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1.
Elife ; 102021 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-33646122

RESUMO

Osteoarthritis, a highly prevalent degenerative joint disorder, is characterized by joint pain and disability. Available treatments fail to modify osteoarthritis progression and decrease joint pain effectively. Here, we show that intermittent parathyroid hormone (iPTH) attenuates osteoarthritis pain by inhibiting subchondral sensory innervation, subchondral bone deterioration, and articular cartilage degeneration in a destabilized medial meniscus (DMM) mouse model. We found that subchondral sensory innervation for osteoarthritis pain was significantly decreased in PTH-treated DMM mice compared with vehicle-treated DMM mice. In parallel, deterioration of subchondral bone microarchitecture in DMM mice was attenuated by iPTH treatment. Increased level of prostaglandin E2 in subchondral bone of DMM mice was reduced by iPTH treatment. Furthermore, uncoupled subchondral bone remodeling caused by increased transforming growth factor ß signaling was regulated by PTH-induced endocytosis of the PTH type 1 receptor-transforming growth factor ß type 2 receptor complex. Notably, iPTH improved subchondral bone microarchitecture, and decreased level of prostaglandin E2 and sensory innervation of subchondral bone in DMM mice by acting specifically through PTH type 1 receptor in Nestin+ mesenchymal stromal cells. Thus, iPTH could be a potential disease-modifying therapy for osteoarthritis.

2.
Metab Brain Dis ; 36(4): 589-599, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33555497

RESUMO

BACKGROUND: Carbonic anhydrase II deficiency syndrome is an autosomal recessive osteopetrosis with renal tubular acidosis and cerebral calcifications. We tried to detect the causative mutation for carbonic anhydrase II deficiency syndrome in a five-generation Chinese family. MATERIALS AND METHODS: Genomic DNA was extracted from whole blood of the proband, his grandmother, parents, aunt, uncle and sister. The exomes were sequenced by whole exon sequencing followed by genetic analysis and Sanger sequencing validation. Then, physical and chemical properties studies and structure analysis were performed on mutated protein. Finally, Minigene model of vector plasmids for wild type and mutant type was constructed and transfected into human embryonic kidney 293T cells to further explore the expression change of CA2 transcript and protein after mutation. RESULTS: Sequencing and genetic analysis have revealed the homozygous nonsense mutation of CA2 gene (c.368G > A, p.W123X) in the exon 4 of chromosome 8 of the proband, while it was not found in his grandmother, parents, aunt, uncle and sister. Furthermore, Sanger sequencing in the proband and his parents validated the mutation. Properties and structure of mutated CA2 proteins changed after mutation, especially in change of protein modification and hindrance of zinc ions binding, which may lead to decreased protein expression level of CA2. CONCLUSIONS: We found a new homozygous nonsense mutation in CA2 gene (c.368G > A, p.W123X), which may be valuable in the early diagnosis and therapy of carbonic anhydrase II deficiency syndrome.

3.
J Biomed Opt ; 26(1)2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33386709

RESUMO

SIGNIFICANCE: Deep-tissue penetration by x-rays to induce optical responses of specific molecular reporters is a new way to sense and image features of tissue function in vivo. Advances in this field are emerging, as biocompatible probes are invented along with innovations in how to optimally utilize x-ray sources. AIM: A comprehensive review is provided of the many tools and techniques developed for x-ray-induced optical molecular sensing, covering topics ranging from foundations of x-ray fluorescence imaging and x-ray tomography to the adaptation of these methods for sensing and imaging in vivo. APPROACH: The ways in which x-rays can interact with molecules and lead to their optical luminescence are reviewed, including temporal methods based on gated acquisition and multipoint scanning for improved lateral or axial resolution. RESULTS: While some known probes can generate light upon x-ray scintillation, there has been an emergent recognition that excitation of molecular probes by x-ray-induced Cherenkov light is also possible. Emission of Cherenkov radiation requires a threshold energy of x-rays in the high kV or MV range, but has the advantage of being able to excite a broad range of optical molecular probes. In comparison, most scintillating agents are more readily activated by lower keV x-ray energies but are composed of crystalline inorganic constituents, although some organic biocompatible agents have been designed as well. Methods to create high-resolution structured x-ray-optical images are now available, based upon unique scanning approaches and/or a priori knowledge of the scanned x-ray beam geometry. Further improvements in spatial resolution can be achieved by careful system design and algorithm optimization. Current applications of these hybrid x-ray-optical approaches include imaging of tissue oxygenation and pH as well as of certain fluorescent proteins. CONCLUSIONS: Discovery of x-ray-excited reporters combined with optimized x-ray scan sequences can improve imaging resolution and sensitivity.

4.
Artigo em Inglês | MEDLINE | ID: mdl-33444695

RESUMO

PURPOSE: In this study, procedures were developed to achieve efficient reversible conversion of a clinical linear accelerator (LINAC) and deliver ultrahigh-dose-rate (UHDR) electron or conventional beams to the treatment room isocenter for FLASH radiation therapy. METHODS AND MATERIALS: The LINAC was converted to deliver UHDR beam within 20 minutes by retracting the x-ray target from the beam's path, positioning the carousel on an empty port, and selecting 10 MV photon beam energy in the treatment console. Dose rate surface and depth dose profiles were measured in solid water phantom at different field sizes with Gafchromic film and an optically stimulated luminescent dosimeter (OSLD). A pulse controller counted the pulses via scattered radiation signal and gated the delivery for a preset pulse count. A fast photomultiplier tube-based Cherenkov detector measured the per pulse beam output at a 2-ns sampling rate. After conversion back to clinical mode, conventional beam output, flatness, symmetry, field size, and energy were measured for all clinically commissioned energies. RESULTS: The surface average dose rates at the isocenter for 1-cm diameter and 1.5-in diameter circular fields and for a jaws-wide-open field were 238 ± 5 Gy/s, 262 ± 5 Gy/s, and 290 ± 5 Gy/s, respectively. The radial symmetry of the beams was within 2.4%, 0.5%, and 0.2%, respectively. The doses from simultaneous irradiation of film and OSLD were within 1%. The photomultiplier tube showed the LINAC required ramp up time in the first 4 to 6 pulses before the output stabilized, after which its stability was within 3%. CONCLUSIONS: At the isocenter of the treatment room, 10 MeV UHDR beams were achieved. The beam output was reproducible but requires further investigation of the ramp up time, equivalent to ∼1 Gy, requiring dose monitoring. The UHDR beam can irradiate both small and large subjects to investigate potential FLASH radiobiological effects in minimally modified clinical settings, and the dose rate can be further increased by reducing the source-to-surface distance.

5.
Bone Res ; 9(1): 7, 2021 Jan 29.
Artigo em Inglês | MEDLINE | ID: mdl-33514693

RESUMO

Low back pain (LBP), as a leading cause of disability, is a common musculoskeletal disorder that results in major social and economic burdens. Recent research has identified inflammation and related signaling pathways as important factors in the onset and progression of disc degeneration, a significant contributor to LBP. Inflammatory mediators also play an indispensable role in discogenic LBP. The suppression of LBP is a primary goal of clinical practice but has not received enough attention in disc research studies. Here, an overview of the advances in inflammation-related pain in disc degeneration is provided, with a discussion on the role of inflammation in IVD degeneration and pain induction. Puncture models, mechanical models, and spontaneous models as the main animal models to study painful disc degeneration are discussed, and the underlying signaling pathways are summarized. Furthermore, potential drug candidates, either under laboratory investigation or undergoing clinical trials, to suppress discogenic LBP by eliminating inflammation are explored. We hope to attract more research interest to address inflammation and pain in IDD and contribute to promoting more translational research.

6.
Redox Biol ; 38: 101813, 2020 Nov 25.
Artigo em Inglês | MEDLINE | ID: mdl-33279869

RESUMO

Diabetic kidney disease is known as a major cause of chronic kidney disease and end stage renal disease. Polysulfides, a class of chemical agents with a chain of sulfur atoms, are found to confer renal protective effects in acute kidney injury. However, whether a polysulfide donor, sodium tetrasulfide (Na2S4), confers protective effects against diabetic nephropathy remains unclear. Our results showed that Na2S4 treatment ameliorated renal dysfunctional and histological damage in diabetic kidneys through inhibiting the overproduction of inflammation cytokine and reactive oxygen species (ROS), as well as attenuating renal fibrosis and renal cell apoptosis. Additionally, the upregulated phosphorylation and acetylation levels of p65 nuclear factor κB (p65 NF-κB) and signal transducer and activator of transcription 3 (STAT3) in diabetic nephropathy were abrogated by Na2S4 in a sirtuin-1 (SIRT1)-dependent manner. In renal tubular epithelial cells, Na2S4 directly sulfhydrated SIRT1 at two conserved CXXC domains (Cys371/374; Cys395/398), then induced dephosphorylation and deacetylation of its targeted proteins including p65 NF-κB and STAT3, thereby reducing high glucose (HG)-caused oxidative stress, cell apoptosis, inflammation response and epithelial-to-mesenchymal transition (EMT) progression. Most importantly, inactivation of SIRT1 by a specific inhibitor EX-527, small interfering RNA (siRNA), a de-sulfhydration reagent dithiothreitol (DTT), or mutation of Cys371/374 and Cys395/398 sites at SIRT1 abolished the protective effects of Na2S4 on diabetic kidney insulting. These results reveal that polysulfides may attenuate diabetic renal lesions via inactivation of p65 NF-κB and STAT3 phosphorylation/acetylation through sulfhydrating SIRT1.

7.
Diabetes Metab Syndr Obes ; 13: 4507-4517, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33262626

RESUMO

Aim: More than half of microRNAs are located in genes. LncRNAs are host genes of intronic microRNAs that regulate intracellular splicing to form pre-miRNAs that are processed to mature miRNAs. MicroRNAs work as partners or antagonists of their host lncRNAs by fine-tuning their target genes. However, whether lncRNA-MIR503HG (miR-503 host gene) is co-transcribed with miR-503 and affects miR-503 splicing, thereby affecting its target gene Bcl-2 expression and cell mitochondrial apoptotic pathway in diabetic nephropathy (DN) is currently unknown. Methods: Human proximal tubular (HK-2) cells cultured in high glucose were transfected with lncRNA MIR503HG overexpression/inhibition plasmid and miR-503 mimics/inhibitor. Real-time quantitative PCR was used to measure the expression levels of lncRNA MIR503HG, pre-miR-503, miR-503 and Bcl-2. Western blot was used to measure the protein expressions of Bcl-2, Bax, Cytc and cleaved-caspase 9/3. Annexin V/PI flow cytometry was used to measure apoptosis. Results: Host lncRNA MIR503HG was co-transcribed with miR-503. MIR503HG regulated the expression of miR-503 by affecting miR-503 splicing synthesis. In the presence of high glucose, the expression levels of lncRNA MIR503HG and miR-503 were up-regulated in HK-2 cells cultured in high glucose. Bcl-2 expression was inhibited and levels of apoptosis-related proteins Cytc and Bax were increased in HK-2 cells cultured in high glucose, all of which promoted the caspase cascade reaction, leading to increased caspase-9 and caspase-3 shear fragments inducing apoptosis of the mitochondrial pathway. Inhibition of MIR503HG led to a reduction in miR-503 expression, up-regulated its target gene Bcl-2, inhibited the expression levels of Bax and other apoptosis-related proteins and attenuated HK-2 cell apoptosis induced by high glucose. Co-transfection of miRNA-503 partially offset the effect of MIR503HG-siRNA. Conclusion: MIR503HG indirectly regulates Bcl-2 by promoting the co-transcription of miRNA-503 to participate high-glucose-induced proximal tubular cell apoptosis, providing a new target for diabetic nephropathy treatment.

8.
Sensors (Basel) ; 20(24)2020 Dec 08.
Artigo em Inglês | MEDLINE | ID: mdl-33302521

RESUMO

In the era of big data, longer time series fault signals will not only be easy to copy and store, but also reduce the labor cost of manual labeling, which can better meet the needs of industrial big data. Aiming to effectively extract the key classification information from a longer time series of bearing vibration signals and achieve high diagnostic accuracy under noise and different load conditions. The one-dimensional adaptive long sequence convolutional network (ALSCN) is proposed. ALSCN can better extract features directly from high-dimensional original signals without manually extracting features and relying on expert knowledge. By adding two improved multi-scale modules, ALSCN can not only extract important features efficiently from noise signals, but also alleviate the problem of losing key information due to continuous down-sampling. Moreover, a Bayesian optimization algorithm is constructed to automatically find the best combination of hyperparameters in ALSCN. Based on two bearing data sets, the model is compared with traditional model such as SVM and deep learning models such as convolutional neural networks (CNN) et al. The results prove that ALSCN has a higher diagnostic accuracy rate on 5120-dimensional sequences under -5 signal to noise ratio (SNR) with better generalization.

9.
Front Cell Dev Biol ; 8: 553733, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33304897

RESUMO

Background: Radioresistance is a major challenge in the use of radiotherapy for the treatment of lung cancer while microRNAs (miRs) have been reported to participate in multiple essential cellular processes including radiosensitization. This study was conducted with the main objective of investigating the potential role of miR-320a in radioresistance of non-small cell lung cancer (NSCLC) via the possible mechanism related to HIF1α, KDM5B, and PTEN. Methods: Firstly, NSCLC radiosensitivity-related microarray dataset GSE112374 was obtained. Then, the expression of miR-320a, HIF1α, KDM5B, and PTEN was detected in the collected clinical NSCLC samples, followed by Pearson's correlation analysis. Subsequently, ChIP assay was conducted to determine the content of the PTEN promoter fragment enriched by the IgG antibody and H3K4me3 antibody. Finally, a series of in vitro and in vivo assays were performed in order to evaluate the effects of miR-320a on radioresistance of NSCLC with the involvement of HIF1α, KDM5B, and PTEN. Results: The microarray dataset GSE112374 presented with a high expression of miR-320a in NSCLC radiosensitivity samples, which was further confirmed in our clinical samples with the use of reverse transcription-quantitative polymerase chain reaction. Moreover, miR-320a negatively targeted HIF1α, inhibiting radioresistance of NSCLC. Interestingly, miR-320a suppressed the expression of KDM5B, and KDM5B was found to enhance the radioresistance of NSCLC through the downregulation of PTEN expression. The inhibition of miR-320a in radioresistance of NSCLC was also reproduced by in vivo assay. Conclusion: Taken together, our findings were suggestive of the inhibitory effect of miR-320a on radioresistance of NSCLC through HIF1α-suppression mediated methylation of PTEN.

10.
Aging (Albany NY) ; 122020 Nov 24.
Artigo em Inglês | MEDLINE | ID: mdl-33231567

RESUMO

OBJECTIVE: Tumor necrosis factor superfamily protein 14 (TNFSF14) was recently identified as a risk factor in some fibrosis diseases. However, the role of TNFSF14 in renal fibrosis pathogenesis remains unknown. RESULTS: It was found that TNFSF14 levels were significantly increased both in UUO-induced renal fibrotic mice and in patients with fibrotic nephropathy, compared with those in controls. Accordingly, Tnfsf14 deficiency led to a marked reduction in renal fibrosis lesions and inflammatory cytokines expression in the UUO mice. Furthermore, the levels of Sphk1, a critical molecule that causes fibrotic nephropathy, were remarkably reduced in Tnfsf14 KO mice with UUO surgery. In vitro recombinant TNFSF14 administration markedly up-regulated the expression of Sphk1 of primary mouse renal tubular epithelial cells (mTECs). CONCLUSION: TNFSF14 is a novel pro-fibrotic factor of renal fibrosis, for which TNFSF14 up-regulates Sphk1 expression, which may be the underlying mechanism of TNFSF14-mediated renal fibrosis. METHODS: We investigated the effect of TNFSF14 on renal fibrosis and the relationship between TNFSF14 and pro-fibrotic factor sphingosine kinase 1 (Sphk1) by using the unilateral urethral obstruction (UUO)-induced mice renal fibrosis as a model and the specimen of patients with fibrosis nephropathy, by Masson trichrome staining, immunohistochemistry, qRT-PCR, and western blot analysis.

11.
Opt Lett ; 45(22): 6130-6133, 2020 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-33186932

RESUMO

Cherenkov light induced from megavolt (MV) X-rays during external beam radiotherapy serves as an internal light source to excite phosphors or fluorophores within biological tissues for molecular imaging. The broad spectrum of Cherenkov light leads to significant spectral overlap with any luminescence emission and, to overcome this problem, a single pixel hyperspectral imaging methodology was demonstrated here by coupling the detection with light sheet scanning and filtered back projection reconstruction of hyperspectral images. Thin scanned sheets of MV X-rays produce Cherenkov light to illuminate the planes deep within the tissue-simulating media. A fluorescence probe was excited by Cherenkov light, and a complete hyperspectral sinogram of the data was obtained through translation and rotation of the beam. Hyperspectral 2D images finally were reconstructed. Through this approach of spectral unmixing, it was possible to resolve hyperspectral images of both the Cherenkov and resulting fluorescence intensity from molecular sensors.

12.
J AOAC Int ; 2020 Aug 10.
Artigo em Inglês | MEDLINE | ID: mdl-33216865

RESUMO

BACKGROUND: Although more information has become available on the occurrence of phthalates and di(2-ethylhexyl) adipate (DEHA) in foods including cow's milk, information on their presence in human milk, the important and recommended sole diet for infants up to six months of age, is very limited, especially for DEHA. OBJECTIVE: To develop a GC-MS method for simultaneous analysis of DEHA and phthalates in human milk samples and generate occurrence data for exposure assessment. METHOD: Human milk samples were extracted with acetonitrile followed by dispersive solid-phase extraction and GC-MS analysis. RESULTS: Among the 305 human milk samples collected from the Canadian Maternal-Infant Research on Environmental Chemicals Study, some phthalates (DHxP, BBzP, and DOP) were not detected in any of the samples, while DEHA and the other phthalates (DMP, DEP, DBP, DiBP, and DEHP) were detected at low frequencies with levels from 30.4-237 ng/g in up to 31 of the 305 human milk samples. CONCLUSIONS: In general, DEHA and phthalates were detected at low frequencies and low levels in the 305 human milk samples. HIGHLIGHTS: A GC-MS method based on dispersive solid phase extraction was developed for analysis of DEHA and eight phthalates in 305 human milk samples for exposure assessment.

13.
Artigo em Inglês | MEDLINE | ID: mdl-33153172

RESUMO

PURPOSE: The aim of this study was to evaluate the home-based physical activity (PA) environmental characteristics, and different types of physical behavior level of adolescents in different genders, and explore the impact of different domains of home-based PA environmental factors on different physical behaviors of adolescents in different genders. METHODS: Five hundred forty-four adolescents aged from 12 to 18 years old (males: n = 358, females: n = 186) and their parents were analyzed in this cross-sectional survey. The volume of various physical behaviors of all adolescent subjects were measured by the ActiGraph wGT3X-BT accelerometer, and the level in different domains of home-based environmental characteristics were assessed by the Gattshall's home-based PA environment questionnaire, which was answered by adolescents' parents. The difference in the volume of different physical behaviors was examined using Kruskal-Wallis analysis. The difference in home physical environment and home social environment for adolescents was examined using one-way analysis of variance (ANOVA). Multiple linear regression analysis in the adjusted model was used to evaluate the influence of different home-based PA environmental domains (PA availability, PA accessibility, Parental role-modeling of PA, and Parental policies around PA) on different physical behaviors (sedentary behavior, SB; light-intensity physical activity, LPA; and moderate-vigorous physical activity, MVPA) of adolescents (boys and girls). RESULTS: The volume of LPA and MVPA, the score of PA accessibility in the home physical environment, and the score of home social environment of boys are significantly higher than those of girls, while the SB volume of boys is significantly lower than that of girls. The PA availability, the parents' role-modeling of PA in same-sex parent-child dyads, and the parents' policies around PA in opposite-sex parent-child dyads are significantly associated with adolescents' decreased SB and increased LPA and MVPA. CONCLUSION: There is significant gender difference in adolescents' physical behaviors and home-based environmental characteristics, as well as in the association between adolescents' physical behaviors and their home-based environment. The PA availability, the parents' role-modeling of PA in same-sex parent-child dyads, and the parents' policies around PA in opposite-sex parent-child dyads can significantly promote adolescents' healthy physical behaviors.

15.
J Biomed Opt ; 25(11)2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-33236619

RESUMO

SIGNIFICANCE: The necessity to use exogenous probes for optical oxygen measurements in radiotherapy poses challenges for clinical applications. Options for implantable probe biotechnology need to be improved to alleviate toxicity concerns in human use and facilitate translation to clinical trial use. AIM: To develop an implantable oxygen sensor containing a phosphorescent oxygen probe such that the overall administered dose of the probe would be below the Federal Drug Administration (FDA)-prescribed microdose level, and the sensor would provide local high-intensity signal for longitudinal measurements of tissue pO2. APPROACH: PtG4, an oxygen quenched dendritic molecule, was mixed into an agarose matrix at 100 µM concentration, allowing for local injection into tumors at the total dose of 10 nmol per animal, forming a gel at the site of injection. Cherenkov-excited luminescence imaging (CELI) was used to acquire the phosphorescence and provide intratumoral pO2. RESULTS: Although PtG4 does not form covalent bonds with agarose and gradually leaches out into the surrounding tissue, its retention time within the gel was sufficiently long to demonstrate the capability to measure intratumoral pO2 with the implantable gel sensors. The sensor's performance was first evaluated in vitro in tissue simulation phantoms, and then the sensor was used to measure changes in oxygen in MDA-MB-231 tumors during hypofractionated radiotherapy. CONCLUSIONS: Our study demonstrates that implantable oxygen sensors in combination with CELI present a promising approach for quantifying oxygen changes during the course of radiation therapy and thus for evaluating the tumor response to radiation. By improving the design of the gel-probe composition in order to prevent leaching of the probe into the tissue, biosensors can be created that should allow longitudinal oxygen measurements in tumors by means of CELI while using FDA-compliant microdose levels of the probe and thus lowering toxicity concerns.

16.
Bone Res ; 8: 37, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33083097

RESUMO

The LIM domain-containing proteins Pinch1/2 regulate integrin activation and cell-extracellular matrix interaction and adhesion. Here, we report that deleting Pinch1 in limb mesenchymal stem cells (MSCs) and Pinch2 globally (double knockout; dKO) in mice causes severe chondrodysplasia, while single mutant mice do not display marked defects. Pinch deletion decreases chondrocyte proliferation, accelerates cell differentiation and disrupts column formation. Pinch loss drastically reduces Smad2/3 protein expression in proliferative zone (PZ) chondrocytes and increases Runx2 and Col10a1 expression in both PZ and hypertrophic zone (HZ) chondrocytes. Pinch loss increases sclerostin and Rankl expression in HZ chondrocytes, reduces bone formation, and increases bone resorption, leading to low bone mass. In vitro studies revealed that Pinch1 and Smad2/3 colocalize in the nuclei of chondrocytes. Through its C-terminal region, Pinch1 interacts with Smad2/3 proteins. Pinch loss increases Smad2/3 ubiquitination and degradation in primary bone marrow stromal cells (BMSCs). Pinch loss reduces TGF-ß-induced Smad2/3 phosphorylation and nuclear localization in primary BMSCs. Interestingly, compared to those from single mutant mice, BMSCs from dKO mice express dramatically lower protein levels of ß-catenin and Yap1/Taz and display reduced osteogenic but increased adipogenic differentiation capacity. Finally, ablating Pinch1 in chondrocytes and Pinch2 globally causes severe osteopenia with subtle limb shortening. Collectively, our findings demonstrate critical roles for Pinch1/2 and a functional redundancy of both factors in the control of chondrogenesis and bone mass through distinct mechanisms.

17.
Chin J Integr Med ; 2020 Oct 10.
Artigo em Inglês | MEDLINE | ID: mdl-33037518

RESUMO

OBJECTIVE: To evaluate whether the efficacy of Getong Tongluo Capsule (, GTC, consisted of total flavone of Radix Puerariae) on improving patients' quality of life and lowering blood pressure are superior to the extract of Ginkgo biloba (EGB) for patients with convalescent-phase ischemic stroke and primary hypertension. METHODS: This randomized, positive-drug- and placebo-controlled, double-blind trial was conducted from September 2015 to October 2017. Totally 477 eligible patients from 18 hospitals in China were randomly assigned in a 2:1:1 ratio to the following interventions, twice a day for 12 weeks: (1) GTC 250 mg plus EGB-matching placebo 40 mg (237 cases, GTC group), (2) EGB 40 mg plus GTC-matching placebo 250 mg (120 cases, EGB group) or (3) GTC-matching placebo 250 mg plus EGB-matching placebo 40 mg (120 cases, placebo group). Moreover, all patients were orally administered aspirin enteric-coated tablets 100 mg, once a day for 12 weeks. The primary outcome was the Barthel Index (BI). The secondary outcomes included the control rate of blood pressure and National Institutes of Health Stroke Scale (NIHSS) scores. The incidence and severity of adverse events (AEs) were calculated and assessed. RESULTS: The BI relative independence rates, the clinical recovery rates of NIHSS, and the total effective rates of NIHSS in the GTC and EGB groups were significantly higher than the placebo group at 12 weeks after treatment (P<0.05), and no statistical significance was found between the GTC and EGB groups (P>0.05). The control rate of blood pressure in the GTC group was significantly higher than the EGB and placebo groups at 12, 18 and 24 weeks after treatment (P<0.01). There were no statistically significant differences in the incidences of AEs, adverse drug reactions, or serious AEs among the 3 groups (P>0.05). CONCLUSION: GTC exhibited significant efficacy in improving patients' quality of life as well as neurological function and controlling hypertension. (Registration No. ChiCTR1800016667).

18.
Antonie Van Leeuwenhoek ; 113(12): 2053-2062, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33047275

RESUMO

A novel cellulase-producing actinomycete strain Gxj-6T, isolated from soil in the cold region (Heihe city, Heilongjiang province, the northernmost part of China), subjected to a taxonomic study using a polyphasic approach. In the neighbour-joining phylogenetic tree based on 16S rRNA gene sequences, strain Gxj-6T fell within the clade comprising the type strains of species of the genus Microbispora. 16S rRNA gene sequence similarity studies exhibited that species Gxj-6T was most closely related to Microbispora bryophytorum NEAU-TX2-2T (99.45%), Microbispora fusca NEAU-HEGS1-5T (99.41%), Microbispora camponoti 2C-HV3T (99.31%) and Microbispora rosea subsp. rosea JCM 3006T (98.68%). Organism Gxj-6T contained MK-9(H2) as the predominant ubiquinone and C18:0 10-methyl as the major fatty acid. The major polar lipids of culture Gxj-6T were diphosphatidylglycerol, phosphatidylethanolamine, phosphatidylinositol mannoside, three unidentified phospholipids, two unidentified glycolipids and two unidentified lipids. The DNA G+C content of strain Gxj-6T was 71.25 mol%. The morphological and chemotaxonomic properties of the strain are also consistent with those members of the genus Microbispora. Combinated with the lower DNA-DNA relatedness values, phenotypic properties, physiology and biochemistry distinctiveness with other recognized species strains, revealed that strain Gxj-6T is separated from other phylogenetically closely species of the genus Microbispora. Therefore, strain Gxj-6T is considered to represent a novel species of the genus Microbispora, for which the name Microbispora cellulosiformans sp. nov. is proposed. The type strain is Gxj-6T (= CGMCC 4.7605T = DSM 109712T).

19.
Small ; 16(43): e2004178, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-33000901

RESUMO

Enslaved to the large-size K-ions, the construction of suitable anode materials with superior and stable potassium-ion storage properties is a major challenge. 1T phase MoS2 possesses higher conductivity, bigger interlayer distance, and more electrochemically active sites than the 2H phase, which offers intriguing benefits for energy-related applications. In this work, the 1T/2H-phase hybrid MoS2 nanosheets are successfully anchored in the N-doped carbon nanotube hollow polyhedron (1T/2H-MoS2 /NCNHP) by a bottom-up solvothermal method. For the synthesized 1T/2H-MoS2 /NCNHP, the fewer-layer 1T/2H-MoS2 nanosheets are embedded in an N-doped carbon nanotube hollow polyhedron, with an enlarged interlayer spacing of 0.96 nm. When evaluated as anode material for potassium-ion batteries, the 1T/2H-MoS2 /NCNHP hybrid presents outstanding potassium storage performance. It delivers a high-specific capacity of 519.2 mAh g-1 at 50 mA g-1 and maintains 281.2 mAh g-1 at 1 A g-1 over 500 cycles. The good potassium-ion electrochemical performance is attributed to the rational structural design and the synergistic effect of the components. Moreover, the 1T-MoS2 nanosheet has excellent electrical conductivity and its enlarged interlayer spacing reduces the barrier for the embedding and stripping of K ions. Finally, the practical application of the 1T/2H-MoS2 /NCNHP electrode material is also evaluated by assembled K-ion full cells.

20.
Artigo em Inglês | MEDLINE | ID: mdl-33002542

RESUMO

PURPOSE: The extreme microscopic heterogeneity of tumors makes it difficult to characterize tumor hypoxia. We evaluated how changes in the spatial resolution of oxygen imaging could alter measures of tumor hypoxia and their correlation to radiation therapy response. METHODS AND MATERIALS: Cherenkov-Excited Luminescence Imaging (CELI) in combination with an oxygen probe, Oxyphor PtG4 was used to directly image tumor pO2 distributions with 0.2 mm spatial resolution at the time of radiation delivery. These pO2 images were analyzed with variations of reduced spatial resolution from 0.2 mm to 5 mm, to investigate the influence of how reduced imaging spatial resolution would affect the observed tumor hypoxia. As an in vivo validation test, mice bearing tumor xenografts were imaged for hypoxic fraction and median pO2 to examine the predictive link with tumor response to radiation therapy, while accounting for spatial resolution. RESULTS: In transitioning from voxel sizes of 200 µm to 3mm, the median pO2 values increased by a few mmHg, while the hypoxic fraction decreased by more than 50%. When looking at radiation-responsive tumors, the median pO2 values changed just a few mmHg as a result of treatment, while the hypoxic fractions changed by as much as 50%. This latter change, however, could only be seen when sampling was performed with high spatial resolution. Median pO2 or similar quantities obtained from low resolution measurements are commonly used in clinical practice, however these parameters are much less sensitive to changes in the tumor microenvironment than the tumor hypoxic fraction obtained from high-resolution oxygen images. CONCLUSIONS: This study supports the hypothesis that for adequate measurements of the tumor response to radiation therapy, oxygen imaging with high spatial resolution is required in order to accurately characterize the hypoxic fraction.

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