Publications by authors named "Jianing Li"

142 Publications

F-RGD PET/CT and Systemic Inflammatory Biomarkers Predict Outcomes of Patients With Advanced NSCLC Receiving Combined Antiangiogenic Treatment.

Front Oncol 2021 4;11:671912. Epub 2021 Jun 4.

Department of Radiation Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, China.

Background: The aim of this study was to evaluate F-AlF-NOTA-PRGD2 positron emission tomography/computed tomography (F-RGD PET/CT) and serum inflammation biomarkers for predicting outcomes of patients receiving combined antiangiogenic treatment for advanced non-small cell lung cancer (NSCLC).

Methods: Patients with advanced NSCLC underwent F-RGD PET/CT examination and provided blood samples before treatments commenced. PET/CT parameters included maximum standard uptake value (SUVmax) and mean standard uptake value (SUVmean), peak standard uptake value (SUVpeak) and metabolic tumor volume (MTV) for all contoured lesions. Biomarkers for inflammation included pretreatment neutrophil-to-lymphocyte ratio (PreNLR), pretreatment platelet-to-lymphocyte ratio (PrePLR), and pretreatment lymphocyte-to-monocyte ratio (PreLMR). Receiver operating characteristic (ROC) curve analysis was used to describe response prediction accuracy. Logistic regression and Cox's regression analysis was implemented to identify independent factors for short-term responses and progression-free survival (PFS).

Results: This study included 23 patients. According to ROC curve analysis, there were significant correlations between the SUVmax, SUVmean, and F-RGD PET/CT MTV and short-term responses (<0.05). SUVmax was identified using logistic regression analysis as a significant predictor of treatment sensitivity (=0.008). Cox's multivariate regression analysis suggested that high SUVpeak (=0.021) and high PreLMR (=0.03) were independent PFS predictors. Combining SUVpeak and PreLMR may also increase the prognostic value for PFS, enabling us to identify a subgroup of patients with intermediate PFS.

Conclusion: F-RGD uptake on PET/CT and serum inflammation biomarker pretreatment may predict outcomes for combined antiangiogenic treatments for advanced NSCLC patients. Higher F-RGD uptake and higher PreLMR also appear to predict improved short-term responses and PFS. Combining biomarkers may therefore provide a basis for risk stratification, although further research is required.
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http://dx.doi.org/10.3389/fonc.2021.671912DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8212050PMC
June 2021

Enhanced Sampling Protocol to Elucidate Fusion Peptide Opening of SARS-CoV-2 Spike Protein.

Biophys J 2021 Jun 1. Epub 2021 Jun 1.

Large-scale conformational transitions in the spike protein S2 domain are required during host cell infection of the SARS-CoV-2 virus. Although conventional molecular dynamics simulations have been extensively used to study therapeutic targets of SARS-CoV-2, it is still challenging to gain molecular insight into the key conformational changes due to the size of the spike protein and the long timescale required to capture these transitions. In this work, we have developed an efficient simulation protocol that leverages many short simulations, a novel selection algorithm, and Markov state models to interrogate the dynamics of the S2 domain. We discovered that the conformational flexibility of the dynamic region upstream of the fusion peptide in S2 is coupled to the proteolytic cleavage state of the spike protein. These results suggest that opening of the fusion peptide likely occurs on a sub-microsecond timescale following cleavage at the S2' site. Building on the structural and dynamical information gained to date about S2 domain dynamics, we provide proof-of-principle that a small molecule bound to a seam neighboring the fusion peptide can slow the opening of the fusion peptide, leading to a new inhibition strategy for experiments to confirm. In aggregate, these results will aid the development of drug cocktails to inhibit infections caused by SARS-CoV-2 and other coronaviruses.
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http://dx.doi.org/10.1016/j.bpj.2021.05.022DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8169235PMC
June 2021

Iterative Exponential Growth of Oxygen-Linked Aromatic Polymers Driven by Nucleophilic Aromatic Substitution Reactions.

Front Chem 2021 28;9:620017. Epub 2021 Apr 28.

Department of Chemistry, University of Vermont, Burlington, VT, United States.

This work presents the first transition metal-free synthesis of oxygen-linked aromatic polymers by integrating iterative exponential polymer growth (IEG) with nucleophilic aromatic substitution (SAr) reactions. Our approach applies methyl sulfones as the leaving groups, which eliminate the need for a transition metal catalyst, while also providing flexibility in functionality and configuration of the building blocks used. As indicated by 1) H-H NOESY NMR spectroscopy, 2) single-crystal X-ray crystallography, and 3) density functional theory (DFT) calculations, the unimolecular polymers obtained are folded by nonclassical hydrogen bonds formed between the oxygens of the electron-rich aromatic rings and the positively polarized C-H bonds of the electron-poor pyrimidine functions. Our results not only introduce a transition metal-free synthetic methodology to access precision polymers but also demonstrate how interactions between relatively small, neutral aromatic units in the polymers can be utilized as new supramolecular interaction pairs to control the folding of precision macromolecules.
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http://dx.doi.org/10.3389/fchem.2021.620017DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8113702PMC
April 2021

Computed Tomography-Based Delta-Radiomics Analysis for Discriminating Radiation Pneumonitis in Patients With Esophageal Cancer After Radiation Therapy.

Int J Radiat Oncol Biol Phys 2021 May 8. Epub 2021 May 8.

Department of Radiation Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, China. Electronic address:

Purpose: Our purpose was to construct a computed tomography (CT)-based delta-radiomics nomogram and corresponding risk classification system for individualized and accurate estimation of severe acute radiation pneumonitis (SARP) in patients with esophageal cancer (EC) after radiation therapy.

Methods And Materials: Four hundred patients with EC were enrolled from 2 independent institutions and were divided into the training (n = 200) and validation (n = 200) cohorts. Eight hundred fifty radiomics features of lung were extracted from treatment planning images, including the positioning CT before radiation therapy (CT) and the resetting CT after receiving 40 to 45 Gy (CT). The longitudinal net changes in radiomics features from CT to CT were calculated and defined as delta-radiomics features. Least absolute shrinkage and selection operator algorithm was performed to features selection and delta-radiomics signature building. Integrating the signature with multidimensional clinicopathologic, dosimetric, and hematological predictors of SARP, a novel CT-based delta-radiomics nomogram was established according to multivariate analysis. The clinical application values of nomogram were both evaluated in the training and validation cohorts by concordance index, calibration curves, and decision curve analysis. Recursive partitioning analysis was used to generate a risk classification system.

Results: The delta-radiomics signature consisting of 24 features was significantly associated with SARP status (P < .001). Incorporating it with other high-risk factors, Subjective Global Assessment score, pulmonary fibrosis score, mean lung dose, and systemic immune inflammation index, the developed delta-radiomics nomogram showed increased improvement in SARP discrimination accuracy with concordance index of 0.975 and 0.921 in the training and validation cohorts, respectively. Calibration curves and decision curve analysis confirmed the satisfactory clinical feasibility and utility of nomogram. The risk classification system displayed excellent performance on identifying SARP occurrence (P < .001).

Conclusions: The delta-radiomics nomogram and risk classification system as low-cost and noninvasive means exhibited superior predictive accuracy and provided individualized probability of SARP stratification for patients with EC.
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http://dx.doi.org/10.1016/j.ijrobp.2021.04.047DOI Listing
May 2021

Molecular Basis of Class B GPCR Selectivity for the Neuropeptides PACAP and VIP.

Front Mol Biosci 2021 25;8:644644. Epub 2021 Mar 25.

Department of Chemistry, University of Vermont, Burlington, VT, United States.

The related neuropeptides PACAP and VIP, and their shared PAC1, VPAC1 and VPAC2 receptors, regulate a large array of physiological activities in the central and peripheral nervous systems. However, the lack of comparative and molecular mechanistic investigations hinder further understanding of their preferred binding selectivity and function. PACAP and VIP have comparable affinity at the VPAC1 and VPAC2 receptor, but PACAP is 400-1,000 fold more potent than VIP at the PAC1 receptor. A molecular understanding of the differing neuropeptide-receptor interactions and the details underlying the receptor transitions leading to receptor activation are much needed for the rational design of selective ligands. To these ends, we have combined structural information and advanced simulation techniques to study PACAP/VIP binding selectivity, full-length receptor conformation ensembles and transitions of the PACAP/VIP receptor variants and subtypes, and a few key interactions in the orthosteric-binding pocket. Our results reveal differential peptide-receptor interactions (at the atomistic detail) important for PAC1, VPAC1 and VPAC2 receptor ligand selectivity. Using microsecond-long molecular dynamics simulations and the Markov State Models, we have also identified diverse receptor conformational ensembles and microstate transition paths for each receptor, the potential mechanisms underlying receptor open and closed states, and the interactions and dynamics at the transmembrane orthosteric pocket for receptor activation. These analyses reveal important features in class B GPCR structure-dynamics-function relationships, which provide novel insights for structure-based drug discovery.
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http://dx.doi.org/10.3389/fmolb.2021.644644DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8027070PMC
March 2021

Analysis of Risk Factors for Thromboembolic Events in 88 Patients with COVID-19 Pneumonia in Wuhan, China: A Retrospective Descriptive Report.

Med Sci Monit 2021 Apr 11;27:e929708. Epub 2021 Apr 11.

Department of Respiratory and Critical Medicine, The Second Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang, China (mainland).

BACKGROUND Since the outbreak of COVID-19 in December 2019, there have been 96 623 laboratory-confirmed cases and 4784 deaths by December 29 in China. We aimed to analyze the risk factors and the incidence of thrombosis from patients with confirmed COVID-19 pneumonia. MATERIAL AND METHODS Eighty-eight inpatients with confirmed COVID-19 pneumonia were reported (31 critical cases, 33 severe cases, and 24 common cases). The thrombosis risk factor assessment, laboratory results, ultrasonographic findings, and prognoses of these patients were analyzed, and compared among groups with different severity. RESULTS Nineteen of the 88 cases developed DVT (12 critical cases, 7 severe cases, and no common cases). In addition, among the 18 patients who died, 5 were diagnosed with DVT. Positive correlations were observed between the increase in D-dimer level (≥5 µg/mL) and the severity of COVID-19 pneumonia (r=0.679, P<0.01), and between the high Padua score (≥4) and the severity (r=0.799, P<0.01). In addition, the CRP and LDH levels on admission had positive correlations with the severity of illness (CRP: r=0.522, P<0.01; LDH: r=0.600, P<0.01). A negative correlation was observed between the lymphocyte count on admission and the severity of illness (r=-0.523, P<0.01). There was also a negative correlation between the lymphocyte count on admission and mortality in critical patients (r=-0.499, P<0.01). Univariable logistic regression analysis showed that the occurrence of DVT was positively correlated with disease severity (crude odds ratio: 3.643, 95% CI: 1.218-10.896, P<0.05). CONCLUSIONS Our report illustrates that critically or severely ill patients have an associated high D-dimer value and high Padua score, and illustrates that a low threshold to screen for DVT may help improve detection of thromboembolism in these groups of patients, especially in asymptomatic patients. Our results suggest that early administration of prophylactic anticoagulant would benefit the prognosis of critical patients with COVID-19 pneumonia and would likely reduce thromboembolic rates.
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http://dx.doi.org/10.12659/MSM.929708DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8047776PMC
April 2021

AMPGAN v2: Machine Learning-Guided Design of Antimicrobial Peptides.

J Chem Inf Model 2021 May 31;61(5):2198-2207. Epub 2021 Mar 31.

Department of Chemistry, University of Vermont, Burlington, Vermont 05405, United States.

Antibiotic resistance is a critical public health problem. Each year ∼2.8 million resistant infections lead to more than 35 000 deaths in the U.S. alone. Antimicrobial peptides (AMPs) show promise in treating resistant infections. However, applications of known AMPs have encountered issues in development, production, and shelf-life. To drive the development of AMP-based treatments, it is necessary to create design approaches with higher precision and selectivity toward resistant targets. Previously, we developed AMPGAN and obtained proof-of-concept evidence for the generative approach to design AMPs with experimental validation. Building on the success of AMPGAN, we present AMPGAN v2, a bidirectional conditional generative adversarial network (BiCGAN)-based approach for rational AMP design. AMPGAN v2 uses generator-discriminator dynamics to learn data-driven priors and controls generation using conditioning variables. The bidirectional component, implemented using a learned encoder to map data samples into the latent space of the generator, aids iterative manipulation of candidate peptides. These elements allow AMPGAN v2 to generate candidates that are novel, diverse, and tailored for specific applications, making it an efficient AMP design tool.
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http://dx.doi.org/10.1021/acs.jcim.0c01441DOI Listing
May 2021

Asynchronous Spatiotemporal Spike Metric for Event Cameras.

IEEE Trans Neural Netw Learn Syst 2021 Mar 8;PP. Epub 2021 Mar 8.

Event cameras as bioinspired vision sensors have shown great advantages in high dynamic range and high temporal resolution in vision tasks. Asynchronous spikes from event cameras can be depicted using the marked spatiotemporal point processes (MSTPPs). However, how to measure the distance between asynchronous spikes in the MSTPPs still remains an open issue. To address this problem, we propose a general asynchronous spatiotemporal spike metric considering both spatiotemporal structural properties and polarity attributes for event cameras. Technically, the conditional probability density function is first introduced to describe the spatiotemporal distribution and polarity prior in the MSTPPs. Besides, a spatiotemporal Gaussian kernel is defined to capture the spatiotemporal structure, which transforms discrete spikes into the continuous function in a reproducing kernel Hilbert space (RKHS). Finally, the distance between asynchronous spikes can be quantified by the inner product in the RKHS. The experimental results demonstrate that the proposed approach outperforms the state-of-the-art methods and achieves significant improvement in computational efficiency. Especially, it is able to better depict the changes involving spatiotemporal structural properties and polarity attributes.
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http://dx.doi.org/10.1109/TNNLS.2021.3061122DOI Listing
March 2021

Author Correction: Ionic shape-morphing microrobotic end-effectors for environmentally adaptive targeting, releasing, and sampling.

Nat Commun 2021 Mar 5;12(1):1598. Epub 2021 Mar 5.

Key Laboratory of Biomimetic Robots and Systems (Beijing Institute of Technology), Ministry of Education, 100081, Beijing, China.

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http://dx.doi.org/10.1038/s41467-021-21986-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7935907PMC
March 2021

Posterior fixation can further improve the segmental alignment of lumbar degenerative spondylolisthesis with oblique lumbar interbody fusion.

BMC Musculoskelet Disord 2021 Feb 23;22(1):218. Epub 2021 Feb 23.

Department of Spine Surgery, Beijing Jishuitan Hospital, No. 31, Xinjiekou East Street, Xicheng District, Beijing, 100035, People's Republic of China.

Background: For patients with degenerative spondylolisthesis, whether additional posterior fixation can further improve segmental alignment is unknown, compared with stand-alone cage insertion in oblique lumbar interbody fusion (OLIF) procedure. The aim of this study was to compare changes of the radiographical segmental alignment following stand-alone cage insertion and additional posterior fixation in the same procedure setting of OLIF for patients with degenerative spondylolisthesis.

Methods: A retrospective observational study. Selected consecutive patients with degenerative spondylolisthesis underwent OLIF procedure from July 2017 to August 2019. Five radiographic parameters of disc height (DH), DH-Anterior, DH-Posterior, slip ratio and segmental lordosis (SL) were measured on preoperative CT scans and intraoperative fluoroscopic images. Comparisons of those radiographic parameters prior to cage insertion, following cage insertion and following posterior fixation were performed.

Results: A total of thirty-three patients including six males and twenty-seven females, with an average age of 66.9 ± 8.7 years, were reviewed. Totally thirty-six slipped levels were assessed with thirty levels at L4/5, four at L3/4 and two at L2/3. Intraoperatively, with only anterior cage support, DH was increased from 8.2 ± 1.6 mm to 11.8 ± 1.7 mm (p < 0.001), DH-Anterior was increased from 9.6 ± 2.3 mm to 13.4 ± 2.1 mm (p < 0.001), DH-Posterior was increased from 6.1 ± 1.9 mm to 9.1 ± 2.1 mm (p < 0.001), the slip ratio was reduced from 11.1 ± 4.6% to 8.3 ± 4.4% (p = 0.020) with the slip reduction ratio 25.6 ± 32.3%, and SL was slightly changed from 8.7 ± 3.7° to 8.3 ± 3.0°(p = 1.000). Following posterior fixation, the DH was unchanged (from 11.8 ± 1.7 mm to 11.8 ± 2.3 mm, p = 1.000), DH-Anterior and DH-Posterior were slightly changed from 13.4 ± 2.1 mm and 9.1 ± 2.1 mm to 13.7 ± 2.3 mm and 8.4 ± 1.8 mm respectively (P = 0.861, P = 0.254), the slip ratio was reduced from 8.3 ± 4.4% to 2.1 ± 3.6% (p < 0.001) with the slip reduction ratio 57.9 ± 43.9%, and the SL was increased from 8.3 ± 3.0° to 10.7 ± 3.6° (p = 0.008).

Conclusions: Compared with stand-alone cage insertion, additional posterior fixation provides better segmental alignment improvement in terms of slip reduction and segmental lordosis in OLIF procedures in the treatment of lumbar degenerative spondylolisthesis.
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http://dx.doi.org/10.1186/s12891-021-04086-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7903758PMC
February 2021

Ionic shape-morphing microrobotic end-effectors for environmentally adaptive targeting, releasing, and sampling.

Nat Commun 2021 01 18;12(1):411. Epub 2021 Jan 18.

Key Laboratory of Biomimetic Robots and Systems (Beijing Institute of Technology), Ministry of Education, 100081, Beijing, China.

Shape-morphing uses a single actuation source for complex-task-oriented multiple patterns generation, showing a more promising way than reconfiguration, especially for microrobots, where multiple actuators are typically hardly available. Environmental stimuli can induce additional causes of shape transformation to compensate the insufficient space for actuators and sensors, which enriches the shape-morphing and thereby enhances the function and intelligence as well. Here, making use of the ionic sensitivity of alginate hydrogel microstructures, we present a shape-morphing strategy for microrobotic end-effectors made from them to adapt to different physiochemical environments. Pre-programmed hydrogel crosslinks were embedded in different patterns within the alginate microstructures in an electric field using different electrode configurations. These microstructures were designed for accomplishing tasks such as targeting, releasing and sampling under the control of a magnetic field and environmental ionic stimuli. In addition to structural flexibility and environmental ion sensitivity, these end-effectors are also characterized by their complete biodegradability and versatile actuation modes. The latter includes global locomotion of the whole end-effector by self-trapping magnetic microspheres as a hitch-hiker and the local opening and closing of the jaws using encapsulated nanoparticles based on local ionic density or pH values. The versatility was demonstrated experimentally in both in vitro environments and ex vivo in a gastrointestinal tract. Global locomotion was programmable and the local opening and closing was achieved by changing the ionic density or pH values. This 'structural intelligence' will enable strategies for shape-morphing and functionalization, which have attracted growing interest for applications in minimally invasive medicine, soft robotics, and smart materials.
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http://dx.doi.org/10.1038/s41467-020-20697-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7814140PMC
January 2021

Molecular basis for the adaptive evolution of environment-sensing by H-NS proteins.

Elife 2021 Jan 7;10. Epub 2021 Jan 7.

Department of Chemistry, The University of Vermont, Burlington, United States.

The DNA-binding protein H-NS is a pleiotropic gene regulator in gram-negative bacteria. Through its capacity to sense temperature and other environmental factors, H-NS allows pathogens like Salmonella to adapt their gene expression to their presence inside or outside warm-blooded hosts. To investigate how this sensing mechanism may have evolved to fit different bacterial lifestyles, we compared H-NS orthologs from bacteria that infect humans, plants, and insects, and from bacteria that live on a deep-sea hypothermal vent. The combination of biophysical characterization, high-resolution proton-less nuclear magnetic resonance spectroscopy, and molecular simulations revealed, at an atomistic level, how the same general mechanism was adapted to specific habitats and lifestyles. In particular, we demonstrate how environment-sensing characteristics arise from specifically positioned intra- or intermolecular electrostatic interactions. Our integrative approach clarified the exact modus operandi for H-NS-mediated environmental sensing and suggested that this sensing mechanism resulted from the exaptation of an ancestral protein feature.
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http://dx.doi.org/10.7554/eLife.57467DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7817174PMC
January 2021

Ormosanine improves neuronal functions in spinal cord-injured rats by blocking peroxynitrite/calpain activity.

Transl Neurosci 2020 29;11(1):182-191. Epub 2020 May 29.

Department Of Spine Surgery, Beijing Jishuitan Hospital, Beijing 100035, China.

The present study was performed to evaluate the effects of ormosanine against spinal cord injury (SCI) in rats and to examine the possible molecular mechanism of action. SCI was induced using an impactor device, and rats were treated with ormosanine 10, 50 or 100 mg/kg, p.o., for 10 days after induction of SCI. The effect of ormosanine on SCI was determined by estimating neurological functions and cytokines and parameters of oxidative stress level were estimated in SCI rats. Quantitative reverse transcription polymerase chain reaction, Western blotting analysis and histopathological study were performed on spinal tissue of SCI rats. The data suggested that treatment with ormosanine reversed the alterations of neurological function in SCI rats. Moreover, the levels of cytokines, oxidative stress and reactive oxygen species production were reduced in the ormosanine treatment group compared to the SCI group. The levels of calpain and neuronal nitric oxide synthase activity were significantly reduced in the spinal tissue of the ormosanine treatment group compared to the SCI group. Moreover, ormosanine treatment reduced the percentage of viable neurons in the spinal tissue of SCI rats. In conclusion, the results of this study showed that ormosanine treatment had a protective effect against neuronal injury in spinal cord-injured rats by regulating the peroxynitrite/calpain activity.
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http://dx.doi.org/10.1515/tnsci-2020-0106DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7711948PMC
May 2020

A nomogram to predict short-term outcome of radiotherapy or chemoradiotherapy based on pre/post-treatment inflammatory biomarkers and their dynamic changes in esophageal squamous cell carcinoma.

Int Immunopharmacol 2021 Jan 18;90:107178. Epub 2020 Nov 18.

Shandong First Medical University & Shandong Academy of Medical Sciences, Jinan, Shandong, China; Department of Radiation Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, China. Electronic address:

Objective: We initially aimed to investigate pre/post-treatment inflammatory biomarkers (pre/post-IBs) and their dynamic changes (delta-IBs) on the short-term outcome (STO) of radiotherapy or chemoradiotherapy in esophageal squamous cell carcinoma (ESCC). Furthermore, a nomogram was built to provide an accurate prediction of STO.

Methods: The STO using the treatment response evaluation was assessed according to RECIST 1.1 at 1 month after radiotherapy or chemoradiotherapy. The IBs (absolute lymphocyte counts (ALC), neutrophil/lymphocyte (NLR), platelet/lymphocyte (PLR), and lymphocyte/monocyte (LMR)) and clinical variables were collected and analyzed from 398 ESCC patients at Shandong Cancer Hospital between 2015 and 2019. The nomogram was then established for predicting STO.

Results: Pre-ALC and pre-LMR significantly increased, pre-NLR and pre-PLR significantly decreased during radiotherapy or chemoradiotherapy (all P < 0.001). Meanwhile, there was a positive correlation between delta-NLR as well as delta-PLR (r = 0.621) and delta-LMR (r = 0.613), whereas a negatively correlated between delta-LMR and delta-PLR (r = -0.573). Multivariate analysis indicated that gender [OR, 0.473; 95%CI, 0.274-0.816; P = 0.007], pre-ALC [OR, 0.554; 95%CI, 0.335-0.915; P = 0.021], pre-NLR [OR, 3.176; 95%CI, 1.733-5.823; P < 0.001], post-NLR [OR, 2.418; 95%CI, 1.271-4.600; P = 0.007] and delta-NLR [OR, 1.929; 95%CI, 1.035-3.595; P = 0.039] were statistically significant with STO. And c-index of the nomogram established by combining all independent predictors for STO was 0.770 [95%CI, 0.719-0.820].

Conclusion: Pre-NLR, pre-ALC, post-NLR, and delta-NLR were significant with STO in ESCC patients treated with radiotherapy or chemoradiotherapy. Further, pre-NLR had the best predictive value, and the developed nomogram with superior prediction ability for STO could assist in patients counseling and guide to make individual treatments.
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http://dx.doi.org/10.1016/j.intimp.2020.107178DOI Listing
January 2021

Mean Apparent Propagator MRI Is Better Than Conventional Diffusion Tensor Imaging for the Evaluation of Parkinson's Disease: A Prospective Pilot Study.

Front Aging Neurosci 2020 24;12:563595. Epub 2020 Sep 24.

Department of Radiology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China.

Background And Purpose: Mean apparent propagator (MAP) MRI is a novel diffusion imaging method to map tissue microstructure. The purpose of this study was to evaluate the diagnostic value of the MAP MRI in Parkinson's disease (PD) in comparison with conventional diffusion tensor imaging (DTI).

Methods: 23 PD patients and 22 age- and gender-matched healthy controls were included. MAP MRI and DTI were performed on a 3T MR scanner with a 20-channel head coil. The MAP metrics including mean square displacement (MSD), return to the origin probability (RTOP), return to the axis probability (RTAP), and return to the plane probability (RTPP), and DTI metrics including fractional anisotropy (FA), and mean diffusivity (MD), were measured in subcortical gray matter and compared between the two groups. The receiver operating characteristic (ROC) curve was used to analyze the diagnostic performance of all the metrics. The association between the diffusion metrics and disease severity was assessed by Pearson correlation analysis.

Results: For MAP MRI, the mean values of MSD in the bilateral caudate, pallidum, putamen, thalamus and substantia nigra (SN) were higher in PD patients than in healthy controls ( ≤ 0.001); the mean values of the zero displacement probabilities (RTOP, RTAP, and RTPP) in the bilateral caudate, pallidum, putamen and thalamus were lower in PD patients ( < 0.001). For DTI, only FA in the bilateral SN was significantly higher in PD patients than those in the controls ( < 0.001). ROC analysis showed that the areas under the curves of MAP MRI metrics (MSD, RTOP, RTAP, and RTPP) in the bilateral caudate, pallidum, putamen and thalamus (range, 0.85-0.94) were greater than those of FA and MD of DTI (range, 0.55-0.69) in discriminating between PD patients and healthy controls. RTAP in the ipsilateral pallidum ( = -0.56, = 0.027), RTOP in the bilateral and contralateral putamen ( = -0.58, = 0.019; = -0.57, = 0.024) were negatively correlated with UPDRS III motor scores.

Conclusion: MAP MRI outperformed the conventional DTI in the diagnosis of PD and evaluation of the disease severity.
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http://dx.doi.org/10.3389/fnagi.2020.563595DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7541835PMC
September 2020

Aggregation State of Synergistic Antimicrobial Peptides.

J Phys Chem Lett 2020 Nov 27;11(21):9501-9506. Epub 2020 Oct 27.

Department of Chemistry, University of Vermont, Burlington, Vermont 05405, United States.

By integrating various simulation and experimental techniques, we discovered that antimicrobial peptides (AMPs) may achieve synergy at an optimal concentration and ratio, which can be caused by aggregation of the synergistic peptides. On multiple time and length scales, our studies obtain novel evidence of how peptide coaggregation in solution can affect the disruption of membranes by synergistic AMPs. Our findings provide crucial details about the complex molecular origins of AMP synergy, which will help guide the future development of synergistic AMPs as well as applications of anti-infective peptide cocktail therapies.
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http://dx.doi.org/10.1021/acs.jpclett.0c02094DOI Listing
November 2020

Application and Prospects of Molecular Imaging in Immunotherapy.

Cancer Manag Res 2020 30;12:9389-9403. Epub 2020 Sep 30.

Department of Radiation Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan 250117, Shandong, People's Republic of China.

Recently, immunotherapies that target the interactions of programmed cell death 1 (PD-1) with its major ligands, programmed death ligand 1 (PD-L1) and programmed death ligand 2 (PD-L2), have achieved significant success. To date, several immune checkpoint inhibitors targeting the PD-1/PD-L1 pathway have been developed to treat melanoma, non-small cell lung cancer, head and neck cancer, renal cell carcinoma, and urothelial carcinoma. Despite promising outcomes with immunotherapy, there are many limitations to several current immune biomarkers for predicting immune benefits and to traditional imaging for evaluating the efficacy and prognosis of immunotherapy and monitoring adverse reactions. In this review, we recommend a novel imaging method, molecular imaging. This paper reviews the application and prospects of molecular imaging in the context of current immunotherapies in regard to the following aspects: 1) detecting the expression of PD-1/PD-L1; 2) evaluating the efficacy of immunotherapy; 3) assessing patient prognosis with immunotherapy; 4) monitoring the toxicity of immunotherapy; and 5) other targets imaging.
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http://dx.doi.org/10.2147/CMAR.S269773DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7533904PMC
September 2020

Osteoprotegerin interacts with syndecan-1 to promote human endometrial stromal decidualization by decreasing Akt phosphorylation.

Hum Reprod 2020 11;35(11):2439-2453

Department of Rheumatology and Clinical Immunology, The First Affiliated Hospital of Xiamen University, Xiamen, Fujian, China.

Study Question: Does osteoprotegerin (OPG) promote human endometrial stromal decidualization?

Summary Answer: OPG is essential for human endometrial stromal decidualization through its interaction with syndecan-1 to decrease Akt phosphorylation.

What Is Known Already: OPG (a cytokine receptor) levels are significantly increased in the circulation of pregnant women. However, the role and mechanism of OPG in human endometrial stromal cell (ESC) decidualization remain elusive.

Study Design, Size, Duration: We analyzed the endometrial expression of OPG in endometrial tissue samples collected from women with regular menstrual cycles (ranging from 25 to 35 days), and decidual tissue samples collected from woman with normal early pregnancy or recurrent pregnancy loss (RPL) who visited the Department of Gynecology and Obstetrics at a tertiary care center from January to October 2018. None of the subjects had hormonal treatment for at least 3 months prior to the procedure. In total, 16 women with normal early pregnancy and 15 with RPL were selected as subjects for this study. The function of OPG in decidualization was explored in a human endometrial stromal cell (HESC) line and primary cultures of HESCs.

Participants/materials, Setting, Methods: We collected endometrial tissues (by biopsy) from the subjects during their menstrual cycle and decidual tissues from subjects with a normal early pregnancy and those with RPL at the time of dilation and curettage. The control group comprised randomly selected women who underwent termination of an apparently normal early pregnancy. The endometrial OPG expression was analyzed using immunohistochemical staining and quantitative RT-PCR (qRT-PCR). Immunofluorescence staining and western blot, and qRT-PCR were used to explore the mRNA and protein expression, respectively, of OPG in an immortalized HESC line and in primary cultures of HESC during proliferation and decidualization. siRNA-mediated knockdown experiments were performed to examine the function of OPG in HESC proliferation and decidualization. Flow cytometry and the cell proliferation MTS assay were performed to further examine the role of OPG in HESC proliferation. We also analyzed decidual marker gene expression by qRT-PCR to assess the consequences of OPG loss for HESC decidualization. A co-immunoprecipitation (IP) assay was used to determine the potential interaction between the OPG and Syndecan-1. Western blot analysis of the rescue experiments performed using the phosphatidylinositol 3-kinase (PI3K) signaling-specific inhibitor LY294002 was used to investigate the downstream signaling pathways through which OPG could mediate HESC decidualization.

Main Results And The Role Of Chance: OPG was expressed in both the human endometrium and in vitro decidualized ESCs. Knockdown experiments revealed that OPG loss impaired the expression of IGF-binding protein-1 (IGFBP-1) (P < 0.05) and prolactin (PRL) (P < 0.05), two specific markers of decidualization, in HESC undergoing decidualization. We also uncovered that OPG knockdown induced the aberrant activation of Akt (protein kinase B) during HESC decidualization (P < 0.05). The inhibition of Akt activation could rescue the impaired expression of the decidual markers PRL (P < 0.05) and IGFBP-1 (P < 0.05) in response to OPG knockdown. Syndecan-1 was considered a potential receptor candidate, as it was expressed in both the endometrium and in vitro cultured stromal cells. Subsequent co-IP experiments demonstrated the interaction between OPG and Syndecan-1 during decidualization. In addition, Syndecan-1 knockdown not only clearly attenuated the decidualization markers PRL (P < 0.05) and IGFBP-1 (P < 0.05) but also induced the aberrant enhancement of Akt phosphorylation in decidualized cells, consistent with the phenotype of OPG knockdown cells. Finally, we revealed that the transcript and protein expression of both OPG and Syndecan-1 was significantly lower in the decidual samples of women with RPL than in those of women with normal pregnancy (P < 0.05).

Large Scale Data: N/A.

Limitations, Reasons For Caution: In this study, based on a number of approaches, it was demonstrated that OPG mediated the repression of Akt that occurs during human stromal cell decidualization, however, the molecular link between OPG and Akt signaling was not determined, and still requires further exploration.

Wider Implications Of The Findings: OPG is required for decidualization, and a decrease in OPG levels is associated with RPL. These findings provide a new candidate molecule for the diagnosis and potential treatment of RPL.

Study Funding/competing Interest(s): This work was supported in part by the National Natural Science Foundation of China U1605223 (to G.S.), 81701457 (to Y.J.) and 81601349 (to Y.J.). The authors have no conflicts of interest to disclose.
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http://dx.doi.org/10.1093/humrep/deaa233DOI Listing
November 2020

Prediction of adverse clinical outcomes in patients with coronavirus disease 2019.

J Clin Lab Anal 2021 Jan 28;35(1):e23598. Epub 2020 Sep 28.

The Respiratory Department, The Second Affiliated Hospital of Harbin Medical University, Harbin, China.

Objective: This study aims to investigate blood and biochemical laboratory findings in patients with coronavirus disease (COVID-19) and analyze the potential predictors of poor outcome in patients with COVID-19.

Methods: The clinical, laboratory, and outcome data of 87 patients with COVID-19 were collected and retrospectively analyzed. Only data collected at the time of admission were used in the analysis for predictors of poor outcome. These patients were divided into two groups: the adverse prognosis group (36 patients) and the non-adverse prognosis group (51 patients). The adverse prognosis of COVID-19 patients was defined as admission to the intensive care unit or death.

Results: On the univariate analysis, age, white blood cell (WBC) count, neutrophil counts, lymphocytes count, neutrophils-to-lymphocytes ratio (NLR), interleukin-6, albumin-to-globulin ratio (AGR), albumin, lactate dehydrogenase, glutamyl transpeptidase, and blood glucose were found to be the significant predictors. On the multivariate analysis, the predictors of poor outcome of patients with COVID-19 were NLR (OR = 2.741, [95% CI = 1.02 ~ 7.35], P = .045) and IL-6 (OR = 1.405, [95% CI = 1.04 ~ 1.89, P = .025]). The receiver operating characteristic (ROC) curve revealed that the AUC of NLR, interleukin-6, pneumonia severity index (PSI) score, and Confusion-Urea-Respiratory Rate-Blood pressure-65 (CURB-65) score were 0.883, 0.852, 0.824, and 0.782, respectively.

Conclusion: High interleukin-6 (6 pg/mL, cuff value) and NLR (4.48, cuff value) can be used to predict poor outcomes in patients with COVID-19 on admission, thus can serve as a beneficial tool for timely identifying COVID-19 patients prone to poor outcome and reduce patient mortality through early intervention.
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http://dx.doi.org/10.1002/jcla.23598DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7536920PMC
January 2021

Poly(3-hydroxybutyrate-3-hydroxyvalerate) production from pretreated waste lignocellulosic hydrolysates and acetate co-substrate.

Bioresour Technol 2020 Nov 28;316:123911. Epub 2020 Jul 28.

College of Light Industry Science and Engineering, Tianjin University of Science & Technology, Tianjin 300222, PR China.

The purpose of this study was to explore the potential of producing Poly(3-hydroxybutyrate-3-hydroxyvalerate) (PHBV) by mixed microbial culture (MMC) with lignocellulosic hydrolysates and acetate co-substrate as feedstock. The addition of co-substrate acetate led to the introduction of HV monomer into the polyhydroxyalkanoate (PHA), and the initial mixed sludge suspension (MLSS) increased with the increase of acetate. Almost 1.91-fold increase in the yield of PHA was achieved with limited nitrogen medium (the carbon to nitrogen ratio (C/N) was 33) compared to the normal nitrogen medium (C/N = 20). Limiting nitrogen source and micro alkaline culture environment was more conducive to the accumulation of PHBV. PHA production achieved to the highest value of about 2308.45 mg/L under the condition of optimized technology. Acidovorax was the dominant genus of all bioreactors using co-substrate. Further, utilizing lignocellulosic hydrolysate and acetate co-substrate as feedstock in mixed microbial culture was a promising approach in a low-cost large-scale PHA production.
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http://dx.doi.org/10.1016/j.biortech.2020.123911DOI Listing
November 2020

Size-selective Catalytic Polymer Acylation with a Molecular Tetrahedron.

Chem 2020 Jun;6(6):1469-1494

Department of Chemistry, University of Vermont, Burlington, VT 05405, USA.

Selective catalysis at the molecular level represents a cornerstone of chemical synthesis. However, it still remains an open question how to elevate tunable catalysis to larger length scales to functionalize whole polymer chains in a selective manner. We now report a hydrazone-linked tetrahedron with wide openings, which acts as a catalyst to size-selectively functionalize polydisperse polymer mixtures. Our experimental and computational evidence supports a dual role of the hydrazone-linked tetrahedron. To accelerate functionalization of the polymer substrates, the tetrahedron (i) unfolds the polymer substrates and/or breaks the polymer aggregates as well as (ii) enables target sites (amino groups) on the polymers to coordinate with catalytic units (triglyme) attached to the tetrahedron. With the tetrahedron as the catalyst, we find that the reactivity of the shorter polymers increases selectively. Our findings enable the possibility to engineer hydrolytically stable molecular polyhedra as organocatalysts for size-selective polymer modification.
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http://dx.doi.org/10.1016/j.chempr.2020.05.011DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7388586PMC
June 2020

A Phase II Trial of Safety, Tolerability and Immunogenicity of V114, a 15-Valent Pneumococcal Conjugate Vaccine, Compared With 13-Valent Pneumococcal Conjugate Vaccine in Healthy Infants.

Pediatr Infect Dis J 2020 08;39(8):763-770

From the Merck & Co., Inc., Kenilworth, New Jersey.

Background: Pneumococcal disease remains a public health priority worldwide. This phase 2 study (V114-008; NCT02987972; EudraCT 2016-001117-25) compared safety and immunogenicity of 2 clinical lots of V114 (investigational 15-valent pneumococcal vaccine: 1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19F, 19A, 22F*, 23F, 33F*) to 13-valent pneumococcal conjugate vaccine (PCV13) in healthy infants (*serotypes unique to V114).

Methods: Healthy infants 6-12 weeks old were randomized to receive a 4-dose regimen of V114 Lot 1, V114 Lot 2 or PCV13 at 2, 4, 6 and 12-15 months old. Adverse events were evaluated after each dose. Primary immunogenicity endpoint was to demonstrate noninferiority of V114 Lot 1 and V114 Lot 2 relative to PCV13 based on proportion of infants achieving serotype-specific IgG concentration ≥0.35 µg/mL for 13 serotypes shared with PCV13 at 1 month postdose 3 (PD3). Serotype-specific IgG geometric mean concentrations (GMCs) for all 15 V114 serotypes were measured at PD3, predose 4 and 1 month postdose 4 (PD4).

Results: Overall, 1044 of 1051 randomized infants received ≥1 dose of vaccine (V114 Lot 1 [n = 350], V114 Lot 2 [n = 347] or PCV13 [n = 347]). Adverse events were generally comparable across groups. At PD3, both V114 lots met noninferiority criteria for all 13 serotypes shared with PCV13. IgG GMCs were comparable among V114 and PCV13 recipients at PD3 and PD4. Serotype 3 responses were higher following receipt of V114 than PCV13. Both V114 lots induced higher GMCs than PCV13 to the 2 unique V114 serotypes.

Conclusions: Immunogenicity of both V114 lots was noninferior to PCV13 for all 13 shared serotypes between the 2 vaccines and displayed comparable safety and tolerability profiles to PCV13.
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http://dx.doi.org/10.1097/INF.0000000000002765DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7360095PMC
August 2020

Neuroprotective effect of novel celecoxib derivatives against spinal cord injury via attenuation of COX-2, oxidative stress, apoptosisand inflammation.

Bioorg Chem 2020 08 25;101:104044. Epub 2020 Jun 25.

Department of Spine Surgery, Beijing Jishuitan Hospital, Beijing 100035,China.

A novel series of celecoxib derivatives were synthesized and evaluated for cyclooxygenase (COX-1/COX-2) inhibitory activities for benefit in spinal cord injury (SCI). The title compounds were synthesized by conventional methods in good yields and subsequently tested for inhibitory activity against COX-1/COX-2. The most potent COX-2 inhibitor among the tested derivatives was further assayed for protective effect against experimental SCI of Sprague-Dawley rats. The designed compounds showed considerable inhibition of COX-2 as compared to COX-1 revealing compound 7m as most potent inhibitor of COX-2 isoenzyme (IC = 0.04 µM). The expression of mitochondrial apoptotic genes (Bcl-2 and Bax) together with COX-2 and iNOS was restored near to normal as evidenced by western blot analysis in SCI rats. Taken altogether, compound 7m was identified as most potent inhibitor of COX-2. It also showed protective action against SCI via attenuation of COX-2, oxidative stress and apoptosis and inflammation in Male Sprague-Dawley rats.
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http://dx.doi.org/10.1016/j.bioorg.2020.104044DOI Listing
August 2020

Transmittance Tunable Smart Window Based on Magnetically Responsive 1D Nanochains.

ACS Appl Mater Interfaces 2020 Jul 6;12(28):31637-31644. Epub 2020 Jul 6.

Key Laboratory of Advanced Functional Materials and Mesoscopic Physics, School of Science, Xi'an Jiaotong University, Xi'an 710049, P. R. China.

Smart optical materials are drawing more and more attention because of their wide application in energy conservation, wearable sensors, optical tuning, and medical devices. However, current smart optical materials, including electroresponsive, thermoresponsive, and mechanoresponsive materials, are greatly restricted in practical applications because of their long response time, complicated preparation, and high cost. This study develops a novel, magnetically tunable, smart optical material with swift and high-contrast optical switching based on one-dimensional (1D) [email protected] nanochains (NCs), which have the large shape anisotropy of the 1D structure and the superparamagnetic properties of FeO particles. The material exhibited a clear transparent state when NCs were arranged parallel to the viewing direction under an applied magnetic field, whereas it showed good shielding effect when the NCs were randomly oriented upon removal of the field. The light transmittance could be dynamically adjusted over the wide range of 20-80% through a small applied magnetic field of 50-100 Oe, which is superior to most of the currently reported systems. This swift, sensitive, and reversible response is attributed to the good responsivity of magnetic NCs. Also, an effective model was proposed to explain the transmittance modulation scheme and forecast its optical potential. The large tunable range and the low triggered field make [email protected] NCs an advantageous candidate for application in smart windows, optical switchers, and other fields.
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http://dx.doi.org/10.1021/acsami.0c08402DOI Listing
July 2020

MicroRNA-466c-3p exerts protective effect on neuronal apoptosis and improves functional recovery post spinal cord injury via mitochondrial apoptotic pathway.

AMB Express 2020 Jun 15;10(1):113. Epub 2020 Jun 15.

Department of Spine Surgery, Beijing Jishuitan Hospital, Beijing, 100035, China.

Spinal cord injury (SCI) is involved with abnormal expression of miRNAs (miRs) which are responsible for some II injury responses which include apoptosis, inflammation and oxidative stress. Mechanisms involving miRs induced apoptosis still needs to be investigated. In the present work we developed a rat model of SCI, followed by microarray analysis for expression of miRs at various time points after SCI. The locomotor activity was assessed by Basso, Beattie and Bresnahan score, lesion volume was analyzed by cresyl violet staining and TUNEL staining for extent of apoptosis at various time points of post SCI. Numbers of miRs were altered after 2 weeks of SCI among which miR-466c-3p was the most significantly down-regulated. Transfection with miR-466c-3p mimics caused overexpression of miR-466c-3p, also improvement in functional recovery, decrease in apoptosis of neuronal cells and lesion size was observed in SCI rats. The Luciferase assay suggested that miR-466c-3p suppressed the expression of Bcl-2 (apoptosis regulator). It was also evidenced that upon restoring the levels of Bcl-2 with the help of pc-DNA3-Bcl-2 halted the attenuating action of miR-466c-3p in hydrogen peroxide exposed N9 microglia cells. The findings suggested that miR-466c-3p may inhibit mitochondrial apoptotic pathway via blocking Bcl-2 and cleaved capase-9/-3in rats after SCI. Altogether, the results suggested that miR-466c-3p may exert attenuating effect on functional recovery and inhibit the apoptosis of neuronal cells via halting the mitochondrial apoptosis cascade in SCI rats indicating that miR-466c-3p can be attractive therapeutic candidate in treating SCI.
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http://dx.doi.org/10.1186/s13568-020-01033-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7295889PMC
June 2020

In-situ formation of carboxylate species on TiO nanosheets for enhanced visible-light photocatalytic performance.

J Colloid Interface Sci 2020 Oct 19;577:512-522. Epub 2020 May 19.

State Key Laboratory of Catalysis, iChEM, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Dalian 116023 China; DICP-Surrey Joint Centre for Future Materials, Department of Chemical and Process Engineering and Advanced Technology Institute, University of Surrey, Guildford, Surrey GU2 7XH, UK. Electronic address:

It still remains challenge for expanding the photo-response range of TiO with dominant {0 0 1} facets due to the hardly achieving modification of the electronic structure without destroying the formation of TiO high energy facets. Herein, we report the construction of carboxylate species modified TiO nanosheets with dominant {0 0 1} facets by employing ethanol as a carbon source through a low-temperature (300 °C) carbonization method. The as-obtained samples were investigated in detail by using various characterization techniques. The results indicate that the carboxylate species derived from the oxidation and carbonization of ethanol are coordinated to the {0 0 1} facets in a bidentate bridging mode. The electron-withdrawing carboxylate species induce TiO to form a lower valence band edge and a narrower bandgap, which enhances the oxidation ability of photogenerated holes and expands the photo-response range. The partially carbonized carboxylate species can also act as a photosensitizer to induce visible-light photocatalytic activity of TiO nanosheets. In addition, the carboxylate species can further promote the separation of photogenerated charge carriers. The findings of this work may provide a new perspective for tuning the band structure of TiO with dominant {0 0 1} facets and improving its photocatalytic performance.
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http://dx.doi.org/10.1016/j.jcis.2020.05.054DOI Listing
October 2020

Selective Monofunctionalization Enabled by Reaction-History-Dependent Communication in Catalytic Rotaxanes.

Angew Chem Int Ed Engl 2020 Sep 22;59(38):16668-16674. Epub 2020 Jul 22.

Department of Chemistry, University of Vermont, Burlington, VT, 05405, USA.

Selective monofunctionalization of substrates with distant, yet equally reactive functional groups is difficult to achieve, as it requires the second functional group to selectively modulate its reactivity once the first functional group has reacted. We now show that mechanically interlocked catalytic rings can effectively regulate the reactivity of stoppering groups in rotaxanes over a distance of about 2 nm. Our mechanism of communication is enabled by a unique interlocked design, which effectively removes the catalytic rings from the substrates by fast dethreading as soon as the first reaction has taken place. Our method not only led to a rare example of selective monofunctionalization, but also to a "molecular if function". Overall, the study presents a way to get distant functional groups to communicate with each other in a reaction-history-dependent manner by creating linkers that can ultimately perform logical operations at the molecular level.
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http://dx.doi.org/10.1002/anie.202006305DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7719090PMC
September 2020

Prediction of the Severity of the Coronavirus Disease and Its Adverse Clinical Outcomes.

Jpn J Infect Dis 2020 Nov 29;73(6):404-410. Epub 2020 May 29.

The Respiratory Department, the Second Affiliated Hospital of Harbin Medical University, China.

This study aims to investigate blood and biochemical laboratory findings in patients with severe coronavirus disease 2019 (COVID-19) and to develop a joint predictor for predicting the likelihood of severe COVID-19 and its adverse clinical outcomes and to provide more information for treatment. We collected the data of 88 patients with laboratory-confirmed COVID-19. Further, the patients were divided into a non-severe group and a critical group (including critically ill cases). Univariate analysis showed that the absolute lymphocyte count, albumin level, albumin/globulin ratio, lactate dehydrogenase level, interleukin-6 (IL-6) level, erythrocyte count, globulin level, blood glucose level, and age were significantly correlated with the severity of COVID-19. The multivariate binary logistic regression model revealed that age, absolute lymphocyte count, and IL-6 level were independent risk factors in patients with COVID-19. The receiver operating characteristic curve revealed that the combination of IL-6 level, absolute lymphocyte count, and age is superior to a single factor as predictors for severe COVID-19, regardless of whether it is in terms of the area under the curve or the prediction sensitivity and specificity. Early application is beneficial to early identification of critically ill patients and timing individual treatments to reduce mortality.
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http://dx.doi.org/10.7883/yoken.JJID.2020.194DOI Listing
November 2020

TNFAIP2 Promotes Non-Small Cell Lung Cancer Cells and Targeted by miR-145-5p.

DNA Cell Biol 2020 Jul 22;39(7):1256-1263. Epub 2020 May 22.

Department of Respiratory, The Second Affiliated Hospital of Harbin Medical University, Harbin, China.

Tumor necrosis factor-alpha (TNFα) is an inflammatory cytokine that regulates inflammation and tumor progression in non-small cell lung cancer (NSCLC). The higher levels of TNF α are known to induce expression of several genes such as TNFα-induced protein 2 (TNFAIP2) with a largely unknown role in NSCLC. We provide the preliminary evidence for the role of TNFAIP2 in NSCLC progression and its epigenetic regulation mediated by microRNA, miR-145-5p. The expression of TNFAIP2 was confirmed using quantitative real-time PCR, immunohistochemistry, and Western blot in NSCLC tissue and paired adjacent normal tissue. All assays were undertaken in A549 and H23 cells and chemoresistance assays were undertaken in A549/Cisplatin (DDP) and H23/DDP cell types. TNFAIP2 silencing was undertaken using lipofectamine transfection of specific siRNA. Cells were co-transfected with miR-145-5p, and -3' untranslated region (UTR) or with mutated 3'UTR using the luciferase vector pGL. Cell viability, transwell migration, and invasion were assessed. The role of caspase 3 proteins in cell viability was ascertained using Western blot. The tumor tissues (and cisplatin-resistant cell lines A549/DDP and H23/DDP) expressed significantly higher levels of TNAIP2 mRNA and protein. Silencing of TNFAIP2 resulted in reduced cell viability, reduced invasion, and migration . Silencing of TNFAIP2 in A549/DDP and H23/DDP had higher expression of TNFAIP2, reduced cell viability, and increased induction of caspase 3. MiR-145-5p binds to the 3'UTR of . Overexpression of MiR-145-5p reduced expression of TNFAIP2, decreased cell viability, reduced cell migration and invasion, and significantly reduced expression of caspase 3 protein. TNFAIP2 mediates tumorigenesis in NSCLC through, not completely known pathways. miR-145-5p negatively regulates TNFAIP2 expression. miR-145-5p-mediated therapies may be explored in NSCLC.
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http://dx.doi.org/10.1089/dna.2020.5415DOI Listing
July 2020

Effects of ginsenosides on bone remodelling for novel drug applications: a review.

Chin Med 2020 6;15:42. Epub 2020 May 6.

Department of Prosthodontics, Stomatology Hospital of Jilin University, Changchun, 130021 Jilin China.

Background: Ginsenosides are pharmacologically active compounds that are often extracted from the Panax plant for their medicinal properties. Ginsenosides have multiple effects, including antitumor effects which have been widely studied. In recent years, studies have found that ginsenosides promote proliferation and osteogenesis of osteoblast-related cells, as well as inhibit the activity of osteoclasts.

Main Body: We briefly introduces the molecules and BMP, WNT, and RANKL signalling pathways involved in bone formation and bone resorption. Next, recent studies on the mechanism of action of ginsenosides in bone remodelling are reviewed from three perspectives: the effects on proliferation of osteoblast-related cells, effects on osteogenesis and effects on osteoclasts. To expedite the development of drugs containing ginsenosides, we summarize the multiple beneficial roles of various types of ginsenosides in bone remodelling; including the promotion of bone formation, inhibition of bone resorption, and anti-inflammatory and antioxidant effects.

Conclusion: Many ginsenosides can promote bone formation and inhibit bone resorption, such as Rb1, Rb2 and Re. Ginsenosides have the potential to be new drugs for the treatment of osteoporosis, promote fracture healing and are strong candidates for cytokines in the tissue-engineered bone. This review provides a theoretical basis for clinical drug applications and proposes several future directions for exploring the beneficial role of ginseng compounds in bone remodelling.
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http://dx.doi.org/10.1186/s13020-020-00323-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7201946PMC
May 2020