 years (70.9%), had > 10 years of working experience (68.5%), and worked at tertiary (34.8%) and secondary hospitals (49.1%); 70% of the clinicians were aware of the endometrial cancer risk caused by estrogen, and 20% considered progestogen to cause the same risk. Regarding breast cancer, while 67.9 and 74.8% of the clinicians viewed natural and synthetic estrogens as risk factors, respectively, only 41.7% identified the carcinogenic effect of progestins as higher than that of progesterone (26.7%). Approximately 75% of the participants believed synthetic estrogens and progestins constituted a risk for ovarian cancer (higher than the percentages for their natural counterparts); 13.0-21.1% of the respondents were worried about choriocarcinoma due to hormone treatment. Finally, 86.8% of obstetricians and gynecologists claimed to have poor knowledge regarding this field.

Conclusion: Misconceptions and a lack of knowledge in this regard may result in the fear of cancer and could be the underlying causes of limited MHT prescriptions. We believe that scientific research, continued education, and the media all have roles to play in changing preconceived ideas regarding MHT prescriptions.
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http://dx.doi.org/10.1007/s00404-021-06052-4DOI Listing
April 2021

Responses of soil moisture to climate variability and livestock grazing in a semiarid Eurasian steppe.

Sci Total Environ 2021 Aug 25;781:146705. Epub 2021 Mar 25.

Department of Civil and Environmental Engineering, Old Dominion University, Norfolk, VA 23529-0241, USA.

Soil water is vital for sustaining semiarid ecosystems. However, data on soil moisture have unlikely been continuously collected for a long time (e.g., >50 years), let alone under various combinations of climates and livestock grazing intensities. The objective of this study was to formulate and parameterize an ecohydrological model for predicting long-term variability of soil moisture, taking a typical Eurasian grassland located in northeast China as the testbed. The parameters were determined by extensive literature review, field reconnaissance, laboratory analyses of soil and grass samples, and model calibration using daily soil temperatures and soil moistures measured at four depths from 2014 to 2017. The model, driven by the daily climate data from 1955 to 2017, performed well in reproducing the measurements. Across the assessment years of 1960 to 2017, the daily soil moistures were predicted to vary from 0.02 to 0.38. Overall, the soil moistures at a shallower depth were smaller but had a wider range than those at a deeper depth, with a largest mean and a widest range around the 30 cm depth. Regardless of the depths, the soil moistures pulsed in beginning March and plateaued from May to September. Livestock grazing was precited to reduce top 1.5-cm soil moistures but increase moistures of the beneath soils. The optimal grazing intensity was determined to be around 3.0 cattle ha, above which wind erosion would become a concern. The grazing impacts on soil moisture were found to monophonically decrease with increase of evapotranspiration or annual precipitation of larger than 220 mm. For the years with an annual precipitation of less than 220 mm, such grazing impacts either increased or decreased with increase of precipitation, depending on the relative magnitude of evapotranspiration. Climate change will diminish soil moisture pulses in early spring, likely intensifying soil erosion by wind.
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http://dx.doi.org/10.1016/j.scitotenv.2021.146705DOI Listing
August 2021

New insights into the fine-scale history of western-eastern admixture of the northwestern Chinese population in the Hexi Corridor via genome-wide genetic legacy.

Mol Genet Genomics 2021 May 1;296(3):631-651. Epub 2021 Mar 1.

Belt and Road Research Center for Forensic Molecular Anthropology Gansu University of Political Science and Law, Lanzhou, 730000, China.

Trans-Eurasian cultural and genetic exchanges have significantly influenced the demographic dynamics of Eurasian populations. The Hexi Corridor, located along the southeastern edge of the Eurasian steppe, served as an important passage of the ancient Silk Road in Northwest China and intensified the transcontinental exchange and interaction between populations on the Central Plain and in Western Eurasia. Historical and archeological records indicate that the Western Eurasian cultural elements were largely brought into North China via this geographical corridor, but there is debate on the extent to which the spread of barley/wheat agriculture into North China and subsequent Bronze Age cultural and technological mixture/shifts were achieved by the movement of people or dissemination of ideas. Here, we presented higher-resolution genome-wide autosomal and uniparental Y/mtDNA SNP or STR data for 599 northwestern Han Chinese individuals and conducted 2 different comprehensive genetic studies among Neolithic-to-present-day Eurasians. Genetic studies based on lower-resolution STR markers via PCA, STRUCTURE, and phylogenetic trees showed that northwestern Han Chinese individuals had increased genetic homogeneity relative to northern Mongolic/Turkic/Tungusic speakers and Tibeto-Burman groups. The genomic signature constructed based on modern/ancient DNA further illustrated that the primary ancestry of the northwestern Han was derived from northern millet farmer ancestors, which was consistent with the hypothesis of Han origin in North China and more recent northwestward population expansion. This was subsequently confirmed via excess shared derived alleles in f/f statistical analyses and by more northern East Asian-related ancestry in the qpAdm/qpGraph models. Interestingly, we identified one western Eurasian admixture signature that was present in northwestern Han but absent from southern Han, with an admixture time dated to approximately 1000 CE (Tang and Song dynasties). Generally, we provided supporting evidence that historic Trans-Eurasian communication was primarily maintained through population movement, not simply cultural diffusion. The observed population dynamics in northwestern Han Chinese not only support the North China origin hypothesis but also reflect the multiple sources of the genetic diversity observed in this population.
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http://dx.doi.org/10.1007/s00438-021-01767-0DOI Listing
May 2021

Successful Treatment of TCF3-HLF-positive Childhood B-ALL with Chimeric Antigen Receptor T-Cell Therapy.

Clin Lymphoma Myeloma Leuk 2021 06 28;21(6):386-392. Epub 2021 Jan 28.

Department of Hematology/Oncology, Key Laboratory of Pediatric Hematology and Oncology Ministry of Health, Shanghai Children's Medical Center, Shanghai Jiao Tong University School of Medicine, Shanghai, China. Electronic address:

Background: TCF3-HLF positive leukemia represents a rare subtype of B-cell acute lymphoblastic leukemia (B-ALL), characterized by a high treatment failure rate despite intensive treatment and hematopoietic stem cell transplantation (HSCT).

Patients And Methods: Four consecutive children with TCF-HLF3-positive B-ALL who were refractory or relapsed with initial chemotherapy were treated with CD19-specific or combined CD19-and CD22-specific chimeric antigen receptor T-cell therapy (19/22 CAR-T) after conditioning regimen with fludarabine and cyclophosphamide. Clinical features, treatment responses, toxicity, and outcomes were analyzed retrospectively.

Results: Four patients received 18.0, 6.0, 5.0, and 7.4 × 10 CAR-T cells per kilogram and developed grade I, III, II, and III cytokine release syndrome, respectively. They all achieved minimal residual disease-negative complete remission (CR). Two of them (patients 1 and 3) underwent haploid HSCT afterward. Patient 1 relapsed after 7.2 months of transplantation and received donor-derived 19/22 CAR-T cell infusion. He had CR2 after he experienced grade II cytokine release syndrome of the second CAR-T and underwent umbilical cord blood transplantation. Unfortunately, this child died of severe lung graft versus host disease 8.4 months after the second transplantation. Patients 2 and 4 experienced reversible neurotoxicity and had a persistent clinical response to CAR-T cells for 13.8 and 6.8 months, respectively, without HSCT. Patient 3 is in continuous CR for 10.6 months until now.

Conclusion: CAR-T cells can effectively treat relapsed/refractory TCF3-HLF-positive childhood B-ALL with acceptable toxicity, which could be a new treatment option for this subtype compared with chemotherapy or HSCT.
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http://dx.doi.org/10.1016/j.clml.2021.01.014DOI Listing
June 2021

Genomic insights into the formation of human populations in East Asia.

Nature 2021 03 22;591(7850):413-419. Epub 2021 Feb 22.

Department of Evolutionary Anthropology, University of Vienna, Vienna, Austria.

The deep population history of East Asia remains poorly understood owing to a lack of ancient DNA data and sparse sampling of present-day people. Here we report genome-wide data from 166 East Asian individuals dating to between 6000 BC and AD 1000 and 46 present-day groups. Hunter-gatherers from Japan, the Amur River Basin, and people of Neolithic and Iron Age Taiwan and the Tibetan Plateau are linked by a deeply splitting lineage that probably reflects a coastal migration during the Late Pleistocene epoch. We also follow expansions during the subsequent Holocene epoch from four regions. First, hunter-gatherers from Mongolia and the Amur River Basin have ancestry shared by individuals who speak Mongolic and Tungusic languages, but do not carry ancestry characteristic of farmers from the West Liao River region (around 3000 BC), which contradicts theories that the expansion of these farmers spread the Mongolic and Tungusic proto-languages. Second, farmers from the Yellow River Basin (around 3000 BC) probably spread Sino-Tibetan languages, as their ancestry dispersed both to Tibet-where it forms approximately 84% of the gene pool in some groups-and to the Central Plain, where it has contributed around 59-84% to modern Han Chinese groups. Third, people from Taiwan from around 1300 BC to AD 800 derived approximately 75% of their ancestry from a lineage that is widespread in modern individuals who speak Austronesian, Tai-Kadai and Austroasiatic languages, and that we hypothesize derives from farmers of the Yangtze River Valley. Ancient people from Taiwan also derived about 25% of their ancestry from a northern lineage that is related to, but different from, farmers of the Yellow River Basin, which suggests an additional north-to-south expansion. Fourth, ancestry from Yamnaya Steppe pastoralists arrived in western Mongolia after around 3000 BC but was displaced by previously established lineages even while it persisted in western China, as would be expected if this ancestry was associated with the spread of proto-Tocharian Indo-European languages. Two later gene flows affected western Mongolia: migrants after around 2000 BC with Yamnaya and European farmer ancestry, and episodic influences of later groups with ancestry from Turan.
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http://dx.doi.org/10.1038/s41586-021-03336-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7993749PMC
March 2021

Laminin-Modified Dental Pulp Extracellular Matrix for Dental Pulp Regeneration.

Front Bioeng Biotechnol 2020 13;8:595096. Epub 2021 Jan 13.

Department of Stomatology, First Affiliated Hospital, Dalian Medical University, Dalian, China.

Native dental pulp extracellular matrix (DPEM) has proven to be an effective biomaterial for dental pulp regeneration. However, as a significant extracellular matrix glycoprotein, partial laminins were lost during the decellularization process, which were essential for odontoblast differentiation. Thereby, this study investigated the feasibility of LN supplementation to improve the surface of DPEM for odontoblast layer regeneration. The influences of laminin on cell adhesion and odontogenic differentiation were evaluated in vitro. Then, we fabricated laminin-modified DPEM based on the physical coating strategy and observed the location and persistency of laminin coating by immunofluorescent staining. Finally, laminin-modified DPEM combined with treated dentin matrix (TDM) was transplanted in orthotopic jaw bone of beagles ( = 3) to assess the effect of LNs on dental pulp tissue regeneration. The in vitro results showed that laminins could improve the adhesion of dental pulp stem cells (DPSCs) and promoted DPSCs toward odontogenic differentiation. Continuous odontoblastic layer-like structure was observed in laminin-modified DPEM group, expressing the markers for odontoblastogenesis, dentine matrix protein-1 (DMP-1) and dentin sialophosphoprotein (DSPP). Overall, these studies demonstrate that the supplementation of laminins to DPEM contributes to the odontogenic differentiation of cells and to the formation of odontoblast layer in dental pulp regeneration.
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http://dx.doi.org/10.3389/fbioe.2020.595096DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7838611PMC
January 2021

Male-Dominated Migration and Massive Assimilation of Indigenous East Asians in the Formation of Muslim Hui People in Southwest China.

Front Genet 2020 11;11:618614. Epub 2021 Jan 11.

Department of Anthropology and Ethnology, Institute of Anthropology, School of Life Sciences, Xiamen University, Xiamen, China.

The origin and diversification of Muslim Hui people in China via demic or simple cultural diffusion is a long-going debate. We here generated genome-wide data at nearly 700,000 single nucleotide polymorphisms (SNPs) from 45 Hui and 14 Han Chinese individuals collected from Guizhou province in southwest China. We applied principal component analysis (PCA), ADMIXTURE, -statistics, , and analysis to infer the population genetic structure and admixture history. Our results revealed the Guizhou Hui people have a limited amount of West Eurasian related ancestry at a proportion of 6%, but show massive genetic assimilation with indigenous southern Han Chinese and Tibetan or Tungusic/Mongolic related northern East Asians. We also detected a high frequency of North Asia or Central Asia related paternal Y-chromosome but not maternal mtDNA lineages in Guizhou Hui. Our observation supports the cultural diffusion has played a vital role in the formation of Hui people and the migration of Hui people to southwest China was probably a sex-biased male-driven process.
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http://dx.doi.org/10.3389/fgene.2020.618614DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7834311PMC
January 2021

Acute myocardial infarction as the first sign of infective endocarditis: a case report.

J Int Med Res 2020 Dec;48(12):300060520980598

Department of Cardiology, Changzheng Hospital, Naval Medical University, Shanghai, China.

Infective endocarditis is a bacterial or fungal infection of the heart valves or endocardial surface, and it frequently forms vegetation and can lead to systemic embolism. Dislodged vegetation rarely results in coronary artery embolism (CAE) and subsequent acute myocardial infarction. A 43-year-old male patient was emergently brought to our hospital for suspected acute myocardial infarction. Coronary angiography was performed and it showed embolism in the left circumflex artery. Thrombus aspiration was performed during coronary angiography. Echocardiography showed formation of vegetation in the posterior leaflet of the mitral valve and multiple blood cultures showed . Infective endocarditis was diagnosed. Three weeks later, debridement of subacute bacterial endocarditis, mitral valve replacement, and tricuspid valvuloplasty were successfully conducted. Our findings suggest that CAE should be considered in the differential diagnosis of acute myocardial infarction. Aspiration of coronary embolus during coronary angiography followed by surgical intervention of diseased heart valves is a plausible strategy for managing CAE in infective endocarditis.
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http://dx.doi.org/10.1177/0300060520980598DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7758667PMC
December 2020

Association of Hyperuricemia With Immune Disorders and Intestinal Barrier Dysfunction.

Front Physiol 2020 27;11:524236. Epub 2020 Nov 27.

Medical Research Center, Affiliated Hospital of Qingdao University, Qingdao, China.

Background: More than 30-40% of uric acid is excreted via the intestine, and the dysfunction of intestinal epithelium disrupts uric acid excretion. The involvement of gut microbiota in hyperuricemia has been reported in previous studies, but the changes and mechanisms of intestinal immunity in hyperuricemia are still unknown.

Methods: This study developed a urate oxidase (Uox)-knockout (Uox-/-) mouse model for hyperuricemia using CRISPR/Cas9 technology. The lipometabolism was assessed by measuring changes in biochemical indicators. Furthermore, 4-kDa fluorescein isothiocyanate-labeled dextran was used to assess gut barrier function. Also, 16S rRNA sequencing was performed to examine the changes in gut microbiota in mouse feces. RNA sequencing, Western blot, Q-PCR, ELISA, and immunohistochemical analysis were used for measuring gene transcription, the number of immune cells, and the levels of cytokines in intestinal tissues, serum, kidney, liver, pancreas, and vascellum.

Results: This study showed that the abundance of inflammation-related microbiota increased in hyperuricemic mice. The microbial pattern recognition-associated Toll-like receptor pathway and inflammation-associated TNF and NF-kappa B signaling pathways were significantly enriched. The increased abundance of inflammation-related microbiota resulted in immune disorders and intestinal barrier dysfunction by upregulating TLR2/4/5 and promoting the release of IL-1β and TNF-α. The levels of epithelial tight junction proteins occludin and claudin-1 decreased. The expression of the pro-apoptotic gene increased. The levels of LPS and TNF-α in systemic circulation increased in hyperuricemic mice. A positive correlation was observed between the increase in intestinal permeability and serum levels of uric acid.

Conclusion: Hyperuricemia was characterized by dysregulated intestinal immunity, compromised intestinal barrier, and systemic inflammation. These findings might serve as a basis for future novel therapeutic interventions for hyperuricemia.
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http://dx.doi.org/10.3389/fphys.2020.524236DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7729003PMC
November 2020

Bisecting GlcNAc modification diminishes the pro-metastatic functions of small extracellular vesicles from breast cancer cells.

J Extracell Vesicles 2020 10 30;10(1):e12005. Epub 2020 Oct 30.

Joint International Research Laboratory of Glycobiology and Medicinal Chemistry College of Life Science Northwest University Xi'an P.R. China.

Small extracellular vesicles (sEVs) are enriched in glycoconjugates and display specific glycosignatures. Aberrant expression of surface glycoconjugates is closely correlated with cancer progression and metastasis. The essential functions of glycoconjugates in sEVs are poorly understood. In this study, we observed significantly reduced levels of bisecting GlcNAc in breast cancer. Introduction of bisecting GlcNAc into breast cancer cells altered the bisecting GlcNAc status on sEVs, and sEVs with diverse bisecting GlcNAc showed differing functions on recipient cells. Carcinogenesis and metastasis of recipient cells were enhanced by sEVs with low bisecting GlcNAc, and the pro-metastatic functions of sEVs was diminished by high bisecting GlcNAc modification. We further identified vesicular integrin β1 as a target protein bearing bisecting GlcNAc. Metastasis of recipient cells was strongly suppressed by high bisecting GlcNAc levels on vesicular β1. Our findings demonstrate the important roles of glycoconjugates on sEVs. Modification of sEV glycosylation may contribute to development of novel targets in breast cancer therapy.
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http://dx.doi.org/10.1002/jev2.12005DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7710122PMC
October 2020

Entropy-Based Image Fusion with Joint Sparse Representation and Rolling Guidance Filter.

Entropy (Basel) 2020 Jan 18;22(1). Epub 2020 Jan 18.

School of Electronic Engineering, Xidian University, Xi'an 710071, China.

Image fusion is a very practical technology that can be applied in many fields, such as medicine, remote sensing and surveillance. An image fusion method using multi-scale decomposition and joint sparse representation is introduced in this paper. First, joint sparse representation is applied to decompose two source images into a common image and two innovation images. Second, two initial weight maps are generated by filtering the two source images separately. Final weight maps are obtained by joint bilateral filtering according to the initial weight maps. Then, the multi-scale decomposition of the innovation images is performed through the rolling guide filter. Finally, the final weight maps are used to generate the fused innovation image. The fused innovation image and the common image are combined to generate the ultimate fused image. The experimental results show that our method's average metrics are: mutual information ( M I )-5.3377, feature mutual information ( F M I )-0.5600, normalized weighted edge preservation value ( Q A B / F )-0.6978 and nonlinear correlation information entropy ( N C I E )-0.8226. Our method can achieve better performance compared to the state-of-the-art methods in visual perception and objective quantification.
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http://dx.doi.org/10.3390/e22010118DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7516424PMC
January 2020

Knowledge of iatrogenic premature ovarian insufficiency among Chinese obstetricians and gynaecologists: a national questionnaire survey.

J Ovarian Res 2020 Nov 18;13(1):134. Epub 2020 Nov 18.

Department of Obstetrics and Gynaecology, Peking Union Medical College Hospital (East), Chinese Academy of Medical Sciences and Peking Union Medical College, No. 1 Shuaifuyuan, Dongcheng District, Beijing, 100730, China.

Background: With increasing cases of iatrogenic premature ovarian insufficiency (POI), more clinicians are required to counsel patients regarding the gonadotoxic effects of iatrogenic treatments. This survey aimed to explore obstetricians and gynaecologists' knowledge regarding iatrogenic POI. A national online questionnaire survey was conducted across China. Respondents were asked to select the iatrogenic condition(s) that can cause POI based on their experience and knowledge.

Results: Of the 5523 returned questionnaires, 4995 were analysed. Among tumour therapies causing POI, most respondents agreed that radiotherapy (73.5% of respondents) and chemotherapy (64.1%) are risk factors for POI. While only 6.5 and 7.8% of the gynaecological oncologists believed that tumour immunotherapy and tumour-targeting therapy, respectively, may cause ovarian impairment, 31.8 and 22.2% of the non-gynaecologic oncologists believed that these therapies could affect ovarian health. Most respondents believed that ovarian cystectomy (54.4%) was a risk factor for POI. In contrast, only a few respondents believed that hysterectomy with bilateral salpingectomy (39.6%) and uterine artery embolisation (33.5%) could cause ovarian impairment. Only 30.5% of respondents believed that immunosuppressants (ISs) increased the risk of POI. Views differed with experience and hospital setting.

Conclusions: The knowledge of gonadal toxicity due to traditional tumour treatments is generally high among Chinese obstetricians and gynaecologists. A misunderstanding may exist in primary care hospitals and general gynaecologists regarding a link between novel tumour treatments and POI, owing to the lack of convincing evidence. Knowledge of POI caused by hysterectomy and ISs should be improved.
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http://dx.doi.org/10.1186/s13048-020-00739-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7677772PMC
November 2020

Genomic insight into the population history of Central Han Chinese.

Ann Hum Biol 2021 Feb 5;48(1):49-55. Epub 2021 Apr 5.

Department of Anthropology and Ethnology, Institute of Anthropology, National Institute for Data Science in Health and Medicine, and School of Life Sciences, Xiamen University, Xiamen, China.

Background: In recent decades, considerable attention has been paid to exploring the population genetic characteristics of Han Chinese, mainly documenting a north-south genetic substructure. However, the central Han Chinese have been largely underrepresented in previous studies.

Aim: To infer a comprehensive understanding of the homogenisation process and population history of Han Chinese.

Subjects And Methods: We collected samples from 122 Han Chinese from seven counties of Hubei province in central China and genotyped 534,000 genome-wide SNPs. We compared Hubei Han with both ancient and present-day Eurasian populations using Principal Component Analysis, ADMIXTURE,  statistics, and .

Results: We observed Hubei Han Chinese are at a genetically intermediate position on the north-south Han Chinese cline. We have not detected any significant genetic substructure in the studied groups from seven different counties. Hubei Han show significant evidence of genetic admixture deriving about 63% of ancestry from Tai-Kadai or Austronesian-speaking southern indigenous groups and 37% from Tungusic or Mongolic related northern populations.

Conclusions: The formation of Han Chinese has involved extensive admixture with Tai-Kadai or Austronesian-speaking populations in the south and Tungusic or Mongolic speaking populations in the north. The convenient transportation and central location of Hubei make it the key region for the homogenisation of Han Chinese.
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http://dx.doi.org/10.1080/03014460.2020.1851396DOI Listing
February 2021

Amplitude randomness of spontaneous emission influence on the coherence properties of a laser.

Appl Opt 2020 Nov;59(32):10143-10148

Based on the randomness of spontaneous emission, the statistical characteristics of phase noise are discussed. A theoretical analysis model, focusing on the amplitude randomness of spontaneous emission, is established to calculate laser phase noise. Then, the coherence of a laser before and after phase-locked control is calculated when an ideal laser and nonideal laser are used as a reference light in an optical phase-locked loop (OPLL). The effects of the amplitude randomness of spontaneous emission on phase-locked laser coherence are analyzed in detail. The results show that phase noise randomness increases with the increase of the expectation or variance of spontaneous emission amplitude, which represents amplitude randomness. When an ideal light is used as reference light, if the expectation and the variance of spontaneous emission amplitude are about 10 and 100, respectively, the time constant of an OPLL should be set as 1 ns, while a favorable noise suppression result can be achieved. However, to achieve a favorable noise suppression result, the time constant of an OPLL should be set as 0.1 ns when a nonideal laser is used as reference light.
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http://dx.doi.org/10.1364/AO.404854DOI Listing
November 2020

TMEM16A-encoded anoctamin 1 inhibition contributes to chrysin-induced coronary relaxation.

Biomed Pharmacother 2020 Nov 24;131:110766. Epub 2020 Sep 24.

Department of Pharmacology, Shanxi Medical University, Xinjiannanlu 56, Taiyuan 030001, Shanxi Province, China. Electronic address:

Background: Chrysin, a natural flavonoid available in honey, propolis and medicinal plants, has been shown to be vasorelaxant in some vascular beds. Proper intake of an alimental vasodilator as a food additive may be a promising strategy for prevention and treatment of coronary spasmodic disorders.

Purpose: TMEM16A-encoded anoctamin 1 (ANO1), a Ca activated Cl channel (CaCC), plays an important role in the modulation of vascular tone. We tested the possibility that inhibition of CaCCs contributes to chrysin-induced coronary arterial relaxation.

Methods: The vascular tone of the rat coronary artery (RCA) was recorded with a wire myograph. CaCC currents were assessed using whole-cell patch clamp in arterial smooth muscle cell (ASMC) freshly isolated from RCAs. An inhibitor study was performed to explore the mechanisms underlying the vasomotor and electrophysiological effects of chrysin.

Results: Pre-incubation with chrysin depressed the contractions elicited by thromboxane A2 analog U46619, vasopressin (VP), depolarization and extracellular Ca elevation/depolarization without significant preference among these vasoconstrictors. Besides, chrysin inhibited both intracellular Ca release-dependent and extracellular Ca influx-dependent components of contractions induced by U46619 or VP. In RCAs pre-contracted with U46619, VP or KCl, chrysin elicited concentration-dependent relaxations, which were weakened by Cl -deprivation. The electrophysiological study showed that chrysin reduced ANO1-antibody-sensitive CaCC currents and depressed CaCC increments induced by U46619. Inhibitor study showed that both the vasorelaxation and the CaCC current reduction induced by chrysin were attenuated by blocking CaCCs and inhibiting cAMP/PKA and NO/PKG pathways.

Conclusion: The present findings indicate that inhibition of RCA ASMC CaCC currents, which may be consequential following intracellular Ca availability reduction and activation of cAMP/PKA and NO/cGMP signaling pathways, contributes to chrysin-induced RCA relaxation.
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http://dx.doi.org/10.1016/j.biopha.2020.110766DOI Listing
November 2020

The Protective Effect of Qishen Granule on Heart Failure after Myocardial Infarction through Regulation of Calcium Homeostasis.

Evid Based Complement Alternat Med 2020 22;2020:1868974. Epub 2020 Oct 22.

School of Life Sciences, Beijing University of Chinese Medicine, Beijing 100029, China.

Qishen granule (QSG) is a frequently prescribed traditional Chinese medicine formula, which improves heart function in patients with heart failure (HF). However, the cardioprotective mechanisms of QSG have not been fully understood. The current study aimed to elucidate whether the effect of QSG is mediated by ameliorating cytoplasmic calcium (Ca) overload in cardiomyocytes. The HF rat model was induced by left anterior descending (LAD) artery ligation surgery. Rats were randomly divided into sham, model, QSG-low dosage (QSG-L) treatment, QSG-high dosage (QSG-H) treatment, and positive drug (diltiazem) treatment groups. 28 days after surgery, cardiac functions were assessed by echocardiography. Levels of norepinephrine (NE) and angiotensin II (AngII) in the plasma were evaluated. Expressions of critical proteins in the calcium signaling pathway, including cell membrane calcium channel CaV1.2, sarcoendoplasmic reticulum ATPase 2a (SERCA2a), calcium/calmodulin-dependent protein kinase type II (CaMKII), and protein phosphatase calcineurin (CaN), were measured by Western blotting (WB) and immunohistochemistry (IHC). Echocardiography showed that left ventricular ejection fraction (EF) and fractional shortening (FS) value significantly decreased in the model group compared to the sham group, and illustrating heart function was severely impaired. Furthermore, levels of NE and AngII in the plasma were dramatically increased. Expressions of CaV1.2, CaMKII, and CaN in the cardiomyocytes were upregulated, and expressions of SERCA2a were downregulated in the model group. After treatment with QSG, both EF and FS values were increased. QSG significantly reduced levels of NE and AngII in the plasma. In particular, QSG prevented cytoplasmic Ca overload by downregulating expression of CaV1.2 and upregulating expression of SERCA2a. Meanwhile, expressions of CaMKII and CaN were inhibited by QSG treatment. In conclusion, QSG could effectively promote heart function in HF rats by restoring cardiac Ca homeostasis. These findings revealed novel therapeutic mechanisms of QSG and provided potential targets in the treatment of HF.
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http://dx.doi.org/10.1155/2020/1868974DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7603572PMC
October 2020

Uric acid drives intestinal barrier dysfunction through TSPO-mediated NLRP3 inflammasome activation.

Inflamm Res 2021 Jan 19;70(1):127-137. Epub 2020 Oct 19.

Medical Research Center, Affiliated Hospital of Qingdao University, No. 167, Wutai Mountain Road, Qingdao, 266003, People's Republic of China.

Background And Aim: Intestinal epithelial dysfunction is the foundation of various intestinal and extra-intestinal diseases, while the effects and mechanism of uric acid on the intestinal barrier are little known. TSPO has been shown to be related to the generation of ROS and is involved in regulating inflammation, whether uric acid drives intestinal epithelial dysfunction through TSPO-mediated NLRP3 inflammasome activation is unknown.

Methods: UOX gene knockout mouse (UOX-/-) were used for models of hyperuricemia. Fluorescein isothiocyanate (FITC)-labeled dextran was used to assess in vivo intestinal permeability. Serum lipopolysaccharide (LPS) and culture supernatants IL-1β were measured using ELISA Kit. IEC-6 exposed to different concentrations of uric acid was used for in vitro experiment. Protein content and mRNA were assessed using Western blotting and Q-PCR, respectively. Intracellular ROS was determined using flow cytometry and fluorescence microscope. Mitochondrial membrane potential was detected on an immunofluorescence. Small interfering RNA transfection was used to assess the interaction between translocator protein (TSPO) and NLRP3 inflammasome. N-acetyl-L-cysteine (NAC) was used as ROS scavenger.

Results: Our results showed that hyperuricemia mice were characteristic by increased intestinal permeability. Hyperuricemia upregulated TSPO, increased production of ROS and activated NLRP3 inflammasome, which resulted in lower expression of occludin and claudin-1. In vitro, we showed that soluble uric acid alone increased the expression of TSPO, depolarized mitochondrial membrane potential, increased ROS release and activated NLRP3 inflammasome, which further reduced the expression of occludin and claudin-1. Silencing TSPO suppressed NLRP3 inflammasome activation and increased expression of claudin-1 and occludin, which was accompanied by lower levels of ROS. Scavenging ROS also significantly inhibited NLRP3 inflammasome activation without change of TSPO, indicating that TSPO-mediated NLRP3 inflammasome activation was dependent on ROS.

Conclusions: In conclusion, uric acid drives intestinal barrier dysfunction through TSPO-mediated NLRP3 inflammasome.
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http://dx.doi.org/10.1007/s00011-020-01409-yDOI Listing
January 2021

Genetic substructure and admixture of Mongolians and Kazakhs inferred from genome-wide array genotyping.

Ann Hum Biol 2020 Dec 23;47(7-8):620-628. Epub 2020 Nov 23.

Department of Anthropology and Ethnology, Institute of Anthropology, National Institute for Data Science in Health and Medicine, and School of Life Sciences, Xiamen University, Xiamen, China.

Background: Mongolian populations are widely distributed geographically, showing abundant ethnic diversity with geographic and tribal differences.

Aim: To infer the genetic substructure, admixture and ancient genetic sources of Mongolians together with Kazakhs.

Subjects And Methods: We genotyped more than 690,000 genome-wide SNPs from 33 Mongolian and Chinese Kazakh individuals and compared these with both ancient and present-day Eurasian populations using Principal Component Analysis (PCA), ADMIXTURE, -IBD, statistics, and .

Results: We found genetic substructures within Mongolians corresponding to Ölöd, Chahar, and Inner Mongolian clusters, which was consistent with tribe classifications. Mongolian and Kazakh groups derived about 6-40% of West Eurasian related ancestry, most likely from Bronze Age Steppe populations. The East Asian related ancestry in Mongolian and Kazakh groups was well represented by the Neolithic DevilsCave related nomadic lineage, comprising 42-64% of studied groups. We also detected 10-51% of Han Chinese related ancestry in Mongolian and Kazakh groups, especially in Inner Mongolians. The average admixture times for Inner Mongolian, Mongolian_Chahar, Mongolian_Ölöd and Chinese Kazakh were about 1381, 626, 635 and 632 years ago, respectively, with Han and French as the sources.

Conclusion: The DevilsCave related ancestry was once widespread westwards covering a wide geographical range from Far East Russia to the Mongolia Plateau. The formation of present-day Mongolic and Turkic-speaking populations has also received genetic influence from agricultural expansion.
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http://dx.doi.org/10.1080/03014460.2020.1837952DOI Listing
December 2020

Identification of functional cooperative mutations of GNAO1 in human acute lymphoblastic leukemia.

Blood 2021 03;137(9):1181-1191

State Key Laboratory of Oncogenes and Related Genes, Renji-Med X Clinical Stem Cell Research Center, Ren Ji Hospital, Shanghai Cancer Institute, School of Medicine, Shanghai Jiao Tong University, Shanghai, China; and.

Leukemogenesis is characterized by chromosomal rearrangements with additional molecular disruptions, yet the cooperative mechanisms are still unclear. Using whole-exome sequencing of a pair of monozygotic twins who were discordant for childhood acute lymphoblastic leukemia (ALL) with ETV6-RUNX1 (E/R) gene fusion successively after birth, we identified the R209C mutation of G protein subunit α o1 (GNAO1) as a new ALL risk loci. Moreover, GNAO1 missense mutations are recurrent in ALL patients and are associated with E/R fusion. Ectopic expression of the GNAO1 R209C mutant increased its GTPase activity and promoted cell proliferation and cell neoplastic transformation. Combined with the E/R fusion, the GNAO1 R209C mutation promoted leukemogenesis through activating PI3K/Akt/mTOR signaling. Reciprocally, activated mTORC1 phosphorylated p300 acetyltransferase, which acetylated E/R and thereby enhanced the E/R transcriptional activity of GNAO1 R209C. Thus, our study provides clinical evidence of the functional cooperation of GNAO1 mutations and E/R fusion, suggesting GNAO1 as a therapeutic target in human leukemia.
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http://dx.doi.org/10.1182/blood.2020005622DOI Listing
March 2021

Demography of Thrips palmi (Thysanoptera: Thripidae) Reared on Brassica oleracea (Brassicales: Brassicaceae) and Phaseolus vulgaris (Fabales: Fabaceae) With Discussion on the Application of the Bootstrap Technique in Life Table Research.

J Econ Entomol 2020 10;113(5):2390-2398

College of Plant Health and Medicine, Qingdao Agricultural University, Qingdao, China.

In order to contrast the fitness of Thrips palmi Karny reared on two of its hosts plants, Brassica oleracea L. leaves and Phaseolus vulgaris L. beans, life tables were constructed for T. palmi individuals reared on the two hostplants at 25°C using the age-stage, two-sex life table. The durations of the egg, first instar larva, pupa, and total immature stages of T. palmi reared on P. vulgaris were significantly longer than those reared on B. oleracea, whereas the adult preoviposition period, female adult longevity, and number of oviposition days of T. palmi reared on B. oleracea were significantly longer/greater than those on P. vulgaris. The fecundity (F) of T. palmi reared on B. oleracea (159.71 offspring/female) was significantly higher than in females reared on P. vulgaris (F = 122.98 offspring/female) despite the higher proportion of female adults that emerged on P. vulgaris. Although there were no significant differences in the intrinsic rate of increase (r), finite rate (λ), net reproductive rate (R0), and mean generation time (T) between the two populations, computer projection showed that the T. palmi population will increase faster when reared on B. oleracea than on P. vulgaris. Our results demonstrate that population projection based on life table data is potentially an important tool in pest management. Furthermore, we used the bootstrap technique to demonstrate the variable effect that survival rate and fecundity at different ages can have on population parameters.
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http://dx.doi.org/10.1093/jee/toaa171DOI Listing
October 2020

Green One-Step Synthesis of Medical Nanoagents for Advanced Radiation Therapy.

Nanotechnol Sci Appl 2020 7;13:61-76. Epub 2020 Aug 7.

Université Paris Saclay, CNRS UMR 8214, Institut des Sciences Moléculaires d'Orsay, 91405 Orsay, France.

Purpose: Metal-based nanoparticles (M-NPs) have attracted great attention in nanomedicine due to their capacity to amplify and improve the tumor targeting of medical beams. However, their simple, efficient, high-yield and reproducible production remains a challenge. Currently, M-NPs are mainly synthesized by chemical methods or radiolysis using toxic reactants. The waste of time, loss of material and potential environmental hazards are major limitations.

Materials And Methods: This work proposes a simple, fast and green strategy to synthesize small, non-toxic and stable NPs in water with a 100% production rate. Ionizing radiation is used to simultaneously synthesize and sterilize the containing NPs solutions. The synthesis of platinum nanoparticles (Pt NPs) coated with biocompatible poly(ethylene glycol) ligands (PEG) is presented as proof of concept. The physicochemical properties of NPs were studied by complementary specialized techniques. Their toxicity and radio-enhancing properties were evaluated in a cancerous in vitro model. Using plasmid nanoprobes, we investigated the elementary mechanisms underpinning radio-enhancement.

Results And Discussion: Pt NPs showed nearly spherical-like shapes and an average hydrodynamic diameter of 9 nm. NPs are zero-valent platinum successfully coated with PEG. They were found non-toxic and have the singular property of amplifying cell killing induced by γ-rays (14%) and even more, the effects of carbon ions (44%) used in particle therapy. They induce nanosized-molecular damage, which is a major finding to potentially implement this protocol in treatment planning simulations.

Conclusion: This new eco-friendly, fast and simple proposed method opens a new era of engineering water-soluble biocompatible NPs and boosts the development of NP-aided radiation therapies.
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http://dx.doi.org/10.2147/NSA.S257392DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7426062PMC
August 2020

Corrigendum to "Antiapoptosis and Antifibrosis Effects of Granules on Heart Failure Rats via Hippo Pathway".

Biomed Res Int 2020 1;2020:8569251. Epub 2020 Jul 1.

School of Life Science, Beijing University of Chinese Medicine, Beijing 100029, China.

[This corrects the article DOI: 10.1155/2019/1642575.].
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http://dx.doi.org/10.1155/2020/8569251DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7368950PMC
July 2020

Soluble uric acid induces inflammation via TLR4/NLRP3 pathway in intestinal epithelial cells.

Iran J Basic Med Sci 2020 Jun;23(6):744-750

Medical Research Center, the Affiliated Hospital of Qingdao University, Qingdao, Shandong Province, 266000, P. R. China.

Objectives: Hyperuricemia is a risk for cardiovascular and metabolic diseases, but the mechanism is ambiguous. Increased intestinal permeability is correlated with metabolic syndrome risk factors. Intestinal epithelial cells play a pivotal role in maintaining intestinal permeability. Uric acid is directly eliminated into intestinal lumen, however, the mechanism and effect of uric acid on intestinal epithelial cells is poorly explored. Here we carried out an analysis to identify the effect and mechanism of uric acid on intestinal epithelial cells.

Materials And Methods: IEC-6 was exposed to different concentrations of uric acid to simulate the effect of uric acid on intestinal epithelial cells. Cell viability was determined by MTS assay. Protein content and mRNA were assessed using Western blotting and Q-PCR, respectively. Intracellular ROS was determined using flow-cytometry and fluorescence microscopy. Mitochondrial membrane potential was detected by immunofluorescence using a mitochondrial membrane potential assay kit with JC-1. Small interfering RNA transfection was used to suppress the expression of TLR4.

Results: We found soluble uric acid alone increased the release of ROS, depolarized the mitochondrial membrane potential, up-regulated TSPO, increased the expression of TLR4 and NLRP3, and then activated NLRP3 inflammasome and NF-κB signaling, which further resulted in lower expression of tight junction protein and exerted adverse effects on intestinal epithelial cells. Furthermore, the elevated IL-1β could be restored by silencing of TLR4, indicating soluble uric acid induces inflammation via the TLR4/NLRP3 pathway.

Conclusion: Soluble uric acid exerted detrimental effect on intestinal epithelial cells through the TLR4/NLRP3 pathway.
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http://dx.doi.org/10.22038/ijbms.2020.44948.10482DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7351448PMC
June 2020

Human Serum Albumin in the Presence of AGuIX Nanoagents: Structure Stabilisation without Direct Interaction.

Int J Mol Sci 2020 Jun 30;21(13). Epub 2020 Jun 30.

Université Paris-Saclay, CNRS, Institut des Sciences Moléculaires d'Orsay, 91405 Orsay, France.

The gadolinium-based nanoagent named AGuIX is a unique radiosensitizer and contrast agent which improves the performance of radiotherapy and medical imaging. Currently tested in clinical trials, AGuIX is administrated to patients via intravenous injection. The presence of nanoparticles in the blood stream may induce harmful effects due to undesired interactions with blood components. Thus, there is an emerging need to understand the impact of these nanoagents when meeting blood proteins. In this work, the influence of nanoagents on the structure and stability of the most abundant blood protein, human serum albumin, is presented. Synchrotron radiation circular dichroism showed that AGuIX does not bind to the protein, even at the high ratio of 45 nanoparticles per protein at 3 mg/L. However, it increases the stability of the albumin. Isothermal thermodynamic calorimetry and fluorescence emission spectroscopy demonstrated that the effect is due to preferential hydration processes. Thus, this study confirms that intravenous injection of AGuIX presents limited risks of perturbing the blood stream. In a wider view, the methodology developed in this work may be applied to rapidly evaluate the impact and risk of other nano-products that could come into contact with the bloodstream.
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http://dx.doi.org/10.3390/ijms21134673DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7369717PMC
June 2020

A trusted medical image super-resolution method based on feedback adaptive weighted dense network.

Artif Intell Med 2020 06 16;106:101857. Epub 2020 May 16.

College of Electrical Engineering, Sichuan University, Chengdu, Sichuan 610065, China.

High-resolution (HR) medical images are preferred in clinical diagnoses and subsequent analysis. However, the acquisition of HR medical images is easily affected by hardware devices. As an effective and trusted alternative method, the super-resolution (SR) technology is introduced to improve the image resolution. Compared with traditional SR methods, the deep learning-based SR methods can obtain more clear and trusted HR images. In this paper, we propose a trusted deep convolutional neural network-based SR method named feedback adaptive weighted dense network (FAWDN) for HR medical image reconstruction. Specifically, the proposed FAWDN can transmit the information of the output image to the low-level features by a feedback connection. To explore advanced feature representation and reduce the feature redundancy in dense blocks, an adaptive weighted dense block (AWDB) is introduced to adaptively select the informative features. Experimental results demonstrate that our FAWDN outperforms the state-of-the-art image SR methods and can obtain more clear and trusted medical images than comparative methods.
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http://dx.doi.org/10.1016/j.artmed.2020.101857DOI Listing
June 2020
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