Publications by authors named "Zhigang Wang"

908 Publications

High throughput proteomic and metabolic profiling identified target correction of metabolic abnormalities as a novel therapeutic approach in head and neck paraganglioma.

Transl Oncol 2021 Jun 9;14(8):101146. Epub 2021 Jun 9.

Department of Otolaryngology Head & Neck Surgery, The Ninth People's Hospital, Shanghai Jiao Tong University, School of Medicine, No. 639, Zhi-Zao-Ju Road, Shanghai 200011, China; Ear Institute, School of Medicine, Shanghai Jiao Tong University, Shanghai, China; Shanghai Key Laboratory of Translational Medicine on Ear and Nose Diseases, Shanghai, China. Electronic address:

Head and neck paragangliomas (HNPGLs) are rare neoplasms that represent difficult treatment paradigms in neurotology. Germline mutations in genes encoding succinate dehydrogenase (SDH) are the cause of nearly all familial HNPGLs. However, the molecular mechanisms underlying tumorigenesis remain unclear. Mutational analysis identified 6 out of 14 HNPGLs harboring clinicopathologic SDH gene mutations. The SDHB gene was most frequently mutated in these patients, and western blot showed loss of SDHB protein in tumors with SDHB mutations. The paraganglioma cell line (PGL-626) was established from a sample that harbored a missense SDHB mutation (c.649C > T). Spectrometric analysis using tandem mass tags identified 151 proteins significantly differentially expressed in HNPGLs compared with normal nerves. Bioinformatics analyses confirmed the high level of enrichment of oxidative phosphorylation and metabolism pathways in HNPGLs. The mitochondrial complex subunits NDUFA2, NDUFA10, and NDUFA4, showed the most significantly increased expression and were localized predominantly in the cytoplasm of PGL-626 cells. The mitochondrial complex I inhibitor metformin exerted dose-dependent inhibitory effects on PGL-626 cells via cooperative down-regulation of NDUFA2, 4, and 10, with a significant decrease in the levels of reactive oxygen species and mitochondrial membrane potential. Further metabolomic analysis of PGL-626 cells showed that metabolites involved in central carbon metabolism in cancer and sphingolipid signaling pathways, pantothenate and CoA biosynthesis, and tryptophan and carbon metabolism were significantly altered after metformin treatment. Thus, this study provides insights into the molecular mechanisms underlying HNPGL tumorigenesis and identifies target correction of metabolic abnormalities as a novel therapeutic approach for this disease.
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http://dx.doi.org/10.1016/j.tranon.2021.101146DOI Listing
June 2021

Biotin-streptavidin-guided two-step pretargeting approach using PLGA for molecular ultrasound imaging and chemotherapy for ovarian cancer.

PeerJ 2021 25;9:e11486. Epub 2021 May 25.

Ultrasound Medicine Department, Chongqing Key Laboratory of Translational Research for Cancer Metastasis and Individualized Treatment, Chongqing University Cancer Hospital, Chongqing, Shapingba District, China.

Background: Ovarian cancer seriously threatens the lives and health of women, and early diagnosis and treatment are still challenging. Pre-targeting is a promising strategy to improve the treatment efficacy of ovarian cancer and the results of ultrasound imaging.

Purpose: To explore the effects of a pre-targeting strategy using streptavidin (SA) and paclitaxel (PTX)-loaded phase-shifting poly lactic-co-glycolic acid (PLGA) nanoparticles with perfluoro-n-pentane (PTX-PLGA-SA/PFPs) on the treatment and ultrasound imaging of ovarian cancer.

Methods: PTX-PLGA/PFPs were prepared with a single emulsion (O/W) solvent evaporation method and SA was attached using carbodiimide. The encapsulation efficiency of PTX and the release characteristics were assessed with high performance liquid chromatography. The phase-change characteristics of the PTX-PLGA-SA/PFPs were investigated. The anti-carcinoembryonic antigen (CEA) antibody (Ab) was covalently attached to PTX-PLGA/PFPs via carbodiimide to create PTX-PLGA-Ab/PFPs. The targeting efficiency of the nanoparticles and the viability of ovarian cancer SKOV3 cells were evaluated in each group using a microscope, flow cytometry, and cell counting kit 8 assays.

Results: THE PTX-PLGA-SA/PFPs were spheres with a size of 383.0 ± 75.59 nm. The encapsulation efficiency and loading capability of the nanoparticles for PTX were 71.56 ±  6.51% and 6.57 ± 0.61%, respectively. PTX was burst-released up to 70% in 2-3 d. When irradiated at 7.5 W for 3 min, the PTX-PLGA-SA/PFPs visibly enhanced the ultrasonography images ( < 0.05). At temperatures of 45°C and 60°C the nanoparticles phase-shifted into micro-bubbles and the sizes increased. The binding efficiencies of SA and Ab to the PTX-PLGA/PFPs were 97.16 ±  1.20% and 92.74 ± 5.75%, respectively. Pre-targeting resulted in a high binding efficacy and killing effect on SKOV3 cells ( < 0.05).

Conclusions: The two-step pre-targeting process can significantly enhance the targeting ability of PTX-loaded PLGA nanoparticles for ovarian cancer cells and substantially improve the therapeutic efficacy. This technique provides a new method for ultrasonic imaging and precise chemotherapy for ovarian cancer.
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http://dx.doi.org/10.7717/peerj.11486DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8162236PMC
May 2021

[Rapid Reconstruction of Craniotomy Defects Based on Surgical Navigation].

Zhongguo Yi Liao Qi Xie Za Zhi 2021 Jun;45(3):246-249

School of Material Science and Engineering, South China University of Technology, Guangzhou, 510641.

In neurosurgery, skull repair caused by surgical approach is one of the important research contents. In this paper, a rapid reconstruction method of the skull defect with optical navigation system is proposed. This method can automatically reconstruct the structure of skull defect with the intraoperative defect edge points and preoperative medical image data. The head model experiment was used to evaluate the effect of the method, the average error of the reconstruction of the defect in the right orbit was 0.424 mm, while the average error of the reconstruction of the defect in the posterior skull base was 0.377 mm. The experimental results show that the structure of the defect is consistent with the actual defect, and the reconstruction accuracy satisfies the clinical requirements in neurosurgery.
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http://dx.doi.org/10.3969/j.issn.1671-7104.2021.03.003DOI Listing
June 2021

Combination Nanotherapeutics for Dry Eye Disease Treatment in a Rabbit Model.

Int J Nanomedicine 2021 26;16:3613-3631. Epub 2021 May 26.

Department of Ophthalmology, Second Affiliated Hospital of Chongqing Medical University, Chongqing, 400010, People's Republic of China.

Purpose: Anti-inflammation is essential for dry eye disease. Traditional anti-inflammation agent corticosteroids applied in dry eye disease (DED) treatment could result in high intraocular pressure, especially in long-term treatment. Thus, we have prepared a liposome loading 1-bromoheptadecafluorooctane and tetrandrine ([email protected]) to treat DED via anti-inflammation that hardly affects intraocular pressure in this study, which provided another therapy strategy for dry eye disease.

Methods: We firstly detected the physicochemical properties of [email protected] Next, we tested the biosafety of synthesized liposomes for corneal epithelium. Then, we explored the accumulations and distribution of [email protected] both in cellular and animal models. And then, we assessed the therapeutic effects of [email protected] formulations by laboratory and clinical examinations. Last, we examined the changes in eye pressure before and after treatment.

Results: [email protected] and Tet showed a characteristic absorption peak at 282 nm while [email protected] did not. Large amounts of [email protected] remained on the ocular surface and accumulated in the corneal epithelial cells in DED rabbits. Corneal staining scores of DED rabbits respectively treated by ATS, [email protected], Tet-ATS and [email protected] for seven days were 3.7±0.5, 3.2±0.4, 1.5±0.5 and 0.5±0.5. The expressions of related cytokines were correspondingly downregulated significantly, indicating that the inflammation of DED was successfully suppressed. The intraocular pressure changes of DED rabbits before and after treatment by [email protected] showed no statistical significance.

Conclusion: We successfully synthesized [email protected], and it could effectively treat dry eye disease via anti-inflammation but hardly affected the intraocular pressure.
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http://dx.doi.org/10.2147/IJN.S301717DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8165218PMC
June 2021

Porcine fibrin sealant combined with autologous chondrocytes successfully promotes full-thickness cartilage regeneration in a rabbit model.

J Tissue Eng Regen Med 2021 May 27. Epub 2021 May 27.

Department of Orthopedics Trauma and Hand Surgery, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, China.

Xenogeneic porcine fibrin sealant (PFS), derived from porcine blood, was used as a scaffold for cartilage tissue engineering. PFS has a porous microstructure, biocompatibility and degradation, and it provides a perfect extracellular matrix environment for the adhesion and proliferation of chondrocytes. Recently, PFS in combination with autologous chondrocytes (ACs) were used to study the microstructure of PFS scaffolds and promotion effect on the proliferation and migration of ACs. In this study, we investigated the effects of PFS in combination with ACs on the healing of cartilage defects in rabbits. A full-thickness cartilage defect was made in the femoral trochlear in rabbits, subsequently, three surgical procedures were used to repair the defect, namely: the defect was treated with microfracture (MF group); the defect was filled with PFS alone (PFS group) or in combination with ACs (PFS + ACs group); the unrepaired cartilage defects served as the control group (CD group). Three and 6 months after the operation, the reparative effect was evaluated using medical imaging, gross scoring, pathological staining, biomechanical testing and biochemical examination. The PFS group showed a limited effect on defect repair, this result was significantly worse than the MF group. The best reparative effect was observed in the PFS + ACs group. These results hinted that PFS in combination with autologous chondrocytes has broad prospects for clinical applications in cartilage tissue engineering.
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http://dx.doi.org/10.1002/term.3224DOI Listing
May 2021

An intramolecular photoswitch can significantly promote photoactivation of Pt(iv) prodrugs.

Chem Sci 2021 Apr 1;12(19):6536-6542. Epub 2021 Apr 1.

Department of Chemistry, City University of Hong Kong Hong Kong SAR P. R. China

Selective activation of prodrugs at diseased tissue through bioorthogonal catalysis represents an attractive strategy for precision cancer treatment. Achieving efficient prodrug photoactivation in cancer cells, however, remains challenging. Herein, we report two Pt(iv) complexes, designated as rhodaplatins {rhodaplatin , [Pt(CBDCA-,)(NH)(RhB)OH]; rhodaplatin , [Pt(DACH)ox(RhB)(OH)], where CBDCA is cyclobutane-1,1-dicarboxylate, RhB is rhodamine B, DACH is (1,2)-1,2-diaminocyclohexane, and ox is oxalate}, that bear an internal photoswitch to realize efficient accumulation, significant co-localization, and subsequent effective photoactivation in cancer cells. Compared with the conventional platform of external photocatalyst plus substrate, rhodaplatins presented up to 4.8 10-fold increased photoconversion efficiency in converting inert Pt(iv) prodrugs to active Pt(ii) species under physiological conditions, due to the increased proximity and covalent bond between the photoswitch and Pt(iv) substrate. As a result, rhodaplatins displayed increased photocytotoxicity compared with a mixture of RhB and conventional Pt(iv) compound in cancer cells including Pt-resistant ones. Intriguingly, rhodaplatin efficiently accumulated in the mitochondria and induced apoptosis without causing genomic DNA damage to overcome drug resistance. This work presents a new approach to develop highly effective prodrugs containing intramolecular photoswitches for potential medical applications.
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http://dx.doi.org/10.1039/d0sc06839jDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8139284PMC
April 2021

Integrative web-based analysis of omics data for study of drugs against SARS-CoV-2.

Sci Rep 2021 05 24;11(1):10763. Epub 2021 May 24.

Department of Biomedical Engineering, Institute of Basic Medical Sciences Chinese Academy of Medical Sciences, School of Basic Medicine Peking Union Medical College, Beijing, 100005, China.

Research on drugs against SARS-CoV-2 (cause of COVID-19) has been one of the major world concerns at present. There have been abundant research data and findings in this field. The interference of drugs on gene expression in cell lines, drug-target, protein-virus receptor networks, and immune cell infiltration of the host may provide useful information for anti-SARS-CoV-2 drug research. To simplify the complex bioinformatics analysis and facilitate the evaluation of the latest research data, we developed OmiczViz ( http://medcode.link/omicsviz ), a web tool that has integrated drug-cell line interference data, virus-host protein-protein interactions, and drug-target interactions. To demonstrate the usages of OmiczViz, we analyzed the gene expression data from cell lines treated with chloroquine and ruxolitinib, the drug-target protein networks of 48 anti-coronavirus drugs and drugs bound with ACE2, and the profiles of immune cell infiltration between different COVID-19 patient groups. Our research shows that chloroquine had a regulatory role of the immune response in renal cell line but not in lung cell line. The anti-coronavirus drug-target network analysis suggested that antihistamine of promethaziney and dietary supplement of Zinc might be beneficial when used jointly with antiviral drugs. The immune infiltration analysis indicated that both the COVID-19 patients admitted to the ICU and the elderly with infection showed immune exhaustion status, yet with different molecular mechanisms. The interactive graphic interface of OmiczViz also makes it easier to analyze newly discovered and user-uploaded data, leading to an in-depth understanding of existing findings and an expansion of existing knowledge of SARS-CoV-2. Collectively, OmicsViz is web program that promotes the research on medical agents against SARS-CoV-2 and supports the evaluation of the latest research findings.
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http://dx.doi.org/10.1038/s41598-021-89578-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8144609PMC
May 2021

C-reactive protein promotes tongue squamous cell carcinoma chemoresistance by inhibiting the activation of caspase-3/9 via the CD64/AKT/mTOR pathway.

Hum Cell 2021 May 21. Epub 2021 May 21.

Department of Stomatology, Zibo Central Hospital, Zibo, 255036, China.

Recent studies have shown that C-reactive protein (CRP) participates in multiple types of cancer development. Here, the aim of this study was to investigate the role of CRP in tongue squamous cell carcinoma (TSCC) chemoresistance. Immunohistochemical staining showed that CRP expression was upregulated in TSCC tissues from cisplatin-resistant patients compared with that in cisplatin-sensitive TSCC samples. The CRP expression level was positively correlated with that of the drug-resistant marker MDR1. Moreover, functional experiments showed that CRP increased cell viability and decreased cisplatin-induced apoptosis. CRP also increased the expression levels of MDR1 and Bcl-2 and decreased the expression level of Bax. Furthermore, CRP decreased the activity of caspase-3. Mechanistically, CRP could bind to Fcγ receptor I (FcγRI, also known as CD64) and activate the AKT/mTOR pathway to inhibit the activation of caspase-3/9, as shown by co-immunoprecipitation (Co-IP) assay and western blotting assays. In addition, CRP promoted tumour growth and decreased cleaved caspase-3/9 expression in BALB/c nude mice. Taken together, our findings indicate that CRP promotes TSCC chemoresistance by inhibiting the activation of caspase-3/9 via the FcγRI/AKT/mTOR pathway. Thus, CRP could potentially be considered as a therapeutic target for reducing TSCC chemoresistance.
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http://dx.doi.org/10.1007/s13577-021-00555-7DOI Listing
May 2021

Soufeng sanjie formula alleviates collagen-induced arthritis in mice by inhibiting Th17 cell differentiation.

Chin Med 2021 May 13;16(1):39. Epub 2021 May 13.

Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing, 210028, China.

Background: Rheumatoid arthritis (RA) is a chronic autoimmune disease. Soufeng sanjie formula (SF), which is composed of scolopendra (dried body of Scolopendra subspinipes mutilans L. Koch), scorpion (dried body of Buthus martensii Karsch), astragali radix (dried root of Astragalus membranaceus (Fisch.) Bge), and black soybean seed coats (seed coats of Glycine max (L.) Merr), is a traditional Chinese prescription for treating RA. However, the mechanism of SF in treating RA remains unclear. This study was aim to investigate the anti-arthritic effects of SF in a collagen-induced arthritis (CIA) mouse model and explore the mechanism by which SF alleviates arthritis in CIA mice.

Methods: For in vivo studies, female DBA/1J mice were used to establish the CIA model, and either SF (183 or 550 mg/kg/day) or methotrexate (MTX, 920 mg/kg, twice/week) was orally administered to the mice from the day of arthritis onset. After administration for 30 days, degree of ankle joint destruction and serum levels of IgG and inflammatory cytokines were determined. The balance of Th17/Treg cells in the spleen and lymph nodes was analyzed using flow cytometry. Moreover, the expression levels of retinoic acid receptor-related orphan nuclear receptor (ROR) γt and phosphorylated STAT3 (pSTAT3, Tyr705) in the spleen were detected by immunohistochemistry. Furthermore, the effect of SF on Th17 cells differentiation in vitro was investigated in CD4 T cells under Th17 polarization conditions.

Results: SF decreased the arthritis score, ameliorated paw swelling, and reduced cartilage loss in the joint of CIA mice. In addition, SF decreased the levels of bovine collagen-specific IgG in sera of CIA mice. SF decreased the levels of inflammatory cytokines (TNF-α, IL-6, and IL-17A) and increased the level of IL-10 both in the sera and the joint of CIA mice. Moreover, SF treatment rebalanced the Th17/Treg ratio in the spleen and lymph nodes of CIA mice. SF also reduced the expression levels of ROR γt and pSTAT3 (Tyr705) in the spleen of CIA mice. In vitro, SF treatment reduced Th17 cell generation and IL-17A production and inhibited the expression of RORγt, IRF4, IL-17A, and pSTAT3 (Tyr705) under Th17 polarization conditions.

Conclusions: Our results suggest that SF exhibits anti-arthritic effects and restores Th17/Treg homeostasis in CIA mice by inhibiting Th17 cell differentiation.
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http://dx.doi.org/10.1186/s13020-021-00448-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8117632PMC
May 2021

Dual mitigation of immunosuppression combined with photothermal inhibition for highly effective primary tumor and metastases therapy.

Biomaterials 2021 Jul 7;274:120856. Epub 2021 May 7.

Department of Ultrasound, The Third Affiliated Hospital, Chongqing Medical University, Chongqing, 400010, PR China. Electronic address:

T-cell based immune response can attack cancer cells formidably when certain immune checkpoint (e.g., PD-1/PD-L1) is blocked. Unfortunately, PD-1/PD-L1 blockade only provoke limited immune response because the differentiation of tumor-reactive T lymphocytes is often suppressed by TGF-β pathway. Namely, the combating cancer weapon is weakened. In this study, other than employing photothermal therapy (PTT) to eliminate the primary tumor, we also aimed to expose in situ tumor-associated antigens and exert immune response for metastases inhibition. This enhanced immunotherapeutic strategy is achieved by IR780/SB-505124 based nanoliposomes ([email protected]). Upon administration, TGF-β pathway is inhibited by SB to drive effector T cells into a responsive state and reduce the infiltration of Treg cells, eventually greatly enhancing the weapon against cancer. In the meantime, the immunosuppressive "protection" of tumor cells is also neutralized by blocking PD-1/PD-L1 immune checkpoint. By virtue of inherent characteristics of IR780, [email protected] can selectively accumulate, penetrate deeply in tumor tissues, and preferentially retain in mitochondria. The above features are of critical importance to tumor therapy. Thus, highly effective cancer immunotherapy is implemented via selective accumulation/deep penetration of [email protected] in tumor, achieving PTT induced immunogenic cell death and dual mitigation of immunosuppression strategy (TGF-β inhibition/PD-1/PD-L1 blockade), which is a promising therapeutic modality for cancer.
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http://dx.doi.org/10.1016/j.biomaterials.2021.120856DOI Listing
July 2021

Macrophages Inhibit Ciliary Protein Levels by Secreting BMP-2 Leading to Airway Epithelial Remodeling Under Cigarette Smoke Exposure.

Front Mol Biosci 2021 26;8:663987. Epub 2021 Apr 26.

Department of Immunology, Key Laboratory of Immune Mechanism and Intervention on Serious Disease in Hebei Province, Hebei Medical University, Shijiazhuang, China.

Chronic obstructive pulmonary disease (COPD) is a chronic respiratory disease with high morbidity and mortality worldwide. So far, smoking is still its leading cause. The characteristics of COPD are emphysema and airway remodeling, as well as chronic inflammation, which were predominated by macrophages. Some studies have reported that macrophages were involved in emphysema and chronic inflammation, but whether there is a link between airway remodeling and macrophages remains unclear. In this study, we found that both acute and chronic cigarette smoke exposure led to an increase of macrophages in the lung and a decrease of ciliated cells in the airway epithelium of a mouse model. The results of experiments showed that the ciliary protein (β-tubulin-IV) levels of BEAS-2B cells could be inhibited when co-cultured with human macrophage line THP-1, and the inhibitory effect was augmented with the stimulation of cigarette smoke extract (CSE). Based on the results of transcriptome sequencing, we focused on the protein, bone morphogenetic protein-2 (BMP-2), secreted by the macrophage, which might mediate this inhibitory effect. Further studies confirmed that BMP-2 protein inhibited β-tubulin-IV protein levels of BEAS-2B cells under the stimulation of CSE. Coincidentally, this inhibitory effect could be nearly blocked by the BMP receptor inhibitor, LDN, or could be interfered with BMP-2 siRNA. This study suggests that activation and infiltration of macrophages in the lung induced by smoke exposure lead to a high expression of BMP-2, which in turn inhibits the ciliary protein levels of the bronchial epithelial cells, contributing to the remodeling of airway epithelium, and aggravates the development of COPD.
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http://dx.doi.org/10.3389/fmolb.2021.663987DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8107431PMC
April 2021

Effects of Transcutaneous Electrical Acupoint Stimulation on Postoperative Cognitive Decline in Elderly Patients: A Pilot Study.

Clin Interv Aging 2021 3;16:757-765. Epub 2021 May 3.

Department of Anesthesiology, The Third Hospital of Hebei Medical University, Shijiazhuang City, Hebei, People's Republic of China.

Background: Postoperative cognitive decline (POCD) in the old ages seriously delays the rapid recovery. Here, we aimed to investigate the effects of transcutaneous electrical acupoint stimulation (TEAS) against POCD in elderly patients undergoing laparoscopic radical colon cancer surgery, as well as the potential mechanism.

Methods: A prospective, single-center, parallel-group, randomized trial was designed. A total of 100 patients (age ≥65 years) undergoing laparoscopic radical resection of colon cancer were involved and randomly divided into TEAS (Group T) and control (Group C) groups. The patients in Group T were performed with percutaneous acupoint electrical stimulation in bilateral Hegu, Neiguan and Zusanli points from 30 minutes before anesthesia induction to the end of surgery. A Z-score based on Mini-Mental State Exam (MMSE) was used to assess the incidence of POCD. The levels of serum IL-6, hs-CRP, CGRP at 0 min before TEAS (T0), 1 h after beginning of surgery (T1) and the end of surgery (T2) were evaluated.

Results: Our data showed that the cumulative duration of POCD on postoperative day 2 and 3 in Group T was significantly decreased compared to Group C ( < 0.05). Compared with T0, the levels of serum IL-6, hs-CRP, and CGRP in both Group T and C were statistically elevated at T1 and T2 ( < 0.05). Moreover, the levels of serum IL-6 and hs-CRP were decreased, but the level of CGRP was increased in Group T compared to Group C at T1 and T2 ( < 0.05).

Conclusion: TEAS is associated with a lower cumulative duration of POCD in elderly patients undergoing laparoscopic radical colon cancer surgery, which may be related to the regulation of inflammatory factors and neuropeptides interacted with gut-brain axis.
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http://dx.doi.org/10.2147/CIA.S309082DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8106456PMC
May 2021

A novel five-gene signature predicts overall survival of patients with hepatocellular carcinoma.

Cancer Med 2021 Jun 2;10(11):3808-3821. Epub 2021 May 2.

Department of Blood Transfusion, The First People's Hospital of Jingmen, Jingmen, China.

Hepatocellular carcinoma (HCC) is one of the most common public health challenges, worldwide. Because of molecular complexity and tumor heterogeneity, there are no effective predictive models for prognosis of HCC. This underlines the unmet need for accurate prognostic models for HCC. Analysis of GSE14520 data from gene omnibus (GEO) database identified multiple differentially expressed mRNAs (DEMs) between HCC and normal tissues. After randomly stratifying the patients into the training and testing groups, we performed univariate, lasso, and multivariable Cox regression analyses to delineate the prognostic gene signature in training set. We then used Kaplan-Meier plot, time-dependent receiver operating characteristic (ROC), multivariable Cox regression analysis of clinical information, nomogram, and decision curve analysis (DCA) to evaluate the predictive and overall survival value of a novel five-gene signature (CNIH4, SOX4, SPP1, SORBS2, and CCL19) within and across sets, separately and combined. We also validated the prognostic value of the five-gene signature using The Cancer Genome Atlas-Liver Hepatocellular Carcinoma (TCGA-LIHC), GSE54236 and International Cancer Genome Consortium (ICGC) sets. Multivariable Cox regression analysis revealed that the five-gene signature and tumor node metastasis (TNM) stage were independent prognostic factors for overall survival of HCC patients in GSE14520 and TCGA-LIHC. Combining TNM stage clinical pathological parameters and nomogram greatly improved the prognosis prediction of HCC. Further gene set enrichment analysis (GSEA) revealed enrichment of KEGG pathways related to cell cycle in the high-risk group and histidine metabolism in the low-risk group. Finally, all these five mRNAs are overexpressed between 12 pairs of HCC and adjacent normal tissues by quantitative real-time PCR validation. In brief, a five-gene prognostic signature and a nomogram were identified and constructed, respectively, and further validated for their HCC prognostic value. The five-gene risk score together with TNM stage models could aid in rationalizing customized therapies in HCC patients.
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http://dx.doi.org/10.1002/cam4.3900DOI Listing
June 2021

CPPU may induce gibberellin-independent parthenocarpy associated with PbRR9 in 'Dangshansu' pear.

Hortic Res 2020 May 1;7(1):68. Epub 2020 May 1.

College of Horticulture, Northwest A&F University, Taicheng, Road No.3, Yangling, Shaanxi, Province, China.

Parthenocarpy is a valuable trait in self-incompatible plants, such as pear. N-(2-chloro-4-pyridyl)-N'-phenylurea (CPPU), a synthetic cytokinin analog, can induce parthenocarpy in pear (Pyrus spp.), but the mechanism of induction is unclear. To investigate the role of gibberellin in CPPU-induced parthenocarpy in pear, CPPU supplemented with paclobutrazol (PAC) was sprayed onto 'Dangshansu' pear. We found that the fruit set rate of pear treated with CPPU supplemented with PAC was identical to that in a CPPU-alone treatment group. In regard to cell development, CPPU mainly promoted hypanthium cell division and expansion, and PAC application had no influence on CPPU-induced cell development. RNA sequencing revealed that gibberellin 20 oxidase and gibberellin 3 oxidase genes were not differentially expressed following CPPU treatment. According to the analysis of fruit phytohormone content, the CPPU treatments did not induce gibberellin biosynthesis. These results suggest that CPPU-induced parthenocarpy may be gibberellin independent in 'Dangshansu' pear. After CPPU treatment, the indole acetic acid (IAA) content in fruit was significantly increased, and the abscisic acid (ABA) content was significantly decreased. Similarly, RNA sequencing revealed that many genes involved in the auxin and ABA pathways were significantly differentially expressed in the CPPU treatment groups; among them, indole-3-pyruvate monooxygenase (YUCCA) was significantly upregulated and 9-cis-epoxycarotenoid dioxygenase (NCED) was significantly downregulated. IAA and ABA may thus play important roles in CPPU-induced parthenocarpy. PbTwo-component response regulator9 (PbRR9), PbYUCCA4, and PbNCED6 were then selected to further elucidate the mechanism of CPPU-induced parthenocarpy. A yeast one-hybrid assay indicated that PbRR9 can combine with the PbYUCCA4 and PbNCED6 promoters. Dual luciferase assays revealed that PbRR9 can promote and repress the activities of the PbYUCCA4 and PbNCED6 promoters, respectively. After the transient expression of PbRR9 in fruits, PbYUCCA4 expression was significantly upregulated, and PbNCED6 expression was significantly downregulated. This study uncovered a CPPU-induced parthenocarpy mechanism that is different from that in tomato. CPPU may upregulate PbYUCCA4 and downregulate PbNCED6 by upregulating PbRR9, thereby increasing IAA content and decreasing ABA content to ultimately induce parthenocarpy in 'Dangshansu' pear. However, because only a single time point was used and because 'botanical' and 'accessory' fruits have different structures, this conclusion is still preliminary.
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http://dx.doi.org/10.1038/s41438-020-0285-5DOI Listing
May 2020

Overexpression of Inhibits the Growth of Rice and Causes Spontaneous Cell Death.

Genes (Basel) 2021 Apr 27;12(5). Epub 2021 Apr 27.

State Key Laboratory for Conservation and Utilization of Subtropical Agro-Bioresources, College of Life Science and Technology, Guangxi University, Nanning 530004, China.

The Mediator complex transduces information from the DNA-bound transcription factors to the RNA polymerase II transcriptional machinery. Research on plant Mediator subunits has primarily been performed in Arabidopsis, while very few of them have been functionally characterized in rice. In this study, the rice Mediator subunit 16, was examined. encodes a putative protein of 1301 amino acids, which is longer than the version previously reported. It was expressed in various rice organs and localized to the nucleus. The knockout of resulted in rice seedling lethality. Its overexpression led to the retardation of rice growth, low yield, and spontaneous cell death in the leaf blade and sheath. RNA sequencing suggested that the overexpression of altered the expression of a large number of genes. Among them, the upregulation of some defense-related genes was verified. can regulate the expression of a wealth of genes, and alterations in its expression have a profound impact on plant growth, development, and defense responses in rice.
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http://dx.doi.org/10.3390/genes12050656DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8145620PMC
April 2021

Sulfonic-Group-Grafted TiCT MXene: A Silver Bullet to Settle the Instability of Polyaniline toward High-Performance Zn-Ion Batteries.

ACS Nano 2021 May 29;15(5):9065-9075. Epub 2021 Apr 29.

College of Materials Science and Engineering, Shenzhen University, Shenzhen 518055, China.

Polyaniline (PANI) is a promising cathode material for Zn-ion batteries (ZIBs) due to its intrinsic conductivity and redox activity; however, the achievements of PANI in high-performance ZIBs are largely hindered by its instability during the repeated charge/discharge. Taking advantage of the high conductivity, flexibility, and grafting ability together, a surface-engineered TiCT MXene is designed as a silver bullet to fight against the deprotonation and swelling/shrinking issues occurring in the redox process of PANI, which are the origins of its instability. Specifically, the sulfonic-group-grafted TiCT(S-TiCT) continuously provides protons to improve the protonation degree of PANI and maintains the polymer backbone at a locally low pH, which effectively inhibits deprotonation and brings high redox activity along with good reversibility. Meanwhile, the conductive and flexible natures of S-TiCT assist the fast redox reaction of PANI and concurrently buffer its corresponding swelling/shrinking. Therefore, the S-TiCT-enhanced PANI cathode simultaneously achieves a high discharge capacity of 262 mAh g at 0.5 A g, a superior rate capability of 160 mAh g at 15 A g, and a good cyclability over 5000 cycles with 100% coulombic efficiency. This work enlightens the development of versatile MXene surface engineering for advanced batteries.
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http://dx.doi.org/10.1021/acsnano.1c02215DOI Listing
May 2021

The tonoplast-localized transporter OsABCC9 is involved in cadmium tolerance and accumulation in rice.

Plant Sci 2021 Jun 26;307:110894. Epub 2021 Mar 26.

State Key Laboratory for Conservation and Utilization of Subtropical Agro-bioresources, College of Life Science and Technology, Guangxi University, Nanning, 530004, China. Electronic address:

Cadmium (Cd) is a highly toxic element to living organisms, and its accumulation in the edible portions of crops poses a potential threat for human health. The molecular mechanisms underlying Cd detoxification and accumulation are not fully understood in plants. In this study, the involvement of a C-type ABC transporter, OsABCC9, in Cd tolerance and accumulation in rice was investigated. The expression of OsABCC9 was rapidly induced by Cd treatment in a concentration-dependent manner in the root. The transporter, localized on the tonoplast, was mainly expressed in the root stele under Cd stress. OsABCC9 knockout mutants were more sensitive to Cd and accumulated more Cd in both the root and shoot compared to the wild-type. Moreover, the Cd concentrations in the xylem sap and grain were also significantly increased in the knockout lines, suggesting that more Cd was distributed from root to shoot and grain in the mutants. Heterologous expression of OsABCC9 in yeast enhanced Cd tolerance along with an increase of intracellular Cd content. Taken together, these results indicated that OsABCC9 mediates Cd tolerance and accumulation through sequestration of Cd into the root vacuoles in rice.
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http://dx.doi.org/10.1016/j.plantsci.2021.110894DOI Listing
June 2021

Functional Immunostimulating DNA Materials: The Rising Stars for Cancer Immunotherapy.

Macromol Biosci 2021 Apr 25:e2100083. Epub 2021 Apr 25.

School of Pharmaceutical Sciences, Health Science Center, Shenzhen University, Shenzhen, 518055, China.

Cancer immunotherapy has risen as a promising method in clinical practice for cancer treatment and DNA-based immune intervention materials, along with DNA nanotechnology, have obtained increasing importance in this field. In this review, various immunostimulating DNA materials are introduced and the mechanisms via which they exerted an immune effect are explained. Then, representative examples in which DNA is used as the leading component for anticancer applications through immune stimulation are provided and their efficacy is evaluated. Finally, the challenges for those materials in clinical applications are discussed and suggestions for possible further research directions are also put forward.
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http://dx.doi.org/10.1002/mabi.202100083DOI Listing
April 2021

Bacteria-driven phthalic acid ester biodegradation: Current status and emerging opportunities.

Environ Int 2021 Apr 15;154:106560. Epub 2021 Apr 15.

Environmental Microbiomics Research Center, School of Environmental Science and Engineering, Southern Marine Science and Engineering Guangdong Laboratory (Zhuhai), Sun Yat-sen University, Guangzhou 510006, China. Electronic address:

The extensive use of phthalic acid esters (PAEs) has led to their widespread distribution across various environments. As PAEs pose significant threats to human health, it is urgent to develop efficient strategies to eliminate them from environments. Bacteria-driven PAE biodegradation has been considered as an inexpensive yet effective strategy to restore the contaminated environments. Despite great advances in bacterial culturing and sequencing, the inherent complexity of indigenous microbial community hinders us to mechanistically understand in situ PAE biodegradation and efficiently harness the degrading power of bacteria. The synthetic microbial ecology provides us a simple and controllable model system to address this problem. In this review, we focus on the current progress of PAE biodegradation mediated by bacterial isolates and indigenous bacterial communities, and discuss the prospective of synthetic PAE-degrading bacterial communities in PAE biodegradation research. It is anticipated that the theories and approaches of synthetic microbial ecology will revolutionize the study of bacteria-driven PAE biodegradation and provide novel insights for developing effective bioremediation solutions.
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http://dx.doi.org/10.1016/j.envint.2021.106560DOI Listing
April 2021

Cell-free decellularized cartilage extracellular matrix scaffolds combined with interleukin 4 promote osteochondral repair through immunomodulatory macrophages: In vitro and in vivo preclinical study.

Acta Biomater 2021 06 31;127:131-145. Epub 2021 Mar 31.

Institute of Orthopedics, The First Medical Center, Chinese PLA General Hospital, Beijing Key Lab of Regenerative Medicine in Orthopedics, Key Laboratory of Musculoskeletal Trauma and War Injuries PLA, No. 28 Fuxing Road, Haidian District, Beijing 100853, China. Electronic address:

Cartilage regeneration is a complex physiological process. Synovial macrophages play a critical immunomodulatory role in the acute inflammatory response surrounding joint injury. Due to the contrasting differences and heterogeneity of macrophage, the phenotype of macrophages are the key determinants of the healing response after cartilage injury. Biomaterials derived from extracellular matrix have been used for the repair and reconstruction of a variety of tissues by modulating the host macrophage response. However, the immunomodulatory effect of decellularized cartilage extracellular matrix (ECM) on macrophages has not been elucidated. It is necessary to clarify the immunomodulatory properties of decellularized cartilage matrix (DCM) to guide the design of cartilage regeneration materials. Here, we prepared porcine articular cartilage derived DCM and determined the response of mouse bone marrow-derived macrophages (BMDMs) to the pepsin-solubilized DCM (PDCM) in vitro. Macrophages activated by the PDCM could promote bone marrow-derived mesenchymal stem cells (BMSCs) invasion, migration, proliferation, and chondrogenic differentiation. Then, we verified that early optimization of the immunomodulatory effects of the cell-free DCM scaffold using IL-4 in vivo could achieve good cartilage regeneration in a rat knee osteochondral defect model. Therefore, this decellularized cartilage ECM scaffold combined with accurate and active immunomodulatory strategies provides a new approach for the development of cartilage regeneration materials. STATEMENT OF SIGNIFICANCE: This work reports a decellularized cartilage extracellular matrix (DCM) scaffold combined with an accurate and active immunomodulatory strategy to improve cartilage regeneration. Our findings demonstrated that the pepsin-solubilized DCM (PDCM) activated bone marrow-derived macrophages to polarize to a constructive macrophage phenotype. These polarized macrophages promoted bone marrow-derived mesenchymal stem cell invasion, migration, proliferation, and chondrogenic differentiation. DCM scaffolds combined with early-stage intra-articular injection of IL-4 created a wound-healing microenvironment and improved cartilage regeneration in a rat knee osteochondral defect model.
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http://dx.doi.org/10.1016/j.actbio.2021.03.054DOI Listing
June 2021

The MIR-Domain of PbbHLH2 Is Involved in Regulation of the Anthocyanin Biosynthetic Pathway in "Red Zaosu" ( Rehd.) Pear Fruit.

Int J Mol Sci 2021 Mar 16;22(6). Epub 2021 Mar 16.

College of Horticulture, Northwest A&F University, Taicheng Road NO.3, Yangling 712100, Shanxi Province, China.

The N-terminal of Myc-like basic helix-loop-helix transcription factors (bHLH TFs) contains an interaction domain, namely the MYB-interacting region (MIR), which interacts with the R2R3-MYB proteins to regulate genes involved in the anthocyanin biosynthetic pathway. However, the functions of MIR-domain bHLHs in this pathway are not fully understood. In this study, PbbHLH2 containing the MIR-domain was identified and its function investigated. The overexpression of in "Zaosu" pear peel increased the anthocyanin content and the expression levels of late biosynthetic genes. Bimolecular fluorescence complementation showed that PbbHLH2 interacted with R2R3-MYB TFs PbMYB9, 10, and 10b in onion epidermal cells and confirmed that MIR-domain plays important roles in the interaction between the MIR-domain bHLH and R2R3-MYB TFs. Moreover, PbbHLH2 bound and activated the dihydroflavonol reductase promoter in yeast one-hybrid (Y1H) and dual-luciferase assays. Taken together these results suggested that the MIR domain of PbbHLH2 regulated anthocyanin biosynthesis in pear fruit peel.
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http://dx.doi.org/10.3390/ijms22063026DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8002321PMC
March 2021

Extraction and purification of cis/trans asarone from Acorus tatarinowii Schott: Accelerated solvent extraction and silver ion coordination high-speed counter-current chromatography.

J Chromatogr A 2021 Apr 18;1643:462080. Epub 2021 Mar 18.

School of Pharmaceutical Sciences and Key Laboratory for Applied Technology of Sophisticated Analytical Instruments of Shandong Province, Shandong Analysis and Test Center, Qilu University of Technology (Shandong Academy of Sciences), Jinan 250014, China. Electronic address:

Acorus tatarinowii Schott is a traditional Chinese medicine used to treat memory and cognitive dysfunction. Because of their efficacy and lower toxic effects, research on α- and β-asarone, the phytoconstituents, has attracted attention owing to their remarkable pharmacological activities. Silver ion coordination complexation high-speed counter-current chromatography was used to separate these isomers from A. tatarinowii extract, coupled with accelerated solvent extraction. Accelerated solvent extraction parameters were investigated with single-factor and orthogonal testing. A two-phase solvent system composed of n-hexane-ethyl acetate-ethanol-water (2:1:2:1, v/v) with 0.50 mol/L silver ions was selected for separation. From 2.0 g crude extract, 1.4 g of β-asarone and 0.09 g of α-asarone were obtained with purities over 98% by sequential sample loading in 20 h. The isolated compounds were identified by electrospray ionization mass spectrometry, H and C NMR. Silver ions significantly increased the separation factor and retention of the stationary phase. The chromatographic behavior indicated that cis-configuration was more strongly complexed with the silver ion. This was further demonstrated with the help of computational analysis. In conclusion, the established method could be employed to separate other cis-trans or E/Z isomers that form coordination complexes.
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http://dx.doi.org/10.1016/j.chroma.2021.462080DOI Listing
April 2021

Pharmacokinetics-based chronoefficacy of Fuzi against chronic kidney disease.

J Pharm Pharmacol 2021 Mar;73(4):535-544

Research Center for Biopharmaceutics and Pharmacokinetics, College of Pharmacy, Jinan University, Guangzhou, China.

Objectives: Identifying drugs with time-varying efficacy or toxicity, and understanding the underlying mechanisms would help to improve treatment efficacy and reduce adverse effects. In this study, we uncovered that the therapeutic effect of Fuzi (the lateral root of Aconitum carmichaelii Debeaux) depended on the dosing time in mice with adenine-induced chronic kidney disease (CKD).

Methods: The Fuzi efficacy was determined by biomarker measurements [i.e. plasma creatinine (CRE), blood urea nitrogen (BUN) and urinary N-acetyl-β-D-glucosaminidase (NAG)], as well as inflammation, fibrosis and histological analyses. Circadian regulation of Fuzi pharmacokinetics and efficacy was evaluated using brain and muscle Arnt-like protein-1 (Bmal1)-deficient (Bmal1-/-) mice.

Key Findings: The Fuzi efficacy was higher when the drug was dosed at ZT10 and was lower when the drug was dosed at other times (ZT2, ZT6, ZT14, ZT18 and ZT22) according to measurements of plasma CRE, BUN and urinary NAG. Consistently, ZT10 (5 PM) dosing showed a stronger protective effect on the kidney (i.e. less extensive tubular injury) as compared to ZT22 (5 AM) dosing. This was supported by lower levels of inflammatory and fibrotic factors (IL-1β, IL-6, Tnf-α, Ccl2, Tgfb1 and Col1a1) at ZT10 than at ZT22. Pharmacokinetic analyses showed that the area under the curve (AUC) values (reflective of systemic exposure) and renal distribution of aconitine, hypaconitine and mesaconitine (three putative active constituents) for Fuzi dosing at ZT10 were significantly higher than those for herb dosing at ZT22, suggesting a role of circadian pharmacokinetics in Fuzi chronoefficacy. Drug efficacy studies confirmed that aconitine, hypaconitine and mesaconitine possessed a kidney-protecting effect. In addition, genetic knockout of Bmal1 in mice abolished the time-dependency of Fuzi pharmacokinetics and efficacy. This reinforced the existence of chronoefficacy for Fuzi and supported the role of circadian pharmacokinetics in Fuzi chronoefficacy.

Conclusions: The efficacy of Fuzi against CKD depends on the dosing time in mice, which is associated with circadian pharmacokinetics of the three main active constituents (i.e. aconitine, hypaconitine and mesaconitine). These findings highlight the relevance of dosing time in the therapeutic outcomes of herbal medicines.
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http://dx.doi.org/10.1093/jpp/rgaa060DOI Listing
March 2021

Hypoxia modulation by dual-drug nanoparticles for enhanced synergistic sonodynamic and starvation therapy.

J Nanobiotechnology 2021 Mar 26;19(1):87. Epub 2021 Mar 26.

Department of Ultrasound, The Third Affiliated Hospital, Chongqing Medical University, Chongqing, 400010, People's Republic of China.

Background: Sonodynamic therapy (SDT) is an emerging non-invasive therapeutic technique. SDT-based cancer therapy strategies are presently underway, and it may be perceived as a promising approach to improve the efficiency of anti-cancer treatment. In this work, multifunctional theranostic nanoparticles (NPs) were synthesized for synergistic starvation therapy and SDT by loading glucose oxidase (GOx, termed G) and 5,10,15,20-tetrakis (4-chlorophenyl) porphyrin) Cl (T (p-Cl) PPMnCl, termed PMnC) in Poly (lactic-co-glycolic) acid (PLGA) NPs (designated as [email protected] NPs).

Results: On account of the peroxidase-like activity of PMnC, [email protected] NPs can catalyze hydrogen peroxide (HO) in tumor regions to produce oxygen (O), thus enhancing synergistic therapeutic effects by accelerating the decomposition of glucose and promoting the production of cytotoxic singlet oxygen (O) induced by ultrasound (US) irradiation. Furthermore, the NPs can also serve as excellent photoacoustic (PA)/magnetic resonance (MR) imaging contrast agents, effectuating imaging-guided cancer treatment.

Conclusion: Multifunctional [email protected] NPs can effectuate the synergistic amplification effect of cancer starvation therapy and SDT by hypoxia modulation, and act as contrast agents to enhance MR/PA dual-modal imaging. Consequently, [email protected] NPs might be a promising nano-platform for highly efficient cancer theranostics.
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http://dx.doi.org/10.1186/s12951-021-00837-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7995598PMC
March 2021

PbEIL1 acts upstream of PbCysp1 to regulate ovule senescence in seedless pear.

Hortic Res 2021 Mar 10;8(1):59. Epub 2021 Mar 10.

College of Horticulture, Northwest A&F University, Yangling, Shaanxi Province, China.

Numerous environmental and endogenous signals control the highly orchestrated and intricate process of plant senescence. Ethylene, a well-known inducer of senescence, has long been considered a key endogenous regulator of leaf and flower senescence, but the molecular mechanism of ethylene-induced ovule senescence has not yet been elucidated. In this study, we found that blockage of fertilization caused ovule abortion in the pear cultivar '1913'. According to transcriptome and phytohormone content data, ethylene biosynthesis was activated by pollination. At the same time, ethylene overaccumulated in ovules, where cells were sensitive to ethylene signals in the absence of fertilization. We identified a transcription factor in the ethylene signal response, ethylene-insensitive 3-like (EIL1), as a likely participant in ovule senescence. Overexpression of PbEIL1 in tomato caused precocious onset of ovule senescence. We further found that EIL1 could directly bind to the promoter of the SENESCENCE-ASSOCIATED CYSTEINE PROTEINASE 1 (PbCysp1) gene and act upstream of senescence. Yeast one-hybrid and dual-luciferase assays revealed the interaction of the transcription factor and the promoter DNA sequence and demonstrated that PbEIL1 enhanced the action of PbCysp1. Collectively, our results provide new insights into how ethylene promotes the progression of unfertilized ovule senescence.
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http://dx.doi.org/10.1038/s41438-021-00491-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7943805PMC
March 2021

Nanomedicine Enables Drug-Potency Activation with Tumor Sensitivity and Hyperthermia Synergy in the Second Near-Infrared Biowindow.

ACS Nano 2021 04 22;15(4):6457-6470. Epub 2021 Mar 22.

Materdicine Lab, School of Life Sciences, Shanghai University, Shanghai 200444, People's Republic of China.

Disulfiram (DSF), a U.S. Food and Drug Administration (FDA)-approved drug for the treatment of chronic alcoholism, is also used as an antitumor drug in combination with Cu ions. However, studies have shown that the endogenous Cu dose in tumor tissues is still insufficient to form relatively high levels of a bis(,diethyldithiocarbamate) copper(II) complex (denoted as Cu(DTC)) to selectively eradicate cancer cells. Here, DSF-loaded hollow copper sulfide nanoparticles ([email protected]) were designed to achieve tumor microenvironment (TME)-activated formation of cytotoxic Cu(DTC) for NIR-II-induced, photonic hyperthermia-enhanced, and DSF-initiated cancer chemotherapy. The acidic TME triggered the gradual degradation of [email protected], promoting the rapid release of DSF and Cu ions, causing the formation of cytotoxic Cu(DTC), to achieve efficient DSF-based chemotherapy. Additionally, [email protected] exhibited a notably high photothermal conversion efficiency of 23.8% at the second near-infrared (NIR-II) biowindow, thus significantly inducing photonic hyperthermia to eliminate cancer cells. Both and studies confirmed the effective photonic hyperthermia-induced chemotherapeutic efficacy of DSF by integrating the formation of toxic Cu(DTC) complexes and evident temperature elevation upon NIR-II laser irradiation. Thus, this study represents a distinctive paradigm of Cu chelation-initiated "nontoxicity-to-toxicity" transformation for photonic hyperthermia-augmented DSF-based cancer chemotherapy.
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http://dx.doi.org/10.1021/acsnano.0c08848DOI Listing
April 2021

Effects of Deep Brain Stimulation in the Subthalamic Nucleus on Neurocognitive Function in Patients With Parkinson's Disease Compared With Medical Therapy: A Meta-Analysis.

Front Neurol 2021 2;12:610840. Epub 2021 Mar 2.

Guangxi Clinical Research Center for Neurological Diseases, Affiliated Hospital of Guilin Medical University, Guilin Medical University, Guilin, China.

DBS has been shown to significantly affect motor symptoms in Parkinson's disease (PD). However, some studies have suggested that it may have adverse effects on patients' neurocognitive function. To clarify this operation's effect on neurocognitive function, we collected studies containing neurocognitive function evaluation for qualitative and quantitative analysis. We searched relevant clinical studies through Pubmed and Embase databases and extracted and sorted out information such as sample size, post-operative scores, pre-operative and post-operative evaluation interval, PD course, and exclusion criteria, from articles meeting the standards. The magnitude and variance of the DBS group's combined effects and the drug therapy group in each neurocognitive domain were calculated and analyzed by the random-effects model. Compared with the drug treatment group, the verbal fluency of patients in the experimental group was significantly decreased at least moderately (ES = -0.553), in which the phonemic fluency declines greatly (ES = -0.842), learning and memory ability was slightly decreased (ES = -0.305), and other neurocognitive functions were not significantly decreased. STN-DBS can affect verbal fluency and damage learning and memory. There was no significant correlation between the above effects and disease progression itself, and it was more likely to be associated with STN-DBS. It is suggested that post-operative patients should be trained and evaluated regularly for their verbal fluency and learning and memory ability. The safety of STN-DBS is acceptable for the majority of patients with motor symptoms.
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http://dx.doi.org/10.3389/fneur.2021.610840DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7960912PMC
March 2021

Comprehensive transcriptomic and proteomic analyses identify intracellular targets for myriocin to induce Fusarium oxysporum f. sp. niveum cell death.

Microb Cell Fact 2021 Mar 17;20(1):69. Epub 2021 Mar 17.

College of Life Science and Agroforestry, Qiqihar University, Qiqihar, 161006, China.

Background: Myriocin is a natural product with antifungal activity and is derived from Bacillus amyloliquefaciens LZN01. Our previous work demonstrated that myriocin can inhibit the growth of Fusarium oxysporum f. sp. niveum (Fon) by inducing membrane damage. In this study, the antifungal actions of myriocin against Fon were investigated with a focus on the effects of myriocin on intracellular molecules.

Results: Analysis of DNA binding and fluorescence spectra demonstrated that myriocin can interact with dsDNA from Fon cells. The intracellular-targeted mechanism of action was also supported by transcriptomic and proteomic analyses; a total of 2238 common differentially expressed genes (DEGs) were identified. The DEGs were further verified by RT-qPCR. Most of the DEGs were assigned metabolism and genetic information processing functions and were enriched in ribosome biogenesis in eukaryotes pathway. The expression of some genes and proteins in ribosome biogenesis in eukaryotes pathway was affected by myriocin, primarily the genes controlled by the C6 zinc cluster transcription factor family and the NFYA transcription factor. Myriocin influenced the posttranscriptional processing of gene products by triggering the main RI (retained intron) events of novel alternative splicing; myriocin targeted key genes (FOXG_09470) or proteins (RIOK2) in ribosome biogenesis in eukaryotes pathway, resulting in disordered translation.

Conclusions: In conclusion, myriocin was determined to exhibit activity against Fon by targeting intracellular molecules. The results of our study may help to elucidate the antifungal actions of myriocin against Fon.
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http://dx.doi.org/10.1186/s12934-021-01560-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7968361PMC
March 2021

Risk factors for and outcomes of prolonged mechanical ventilation in patients received DeBakey type I aortic dissection repairment.

J Thorac Dis 2021 Feb;13(2):735-742

Department of Cardio-thoracic Surgery, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing, China.

Background: This study aimed to identify risk factors for prolonged mechanical ventilation (PMV) and its association with disease prognosis following acute DeBakey type I aortic dissection surgery.

Methods: A total of 582 patients who received emergency surgery for acute DeBakey type I aortic dissection from 2014 to 2018 were enrolled in this study. Mechanical ventilation period after surgery longer than 48 hours was defined as postoperative PMV. Multiple logistic regression analysis was used to identify risk factors for PMV. This study also compared short- and long-term outcomes in patients who developed PMV with patients who did not develop this complication. To identify and compare long-term cumulative survival rate, Kaplan-Meier survival curve was plotted.

Results: Among all enrolled patients, 259 (44.5%) received PMV treatment. Our data suggested that the length of intensive care unit and hospital stay were longer for patients who received PMV treatment. Thirty-day mortality was also higher in patients with PMV than in patients without PMV. Elevated leukocyte count and increased serum cystatin C level upon admission, lower preoperative platelet count and longer cardiopulmonary bypass (CPB) duration were identified as risk factors for PMV. Interestingly, our data suggested that there was no significant difference of survival rate between patients with or without PMV history.

Conclusions: PMV after DeBakey type I aortic dissection repair surgery was a common complication and associated with increased short-term mortality rate but did not affect long-term mortality rate. Elevated preoperative leukocyte count, increased preoperative serum cystatin C level, lower preoperative platelet count and longer CPB duration were risk factors for PMV.
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http://dx.doi.org/10.21037/jtd-20-2736DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7947516PMC
February 2021

Endothelial Regulation by Exogenous Annexin A1 in Inflammatory Response and BBB Integrity Following Traumatic Brain Injury.

Front Neurosci 2021 18;15:627110. Epub 2021 Feb 18.

Department of Neurosurgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China.

Background And Target: Following brain trauma, blood-brain barrier (BBB) disruption and inflammatory response are critical pathological steps contributing to secondary injury, leading to high mortality and morbidity. Both pathologies are closely associated with endothelial remodeling. In the present study, we concentrated on annexin A1 (ANXA1) as a novel regulator of endothelial function after traumatic brain injury.

Methods: After establishing controlled cortical impact (CCI) model in male mice, human recombinant ANXA1 (rANXA1) was administered intravenously, followed by assessments of BBB integrity, brain edema, inflammatory response, and neurological deficits.

Result: Animals treated with rANXA1 (1 μg/kg) at 1 h after CCI exhibited optimal BBB protection including alleviated BBB disruption and brain edema, as well as endothelial junction proteins loss. The infiltrated neutrophils and inflammatory cytokines were suppressed by rANXA1, consistent with decreased adhesive and transmigrating molecules from isolated microvessels. Moreover, rANXA1 attenuated the neurological deficits induced by CCI. We further found that the Ras homolog gene family member A (RhoA) inhibition has similar effect as rANXA1 in ameliorating brain injuries after CCI, whereas rANXA1 suppressed CCI-induced RhoA activation.

Conclusion: Our findings suggest that the endothelial remodeling by exogenous rANXA1 corrects BBB disruption and inflammatory response through RhoA inhibition, hence improving functional outcomes in CCI mice.
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http://dx.doi.org/10.3389/fnins.2021.627110DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7930239PMC
February 2021