Publications by authors named "Xiaoyu Zhang"

976 Publications

Synchronization of Uncertain Coupled Neural Networks With Time-Varying Delay of Unknown Bound via Distributed Delayed Impulsive Control.

IEEE Trans Neural Netw Learn Syst 2021 Oct 25;PP. Epub 2021 Oct 25.

This article investigates the issue of synchronization for a type of uncertain coupled neural networks (CNNs) involving time-varying delay with unmeasured or unknown bound by delayed impulsive control with distributed delay. A new Halanay-like delayed differential inequality is presented, and both cases of impulsive control and impulsive perturbation are well-considered. Stemmed from this new inequality and techniques of linear matrix inequalities (LMIs), some sufficient criteria are obtained to achieve both dynamically and statically global μ-synchronization of the delayed CNNs, and a distributed-delay-dependent impulsive controller is designed. A numerical simulation is provided to demonstrate the validity of the obtained theoretical results.
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http://dx.doi.org/10.1109/TNNLS.2021.3116069DOI Listing
October 2021

Pore Fractal Characteristics of Suancigou Long-Flame Coal after Electrochemical Treatment: An Experimental Study through the Implementation of N Adsorption and Mercury Intrusion Prosimetry Techniques.

ACS Omega 2021 Oct 11;6(41):27358-27367. Epub 2021 Oct 11.

College of Economics and Management, Taiyuan University of Technology, Taiyuan 030024, PR China.

The application of electrochemical treatment in coal seams for enhancing coalbed methane (CBM) recovery can also decrease the risks of outburst disasters. The long-flame coal samples were electrochemically modified with 0, 1, 2, and 4 V/cm electric potential gradients, and the pore structures were measured and analyzed by combined low-temperature nitrogen gas adsorption, mercury intrusion prosimetry, and fractal theory. The experimental test results indicated that the pore volumes of macropores (>50 nm) and mesopores (2-50 nm) increased after electrochemical modification and further increased with the increase in electric potential gradient. The fractal dimensions of pores showed a decreasing trend except for the slight fluctuation of the mesopores with a size of 2-4.5 nm after modification, which indicated that the overall roughness and irregularity index of pores decreased. The evolution mechanisms of pore size distributions and their fractal dimensions were explained by the dissolution of minerals and the falling off of alkane side chains in the coal surface, which would expand and connect the pores during the electrochemical modification process. The results obtained from this work were crucial for CBM exploration via an electrochemical method.
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http://dx.doi.org/10.1021/acsomega.1c04231DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8529665PMC
October 2021

Dyspnea Measurement in Acute Heart Failure: A Systematic Review and Evidence Map of Randomized Controlled Trials.

Front Med (Lausanne) 2021 6;8:728772. Epub 2021 Oct 6.

Key Laboratory of Chinese Internal Medicine of Ministry of Education, Dongzhimen Hospital, Beijing University of Chinese Medicine, Beijing, China.

Dyspnea is the most common presenting symptom among patients hospitalized for acute heart failure (AHF). Dyspnea relief constitutes a clinically relevant therapeutic target and endpoint for clinical trials and regulatory approval. However, there have been no widely accepted dyspnea measurement standards in AHF. By systematic review and mapping the current evidence of the applied scales, timing, and results of measurement, we hope to provide some new insights and recommendations for dyspnea measurement. PubMed, Embase, Cochrane Library, and Web of Science were searched from inception until August 27, 2020. Randomized controlled trials (RCTs) with dyspnea severity measured as the endpoint in patients with AHF were included. Out of a total of 63 studies, 28 had dyspnea as the primary endpoint. The Likert scale (34, 54%) and visual analog scale (VAS) (22, 35%) were most widely used for dyspnea assessment. Among the 43 studies with detailed results, dyspnea was assessed most frequently on days 1, 2, 3, and 6 h after randomization or drug administration. Compared with control groups, better dyspnea relief was observed in the experimental groups in 21 studies. Only four studies that assessed tolvaptan compared with control on the proportion of dyspnea improvement met the criteria for meta-analyses, which did not indicate beneficial effect of dyspnea improvement on day 1 (RR: 1.16; 95% CI: 0.99-1.37; = 0.07; = 61%). The applied scales, analytical approaches, and timing of measurement are in diversity, which has impeded the comprehensive evaluation of clinical efficacy of potential therapies managing dyspnea in patients with AHF. Developing a more general measurement tool established on the unified unidimensional scales, standardized operation protocol to record the continuation, and clinically significant difference of dyspnea variation may be a promising approach. In addition, to evaluate the effect of experimental therapies on dyspnea more precisely, the screening time and blinded assessment are factors that need to be considered.
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http://dx.doi.org/10.3389/fmed.2021.728772DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8526558PMC
October 2021

Ultrasound-guided five-point injection of botulinum toxin for patients with trapezius hypertrophy.

J Orthop Surg Res 2021 Oct 22;16(1):634. Epub 2021 Oct 22.

Department of Plastic Surgery, The Third Hospital of Jilin University, No.126, Xiantai Street, Erdao District, Changchun, 130000, Jilin, China.

Objectives: Our study aimed to explore the clinical therapeutic effects of ultrasound-guided five-point injection of botulinum toxin type A for patients with trapezius hypertrophy.

Methods: Twenty female patients diagnosed with trapezius hypertrophy were enrolled in this study. The thicknesses of the trapezius muscle were measured by using the ultrasound scanner to locate the thickest point of trapezius, followed by labelling the other four points around the first point. Botulinum toxin type A was injected bilaterally (50 IU/side, 5 points/side) in the trapezius muscle of these patients. The surgery effects were evaluated by thicknesses of the trapezius muscle, intramuscular needle electromyographic and electroneurographic examinations, appearance changes and patients' satisfactions.

Results: Statistically significant differences in thicknesses of the trapezius muscle were observed at 4 weeks (p < 0.001), 12 weeks (p < 0.001), 20 weeks (p < 0.001), 28 weeks (p = 0.011), 36 weeks (p = 0.022), and 44 weeks (p = 0.032) after surgery. The latencies of trapezius muscle became longer at 12 weeks after surgery (left: 2.40 ms, right: 2.53 ms vs. left: 1.75 ms, right: 2.00 ms). Electroneurographic results showed amplitude reduction of compound muscle action potentials (CMAPs) at 12 weeks after surgery (left: 1.91 uV, right: 3.10 uV vs. left: 15.00 uV, right: 15.40 uV). Obvious appearance changes were revealed at 12 weeks after surgery. All of 80% patients were very satisfied, 15% patients were relatively satisfied, and 5% patients were not satisfied with the surgery.

Conclusion: Ultrasound-guided five-point injection of botulinum toxin type A might be effective for patients with trapezius hypertrophy.
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http://dx.doi.org/10.1186/s13018-021-02758-yDOI Listing
October 2021

Potentilla discolor ameliorates LPS-induced inflammatory responses through suppressing NF-κB and AP-1 pathways.

Biomed Pharmacother 2021 Oct 19;144:112345. Epub 2021 Oct 19.

Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100193, China. Electronic address:

Potentilla discolor Bunge (PD) is a traditional Chinese medicine which has been widely used for the treatment of various inflammatory diseases (e.g., diarrhea, fever and furuncle). However, few studies focused on its effect on classical inflammation. This study aimed to investigate the anti-inflammatory effect and potential mechanism of the ethanol extract of the whole herbs of PD (EPD) in lipopolysaccharide (LPS)-induced inflammatory models. The obtained results showed that EPD decreased supernatant NO, tumor necrosis factor-α (TNF-α) and monocyte chemoattractant protein-1 (MCP-1) in LPS-activated RAW264.7 cells and mouse peritoneal macrophages. Moreover, its effect on NO was attributed to the suppression of iNOS expression rather than its activity. At the transcriptional level, EPD suppressed iNOS, TNF-α and MCP-1 mRNA expressions in LPS-stimulated RAW264.7 cells. Further study showed that EPD didn't affect the phosphorylation and degradation of IκBα, but yet impeded the nuclear translocation of p65 to inhibit NF-κB activation. Meanwhile, it also prevented JNK, ERK1/2 and p38 phosphorylation to dampen the activation of AP-1. In endotoxemia mouse model, EPD not only decreased interleukin-6, TNF-α and MCP-1 levels in serum, but also potently ameliorated diarrhea. These findings provide the theoretical basis for PD to treat inflammatory diseases, especially intestinal inflammation.
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http://dx.doi.org/10.1016/j.biopha.2021.112345DOI Listing
October 2021

Cancer-associated fibroblast-secreted collagen triple helix repeat containing-1 promotes breast cancer cell migration, invasiveness and epithelial-mesenchymal transition by activating the Wnt/β-catenin pathway.

Oncol Lett 2021 Dec 28;22(6):814. Epub 2021 Sep 28.

Department of Neurosurgery, Affiliated Hospital of Hebei Engineering University, Handan, Hebei 056002, P.R. China.

Cancer-associated fibroblasts (CAFs) are continuously activated and are one of the most important cellular components of the tumor matrix. The role of CAFs in the tumor microenvironment has been widely recognized. However, the underlying molecular mechanism by which CAFs promote tumor characteristics in breast cancer (BC) remains poorly understood. The aim of the present study was to investigate the potential mechanisms and the possible pathways of collagen triple helix repeat containing-1 (CTHRC1) in the epithelial-mesenchymal transition (EMT) of BC cells. The level of CTHRC1 in BC tissues was found to be higher than that in adjacent-normal tissues. CAFs isolated from BC tissues secreted significantly greater amounts of CTHRC1 than normal fibroblasts. Furthermore, CAFs promoted the migration, invasiveness and EMT of BC cells by secreting CTHRC1, which activates the Wnt/β-catenin signaling pathway. However, the use of neutralizing antibodies towards CTHRC1, or the specific inhibitor Dickkopf-1, to inhibit the Wnt/β catenin pathway significantly alleviated the CAF-induced malignant phenotypes of BC cells. Collectively, the data indicate that CAFs in the tumor microenvironment promote BC cell malignant behaviors via the CTHRC1/Wnt/β-catenin signaling pathway. Furthermore, weakening CAF-BC cell communication by suppressing CTHRC1 expression may be a novel strategy for treating BC.
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http://dx.doi.org/10.3892/ol.2021.13075DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8503808PMC
December 2021

Structural Characterization of Lignin-Carbohydrate Complexes (LCCs) and Their Biotransformation by Intestinal Microbiota .

J Agric Food Chem 2021 Oct 12. Epub 2021 Oct 12.

Key Laboratory of Molecular Biophysics of MOE, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan 430074, China.

Lignin-carbohydrate complexes (LCCs) have recently emerged as natural products with pharmaceutical and nutraceutical potential. Here, we compared the structure of LCCs from ginkgo (GK, gymnosperms), wheat straw (WST, monocotyledons), and aspen white poplar (AW, dicotyledons). We also investigated the biotransformation of LCCs by intestinal microbiota in vitro. We found that human intestinal microbiota could use LCCs as a carbon source for growth, breaking resistant cross-linkages in LCCs to generate a plethora of short-chain fatty acids (SCFAs) and aromatic compounds with putative beneficial effects on human health. The yield of SCFAs reached 1837.8 ± 44.1 μmol/g using AW LCCs as a carbon source. The biomass of intestinal microbiota increased the fastest using GK LCCs. The greatest amounts of phenolics were present at 4 h in a WST LCCs fermentation system. Many phenolic acids with potential bioactivity were obtained after 24 h fermentation using each LCCs, such as ferulic acid.
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http://dx.doi.org/10.1021/acs.jafc.1c03519DOI Listing
October 2021

Au Nanoflowers for Catalyzing and In Situ Surface-Enhanced Raman Spectroscopy Monitoring of the Dimerization of -Aminothiophenol.

ACS Omega 2021 Oct 21;6(39):25720-25728. Epub 2021 Sep 21.

State Key Laboratory of Inorganic Synthesis and Preparative Chemistry, College of Chemistry, Jilin University, Changchun 130012, China.

In this work, we demonstrated a facile approach for fabrication of Au nanoflowers (Au NFs) using an amino-containing organosilane, 3-aminopropyltriethoxysilane (APTES), as a shape-directing agent. In this approach, the morphology of the Au particles evolved from sphere-like to flower-like with increasing the concentration of APTES, accompanied by a red shift in the localized surface plasmon resonance peak from 520 to 685 nm. It was identified that the addition of APTES is profitable to direct the preferential growth of the (111) plane of face-centered cubic gold and promote the formation of anisotropic Au NFs. The as-prepared Au NFs, with APTES on their surface, presented effective catalytic and surface-enhanced Raman scattering (SERS) performances, as evidenced by their applications in catalyzing the dimerization of -aminothiophenol and monitoring the reaction process via in situ SERS analysis.
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http://dx.doi.org/10.1021/acsomega.1c03933DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8495860PMC
October 2021

Predicting the Risk of Hypertension Based on Several Easy-to-Collect Risk Factors: A Machine Learning Method.

Front Public Health 2021 24;9:619429. Epub 2021 Sep 24.

Institute of Health Management, Chinese People's Liberation Army (PLA) General Hospital, Beijing, China.

Hypertension is a widespread chronic disease. Risk prediction of hypertension is an intervention that contributes to the early prevention and management of hypertension. The implementation of such intervention requires an effective and easy-to-implement hypertension risk prediction model. This study evaluated and compared the performance of four machine learning algorithms on predicting the risk of hypertension based on easy-to-collect risk factors. A dataset of 29,700 samples collected through a physical examination was used for model training and testing. Firstly, we identified easy-to-collect risk factors of hypertension, through univariate logistic regression analysis. Then, based on the selected features, 10-fold cross-validation was utilized to optimize four models, random forest (RF), CatBoost, MLP neural network and logistic regression (LR), to find the best hyper-parameters on the training set. Finally, the performance of models was evaluated by AUC, accuracy, sensitivity and specificity on the test set. The experimental results showed that the RF model outperformed the other three models, and achieved an AUC of 0.92, an accuracy of 0.82, a sensitivity of 0.83 and a specificity of 0.81. In addition, Body Mass Index (BMI), age, family history and waist circumference (WC) are the four primary risk factors of hypertension. These findings reveal that it is feasible to use machine learning algorithms, especially RF, to predict hypertension risk without clinical or genetic data. The technique can provide a non-invasive and economical way for the prevention and management of hypertension in a large population.
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http://dx.doi.org/10.3389/fpubh.2021.619429DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8497705PMC
October 2021

Prediction of the Postoperative Fat Volume Retention Rate After Augmentation Mammoplasty with Autologous Fat Grafting: From the Perspective of Preoperative Inflammatory Level.

Aesthetic Plast Surg 2021 Oct 1. Epub 2021 Oct 1.

Department of Aesthetic and Reconstructive Breast Surgery, Plastic Surgery Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, 33 Badachu Road, Shijingshan District, Beijing, 100144, People's Republic of China.

Background: Postoperative fat volume retention rate (PFVRR) after augmentation mammoplasty with autologous fat grafting is highly variable on an individual basis and challenging to be predicted. However, at present, there is a lack of further research on the relevant preoperative patient's self-related influencing factors. The early inflammatory response degree, directly influenced by preoperative inflammatory level, is an indispensable part of angiogenesis, which is a key factor in adipocyte survival.

Methods: A retrospective review was conducted of patients who underwent breast augmentation with autologous fat grafting performed by a senior surgeon. Preoperative patient demographics and laboratory findings relevant to inflammatory level, such as monocyte to lymphocyte ratio (MLR), were included as the independent variables. The PFVRR more than 3 months after the operation was included as the dependent variable. Key factors influencing the PFVRR were analyzed.

Results: Sixty-three patients were included. The total volume of bilateral fat injection was 375.00 (range, 320.00-400.00) mL, and the long-term bilateral volumetric change was 106.98 (range, 69.90-181.58) mL. The mean PFVRR was 35.36% ± 15.87%, and the preoperative MLR was an independent positive influencing factor of it, while the lymphocyte (L) count was negative. By ROC curve analysis, a value of MLR equal to 0.23 was the diagnostic cut-off point for whether PFVRR was greater than 50%, and its area under the curve was 0.870, with a sensitivity of 93.33% and a specificity of 81.25%. The other hematological parameters and demographics such as age, body mass index, and donor site were not significantly correlated with the PFVRR.

Conclusion: Preoperative peripheral blood inflammatory indicators can influence the PFVRR, with the MLR positively and L count negatively. Based on the diagnostic threshold of MLR = 0.23 derived from this study, clinicians can make reasonable predictions of whether half of the injected fat volume would be retained based on preoperative blood routine tests that are readily available.

Level Of Evidence Iv: This journal requires that authors assign a level of evidence to each article. For a full description of these evidence-based medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .
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http://dx.doi.org/10.1007/s00266-021-02604-wDOI Listing
October 2021

Electrochemical Modification on CH and HO Wettability of Qinshui Anthracite Coal: A Combined Experimental and Molecular Dynamics Simulation Study.

ACS Omega 2021 Sep 6;6(37):24147-24155. Epub 2021 Sep 6.

Key Laboratory of In-situ Property Improving Mining of Ministry of Education, Taiyuan University of Technology, Taiyuan 030024, P. R. China.

The wettability of gas and liquid on the coal surface is one of the fundamental factors that affect the depressurization process during the coalbed methane (CBM) extraction. The wettability of coal surface changed after electrochemical modification, leading to the change in methane adsorption/desorption and water movement in coal reservoirs. Thus, the CH adsorption amount, desorption ratio, and coal-water contact angle of raw and modified anthracite samples were measured and simulated. The mechanism of electrochemical modification was analyzed by functional groups, surface free energy, pore characteristics, interaction energies, and coal swelling. The experimental results showed that the saturated adsorption amount of methane decreased from 41.49 to 34.72 mL/g, and the simulation results showed that the saturated adsorption amount of methane decreased from 2.01 to 1.83 mmol/g. The coal-water contact angle also decreased from 81.9 to 68.6°. Electrochemical modification mainly affects the wettability of CH and HO by changing the functional groups and pore structures of anthracite, and the influence on functional groups of coal surface is greater. This work provided a basis for enhancing CBM extraction by electrochemical modification.
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http://dx.doi.org/10.1021/acsomega.1c03661DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8459427PMC
September 2021

Clinical features of Trousseau's syndrome with multiple acute ischemic strokes.

Neurol Sci 2021 Sep 26. Epub 2021 Sep 26.

Department of Neurology, Rizhao People's Hospital, Rizhao, 276826, Shandong, China.

Background: Trousseau's syndrome or migrating thrombophlebitis can cause venous or arterial thrombosis; however, multiple acute ischemic strokes (MAIS) caused by Trousseau's syndrome are rare. The aim of this study was to analyse the clinical features of Trousseau's syndrome with MAIS and to improve the awareness and the knowledge of this disease.

Methods: Clinical data from fifteen patients who were diagnosed as Trousseau's syndrome with MAIS in Rizhao People's Hospital from January 2017 to April 2020 were collected and analysed. The clinical data included the following: patients' basic information (including gender, age, underlying diseases, and tumour stage), laboratory results, imaging features, treatment regimens, and short-term prognoses were collected.

Results: The mean age was 65.5 years, with thirteen males and two females. Most patients (11/15) had a history of smoking and (or) drinking. The average score of NIHSS was 2.13. 6 of the 15 patients first presented with ischemic stroke and then found the primary tumour. Most common types of primary tumour was lung cancer (11/15), and other types of primary tumour were gastric adenocarcinoma, renal cell carcinoma, oesophageal adenosquamous carcinoma, and cholangiocarcinoma (one in each). All the 15 patients showed different levels of increase of D-dimer. The increase in CRP appears in 10 of the 15 patients. Various tumour markers were increased in the 15 patients, especially for CYFRA-211, all the patients of which were higher than normal. All of the 15 patients had multiple vascular territory lesions in DWI, and most lesions were near the cortex areas. Only 4 of the 15 patients (26.7%) occurred with peripheral venous thrombosis. Thirteen patients were given low molecular heparin for anticoagulant therapy, of which 9 patients were improved in short-term while 4 patients were not.

Conclusion: Trousseau's syndrome with MAIS was associated with old-age male, smoking and (or) drinking history, low NIHSS score, increased D-dimer, CRP and tumour markers, and lesions near the cortex areas with multiple vascular territories in DWI. Patients with these features should be alert of malignant tumour. Most common types of primary tumour were lung cancer. Treatment with low molecular heparin may be effective in short term.
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http://dx.doi.org/10.1007/s10072-021-05619-yDOI Listing
September 2021

Evaluation of Epidural Analgesia Use During Labor and Infection in Full-term Neonates Delivered Vaginally.

JAMA Netw Open 2021 Sep 1;4(9):e2123757. Epub 2021 Sep 1.

Department of Anesthesia, the International Peace Maternity and Child Health Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.

Importance: Quantification of potential consequences associated with the use of epidural analgesia during labor could help to improve the safety and quality of labor and delivery care for parturient women.

Objective: To evaluate the association between epidural analgesia use during labor and neonatal infection in a large cohort of parturient women.

Design, Setting, And Participants: This propensity score-matched cohort study was conducted at a university-affiliated hospital in Shanghai, China. Women at full-term pregnancy undergoing vaginal delivery between January 2013 and October 2018 were included in the study. Parturient women who were parous, experiencing premature delivery (gestational age <37 weeks), were pregnant with more than 1 fetus, or had experienced a stillbirth were excluded. Data were analyzed from October 2019 to June 2020.

Exposures: The use of epidural analgesia during labor.

Main Outcomes And Measures: The primary outcome was the incidence of neonatal infection, including neonatal sepsis, neonatal uncharacterized infection, neonatal pneumonia, and neonatal necrotizing enterocolitis reported in the medical record. Secondary outcomes included the incidence of maternal intrapartum fever and histologic chorioamnionitis.

Results: Among 37 786 parturient women included (mean [SD] age, 29.5 [3.0] years), 19 968 (52.8%) received epidural analgesia during labor. In the propensity score-matched cohort (including 15 401 parturient women in each group), use of epidural analgesia was associated with a higher incidence of neonatal infection (absolute risk difference, 2.6%, 95% CI, 2.2%-3.0%; relative risk [RR], 2.43; 95% CI, 2.11-2.78), including higher incidence of sepsis (absolute risk difference, 0.1%, 95% CI, 0.1%-0.2%; RR, 3.50; 95% CI, 1.73-7.07) and uncharacterized infection (absolute risk difference, 2.2%, 95% CI, 1.9% to 2.6%; RR, 2.69; 95% CI, 2.30-3.15), compared with no epidural analgesia use. Use of epidural analgesia was also associated with greater incidence of maternal intrapartum fever (RR, 4.12; 95% CI, 3.78-4.50) and histologic chorioamnionitis (RR, 4.08; 95% CI, 3.59-4.64) compared with no epidural analgesia use.

Conclusions And Relevance: This cohort study found that use of epidural analgesia in full-term nulliparous women undergoing vaginal delivery was associated with an increased risk of neonatal infection, pending further investigation. These findings support efforts to further improve safety and quality of labor and delivery care for parturient women.
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http://dx.doi.org/10.1001/jamanetworkopen.2021.23757DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8444029PMC
September 2021

The role of dorsal root ganglia alpha-7 nicotinic acetylcholine receptor in complete Freund's adjuvant-induced chronic inflammatory pain.

Inflammopharmacology 2021 Oct 12;29(5):1487-1501. Epub 2021 Sep 12.

Department of Anesthesiology, Shanghai General Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, 200080, China.

Background: Alpha-7 nicotinic acetylcholine receptor (α7 nAChR) was reported to have a critical role in the regulation of pain sensitivity and neuroinflammation. However, the expression level of α7 nAChR in dorsal root ganglion (DRG) and the underlying neuroinflammatory mechanisms associated with hyperalgesia are still unknown.

Methods: In the present study, the expression and mechanism of α7 nAChR in chronic inflammatory pain was investigated using a complete Freund's adjuvant (CFA)-induced chronic inflammatory pain model. Subsequently, a series of assays including immunohistochemistry, western blotting, and quantitative real-time polymerase chain reaction (qRT-PCR) were performed.

Results: α7 nAChR was mostly colocalized with NeuN in DRG and upregulated after CFA injection. Microinjection of α7 nAChR siRNA into ipsilateral L4/5 DRGs aggravated the CFA-induced pain hypersensitivity. Intrathecal α7 nAChR agonist GTS-21 attenuated the development of CFA-induced mechanical and temperature-related pain hypersensitivities. In neuronal the SH-SY5Y cell line, the knockdown of α7 nAChRs triggered the upregulation of TRAF6 and NF-κB under CFA-induced inflammatory conditions, while agitation of α7 nAChR suppressed the TRAF6/NF-κB activation. α7 nAChR siRNA also exacerbated the secretion of pro-inflammatory mediators from LPS-induced SH-SY5Y cells. Conversely, α7 nAChR-specific agonist GTS-21 diminished the release of interleukin-1beta (IL-1β), IL-6, IL-8, and tumor necrosis factor-α (TNFα) in SH-SY5Y cells under inflammatory conditions. Mechanistically, the modulation of pain sensitivity and neuroinflammatory action of α7 nAChR may be mediated by the TRAF6/NF-κB signaling pathway.

Conclusions: The findings of this study suggest that α7 nAChR may be potentially utilized as a therapeutic target for therapeutics of chronic inflammatory pain.
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http://dx.doi.org/10.1007/s10787-021-00873-0DOI Listing
October 2021

A versatile photodetector assisted by photovoltaic and bolometric effects.

Light Sci Appl 2020 Sep 10;9(1):160. Epub 2020 Sep 10.

State Key Laboratory of Infrared Physics, Shanghai Institute of Technical Physics, Chinese Academy of Sciences, 500 Yutian Road, Shanghai, 200083, China.

The advent of low-dimensional materials with peculiar structure and superb band properties provides a new canonical form for the development of photodetectors. However, the limited exploitation of basic properties makes it difficult for devices to stand out. Here, we demonstrate a hybrid heterostructure with ultrathin vanadium dioxide film and molybdenum ditelluride nanoflake. Vanadium dioxide is a classical semiconductor with a narrow bandgap, a high temperature coefficient of resistance, and phase transformation. Molybdenum ditelluride, a typical two-dimensional material, is often used to construct optoelectronic devices. The heterostructure can realize three different functional modes: (i) the p-n junction exhibits ultrasensitive detection (450 nm-2 μm) with a dark current down to 0.2 pA and a response time of 17 μs, (ii) the Schottky junction works stably under extreme conditions such as a high temperature of 400 K, and (iii) the bolometer shows ultrabroad spectrum detection exceeding 10 μm. The flexible switching between the three modes makes the heterostructure a potential candidate for next-generation photodetectors from visible to longwave infrared radiation (LWIR). This type of photodetector combines versatile detection modes, shedding light on the hybrid application of novel and traditional materials, and is a prototype of advanced optoelectronic devices.
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http://dx.doi.org/10.1038/s41377-020-00396-3DOI Listing
September 2020

Screening of Key Fungal Strains in the Fermentation Process of the Chinese Medicinal Preparation "Lianzhifan Solution" Based on Metabolic Profiling and High-Throughput Sequencing Technology.

Front Microbiol 2021 23;12:727968. Epub 2021 Aug 23.

Department of Biotechnology, School of Bioscience and Technology, Chengdu Medical College, Chengdu, China.

"Lianzhifan solution" (LZF) is produced by the natural fermentation of coptis root and gardenia fruit, and it is a classic prescription for external use in anorectal department. During the fermentation process, the structural evolution of microbial communities led to significant changes in the chemical profile. In this study, we first analyzed the dynamic changes of chemical components as well as the composition and succession of microbial community during the whole fermentation process of LZF, and confirmed the changes of characteristics of nine compounds during the whole fermentation process by metabolic profile. Further analysis found that there was no significant change of alkaloids in all stages of fermentation of LZF, but there were significant changes of iridoids in the middle and late stage of fermentation by deglycosylation. Genipin gentiobioside and geniposide were converted to genipin by biotransformation, showing that deglycosylation was the main event occurring in the fermentation. The community composition and abundance of species in 10 and 19days LZF fermentation broth were analyzed with high-throughput sequencing technology, and 16 dominant bacterial genera and 15 dominant fungal genera involved in the fermentation process were identified. Correlation analysis revealed that and involved in the fermentation were the dominant genera closely related to the dynamic changes of the deglycosylation of the main chemical components, and YY-46 and YY-9 strains were obtained by the further fractionation. Then the monoculture fermentation process was evaluated, whereby we found that the deglycoside conversion rate of iridoid glycosides was greatly improved and the fermentation cycle was shortened by 3-4 times. This finding combined with equivalence evaluation of chemical component and pharmacodynamics to confirm that YY-46 and YY-9 strains were key strains for fermentation concoction. This study established an efficient and practical screening strategy "Microfauna communities-Chemical component-Pharmacodynamic" axis for key strain, to improve the production process and formulating good manufacturing practice (GMP) work, and it is also applicable to the whole fermentation drugs industry. Graphical AbstractThe figure highly summarizes the research content of this study and shows the screening process of key strains in LZF fermentation.
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http://dx.doi.org/10.3389/fmicb.2021.727968DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8420715PMC
August 2021

Enzymatic Beacons for Specific Sensing of Dilute Nucleic Acid and Potential Utility for SARS-CoV-2 Detection.

bioRxiv 2021 Aug 31. Epub 2021 Aug 31.

Enzymatic beacons, or E-beacons, are 1:1 bioconjugates of the nanoluciferase enzyme linked covalently at its C-terminus to hairpin forming DNA oligonucleotides equipped with a dark quencher. We prepared E-beacons biocatalytically using the promiscuous "hedgehog" protein-cholesterol ligase, HhC. Instead of cholesterol, HhC attached nanoluciferase site-specifically to mono-sterylated hairpin DNA, prepared in high yield by solid phase synthesis. We tested three potential E-beacon dark quenchers: Iowa Black, Onyx-A, and dabcyl. Prototype E-beacon carrying each of those quenchers provided sequence-specific nucleic acid sensing through turn-on bioluminescence. For practical application, we prepared dabcyl-quenched E-beacons for potential use in detecting the COVID-19 virus, SARS-CoV-2. Targeting the E484 codon of the SARS-CoV-2 Spike protein, E-beacons (80 × 10 M) reported wild-type SARS-CoV-2 nucleic acid at ≥1 × 10 M with increased bioluminescence of 8-fold. E-beacon prepared for the E484K variant of SARS-CoV-2 functioned with similar sensitivity. These E-beacons could discriminate their complementary target from nucleic acid encoding the E484Q mutation of the SARS-CoV-2 Kappa variant. Along with specificity, detection sensitivity with E-beacons is two to three orders of magnitude better than synthetic molecular beacons, rivaling the most sensitive nucleic acid detection agents reported to date.
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http://dx.doi.org/10.1101/2021.08.30.458287DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8423218PMC
August 2021

BSC2 induces multidrug resistance via contributing to the formation of biofilm in Saccharomyces cerevisiae.

Cell Microbiol 2021 Sep 5:e13391. Epub 2021 Sep 5.

State Key Laboratory of Bioreactor Engineering, East China University of Science and Technology, Shanghai, China.

Biofilm plays an important role in fungal multidrug resistance (MDR). Our previous studies showed that BSC2 is involved in resistance to amphotericin B (AMB) through antioxidation in Saccharomyces cerevisiae. In this study, the overexpression of BSC2 and IRC23 induced strong MDR in S. cerevisiae. BSC2-overexpression affected cellular flocculation, cell surface hydrophobicity, biofilm formation and invasive growth. However, it failed to induce caspofungin (CAS) resistance and affect the invasive growth in FLO mutant strains (FLO11Δ, FLO1Δ, FLO8Δ and TUP1Δ). Furthermore, the overexpression of BSC2 compensated for chitin synthesis defects to maintain the cell wall integrity and significantly reduced the cell morphology abnormality induced by CAS. However, it could not repair the cell wall damage caused by CAS in the FLO mutant strains. Although BSC2 overexpression increased the level of mannose in the cell wall, DPM1 overexpression in both BY4741 and bsc2∆ could confer resistance to CAS and AMB. In addition, BSC2 overexpression significantly increased the mRNA expression of FLO11, FLO1, FLO8 and TUP1. BSC2 may function as a regulator of FLO genes and be involved in cell wall integrity in yeast. Taken together, our data demonstrate that BSC2 induces MDR in a FLO pathway-dependent manner via contributing to the formation of biofilms in S. cerevisiae. TAKE AWAYS: Overexpression of BSC2 induced strong MDR in S. cerevisiae. BSC2 affected cellular flocculation, CSH, biofilm formation and invasive growth. BSC2 could not repair the cell wall damage caused by CAS in the FLO mutants. BSC2 may function as a regulator of FLO genes to maintain cell wall integrity. BSC2 promotes biofilm formation in a FLO pathway-dependent manner to induce MDR.
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http://dx.doi.org/10.1111/cmi.13391DOI Listing
September 2021

Inflammatory macrophages exacerbate neutrophil-driven joint damage through ADP/P2Y signaling in rheumatoid arthritis.

Sci China Life Sci 2021 Aug 31. Epub 2021 Aug 31.

Changning Maternity and Infant Health Hospital and School of Life Sciences, Shanghai Key Laboratory of Regulatory Biology, East China Normal University, Shanghai, 200241, China.

Rheumatoid arthritis (RA) is a chronic autoimmune disease that primarily affects the joints and is associated with excessive immune cell infiltration. However, the complex interactions between the immune cell populations in the RA synovium remain unknown. Here, we demonstrate that inflammatory macrophages in the synovium exacerbate neutrophil-driven joint damage in RA through ADP/P2Y signaling. We show that extracellular ADP (eADP) and its receptors are obviously increased in synovial tissues of RA patients as well as collagen-induced arthritis (CIA) mice, and eADP enhances neutrophil infiltration into joints through macrophages producing the chemokine CXCL2, aggravating disease development. Accordingly, the arthritis mouse model had more neutrophils in inflamed joints following ADP injection, whereas P2Y deficiency and pharmacologic inhibition restored arthritis severity to basal levels, suggesting a dominant role of ADP/P2Y signaling in RA pathology. Moreover, cellular activity of ADP/P2Y-mediated CXCL2 production was dependent on the G/Ca-NF-κB/NFAT pathway in macrophages. Overall, this study reveals a non-redundant role of eADP as a trigger in the pathogenesis of RA through neutrophil recruitment and disrupted tissue homeostasis and function.
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http://dx.doi.org/10.1007/s11427-020-1957-8DOI Listing
August 2021

Comprehensive analysis of pan-cancer reveals potential of ASF1B as a prognostic and immunological biomarker.

Cancer Med 2021 Oct 2;10(19):6897-6916. Epub 2021 Sep 2.

Department of Oncology, Renmin Hospital of Wuhan University, Wuhan, China.

Background: Anti-silencing function 1 (ASF1) is a conserved histone H3-H4 chaperone protein. ASF1B, a paralog of ASF1, acts by promoting cell proliferation and influencing cell cycle progression. Although there is some evidence demonstrating that ASF1B plays a key role in the development, progression, and prognosis of certain cancers, there are no pan-cancer analyses of ASF1B.

Methods: We used a range of bioinformatics approaches to investigate the predictive role of ASF1B, including its correlation with prognosis, tumor mutational burden (TMB), microsatellite instability (MSI), tumor microenvironment (TME), and immune cell infiltration, in diverse cancer types.

Results: We found that ASF1B was highly expressed in 22 cancers and was negatively correlated with the prognosis of multiple major cancer types. Furthermore, ASF1B expression was correlated with TMB in 21 cancers and with MSI in 7 cancers. We found that ASF1B was coexpressed with genes encoding immune activators, immune suppressors, major histocompatibility complexes, chemokines, and chemokine receptors. We further found that the role of ASF1B in the infiltration of different types of immune cells varied across tumor types. ASF1B may potentially affect several key immune-related pathways, such as those involved in antigen processing and presentation, natural killer cell-mediated cytotoxicity, and autoimmune thyroid disease.

Conclusions: Our findings show that ASF1B may serve as a prognostic marker and potential immunotherapeutic target for several malignancies due to its role in tumorigenesis and immune infiltration.
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http://dx.doi.org/10.1002/cam4.4203DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8495294PMC
October 2021

SnS Nanosheets with RGO Modification as High-Performance Anode Materials for Na-Ion and K-Ion Batteries.

Nanomaterials (Basel) 2021 Jul 27;11(8). Epub 2021 Jul 27.

School of Environmental and Material Engineering, Yantai University, Yantai 264005, China.

To date, the fabrication of advanced anode materials that can accommodate both Na and K storage is still very challenging. Herein, we developed a facile solvothermal and subsequent annealing process to synthesize SnS/RGO composite, in which SnS nanosheets are bonded on RGO, and investigated their potential as anodes for Na and K storage. When used as an anode in SIBs, the as-prepared SnS/RGO displays preeminent performance (581 mAh g at 0.5 A g after 80 cycles), which is a significant improvement compared with pure SnS. More encouragingly, SnS/RGO also exhibits good cycling stability (130 mAh g at 0.3 A g after 300 cycles) and excellent rate capability (520.8 mAh g at 0.05 A g and 281.4 mAh g at 0.5 A g) when used as anode for PIBs. The well-engineered structure not only guarantees the fast electrode reaction kinetics, but also ensures superior pseudocapacitance contribution during repeated cycles, which has been proved by kinetic analysis.
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http://dx.doi.org/10.3390/nano11081932DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8401318PMC
July 2021

Heat-inactivated Escherichia coli promotes hematopoietic regeneration after irradiation with IL-1β.

Cytotherapy 2021 Aug 20. Epub 2021 Aug 20.

The State Key Laboratory of Experimental Hematology, National Clinical Research Center for Blood Diseases, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin, China. Electronic address:

Background Aims: Hematopoietic stem and progenitor cells (HSPCs) are known to produce short-lived mature blood cells via proliferation and differentiation in a process that depends partially on regulatory cytokines from the bone marrow (BM) microenvironment. Delayed BM recovery after tremendous damage to the hematopoietic system can lead to neutropenia, anemia, thrombopenia and even death. However, efficiently promote BM recovery is still a big problem to be solved. Here, the authors aim to use heat-inactivated Escherichia coli (HIEC) to enhance BM recovery and further to find out the potential mechanism.

Methods: X-rad was used to establish HIEC/IL-1β-induced radioprotection model. Single-cell RNA sequencing, RT-PCR, and western blotting were performed to detect the expression of IL-1R1 on HSPCs. Flow cytometry and automated hematology analyzer were used to analyze the percentage and absolute number of different populations of hematopoietic cells. The effects of IL-1β on HSPCs were studied using in vivo and in vitro experiments.

Results: HIEC/IL-1β pre-treatment can significantly increase the survival rate of lethally irradiated mice, and these mice showed better hematopoietic regeneration compared with control group. IL-1R was expressed on HSPCs, and IL-1β could directly function on HSPCs to promote the proliferation and differentiation of HSPCs, and inhibit the apoptosis of HSPCs.

Conclusions: HIEC pre-treatment can rescue lethally irradiated mice by promoting hematopoietic recovery via IL-1β/IL-1R1 signaling, which can promote the proliferation of HSPCs by enhancing the cell cycle and attenuating the apoptosis of HSPCs.
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http://dx.doi.org/10.1016/j.jcyt.2021.07.003DOI Listing
August 2021

A comparative study on knowledge towards COVID-19 prevention among undergraduate students in Macao and Zhuhai, China.

PeerJ 2021 3;9:e11833. Epub 2021 Aug 3.

Faculty of Medicine, Macau University of Science and Technology, Macao, China.

In order to develop the strategy more suitable campus-based coronavirus disease 2019 (COVID-19) prevention programs for undergraduate students, it is critical to identify discrepancies in knowledge of COVID-19 prevention among students from different campuses in China. The present study examined the difference in preventive knowledge about COVID-19 pandemic in undergraduate students from two cities of Guangdong-Hong Kong-Macao Greater Bay Area (GBA), Macao Special Administrative Region (SAR), which had very few cases of COVID-19 patients, and Zhuhai, which is borders Macao SAR. In August 2020, two cohorts of undergraduate students from universities in Macao ( = 977) and Zhuhai ( = 2,818) were recruited for online. The self-rating questionnaire was used to gain information about their knowledge in COVID-19 prevention. Macao and Zhuhai students had similar correct rates in terms of heat inactivation conditions of SARS-CoV-2, (76.8% 76.9%, = 0.950), etiquette when coughing and sneezing (75.9% 75.0%, = 0.562), and use of disposable masks (92.2% 90.6%, = 0.126). However, students from Macao had significantly higher rates in correct use of disinfectants against SARS-CoV-2 (24.6% 17.5%, < 0.001) and in the route of transmission of SARS-CoV-2 (84.5% 79.6%, < 0.001) than those from Zhuhai. In conclusion, the knowledge level of COVID-19 prevention differs among undergraduate students from Macao and Zhuhai, which warrants an appropriate region-specific health education strategie for COVID-19 prevention.
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http://dx.doi.org/10.7717/peerj.11833DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8344680PMC
August 2021

XOmiVAE: an interpretable deep learning model for cancer classification using high-dimensional omics data.

Brief Bioinform 2021 Aug 17. Epub 2021 Aug 17.

Data Science Institute Imperial College London, SW7 2AZ London, UK.

The lack of explainability is one of the most prominent disadvantages of deep learning applications in omics. This 'black box' problem can undermine the credibility and limit the practical implementation of biomedical deep learning models. Here we present XOmiVAE, a variational autoencoder (VAE)-based interpretable deep learning model for cancer classification using high-dimensional omics data. XOmiVAE is capable of revealing the contribution of each gene and latent dimension for each classification prediction and the correlation between each gene and each latent dimension. It is also demonstrated that XOmiVAE can explain not only the supervised classification but also the unsupervised clustering results from the deep learning network. To the best of our knowledge, XOmiVAE is one of the first activation level-based interpretable deep learning models explaining novel clusters generated by VAE. The explainable results generated by XOmiVAE were validated by both the performance of downstream tasks and the biomedical knowledge. In our experiments, XOmiVAE explanations of deep learning-based cancer classification and clustering aligned with current domain knowledge including biological annotation and academic literature, which shows great potential for novel biomedical knowledge discovery from deep learning models.
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http://dx.doi.org/10.1093/bib/bbab315DOI Listing
August 2021

3D-Printing Damage-Tolerant Architected Metallic Materials with Shape Recoverability via Special Deformation Design of Constituent Material.

ACS Appl Mater Interfaces 2021 Aug 16;13(33):39915-39924. Epub 2021 Aug 16.

Department of Nuclear Science and Engineering and Department of Materials Science and Engineering, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, United States.

Architected metallic materials generally suffer from a serious engineering problem of mechanical instability manifested as the emergence of localized deformation bands and collapse of strength. They usually cannot exhibit satisfactory shape recoverability due to the little recoverable strain of metallic constituent material. After yielding, the metallic constituent material usually exhibits a continuous low strain-hardening capacity, giving the local yielded regions of architecture low load resistance and easily developing into excessive deformation bands, accompanied by the collapse of strength. Here, a novel constituent material deformation design strategy has been skillfully proposed, where the low load resistance of yielded regions of the architecture can be effectively compensated by the significant self-strengthening behavior of constituent material, thus avoiding the formation of localized deformation bands and collapse of strength. To substantiate this strategy, shape-memory alloys (SMAs) are considered as suitable constituent materials for possessing both self-strengthening behavior and shape-recovery function. A 3D-printing technique was adopted to prepare various NiTi SMA architected materials with different geometric structures. It is demonstrated that all of these architected metallic materials can be stably and uniformly compressed by up to 80% without the formation of localized bands, collapse of strength, and structural failure, exhibiting ultrahigh damage tolerance. Furthermore, these SMA architected materials can display more than 98% shape recovery even after 80% deformation and excellent cycle stability during 15 cycles. This work exploits the amazing impact of constituent materials on constructing supernormal properties of architected materials and will open new avenues for developing high-performance architected metallic materials.
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http://dx.doi.org/10.1021/acsami.1c11226DOI Listing
August 2021

Disc measurement and nucleus calibration in a smoothened lumbar model increases the accuracy and efficiency of in-silico study.

J Orthop Surg Res 2021 Aug 13;16(1):498. Epub 2021 Aug 13.

Department of Orthopedic Surgery and Orthopedic Research Institute, West China Hospital/West China School of Medicine for Sichuan University, Chengdu, 610041, China.

Backgrounds: Finite element analysis (FEA) is an important tool during the spinal biomechanical study. Irregular surfaces in FEA models directly reconstructed based on imaging data may increase the computational burden and decrease the computational credibility. Definitions of the relative nucleus position and its cross-sectional area ratio do not conform to a uniform standard in FEA.

Methods: To increase the accuracy and efficiency of FEA, nucleus position and cross-sectional area ratio were measured from imaging data. A FEA model with smoothened surfaces was constructed using measured values. Nucleus position was calibrated by estimating the differences in the range of motion (RoM) between the FEA model and that of an in-vitro study. Then, the differences were re-estimated by comparing the RoM, the intradiscal pressure, the facet contact force, and the disc compression to validate the measured and calibrated indicators. The computational time in different models was also recorded to evaluate the efficiency.

Results: Computational results indicated that 99% of accuracy was attained when measured and calibrated indicators were set in the FEA model, with a model validation of greater than 90% attained under almost all of the loading conditions. Computational time decreased by around 70% in the fitted model with smoothened surfaces compared with that of the reconstructed model.

Conclusions: The computational accuracy and efficiency of in-silico study can be improved in the lumbar FEA model constructed using smoothened surfaces with measured and calibrated relative nucleus position and its cross-sectional area ratio.
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http://dx.doi.org/10.1186/s13018-021-02655-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8362282PMC
August 2021

Personalized Neoantigen-Pulsed DC Vaccines: Advances in Clinical Applications.

Front Oncol 2021 26;11:701777. Epub 2021 Jul 26.

State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, and Collaborative Innovation Center for Biotherapy, Chengdu, China.

In the past few decades, great progress has been made in the clinical application of dendritic cell (DC) vaccines loaded with personalized neoantigens. Personalized neoantigens are antigens arising from somatic mutations in cancers, with specificity to each patient. DC vaccines work based on the fundamental characteristics of DCs, which are professional antigen-presenting cells (APCs), responsible for the uptake, processing, and presentation of antigens to T cells to activate immune responses. Neoantigens can exert their antitumor effects only after they are taken up by APCs and presented to T cells. In recent years, neoantigen-based personalized tumor therapeutic vaccines have proven to be safe, immunogenic and feasible treatment strategies in patients with melanoma and glioblastoma that provide new hope in the treatment of cancer patients and a new approach to cure cancer. In addition, according to ClinicalTrials.gov, hundreds of registered DC vaccine trials are either completed or ongoing worldwide, of which 9 are in early phase I, 191 in phase I, 166 in phase II and 8 in phase III. Hundreds of clinical studies on therapeutic tumor vaccines globally have proven that DC vaccines are stable, reliable and very safe. However, in this process, many other factors still limit the effectiveness of the vaccine. This review will focus on the current research progress on personalized neoantigen-pulsed DC vaccines, their limitations and future research directions of DC vaccines loaded with neoantigens. This review aims to provide a better understanding of DCs biology and manipulation of activated DCs for DCs researchers to produce the next generation of highly efficient cancer vaccines for patients.
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http://dx.doi.org/10.3389/fonc.2021.701777DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8350509PMC
July 2021

Advances in the application of nanotechnology in reducing cardiotoxicity induced by cancer chemotherapy.

Semin Cancer Biol 2021 Aug 8. Epub 2021 Aug 8.

Key Laboratory of Chinese Internal Medicine of Ministry of Education, Dongzhimen Hospital, Beijing University of Chinese Medicine, Beijing, China; College of Integrated Traditional Chinese and Western Medicine, Hunan University of Chinese Medicine, Changsha, Hunan, China. Electronic address:

Advances in the development of anti-tumour drugs and related technologies have resulted in a significant increase in the number of cancer survivors. However, the incidence of chemotherapy-induced cardiotoxicity (CIC) has been rising continuously, threatening their long-term survival. The integration of nanotechnology and biomedicine has brought about an unprecedented technological revolution and has promoted the progress of anti-tumour therapy. In this review, we summarised the possible mechanisms of CIC, evaluated the role of nanoparticles (including liposomes, polymeric micelles, dendrimers, and hydrogels) as drug carriers in preventing cardiotoxicity and proposed five advantages of nanotechnology in reducing cardiotoxicity: Liposomes cannot easily penetrate the heart's endothelial barrier; optimized delivery strategies reduce distribution in important organs, such as the heart; targeting the tumour microenvironment and niche; stimulus-responsive polymer nano-drug carriers rapidly iterate; better economic benefits were obtained. Nanoparticles can effectively deliver chemotherapeutic drugs to tumour tissues, while reducing the toxicity to heart tissues, and break through the dilemma of existing chemotherapy to a certain extent. It is important to explore the interactions between the physicochemical properties of nanoparticles and optimize the highly specific tumour targeting strategy in the future.
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http://dx.doi.org/10.1016/j.semcancer.2021.08.003DOI Listing
August 2021

High-Throughput Enzyme Assay for Screening Inhibitors of the ZDHHC3/7/20 Acyltransferases.

ACS Chem Biol 2021 08 10;16(8):1318-1324. Epub 2021 Aug 10.

Department of Chemistry and Chemical Biology, Cornell University, Ithaca, New York 14853, United States.

As enzymes that mediate the attachment of long-chain fatty acids to cysteine residues, ZDHHC proteins have been reported to be promising therapeutic targets for treating cancer and autoimmune diseases. Yet, due to the lack of potent selective inhibitors, scrutiny of the biological functions of ZDHHCs has been limited. The main hindrance for developing ZDHHC inhibitors is the lack of a facile high-throughput assay. Here, we developed a ZDHHC3/7/20 high-throughput assay based on the acylation-coupled lipophilic induction of polarization (Acyl-cLIP) method and screened several potential ZDHHC inhibitors. Furthermore, we demonstrated that in vitro results from the Acyl-cLIP assay are supported by the results from cell-based assays. We envision that this new ZDHHC3/7/20 Acyl-cLIP assay will accelerate the high-throughput screening of large compound libraries for improved ZDHHC inhibitors and provide therapeutic benefits for cancer and autoimmune diseases.
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http://dx.doi.org/10.1021/acschembio.1c00258DOI Listing
August 2021
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