Publications by authors named "Ke Jiang"

227 Publications

2  Gbps free-space ultraviolet-C communication based on a high-bandwidth micro-LED achieved with pre-equalization.

Opt Lett 2021 May;46(9):2147-2150

In this Letter, we experimentally achieve high-speed ultraviolet-C (UVC) communication based on a 276.8 nm UVC micro-LED. A record ${-}{{3}}\;{\rm{dB}}$ optical bandwidth of 452.53 MHz and light output power of 0.854 mW at a current density of ${{400}}\;{\rm{A/c}}{{\rm{m}}^2}$ are obtained with a chip size of 100 µm. A UVC link over 0.5 m with a data rate of 2 Gbps is achieved using 16-ary quadrature amplitude modulation orthogonal frequency division multiplexing and pre-equalization, and an extended distance over 3 m with a data rate of 0.82 Gbps is also presented. The demonstrated high-speed performance shows that micro-LEDs have great potential in the field of UVC communication.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1364/OL.423311DOI Listing
May 2021

Unraveling Heterogeneity of Tumor Cells and Microenvironment and Its Clinical Implications for Triple Negative Breast Cancer.

Front Oncol 2021 29;11:557477. Epub 2021 Mar 29.

Department of Breast Diseases, Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, China.

Triple negative breast cancer (TNBC) is an aggressive subtype of breast cancer, characterized by extensive intratumoral heterogeneity. We aimed to systematically characterize the tumor heterogeneity of TNBC. Single-cell RNA sequencing (scRNA-seq) of TNBC cells were obtained from the GSE118389 and GSE75688 datasets. After integration of the two datasets, cell clustering analysis was performed using the Seurat package. According to the marker genes of cell cycle, cell cycle of each cell cluster was determined. Then, function enrichment analysis of marker genes in each cell cluster was performed, followed by ligand-receptor signaling network analysis. CIBERSORT was used to estimate the proportion of 22 immune cells in each sample based on RNA-seq data of 58 normal adjacent tissues and 101 TNBC tissues. After that, prognostic value of immune cells was assessed. In the integrated datasets, five cells types including B cells, myeloid cells, stromal cells, T cells, and tumor cells were clustered. Functional enrichment analysis revealed the functional heterogeneity of genes in each cell. Intercellular communication networks were conducted based on ligand-receptor pairs. The heterogeneity in the fractions of 22 immune cells was found in TNBC tissues. Furthermore, there was a significant difference in the fractions of these immune cells between adjacent normal tissues and TNBC tissues. Among them, M2 macrophages and neutrophils were significantly associated with clinical outcomes of TNBC. Moreover, the fractions of T cells CD4 memory resting, monocytes, neutrophils, M1 macrophages, and T cells CD4 memory activated were significantly correlated with clinical characteristics of TNBC. As shown in PCA results, these immune cells could significantly distinguish TNBC tissues into adjacent normal tissues. Our findings characterized the tumor heterogeneity of TNBC, which deepened the understanding of the complex interactions between tumor cells and their microenvironment, especially immune cells.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fonc.2021.557477DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8040954PMC
March 2021

Therapeutic targeting of FOS in mutant cancers through removing TERT suppression of apoptosis via regulating and .

Proc Natl Acad Sci U S A 2021 Mar;118(11)

Laboratory for Cellular and Molecular Thyroid Research, Division of Endocrinology, Diabetes, and Metabolism, The Johns Hopkins University School of Medicine, Baltimore, MD 21287

The telomerase reverse transcriptase (TERT) has long been pursued as a direct therapeutic target in human cancer, which is currently hindered by the lack of effective specific inhibitors of TERT. The FOS/GABPB/(mutant) cascade plays a critical role in the regulation of mutant , in which FOS acts as a transcriptional factor for to up-regulate the expression of GABPB, which in turn activates mutant but not wild-type promoter, driving TERT-promoted oncogenesis. In the present study, we demonstrated that inhibiting this cascade by targeting FOS using FOS inhibitor T-5224 suppressed mutant cancer cells and tumors by inducing robust cell apoptosis; these did not occur in wild-type cells and tumors. Mechanistically, among 35 apoptotic cascade-related proteins tested, the apoptosis induced in this process specifically involved the transcriptional activation of tumor necrosis factor-related apoptosis-inducing ligand receptor 2 () and inactivation of two key players in the apoptotic cascade, which normally initiate and suppress the apoptotic cascade, respectively. These findings with suppression of FOS were reproduced by direct knockdown of TERT and prevented by prior knockdown of TRAIL-R2. Further experiments demonstrated that TERT acted as a direct transcriptional factor of up-regulating its expression. Thus, this study identifies a therapeutic strategy for promoter mutation-driven cancers by targeting FOS in the FOS/GABPB/(mutant) cascade, circumventing the current challenge in pharmacologically directly targeting TERT itself. This study also uncovers a mechanism through which TERT controls cell apoptosis by transcriptionally regulating two key players in the apoptotic cascade.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1073/pnas.2022779118DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7980366PMC
March 2021

Quantum engineering of non-equilibrium efficient p-doping in ultra-wide band-gap nitrides.

Light Sci Appl 2021 Mar 31;10(1):69. Epub 2021 Mar 31.

State Key Laboratory of Luminescence and Applications, Changchun Institute of Optics, Fine Mechanics and Physics, Chinese Academy of Sciences, Dongnanhu Road No. 3888, Changchun, 130033, China.

Ultra-wide band-gap nitrides have huge potential in micro- and optoelectronics due to their tunable wide band-gap, high breakdown field and energy density, excellent chemical and thermal stability. However, their application has been severely hindered by the low p-doping efficiency, which is ascribed to the ultrahigh acceptor activation energy originated from the low valance band maximum. Here, a valance band modulation mode is proposed and a quantum engineering doping method is conducted to achieve high-efficient p-type ultra-wide band-gap nitrides, in which GaN quantum-dots are buried in nitride matrix to produce a new band edge and thus to tune the dopant activation energy. By non-equilibrium doping techniques, quantum engineering doped AlGaN:Mg with Al content of 60% is successfully fabricated. The Mg activation energy has been reduced to about 21 meV, and the hole concentration reaches higher than 10 cm at room temperature. Also, similar activation energies are obtained in AlGaN with other Al contents such as 50% and 70%, indicating the universality of the quantum engineering doping method. Moreover, deep-ultraviolet light-emission diodes are fabricated and the improved performance further demonstrates the validity and merit of the method. With the quantum material growth techniques developing, this method would be prevalently available and tremendously stimulate the promotion of ultra-wide band-gap semiconductor-based devices.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41377-021-00503-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8012702PMC
March 2021

Nuclear receptor coactivator 4-mediated ferritinophagy drives proliferation of dental pulp stem cells in hypoxia.

Biochem Biophys Res Commun 2021 May 27;554:123-130. Epub 2021 Mar 27.

Nanjing Stomatological Hospital, Medical School of Nanjing University, Nanjing, China. Electronic address:

Nuclear receptor coactivator 4 (NCOA4)-mediated ferritinophagy has been implicated in the ferroptosis in cancer cells and hematopoiesis in the bone marrow. However, the role of iron metabolism, especially NCOA4-mediated degradation of ferritin, has not been explored in the proliferation of mesenchymal stem cells. The present study was designed to explore the role of NCOA4-mediated ferritinophagy in hypoxia-treated dental pulp stem cells (DPSCs). Hypoxia treatment increased ROS generation, boosted cytosolic labile iron pool, increased expression of transferrin receptor 1 and NCOA4. Moreover, colocalization of LC3B with NCOA4 and ferritin was observed in hypoxia-treated DPSCs, indicating the development of ferritinophagy. Hypoxia promoted the proliferation of DPSCs, but not ferroptosis, under normal serum supplement and serum deprivation. NCOA4 knock-down reduced ferritin degradation and inhibited proliferation of DPSCs under hypoxia. Furthermore, the activation of hypoxia inducible factor 1α and p38 mitogen-activated protein kinase signaling pathway was involved in the upregulation of NCOA4 in hypoxia. Therefore, our present study suggested that NCOA4-mediated ferritinophagy promoted the level of labile iron pool, leading to enhanced iron availability and elevated cell proliferation of DPSCs. Our present study uncovered a physiological role of ferritinophagy in the proliferation and growth of mesenchymal stem cells under hypoxia.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.bbrc.2021.03.075DOI Listing
May 2021

Vortex laser beam generation from laser interaction with azimuthal plasma phase slab at relativistic intensities.

Phys Rev E 2021 Feb;103(2-1):023204

Center for Applied Physics and Technology, HEDPS, and School of Physics, Peking University, Beijing 100871, China.

It is shown theoretically and by simulation that a Gaussian laser beam of relativistic intensity interacting with a uniform-thickness plasma slab of azimuthally varying density can acquire orbital angular momentum (OAM). During the interaction, the laser ponderomotive force and the charge-separation force impose a torque on the plasma particles. The affected laser light and plasma ions gain oppositely directed axial OAM, but the plasma electrons remain almost OAM free. High OAM conversion efficiency is achieved due to the strong azimuthal electromagnetic energy flow during the laser phase modulation. The present scheme should provide useful reference for applications requiring relativistic-intense vortex light.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1103/PhysRevE.103.023204DOI Listing
February 2021

Effects of shRNA-mediated silencing of PDE5A3 on intracellular cGMP and free Ca levels and human prostate smooth muscle cell proliferation from benign prostatic hyperplasia.

Exp Ther Med 2021 Apr 5;21(4):322. Epub 2021 Feb 5.

Department of Andrology, Nanjing First Hospital, Nanjing Medical University, Nanjing, Jiangsu 210006, P.R. China.

Benign prostatic hyperplasia (BPH) with lower urinary tract symptoms (LUTS) is a common disease among elderly men, for which safe and effective treatment strategies remain limited. The aim of the present study was to explore the potential effects of phosphodiesterase 5A3 (PDE5A3) silencing on human prostate smooth muscle cells (HPSMCs). HPSMCs were initially obtained from patients with BPH/LUTS. Short hairpin RNA (shRNA) targeting the PDE5A3 gene was subsequently transfected into cultured HPSMCs. The expression of PDE5A3 was measured using reverse transcription-quantitative PCR and western blotting. cGMP levels were then measured using western blotting and immunocytochemical staining and intracellular Ca concentration was measured using rhod2-AM in HPSMCs after transfection. HPSMC proliferation was also observed within 4 days. Cells transfected with PDE5A3-shRNA2 exhibited the most notable decline in PDE5A3 expression compared with that in the Control or NC groups. cGMP levels in HPSMCs transfected with PDE5A3-shRNA2 was significantly increased compared with those in the Control or NC groups, whereas intracellular Ca concentrations in cells in the PDE5A3-shRNA2 group were decreased compared with that in the Control or NC groups. The proliferation of HPSMCs in the PDE5A3-shRNA2 group was also inhibited compared with that in the Control or NC groups after 72 h of culture. In conclusion, shRNA-mediated silencing of PDE5A3 was able to increase the levels of cGMP whilst reducing the concentration of Ca in HPSMCs, in turn suppressing their proliferation. These findings may potentially provide a novel therapeutic target for treating BPH/LUTS.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3892/etm.2021.9753DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7903389PMC
April 2021

Pharmaceutical immunoglobulin G impairs anti-carcinoma activity of oxaliplatin in colon cancer cells.

Br J Cancer 2021 Apr 9;124(8):1411-1420. Epub 2021 Feb 9.

Department of General Surgery, Molecular Oncology and Immunotherapy, Rostock University Medical Center, Schillingallee 69, 18057, Rostock, Germany.

Background: Recent evidence proves that intravenous human immunoglobulin G (IgG) can impair cancer cell viability. However, no study evaluated whether IgG application benefits cancer patients receiving chemotherapeutics.

Methods: Influence of pharmaceutical-grade human IgG on the viability of a series of patient-derived colon cancer cell lines with and without chemotherapeutic intervention was determined. Cell death was analysed flow cytometrically. In addition, the influence of oxaliplatin and IgG on the ERK1/2-signalling pathway was evaluated by western blots.

Results: We evaluated the effects of pharmaceutical IgG, such as PRIVIGEN IgG and Tonglu IgG, in combination with chemotherapeutics. We did not observe any significant effects of IgG on tumour cell viability directly; however, human IgG significantly impaired the anti-tumoral effects of oxaliplatin. Primary cancer cell lines express IgG receptors and accumulate human IgG intracellularly. Moreover, while oxaliplatin induced the activation of ERK1/2, the pharmaceutical IgG inhibited ERK1/2 activity.

Conclusions: The present study demonstrates that pharmaceutical IgG, such as PRIVIGEN IgG and Tonglu IgG, can impair the anti-carcinoma activity of oxaliplatin. These data strongly suggest that therapeutic IgG as co-medication might have harmful side effects in cancer patients. The clinical significance of these preclinical observations absolutely advises further preclinical, as well as epidemiological and clinical research.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41416-021-01272-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8039037PMC
April 2021

Emotion Recognition Based on Skin Potential Signals with a Portable Wireless Device.

Sensors (Basel) 2021 Feb 2;21(3). Epub 2021 Feb 2.

College of Information Science and Electronic Engineering, Zhejiang University, Hangzhou 310027, China.

Emotion recognition is of great importance for artificial intelligence, robots, and medicine etc. Although many techniques have been developed for emotion recognition, with certain successes, they rely heavily on complicated and expensive equipment. Skin potential (SP) has been recognized to be correlated with human emotions for a long time, but has been largely ignored due to the lack of systematic research. In this paper, we propose a single SP-signal-based method for emotion recognition. Firstly, we developed a portable wireless device to measure the SP signal between the middle finger and left wrist. Then, a video induction experiment was designed to stimulate four kinds of typical emotion (happiness, sadness, anger, fear) in 26 subjects. Based on the device and video induction, we obtained a dataset consisting of 397 emotion samples. We extracted 29 features from each of the emotion samples and used eight well-established algorithms to classify the four emotions based on these features. Experimental results show that the gradient-boosting decision tree (GBDT), logistic regression (LR) and random forest (RF) algorithms achieved the highest accuracy of 75%. The obtained accuracy is similar to, or even better than, that of other methods using multiple physiological signals. Our research demonstrates the feasibility of the SP signal's integration into existing physiological signals for emotion recognition.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/s21031018DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7867357PMC
February 2021

Dynamic changes in lymphocyte subsets and parallel cytokine levels in patients with severe and critical COVID-19.

BMC Infect Dis 2021 Jan 18;21(1):79. Epub 2021 Jan 18.

Division of Pulmonary and Critical Care Medicine, The First Affiliated Hospital of Sun Yat-sen University, Institute of Pulmonary Diseases, Sun Yat-sen University, Guangzhou, 510080, Province Guangdong, People's Republic of China.

Background: The lack of knowledge regarding the pathogenesis and host immune response during SARS-CoV-2 infection has limited the development of effective treatments. Thus, we longitudinally investigated the dynamic changes in peripheral blood lymphocyte subsets and parallel changes in cytokine levels in COVID-19 patients with different disease severities to further address disease pathogenesis.

Methods: A total of 67 patients (10 moderate, 38 severe and 19 critical cases) with COVID-19 admitted to a tertiary care hospital in Wuhan from February 8th to April 6th, 2020 were retrospectively studied. Dynamic data of lymphocyte subsets and inflammatory cytokines were collected.

Results: On admission, compared with moderate cases, severe and critical cases showed significantly decreased levels of total lymphocytes, T lymphocytes, CD4 T cells, CD8 T cells, B cells and NK cells. IL-6 and IL-10 were significantly higher in the critical group. During the following hospitalization period, most of the lymphocyte subsets in the critical group began to recover to levels comparable to those in the severe group from the fourth week after illness onset, except for NK cells, which recovered after the sixth week. A sustained decrease in the lymphocyte subsets and an increase in IL-6 and IL-10 were observed in the nonsurvivors until death. There was a strong negative correlation between IL-6 and IL-10 and total lymphocytes, T lymphocytes, CD4 T cells, CD8 T cells and NK cells.

Conclusions: A sustained decrease in lymphocyte subsets, especially CD4 T cells and NK cells, interacting with proinflammatory cytokine storms was associated with severe disease and poor prognosis in COVID-19.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s12879-021-05792-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7812569PMC
January 2021

Fiber Bragg grating accelerometer-based nonintrusive flow rate measurements and leak detection.

Appl Opt 2020 Dec;59(34):10680-10687

We aim to develop a nonintrusive, reliable, convenient flow rate measurement and leak detection method. The flow rate is known to be related to the vibration excited by the turbulent internal flow, but there exists some scatter in the vibration data at low flow speeds (<2/) due to the resolution limits of the sensor. A customized fiber Bragg grating acceleration sensor is designed and applied to measure the low flow rate and detect leakage in the pipeline. Experimental tests show the relationship between the standard deviation of vibration data and flow rate at low velocity is quadratic; the of quadratic curve fitting is 0.990. Moreover, for leak detection, selected features are used as the input of support vector machine classifiers to identify the leak in the pipeline. The results demonstrate that the proposed method achieves a high accuracy of 99.00% to determine the leak state and nonleak state.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1364/AO.408548DOI Listing
December 2020

The crucial role of a protein corona in determining the aggregation kinetics and colloidal stability of polystyrene nanoplastics.

Water Res 2021 Feb 11;190:116742. Epub 2020 Dec 11.

School of Environmental Science and Engineering, Shanghai Jiao Tong University, Shanghai, 200240, China.

Nanosized plastics are considered as being a class of contaminants of emerging concern. The interaction between nanoplastics and proteins may significantly influence the environmental behavior and fate of nanoplastics. Here, we employed time-resolved dynamic light scattering to explore the aggregation kinetics and stability of polystyrene nanoparticles (PSNPs) exposed to a model globular protein (bovine serum albumin, BSA) in the presence of a number of typical electrolytes (NaCl, CaCl, and NaSO). With the increase of the BSA concentration, the amount of BSA adsorbed on the surface of negatively charged PS-Bare (non-modified) and PS-COOH (carboxyl-modified) increased, resulting in higher dispersibility in comparison to the treatment without BSA. This stabilization effect derived from the protein corona structure was revealed by combining characterization techniques and visualized by transmission electron microscopy. Upon addition of NaCl and CaCl, the aggregation of positively charged PS-NH (amino-modified) was inhibited by the BSA addition possibly due to the screening of the attractive patch-charge force and the competition for adsorption of cations between PS-NH and the protein. When NaSO was present in the suspension, BSA addition significantly increased PS-NH aggregation rate due to patch-charge attraction and the high performance of SO in attaching to particles and charge neutralization. These findings shed light on the interactions between PSNPs and proteins, which were shown to vary with the composition of the surface coatings of PSNPs. The newly gained knowledge will help us to forecast the transport and fate of PSNPs in natural aqueous systems.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.watres.2020.116742DOI Listing
February 2021

Identification by Comprehensive Bioinformatics Analysis of KIF15 as a Candidate Risk Gene for Triple-Negative Breast Cancer.

Cancer Manag Res 2020 1;12:12337-12348. Epub 2020 Dec 1.

Department of Breast Diseases, Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, People's Republic of China.

Background: Previous studies have shown that kinesin family proteins () play an indispensable roles in several types of cancer. However, the expression and clinical significance of in triple-negative breast cancer remain unclear.

Methods: In this study, the role of , including gene expression analysis, methylation characteristic, CNV characteristic, and miRNA target regulation, was evaluated using multiple bioinformatic tools based on TCGA database. Quantitative real-time PCR and Western blot were used to determine the expression level of in triple-negative breast cancer cell lines. Then, functional experiments were employed to explore the effects of on tumor growth and metastasis in triple-negative breast cancer.

Results: Our data showed that was significantly upregulated in triple-negative breast cancer (TNBC). Functionally, downregulation of significantly facilitated apoptosis and G2/M phase arrest, and inhibited the migration and invasion of TNBC cells. The mechanism of action of was closely related to DNA replication checkpoint and cell cycle regulation in TNBC based on GSEA. In addition, bioinformatics analysis demonstrated that high expression of in TNBC was correlated with copy number aberration and DNA methylation levels.

Conclusion: Our findings suggest that is a novel oncogene in TNBC and provide us a strong evidence that it might be served as a potential clinical target and biomarker in triple-negative breast cancer.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.2147/CMAR.S262017DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7718892PMC
December 2020

Multi-task convolutional neural network-based design of radio frequency pulse and the accompanying gradients for magnetic resonance imaging.

NMR Biomed 2021 02 16;34(2):e4443. Epub 2020 Nov 16.

MSC Clinical & Technical Solutions, Philips Healthcare, Beijing, China.

Modern MRI systems usually load the predesigned RFs and the accompanying gradients during clinical scans, with minimal adaption to the specific requirements of each scan. Here, we describe a neural network-based method for real-time design of excitation RF pulses and the accompanying gradients' waveforms to achieve spatially two-dimensional selectivity. Nine thousand sets of radio frequency (RF) and gradient waveforms with two-dimensional spatial selectivity were generated as the training dataset using the Shinnar-Le Roux (SLR) method. Neural networks were created and trained with five strategies (TS-1 to TS-5). The neural network-designed RF and gradients were compared with their SLR-designed counterparts and underwent Bloch simulation and phantom imaging to investigate their performances in spin manipulations. We demonstrate a convolutional neural network (TS-5) with multi-task learning to yield both the RF pulses and the accompanying two channels of gradient waveforms that comply with the SLR design, and these design results also provide excitation spatial profiles comparable with SLR pulses in both simulation (normalized root mean square error [NRMSE] of 0.0075 ± 0.0038 over the 400 sets of testing data between TS-5 and SLR) and phantom imaging. The output RF and gradient waveforms between the neural network and SLR methods were also compared, and the joint NRMSE, with both RF and the two channels of gradient waveforms considered, was 0.0098 ± 0.0024 between TS-5 and SLR. The RF and gradients were generated on a commercially available workstation, which took ~130 ms for TS-5. In conclusion, we present a convolutional neural network with multi-task learning, trained with SLR transformation pairs, that is capable of simultaneously generating RF and two channels of gradient waveforms, given the desired spatially two-dimensional excitation profiles.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/nbm.4443DOI Listing
February 2021

Divergent Effects of HSP70 Overexpression in Photoreceptors During Inherited Retinal Degeneration.

Invest Ophthalmol Vis Sci 2020 10;61(12):25

Neurobiology, Neurodegeneration, and Repair Laboratory (NNRL), National Eye Institute, National Institutes of Health, Bethesda, Maryland, United States.

Purpose: Disruption of proteostasis is a key event in many neurodegenerative diseases. Heat shock proteins (HSPs) participate in multiple functions associated with intracellular transport and proteostasis. We evaluated the effect of augmented HSP70 expression in mutant photoreceptors of mouse retinal degeneration models to test the hypothesis that failure to sustain HSP70 expression contributes to photoreceptor cell death.

Methods: We examined HSP70 expression in retinas of wild-type and mutant mice by RNA and protein analysis. A transgenic mouse line, TgCrx-Hspa1a-Flag, was generated to express FLAG-tagged full-length HSP70 protein under control of a 2.3 kb mouse Crx promoter. This line was crossed to three distinct retinal degeneration mouse models. Retinal structure and function were evaluated by histology, immunohistochemistry, and electroretinography.

Results: In seven different mouse models of retinal degeneration, we detected transient elevation of endogenous HSP70 expression at early stages, followed by a dramatic reduction as cell death ensues, suggesting an initial adaptive response to cellular stress. Augmented expression of HSP70 in RHOT17M mice, in which mutant rhodopsin is misfolded, marginally improved photoreceptor survival, whereas elevated HSP70 led to more severe retinal degeneration in rd10 mutants that produce a partially functional PDE6B. In Rpgrip1-/- mice that display a ciliary defect, higher HSP70 had no impact on photoreceptor survival or function.

Conclusions: HSP70 overexpression has divergent effects in photoreceptors determined, at least in part, by the nature of the mutant protein each model carries. Additional investigations on HSP pathways and associated chaperone networks in photoreceptors are needed before designing therapeutic strategies targeting proteostasis.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1167/iovs.61.12.25DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7594617PMC
October 2020

The prophylactic and therapeutic effects of moxibustion combined with traditional Chinese medicine decoction for treating chemotherapy-induced myelosuppression in early-stage breast cancer: study protocol for a randomized controlled trial.

Trials 2020 Oct 12;21(1):844. Epub 2020 Oct 12.

Department of Breast Surgery, Yueyang Hospital of Integrated Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, 200437, China.

Background: Traditional Chinese medicine (TCM) has a long history of use in breast cancer, but lacking systematic evidence to support its clinical benefits. In this study, we evaluated the prophylactic and therapeutic effects of moxibustion combined with decoctions for treating chemotherapy-induced myelosuppression (CIM) in early-stage breast cancer patients.

Methods: This is a randomized controlled clinical trial single-blinded for TCM decoction but not moxibustion. Patients are equally divided into the control group without decoction and moxibustion treatment (control), the decoction+moxibustion group (MD), and the placebo+moxibustion group (MP), according to the following stratification factors: age (below 40s, 40s, 50s, and 60s or above), chemotherapy regimen (anthracyclines, taxanes, anthracyclines+taxane, and others), and chemotherapy strategy (adjuvant and neoadjuvant). The TCM decoction is Wenshen Shengbai Decoction. The anticipated sample size is 462 cases (154 cases in each group). All participants are expected to treat with chemotherapy and recombinant human granulocyte colony-stimulating factor (rhG-CSF). The primary outcomes include the proportion of patients with relief of leukopenia and/or neutropenia, the myelosuppression-associated serious adverse event including grade 3-4 leukopenia and/or neutropenia, and febrile neutropenia, and the dose of rhG-CSF. The secondary outcomes include chemotherapy adherence, stratified analysis, adverse reactions, quality of life by EORTC Breast-Cancer-Specific Quality of Life Questionnaire including EORTC QLQ-C30 (V3.0) and QLQ-BR23, TCM Constitution, and 3-year disease-free survival and overall survival. Baseline information including age, surgical approach, chemotherapy regimen and strategy, pathological stage, and molecular subtype will be recorded.

Discussion: This will be the first randomized controlled trial to evaluate the efficacy of moxibustion combined with TCM decoction in treating CIM in early-stage breast cancer patients, aiming to standardize the TCM decoction and moxibustion method, thus providing evidence for its clinical benefit.

Trial Registration: chictr.org.cn ChiCTR-INR-16009557 . Registered on 23 October 2016.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s13063-020-04749-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7549227PMC
October 2020

Kinetics and Thermodynamic Analysis of Recent and Ancient Buried Wood.

ACS Omega 2020 Aug 13;5(33):20943-20952. Epub 2020 Aug 13.

College of Forestry, Sichuan Agricultural University, Chengdu 611130, Sichuan, China.

Kinetics and thermogravimetric analysis of recent wood (RZ) and ancient buried wood (ABZ) were investigated under a nitrogen atmosphere at different heating rates of 5, 10, 15, and 20 K/min. The activation energy values were estimated based on the Flynn-Wall-Ozawa model-free method, and then, the Coats-Redfern model-fitting method was used to predict the reaction mechanism. The best model of RZ for regions 1 and 2 was based on the diffusional and reaction order (second-order) mechanism, respectively, while a diffusional (Jander equation) mechanism is the best model for ABZ. The change in enthalpy and activation energy of the RZ was lower than that of the ABZ at different conversion rates. When the conversion rate was less than 0.4, the RZ may require lower thermal decomposition reaction energy, but the overall energy of thermal decomposition reactions and the degree of disorder was not much different.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1021/acsomega.0c02395DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7450622PMC
August 2020

Thyroid receptor-interacting protein 13 and EGFR form a feedforward loop promoting glioblastoma growth.

Cancer Lett 2020 11 27;493:156-166. Epub 2020 Aug 27.

Institute of Cancer Stem Cell, Dalian Medical University, Dalian, 116044, PR China. Electronic address:

Epidermal growth factor receptor (EGFR) amplification and EGFRvIII mutation drive glioblastoma (GBM) pathogenesis, but their regulation remains elusive. Here we characterized the EGFR/EGFRvIII "interactome" in GBM and identified thyroid receptor-interacting protein 13 (TRIP13), an AAA + ATPase, as an EGFR/EGFRvIII-associated protein independent of its ATPase activity. Functionally, TRIP13 augmented EGFR pathway activation and contributed to EGFR/EGFRvIII-driven GBM growth in GBM spheroids and orthotopic GBM xenograft models. Mechanistically, TRIP13 enhanced EGFR protein abundance in part by preventing Cbl-mediated ubiquitination and proteasomal degradation. Reciprocally, TRIP13 was phosphorylated at tyrosine(Y) 56 by EGFRvIII and EGF-activated EGFR. Abrogating TRIP13 Y56 phosphorylation dramatically attenuated TRIP13 expression-enhanced EGFR signaling and GBM cell growth. Clinically, TRIP13 expression was upregulated in GBM specimens and associated with poor patient outcome. In GBM, TRIP13 localized to cell membrane and cytoplasma and exhibited oncogenic effects in vitro and in vivo, depending on EGFR signaling but not the TRIP13 ATPase activity. Collectively, our findings uncover that TRIP13 and EGFR form a feedforward loop to potentiate EGFR signaling in GBM growth and identify a previously unrecognized ATPase activity-independent mode of action of TRIP13 in GBM biology.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.canlet.2020.08.023DOI Listing
November 2020

A Fluorogenic Trehalose Probe for Tracking Phagocytosed .

J Am Chem Soc 2020 09 27;142(36):15259-15264. Epub 2020 Aug 27.

Department of Chemistry, Stanford University, Stanford, California 94305, United States.

Tuberculosis (TB) disease is a global epidemic caused by the pathogenic (Mtb). Tools that can track the replication status of viable Mtb cells within macrophages are vital for the elucidation of host-pathogen interactions. Here, we present a cephalosphorinase-dependent green trehalose (CDG-Tre) fluorogenic probe that enables fluorescence labeling of single live Bacille Calmette-Guérin (BCG) cells within macrophages at concentrations as low as 2 μM. CDG-Tre fluoresces upon activation by BlaC, the β-lactamase uniquely expressed by Mtb, and the fluorescent product is subsequently incorporated within the bacterial cell wall via trehalose metabolic pathway. CDG-Tre showed high selectivity for mycobacteria over other clinically prevalent species in the suborder. The unique labeling strategy of BCG by CDG-Tre provides a versatile tool for tracking Mtb in both pre- and postphagocytosis and elucidating fundamental physiological and pathological processes related to the mycomembrane.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1021/jacs.0c07700DOI Listing
September 2020

3D Context-Aware Convolutional Neural Network for False Positive Reduction in Clustered Microcalcifications Detection.

IEEE J Biomed Health Inform 2021 Mar 5;25(3):764-773. Epub 2021 Mar 5.

False positives (FPs) reduction is indispensable for clustered microcalcifications (MCs) detection in digital breast tomosynthesis (DBT), since there might be excessive false candidates in the detection stage. Considering that DBT volume has an anisotropic resolution, we proposed a novel 3D context-aware convolutional neural network (CNN) to reduce FPs, which consists of a 2D intra-slices feature extraction branch and a 3D inter-slice features fusion branch. In particular, 3D anisotropic convolutions were designed to learn representations from DBT volumes and inter-slice information fusion is only performed on the feature map level, which could avoid the influence of anisotropic resolution of DBT volume. The proposed method was evaluated on a large-scale Chinese women population of 877 cases with 1754 DBT volumes and compared with 8 related methods. Experimental results show that the proposed network achieved the best performance with an accuracy of 92.68% for FPs reduction with an AUC of 97.65%, and the FPs are 0.0512 per DBT volume at a sensitivity of 90%. This also proved that making full use of 3D contextual information of DBT volume can improve the performance of the classification algorithm.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1109/JBHI.2020.3003316DOI Listing
March 2021

Evaluation of Nutrition Risk and Its Association With Mortality Risk in Severely and Critically Ill COVID-19 Patients.

JPEN J Parenter Enteral Nutr 2021 01 20;45(1):32-42. Epub 2020 Jul 20.

Department of Paediatrics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei Province, P. R. China.

Background: The nutrition status of coronavirus disease 2019 patients is unknown. This study evaluates clinical and nutrition characteristics of severely and critically ill patients infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and investigates the relationship between nutrition risk and clinical outcomes.

Methods: A retrospective, observational study was conducted at West Campus of Union Hospital in Wuhan. Patients confirmed with SARS-CoV-2 infection by a nucleic acid-positive test and identified as severely or critically ill were enrolled in this study. Clinical data and outcomes information were collected and nutrition risk was assessed using Nutritional Risk Screening 2002 (NRS).

Results: In total, 413 patients were enrolled in this study, including 346 severely and 67 critically ill patients. Most patients, especially critically ill patients, had significant changes in nutrition-related parameters and inflammatory markers. As for nutrition risk, the critically ill patients had significantly higher proportion of high NRS scores (P < .001), which were correlated with inflammatory and nutrition-related markers. Among 342 patients with NRS score ≥3, only 84 (of 342, 25%) received nutrition support. Critically ill patients and those with higher NRS score had a higher risk of mortality and longer stay in hospital. In logistic regression models, 1-unit increase in NRS score was associated with the risk of mortality increasing by 1.23 times (adjusted odds ratio, 2.23; 95% CI, 1.10-4.51; P = .026).

Conclusions: Most severely and critically ill patients infected with SARS-CoV-2 are at nutrition risk. The patients with higher nutrition risk have worse outcome and require nutrition therapy.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/jpen.1953DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7361906PMC
January 2021

A revised taxonomy of Asian snail-eating snakes (Squamata, Pareidae): evidence from morphological comparison and molecular phylogeny.

Zookeys 2020 9;939:45-64. Epub 2020 Jun 9.

College of Life Science and Food Engineering, Yibin University, Yibin 644007, China Xinjiang Agricultural University Urumqi China.

The Asian snail-eating snakes is the largest genus of the family Pareidae (formerly Pareatidae), and widely distributed in Southeast Asia. However, potential diversity remains poorly explored due to their highly conserved morphology and incomplete samples. Here, on basis of more extensive sampling, interspecific phylogenetic relationships of the genus were reconstructed using two mitochondrial fragments (cyt b and ND4) and two nuclear genes (c-mos and Rag1), and multivariate morphometrics conducted for external morphological data. Both Bayesian Inference and Maximum Likelihood analyses consistently showed that the genus was comprised of two distinct, monophyletic lineages with moderate to low support values. Based on evidences from molecular phylogeny and morphological data, cryptic diversity of this genus was uncovered and two new species were described. In additional, the validity of is confirmed.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3897/zookeys.939.49309DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7297803PMC
June 2020

SASH1 suppresses triple-negative breast cancer cell invasion through YAP-ARHGAP42-actin axis.

Oncogene 2020 07 10;39(27):5015-5030. Epub 2020 Jun 10.

Institute of Cancer Stem Cell, Dalian Medical University Cancer Center, 116044, Dalian, China.

Triple-negative breast cancer (TNBC) is extremely aggressive and lacks effective therapy. SAM and SH3 domain containing1 (SASH1) has been implicated in TNBC as a candidate tumor suppressor; however, the mechanisms of action of SASH1 in TNBC remain underexplored. Here, we show that SASH1 was significantly downregulated in TNBC patients samples compared with other subtypes of breast cancer. Ectopic SASH1 expression inhibited, while depletion of SASH1 enhanced, the invasive phenotype of TNBC cells, accompanied by deregulated expression of MMP2 and MMP9. The functional effects of SASH1 depletion were confirmed in the chicken chorioallantoic membrane and mouse xenograft models. Mechanistically, SASH1 knockdown downregulated the phosphorylation levels of the Hippo kinase LATS1 and its effector YAP (Yes associated protein), thereby upregulating YAP accumulation together with its downstream target CYR61. Consistently, forced SASH1 expression exhibited opposite effects. Pharmacological inhibition of YAP or knockdown of YAP reversed the enhanced cell invasion of TNBC cells following SASH1 depletion. Furthermore, SASH1-induced YAP signaling was LATS1-dependent, which in reverse enhanced phosphorylation of SASH1. The SASH1 S407A mutant (phosphorylation deficient) failed to rescue the altered YAP signaling by SASH1 knockdown. Notably, SASH1 depletion upregulated ARHGAP42 levels via YAP-TEAD and the YAP-ARHGAP42-actin axis contributed to SASH1-regulated TNBC cell invasion. Therefore, our findings uncover a new mechanism for the tumor-suppressive activity of SASH1 in TNBC, which may serve as a novel target for therapeutic intervention.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41388-020-1356-7DOI Listing
July 2020

GFP expression pattern in pituitary and gonads under the control of nuclear progesterone receptor promoter in transgenic zebrafish.

Dev Dyn 2020 11 29;249(11):1365-1376. Epub 2020 Jun 29.

State Key Laboratory of Marine Environmental Science, College of Ocean and Earth Sciences, Xiamen University, Xiamen, China.

Background: The nuclear progesterone receptor (Pgr) is a ligand-dependent transcription factor primarily responsible for mediating progesterone actions relevant for reproduction across vertebrates. Information on the cellular localization of Pgr expression in the reproductive system is required for developing a comprehensive approach to elucidate the role of Pgr in reproduction.

Results: We generated transgenic zebrafish Tg(pgr:eGFP) that express enhanced green fluorescent protein (eGFP) driven by promoter sequence of pgr gene. The tissue distribution pattern of egfp mRNA is consistent with the pgr mRNA expression in Tg(pgr:eGFP). In the pituitary, GFP signals are found in the proximal pars distalis. In order to better discern the cellular localization of GFP signals in gonads, Tg(pgr:eGFP) line was crossed with Tg(gsdf:nfsB-mCherry) line, specifically expressing nitroreductase-mCherry fusion protein in granulosa and Sertoli cells in ovary and testis, respectively. Imaging of testis tissue showed that GFP expression was confined to Leydig cells. In the ovary, GFP expression colocalized with the mCherry signal in granulosa cells. Intriguingly, we also identified some non-granulosa cells close to where blood vessels branched, expressing stronger GFP signals than granulosa cells.

Conclusions: Analyzing Tg(pgr:eGFP) expression in zebrafish provided leads toward new routes to study the role of Pgr in reproduction.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/dvdy.213DOI Listing
November 2020

Clinical characteristics, outcomes, and risk factors for mortality in patients with cancer and COVID-19 in Hubei, China: a multicentre, retrospective, cohort study.

Lancet Oncol 2020 07 29;21(7):904-913. Epub 2020 May 29.

Cancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. Electronic address:

Background: Patients with cancer are a high-risk population in the COVID-19 pandemic. We aimed to describe clinical characteristics and outcomes of patients with cancer and COVID-19, and examined risk factors for mortality in this population.

Methods: We did a retrospective, multicentre, cohort study of 205 patients with laboratory-confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and with a pathological diagnosis of a malignant tumour in nine hospitals within Hubei, China, from Jan 13 to March 18, 2020. All patients were either discharged from hospitals or had died by April 20, 2020. Clinical characteristics, laboratory data, and cancer histories were compared between survivors and non-survivors by use of χ test. Risk factors for mortality were identified by univariable and multivariable logistic regression models.

Findings: Between Jan 13 and Mar 18, 2020, 205 patients with cancer and laboratory-confirmed SARS-CoV-2 infection were enrolled (median age 63 years [IQR 56-70; range 14-96]; 109 [53%] women). 183 (89%) had solid tumours and 22 (11%) had haematological malignancies. The median duration of follow-up was 68 days (IQR 59-78). The most common solid tumour types were breast (40 [20%] patients), colorectal (28 [14%]), and lung cancer (24 [12%]). 54 (30%) of 182 patients received antitumour therapies within 4 weeks before symptom onset. 30 (15%) of 205 patients were transferred to an intensive care unit and 40 (20%) died during hospital admission. Patients with haematological malignancies had poorer prognoses than did those with solid tumours: nine (41%) of 22 patients with haematological malignancies died versus 31 (17%) of 183 patients with solid tumours (hazard ratio for death 3·28 [95% CI 1·56-6·91]; log rank p=0·0009). Multivariable regression analysis showed that receiving chemotherapy within 4 weeks before symptom onset (odds ratio [OR] 3·51 [95% CI 1·16-10·59]; p=0·026) and male sex (OR 3·86 [95% CI 1·57-9·50]; p=0·0033) were risk factors for death during admission to hospital.

Interpretation: Patients with cancer and COVID-19 who were admitted to hospital had a high case-fatality rate. Unfavourable prognostic factors, including receiving chemotherapy within 4 weeks before symptom onset and male sex, might help clinicians to identify patients at high risk of fatal outcomes.

Funding: National Natural Science Foundation of China.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/S1470-2045(20)30310-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7259917PMC
July 2020

Estrogen receptor α promotes lung cancer cell invasion via increase of and cross-talk with infiltrated macrophages through the CCL2/CCR2/MMP9 and CXCL12/CXCR4 signaling pathways.

Mol Oncol 2020 08 28;14(8):1779-1799. Epub 2020 Jun 28.

George Whipple Lab for Cancer Research, Departments of Urology and Pathology and the Wilmot Cancer Center, University of Rochester Medical Center, Rochester, NY, USA.

Data analysis of clinical samples suggests that higher estrogen receptor α (ERα) expression could be associated with worse overall survival in some patients with non-small-cell lung cancer (NSCLC). Immunofluorescence results further showed that higher ERα expression was linked to larger numbers of infiltrated macrophages in NSCLC tissues. However, the detailed mechanisms underlying this phenomenon remain unclear. Results from in vitro studies with multiple cell lines revealed that, in NSCLC cells, ERα can activate the CCL2/CCR2 axis to promote macrophage infiltration, M2 polarization, and MMP9 production, which can then increase NSCLC cell invasion. Mechanistic studies using chromatin immunoprecipitation and promoter luciferase assays demonstrated that ERα could bind to estrogen response elements (EREs) on the CCL2 promoter to increase CCL2 expression. Furthermore, ERα-increased macrophage infiltration can induce a positive feedback mechanism to increase lung cancer cell ERα expression via the up-regulation of the CXCL12/CXCR4 pathway. Targeting these newly identified pathways, NSCLC ERα-increased macrophage infiltration or the macrophage-to-NSCLC CXCL12/CXCR4/ERα signal, with anti-estrogens or CCR2/CXCR4 antagonists, may help in the development of new alternative therapies to better treat NSCLC.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/1878-0261.12701DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7400793PMC
August 2020

Genome-wide Profiling Identifies DNA Methylation Signatures of Aging in Rod Photoreceptors Associated with Alterations in Energy Metabolism.

Cell Rep 2020 04;31(3):107525

Neurobiology, Neurodegeneration & Repair Laboratory, 6 Center Drive, MSC0610, National Eye Institute, National Institutes of Health, Bethesda, MD 20892, USA. Electronic address:

Aging-associated functional decline is accompanied by alterations in the epigenome. To explore DNA modifications that could influence visual function with age, we perform whole-genome bisulfite sequencing of purified mouse rod photoreceptors at four ages and identify 2,054 differentially methylated regions (DMRs). We detect many DMRs during early stages of aging and in rod regulatory regions, and some of these cluster at chromosomal hotspots, especially on chromosome 10, which includes a longevity interactome. Integration of methylome to age-related transcriptome changes, chromatin signatures, and first-order protein-protein interactions uncover an enrichment of DMRs in altered pathways that are associated with rod function, aging, and energy metabolism. In concordance, we detect reduced basal mitochondrial respiration and increased fatty acid dependency with retinal age in ex vivo assays. Our study reveals age-dependent genomic and chromatin features susceptible to DNA methylation changes in rod photoreceptors and identifies a link between DNA methylation and energy metabolism in aging.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.celrep.2020.107525DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7228806PMC
April 2020

[Application of intravenous injection of tranexamic acid combined with local use of tranexamic acid cocktail in intertrochanteric fracture fixation].

Zhongguo Xiu Fu Chong Jian Wai Ke Za Zhi 2020 Apr;34(4):463-468

Department of Orthopaedics, Affiliated Hospital of North Sichuan Medical College, Nanchong Sichuan, 637000, P.R.China.

Objective: To explore the efficacy and safety of intravenous injection of tranexamic acid (TXA) combined with local use of TXA cocktail in intertrochanteric fracture fixation with proximal femoral nail antirotation (PFNA).

Methods: Patients with intertrochanteric fractures who underwent close reduction and internal fixation with PFNA between February 2018 and March 2019 were enrolled in the study. Among them, 45 patients who met the selection criteria were included in the study and randomly allocated into 3 groups ( =15). The patients in group A were not received TXA during perioperative period. The patients were intravenously injected of 1.0 g TXA before operation in group B and combined with local use of TXA cocktail during operation in group C. There was no significant difference in the age, gender, body mass index, fracture classification, disease duration, and complications between groups ( >0.05). The perioperative blood loss and blood transfusion rate, the visual analogue scale (VAS) score before operation and at 12, 24, and 48 hours after operation, the levels of prostaglandin E2 (PGE2) and bradykinin (BK) before operation and at 1 and 3 days after operation, postoperative complications, and the maximum amplitude (MA) of thromboelastogram were recorded and compared between groups.

Results: The total blood loss, hidden blood loss, and visible blood loss were significantly lower in groups B and C than those in group A ( <0.05), and the total blood loss and hidden blood loss were significantly lower in group C than those in group B ( <0.05). There was no significant difference in the blood transfusion rate, preoperative VAS scores and the levels of PGE2 and BK between groups ( >0.05). The postoperative VAS scores and the levels of PGE2 and BK were significantly lower in group C than in groups A and B ( <0.05). There was no significant difference in pre- and post-operative MA of thromboelastogram between groups ( >0.05). The incidences of postoperative complications were 33.33% (5/15), 20.00% (3/15), and 13.33% (2/15) in groups A, B, and C, respectively, with no significant difference between groups ( =1.721, =0.550).

Conclusion: For intertrochanteric fractures, application of intravenous injection of TXA combined with local use of TXA cocktail in PFNA fixation can reduce perioperative blood loss, relieve pain after operation, and do not increase the risk of complications.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.7507/1002-1892.201908138DOI Listing
April 2020

MOB2 suppresses GBM cell migration and invasion via regulation of FAK/Akt and cAMP/PKA signaling.

Cell Death Dis 2020 04 14;11(4):230. Epub 2020 Apr 14.

Department of Neurosurgery, Cancer Hospital of China Medical University, Liaoning Cancer Hospital & Institute, Shenyang, China.

Mps one binder 2 (MOB2) regulates the NDR kinase family, however, whether and how it is implicated in cancer remain unknown. Here we show that MOB2 functions as a tumor suppressor in glioblastoma (GBM). Analysis of MOB2 expression in glioma patient specimens and bioinformatic analyses of public datasets revealed that MOB2 was downregulated at both mRNA and protein levels in GBM. Ectopic MOB2 expression suppressed, while depletion of MOB2 enhanced, the malignant phenotypes of GBM cells, such as clonogenic growth, anoikis resistance, and formation of focal adhesions, migration, and invasion. Moreover, depletion of MOB2 increased, while overexpression of MOB2 decreased, GBM cell metastasis in a chick chorioallantoic membrane model. Overexpression of MOB2-mediated antitumor effects were further confirmed in mouse xenograft models. Mechanistically, MOB2 negatively regulated the FAK/Akt pathway involving integrin. Notably, MOB2 interacted with and promoted PKA signaling in a cAMP-dependent manner. Furthermore, the cAMP activator Forskolin increased, while the PKA inhibitor H89 decreased, MOB2 expression in GBM cells. Functionally, MOB2 contributed to the cAMP/PKA signaling-regulated inactivation of FAK/Akt pathway and inhibition of GBM cell migration and invasion. Collectively, these findings suggest a role of MOB2 as a tumor suppressor in GBM via regulation of FAK/Akt signaling. Additionally, we uncover MOB2 as a novel regulator in cAMP/PKA signaling. Given that small compounds targeting FAK and cAMP pathway have been tested in clinical trials, we suggest that interference with MOB2 expression and function may support a theoretical and therapeutic basis for applications of these compounds.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41419-020-2381-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7156523PMC
April 2020

In vitro and in vivo evaluations of nano-hydroxyapatite/polyamide 66/yttria-stabilized zirconia as a novel bioactive material for bone screws: Biocompatibility and bioactivity.

J Biomater Appl 2020 07 4;35(1):108-122. Epub 2020 Apr 4.

Department of Orthopaedics, Affiliated Hospital of North Sichuan Medical College, Nanchong City, China.

Zirconia and its derivatives have been receiving increased levels of attention with regard to their potential application in bone tissue engineering. These materials are of particular interest because of their excellent characteristics, such as superior biological and mechanical properties. In this study, yttria-stabilized tetragonal zirconia (YTZ)-reinforced nanohydroxyapatite/polyamide 66 (nHA/PA66) bone screws were prepared. The biocompatibility and bioactivity of nHA/PA66/YTZ were evaluated in vitro using MC3T3-E1 cells. Biocompatibility and bioactivity experiments (cell counting kit-8 tests, cell immunofluorescence analysis, and polymerase chain reaction) showed that nHA/PA66/YTZ could facilitate the biological functions of MC3T3-E1 cells. The attachment, proliferation, spreading, and expression of genes associated with osteogenesis (collagen 1, osteopontin, and osteocalcin) in cells cultured with the nHA/PA66/YTZ composite were all superior compared with the control groups ( < 0.05). In addition, nHA/PA66/YTZ bone screws were implanted into the femoral condyles of rabbits, and titanium screws were employed as a control group; postoperative histology and blood analysis revealed no obvious damage to the liver, kidneys, or any other major organs in either of the experimental groups. Moreover, nHA/PA66/YTZ screws resulted in significantly better bone-implant contact interfaces and enhanced formation of trabecular bone ( < 0.05); these characteristics were markedly better than those in the group that received titanium screws. These observations indicate that YTZ-reinforced nHA/PA66 composites have significant potential for applications in bone tissue engineering.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1177/0885328220916618DOI Listing
July 2020