Publications by authors named "Bing Hou"

58 Publications

A Noninvasive Multianalytical Approach for Lung Cancer Diagnosis of Patients with Pulmonary Nodules.

Adv Sci (Weinh) 2021 07 7;8(13):2100104. Epub 2021 May 7.

Department of Thoracic Surgery, Xinqiao Hospital Third Military Medical University (Army Medical University) Xinqiao Main Street Chongqing 400037 China.

Addressing the high false-positive rate of conventional low-dose computed tomography (LDCT) for lung cancer diagnosis, the efficacy of incorporating blood-based noninvasive testing for assisting practicing clinician's decision making in diagnosis of pulmonary nodules (PNs) is investigated. In this prospective observative study, next generation sequencing- (NGS-) based cell-free DNA (cfDNA) mutation profiling, NGS-based cfDNA methylation profiling, and blood-based protein cancer biomarker testing are performed for patients with PNs, who are diagnosed as high-risk patients through LDCT and subsequently undergo surgical resections, with tissue sections pathologically examined and classified. Using pathological classification as the gold standard, statistical and machine learning methods are used to select molecular markers associated with tissue's malignant classification based on a 98-patient discovery cohort (28 benign and 70 malignant), and to construct an integrative multianalytical model for tissue malignancy prediction. Predictive models based on individual testing platforms have shown varying levels of performance, while their final integrative model produces an area under the receiver operating characteristic curve (AUC) of 0.85. The model's performance is further confirmed on a 29-patient independent validation cohort (14 benign and 15 malignant, with power > 0.90), reproducing AUC of 0.86, which translates to an overall sensitivity of 80% and specificity of 85.7%.
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http://dx.doi.org/10.1002/advs.202100104DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8261512PMC
July 2021

Selinexor, a novel selective inhibitor of nuclear export, reduces SARS-CoV-2 infection and protects the respiratory system in vivo.

Antiviral Res 2021 08 19;192:105115. Epub 2021 Jun 19.

Karyopharm Therapeutics, Newton, MA, USA. Electronic address:

The novel coronavirus disease 2019 (COVID-19) caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is responsible for the recent global pandemic. The nuclear export protein (XPO1) has a direct role in the export of SARS-CoV proteins including ORF3b, ORF9b, and nucleocapsid. Inhibition of XPO1 induces anti-inflammatory, anti-viral, and antioxidant pathways. Selinexor is an FDA-approved XPO1 inhibitor. Through bioinformatics analysis, we predicted nuclear export sequences in the ACE-2 protein and confirmed by in vitro testing that inhibition of XPO1 with selinexor induces nuclear localization of ACE-2. Administration of selinexor inhibited viral infection prophylactically as well as therapeutically in vitro. In a ferret model of COVID-19, selinexor treatment reduced viral load in the lungs and protected against tissue damage in the nasal turbinates and lungs in vivo. Our studies demonstrated that selinexor downregulated the pro-inflammatory cytokines IL-1β, IL-6, IL-10, IFN-γ, TNF-α, and GMCSF, commonly associated with the cytokine storm observed in COVID-19 patients. Our findings indicate that nuclear export is critical for SARS-CoV-2 infection and for COVID-19 pathology and suggest that inhibition of XPO1 by selinexor could be a viable anti-viral treatment option.
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http://dx.doi.org/10.1016/j.antiviral.2021.105115DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8213878PMC
August 2021

Simulation analysis of impact damage to the bone tissue surrounding a dental implant.

Sci Rep 2020 04 24;10(1):6927. Epub 2020 Apr 24.

State Key Laboratory of Military Stomatology & National Clinical Research Center for Oral Diseases & Shaanxi Key Laboratory of Stomatology, Department of Prosthodontics, School of Stomatology, The Fourth Military Medical University, Xi'an, 710032, China.

Dental implant may suffer transient external impacts. To simulate the effect of impact forces on bone damage is very important for evaluation of damage and guiding treatment in clinics. In this study, an animal model was established by inserting an implant into the femoral condyle of New Zealand rabbit. Implant with good osseointegration was loaded with impact force. A three-dimensional finite element model was established based on the data of the animal model. Damage process to bone tissue was simulated with Abaqus 6.13 software combining dynamic mechanical properties of the femur. The characteristics of bone damage were analyzed by comparing the results of animal testing with numerical simulation data. After impact, cortical bone around the implant and trabecular at the bottom of the implant were prone to damage. The degree of damage correlated with the direction of loading and the magnitude of the impact. Lateral loading was most likely performed to damage cancellous bone. The stress wave formed by the impact force can damage the implant-bone interface and peri-implant trabeculae. The data from numerical simulations were consistent with data from animal experiments, highlighting the importance of a thorough examination and evaluation based on the patient's medical history.
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http://dx.doi.org/10.1038/s41598-020-63666-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7181623PMC
April 2020

An array of 60,000 antibodies for proteome-scale antibody generation and target discovery.

Sci Adv 2020 03 11;6(11):eaax2271. Epub 2020 Mar 11.

School of Life Sciences, Northwest University, Xi'an, Shanxi 710069, China.

Antibodies are essential for elucidating gene function. However, affordable technology for proteome-scale antibody generation does not exist. To address this, we developed Proteome Epitope Tag Antibody Library (PETAL) and its array. PETAL consists of 62,208 monoclonal antibodies (mAbs) against 15,199 peptides from diverse proteomes. PETAL harbors binders for a great multitude of proteins in nature due to antibody multispecificity, an intrinsic antibody feature. Distinctive combinations of 10,000 to 20,000 mAbs were found to target specific proteomes by array screening. Phenotype-specific mAb-protein pairs were found for maize and zebrafish samples. Immunofluorescence and flow cytometry mAbs for membrane proteins and chromatin immunoprecipitation-sequencing mAbs for transcription factors were identified from respective proteome-binding PETAL mAbs. Differential screening of cell surface proteomes of tumor and normal tissues identified internalizing tumor antigens for antibody-drug conjugates. By finding high-affinity mAbs at a fraction of current time and cost, PETAL enables proteome-scale antibody generation and target discovery.
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http://dx.doi.org/10.1126/sciadv.aax2271DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7065887PMC
March 2020

Long non-coding RNA LNC01133 promotes the tumorigenesis of ovarian cancer by sponging miR-126.

Int J Clin Exp Pathol 2018 1;11(12):5809-5819. Epub 2018 Dec 1.

Prevention and Health Care Department of Changhai Hospital of Shanghai Shanghai 200433, China.

Background: Ovarian cancer (OC) is the gynecologic malignancy with the highest mortality rate (70%), and it is urgent to find out a powerful prognostic marker for OC patients. LncRNAs are recently thought to be oncogenes in various cancers, and its expression levels are validated that can be inhibited by miRNAs. There are several studies indicating that sponging miRNAs will contribute to the tumorigenesis of cancers.

Methods: In the present study, bioinformatics analysis is used to explore the potential oncogene and its target miRNAs; QRT-PCR is performed to count the expression level of several genes; Flow cytometric analysis is conducted to assess the apoptosis rate of several cell lines; Western blot assays are used to evaluate the expression levels of several proteins; Cells proliferation, migration and invasion abilities are detected by CCK-8 assay, Wound scratch assay and Transwell invasion assay, respectively. In vivo experiments are performed to assess the influence of LNC01133 on the formation of tumor.

Results: We found LNC01133 was related to poor survival of OC patients, and identified that LNC01133 had significant influence on OC cells' apoptosis, proliferation, migration and invasion abilities. Furthermore, we observed miR-126 could target LNC01133 and decreased the expression level of LNC01133 in OC cells. Therefore, we sponged miR-126 to further study the molecular mechanism of OC tumorigenesis, and found an elevation in proliferation, migration and invasion abilities of OC cells, which suggested that miR-126 could serve as a powerful prognostic marker for OC patients, and had great clinical significance on OC diagnosis and treatment.

Conclusion: We found LNC01133 was an oncogene in OC, which is targeted by miR-126. miR-126 served as a powerful prognostic marker for OC patients because of its ability of promoting OC tumorigenesis after sponging.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6963098PMC
December 2018

Attenuated sporozoite expressing MAGE-A3 induces antigen-specific CD8+ T cell response against lung cancer in mice.

Cancer Biol Med 2019 May;16(2):288-298

Department of Thoracic Surgery, Xinqiao Hospital, Third Military Medical University, Chongqing 400037, China.

Objective: Cancer vaccines that rely on tumor antigen-specific CD8 T cell responses, are promising anti-cancer adjuvant immunotherapies. This study investigated whether genetically attenuated sporozoite (GAS) could be used as a novel vector to induce antigen-specific CD8 T cell responses against lung cancer.

Methods: We constructed GAS/MAGE-A3, a recombinant GAS engineered to express the lung cancer-specific antigen, melanoma-associated antigen 3 (MAGE-A3), and assessed its therapeutic effects against lung cancer.

Results: Robust parasite-specific CD8αCD11a and CD49dCD11a CD4 T cell responses as well as a MAGE-A3-specific CD8 T cell response were induced in GAS/MAGE-A3-immunized mice. Adoptive transfer of GAS/MAGE-A3-induced CD8 T cells from HLA-A2 transgenic mice into lung cancer-bearing nude mice inhibited tumor growth and prolonged survival.

Conclusions: These findings demonstrate that GAS/MAGE-A3 induces a strong MAGE-A3-specific CD8 T cell response against lung cancer , and indicate that GAS is a novel and efficacious antigen delivery vector for antitumor immunotherapy.
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http://dx.doi.org/10.20892/j.issn.2095-3941.2018.0309DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6713645PMC
May 2019

Fine-Grained Parcellation of the Macaque Nucleus Accumbens by High-Resolution Diffusion Tensor Tractography.

Front Neurosci 2019 10;13:709. Epub 2019 Jul 10.

Brainnetome Center, Institute of Automation, Chinese Academy of Sciences, Beijing, China.

Limited in part by the spatial resolution of typical magnetic resonance imaging (MRI) data, recent neuroimaging studies have only identified a connectivity-based shell-core-like partitioning of the nucleus accumbens (Acb) in humans. This has hindered the process of making a more refined description of the Acb using non-invasive neuroimaging technologies and approaches. In this study, high-resolution macaque brain diffusion MRI data were acquired to investigate the tractography-based parcellation of the Acb. Our results identified a shell-core-like partitioning in macaques that is similar to that in humans as well as an alternative solution that subdivided the Acb into four parcels, the medial shell, the lateral shell, the ventral core, and the dorsal core. Furthermore, we characterized the specific anatomical and functional connectivity profiles of these Acb subregions and generalized their specialized functions to establish a fine-grained macaque Acb brainnetome atlas. This atlas should be helpful in neuroimaging, stereotactic surgery, and comparative neuroimaging studies to reveal the neurophysiological substrates of various diseases and cognitive functions associated with the Acb.
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http://dx.doi.org/10.3389/fnins.2019.00709DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6635473PMC
July 2019

Prognostic Values of Serum Chloride and Sodium Levels in Patients with Three-vessel Disease.

Biomed Environ Sci 2019 Apr;32(4):250-259

Department of Cardiology, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100037, China; State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100037, China.

Objective: Identification of new risk factors is needed to improve prediction of adverse outcomes in patients with three-vessel disease (TVD). The present study aimed to evaluate the prognostic values of serum chloride and sodium levels in patients with TVD.

Methods: We used data from a prospective cohort of consecutive patients with angiographically confirmed TVD. The primary endpoint was all-cause death. Cox proportional hazard regression was used to analyze the relationship of serum chloride and sodium levels with long-term outcomes of TVD patients.

Results: A total of 8,318 participants with available serum chloride and sodium data were included in this analysis. At baseline, patients in the low tertiles group of serum chloride level (⪕ 102.0 mmol/L) or serum sodium level (⪕ 139.0 mmol/L) had more severe disease conditions. During a median follow-up of 7.5-year, both low serum chloride level and low serum sodium level were found to be associated with an increased risk for mortality in univariate analysis. However, when both parameters were incorporated into a multivariate model, only low serum sodium level remained to be an independent predictor of all-cause death (hazard ratio: 1.16, 95% confidence interval: 1.01-1.34, P = 0.041). Modest but significant improvement of discrimination was observed after incorporating serum sodium level into the Synergy between percutaneous coronary intervention (PCI) with Taxus and Cardiac Surgery score.

Conclusion: Serum sodium level is more strongly associated with long-term outcomes of TVD patients compared with serum chloride level. Low serum sodium level is an independent risk factor for mortality, but only provides modest prognostic information beyond an established risk model.
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http://dx.doi.org/10.3967/bes2019.035DOI Listing
April 2019

Alirocumab after Acute Coronary Syndrome.

Authors:
Yuan Gao Bing Hou

N Engl J Med 2019 05;380(21):2074-2075

Xenorm MedInfo Center, Beijing, China

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http://dx.doi.org/10.1056/NEJMc1902955DOI Listing
May 2019

Vitamin D Supplementation in Young Infants and Recurrent Wheezing.

JAMA 2018 10;320(16):1708

Xenorm MedInfo Center, Beijing, China.

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http://dx.doi.org/10.1001/jama.2018.11533DOI Listing
October 2018

(+)-Usnic Acid Inhibits Migration of c-KIT Positive Cells in Human Colorectal Cancer.

Evid Based Complement Alternat Med 2018 12;2018:5149436. Epub 2018 Sep 12.

School of Clinical Medicine, Chengdu University of Traditional Chinese Medicine, Chengdu 610075, China.

Inhibition of tumor cell migration is a treatment strategy for patients with colorectal cancer (CRC). SCF-dependent activation of c-KIT is responsible for migration of c-KIT positive [c-KIT(+)] cells of CRC. Drug resistance to Imatinib Mesylate (c-KIT inhibitor) has emerged. Inhibition of mTOR can induce autophagic degradation of c-KIT. (+)-usnic acid [(+)-UA], isolated from lichens, has two major functions including induction of proton shuttle and targeting inhibition of mTOR. To reduce hepatotoxicity, the treatment concentration of (+)-UA should be lower than 10 M. HCT116 cells and LS174 cells were employed to investigate the inhibiting effect of (+)-UA (<10 M) on SCF-mediated migration of c-KIT(+) CRC cells. HCT116 cells were employed to investigate the molecular mechanisms. The results indicated that firstly, 8 M (+)-UA decreased ATP content via uncoupling; secondly, 8 M (+)-UA induced mTOR inhibition, thereby mediated activation suppression of PKC-A, and induced the autophagy of the completed autophagic flux that resulted in the autophagic degradation and transcriptional inhibition of c-KIT and the increase in LDH release; ultimately, 8 M (+)-UA inhibited SCF-mediated migration of CRC c-KIT(+) cells. Taken together, 8 M could be determined as the effective concentration for (+)-UA to inhibit SCF-mediated migration of CRC c-KIT(+) cells.
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http://dx.doi.org/10.1155/2018/5149436DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6157178PMC
September 2018

Prognostication of chronic disorders of consciousness using brain functional networks and clinical characteristics.

Elife 2018 08 14;7. Epub 2018 Aug 14.

National Laboratory of Pattern Recognition, Institute of Automation, Chinese Academy of Sciences, Beijing, China.

Disorders of consciousness are a heterogeneous mixture of different diseases or injuries. Although some indicators and models have been proposed for prognostication, any single method when used alone carries a high risk of false prediction. This study aimed to develop a multidomain prognostic model that combines resting state functional MRI with three clinical characteristics to predict one year-outcomes at the single-subject level. The model discriminated between patients who would later recover consciousness and those who would not with an accuracy of around 88% on three datasets from two medical centers. It was also able to identify the prognostic importance of different predictors, including brain functions and clinical characteristics. To our knowledge, this is the first reported implementation of a multidomain prognostic model that is based on resting state functional MRI and clinical characteristics in chronic disorders of consciousness, which we suggest is accurate, robust, and interpretable.
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http://dx.doi.org/10.7554/eLife.36173DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6145856PMC
August 2018

Separate Neural Networks for Gains and Losses in Intertemporal Choice.

Neurosci Bull 2018 Oct 7;34(5):725-735. Epub 2018 Aug 7.

Brainnetome Center, Institute of Automation, University of Chinese Academy of Sciences, Beijing, 100190, China.

An important and unresolved question is how human brain regions process information and interact with each other in intertemporal choice related to gains and losses. Using psychophysiological interaction and dynamic causal modeling analyses, we investigated the functional interactions between regions involved in the decision-making process while participants performed temporal discounting tasks in both the gains and losses domains. We found two distinct intrinsic valuation systems underlying temporal discounting in the gains and losses domains: gains were specifically evaluated in the medial regions, including the medial prefrontal and orbitofrontal cortices, and losses were evaluated in the lateral dorsolateral prefrontal cortex. In addition, immediate reward or punishment was found to modulate the functional interactions between the dorsolateral prefrontal cortex and distinct regions in both the gains and losses domains: in the gains domain, the mesolimbic regions; in the losses domain, the medial prefrontal cortex, anterior cingulate cortex, and insula. These findings suggest that intertemporal choice of gains and losses might involve distinct valuation systems, and more importantly, separate neural interactions may implement the intertemporal choices of gains and losses. These findings may provide a new biological perspective for understanding the neural mechanisms underlying intertemporal choice of gains and losses.
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http://dx.doi.org/10.1007/s12264-018-0267-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6129240PMC
October 2018

Dichloroacetate enhances the antitumor efficacy of chemotherapeutic agents via inhibiting autophagy in non-small-cell lung cancer.

Cancer Manag Res 2018 16;10:1231-1241. Epub 2018 May 16.

Department of Thoracic Surgery, Xinqiao Hospital, Third Military Medical University, Chongqing, People's Republic of China.

Background: Chemotherapy is still the primary adjuvant strategy of cancer therapy; however, the emergence of multi-drug resistance has been a cause for concern. Autophagy has been demonstrated to have a protective role against chemotherapeutic drugs in cancer cells, and autophagy inhibition is generally considered to be a promising therapeutic strategy. However, the paucity of effective and specific autophagy inhibitors limits its application.

Purpose: The objective of this study was to explore the effect of DCA, small molecular anti-tumor agent, on the autophagy regulation and chemosensitization in NSCLC cells.

Methods: We investigated the autophagy regulation of dichloroacetate (DCA) by laser confocal microscopy and western blotting in A549 and H1975 cell lines. The MTT assay and flow cytometry was performed for explore the chemosensitization effectiveness of DCA. The results were verified with subcutaneous tumor model in nude mice and the immunohistochemistry was applied for assessing the level of cell apoptosis and autophagy in vivo post treatment.

Results: We found that DCA, which exhibited antitumor properties in various carcinoma models, induced apoptosis of non-small cell lung cancer cells (NSCLC) by inhibiting cancer cell autophagy. Furthermore, Perifosine, an AKT inhibitor, can greatly weaken the capacity of inducing apoptosis by DCA. The results indicate that the AKT-mTOR pathway, a main negative regulator of autophagy, is involved in the DCA-induced inhibition of autophagy. Then, we detected the effectiveness of autophagy inhibition by DCA. When used in co-treatment with the chemotherapeutic drug paclitaxel (PTX), DCA markedly decreased cell autophagy, enhanced apoptosis and inhibited proliferation in A549 and H1975 cells. The results of the xenograft experiment demonstrate that co-treatment of PTX and DCA can significantly decrease cell proliferation in vivo and prolong the survival of mice.

Conclusion: Our results suggest that DCA can inhibit cell autophagy induced by chemotherapeutics, providing a new avenue for cancer chemotherapy sensitization.
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http://dx.doi.org/10.2147/CMAR.S156530DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5962308PMC
May 2018

Californium-252 neutron brachytherapy combined with external pelvic radiotherapy plus concurrent chemotherapy for cervical cancer: a retrospective clinical study.

Chin J Cancer 2017 Feb 28;36(1):24. Epub 2017 Feb 28.

Department of Oncology, Armed Police Hospital of Guangdong Affiliated with Guangzhou Medical University, No. 268 of Yanling Road, Tianhe District, Guangzhou, 510507, Guangdong, P. R. China.

Background: Cervical cancer is the sixth most common cancer in Chinese women. A standard treatment modality for cervical cancer is the combination of surgery, chemotherapy, external-beam radiotherapy and intracavitary brachytherapy. The aim of this study was to retrospectively assess the long-term treatment outcomes of patients with cervical cancer who were treated with californium-252 neutron brachytherapy combined with external-beam radiotherapy plus concurrent chemotherapy.

Methods: We retrospectively analyzed the medical records of 150 patients with primary stages IB-IVB cervical cancer who received neutron brachytherapy combined with external-beam radiotherapy concurrently with cisplatin chemotherapy. All patients were followed up. Using an actuarial analysis, patient outcomes and treatment-related adverse effects were evaluated and compared.

Results: The median overall survival (OS) was 33.2 months. The 3-year progression-free survival rates for patients with stages I-II, III, and IV diseases were 81.0% (68/84), 65.0% (39/60), and 0% (0/6), respectively; the 3-year OS rates were 90.5% (76/84), 85.0% (51/60), and 16.7% (1/6), respectively. Vaginal bleeding was controlled within the median time of 4.0 days. One month after treatment, 97.3% of patients achieved short-term local control. The local recurrence rates for patients with stages I-II, III, and IV disease were 4.8% (4/84), 11.7% (7/60), and 33.3% (2/6), respectively, and the occurrence rates of distant metastasis were 16.7% (14/84), 25.0% (15/60), and 100.0% (6/6), respectively. Cancer stage, tumor size, and lymph node metastasis were identified as prognostic risk factors, but only lymph node metastasis was found to be an independent prognostic factor. The most common adverse effects during treatment were grades 1 and 2 irradiation-related proctitis and radiocystitis.

Conclusion: For patients with cervical cancer, neutron brachytherapy combined with external-beam radiotherapy plus concurrent chemotherapy produces a rapid response and greatly improves local control and long-term survival rates with tolerable adverse effects.
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http://dx.doi.org/10.1186/s40880-017-0191-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5331714PMC
February 2017

A 11 mW 2.4 GHz 0.18 µm CMOS Transceivers for Wireless Sensor Networks.

Sensors (Basel) 2017 Jan 24;17(2). Epub 2017 Jan 24.

School of Information and Communication Engineering, Beijing University of Posts and Telecommunications, Beijing 100876, China.

In this paper, a low power transceiver for wireless sensor networks (WSN) is proposed. The system is designed with fully functional blocks including a receiver, a fractional-N frequency synthesizer, and a class-E transmitter, and it is optimized with a good balance among output power, sensitivity, power consumption, and silicon area. A transmitter and receiver (TX-RX) shared input-output matching network is used so that only one off-chip inductor is needed in the system. The power and area efficiency-oriented, fully-integrated frequency synthesizer is able to provide programmable output frequencies in the 2.4 GHz range while occupying a small silicon area. Implemented in a standard 0.18 μm RF Complementary Metal Oxide Semiconductor (CMOS) technology, the whole transceiver occupies a chip area of 0.5 mm² (1.2 mm² including bonding pads for a QFN package). Measurement results suggest that the design is able to work at amplitude shift keying (ASK)/on-off-keying (OOK) and FSK modes with up to 500 kbps data rate. With an input sensitivity of -60 dBm and an output power of 3 dBm, the receiver, transmitter and frequency synthesizer consumes 2.3 mW, 4.8 mW, and 3.9 mW from a 1.8 V supply voltage, respectively.
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http://dx.doi.org/10.3390/s17020223DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5335926PMC
January 2017

Effect of the existing form of Cu element on the mechanical properties, bio-corrosion and antibacterial properties of Ti-Cu alloys for biomedical application.

Mater Sci Eng C Mater Biol Appl 2016 Dec 13;69:1210-21. Epub 2016 Aug 13.

Northeastern University, Shenyang 110819, China.

Ti-Cu alloys have exhibited strong antibacterial ability, but Ti-Cu alloys prepared by different processes showed different antibacterial ability. In order to reveal the controlling mechanism, Ti-Cu alloys with different existing forms of Cu element were prepared in this paper. The effects of the Cu existing form on the microstructure, mechanical, corrosion and antibacterial properties of Ti-Cu alloys have been systematically investigated. Results have shown that the as-cast Ti-Cu alloys showed a higher hardness and mechanical strength as well as a higher antibacterial rate (51-64%) but a relatively lower corrosion resistance than pure titanium. Treatment at 900°C/2h (T4) significantly increased the hardness and the strength, improved the corrosion resistance but had little effect on the antibacterial property. Treatment at 900°C/2h+400°C/12h (T6) increased further the hardness and the mechanical strength, improved the corrosion resistance and but also enhanced the antibacterial rate (>90%) significantly. It was demonstrated that the Cu element in solid solution state showed high strengthening ability but low antibacterial property while Cu element in Ti2Cu phase exhibited strong strengthening ability and strong antibacterial property. Ti2Cu phase played a key role in the antibacterial mechanism. The antibacterial ability of Ti-Cu alloy was strongly proportional to the Cu content and the surface area of Ti2Cu phase. High Cu content and fine Ti2Cu phase would contribute to a high strength and a strong antibacterial ability.
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http://dx.doi.org/10.1016/j.msec.2016.08.033DOI Listing
December 2016

Segmentectomy versus wedge resection for the treatment of high-risk operable patients with stage I non-small cell lung cancer: a meta-analysis.

Ther Adv Respir Dis 2016 10 1;10(5):435-43. Epub 2016 Sep 1.

Xinqiao Hospital, Third Military Medical University, Chongqing 400037, China

Background: Although lobectomy is still the preferred treatment for patients with stage I non-small cell lung cancer (NSCLC), segmentectomy or wedge resection is frequently performed on patients who cannot withstand the physiological rigors of lobectomy. The objective of this study was to compare the overall survival (OS), cancer-specific survival (CSS), and disease-free survival outcomes among patients with stage I NSCLC who have undergone these procedures.

Methods: A systematic electronic search in three online databases was conducted from their earliest publication dates to June 2015. The studies were evaluated according to rigorous, predefined inclusion criteria. The hazard ratio (HR) was used as the outcome measure for data combining.

Results: There were nine eligible studies. These studies included 1181 patients who underwent segmentectomy and 2003 patients who underwent wedge resection. Stage I NSCLC patients who underwent segmentectomy had significantly better OS (HR 0.80; 95% confidence interval [CI], 0.68-0.93; p = 0.004) and CSS (HR 0.42; 95% CI, 0.20-0.88; p = 0.02) rates than those who underwent wedge resection. However, there were no significant differences in OS (HR 0.39; 95% CI, 0.15-1.02; p = 0.06) and CSS (HR 1.87; 95% CI, 0.29-12.06; p = 0.51) rates between segmentectomy and wedge resection in patients with stage Ia NSCLC with tumor size ⩽ 2 cm.

Conclusions: For patients with stage I NSCLC, segmentectomy results in higher survival rates than wedge resection, whereas the outcomes of wedge resection are comparable to those of segmentectomy for patients with stage Ia NSCLC with tumor size ⩽ 2 cm. Considering the limitations and heterogeneity of the included studies, this conclusion should be further confirmed by rigorous randomized clinical trials.
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http://dx.doi.org/10.1177/1753465816667121DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5933623PMC
October 2016

Engineering Lysosome-Targeting BODIPY Nanoparticles for Photoacoustic Imaging and Photodynamic Therapy under Near-Infrared Light.

ACS Appl Mater Interfaces 2016 05 5;8(19):12039-47. Epub 2016 May 5.

Key Laboratory of Flexible Electronics (KLOFE) & Institute of Advanced Materials (IAM), Jiangsu National Synergetic Innovation Center for Advanced Materials (SICAM), Nanjing Tech University (NanjingTech) , Nanjing 211816, China.

Developing lysosome-targeting organic nanoparticles combined with photoacoustic imaging (PAI) and photodynamic therapy (PDT) functions toward personalized medicine are highly desired yet challenging. Here, for the first time, lysosome-targeting BODIPY nanoparticles were engineered by encapsulating near-infrared (NIR) absorbed BODIPY dye within amphiphilic DSPE-mPEG5000 for high-performing lysosomal PAI and acid-activatable PDT against cancer cells under NIR light.
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http://dx.doi.org/10.1021/acsami.6b02721DOI Listing
May 2016

Lymph node micrometastases are associated with disease recurrence and poor survival for early-stage non-small cell lung cancer patients: a meta-analysis.

J Cardiothorac Surg 2016 Feb 16;11:28. Epub 2016 Feb 16.

Department of Thoracic Surgery, Xinqiao Hospital, Third Military Medical University, Chongqing, 400037, China.

Background: We performed a meta-analysis to clarify whether the molecular detection of tumor cells or micrometastases in the lymph node (LN) indicates a high risk of disease recurrence and poor survival in negative pathologic lymph node status non-small cell lung cancer (NSCLC).

Methods: A literature search was performed using relevant keywords. We searched relevant studies from PubMed, Embase, and the Cochrane Library. Direct and indirect meta-estimates were generated using Review Manager software with fixed effects for the study. Study-to-study heterogeneity was summarized using I (2) statistics and predictive intervals (PIs).

Results: Our analysis of eight eligible studies revealed that patients with lymph node micrometastases (LNMM) were associated with poor overall survival (OS) (HR, 1.98; 95 % CI, 1.50 to 2.62; p < 0.00001) and disease-free survival (DFS) (HR, 2.34; 95 % CI, 1.67-3.27; p < 0.00001).

Conclusion: LNMM is associated with an increased risk of disease recurrence and poor survival in patients with negative pathologic node negative NSCLC. Thus, these patients need to be carefully followed up after the initial pulmonary resection.
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http://dx.doi.org/10.1186/s13019-016-0427-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4754980PMC
February 2016

Genetic Effects on Fine-Grained Human Cortical Regionalization.

Cereb Cortex 2016 09 6;26(9):3732-43. Epub 2015 Aug 6.

Brainnetome Center National Laboratory of Pattern Recognition CAS Center for Excellence in Brain Science, Institute of Automation, Chinese Academy of Sciences, Beijing 100190, China Key Laboratory for NeuroInformation of Ministry of Education, School of Life Science and Technology, University of Electronic Science and Technology of China, Chengdu 610054, China Queensland Brain Institute, University of Queensland, Brisbane QLD 4072, Australia.

Various brain structural and functional features such as cytoarchitecture, topographic mapping, gyral/sulcal anatomy, and anatomical and functional connectivity have been used in human brain parcellation. However, the fine-grained intrinsic genetic architecture of the cortex remains unknown. In the present study, we parcellated specific regions of the cortex into subregions based on genetic correlations (i.e., shared genetic influences) between the surface area of each pair of cortical locations within the seed region. The genetic correlations were estimated by comparing the correlations of the surface area between monozygotic and dizygotic twins using bivariate twin models. Our genetic subdivisions of diverse brain regions were reproducible across 2 independent datasets and corresponded closely to fine-grained functional specializations. Furthermore, subregional genetic correlation profiles were generally consistent with functional connectivity patterns. Our findings indicate that the magnitude of the genetic covariance in brain anatomy could be used to delineate the boundaries of functional subregions of the brain and may be of value in the next generation human brain atlas.
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http://dx.doi.org/10.1093/cercor/bhv176DOI Listing
September 2016

Orai3 Surface Accumulation and Calcium Entry Evoked by Vascular Endothelial Growth Factor.

Arterioscler Thromb Vasc Biol 2015 Sep 9;35(9):1987-94. Epub 2015 Jul 9.

From the Leeds Institute of Cardiovascular and Metabolic Medicine, School of Medicine (J.L., A.-F.B., B.H., B.R., P.J.W., M.A.B., H.L.A., N.K.M., J.E.R., N.Y.Y., S.T., M.Q., L.M., H.T., K.E.P., D.J.B.) and School of Chemistry (R.F.), University of Leeds, Leeds, United Kingdom; Departments of Hepatobiliary and Transplant Surgery (K.R.P.) and Colorectal Surgery (D.B.), St. James's University Hospital, Leeds, United Kingdom; and Yorkshire Heart Centre, Leeds General Infirmary, Leeds, United Kingdom (D.O.R.).

Objective: Vascular endothelial growth factor (VEGF) acts, in part, by triggering calcium ion (Ca(2+)) entry. Here, we sought understanding of a Synta66-resistant Ca(2+) entry pathway activated by VEGF.

Approach And Results: Measurement of intracellular Ca(2+) in human umbilical vein endothelial cells detected a Synta66-resistant component of VEGF-activated Ca(2+) entry that occurred within 2 minutes after VEGF exposure. Knockdown of the channel-forming protein Orai3 suppressed this Ca(2+) entry. Similar effects occurred in 3 further types of human endothelial cell. Orai3 knockdown was inhibitory for VEGF-dependent endothelial tube formation in Matrigel in vitro and in vivo in the mouse. Unexpectedly, immunofluorescence and biotinylation experiments showed that Orai3 was not at the surface membrane unless VEGF was applied, after which it accumulated in the membrane within 2 minutes. The signaling pathway coupling VEGF to the effect on Orai3 involved activation of phospholipase Cγ1, Ca(2+) release, cytosolic group IV phospholipase A2α, arachidonic acid production, and, in part, microsomal glutathione S-transferase 2, an enzyme which catalyses the formation of leukotriene C4 from arachidonic acid. Shear stress reduced microsomal glutathione S-transferase 2 expression while inducing expression of leukotriene C4 synthase, suggesting reciprocal regulation of leukotriene C4-synthesizing enzymes and greater role of microsomal glutathione S-transferase 2 in low shear stress.

Conclusions: VEGF signaling via arachidonic acid and arachidonic acid metabolism causes Orai3 to accumulate at the cell surface to mediate Ca(2+) entry and downstream endothelial cell remodeling.
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http://dx.doi.org/10.1161/ATVBAHA.115.305969DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4548547PMC
September 2015

Scalable and DiI-compatible optical clearance of the mammalian brain.

Front Neuroanat 2015 24;9:19. Epub 2015 Feb 24.

Brainnetome Center, Institute of Automation, Chinese Academy of Sciences Beijing, China ; National Laboratory of Pattern Recognition, Institute of Automation, Chinese Academy of Sciences Beijing, China ; Queensland Brain Institute, The University of Queensland Brisbane, QLD, Australia ; Key Laboratory for NeuroInformation of Ministry of Education, School of Life Science and Technology, University of Electronic Science and Technology of China Chengdu, China ; CAS Center for Excellence in Brain Science, Institute of Automation, Chinese Academy of Sciences Beijing, China.

Efficient optical clearance is fundamental for whole brain imaging. In particular, clearance of the brain without membrane damage is required for the imaging of lipophilic tracer-labeled neural tracts. Relying on an ascending gradient of fructose solutions, SeeDB can achieve sufficient transparency of the mouse brain while ensuring that the plasma membrane remains intact. However, it is challenging to extend this method to larger mammalian brains due to the extremely high viscosity of the saturated fructose solution. Here we report a SeeDB-derived optical clearing method, termed FRUIT, which utilizes a cocktail of fructose and urea. As demonstrated in the adult mouse brain, combination of these two highly water-soluble clearing agents exerts a synergistic effect on clearance. More importantly, the final FRUIT solution has low viscosity so as to produce transparency of the whole adult rabbit brain via arterial perfusion, which is impossible to achieve with a saturated fructose solution. In addition to good compatibility with enhanced yellow fluorescent protein, the cocktail also preserves the fluorescence of the lipophilic tracer DiI. This work provides a volume-independent optical clearing method which retains the advantages of SeeDB, particularly compatibility with lipophilic tracers.
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http://dx.doi.org/10.3389/fnana.2015.00019DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4338786PMC
March 2015

Endothelial Piezo1: life depends on it.

Channels (Austin) 2015 ;9(1):1-2

a School of Medicine ; University of Leeds ; Leeds , UK.

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http://dx.doi.org/10.4161/19336950.2014.986623DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4594609PMC
July 2015

Preventing and localizing esophagogastric anastomosis leakage by sleeve-wrapping of the pedicled omentum.

World J Gastroenterol 2014 Nov;20(43):16282-6

Quan-Xing Liu, Xu-Feng Deng, Bing Hou, Jia-Xin Min, Ji-Gang Dai, Department of Thoracic Surgery, Xinqiao Hospital, Third Military Medical University, Chongqing 400037, China.

Aim: To develop a technique of sleeve-wrapping the pedicled omentum around the esophagogastric anastomosis for preventing and localizing leakage.

Methods: This study includes data from 86 patients who were diagnosed with esophageal cancer and underwent the technique of sleeve-wrapping the pedicled omentum around esophagogastric anastomosis after esophagectomy between November 2011 and July 2013. The early complications that occurred during follow-up were analyzed.

Results: Postoperative complications included pulmonary complications (13/86; 15.1%) and abdominal or thoracic wound infection (3/86; 3.5%). Complications that occurred during follow-up included one case of anastomosis leakage (limited by omentum; 1.2%) and five case of anastomosis stricture (5.8%). No deaths occurred. All complications were resolved through traditional treatment. No additional surgery was needed.

Conclusion: Sleeve-wrapping of the pedicled omentum around esophagogastric anastomosis after esophagectomy is safe and effective for preventing and localizing anastomosis leakage without increasing anastomosis stricture.
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http://dx.doi.org/10.3748/wjg.v20.i43.16282DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4239518PMC
November 2014

Junctional adhesion molecule-A, an epithelial-mesenchymal transition inducer, correlates with metastasis and poor prognosis in human nasopharyngeal cancer.

Carcinogenesis 2015 Jan 21;36(1):41-8. Epub 2014 Nov 21.

Cancer Research Institute, Southern Medical University, Guangzhou 510515, Guangdong Province, China,

Junctional adhesion molecule-A (JAM-A) is preferentially concentrated at tight junctions and influences epithelial cell morphology and migration. Epithelial-to-mesenchymal transition (EMT) is the conversion process of epithelial cells into mesenchymal cells, and it plays an important role in the invasiveness and metastasis of various cancers. However, the role of JAM-A in regulating the invasive behaviours of human nasopharyngeal carcinoma (NPC) is unknown. In this study, we found that JAM-A upregulation induced EMT, whereas silencing of endogenous JAM-A expression reversed EMT. Furthermore, upregulation of JAM-A led to EMT via activation phosphoinositide 3-kinase/protein kinase B (PI3K/Akt) pathway. PI3K inhibitors blocked JAM-A-induced EMT, suggesting that the kinase acts downstream of JAM-A. Finally, results from 172 human patients with NPC showed that high expression levels of JAM-A correlated with metastasis and poor prognosis in NPC. Taken together, these results suggest that high JAM-A expression positively correlates with poor prognosis in patients with NPC, and induces EMT of NPC cells in vitro and in vivo via the PI3K/Akt pathway. These data indicate novel functions in the JAM-A repertoire, and have clinical implications for the treatment of patients with NPC.
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http://dx.doi.org/10.1093/carcin/bgu230DOI Listing
January 2015

Identification and characterization of microRNAs related to salt stress in broccoli, using high-throughput sequencing and bioinformatics analysis.

BMC Plant Biol 2014 Sep 3;14:226. Epub 2014 Sep 3.

Cancer Research Institute, Southern Medical University, Guangzhou, Guangdong Province, People's Republic of China.

Background: MicroRNAs (miRNAs) are a new class of endogenous regulators of a broad range of physiological processes, which act by regulating gene expression post-transcriptionally. The brassica vegetable, broccoli (Brassica oleracea var. italica), is very popular with a wide range of consumers, but environmental stresses such as salinity are a problem worldwide in restricting its growth and yield. Little is known about the role of miRNAs in the response of broccoli to salt stress. In this study, broccoli subjected to salt stress and broccoli grown under control conditions were analyzed by high-throughput sequencing. Differential miRNA expression was confirmed by real-time reverse transcription polymerase chain reaction (RT-PCR). The prediction of miRNA targets was undertaken using the Kyoto Encyclopedia of Genes and Genomes (KEGG) Orthology (KO) database and Gene Ontology (GO)-enrichment analyses.

Results: Two libraries of small (or short) RNAs (sRNAs) were constructed and sequenced by high-throughput Solexa sequencing. A total of 24,511,963 and 21,034,728 clean reads, representing 9,861,236 (40.23%) and 8,574,665 (40.76%) unique reads, were obtained for control and salt-stressed broccoli, respectively. Furthermore, 42 putative known and 39 putative candidate miRNAs that were differentially expressed between control and salt-stressed broccoli were revealed by their read counts and confirmed by the use of stem-loop real-time RT-PCR. Amongst these, the putative conserved miRNAs, miR393 and miR855, and two putative candidate miRNAs, miR3 and miR34, were the most strongly down-regulated when broccoli was salt-stressed, whereas the putative conserved miRNA, miR396a, and the putative candidate miRNA, miR37, were the most up-regulated. Finally, analysis of the predicted gene targets of miRNAs using the GO and KO databases indicated that a range of metabolic and other cellular functions known to be associated with salt stress were up-regulated in broccoli treated with salt.

Conclusion: A comprehensive study of broccoli miRNA in relation to salt stress has been performed. We report significant data on the miRNA profile of broccoli that will underpin further studies on stress responses in broccoli and related species. The differential regulation of miRNAs between control and salt-stressed broccoli indicates that miRNAs play an integral role in the regulation of responses to salt stress.
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http://dx.doi.org/10.1186/s12870-014-0226-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4167151PMC
September 2014

Piezo1 integration of vascular architecture with physiological force.

Nature 2014 Nov 10;515(7526):279-282. Epub 2014 Aug 10.

School of Medicine and Multidisciplinary Cardiovascular Research Centre, University of Leeds, Leeds, LS2 9JT, UK.

The mechanisms by which physical forces regulate endothelial cells to determine the complexities of vascular structure and function are enigmatic. Studies of sensory neurons have suggested Piezo proteins as subunits of Ca(2+)-permeable non-selective cationic channels for detection of noxious mechanical impact. Here we show Piezo1 (Fam38a) channels as sensors of frictional force (shear stress) and determinants of vascular structure in both development and adult physiology. Global or endothelial-specific disruption of mouse Piezo1 profoundly disturbed the developing vasculature and was embryonic lethal within days of the heart beating. Haploinsufficiency was not lethal but endothelial abnormality was detected in mature vessels. The importance of Piezo1 channels as sensors of blood flow was shown by Piezo1 dependence of shear-stress-evoked ionic current and calcium influx in endothelial cells and the ability of exogenous Piezo1 to confer sensitivity to shear stress on otherwise resistant cells. Downstream of this calcium influx there was protease activation and spatial reorganization of endothelial cells to the polarity of the applied force. The data suggest that Piezo1 channels function as pivotal integrators in vascular biology.
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http://dx.doi.org/10.1038/nature13701DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4230887PMC
November 2014
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