Publications by authors named "Yang Liu"

12,113 Publications

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Intranasal oxytocin restoration of maternal behavior and oxytocin neuronal activity in the supraoptic nucleus in rat dams with pre-labor cesarean delivery.

Neuroscience 2021 Jun 21. Epub 2021 Jun 21.

Department of Physiology, School of Basic Medical Sciences, Harbin Medical University, Harbin, China. Electronic address:

Oxytocin (OT) is a key factor for maternal behavior; however, neurochemical regulation of OT neurons, the major source of OT, remains incompletely understood. Here we report the effect of intranasally-applied OT (IAO) on OT neuronal activity in the supraoptic nucleus (SON) and maternal behavior in a rat model of cesarean delivery (CD) at day 4-5 (stage I) and day 8-9 (stage II) following the delivery. We found that at stage I, CD dams exhibited significantly longer latency of pup retrieval, lower number of anogenital licking and smaller acinar area of the mammary glands. In the SON, the number of OT neurons expressing phosphorylated extracellular signal-regulated protein kinase 1/2 (pERK 1/2) decreased significantly. IAO reversed the depressive-like maternal behavior and involution-like change in the mammary glands, and restored the number of pERK1/2-positive OT neurons in CD dams. At stage II, CD did not significantly influence the latency of retrieval and pERK1/2 expression in the SON; however, CD still reduced the number of anogenital licking during suckling, which was reversed by IAO. Notably, IAO but not hypodermic OT application in CD dams significantly increased litter's body weight gains. In brain slices, CD but not CD plus IAO depolarized membrane potential significantly and increased spike duration in OT neurons. In vasopressin neurons, CD but not CD plus IAO significantly depolarized membrane potential and increased the firing rate. Thus, the decreased OT neuronal activity and increased vasopressin neuronal activity impair maternal behavior in CD dams, which can be prevented by IAO through nose-brain axis.
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http://dx.doi.org/10.1016/j.neuroscience.2021.06.020DOI Listing
June 2021

Targeting Hypoxia for Sensitization of Tumors to Apoptosis Enhancement through Supramolecular Biohybrid Bacteria.

Int J Pharm 2021 Jun 21:120817. Epub 2021 Jun 21.

School of Life and Pharmaceutical Sciences, Hainan University, Haikou 570228, China. Electronic address:

Bacteria-driven drug-delivery systems have drawn considerable interests for their highly selective hypoxia-targeting and efficacy in tumor inhibition. For the first time, a supramolecular biohybrid bacterium ([email protected]) is constructed by coating attenuated Salmonella typhimurium (S. typhimurium ΔppGpp/Lux) with nanoassemblies. In addition, the host-guest inclusion complexes based on hydroxypropyl-β-cyclodextrin (HPCD) and amantadine (AMA) was developed to encapsulate the natural antineoplastic product, ursolic acid (UA). It is found that the drug-carried coating layer has no significant impact on the antitumor activity or tumor-targeting capacity of bacteria. Significant restraint of tumor progression is achieved by [email protected] due to the synergy of cellular immune activation and apoptosis enhancement. Most importantly, intravenous delivery of UA by this biohybrid vector can cause tumor lysis, as the bacteria-attracting nutrients beneficial for preferential accumulation of bacteria in tumor. The mutual promotion of bacteria and UA may also contribute to a superior anticancer effect. Hence, the [email protected] biotic/abiotic supramolecular therapeutic system represents a novel strategy for combined chemo-bacterial therapy.
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http://dx.doi.org/10.1016/j.ijpharm.2021.120817DOI Listing
June 2021

A novel nonlinear creep model based on damage characteristics of mudstone strength parameters.

PLoS One 2021 24;16(6):e0253711. Epub 2021 Jun 24.

School of Resources and Environmental Engineering, Wuhan University of Science and Technology, Wuhan, China.

Mudstone interlayer is a weak layer in rock engineering. When it is subjected to continuous stress higher than its damage threshold, due to the dislocation of particles in mudstone crystals and the expansion of cracks, mudstone strength is gradually damaged and deteriorated and the strain gradually increases, thus accelerating the phenomenon of creep damage. In order to describe the characteristics of the whole process of mudstone aging deformation, based on the damage evolution of strength parameters (cohesion and internal friction coefficient) with stress and time in mudstone creep tests, a novel damage nonlinear viscoelastoplastic body (D-NVPB) is proposed through improving traditional plastic element. D-NVPB describes the nonlinear characteristics of the accelerated creep stage of mudstone. With the element combination method, D-NVPB is connected with the Burgers model in series to form a new nonlinear damage creep model (D-NVEP model). The analysis results of creep characteristics theoretically verified the rationality of the model in describing the instantaneous elasticity, viscoelasticity, and nonlinear viscoplastic characteristics of the complete creep curve of mudstone. With the data obtained in the uniaxial compression creep test of mudstone under the action of a stress level of 14 MPa, based on the Levenberg-Marquardt nonlinear least squares method, the fitting calculation was performed through piecewise fitting and overall fitting. The correlation coefficient was 0.9909, which verified the applicability of the model. The obtained model parameters by the identification were used to predict the mudstone creep curve under the stress levels of 13 MPa and 15 MPa. The good prediction results further verified the feasibility of the model. Compared with the traditional creep model, the D-NVEP model can better describe the nonlinear characteristics of the accelerated creep stage and quantitatively display the strength damage evolution process of rock in the creep failure process.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0253711PLOS
June 2021

Will land circulation sway "grain orientation"? The impact of rural land circulation on farmers' agricultural planting structures.

PLoS One 2021 24;16(6):e0253158. Epub 2021 Jun 24.

School of Economics, Jiangxi University of Finance and Economics, Nanchang, China.

This study calculates the effect of different types of land circulation on farmers' decision-making regarding agricultural planting structure, using field survey data involving 1,120 households in Hubei province, China, and PSM (propensity score matching) and GPSM (general propensity score matching) methods. Results from PSM showed that land circulation could significantly increase farmers' decisions to plant food crops, which confirms the positive effect of rural land circulation on the "grain orientation" of crop planting structure. Results from GPSM further indicate that the total land circulation, the paddy land circulation, and the dry land circulation all have significantly positive effects on planting structure adjustment towards "grain orientation." Additionally, planting structure adjustment towards "grain orientation" increases as the scale of land circulation increases, and the former shows a higher rate of increase than the latter, which confirms that rural land circulation facilitates an adjustment in structure towards planting food crops.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0253158PLOS
June 2021

A daily diary study of minority stress and negative and positive affect among racially diverse sexual minority adolescents.

J Couns Psychol 2021 Jun 24. Epub 2021 Jun 24.

Department of Behavioral and Community Health, University of Maryland School of Public Health.

We conducted an intensive longitudinal study of sexual minority adolescents to address gaps in the literature, limitations in retrospective reporting, and test tenets of the minority stress model. We examined the frequency of daily minority stressors and their within-person associations with negative and positive affect. We also tested the moderating effects of depressive symptomology on these associations. Sexual minority adolescents (N = 94; 35.1% were bisexual; 31.9% were gender minority; 45.2% were racial/ethnic minority), ages 12-18 years old (M = 16.1, SD = 1.5), were recruited from the community and completed a baseline questionnaire and then a 21-day daily dairy (82.5% response rate). Participants experienced at least one minority stressor, with an average of 16.96 minority stressors (SD = 18.7, Range: 0-83), over the 21-day monitoring period. Some minority stressors were more commonly experienced than others (e.g., vicarious minority stress) and most participants attributed their sexual orientation to these stressors. Participants also attributed other marginalized identities to these stressors (e.g., gender identity, race). Daily minority stressors were associated with greater negative affect but not positive affect. Participants had greater negative affect on days where sexual-orientation-specific minority stressors were endorsed compared to days where minority stressors were not reported. These associations were not moderated by depression symptomology. The results underscore that minority stressors are pervasive experiences of sexual minority adolescents' daily life and natural environment and they are associated with daily emotions. The findings have implications for the minority stress model and future research and interventions. (PsycInfo Database Record (c) 2021 APA, all rights reserved).
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http://dx.doi.org/10.1037/cou0000556DOI Listing
June 2021

Capturing Membrane Phase Separation by Dual Resolution Molecular Dynamics Simulations.

J Chem Theory Comput 2021 Jun 24. Epub 2021 Jun 24.

Groningen Biomolecular Sciences and Biotechnology Institute and the Zernike Institute for Advanced Material, University of Groningen, Groningen 9747AG, The Netherlands.

Understanding the lateral organization in plasma membranes remains an open problem and is of great interest to many researchers. Model membranes consisting of coexisting domains are commonly used as simplified models of plasma membranes. The coarse-grained (CG) Martini force field has successfully captured spontaneous separation of ternary membranes into a liquid-disordered and a liquid-ordered domain. With all-atom (AA) models, however, phase separation is much harder to achieve due to the slow underlying dynamics. To remedy this problem, here, we apply the virtual site (VS) hybrid method on a ternary membrane composed of saturated lipids, unsaturated lipids, and cholesterol to investigate the phase separation. The VS scheme couples the two membrane leaflets at CG and AA resolution. We found that the rapid phase separation reached by the CG leaflet can accelerate and guide this process in the AA leaflet.
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http://dx.doi.org/10.1021/acs.jctc.1c00151DOI Listing
June 2021

Combined strategies for effective cancer immunotherapy with a novel anti-CD47 monoclonal antibody.

Cancer Immunol Immunother 2021 Jun 24. Epub 2021 Jun 24.

Innovent Biologics (Suzhou) Co., Ltd, 168 Dongping Street, Suzhou Industrial Park, Suzhou, 215123, Jiangsu, China.

CD47 is a widely expressed cell-surface protein that regulates phagocytosis mediated by cells of the innate immune system, such as macrophages and dendritic cells. CD47 serves as the ligand for a receptor on these innate immune cells, signal regulatory protein (SIRP)-α, which in turn inhibits phagocytosis. Several targeted CD47 therapeutic antibodies have been investigated clinically; however, how to improve its therapeutic efficacy remains unclear. Herein, we developed a CD47 blocking antibody, named IBI188, that could specifically block the CD47-SIRP-α axis, which transduces the "don't eat me" signal to macrophages. In vitro phagocytosis assays demonstrated the pro-phagocytosis ability of IBI188. Furthermore, several in vivo models were chosen to evaluate the anti-tumor efficacy of IBI188. IBI188 treatment upregulated cell movement- and inflammation-related genes in macrophages. Synergism was observed when combined with an anti-CD20 therapeutic antibody, whose function depends on antibody-dependent cellular cytotoxicity/phagocytosis (ADCC/ADCP). CD47 expression was evaluated following azacytidine (AZA) treatment, a standard-of-care for patients with multiple myeloma; enhanced anti-tumor efficacy was observed in the combination group in AML xenograft models. Notably, IBI188 treatment increased vascular endothelial growth factor-A (VEGF-A) levels in a solid tumor model, and combined treatment with an anti-VEGF-A antibody and IBI188 resulted in an enhanced anti-tumor effect. These data indicate that IBI188 is a therapeutic anti-CD47 antibody with anti-tumor potency, which can be enhanced when used in combination with standard-of-care drugs for cancer treatment.
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http://dx.doi.org/10.1007/s00262-021-02989-2DOI Listing
June 2021

LINC00662 Promotes Oral Squamous Cell Carcinoma Cell Growth and Metastasis through miR-144-3p/EZH2 Axis.

Yonsei Med J 2021 Jul;62(7):640-649

Department of Stomatology, Dongping Hospital Affiliated to Shandong First Medical University, Dongping, China.

Purpose: Long non-coding RNA (lncRNA) is identified as an important regulator involved in oral squamous cell carcinoma (OSCC) tumorigenesis. This study aimed to investigate the functional role and underlying mechanism of LINC00662 in OSCC.

Materials And Methods: The expression levels of LINC00662, miR-144-3p, and enhancer of zeste homolog 2 (EZH2) mRNA were quantified with quantitative real-time polymerase chain reaction in OSCC tissues and cell lines. Western blot analysis was used to assay the expression levels of E-cadherin, Vimentin, and EZH2. Cell proliferation, migration, and invasion were monitored by cell counting kit-8 and Transwell assays. Dual-luciferase reporter and RNA immunoprecipitation assays were employed to verify the regulatory relationship between LINC00662 and miR-144-3p.

Results: The expression of LINC00662, positively associated with the increased TNM stage and lymph node metastasis of the patients, was up-regulated in OSCC tissues and cells. The overexpression of LINC00662 facilitated the proliferation, migration, and invasion of OSCC cells. MiR-144-3p could bind to LINC00662, and the promoting effect of LINC00662 overexpression was counteracted by miR-144-3p mimic. Moreover, EZH2 expression was negatively regulated by miR-144-3p and positively regulated by LINC00662. The silencing of EZH2 attenuated the promoting effects of overexpression of LINC00662 on cell proliferation, migration, invasion, and epithelial-mesenchymal transition.

Conclusion: LINC00662, as an oncogenic lncRNA of OSCC, accelerates OSCC progression by repressing miR-144-3p expression and increasing EZH2 expression.
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http://dx.doi.org/10.3349/ymj.2021.62.7.640DOI Listing
July 2021

Halogenated salt assisted Cu-catalyzed asymmetric 1,4-borylstannation of 1,3-enynes: enantioselective synthesis of allenylstannes.

Chem Sci 2020 Dec 22;12(8):3032-3038. Epub 2020 Dec 22.

College of Chemical Engineering, Sichuan University Chengdu 610065 China.

An enantioselective 1,4-borylstannation of 1,3-enynes employed a chiral sulfoxide phosphine ()/Cu complex as a catalyst, and the desired products, chiral allenylstannes, were first synthesized by asymmetric catalysis with satisfactory yields and enantioselectivies. In this protocol, a catalytic amount of additive, a halogenated salt, plays a crucial role in the success. Control experiments and theoretical studies disclosed that the four-membered ring transmetallation transition states which were stabilized by a halide anion are the key to yields and stereochemical outcomes.
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http://dx.doi.org/10.1039/d0sc05425aDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8179376PMC
December 2020

Hybridized local and charge-transfer excited state fluorophores enabling organic light-emitting diodes with record high efficiencies close to 20.

Chem Sci 2021 Feb 23;12(14):5171-5176. Epub 2021 Feb 23.

PCFM Lab, GDHPPC Lab, Guangdong Engineering Technology, Research Center for High-performance Organic and Polymer Photoelectric Functional Films, State Key Laboratory of OEMT, School of Chemistry, Sun Yat-sen University Guangzhou 510275 China

Pure organic emitters with full utilization of triplet excitons are in high demand for organic light-emitting diodes (OLEDs). Herein, through modulation of electron donors and introduction of phenyl rings as π spacers, we present three pure organic fluorophores (BCz, BTCz and BPTCz) with the hybridized local and charge-transfer (HLCT) excited state feature for OLED fabrication. Importantly, the introduction of π spacers in BPTCz not only enhances locally excited character with a fast radiative decay but also promotes intermolecular interactions to suppress non-radiative decays, contributing to a high solid-state fluorescence efficiency over 90%. Significantly, BPTCz not only endows its doped OLEDs with an external quantum efficiency (EQE) up to 19.5%, but also its non-doped OLED with a high EQE of 17.8%, and these outstanding efficiencies are the state-of-the-art performances of HLCT-based OLEDs.
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http://dx.doi.org/10.1039/d1sc00272dDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8179597PMC
February 2021

Correction: Dependence of the fluorination intercalation of graphene toward high-quality fluorinated graphene formation.

Chem Sci 2020 Dec 16;12(1):490-491. Epub 2020 Dec 16.

College of Polymer Science and Engineering, State Key Laboratory of Polymer Material and Engineering, Sichuan University Chengdu 610065 People's Republic of China +86 28 85405138 +86 28 85403948.

[This corrects the article DOI: 10.1039/C9SC00975B.].
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http://dx.doi.org/10.1039/d0sc90268cDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8178970PMC
December 2020

High SQLE Expression and Gene Amplification Correlates with Poor Prognosis in Head and Neck Squamous Cell Carcinoma.

Cancer Manag Res 2021 14;13:4709-4723. Epub 2021 Jun 14.

Department of Oral Surgery, Shengjing Hospital of China Medical University, Shenyang, Liaoning Province, People's Republic of China.

Objective: Squalene epoxidase (SQLE) is considered a metabolic oncogene, but its biological function and prognostic value in head and neck squamous cell carcinoma (HNSCC) remain unclear. We aimed to evaluate the role of SQLE in the occurrence and development of HNSCC through bioinformatics analysis, and validation experiments.

Methods: Transcriptomic, genomic, and clinical data from The Cancer Genome Atlas were used for pan-cancer analysis. SQLE expression in HNSCC was evaluated using Gene Expression Omnibus datasets and immunohistochemistry. The biological significance of SQLE in the tumor microenvironment (TME) of HNSCC was determined using TISCH, HuRI, LinkedOmics, and TIMER 2.0. The prognostic value of SQLE in HNSCC was analyzed using univariate Cox regression and Kaplan-Meier survival curves. Effect of SQLE on the Cal27 HNSCC cell line was evaluated using cell counting kit 8, wound healing, and EdU assays.

Results: SQLE was overexpressed and amplified in various cancers, including HNSCC. High SQLE expression promoted cell proliferation, associated with T stage in HNSCC patients. Copy number amplification and DNA demethylation contributed to high SQLE expression in HNSCC, which was associated with poor prognosis. SQLE was related to HNSCC TME, and its mRNA expression/copy number alterations were negatively correlated with the infiltration of CD8+ T cells, follicular helper T cells, and regulatory T cell infiltration and mast cell activation and positively correlated with the infiltration of M0 macrophages and resting mast cells in HNSCC.

Conclusion: SQLE was identified as a prognostic biomarker and a potential pharmaceutical target for HNSCC.
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http://dx.doi.org/10.2147/CMAR.S305719DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8213972PMC
June 2021

Study on the compatibility effect and active constituents of Atractylodis Rhizoma in Ermiao Wan against Acute Gouty Arthritis.

J Ethnopharmacol 2021 Jun 20:114353. Epub 2021 Jun 20.

State Key Laboratory of Natural Medicines, Department of Pharmacognosy, China Pharmaceutical University, Nanjing, 210009, China. Electronic address:

Ethnopharmacological Relevance: Ermiao Wan (EMW), composed of Atractylodis Rhizoma (AR) and Phellodendri Chinensis Cortex (PC), is a classical traditional Chinese medicine prescription having been used to treat the disease named "Tong Feng", which is described as "ache in bones and joints" with the same symptom of modern disease named acute gouty arthritis for many years in TCM clinical practice. Besides, both PC and AR were considered to be effective in anti-inflammatory according to modern pharmacological research.

Aim Of The Study: Present study was undertaken to probe the compatibility rationality between the two herbs PC and AR in EMW and the active constituents of AR against acute gouty arthritis (AGA).

Materials And Methods: Rat model of AGA was induced by intra-articular injection of monosodium urate (MSU) crystal suspension, and PC combined with or without different AR extracts were used for AGA treatment. Ankle joint swelling, proinflammatory cytokines in serum and pathological changes of synovium were investigated. Using the developed UHPLC-QQQ-MS method, the plasma concentrations of the primary alkaloids in PC, such as berberine, phellodendrine, magnoflorine, jatrorrhizine, berberrubine, palmatine, and tetrahydropalmatine, in AGA rat were determined, and pharmacokinetics properties were compared following oral administration of PC, PC combined with or without different AR extracts.

Results: PC, PC combined with AR volatile oil (VO) extract or PC combined with whole AR extract significantly attenuated the ankle joint swelling of AGA rats. Besides, the combination of PC and VO extract of AR showed superior efficacy than other groups in ameliorating ankle joint swelling, reducing the IL-6 expression in serum and improving tissue lesions of ankle joints. Furthermore, it turned out that the VO extract of AR increased the blood exposure level of PC related alkaloids than non-volatile oil (NVO) extract of AR, by comparing the pharmacokinetic results of each group.

Conclusions: The VO components of AR were the key compatible materials to combine with PC in EMW for AGA treatment. Moreover, the enhanced anti-AGA activity of PC after combining with VO extract of AR may attribute to the influence of VO on the pharmacokinetics of PC. This study may provide useful information for elucidating the compatibility effects of AR in EMW against AGA.
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http://dx.doi.org/10.1016/j.jep.2021.114353DOI Listing
June 2021

Survival Outcomes of Lobectomy Versus Segmentectomy in Clinical Stage I Non-Small Cell Lung Cancer: A Meta-Analysis.

Adv Ther 2021 Jun 23. Epub 2021 Jun 23.

Department of Thoracic Surgery, Funing People's Hospital, No. 111 Fcheng Street Road, Funing County, Yancheng City, 224400, Jiangsu Province, China.

Introduction: The gold standard surgical therapy for patients with clinical stage I non-small cell lung cancer (NSCLC) is lobectomy with mediastinal lymph node dissection. Meanwhile, segmentectomy has emerged as an alternative choice with the advantage of fewer postoperative complications. The acceptance of this procedure remains controversial, and conflicting results exist in the retrospective trials.

Objectives: The aim of this meta-analysis was to analyze the survival outcomes of lobectomy versus segmentectomy in clinical stage I NSCLC.

Methods: A computerized literature search was done on published trials in PubMed, Embase, and the Cochrane Library to June 2019 to identify clinical trials. Lung cancer-specific survival (LCSS) and overall survival (OS) were measured as outcomes. Statistical analysis was performed in the Meta-analysis Revman 5.3 software.

Results: A systematic literature search was conducted including seven studies. In this meta-analysis, the LCSS and OS in the lobectomy group were linked to a markedly lower trend in comparison to the segmentectomy group without significant statistical difference (P > 0.05), indicating that lobectomy confers an equivalent survival outcome compared with segmentectomy.

Conclusion: No significant differences were found in survival outcomes between lobectomy and segmentectomy. Further large-scale, prospective, randomized trials are needed to explore reasonable surgical treatments for early-stage lung cancer.
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http://dx.doi.org/10.1007/s12325-021-01793-9DOI Listing
June 2021

Dietary supplementary glutamine and L-carnitine enhanced the anti-cold stress of Arbor Acres broilers.

Arch Anim Breed 2021 4;64(1):231-243. Epub 2021 Jun 4.

National Experimental Teaching Demonstration Center of Animal Medicine Foundation, College of Animal Science and Veterinary Medicine, Heilongjiang Bayi Agricultural University, Daqing, 163319, PR China.

Newborn poultry in cold regions often suffer from cold stress, causing a series of changes in their physiology and metabolism, leading to slow growth and decreased production performance. However, a single anti-stress substance cannot completely or maximally eliminate or alleviate the various effects of cold stress on animals. Therefore, the effects of the supplemented glutamine and L-carnitine on broilers under low temperature were evaluated in this study. Broilers were randomly allocated into 16 groups which were respectively fed with different levels of glutamine and L-carnitine according to the L (4 ) orthogonal experimental design for 3 weeks (the first week is the adaptive feeding period; the second and third weeks are the cold exposure period). Growth performance was recorded, and blood samples were collected during cold exposure. The results showed the supplementation had altered the plasma parameters, growth performance and cold-induced oxidative stress. The increase of corticosterone and suppression of thyroid hormone was ameliorated. Supplemented groups had lower daily feed intake and feed-to-gain ratio, higher daily weight gain and better relative weights of immune organs. Plasma glucose, total protein, blood urea nitrogen and alkaline phosphatase changed as well. Oxidative stress was mollified due to the improved activities of superoxide dismutase and glutathione peroxidase, heightened total antioxidant capacity and stable malondialdehyde. Dietary glutamine and L-carnitine improve the growth performance, nutritional status and cold stress response of broilers at low temperature, and their interaction occurred.
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http://dx.doi.org/10.5194/aab-64-231-2021DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8209504PMC
June 2021

Erratum to "Identifying biomolecules and constructing a prognostic risk prediction model for recurrence in osteosarcoma" [J. Bone Oncol. 26 (2021) 100331].

J Bone Oncol 2021 Aug 29;29:100371. Epub 2021 May 29.

Department of Orthopaedics, The Third Hospital of Jilin University, No. 126, Xiantai Street, Changchun, Jilin 130033, China.

[This corrects the article DOI: 10.1016/j.jbo.2020.100331.].
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http://dx.doi.org/10.1016/j.jbo.2021.100371DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8203842PMC
August 2021

Sohlh2 suppresses angiogenesis by downregulating HIF-1α expression in breast cancer.

Mol Cancer Res 2021 Jun 22. Epub 2021 Jun 22.

Dept. of Histology and Embryology, Shandong University

SOHLH2 has been demonstrated the downregulation in various cancers and the involvement in tumor growth and metastasis. However, the function of SOHLH2 on tumor angiogenesis and the underlying molecular mechanisms have not been interrogated. IHC staining results revealed that SOHLH2 was negatively associated with microvessel density (MVD), tumor size, histology grade and metastasis. Overexpression of SOHLH2 inhibited the angiogenic behavior of HUVECs by a tumor cell-mediated paracrine signal, whilst knockdown of SOHLH2 promoted HUVEC angiogenic behavior. Ectopic SOHLH2 expression remarkably suppressed tumor growth and MVD in xenograft tumors, downregulated the expression of HIF-1α-mediated proangiogenic genes in vivo and in vitro, whilst knockdown of SOHLH2 had an opposite result. Furthermore, we found that upregulation of HIF-1α reversed SOHLH2-induced suppression of breast cancer angiogenesis, while KC7F2, the inhibitor of HIF-1α, could attenuate the promotion of angiogenesis by SOHLH2-silencing. Using CHIP and luciferase reporter assays, we validated that SOHLH2 could directly bind to HIF-1α promoter and repress its transcriptional activity. Collectively, SOHLH2 suppresses breast cancer angiogenesis by downregulating HIF-1α transcription and may be a potential biomarker for anti-angiogenesis therapy. Implications: SOHLH2 directly represses HIF-1α mediated angiogenesis and serves as an important inhibitor of angiogenesis in breast cancer.
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http://dx.doi.org/10.1158/1541-7786.MCR-20-0771DOI Listing
June 2021

Pyruvate carboxylase promotes thyroid cancer aggressiveness through fatty acid synthesis.

BMC Cancer 2021 Jun 22;21(1):722. Epub 2021 Jun 22.

Department of Nuclear Medicine, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, No. 197, Ruijin 2nd Road, Shanghai, 200025, China.

Background: Pyruvate carboxylase (PC) is an important anaplerotic enzyme in the tricarboxylic acid cycle (TCA) in cancer cells. Although PC overexpression has been observed in thyroid cancer (TC), the mechanisms involved in the carcinogenic effects of PC are still unclear.

Methods: Bioinformatics analysis and clinical specimens were used to analyze the relationship of PC expression with clinicopathological variables in TC. Fatty acid synthesis was monitored by LC/MS, Nile red staining, and triglyceride analysis. Mitochondrial oxygen consumption was evaluated by the Seahorse XF Mito Cell Stress Test. The correlation of PC with FASN and SREBP1c was assessed by qRT-PCR and IHC in 38 human TC tissues. Western blotting was used to evaluate the protein expression of PC, FASN, and SREBP1c and members of the AKT/mTOR and EMT pathways in TC cell lines. Wound-healing, CCK-8, and Transwell assays and a nude mouse xenograft model were used to verify the regulatory effects of PC and SREBP1c on thyroid tumor cell proliferation, migration and invasion.

Results: We demonstrated that PC increased fatty acid synthesis, which then promoted TC progression and metastasis. Analysis of GEO data showed that the overexpression of PC in papillary thyroid cancer (PTC) was associated with PTC invasion and the fatty acid synthesis pathway. Analysis of clinical tissue specimens from PTC patients revealed that PC was more highly expressed in specimens from PTC patients with lymph node metastasis than in those from patients without metastasis. Multiple genes in the fatty acid synthesis signaling pathway, including FASN and SREBP1c, were downregulated in PC-knockdown TC cells compared to control cells. Lipid levels were also decreased in the PC-knockdown TC cells. Moreover, the ability of cells to grow, invade, and metastasize was also suppressed upon PC knockdown, suggesting that PC-mediated lipogenesis activation increases the aggressiveness of TC cells. In addition, PC was found to activate the AKT/mTOR pathway, thus improving FASN-mediated de novo lipogenesis in TC cells by upregulating SREBP1c expression. Studies in a nude mouse xenograft model showed that PC knockdown decreased tumor weight, but this effect was attenuated by forced expression of SREBP1c.

Conclusions: Our results demonstrate that PC is strongly involved in the tumor aggressiveness of TC via its stimulation of fatty acid synthesis.
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http://dx.doi.org/10.1186/s12885-021-08499-9DOI Listing
June 2021

Fetal growth standards for Chinese twin pregnancies.

BMC Pregnancy Childbirth 2021 Jun 22;21(1):436. Epub 2021 Jun 22.

Department of Fetal Medicine and Prenatal Diagnosis Center, Shanghai First Maternity and Infant Hospital, Tongji University School of Medicine, 2699 West Gaoke Rd, Shanghai, 201204, China.

Background: The common use of singleton fetal growth standard to access twin growth might lead to over-monitoring and treatment. We aimed to develop fetal growth standards for Chinese twins based on ultrasound measurements, and compare it with Zhang's and other twin fetal growth charts.

Methods: A cohort of uncomplicated twin pregnancies were prospectively followed in 2014-2017. Smoothed estimates of fetal growth percentiles for both monochorionic (MC) and dichorionic (DC) twins were obtained using a linear mixed model. We also created growth charts for twins using a model-based approach proposed by Zhang et al. Our twin standards were compared with Hadlock's (singleton) in predicting adverse perinatal outcomes.

Results: A total of 398 twin pregnancies were included, with 214 MC and 582 DC live-born twins. The MC twins were slightly lighter than the DC twins, with small differences throughout the gestation. Our ultrasound-based fetal weight standards were comparable to that using Zhang's method. Compared with previous references/standards from the US, Brazil, Italy and UK, our twins had very similar 50th percentiles, but narrower ranges between the 5th and 95th or 10th and 90th percentiles. Compared with the Hadlock's standard, the risks of neonatal death and adverse perinatal outcomes for small for gestational age (SGA) versus non-SGA were substantially elevated using our standards.

Conclusions: A normal fetal growth standard for Chinese twins was created. The differences between MC and DC twins were clinically insignificant. The 50th weight percentiles of the Chinese twins were identical to those in other races/ethnicities but the ranges were markedly narrower. Our standard performed much better than the Hadlock's in predicting low birth weight infants associated with adverse perinatal outcomes in twin pregnancies. The present study also indicated that Zhang's method is applicable to Chinese twins, and other areas may use Zhang's method to generate their own curves for twins if deemed necessary.
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http://dx.doi.org/10.1186/s12884-021-03926-yDOI Listing
June 2021

Pathogenicity and transmissibility of current H3N2 swine influenza virus in Southern China: A zoonotic potential.

Transbound Emerg Dis 2021 Jun 15. Epub 2021 Jun 15.

College of Veterinary Medicine, South China Agricultural University, Guangzhou, China.

Swine are considered as 'mixing vessels' of influenza A viruses and play an important role in the generation of novel influenza pandemics. In this study, we described that the H3N2 swine influenza (swH3N2) viruses currently circulating in pigs in Guangdong province carried six internal genes from 2009 pandemic H1N1 virus (pmd09), and their antigenicity was obviously different from that of current human H3N2 influenza viruses or recommended vaccine strains (A/Guangdong/1194/2019, A/Hong Kong/4801/2014). These swH3N2 viruses preferentially bonded to the human-like receptors, and efficiently replicated in human, canine and swine cells. In addition, the virus replicated in turbinate and trachea of guinea pigs, and efficiently transmitted among guinea pigs, and virus shedding last for 6 days post-infection (dpi). The virus replicated in the respiratory tract of pigs, effectively transmitted among pigs, and virus shedding last until 9 dpi. Taken together, these current swH3N2 viruses might have the zoonotic potential. Strengthening surveillance and monitoring the pathogenicity of such swH3N2 viruses are urgently needed.
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http://dx.doi.org/10.1111/tbed.14190DOI Listing
June 2021

Enhanced trichloroethylene biodegradation: Roles of biochar-microbial collaboration beyond adsorption.

Sci Total Environ 2021 Jun 16;792:148451. Epub 2021 Jun 16.

School of Environmental Science and Engineering, Shanghai Jiao Tong University, Shanghai 200240, China; China-UK Low Carbon College, Shanghai Jiao Tong University, Shanghai 201306, China.

Trichloroethylene (TCE) is a pollutant widely found in groundwater, especially in the heavily contaminated industrial sites. Biological dechlorination method is environmentally friendly and low-cost. However, microorganisms grow slowly and their activity is susceptible to environmental fluctuations. This study used biochar as an additive to promote anaerobic biodegradation of TCE with mixed culture. Results showed that biochar with dose of 0.1-0.4% (w/v) brought a rapid initial decrease of TCE concentration by 39.4-88.8% in 24 h via adsorption mechanism. Biochar produced at 500 °C pyrolysis temperature (BC500) achieved the highest TCE adsorption in comparison to BC300 and BC700. Subsequently, a significantly shortened microbial stagnation phase (from 85 h to 37 h) was observed in the system with the presence of biochar. During the exponential growth phase, BC700 outperformed BC300 and BC500 in terms of TCE degradation efficiency. Electrochemical analysis demonstrated that BC700 possessed the greatest electron transfer capability. Finally, biochar shortened the time for achieving 100% removal of TCE by 54.5-69.7% (from approximate 330 h to 100-150 h). Even at high concentration of TCE (20-30 mg·L) that could lead to serious microbial growth inhibition, the TCE degradation efficiency could be recovered in the presence of BC500. The high-throughput sequencing data revealed that biochar promoted the relative abundance of co-metabolizing dechlorinating microorganisms (Pseudomonas, Burkholderia) in the aqueous solution, and simultaneously led to the selective colonization of reductive dechlorinating microorganisms (Enterobacteriaceae, Clostridium) attached on biochar surface. On the other hand, biochar addition decreased the relative abundance of hydrogen-competing microorganisms, thereby forming an efficient co-metabolism-reductive dechlorination system. These findings allow a better understanding of the promotion mechanism of biochar for microbial dechlorination technology supporting the biochar-assisted bioremediation in practice.
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http://dx.doi.org/10.1016/j.scitotenv.2021.148451DOI Listing
June 2021

Anthocyanins from purple passion fruit (Passiflora edulia Sims) rind-An innovative source for nonbleachable pigment production.

J Food Sci 2021 Jun 22. Epub 2021 Jun 22.

School of Chemical Engineering and Advanced Materials, The University of Adelaide, Adelaide, South Australia, Australia.

Passion fruit rind is a waste product from the beverage industry that is rich in anthocyanins that can be potentially applied as a natural colorant. However, the inherent instability of anthocyanins causes rapid discoloration. In this study, the cyanidin-3-glucoside (C-3-G) in passion fruit rind was extracted using 50% ethanol and converted into nonbleachable pigments by reaction with Oolong tea extracts and acetaldehyde. Reactions over 70 days formed high concentrations of stable nonbleachable pigments (3.07-6.68 absorbance unit [A.U.], in total) such as pyranoanthocyanins, as well as oligomeric and polymeric pigments with ethyl-linked bridges. In C-3-G and acetaldehyde reaction, positive relations were found among acetaldehyde concentration, color density, and nonbleachable pigment concentrations. As for reactions with C-3-G and Oolong tea extract combined with acetaldehyde, greater color density and greater concentrations of nonbleachable pigments (10.80-12.34, 4.25-4.40 A.U., respectively) were formed compared with acetaldehyde alone. In addition, the antioxidant capabilities of the extracts were enhanced after reaction with Oolong tea extracts. The results of this study show a useful method to enhance the stability of anthocyanins from passion fruit rind and also provide greater economic value to this waste product. PRACTICAL APPLICATION: Ripened passion fruits contain a high concentration of anthocyanins in their rind. These anthocyanins can be optimally extracted by ultrasonic assisted solvent extraction to provide stable pigments by inducing acetaldehyde (a volatile compound often found in foods and beverages) into the anthocyanins. These stable pigments have a greater reddish hue in solution than the anthocyanin extracted from the rind and are more stable over a greater pH range. In addition, these stable pigments can be potentially used as colorant throughout the food and cosmetic industry to provide high economical values.
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http://dx.doi.org/10.1111/1750-3841.15807DOI Listing
June 2021

A radioiodinated FR-β-targeted tracer with improved pharmacokinetics through modification with an albumin binder for imaging of macrophages in AS and NAFL.

Eur J Nucl Med Mol Imaging 2021 Jun 21. Epub 2021 Jun 21.

State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics & Center for Molecular Imaging and Translational Medicine, School of Public Health, Xiamen University, 4221-116 Xiang'An South Rd, Xiamen, 361102, China.

Purpose: The formation of advanced plaques, which is characterized by the uninterrupted aggregation of macrophages with high expression of folate receptor-β (FR-β), is observed in several concomitant metabolic syndromes. The objective of this study was to develop a novel FR-β-targeted single-photon emission computed tomography (SPECT) radiotracer and validate its application to the noninvasive detection of atherosclerosis (AS) plaque and non-alcoholic fatty liver (NAFL).

Methods: Two radioiodinated probes, [I]IPBF and [I]IBF, were developed, and cell uptake studies were used to identify their specific targets for activated macrophages. Biodistribution in normal mice was performed to obtain the pharmacokinetic information of the probes. Apolipoprotein E knockout (ApoE) mice with atherosclerotic aortas were induced by a high-fat and high-cholesterol (HFHC) diet. To investigate the affinity of radiotracers to FR-β, K values were determined using in vitro assays. In addition, the assessments of the aorta in the ApoE mice at different stages were performed using in vivo SPECT/CT imaging, and the findings were compared by histology.

Results: Both [I]IPBF and [I]IBF were synthesized with > 95% radiochemical purity and up to 3 MBq/nmol molar activity. In vitro assay of [I]IPBF showed a moderate binding affinity to plasma proteins and specific uptake in activated macrophages. The prolonged blood elimination half-life (t) of [I]IPBF (8.14 h) was observed in a pharmacokinetic study of normal mice, which was significantly longer than that of [I]IBF (t = 2.95 h). As expected, the K values of [I]IPBF and [I]IBF in the Raw 264.7 cells were 43.94 ± 9.83 nM and 61.69 ± 15.19 nM, respectively. SPECT imaging with [I]IPBF showed a high uptake in advanced plaques and NAFL. Radioactivity in excised aortas examined by ex vivo autoradiography further confirmed the specific uptake of [I]IPBF in high-risk AS plaques.

Conclusions: In summary, we reported a proof-of-concept study of an albumin-binding folate derivative for macrophage imaging. The FR-β-targeted probe, [I]IPBF, significantly prolongs the plasma elimination half-life and has the potential for the monitoring of AS plaques and concomitant fatty liver.
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http://dx.doi.org/10.1007/s00259-021-05447-4DOI Listing
June 2021

Targeting the HIF-1α-IGFBP2 axis therapeutically reduces IGF1-AKT signaling and blocks the growth and metastasis of relapsed anaplastic Wilms tumor.

Oncogene 2021 Jun 21. Epub 2021 Jun 21.

Division of Cancer and Immunology Research, Institute of Human Virology, University of Maryland School of Medicine, Baltimore, MD, USA.

For patients with anaplastic Wilms tumor (WiT), metastasis and recurrence are common, and prognosis is generally poor. Novel therapies are needed to improve outcomes for patients with this high-risk WiT. A potential contributor to WiT development is constitutive activation of AKT by insulin-like growth factor 1 (IGF1) and its receptor (IGF1R) signaling pathway, but the complete underlying mechanism remains unclear. Here, we demonstrate that the hypoxia-inducible factor 1α (HIF-1α)-IGF binding protein 2 (IGFBP2) axis and the tumor-specific IGF1A are key players for constitutive activation of IGF1-AKT signaling leading to the tumor malignancy. HIF-1α and IGFBP2 are highly expressed in a majority of WiT patient samples. Deficiency of either HIF-1α or IGFBP2 or IGF1 in the tumor cells significantly impairs tumor growth and nearly abrogates metastasis in xenografted mice. Pharmacologic targeting of HIF-1α by echinomycin delivered via nanoliposomes can efficiently restrain growth and metastasis of patient-derived relapsed anaplastic WiT xenografts. Liposomal echinomycin is more potent and effective in inhibiting WiT growth than vincristine in an anaplastic WiT mouse model, and eliminates metastasis by suppressing HIF-1α targets and the HIF-1α-IGFBP2 axis, which governs IGF1-AKT signaling.
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http://dx.doi.org/10.1038/s41388-021-01907-1DOI Listing
June 2021

Employing DIALux to relieve machine-learning training data collection when designing indoor positioning systems.

Opt Express 2021 May;29(11):16887-16892

We propose and demonstrate using the DIALux software with our proposed linear-regression machine-learning (LRML) algorithm for designing a practical indoor visible light positioning (VLP) system. Experimental results reveal that the average position errors and error distributions of the model trained via the DIALux simulation and trained via the experimental data match with each other. This implies that the training data can be generated in DIALux if the room dimensions and LED luminary parameters are available. The proposed scheme could relieve the burden of training data collection in VLP systems.
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http://dx.doi.org/10.1364/OE.422851DOI Listing
May 2021

Human biomonitoring of toxic and essential metals in younger elderly, octogenarians, nonagenarians and centenarians: Analysis of the Healthy Ageing and Biomarkers Cohort Study (HABCS) in China.

Environ Int 2021 Jun 19;156:106717. Epub 2021 Jun 19.

China CDC Key Laboratory of Environment and Population Health, National Institute of Environmental Health, Chinese Center for Disease Control and Prevention, Beijing, China; School of Public Health, Anhui Medical University, Hefei, Anhui, China. Electronic address:

Background: Metals can be either toxic or essential to health, as they play different role in oxidative stress and metabolic homeostasis during the ageing process. Population-based biomonitoring have documented levels and ranges in concentrations among general population of 0-79 years of age. In people aged 80 and above, toxic metals and essential metals may have different risk profiles, and thus need to be better studied.

Objective: Our aim is to investigate concentrations of toxic metals (arsenic, cadmium, lead and mercury) and essential metals (chromium, cobalt, molybdenum, manganese, nickel and selenium) and their role in diseases, nutritional status among younger elderly, octogenarians, nonagenarians and centenarians.

Methods: A total of 932 younger elderly, 643 octogenarians, 540 nonagenarians, 386 centenarians were included from the cross-sectional Healthy Aging and Biomarkers Cohort Study in 2017-2018. Blood or urine biological substrates were collected from each participant to determine the concentrations of toxic metals and essential metals by inductively coupled plasma mass spectrometry. Random forest was constructed to rank the importance of toxic metals and essential metals in longevity. LASSO penalized regressions were performed to select the most significant metals associated with diseases and nutritional status, of which simultaneously included all metals and adjusted for the confounding factors.

Results: Compared to women, we found higher biomarker concentrations in men for toxic metals (41.2 µg/L vs 34.4 µg/L for blood lead, 1.56 µg/L vs 1.19 µg/L for blood mercury) and lower concentration of essential metals (0.48 µg/L vs 0.58 µg/L for blood molybdenum, 10.0 µg/L vs 11.1 µg/L for blood manganese). These factors may contribute to gender difference observed in longevity, that women live longer than men. Blood lead and urine cadmium tended to increase with age (P <0.001); blood cobalt, molybdenum, manganese increased with age, blood selenium decreased with age while the prevalence of selenium deficiency was extremely low in centenarians. Among toxic metals and essential metals, LASSO penalized regression identified the most significant metals associated with chronic kidney disease was cadmium and arsenic; and it was manganese, cobalt, and selenium for diabetes; it was selenium, molybdenum, lead for anemia; it was mercury for underweight. In random forest model, the top four important metals in longevity were selenium, arsenic, lead and manganese both in men and women.

Conclusions: Generally, toxic metals levels were significantly higher while essential metals were relatively sufficient in Chinese centenarians. Toxic metals and essential metals played different role in diseases, nutritional status and longevity in the process of aging. Our research provided real world evidence of biomonitoring reference values to be used for the ongoing population health surveillance in longevity.
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http://dx.doi.org/10.1016/j.envint.2021.106717DOI Listing
June 2021

Experimental Investigation of the Basic Characteristics and Wettability of Oil Shale Dust.

ACS Omega 2021 Jun 2;6(23):14788-14795. Epub 2021 Jun 2.

School of Safety and Environmental Engineering, Shandong University of Science and Technology, Qingdao 266590, China.

To investigate the influence of basic characteristics of oil shale dust on wet dust removal, oil shales (Longkou oil shales Y, YS, and YS and Fushun oil shale) with different oil contents, brown coal (M), and bituminous coal (M) were selected from a typical mining area in China to test their physiochemical parameters. Their proximate component, chemical structures, surface morphology, and mineral contents were determined. The sedimentation experiments of oil shale dust and coal dust were implemented using three anionic surfactants (AOS, SDS, and SDBS) and a nonionic surfactant (AEO-9), and the wettability of oil shale dust was analyzed and compared with that of coal dust. The experimental results indicate that the moisture content, volatile content, fixed carbon content, and content of oxygen-containing functional groups of oil shale are higher than those of the coal sample; otherwise, contents of ash, SiO, aliphatic hydrocarbon, and aromatic hydrocarbon are lower. It can be found that oil shale has semiclosed pores, poor connectivity, a small pore size, a large specific surface area, and a rougher surface, which will lead to poorer wettability of oil shale. The wettability of oil shale can be improved by adding surfactants but is still weaker than that of the coal samples. Anionic surfactants are better than nonionic surfactants in improving the wetting performance. Among them, AOS shows strong wetting ability to oil shale dust. The research results of this paper have an important practical significance for analyzing the wettability of oil shale and controlling oil shale dust.
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http://dx.doi.org/10.1021/acsomega.1c00105DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8209823PMC
June 2021

Development, Preparation, and Biomedical Applications of DNA-Based Hydrogels.

Front Bioeng Biotechnol 2021 2;9:661409. Epub 2021 Jun 2.

Hunan Provincial Key Laboratory of Tumor Microenvironment Responsive Drug Research, Hunan Province Cooperative Innovation Center for Molecular Target New Drug Study, College of Pharmacy, University of South China, Hengyang, China.

Hydrogels have outstanding research and application prospects in the biomedical field. Among them, the design and preparation of biomedical hydrogels with deoxyribonucleic acid (DNA) as building blocks have attracted increasing research interest. DNA-based hydrogel not only has the skeleton function of hydrogel, but also retains its biological functions, including its excellent selection specificity, structural designability, precise molecular recognition ability, outstanding biocompatibility, and so on. It has shown important application prospects in the biomedical field, such as drug delivery, biosensing, and tissue engineering. In recent years, researchers have made full use of the characteristics of DNA molecules and constructed various pure DNA-based hydrogels with excellent properties through various crosslinking methods. Moreover, via introducing functional molecules or elements, or combining with other functional materials, a variety of multifunctional DNA-based hybrid hydrogels have also been constructed, which expand the breadth and depth of their applications. Here, we described the recent development trend in the area of DNA-based hydrogels and highlighted various preparation methods of DNA-based hydrogels. Representative biomedical applications are also exemplified to show the high performance of DNA-based hydrogels. Meanwhile, the existing problems and prospects are also summarized. This review provided references for the further development of DNA-based hydrogels.
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http://dx.doi.org/10.3389/fbioe.2021.661409DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8206814PMC
June 2021

Low Infiltration of CD8+ PD-L1+ T Cells and M2 Macrophages Predicts Improved Clinical Outcomes After Immune Checkpoint Inhibitor Therapy in Non-Small Cell Lung Carcinoma.

Front Oncol 2021 4;11:658690. Epub 2021 Jun 4.

Department of Thoracic Surgery, Shenzhen People's Hospital/2nd Clinical Medical College of Jinan University, Shenzhen, China.

Background: Many clinical studies have shown that patients with non-small cell lung carcinoma (NSCLC) can benefit from immune checkpoint inhibitor (ICI) therapy; however, PD-L1 and tumor mutation burden (TMB), which are recommended by the NCCN guidelines, are still insufficient in predicting the response to and prognosis of immunotherapy. Given the widespread use of ICIs, it is important to find biomarkers that can predict immunotherapy outcomes in NSCLC patients, and the exploration of additional effective biomarkers for ICI therapy is urgently needed.

Methods: A total of 33 stage II-IV NSCLC patients were included in this study. We analyzed immune markers in biopsy and surgical tissue resected from these patients before treatment with ICIs. We examined the infiltration of immune cells and expression of PD-L1 in immune cells using fluorescent multiplex immunohistochemistry (mIHC) stained with CD8/CD68/CD163/PD-L1 antibodies.

Results: In this cohort, we observed that the levels of CD8+ T cells, CD8+PD-L1+ T cells, and CD68+CD163+ M2 macrophages in the total region were independent prognostic factors for progression-free survival (PFS) in NSCLC patients treated with ICIs (HR=0.04, P=0.013; HR=17.70, P=0.026; and HR=17.88, P=0.011, respectively). High infiltration of CD8+ T cells and low infiltration of CD8+PD-L1+ T cells throughout the region were correlated with prolonged PFS (P=0.016 and P=0.02, respectively). No statistically significant difference was observed for CD68+CD163+ M2 macrophages. The joint parameters CD8+ high/CD8+PD-L1+ low, CD8+ high/CD68+CD163+ low and CD8+PD-L1+ low/CD68+CD163+ low predicted better PFS than other joint parameters (P<0.01, P<0.01, and P<0.001, respectively), and they also demonstrated stronger stratification than single biomarkers. The response rate of patients with high infiltration of CD8+ T cells was significantly higher than that of those with low infiltration (P<0.01), and the joint parameters CD8+/CD8+PD-L1+ and CD8+/CD68+CD163+ also demonstrated stronger stratification than single biomarkers.

Conclusions: This retrospective study identified the predictive value of CD8+PD-L1+ T cells, CD8+ T cells, and CD68+CD163+ M2 macrophages in NSCLC patients who received ICIs. Interestingly, our results indicate that the evaluation of joint parameters has certain significance in guiding ICI treatment in NSCLC patients.
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http://dx.doi.org/10.3389/fonc.2021.658690DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8213070PMC
June 2021

Single NIR Laser-Activated Multifunctional Nanoparticles for Cascaded Photothermal and Oxygen-Independent Photodynamic Therapy.

Nanomicro Lett 2019 Aug 19;11(1):68. Epub 2019 Aug 19.

Key Laboratory of Functional Polymer Materials of Ministry of Education, Institute of Polymer Chemistry, Collaborative Innovation Center of Chemical Science and Engineering (Tianjin), Nankai University, Tianjin, 300071, People's Republic of China.

Inconvenient dual-laser irradiation and tumor hypoxic environment as well as limited judgment of treating region have impeded the development of combined photothermal and photodynamic therapies (PTT and PDT). Herein, [email protected] nanoparticles (NPs) are facilely developed to overcome these problems. Through a one-step method, free radical generator (AIPH) and phase transition material (lauric acid, LA, 44-46 °C) are encapsulated in hollow bismuth selenide nanoparticles (BiSe NPs). Under a single 808-nm laser irradiation at the tumor area, hyperthermia produced by BiSe not only directly leads to cell death, but also promotes AIPH release by melting LA and triggers free radical generation, which could further eradicate tumor cells in hypoxic environments. Moreover, BiSe with high X-ray attenuation coefficient endows the NPs with high computed tomography (CT) imaging capability, which is important for treating area determination. The results exhibit that [email protected] NPs possesses 31.2% photothermal conversion efficiency for enhanced PTT, ideal free radical generation for oxygen-independent PDT, and 37.77 HU mL mg X-ray attenuation coefficient for CT imaging with high quality. Most importantly, the tumor growth inhibition rate by synergistic PTT, PDT, and following immunotherapy is 99.6%, and even one tumor disappears completely, which demonstrates excellent cascaded synergistic effect of [email protected] NPs for the tumor therapy.
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http://dx.doi.org/10.1007/s40820-019-0298-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7770756PMC
August 2019