Publications by authors named "Xuan He"

181 Publications

Co-delivery of autophagy inhibitor and gemcitabine using a pH-activatable core-shell nanobomb inhibits pancreatic cancer progression and metastasis.

Theranostics 2021 4;11(18):8692-8705. Epub 2021 Aug 4.

Key Laboratory of Drug-Targeting and Drug Delivery System of the Education Ministry and Sichuan Province, Sichuan Engineering Laboratory for Plant-Sourced Drug and Sichuan Research Center for Drug Precision Industrial Technology, West China School of Pharmacy, Sichuan University, Chengdu 610041, People's Republic of China.

Metastasis is one of the main reasons for the high mortality associated with pancreatic ductal adenocarcinoma (PDAC), and autophagy regulates the metastatic migration of tumor cells, their invasion of tissues, and their formation of focal adhesions. Inhibiting autophagy may suppress tumor growth and metastasis, but the abundant extracellular matrix hinders the deep penetration of therapeutic agents. To enhance the penetration of drugs that can inhibit metastasis of pancreatic cancer, a pH-responsive drug delivery system was formulated. Gemcitabine (GEM), a first-line chemotherapeutic drug against PDAC, was loaded in 6PA-modified DGL (PDGL) nanoparticles to afford PDGL-GEM. Then PDGL-GEM was co-precipitated with the autophagy inhibitor chloroquine phosphate (CQ) and calcium phosphate to formulate [email protected]/CQ. The size and morphology of the resulting "nanobomb" [email protected]/CQ were characterized, and their uptake into cells, cytotoxicity and ability to inhibit autophagy were analyzed at pH 6.5 and 7.4. The anti-tumor and anti-metastasis effects of the nanobomb were explored on mice carrying Pan 02 pancreatic tumor xenografts or orthotopic tumors. The pH-induced dissolution of calcium phosphate facilitated the release of CQ from the nanobomb and deep penetration of PDGL-GEM. The internalization of PDGL-GEM and subsequent intracellular release of GEM inhibited tumor growth, while CQ downregulated autophagy in tumor cells and fibroblasts. In fact, inhibition of xenograft and orthotopic tumor growth was greater with the complete [email protected]/CQ than with subassemblies lacking GEM or CQ. More importantly, mechanistic studies and suggested that the nanobomb inhibits metastasis by downregulating MMP-2 and paxillin, as well as reducing fibrosis. The pH-sensitive [email protected]/CQ shows potential for inhibiting proliferation and metastasis of pancreatic cancer through an autophagy-dependent pathway.
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http://dx.doi.org/10.7150/thno.60437DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8419034PMC
August 2021

Fano-Resonant Hybrid Metamaterial for Enhanced Nonlinear Tunability and Hysteresis Behavior.

Research (Wash D C) 2021 13;2021:9754083. Epub 2021 Aug 13.

Institute of Radio Astronomy, National Academy of Sciences of Ukraine, Kharkiv 61002, Ukraine.

Artificial resonant metamaterial with subwavelength localized filed is promising for advanced nonlinear photonic applications. In this article, we demonstrate enhanced nonlinear frequency-agile response and hysteresis tunability in a Fano-resonant hybrid metamaterial. A ceramic cuboid is electromagnetically coupled with metal cut-wire structure to excite the high-Q Fano-resonant mode in the dielectric/metal hybrid metamaterial. It is found that the significant nonlinear response of the ceramic cuboid can be employed for realization of tunable metamaterials by exciting its magnetic mode, and the trapped mode with an asymmetric Fano-like resonance is beneficial to achieve notable nonlinear modulation on the scattering spectrum. The nonlinear tunability of both the ceramic structure and the ceramic/metal hybrid metamaterial is promising to extend the operation band of metamaterials, providing possibility in practical applications with enhanced light-matter interactions.
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http://dx.doi.org/10.34133/2021/9754083DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8380421PMC
August 2021

Paricalcitol versus Calcitriol + Cinacalcet for the Treatment of Secondary Hyperparathyroidism in Chronic Kidney Disease in China: A Cost-Effectiveness Analysis.

Front Public Health 2021 21;9:712027. Epub 2021 Jul 21.

Department of Clinical Pharmacy, School of Pharmacy, Nanjing Medical University, Nanjing, China.

Chronic Kidney Disease (CKD) is a global chronic disease with increasing prevalence in recent years, particularly CKD accompanied by Secondary Hyperparathyroidism (SHPT) leads to reduced quality of life, increased mortality, a considerable economic burden for patients and society. The aim of this study was to investigate the cost-effectiveness analysis of paricalcitol vs. calcitriol + cinacalcet for CKD patients with SHPT in China in 2020. A Markov model was conducted employing data derived from published literature, clinical trials, official sources, and tertiary public hospital data in China, based on a 10-year horizon from the perspective of the healthcare system. Calcitriol + Cinacalcet was used as the reference group. CKD stage 5 (CKD-5) dialysis patients suffering from SHPT were included in the study. Effectiveness was measured in quality-adjusted life years (QALYs). The discount rate (5%) was applied to costs and effectiveness. Sensitivity analysis was performed to confirm the robustness of the findings. The base case analysis demonstrated that Patients treated with paricalcitol could gain an increase in utility (0.183 QALYs) and require fewer expenditures (6925.612 yuan). One-way sensitivity analysis was performed to showed that impact factors were the price of cinacalcet, the hospitalization costs of patients with paricalcitol and calcitriol, the costs and utilities of hemodialysis and the costs of calcitriol, the costs of paricalcitol regardless of period. Probabilistic simulation analysis displayed when willingness-to-pay was ¥217113, the probability that Paricalcitol was dominant is 96.20%. The results showed that paricalcitol administrated to treat patients diagnosed with Secondary hyperparathyroidism in Chronic Kidney Disease, compared to calcitriol and cinacalcet, might be dominant in China.
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http://dx.doi.org/10.3389/fpubh.2021.712027DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8333861PMC
August 2021

[Pendelluft volume during double-triggered asynchronous breaths under pressure support ventilation: a prospective physiological study].

Zhonghua Wei Zhong Bing Ji Jiu Yi Xue 2021 Jun;33(6):680-685

Department of Critical Care Medicine, Beijing Tiantan Hospital, Capital Medical University, Beijing 100070, China. Corresponding author: Zhou Jianxin, Email:

Objective: To investigate the relationship between double-triggering and abnormal movement of air in the lungs (pendelluft phenomenon) under pressure support ventilation (PSV).

Methods: A prospective observational study was conducted, postoperative patients admitted to department of critical care medicine of Beijing Tiantan Hospital, Capital Medical University from April 1, 2019 to August 31, 2020 and received invasive mechanical ventilation with PSV mode were enrolled. Electrical impedance tomography (EIT) monitoring was performed. Airway pressure-time, flow-time, global and regional impedance-time curves were synchronously collected and analyzed offline. The volume of abnormal movement of air in the lungs at the beginning of inspiration was measured and defined as pendelluft volume. Double-triggered breaths were identified by trained researchers. Pendelluft volume during double-triggering was measured including the first triggered breath, the double-triggered breath, and the breath immediately following the double-triggered breath. Pendelluft volume was also measured for normal breath during the study. According to the frequency of double-triggering, patients were divided into severe (≥ 1 time/min) and non-severe double-triggering group. Pendelluft volume, parameters of respiratory mechanics, and clinical outcomes between the two groups were compared.

Results: In 40 enrolled patients, a total of 9 711 breaths [(243±63) breaths/patient] were collected and analyzed, among which 222 breaths (2.3%) were identified as double-triggering. The Kappa of interobserver reliability to detect double-triggering was 0.964 [95% confidence interval (95%CI) was 0.946-0.982]. In 222 double-triggered breaths, pendelluft volume could not be measured in 7 breaths (3.2%), but the pendelluft phenomenon did exist as shown by opposite regional impedance change at the beginning of double-triggered inspiration. Finally, pendelluft volume was measured in 215 double-triggered breaths. Meanwhile, 400 normal breaths (10 normal breaths randomly selected for each patient) were identified as control. Compared with normal breath, pendelluft volume significantly increased in the first breath, the double-triggered breath, and the following normal breath [mL: 3.0 (1.4, 6.4), 8.3 (3.6, 13.2), 4.3 (1.9, 9.1) vs. 1.4 (0.7, 2.8), all P < 0.05]. Patients in severe double-triggering, pendelluft volume of normal breath and double-triggered breath were significantly higher than those in non-severe double-triggering group [mL: 1.8 (0.9, 3.2) vs. 1.1 (0.5, 2.1), P < 0.001; 8.5 (3.9, 13.4) vs. 2.0 (0.6, 9.1), P = 0.008]. Patients in severe double-triggering group had significantly higher respiratory rate than that in the non-severe double-triggering group (breaths/min: 20.9±3.5 vs. 15.2±3.7, P < 0.001). There were no significant differences in other respiratory mechanics parameters and main clinical outcomes between the two groups.

Conclusions: During PSV, the abnormal movement of air in the lungs (pendelluft phenomenon) was more likely to occur in double-triggering especially in double-triggered breath. The more frequent the double-triggering occurred, the more serious the pendelluft phenomenon was. A higher pendelluft volume of normal breath and a higher respiratory rate were related to severity of double-triggering.
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http://dx.doi.org/10.3760/cma.j.cn121430-20210115-00064DOI Listing
June 2021

Therapeutic Agents Rounding Up the Immunopathology of COVID-19.

Ther Clin Risk Manag 2021 29;17:657-668. Epub 2021 Jun 29.

Department of Respiratory and Critical Care Medicine, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, People's Republic of China.

COVID-19 pandemic has caused more than 3 million deaths globally during the past year. The direct attack from SARS-CoV-2 and hyperactivated immune response contribute to the progress and deterioration of COVID-19. After the virus invades, the activation and release of cytokines/chemokines cause "cytokine storm", leading to acute respiratory distress syndrome (ARDS) and multiple organs dysfunction syndrome (MODS). Eliminating virus and blocking cytokines are important checkpoints of COVID-19 therapy, and several agents targeting immunopathology, including interferons, thymosin, glucocorticoids and immunoglobulin, have shown therapeutic effects in severe patients with COVID-19. Herein, we reviewed the practice evidences and concluded that several agents rounding up the immunopathology of COVID-19 may be the alternative approaches under the scenario of the lacking of effective antiviral drugs.
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http://dx.doi.org/10.2147/TCRM.S313003DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8254585PMC
June 2021

Biodegradable magnesium combined with distraction osteogenesis synergistically stimulates bone tissue regeneration via CGRP-FAK-VEGF signaling axis.

Biomaterials 2021 08 23;275:120984. Epub 2021 Jun 23.

Musculoskeletal Research Laboratory of Department of Orthopaedics & Traumatology and Innovative Orthopaedic Biomaterial and Drug Translational Research Laboratory, Li Ka Shing Institute of Health, The Chinese University of Hong Kong, Hong Kong SAR, China; CHUK Hong Kong - Shenzhen Innovation and Technology Institute (Futian), China. Electronic address:

Critical size bone defects are frequently caused by accidental trauma, oncologic surgery, and infection. Distraction osteogenesis (DO) is a useful technique to promote the repair of critical size bone defects. However, DO is usually a lengthy treatment, therefore accompanied with increased risks of complications such as infections and delayed union. Here, we demonstrated that magnesium (Mg) nail implantation into the marrow cavity degraded gradually accompanied with about 4-fold increase of new bone formation and over 5-fold of new vessel formation as compared with DO alone group in the 5 mm femoral segmental defect rat model at 2 weeks after distraction. Mg nail upregulated the expression of calcitonin gene-related peptide (CGRP) in the new bone as compared with the DO alone group. We further revealed that blockade of the sensory nerve by overdose capsaicin blunted Mg nail enhanced critical size bone defect repair during the DO process. CGRP concentration-dependently promoted endothelial cell migration and tube formation. Meanwhile, CGRP promoted the phosphorylation of focal adhesion kinase (FAK) at Y397 site and elevated the expression of vascular endothelial growth factor A (VEGFA). Moreover, inhibitor/antagonist of CGRP receptor, FAK, and VEGF receptor blocked the Mg nail stimulated vessel and bone formation. We revealed, for the first time, a CGRP-FAK-VEGF signaling axis linking sensory nerve and endothelial cells, which may be the main mechanism underlying Mg-enhanced critical size bone defect repair when combined with DO, suggesting a great potential of Mg implants in reducing DO treatment time for clinical applications.
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http://dx.doi.org/10.1016/j.biomaterials.2021.120984DOI Listing
August 2021

[Research on entity relationship extraction of Chinese medical literature and application in diabetes medical literature].

Sheng Wu Yi Xue Gong Cheng Xue Za Zhi 2021 Jun;38(3):563-573

College of Health Science and Environmental Engineering, Shenzhen Technology University, Shenzhen, Guangdong 518118, P.R.China.

The medical literature contains a wealth of valuable medical knowledge. At present, the research on extraction of entity relationship in medical literature has made great progress, but with the exponential increase in the number of medical literature, the annotation of medical text has become a big problem. In order to solve the problem of manual annotation time such as consuming and heavy workload, a remote monitoring annotation method is proposed, but this method will introduce a lot of noise. In this paper, a novel neural network structure based on convolutional neural network is proposed, which can solve a large number of noise problems. The model can use the multi-window convolutional neural network to automatically extract sentence features. After the sentence vectors are obtained, the sentences that are effective to the real relationship are selected through the attention mechanism. In particular, an entity type (ET) embedding method is proposed for relationship classification by adding entity type characteristics. The attention mechanism at sentence level is proposed for relation extraction in allusion to the unavoidable labeling errors in training texts. We conducted an experiment using 968 medical references on diabetes, and the results showed that compared with the baseline model, the present model achieved good results in the medical literature, and F1-score reached 93.15%. Finally, the extracted 11 types of relationships were stored as triples, and these triples were used to create a medical map of complex relationships with 33 347 nodes and 43 686 relationship edges. Experimental results show that the algorithm used in this paper is superior to the optimal reference system for relationship extraction.
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http://dx.doi.org/10.7507/1001-5515.202001009DOI Listing
June 2021

A Minimally Invasive Exosome Spray Repairs Heart after Myocardial Infarction.

ACS Nano 2021 Jun 21. Epub 2021 Jun 21.

Department of Molecular Biomedical Sciences and Comparative Medicine Institute, North Carolina State University, Raleigh, North Carolina 27607, United States.

Myocardial infarction (MI) remains the most common cause of death worldwide. Many MI survivors will suffer from recurrent heart failure (HF), which has been recognized as a determinant of adverse prognosis. Despite the success of improved early survival after MI by primary percutaneous coronary intervention, HF after MI is becoming the major driver of late morbidity, mortality, and healthcare costs. The development of regenerative medicine has brought hope to MI treatment in the past decade. Mesenchymal stem cell (MSC)-derived exosomes have been established as an essential part of stem cell paracrine factors for heart regeneration. However, its regenerative power is hampered by low delivery efficiency to the heart. We designed, fabricated, and tested a minimally invasive exosome spray (EXOS) based on MSC exosomes and biomaterials. In a mouse model of acute myocardial infarction, EXOS improved cardiac function and reduced fibrosis, and promoted endogenous angiomyogenesis in the post-injury heart. We further tested the feasibility and safety of EXOS in a pig model. Our results indicate that EXOS is a promising strategy to deliver therapeutic exosomes for heart repair.
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http://dx.doi.org/10.1021/acsnano.1c00628DOI Listing
June 2021

Low-dose Ad26.COV2.S protection against SARS-CoV-2 challenge in rhesus macaques.

Cell 2021 06 1;184(13):3467-3473.e11. Epub 2021 Jun 1.

Bioqual, Rockville, MD 20852, USA.

We previously reported that a single immunization with an adenovirus serotype 26 (Ad26)-vector-based vaccine expressing an optimized SARS-CoV-2 spike (Ad26.COV2.S) protected rhesus macaques against SARS-CoV-2 challenge. To evaluate reduced doses of Ad26.COV2.S, 30 rhesus macaques were immunized once with 1 × 10, 5 × 10, 1.125 × 10, or 2 × 10 viral particles (vp) Ad26.COV2.S or sham and were challenged with SARS-CoV-2. Vaccine doses as low as 2 × 10 vp provided robust protection in bronchoalveolar lavage, whereas doses of 1.125 × 10 vp were required for protection in nasal swabs. Activated memory B cells and binding or neutralizing antibody titers following vaccination correlated with protective efficacy. At suboptimal vaccine doses, viral breakthrough was observed but did not show enhancement of disease. These data demonstrate that a single immunization with relatively low dose of Ad26.COV2.S effectively protected against SARS-CoV-2 challenge in rhesus macaques, although a higher vaccine dose may be required for protection in the upper respiratory tract.
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http://dx.doi.org/10.1016/j.cell.2021.05.040DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8166510PMC
June 2021

Dual-state emission difluoroboron derivatives for selective detection of picric acid and reversible acid/base fluorescence switching.

Anal Methods 2021 07 3;13(25):2830-2835. Epub 2021 Jun 3.

College of Chemistry and Chemical Engineering, Anhui Province Key Laboratory of Chemistry for Inorganic/Organic Hybrid Functional Materials, Anhui University, Hefei 230601, P. R. China.

A novel difluoroboron derivative (TPEBF) containing α-cyanostilbene and tetraphenylethylene units has been designed and synthesized. TPEBF emits strong fluorescence both in dilute solutions (Φ = 19.3% in THF) and in the solid state (Φ = 49.3%), which is significantly distinct from the case of the aggregation-caused quenching (ACQ) and aggregation-induced emission (AIE) chromophores. The dual-state emission properties of the compound overcome the limitation of single-state luminescence and enable it to be used in both solid and solution states. TPEBF with strong emission in solution is utilized for sensing picric acid (PA) with high selectivity and sensitivity in THF (LOD = 497 nM) and aqueous media (LOD = 355 nM). The mechanism was described for the synergy of fluorescence resonance energy transfer (FRET) and photoinduced energy transfer (PET) based on the UV-vis absorption and fluorescence spectra, H NMR and theoretical calculations results. On the other hand, the highly efficient emission in the solid state allows the compound to be cast on paper to switch external acid/base stimuli.
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http://dx.doi.org/10.1039/d1ay00477hDOI Listing
July 2021

Mild hyperthermia promotes immune checkpoint blockade-based immunotherapy against metastatic pancreatic cancer using size-adjustable nanoparticles.

Acta Biomater 2021 May 14. Epub 2021 May 14.

Key Laboratory of Drug-Targeting and Drug Delivery System of the Education Ministry, Sichuan Engineering Laboratory for Plant-Sourced Drug and Sichuan Research Center for Drug Precision Industrial Technology, West China School of Pharmacy Sichuan University, Chengdu 610064, P.R. China. Electronic address:

Immune checkpoint blockade treatment is one of the most promising immunotherapies, which exhibits promising therapeutic effects on inhibition of metastasis. However, immunotherapy has little effect on pancreatic cancer, due to its extensive fibrotic matrix and immunosuppressive tumor microenvironment. Mild hyperthermia induced by photothermal therapy (PTT) has been proven to activate the immune responses in the tumor microenvironment. Herein, we designed a combine strategy of mild hyperthermia and immune checkpoint blockade (BMS-202) treatment with size-adjustable thermo- and fibrotic matrix- sensitive liposomes ([email protected]), in which BMS-202 loaded small-sized albumin nanoparticle (HSA-BMS) was encapsulated. Mild hyperthermia reduced the tumor hypoxia, relieved the interstitial pressure and increased the recruitment of endogenous immune cells in tumors. In the meantime, small-sized HSA-BMS was released from large-sized [email protected] in response to fibroblast activation protein-α (FAP-α) and near-infrared (NIR) laser, and enhanced the immunological responses by recovering the activity of T lymphocytes, accompanied by secreting relevant cytokines (TNF-α and IFN-γ). The combined therapy ([email protected]) could not only significantly suppress the tumor growth in vivo, but also decrease the amounts of metastatic nodules in distant organs. These results suggested that size-adjustable nanoparticles had a great potential in the treatment of metastatic pancreatic cancer. STATEMENT OF SIGNIFICANCE: The desmoplastic stroma and hypoperfusion of pancreatic cancer imposed physical barriers to effective therapies, including chemotherapy, radiotherapy, targeted therapy, and immunotherapy. We constructed size-adjustable thermo- and fibrotic matrix- sensitive liposomes ([email protected]) with size around 120 nm, where small sized albumin nanoparticle (10 nm) of immune checkpoint inhibitor (HSA-BMS) were encapsulated inside. Mild hyperthermia not only contributed to release HSA-BMS for penetration (blocking the immunosuppressive signals deep in the tumor), but enhanced tumor blood perfusion for infiltration of endogenous immune cells. In the two-pronged treatment, the pancreatic cancer immunotherapy significantly enhanced and the risk of cancer metastasis was reduced. Overall, the strategy provides a promising approach to increase drug accumulation and improve the anti-tumor immune activity in pancreatic cancer.
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http://dx.doi.org/10.1016/j.actbio.2021.05.002DOI Listing
May 2021

Safety and Efficacy of Vitamin K Antagonists vs. Novel Oral Anticoagulants in Patients With Left Ventricular Thrombus: A Meta-Analysis.

Front Cardiovasc Med 2021 29;8:636491. Epub 2021 Apr 29.

Department of Cardiology, Dushu Lake Hospital Affiliated to Soochow University, Suzhou, China.

A meta-analysis was conducted to evaluate the safety and efficacy of novel oral anticoagulants (NOACs) compared with vitamin K antagonists (VKAs) in patients with left ventricular thrombus (LVT). We searched PubMed, Web of Science, and Cochrane Library for cohort studies comparing the use of VKAs vs. NOACs for the treatment of LVT from the earliest date available to September 30, 2020. The predetermined efficacy and safety outcomes included thromboembolic events, resolution of LVT, clinically significant bleedings, and all-cause death. Fixed-effects model was used to estimate the pooled effects. Publication bias analyses and sensitivity analyses were conducted to check the robustness of results. A total of 6 studies enrolling 837 patients (mean age 60.2 ± 1.6 years; 77.2% were male) were included. We found no significant differences in thromboembolic events [relative risk (RR) 1.69, 95% confidence interval (CI) 0.94-3.06, 0.08, I 12.7%], the rate of resolution of thrombus (RR 1.08, 95% CI 0.96-1.21, 0.21, I 4.8%), and clinically significant bleedings (RR 0.70, 95% CI 0.37-1.32, 0.27, I 0%) between the VKAs and NOACs group. Additionally, no significant difference in all-cause mortality was found between the two groups (RR 1.24, 95% CI 0.79-1.96, 0.35, I 0.0%). Sensitivity analyses, using the "1-study removed" method, detected no significant differences. NOACs and VKAs have similar efficacy and safety in treating LVT, prompting the inference that NOACs are the possible alternatives of VKAs in LVT therapy.
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http://dx.doi.org/10.3389/fcvm.2021.636491DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8118127PMC
April 2021

mGPDH Deficiency leads to melanoma metastasis via induced NRF2.

J Cell Mol Med 2021 06 3;25(11):5305-5315. Epub 2021 May 3.

Department of Endocrinology, Translational Research Key Laboratory for Diabetes, Xinqiao Hospital, Army Medical University, Chongqing, China.

Oxidative stress critically influences carcinogenesis and the progression of melanoma, and aggressive malignant melanoma activity is due to its high metastatic ability. Some findings in several cancer cell lines have indicated that mGPDH, a component of the mitochondrial respiratory chain, also modulates oxidative stress. However, the role of mGPDH in melanoma remains elusive. Here, we report that the mGPDH protein level is decreased in human skin melanoma compared to normal skin and decreased in metastatic melanoma compared to primary melanoma. Our in vivo and in vitro experiments indicated that mGPDH depletion accelerated melanoma migration and invasion without affecting proliferation or apoptosis. Mechanistically, we found elevated NRF2 protein levels in human skin melanoma and mGPDH-knockout (ko) metastatic xenografts in the lungs of nude mice. Moreover, in A375 melanoma cells, the loss of mGPDH-induced NRF2 expression but did not affect NRF2 protein degradation. Additionally, melanoma metastasis induced by the loss of mGPDH was rescued by the further down-regulation of NRF2 in vivo and in vitro. Consistently, mGPDH overexpression (oe) depressed NRF2 expression and attenuated the malignant properties of melanoma cells. In conclusion, our findings suggest that mGPDH suppresses melanoma metastasis by inhibiting NRF2 and downstream oxidative signals, highlighting the therapeutic potential of mGPDH for melanoma treatment.
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http://dx.doi.org/10.1111/jcmm.16542DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8178277PMC
June 2021

Acute cardiac complications and subclinical myocardial injuries associated with pheochromocytoma and paraganglioma.

BMC Cardiovasc Disord 2021 04 21;21(1):203. Epub 2021 Apr 21.

Department of Cardiology, The First Affiliated Hospital of Soochow University, 188 Shizi Road, Suzhou City, 215006, People's Republic of China.

Background: Catecholamine excess arising from pheochromocytomas and paragangliomas (PPGLs) can cause a wide spectrum of cardiac manifestations, including acute cardiac complications (ACCs) and subclinical myocardial injuries (SMIs). In this study, we aimed to conduct a comprehensive analysis of ACCs and SMIs in a large cohort of patients with PPGLs.

Methods: We retrospectively analyzed the clinical data of consecutive patients with PPGLs admitted between January 2013 and July 2020 (n = 189). The prevalence of ACCs and SMIs and characteristics of patients identified with ACCs and SMIs were investigated. Moreover, comparisons were performed between patients with and without ACCs.

Results: Fourteen patients (7.4%) fulfilled the criteria for ACCs, including nine (4.8%) who presented with Takotsubo-like cardiomyopathy, four (2.1%) with heart failure with preserved ejection fraction, and finally one (0.5%) with catecholamine-induced cardiomyopathy. Compared to those without ACCs (n = 175), patients with ACCs had a higher prevalence of epinephrine-producing PPGLs (81.8% vs 33.9%, P = 0.006) and were more likely to show invasive behavior (61.5% vs 27.3%, P = 0.022) or hemorrhage/necrosis (53.9% vs 17.4%, P = 0.005) on histology. The apical sparing pattern (5/7, 71.4%) was the dominant impairment pattern of longitudinal strain (LS) for patients displaying Takotsubo-like cardiomyopathy. In patients without cardiac symptoms, a fairly high proportion (21/77, 27.3%) of patients who underwent screening for troponin and/or natriuretic peptide and/or echocardiography had SMIs.

Conclusions: One in every fourteen PPGL patients presented with ACCs, and in the patients with Takotsubo-like cardiomyopathy, the apical sparing pattern was the primary impairment pattern of LS. Additionally, nearly one-third of patients without symptoms had SMIs. The diagnosis of PPGLs should be considered in patients with acute reversible cardiomyopathy, especially in those exhibiting an apical sparing pattern of LS.
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http://dx.doi.org/10.1186/s12872-021-02013-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8060996PMC
April 2021

Impact of the gut microbiota on heat stroke rat mediated by Xuebijing metabolism.

Microb Pathog 2021 Jun 20;155:104861. Epub 2021 Apr 20.

The First Clinical Medical College, Southern Medical University, Guangzhou, China; Department of Critical Care Medicine, General Hospital of Guangzhou Military Command, Guangzhou, China. Electronic address:

The goal of the present study was to evaluate the fecal microbiome and serum metabolites in Xuebijing (XBJ)-injected rats after heat stroke using 16S rRNA gene sequencing and gas chromatography-mass spectrometry (GC-MS) metabolomics. Eighteen rats were divided into the control group (CON), heat stroke group (HS), and XBJ group. The 16S rRNA gene sequencing results revealed that the abundance of Bacteroidetes was overrepresented in the XBJ group compared to the HS group, while Actinobacteria was underrepresented. Metabolomic profiling showed that the pyrimidine metabolism pathway, pentose phosphate pathway, and glycerophospholipid metabolism pathway were upregulated in the XBJ group compared to the HS group. Taken together, these results demonstrated that heat stroke not only altered the gut microbiome community structure of rats but also greatly affected metabolic functions, leading to gut microbiome toxicity.
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http://dx.doi.org/10.1016/j.micpath.2021.104861DOI Listing
June 2021

Modeling multi-species RNA modification through multi-task curriculum learning.

Nucleic Acids Res 2021 04;49(7):3719-3734

Institute for Interdisciplinary Information Sciences, Tsinghua University, Beijing 100084, China.

N6-methyladenosine (m6A) is the most pervasive modification in eukaryotic mRNAs. Numerous biological processes are regulated by this critical post-transcriptional mark, such as gene expression, RNA stability, RNA structure and translation. Recently, various experimental techniques and computational methods have been developed to characterize the transcriptome-wide landscapes of m6A modification for understanding its underlying mechanisms and functions in mRNA regulation. However, the experimental techniques are generally costly and time-consuming, while the existing computational models are usually designed only for m6A site prediction in a single-species and have significant limitations in accuracy, interpretability and generalizability. Here, we propose a highly interpretable computational framework, called MASS, based on a multi-task curriculum learning strategy to capture m6A features across multiple species simultaneously. Extensive computational experiments demonstrate the superior performances of MASS when compared to the state-of-the-art prediction methods. Furthermore, the contextual sequence features of m6A captured by MASS can be explained by the known critical binding motifs of the related RNA-binding proteins, which also help elucidate the similarity and difference among m6A features across species. In addition, based on the predicted m6A profiles, we further delineate the relationships between m6A and various properties of gene regulation, including gene expression, RNA stability, translation, RNA structure and histone modification. In summary, MASS may serve as a useful tool for characterizing m6A modification and studying its regulatory code. The source code of MASS can be downloaded from https://github.com/mlcb-thu/MASS.
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http://dx.doi.org/10.1093/nar/gkab124DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8053129PMC
April 2021

Deletion of the SARS-CoV-2 Spike Cytoplasmic Tail Increases Infectivity in Pseudovirus Neutralization Assays.

J Virol 2021 Mar 16. Epub 2021 Mar 16.

Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA

Pseudotyped viruses are valuable tools for studying virulent or lethal viral pathogens that need to be handled in biosafety level 3 (BSL-3) or higher facilities. With the explosive spread of the coronavirus disease 2019 (COVID-19) pandemic, the establishment of a BSL-2 adapted SARS-CoV-2 pseudovirus neutralization assay is needed to facilitate the development of countermeasures. Here we describe an approach to generate a single-round lentiviral vector-based SARS-CoV-2 pseudovirus, which produced a signal more than 2 logs above background. Specifically, a SARS-CoV-2 spike variant with a cytoplasmic tail deletion of 13 amino acids, termed SΔCT13, conferred enhanced spike incorporation into pseudovirions and increased viral entry into cells as compared with full-length spike (S). We further compared S and SΔCT13 in terms of their sensitivity to vaccine sera, purified convalescent IgG, hACE2-mIgG, and the virus entry inhibitor BafA1. We developed a SΔCT13-based pseudovirus neutralization assay and defined key assay characteristics, including linearity, limit of detection, and intra- and intermediate-assay precision. Our data demonstrate that the SΔCT13-based pseudovirus shows enhanced infectivity in target cells, which will facilitate the assessment of humoral immunity to SARS-CoV-2 infection, antibody therapeutics, and vaccination. This pseudovirus neutralization assay can also be readily adapted to SARS-CoV-2 variants that emerge.SARS-CoV-2 is the etiologic agent of the COVID-19 pandemic. The development of a high throughput pseudovirus neutralization assay is critical for the development of vaccines and immune-based therapeutics. In this study, we show that deletion of the cytoplasmic tail of the SARS-CoV-2 spike leads to pseudoviruses with enhanced infectivity. This SΔCT13-based pseudovirus neutralization assay should be broadly useful for the field.
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http://dx.doi.org/10.1128/JVI.00044-21DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8139703PMC
March 2021

A computational and experimental investigation of donor-acceptor BODIPY based near-infrared fluorophore for in vivo imaging.

Bioorg Chem 2021 05 4;110:104789. Epub 2021 Mar 4.

College of Chemistry and Chemical Engineering, Key Laboratory of Functional Inorganic Materials of Anhui Province, Anhui University, Hefei 230039, PR China. Electronic address:

TD-DFT quantum calculation was performed to predict and/or illustrate the electronic transition, the related absorption and emission maxima of some pyrrole-difluoroboron derivatives with different electron donor-acceptor unit or π-conjugated degree. Upon the calculated results, a new near infrared (NIR) fluorophore (abbreviated as TPBD-BP) was designed and fabricated through linking triphenylamine and pyrrole-difluoroboron units to benzothiadiazole (BTD) backbone. The fluorescence of TPBD-BP in solid state centered at 932 nm, which was 985 nm for TPBD-BP nanoparticles (TPBD-BP dots) encapsulated in PEG-6000. The fluorescence of TPBD-BP in both solid state and dots exhibited off-peak tail emission to NIR-II region (extended to 1300 nm). The TPBD-BP dots showed excellent water solubility, biocompatibility and aggregation induced emission (AIE), which was suitable to be applied in vivo imaging. NIR-II emission signal of TPBD-BP dots can be observed in the reproductive organ of normal nude mice after tail vein injection. This attractive combination of computational and experimental investigation would help to develop new-typed small-molecular NIR fluorophores.
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http://dx.doi.org/10.1016/j.bioorg.2021.104789DOI Listing
May 2021

Characterizing RNA Pseudouridylation by Convolutional Neural Networks.

Genomics Proteomics Bioinformatics 2021 Feb 22. Epub 2021 Feb 22.

Institute for Interdisciplinary Information Sciences, Tsinghua University, Beijing 100084, China; MOE Key Laboratory of Bioinformatics, Tsinghua University, Beijing 100084, China. Electronic address:

Pseudouridine (Ψ) is the most prevalent post-transcriptional RNA modification and is widespread in small cellular RNAs and mRNAs. However, the functions, mechanisms and precise distribution of Ψs (especially in mRNAs) still remain largely unclear. The landscape of Ψs across the transcriptome has not yet been fully delineated. Here, we present a highly effective model based on a convolutional neural network (CNN), called PULSE, to analyze large-scale profiling data of Ψ sites and characterize the contextual sequence features of pseudouridylation. PULSE, consisting of two alternatively stacked convolution and pooling layers followed by a fully-connected neural network, can automatically learn the hidden patterns of pseudouridylation from the local sequence information. Extensive validation tests demonstrated that PULSE can outperform other state-of-the-art prediction methods and achieve high prediction accuracy, thus enabling us to further characterize the transcriptome-wide landscape of Ψ sites. We further showed that the prediction results derived from PULSE can provide novel insights into understanding the functional roles of pseudouridylation, such as the regulations of RNA secondary structure, codon usage, translation, and RNA stability, and the connection to single nucleotide variants.
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http://dx.doi.org/10.1016/j.gpb.2019.11.015DOI Listing
February 2021

Transcriptomic and genome-wide association study reveal long noncoding RNAs responding to nitrogen deficiency in maize.

BMC Plant Biol 2021 Feb 12;21(1):93. Epub 2021 Feb 12.

Maize Research Institute, Sichuan Agricultural University, Chengdu, 611130, Sichuan, China.

Background: Long noncoding RNAs (lncRNAs) play important roles in essential biological processes. However, our understanding of lncRNAs as competing endogenous RNAs (ceRNAs) and their responses to nitrogen stress is still limited.

Results: Here, we surveyed the lncRNAs and miRNAs in maize inbred line P178 leaves and roots at the seedling stage under high-nitrogen (HN) and low-nitrogen (LN) conditions using lncRNA-Seq and small RNA-Seq. A total of 894 differentially expressed lncRNAs and 38 different miRNAs were identified. Co-expression analysis found that two lncRNAs and four lncRNA-targets could competitively combine with ZmmiR159 and ZmmiR164, respectively. To dissect the genetic regulatory by which lncRNAs might enable adaptation to limited nitrogen availability, an association mapping panel containing a high-density single-nucleotide polymorphism (SNP) array (56,110 SNPs) combined with variable LN tolerant-related phenotypes obtained from hydroponics was used for a genome-wide association study (GWAS). By combining GWAS and RNA-Seq, 170 differently expressed lncRNAs within the range of significant markers were screened. Moreover, 40 consistently LN-responsive genes including those involved in glutamine biosynthesis and nitrogen acquisition in root were identified. Transient expression assays in Nicotiana benthamiana demonstrated that LNC_002923 could inhabit ZmmiR159-guided cleavage of Zm00001d015521.

Conclusions: These lncRNAs containing trait-associated significant SNPs could consider to be related to root development and nutrient utilization. Taken together, the results of our study can provide new insights into the potential regulatory roles of lncRNAs in response to LN stress, and give valuable information for further screening of candidates as well as the improvement of maize resistance to LN stress.
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http://dx.doi.org/10.1186/s12870-021-02847-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7879672PMC
February 2021

Overview of methods for enhancing bone regeneration in distraction osteogenesis: Potential roles of biometals.

J Orthop Translat 2021 Mar 2;27:110-118. Epub 2021 Feb 2.

Musculoskeletal Research Laboratory, Department of Orthopaedics & Traumatology, The Chinese University of Hong Kong, Hong Kong.

Background: Distraction osteogenesis (DO) is a functional tissue engineering approach that applies gradual mechanical traction on the bone tissues after osteotomy to stimulate bone regeneration. However, DO still has disadvantages that limit its clinical use, including long treatment duration.

Methods: Review the current methods of promoting bone formation and consolidation in DO with particular interest on biometal.

Results: Numerous approaches, including physical therapy, gene therapy, growth factor-based therapy, stem-cell-based therapy, and improved distraction devices, have been explored to reduce the DO treatment duration with some success. Nevertheless, no approach to date is widely accepted in clinical practice due to various reasons, such as high expense, short biologic half-life, and lack of effective delivery methods. Biometals, including calcium (Ca), magnesium (Mg), zinc (Zn), copper (Cu), manganese (Mn), and cobalt (Co) have attracted attention in bone regeneration attributed to their biodegradability and bioactive components released during in vivo degradation.

Conclusion: This review summarizes the current therapies accelerating bone formation in DO and the beneficial role of biometals in bone regeneration, particularly focusing on the use of biometal Mg and its alloy in promoting bone formation in DO. Translational potential: The potential clinical applications using Mg-based devices to accelerate DO are promising. Mg stimulates expression of multiple intrinsic biological factors and the development of Mg as an implantable component in DO may be used to argument bone formation and consolidation in DO.
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http://dx.doi.org/10.1016/j.jot.2020.11.008DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7859169PMC
March 2021

Low-Dose Ad26.COV2.S Protection Against SARS-CoV-2 Challenge in Rhesus Macaques.

bioRxiv 2021 Jan 27. Epub 2021 Jan 27.

We previously reported that a single immunization with an adenovirus serotype 26 (Ad26) vector-based vaccine expressing an optimized SARS-CoV-2 spike (Ad26.COV2.S) protected rhesus macaques against SARS-CoV-2 challenge. In this study, we evaluated the immunogenicity and protective efficacy of reduced doses of Ad26.COV2.S. 30 rhesus macaques were immunized once with 1×10 , 5×10 , 1.125×10 , or 2×10 vp Ad26.COV2.S or sham and were challenged with SARS-CoV-2 by the intranasal and intratracheal routes. Vaccine doses as low as 2×10 vp provided robust protection in bronchoalveolar lavage, whereas doses of 1.125×10 vp were required for protection in nasal swabs. Activated memory B cells as well as binding and neutralizing antibody titers following vaccination correlated with protective efficacy. At suboptimal vaccine doses, viral breakthrough was observed but did not show evidence of virologic, immunologic, histopathologic, or clinical enhancement of disease compared with sham controls. These data demonstrate that a single immunization with a relatively low dose of Ad26.COV2.S effectively protected against SARS-CoV-2 challenge in rhesus macaques. Moreover, our findings show that a higher vaccine dose may be required for protection in the upper respiratory tract compared with the lower respiratory tract.
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http://dx.doi.org/10.1101/2021.01.27.428380DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7852276PMC
January 2021

Biomaterials developed for facilitating healing outcome after anterior cruciate ligament reconstruction: Efficacy, surgical protocols, and assessments using preclinical animal models.

Biomaterials 2021 02 23;269:120625. Epub 2020 Dec 23.

Musculoskeletal Research Laboratory of Department of Orthopaedics & Traumatology and Innovative Orthopaedic Biomaterial and Drug Translational Research Laboratory of Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Hong Kong Special Administrative Region. Electronic address:

Anterior cruciate ligament (ACL) reconstruction is the recommended treatment for ACL tear in the American Academy of Orthopaedic Surgeons (AAOS) guideline. However, not a small number of cases failed because of the tunnel bone resorption, unsatisfactory bone-tendon integration, and graft degeneration. The biomaterials developed and designed for improving ACL reconstruction have been investigated for decades. According to the Food and Drug Administration (FDA) and the International Organization for Standardization (ISO) regulations, animal studies should be performed to prove the safety and bioeffect of materials before clinical trials. In this review, we first evaluated available biomaterials that can enhance the healing outcome after ACL reconstruction in animals and then discussed the animal models and assessments for testing applied materials. Furthermore, we identified the relevance and knowledge gaps between animal experimental studies and clinical expectations. Critical analyses and suggestions for future research were also provided to design the animal study connecting basic research and requirements for future clinical translation.
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http://dx.doi.org/10.1016/j.biomaterials.2020.120625DOI Listing
February 2021

Robust Supramolecular Nano-Tunnels Built from Molecular Bricks*.

Angew Chem Int Ed Engl 2021 Mar 9;60(13):7148-7154. Epub 2021 Feb 9.

Department of Chemistry, The Hong Kong Branch of Chinese National Engineering Research Center for Tissue Restoration and Reconstruction, SCUT-HKUST Joint Research Institute, Institute for Advanced Study, Department of Chemical and Biological Engineering, The Hong Kong University of Science and Technology, Clear Water Bay, Kowloon, Hong Kong, China.

Herein we report a linear ionic molecule that assembles into a supramolecular nano-tunnel structure through synergy of trident-type ionic interactions and π-π stacking interactions. The nano-tunnel crystal exhibits anisotropic guest adsorption behavior. The material shows good thermal stability and undergoes multi-stage single-crystal-to-single-crystal phase transformations to a nonporous structure on heating. The material exhibits a remarkable chemical stability under both acidic and basic conditions, which is rarely observed in supramolecular organic frameworks and is often related to structures with designed hydrogen-bonding interactions. Because of the high polarity of the tunnels, this molecular crystal also shows a large CO -adsorption capacity while excluding other gases at ambient temperature, leading to high CO /CH selectivity. Aggregation-induced emission of the molecules gives the bulk crystals vapochromic properties.
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http://dx.doi.org/10.1002/anie.202013117DOI Listing
March 2021

Dexmedetomidine for the prevention of postoperative delirium in patients after intracranial operation for brain tumours (DEPOD study): a study protocol and statistical plan for a multicentre randomised controlled trial.

BMJ Open 2020 11 23;10(11):e040939. Epub 2020 Nov 23.

Department of Critical Care Medicine, Beijing Tiantan Hospital, Capital Medical University, Beijing, China

Introduction: Postoperative delirium (POD) is prevalent in patients after major surgery and is associated with adverse outcomes. Several studies have reported that dexmedetomidine, a highly selective α2-adrenergic receptor agonist, can decrease the incidence of POD. However, neurosurgical patients are usually excluded from previous studies. The present study was designed to investigate the impact of prophylactic use of low-dose dexmedetomidine on the incidence of POD in patients after intracranial operation.

Methods And Analysis: This is a multicentre, randomised, double-blinded and placebo-controlled trial. Seven hundred intensive care unit admitted patients after elective intracranial operation for brain tumours under general anaesthesia are randomly assigned to the dexmedetomidine group or the placebo group with a 1:1 ratio. For patients in the dexmedetomidine group, a continuous infusion of dexmedetomidine will be started at a rate of 0.1 μg/kg/hour immediately after enrolment on the day of operation and continued until 08:00 on postoperative day 1. For patients in the placebo group, normal saline will be administered at the same rate as in the dexmedetomidine group. The patients will be followed up for 28 days after enrolment. The primary endpoint is the incidence of POD, which is assessed two times per day using the Confusion Assessment Method for the intensive care unit (ICU), during the first 5 postoperative days. The secondary endpoints include the incidence of dexmedetomidine-related adverse events and non-delirium complications, the length of stay in the ICU and hospital and all-cause 28-day mortality after the operation.

Ethics And Dissemination: The study protocol was approved by the Institutional Review Board of Beijing Tiantan Hospital Affiliated to Capital Medical University (No KY2019-091-02) and registered at ClinicalTrials.gov. The results of the trial will be presented at national and international conferences relevant to subject fields and submitted to international peer-reviewed journals.

Trial Registration Number: Trial registration number: NCT04399343; Pre-results.
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http://dx.doi.org/10.1136/bmjopen-2020-040939DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7684814PMC
November 2020

Idiopathic Pulmonary Fibrosis Registry China study (PORTRAY): protocol for a prospective, multicentre registry study.

BMJ Open 2020 11 11;10(11):e036809. Epub 2020 Nov 11.

Department of Pulmonary and Critical Care Medicine, Center of Respiratory Medicine, China-Japan Friendship Hospital, Capital Medical University, National Center for Respiratory Medicine, National Clinical Research Center for Respiratory Diseases, Institute of Respiratory Medicine, Chinese Academy of Medical Science, Beijing, China.

Introduction: Idiopathic pulmonary fibrosis (IPF) is a progressive and lethal lung disease characterised by a fibrotic histological pattern found in usual interstitial pneumonia. Its causes, pathogenesis, clinical phenotype and molecular mechanisms are poorly defined. Large-scale, multicentre studies are warranted to better understand IPF as a disease in China, its associated risk factors, clinical characteristics, diagnosis, disease progression and treatment.

Methods And Analysis: The Idiopathic Pulmonary Fibrosis Registry China Study (PORTRAY) is a prospective, multicentre registry study of patients with IPF in China. Eight hundred patients will be enrolled over a 36-month period and followed for at least 3 years to generate a comprehensive database on baseline characteristics and various follow-up parameters including patient-reported outcomes. Biological specimens will also be collected from patients to develop a library of blood, bronchoalveolar lavage fluid and lung biopsy samples, to support future research. As of 15 December 2019, 204 patients from 19 large medical centres with relatively high IPF diagnosis and treatment rates had been enrolled. Patient characteristics will be presented using descriptive statistics. The Kaplan-Meier method will be used for survival analyses. Repeated measures will be used to compare longitudinal changes in lung function, imaging and laboratory tests. Results following analysis have been projected to be available by July 2025.

Ethics And Dissemination: The study protocol was reviewed and approved by the Institutional Review Board from all the study sites currently recruiting patients. Study results will be published in peer-reviewed journals.

Trial Registration Number: NCT03666234.
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http://dx.doi.org/10.1136/bmjopen-2020-036809DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7661367PMC
November 2020

The Novel Target of Colorectal Carcinoma: TRIM44 Regulates Cell Migration and Invasion via Activation of CXCR4/NF-κB Signaling.

Cell Biochem Biophys 2021 Mar 5;79(1):113-121. Epub 2020 Nov 5.

Pathology Department, Characteristic Medical Center of Chinese People's Armed Police Force, Tianjin, 300162, China.

Tripartite motif containing 44 (TRIM44) has been reported to regulate various biological effects in malignant cancers and matrix Metalloproteinases has been demonstrated to be associated with cancer cell migration and invasion. Nonetheless, the expression and molecular mechanism of TRIM44 in colorectal cancer (CRC) remain rarely known. TRIM44 was overexpressed or knocked down in CRC cells. Subsequently, the effects of TRIM44 on cell migration and invasion as well as underlying molecular mechanisms were detected. Data showed that TRIM44 was highly expressed in CRC cell lines. Downregulation of TRIM44 inhibited the cell viability, migration, and invasion in SW-480 cells. In addition, overexpression of TRIM44 enhanced the expression of NF-κB and CXCR4, and enhanced the binding between NF-κB and CXCR4 promoter region. In summarize, TRIM44 may serve as a potential target for CRC diagnosis and progression.
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http://dx.doi.org/10.1007/s12013-020-00955-wDOI Listing
March 2021

Identification, Association of Natural Variation and Expression Analysis of Gene Response to Low Phosphorus in Maize Seedling Stage.

Plants (Basel) 2020 Oct 27;9(11). Epub 2020 Oct 27.

Key Laboratory of Crop Gene and Exploration and Utilization in Southwest Region, Maize Research Institute, Sichuan Agriculture University, Chengdu 611130, China.

Phosphorus (P) is an essential macroelement supporting maize productivity and low-P stress is a limiting factor of maize growth and yield. Improving maize plant tolerance to low P through molecular breeding is an effective alternative to increase crop productivity. In this study, a total of 111 diverse maize inbred lines were used to identify the favorable alleles and nucleotide diversity of candidate , which plays an important role in response to low P and regulation in root architecture. A significant difference was found under low- and sufficient-P conditions for each of the 22 seedling traits, and a total of 41 polymorphic sites including 32 single nucleotide polymorphisms (SNPs) and 9 insertion and deletions (InDels) were detected in among 111 inbred lines. Among the 41 polymorphic studied sites, a total of 39 polymorphic sites were associated with 20 traits except for the dry weight of shoots and forks, of which six sites were highly significantly associated with a diverse number of low-P tolerant root trait index values by using a mixed linear model (MLM) at -log10 P = 3.61. In addition, 29 polymorphic sites under P-sufficient and 32 polymorphic sites under P-deficient conditions were significantly associated with a diverse number of seedling traits, of which five polymorphic sites (position S327, S513, S514, S520, and S827) were strongly significantly associated with multiple seedling traits under low-P and normal-P conditions. Among highly significant sites, most of the sites were associated with root traits under low-P, normal-P, and low-P trait index values. Linkage disequilibrium (LD) was strong at (r2 > 1.0) in 111 inbred lines. Furthermore, the effect of five significant sites was verified for haplotypes in 111 lines and the favorable allele S520 showed a positive effect on the dry weight of roots under the low-P condition. Furthermore, the expression pattern confirmed that was highly induced by low P in the roots of the P-tolerant 178 inbred line. Moreover, the subcellular localization of encoded by protein was located in the cytoplasm and nucleus. Haplotypes carrying more favorable alleles exhibited superior effects on phenotypic variation and could be helpful in developing molecular markers in maize molecular breeding programs. Taken together, the finding of this study might lead to further functions of and genes that might be involved in responses to low-P stress in maize.
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http://dx.doi.org/10.3390/plants9111447DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7716212PMC
October 2020

A Two-Stage Cooperative Evolutionary Algorithm With Problem-Specific Knowledge for Energy-Efficient Scheduling of No-Wait Flow-Shop Problem.

IEEE Trans Cybern 2020 Oct 23;PP. Epub 2020 Oct 23.

Green scheduling in the manufacturing industry has attracted increasing attention in academic research and industrial applications with a focus on energy saving. As a typical scheduling problem, the no-wait flow-shop scheduling has been extensively studied due to its wide industrial applications. However, energy consumption is usually ignored in the study of typical scheduling problems. In this article, a two-stage cooperative evolutionary algorithm with problem-specific knowledge called TS-CEA is proposed to address energy-efficient scheduling of the no-wait flow-shop problem (EENWFSP) with the criteria of minimizing both makespan and total energy consumption. In TS-CEA, two constructive heuristics are designed to generate a desirable initial solution after analyzing the properties of the problem. In the first stage of TS-CEA, an iterative local search strategy (ILS) is employed to explore potential extreme solutions. Moreover, a hybrid neighborhood structure is designed to improve the quality of the solution. In the second stage of TS-CEA, a mutation strategy based on critical path knowledge is proposed to extend the extreme solutions to the Pareto front. Moreover, a co-evolutionary closed-loop system is generated with ILS and mutation strategies in the iteration process. Numerical results demonstrate the effectiveness and efficiency of TS-CEA in solving the EENWFSP.
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http://dx.doi.org/10.1109/TCYB.2020.3025662DOI Listing
October 2020
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