Publications by authors named "Feng Li"

4,987 Publications

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Pharmacokinetic characteristics of hydroxysafflor yellow A in normal and diabetic cardiomyopathy mice.

Biomed Chromatogr 2021 May 12:e5173. Epub 2021 May 12.

Department of Chinese Materia Medica and Natural Medicines, School of Pharmacy, The Air Force Medical University, Xi'an, Shanxi, China.

Hydroxysafflor yellow A (HSYA), a major active water-soluble component in Carthamus tinctorius L., is considered a potential antioxidant with protective effects against myocardial injury. However, its pharmacokinetic characteristics in normal and diabetic cardiomyopathy (DCM) mice remain unknown. This study was designed to investigate the differences in the pharmacokinetics of HSYA between normal and streptozotocin-induced DCM mice. HSYA in the mouse plasma was quantified by liquid chromatography-tandem mass spectrometry. Compared with the normal group, the DCM group showed a significantly higher area under curve (AUC , AUC ) value and peak plasma concentration, suggesting a higher uptake of HSYA in the DCM mice, and a significantly lower plasma clearance and apparent volume of distribution, suggesting slower elimination of HSYA in the DCM mice. The serum superoxide dismutase and glutathione peroxidase levels were significantly higher and malondialdehyde content was significantly lower in DCM mice than in normal mice, indicating the antioxidative stress effect of HSYA. Furthermore, the correlation analysis revealed that the serum HSYA content in the DCM mice significantly positively correlated with antioxidant enzyme levels. These results showed that the pharmacokinetics of HSYA changed significantly in the DCM mice, and this may improve the antioxidative stress effect of the drug.
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http://dx.doi.org/10.1002/bmc.5173DOI Listing
May 2021

Inhibition of Antiviral Innate Immunity by Foot-and-Mouth Disease Virus L through Interaction with N-terminal Domain of Swine RNase L.

J Virol 2021 May 12. Epub 2021 May 12.

Shandong Key Laboratory of Animal Disease Control and Breeding, Institute of Animal Science and Veterinary Medicine, Shandong Academy of Agricultural Sciences, Jinan, Shandong, China

Foot-and-mouth disease virus (FMDV) is the pathogen of foot-and-mouth disease (FMD), which is a highly contagious disease in cloven-hoofed animals. To survive in the host, FMDV has evolved multiple strategies to antagonize host innate immune responses. In this study, we showed that the leader protease (L) of FMDV, a papain-like proteinase, promoted viral replication by evading the antiviral interferon response through counteracting the 2',5'-oligoadenylate synthetase (OAS)/RNase L system. Specifically, we observed that the titers of L deletion virus were significantly lower than those of wild type FMDV (FMDV-WT) in cultured cells. Our mechanistic studies demonstrated that L interfered with the OAS/RNase L pathway by interacting with N-terminal domain of swine RNase L (sRNase L). Remarkably, L of FMDV exhibited species-specific binding to RNase L in that the interaction was observed only in swine cells, not human, monkey or canine cells. Lastly, we presented evidence that by interacting with sRNase L, FMDV L inhibited cellular apoptosis. Taken together, these results demonstrate a novel mechanism that L utilizes to escape the OAS/RNase L-mediated antiviral defense pathway.FMDV is a picornavirus that causes a significant disease in agricultural animals. FMDV has developed diverse strategies to escape the host interferon response. Here we show that L of FMDV antagonizes the OAS/RNase L pathway, an important interferon effector pathway, by interacting with N-terminal domain of sRNase L. Interestingly, such a virus-host interaction is species-specific because the interaction is detected only in swine cells, not in human, monkey, or canine cells. Furthermore, L inhibits apoptosis through interacting with sRNase L. This study demonstrates a novel mechanism by which FMDV has evolved to inhibit host innate immune responses.
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http://dx.doi.org/10.1128/JVI.00361-21DOI Listing
May 2021

Synthesis of Oxygen-Rich Bismuth Oxybromide (BiOBr) Photocatalyst for High Efficiency Degradation of Sulfadiazine Under Simulated Sunlight.

J Nanosci Nanotechnol 2021 Nov;21(11):5477-5485

School of Materials Science and Engineering, Hebei University of Engineering, Handan 056038, p. R. China.

At present, compared with other antibiotic degradation systems, there are few literatures on pho- tocatalytic degradation of sulfadiazine (SDZ). In this research, it was firstly discovered that the oxygen-rich bismuth oxybromide (BiO Br) photocatalyst can efficiently degrade SDZ under simulated sunlight. In this paper, the prepared BiOBr photocatalyst by mixed solvothermal method represented outstanding photocatalytic performance. The catalyst synthesized at 120 °C and pH = 10 showed optimum degradation function in the samples prepared at various temperatures and pH value. After 3 h of irradiation, 96.2% of SDZ solution could be decomposed. The effects of preparation conditions, catalyst dosage, initial SDZ concentration and initial SDZ pH value on photocatalytic degradation efficiency were investigated systematically. Besides, the effect of active species was studied by trapping tests, and it was concluded that 'O₂ contributes the most to the photocatalytic process. A possible photocatalytic degradation mechanism was proposed.
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http://dx.doi.org/10.1166/jnn.2021.19479DOI Listing
November 2021

DSCMF: prediction of LncRNA-disease associations based on dual sparse collaborative matrix factorization.

BMC Bioinformatics 2021 May 12;22(Suppl 3):241. Epub 2021 May 12.

School of Computer Science, Qufu Normal University, Rizhao, China.

Background: In the development of science and technology, there are increasing evidences that there are some associations between lncRNAs and human diseases. Therefore, finding these associations between them will have a huge impact on our treatment and prevention of some diseases. However, the process of finding the associations between them is very difficult and requires a lot of time and effort. Therefore, it is particularly important to find some good methods for predicting lncRNA-disease associations (LDAs).

Results: In this paper, we propose a method based on dual sparse collaborative matrix factorization (DSCMF) to predict LDAs. The DSCMF method is improved on the traditional collaborative matrix factorization method. To increase the sparsity, the L-norm is added in our method. At the same time, Gaussian interaction profile kernel is added to our method, which increase the network similarity between lncRNA and disease. Finally, the AUC value obtained by the experiment is used to evaluate the quality of our method, and the AUC value is obtained by the ten-fold cross-validation method.

Conclusions: The AUC value obtained by the DSCMF method is 0.8523. At the end of the paper, simulation experiment is carried out, and the experimental results of prostate cancer, breast cancer, ovarian cancer and colorectal cancer are analyzed in detail. The DSCMF method is expected to bring some help to lncRNA-disease associations research. The code can access the https://github.com/Ming-0113/DSCMF website.
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http://dx.doi.org/10.1186/s12859-020-03868-wDOI Listing
May 2021

Modeling genome-wide by environment interactions through omnigenic interactome networks.

Cell Rep 2021 May;35(6):109114

Beijing Advanced Innovation Center for Tree Breeding by Molecular Design, College of Biological Sciences and Technology, Beijing Forestry University, Beijing 100083, China; Center for Statistical Genetics, Departments of Public Health Sciences and Statistics, The Pennsylvania State University, Hershey, PA 17033, USA. Electronic address:

How genes interact with the environment to shape phenotypic variation and evolution is a fundamental question intriguing to biologists from various fields. Existing linear models built on single genes are inadequate to reveal the complexity of genotype-environment (G-E) interactions. Here, we develop a conceptual model for mechanistically dissecting G-E interplay by integrating previously disconnected theories and methods. Under this integration, evolutionary game theory, developmental modularity theory, and a variable selection method allow us to reconstruct environment-induced, maximally informative, sparse, and casual multilayer genetic networks. We design and conduct two mapping experiments by using a desert-adapted tree species to validate the biological application of the model proposed. The model identifies previously uncharacterized molecular mechanisms that mediate trees' response to saline stress. Our model provides a tool to comprehend the genetic architecture of trait variation and evolution and trace the information flow of each gene toward phenotypes within omnigenic networks.
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http://dx.doi.org/10.1016/j.celrep.2021.109114DOI Listing
May 2021

Smartphone-based reading system integrated with phycocyanin-enhanced latex nanospheres immunoassay for on-site determination of aflatoxin B1 in foodstuffs.

Food Chem 2021 May 6;360:130019. Epub 2021 May 6.

College of Biological Science and Engineering, Fuzhou University, No. 2 Xueyuan Road, Fuzhou 350108, China; Fujian Key Laboratory of Medical Instrument and Pharmaceutical Technology, Fuzhou University, No. 2 Xueyuan Road, Fuzhou 350108, China. Electronic address:

Traditional methods for aflatoxin B1 (AFB1) detection are complex, time-consuming, labor-intensive, and high cost. Moreover, they require sophisticated large-scale instrumentation, which limits their on-site rapid detection. Herein, phycocyanin fluorescent nanospheres based on fluorescence immunochromatographic assay were developed for quantitative detection of AFB1 at parts-per-billion (ppb) levels in foodstuffs. Phycocyanin and anti-AFB1 monoclonal antibodies were coupled on the surface of latex nanospheres to amplify the fluorescence signal and improve the sensitivity. The fluorescence intensity was measured by a self-developed smartphone-based reading system. Under the optimal conditions, this approach achieved quantitative point-of-care detection of AFB1 within 25 min. The calibration curve for AFB1 was linear in the range of 0.2-48 ppb, and the limit of detection was 0.16 ppb. The practical applicability of the proposed approach was demonstrated by the determination of AFB1 in naturally contaminated samples, and the results were consistent with HPLC detection.
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http://dx.doi.org/10.1016/j.foodchem.2021.130019DOI Listing
May 2021

Advances and Insights of APC-Asef Inhibitors for Metastatic Colorectal Cancer Therapy.

Front Mol Biosci 2021 22;8:662579. Epub 2021 Apr 22.

Department of Pathophysiology, Key Laboratory of Cell Differentiation and Apoptosis of Chinese Ministry of Education, Shanghai Jiao Tong University School of Medicine, Shanghai, China.

In Colorectal cancer (CRC), adenomatous polyposis coli (APC) directly interacts with the Rho guanine nucleotide exchange factor 4 (Asef) and releases its GEF activity. Activated Asef promotes the aberrant migration and invasion of CRC cell through a CDC42-mediated pathway. Knockdown of either APC or Asef significantly decreases the migration of CRC cells. Therefore, disrupting the APC-Asef interaction is a promising strategy for the treatment of invasive CRC. With the growth of structural information, APC-Asef inhibitors have been designed, providing hope for CRC therapy. Here, we will review the APC-Asef interaction in cancer biology, the structural complex of APC-Asef, two generations of peptide inhibitors of APC-Asef, and small molecule inhibitors of APC-Asef, focusing on research articles over the past 30 years. We posit that these advances in the discovery of APC-Asef inhibitors establish the protein-protein interaction (PPI) as targetable and provide a framework for other PPI programs.
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http://dx.doi.org/10.3389/fmolb.2021.662579DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8100458PMC
April 2021

Communication Between Epithelial-Mesenchymal Plasticity and Cancer Stem Cells: New Insights Into Cancer Progression.

Front Oncol 2021 21;11:617597. Epub 2021 Apr 21.

Department of Liver Surgery, West China Hospital, Sichuan University, Chengdu, China.

The epithelial-mesenchymal transition (EMT) is closely associated with the acquisition of aggressive traits by carcinoma cells and is considered responsible for metastasis, relapse, and chemoresistance. Molecular links between the EMT and cancer stem cells (CSCs) have indicated that EMT processes play important roles in the expression of CSC-like properties. It is generally thought that EMT-related transcription factors (EMT-TFs) need to be downregulated to confer an epithelial phenotype to mesenchymal cells and increase cell proliferation, thereby promoting metastasis formation. However, the genetic and epigenetic mechanisms that regulate EMT and CSC activation are contradictory. Emerging evidence suggests that EMT need not be a binary model and instead a hybrid epithelial/mesenchymal state. This dynamic process correlates with epithelial-mesenchymal plasticity, which indicates a contradictory role of EMT during cancer progression. Recent studies have linked the epithelial-mesenchymal plasticity and stem cell-like traits, providing new insights into the conflicting relationship between EMT and CSCs. In this review, we examine the current knowledge about the interplay between epithelial-mesenchymal plasticity and CSCs in cancer biology and evaluate the controversies and future perspectives. Understanding the biology of epithelial-mesenchymal plasticity and CSCs and their implications in therapeutic treatment may provide new opportunities for targeted intervention.
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http://dx.doi.org/10.3389/fonc.2021.617597DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8097085PMC
April 2021

Identification of Candidate Susceptibility Genes to f. sp. in Wheat.

Front Plant Sci 2021 21;12:657796. Epub 2021 Apr 21.

Commonwealth Scientific and Industrial Research Organisation, Agriculture and Food, Canberra, ACT, Australia.

Wheat stem rust disease caused by f. sp. () is a global threat to wheat production. Fast evolving populations of limit the efficacy of plant genetic resistance and constrain disease management strategies. Understanding molecular mechanisms that lead to rust infection and disease susceptibility could deliver novel strategies to deploy crop resistance through genetic loss of disease susceptibility. We used comparative transcriptome-based and orthology-guided approaches to characterize gene expression changes associated with infection in susceptible and resistant genotypes as well as the non-host . We targeted our analysis to genes with differential expression in and genes suppressed or not affected in and report several processes potentially linked to susceptibility to , such as cell death suppression and impairment of photosynthesis. We complemented our approach with a gene co-expression network analysis to identify wheat targets to deliver resistance to through removal or modification of putative susceptibility genes.
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http://dx.doi.org/10.3389/fpls.2021.657796DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8097158PMC
April 2021

Rubioncolin C, a natural naphthohydroquinone dimer isolated from Rubia yunnanensis, inhibits the proliferation and metastasis by inducing ROS-mediated apoptotic and autophagic cell death in triple-negative breast cancer cells.

J Ethnopharmacol 2021 May 4:114184. Epub 2021 May 4.

State Key Laboratory of Natural Medicines, Department of TCMs Pharmaceuticals, School of Traditional Chinese Pharmacy, China Pharmaceutical University, Nanjing, 211198, China. Electronic address:

Ethnopharmacological Relevance: Rubia yunnanensis Diels is a traditional Chinese medicine that has diverse pharmacological activities, including antituberculosis, antirheumatism and anticancers. Rubioncolin C (RC), a natural naphthohydroquinone dimer isolated from the roots and rhizomes of R. yunnanensis Diels, has shown potent antitumor activity. However, the antitumor activity and its potential mechanism of RC in triple negative breast cancer (TNBC) cell lines remained unclear.

Aim Of The Study: This study was aim to investigate the anti-proliferation and anti-metastasis activity as well as the potential mechanism of RC on triple-negative breast cancer cells in vitro and in vivo.

Materials And Methods: The sulforhodamine B assay, colony formation assay and cell cycle analysis were used to determine the anti-proliferative activity of RC on TNBC. The anti-metastatic activity in vitro of RC was detected through the scratch wound assay, cell migration and invasion assays and gelatin zymography. The flow cytometry, JC-1, GFP-LC3B plasmid transfection, MDC, Lysotracker red and Carboxy-HDCFDA, DHE, and MitoSOX™ Red staining were performed to investigate the effect of RC on apoptosis, autophagy and ROS level. The apoptosis inhibitor, autophagy inhibitors and ROS inhibitors were used to further verify the antitumor mechanism of RC. The protein levels related with cell cycle, apoptosis, and autophagy were examined with western blotting. In addition, the anti-tumor activity of RC in vivo was assessed in an experimental metastatic model.

Results: In the present study, RC suppressed the proliferation of TNBC cells in a time- and dose-dependent manner via regulating cell cycle. Further experiments showed that RC inhibited the migration and invasion of TNBC cells by downregulating MMPs and inhibiting EMT. Moreover, we demonstrated that RC induced obviously apoptotic and autophagic cell death, activated MAPK signaling pathway and inhibited mTOR/Akt/p70S6K and NF-κB signaling pathways. Furthermore, the excessive ROS was produced after treatment with RC. The antioxygen NAC and GSH could rescue the cell viability and reestablish the ability of cell metastasis, and inhibit the RC-induced apoptosis and autophagy. In a mice lung metastasis model of breast cancer, RC inhibited lung metastasis, and induced autophagy and apoptosis.

Conclusion: These findings clarified the antitumor mechanism of RC on TNBC cell lines and suggested that RC is a key active ingredient for the cancer treatment of R. yunnanensis, which would help RC develop as a new potential chemotherapeutic agent for TNBC treatment.
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http://dx.doi.org/10.1016/j.jep.2021.114184DOI Listing
May 2021

pH and Redox Dual-Response Disulfide Bond-Functionalized Red-Emitting Gold Nanoclusters for Monitoring the Contamination of Organophosphorus Pesticides in Foods.

Anal Chem 2021 May 7. Epub 2021 May 7.

College of Chemistry and Pharmaceutical Sciences, Qingdao Agricultural University, Qingdao 266109, People's Republic of China.

Most of the fluorescence sensors require choline oxidase or quenchers to detect organophosphorus pesticides (OPs) based on a single hydrolysate and suffer from high cost, complex procedures, weak stability, and low sensitivity. Here, we proposed a brand-new fluorescence strategy for highly sensitive detection of OPs based on both hydrolysate-response disulfide bond-functionalized gold nanoclusters (S-S-AuNCs) without additional substances. S-S-AuNCs were synthesized via a facile one-step redox reaction and emitted bright red light with ultrasmall size and high water dispersion. Interestingly, S-S-AuNCs displayed a unique response to thiol compounds and low pH values and were thus pioneered as a high-efficiency sensor for OPs based on acetylcholinesterase (AChE)-catalyzed hydrolysis of acetylthiocholine into thiocholine and CHCOOH and OP inhibition of AChE activity. Further, S-S-AuNCs were employed to monitor the residue, distribution, and metabolization of methidathion in pakchoi with acceptable results. We believe that this work supplies a simpler and more highly sensitive approach for OP assay than the known ones and opens a new avenue to development of multistimulus-responsive and high-performance fluorescence substances.
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http://dx.doi.org/10.1021/acs.analchem.1c01414DOI Listing
May 2021

miR-142-3p and HMGB1 Are Negatively Regulated in Proliferation, Apoptosis, Migration, and Autophagy of Cartilage Endplate Cells.

Cartilage 2021 May 6:19476035211012444. Epub 2021 May 6.

Surgical Department of Thoracolumbar, the Second Affiliated Hospital of Inner Mongolia Medical University, Hohhot, Inner Mongolia, China.

Background: Cartilage endplate (CEP) degeneration plays a vital role in the pathological process of intervertebral disc degeneration. It has been previously reported that microRNAs may participate in the occurrence and development of intervertebral disc degeneration through regulating its target genes directly. The regulatory roles of miR-142-3p/HMGB1 in some orthopedic diseases have been determined successively, but there was no report about the degeneration of CEP. Therefore, we aimed to determine the regulation of miR-142-3p/HMGB1 or potential molecular mechanisms on proliferation, apoptosis, migration, and autophagy of CEP cells.

Methods: The target gene of miR-142-3p was determined by double luciferase assay. We selected ATDC5 cell lines. CCK-8 method was used to detect cell proliferation. Real-time fluorescence quantitative polymerase chain reaction was used to determine gene expression levels, and western blot analysis was used to determine protein expression levels. We chose flow cytometry to measure cell apoptosis and cell cycle.

Results: The result of luciferase detection showed that the target gene of miR-142-3p in CEP cells was HMGB1. Knockdown of the miR-142-3p inhibited the expression level of HMGB1, the proliferation and migration of CEP cells, but it promoted apoptosis of CEP cells. In addition, the detection results of the proteins related to apoptosis or autophagy showed that knockdown of miR-142-3p promoted apoptosis and autophagy.

Conclusion: The negative regulation of miR-142-3p/HMGB1 can affect the proliferation, apoptosis, migration, and autophagy of CEP cells. Our results provide a new idea for the targeted treatment of CEP degeneration by inhibiting the expression of HMGB1.
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http://dx.doi.org/10.1177/19476035211012444DOI Listing
May 2021

Targeted polymeric nanoparticles for drug delivery to hypoxic, triple-negative breast tumors.

ACS Appl Bio Mater 2021 Feb 23;4(2):1450-1460. Epub 2020 Dec 23.

Department of Pharmaceutical Sciences, North Dakota State University, Fargo, North Dakota 58102, United States.

High recurrence and metastasis to vital organs are the major characteristics of triple-negative breast cancer (TNBC). Low vascular oxygen tension promotes resistance to chemo- and radiation therapy. Neuropilin-1 (NRP-1) receptor is highly expressed on TNBC cells. The tumor-penetrating iRGD peptide interacts with the NRP-1 receptor, triggers endocytosis and transcytosis, and facilitates penetration. Herein, we synthesized a hypoxia-responsive diblock PLA-diazobenzene-PEG copolymer and prepared self-assembled hypoxia-responsive polymersomes (Ps) in an aqueous buffer. The iRGD peptide was incorporated into the polymersome structure to make hypoxia-responsive iRGD-conjugated polymersomes (iPs). Doxorubicin (DOX) was encapsulated in the polymersomes to prepare both targeted and non-targeted hypoxia-responsive polymersomes (DOX-iPs and DOX-Ps, respectively). The polymeric nanoparticles released less than 30% of their encapsulated DOX within 12 hours under normoxic conditions (21% oxygen), whereas under hypoxia (2% Oxygen), doxorubicin release remarkably increased to over 95%. The targeted polymersomes significantly decreased TNBC cells' viability in monolayer and spheroid cultures under hypoxia compared to normoxia. Animal studies displayed that targeted polymersomes significantly diminished tumor growth in xenograft nude mice. Overall, the targeted polymersomes exhibited potent anti-tumor activity in monolayer, spheroid, and animal models of TNBC. With further developments, the targeted nanocarriers discussed here might have the translational potential as drug carriers for the treatment of TNBC.
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http://dx.doi.org/10.1021/acsabm.0c01336DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8096163PMC
February 2021

Case report: histopathology and molecular pathology analysis on enteric tissue of a COVID-19 patient.

Diagn Pathol 2021 May 5;16(1):40. Epub 2021 May 5.

Department of Infectious Disease, Shanghai Public Health Clinical center, Fudan University, Shanghai, China.

Aims: Patients with COVID-19 can also have enteric symptoms. Here we analyzed the histopathology of intestinal detachment tissue from a patient with COVID-19.

Methods: The enteric tissue was examined by hematoxylin & eosin stain, PAS (Periodic acid-Schiff) staining, Gram staining, Ziehl-Neelsen stain and Grocott's Methenamine Silver (GMS) Stain. The distribution of CD3, CD4, CK20 and CD68, cytomegalovirus (CMV) and Herpes Simplex Virus (HSV) antigen were determined by immunohistochemistry. In situ hybridization (ISH) of SARS-CoV-2 and Epstein-Barr virus-encoded small RNA (EBER) were also performed.

Results: We observed mucosal epithelium shedding, intestinal mucosal erosion, focal inflammatory necrosis with hemorrhage, massive neutrophil infiltration, macrophage proliferation accompanied by minor lymphocyte infiltration. Fungal spores and gram positive cocci but not mycobacteria tuberculosis were identified. Immunohistochemistry staining showed abundant CD68 macrophages but few lymphocytes infiltration. HSV, CMV and EBV were negative. ISH of SARS-CoV-2 RNA showed positive signal which mostly overlapped with CD68 positivity.

Conclusions: The in situ detection of SARS-CoV-2 RNA in intestinal macrophages implicates a possible route for gastrointestinal infection. Further study is needed to further characterize the susceptibility of enteric cells to SARS-CoV-2 infection.
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http://dx.doi.org/10.1186/s13000-021-01082-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8097675PMC
May 2021

Biomimetic camouflage delivery strategies for cancer therapy.

Nanoscale 2021 May 4. Epub 2021 May 4.

State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, 501 Haike Road, Shanghai 201203, China. and Zhongshan Institute for Drug Discovery, Institutes of Drug Discovery and Development, Chinese Academy of Sciences, Zhongshan 528437, China and NMPA Key Laboratory for Quality Research and Evaluation of Pharmaceutical Excipients, Shanghai 201203, China.

Cancer remains a significant challenge despite the progress in developing different therapeutic approaches. Nanomedicine has been explored as a promising novel cancer therapy. Recently, biomimetic camouflage strategies have been investigated to change the bio-fate of therapeutics and target cancer cells while reducing the unwanted exposure on normal tissues. Endogenous components (e.g., proteins, polysaccharides, and cell membranes) have been used to develop anticancer drug delivery systems. These biomimetic systems can overcome biological barriers and enhance tumor cell-specific uptake. The tumor-targeting mechanisms include ligand-receptor interactions and stimuli-responsive (e.g., pH-sensitive and light-sensitive) delivery. Drug delivery carriers composed of endogenous components represent a promising approach for improving cancer treatment efficacy. In this paper, different biomimetic drug delivery strategies for cancer treatment are reviewed with a focus on the discussion of their advantages and potential applications.
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http://dx.doi.org/10.1039/d1nr01127hDOI Listing
May 2021

Pterostilbene nanoparticles with small particle size show excellent anti-breast cancer activity in vitro and in vivo.

Nanotechnology 2021 May 4. Epub 2021 May 4.

Chinese Academy of Medical Sciences and Peking Union Medical College Institute of Medicinal Plant Development, Beijing, CHINA.

Pterostilbene (PTE) is known as resveratrol of the next generation and it has attracted extensive attention in recent years. PTE can inhibit the growth of a variety of tumor cells. To overcome the problem of insolubility, PTE was loaded into nanoparticles (NPs) by anti-solvent precipitation technique using soybean lecithin (SPC) and D-α-tocopheryl polyethylene glycol succinate (TPGS) as stabilizers. The obtained PTE-NPs had an average particle size of 71.0 nm, a polydispersity index (PDI) value of 0.258, and a high zeta potential of -40.8 mV. PTE-NPs can maintain particle size stability in various physiological media. The entrapment efficiency of PTE-NPs was 98.24%. And the apparently water solubility of PTE-NPs was about 53 times higher than the solubility of PTE (54.41 μg/mL vs. 2.89 mg/mL). MTT assay showed that the antitumor activity of PTE-NPs on 4T1 breast cancer cells, MCF-7 breast cancer cells and Hela cervical cancer cells was significantly increased by 4, 6 and 8 times than that of free PTE, respectively. In vivo studies have shown that PTE-NPs has a certain dose dependence. When injected intraperitoneally, PTE-NPs showed a similar therapeutic effect as paclitaxel injection (TIR was 57.53% vs. 57.23%) against 4T1 tumor-bearing mice. This should be due to the improved bioavailability of the drug caused by nano-drug delivery system (nano-DDS). These results indicate that PTE-NPs may be a clinically promising anti-tumor drug for breast cancer treatment.
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http://dx.doi.org/10.1088/1361-6528/abfdecDOI Listing
May 2021

Germline IGHV3-53-encoded RBD-targeting neutralizing antibodies are commonly present in the antibody repertoires of COVID-19 patients.

Emerg Microbes Infect 2021 May 4:1-48. Epub 2021 May 4.

Bioland Laboratory, Guangdong Laboratory of Computational Biomedicine, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, China.

Monoclonal antibodies (mAbs) encoded by IGHV3-53 (VH3-53) targeting the spike receptor-binding domain (RBD) have been isolated from different COVID-19 patients. However, the existence and prevalence of shared VH3-53-encoded antibodies in the antibody repertoires is not clear. Using antibody repertoire sequencing, we found that the usage of VH3-53 increased after SARS-CoV-2 infection. A highly shared VH3-53-J6 clonotype was identified in 9 out of 13 COVID-19 patients. This clonotype was derived from convergent gene rearrangements with few somatic hypermutations and was evolutionary conserved. We synthesized 34 repertoire-deduced novel VH3-53-J6 heavy chains and paired with a common IGKV1-9 light chain to produce recombinant mAbs. Most of these recombinant mAbs (23/34) possess RBD binding and virus neutralizing activities, and recognize ACE2 binding site via the same molecular interface. Our computational analysis, validated by laboratory experiments, revealed that VH3-53 antibodies targeting RBD are commonly present in COVID-19 patients' antibody repertoires, indicating many people have germline-like precursor sequences to rapidly generate SARS-CoV-2 neutralizing antibodies. Moreover, antigen-specific mAbs can be digitally obtained through antibody repertoire sequencing and computational analysis.
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http://dx.doi.org/10.1080/22221751.2021.1925594DOI Listing
May 2021

Germline IGHV3-53-encoded RBD-targeting neutralizing antibodies are commonly present in the antibody repertoires of COVID-19 patients.

Emerg Microbes Infect 2021 May 4:1-48. Epub 2021 May 4.

Bioland Laboratory, Guangdong Laboratory of Computational Biomedicine, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, China.

Monoclonal antibodies (mAbs) encoded by IGHV3-53 (VH3-53) targeting the spike receptor-binding domain (RBD) have been isolated from different COVID-19 patients. However, the existence and prevalence of shared VH3-53-encoded antibodies in the antibody repertoires is not clear. Using antibody repertoire sequencing, we found that the usage of VH3-53 increased after SARS-CoV-2 infection. A highly shared VH3-53-J6 clonotype was identified in 9 out of 13 COVID-19 patients. This clonotype was derived from convergent gene rearrangements with few somatic hypermutations and was evolutionary conserved. We synthesized 34 repertoire-deduced novel VH3-53-J6 heavy chains and paired with a common IGKV1-9 light chain to produce recombinant mAbs. Most of these recombinant mAbs (23/34) possess RBD binding and virus neutralizing activities, and recognize ACE2 binding site via the same molecular interface. Our computational analysis, validated by laboratory experiments, revealed that VH3-53 antibodies targeting RBD are commonly present in COVID-19 patients' antibody repertoires, indicating many people have germline-like precursor sequences to rapidly generate SARS-CoV-2 neutralizing antibodies. Moreover, antigen-specific mAbs can be digitally obtained through antibody repertoire sequencing and computational analysis.
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http://dx.doi.org/10.1080/22221751.2021.1925594DOI Listing
May 2021

Role of endogenous melatonin in pathophysiologic and oxidative stress responses to personal air pollutant exposures in asthmatic children.

Sci Total Environ 2021 Jun 6;773:145709. Epub 2021 Feb 6.

Nicholas School of the Environment, Duke University, Durham, NC, USA; Duke Global Health Institute, Duke University, Durham, NC, USA; Duke Kunshan University, Kunshan, Jiangsu Province, China. Electronic address:

Background: Heightening oxidative stress and inflammation is an important pathophysiological mechanism underlying air pollution health effects in people with asthma. Melatonin can suppress oxidative stress and inflammation in pulmonary and circulatory systems. However, the role of melatonin in the oxidative stress and physiological responses to air pollution exposure has not been examined in children with asthma.

Methods: In this panel study of 43 asthmatic children (5-13 years old), each child had 4 clinic visits with a 2-week interval between two consecutive visits. At each visit, urine samples were collected and subsequently analyzed for 6-sulfatoxymelatonin (aMT6s) as a surrogate of circulating melatonin and for malondialdehyde (MDA) and 8-hydroxy-2'-deoxyguanosine (8-OHdG) as two biomarkers of systemic oxidative stress. At each clinic visit, children were measured for pulmonary function and fractional exhaled nitric oxide (FeNO, a marker of pulmonary inflammation). None of the children reported to have taking melatonin supplementation. Concentrations of indoor and ambient PM and ozone (O) were combined with individual time-activity data to calculate personal air pollutant exposures.

Results: We found that interquartile range increases in urinary MDA and 8-OHdG concentrations were associated with significantly increased urinary aMT6s concentrations by 73.4% (95% CI: 52.6% to 97.0%) and 41.7% (22.8% to 63.4%), respectively. Increases in daily personal exposure to O and to PM were each associated with increased urinary aMT6s concentrations. Increasing urinary aMT6s concentrations were associated with decreased FeNO and resonant frequency, indicating improved airway inflammation and lung elasticity, respectively.

Conclusion: The results suggest that systemic oxidative stress heightened by air pollution exposure may stimulate melatonin excretion as a defense mechanism to alleviate the adverse effects.
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http://dx.doi.org/10.1016/j.scitotenv.2021.145709DOI Listing
June 2021

Analysis of pathogens and risk factors of secondary pulmonary infection in patients with COVID-19.

Microb Pathog 2021 May 1;156:104903. Epub 2021 May 1.

Department of Respiratory and Critical Care Medicine, Shanghai Public Health Clinical Center, Fudan University, Shanghai, China. Electronic address:

To investigate the distribution and risk factors of pathogens in secondary pulmonary infection in patients with COVID-19.142 patients with confirmed COVID-19 from Shanghai Public Health Clinical Center were collected, and 32 patients with pulmonary infection were taken as the infection group. The distribution of pathogens in the sputum specimens was applied for retrospective analysis. Meanwhile, 110 patients diagnosed with COVID-19, but without pulmonary infection were regarded as the asymptomatic group. The risk factors of pulmonary infection were analyzed with generalized linear models and logistic regression. The pathogens in the lung infection group were mainly gram-negative bacteria (22, 68.8%), especially Klebsiella pneumoniae. Gram-positive bacteria and fungi accounted for 13 (40.6%), mainly Staphylococcus aureus, and 11 (34.4%), mainly Candida albicans. There were 14 cases (43.8%) infected with two or more pathogens. The comparison between the two groups found that, patients with elder age, underlying diseases, more lung lesions and low protein contents, were more likely to develop lung infections. At last, univariate analysis showed that 6 factors, including indwelling gastric catheter, the number of deep vein catheters, tracheal intubation tracheotomy, invasive mechanical ventilation, hormonal application, and the use of more than three antibacterial drugs, are risk factors for COVID-19 secondary pulmonary infection. Generalized linear models and logistic regression analysis showed antimicrobial use as an independent risk factor for COVID-19 secondary lung infection. There are many risk factors for secondary lung infection in severe COVID-19 patients, and it is recommended to use antibiotics reasonably.
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http://dx.doi.org/10.1016/j.micpath.2021.104903DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8087576PMC
May 2021

Novel Biomarkers of Dynamic Blood PD-L1 Expression for Immune Checkpoint Inhibitors in Advanced Non-Small-Cell Lung Cancer Patients.

Front Immunol 2021 16;12:665133. Epub 2021 Apr 16.

Cancer Institute, Xinqiao Hospital, Army Medical University, Chongqing, China.

Background: Immune checkpoint inhibitors (ICIs) have become a high-profile regimen for malignancy recently. However, only a small subpopulation obtains long-term clinical benefit. How to select optimal patients by reasonable biomarkers remains a hot topic.

Methods: Paired tissue samples and blood samples from 51 patients with advanced malignancies were collected for correlation analysis. Dynamic changes in blood PD-L1 (bPD-L1) expression, including PD-L1 mRNA, exosomal PD-L1 (exoPD-L1) protein and soluble PD-L1 (sPD-L1), were detected after 2 months of ICIs treatment in advanced non-small-cell lung cancer (NSCLC) patients. The best cutoff values for progression-free survival (PFS) and overall survival (OS) of all three biomarkers were calculated with R software.

Results: In 51 cases of various malignancies, those with positive tissue PD-L1 (tPD-L1) had significantly higher PD-L1 mRNA than those with negative tPD-L1. In 40 advanced NSCLC patients, those with a fold change of PD-L1 mRNA ≥ 2.04 had better PFS, OS and best objective response (bOR) rate. In addition, a fold change of exoPD-L1 ≥ 1.86 was also found to be associated with better efficacy and OS in a cohort of 21 advanced NSCLC cases. The dynamic change of sPD-L1 was not associated with efficacy and OS. Furthermore, the combination of PD-L1 mRNA and exoPD-L1 could screen better patients for potential benefit from ICIs treatment.

Conclusion: There was a positive correlation between bPD-L1 and tPD-L1 expression. Increased expression of PD-L1 mRNA, exoPD-L1, or both in early stage of ICIs treatment could serve as positive biomarkers of efficacy and OS in advanced NSCLC patients.
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http://dx.doi.org/10.3389/fimmu.2021.665133DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8085403PMC
April 2021

Patenting antibody combination therapies.

Antib Ther 2020 Dec 3;3(4):265-270. Epub 2020 Dec 3.

Finnegan, Henderson, Farabow, Garrett & Dunner LLP., 901 New York Avenue, NW, Washington, DC 20001-4413, USA.

There is emerging, intense interest in antibody combination therapies. However, antibody combination therapies pose unique intellectual property challenges. In some instances, it may be difficult to obtain patents with claims that provide innovators with adequate protection for such inventions. Patent examiners often regard claims to a composition or use of an antibody in combination with another therapeutic agent as obvious if the individual components of the combination were both known and well-studied in the field for use in treating similar indications. Nevertheless, even if the individual components of a combination were known and generally effective, the combination therapy may not be obvious if there would not have been a motivation to specifically combine the individual components or if there was no reasonable expectation of success in combining the components. Antibody combination therapies may also offer fertile grounds for demonstrating objective evidence of nonobviousness for a particular combination, such as through unexpected results, if a sufficient nexus can be established across the scope of the claims and if the superior results constitute a significant improvement.
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http://dx.doi.org/10.1093/abt/tbaa026DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7990264PMC
December 2020

The facile synthesis of a CoO-NiNP composite as an electrochemical non-enzymatic sensing platform for small chemical molecules.

Anal Methods 2021 Apr 29. Epub 2021 Apr 29.

College of Chemistry, Nanchang University, Nanchang 330031, China.

In this paper, a new Co3O4-Ni nanocomposite-modified glassy carbon electrode (Co3O4-NiNPs/GCE) was successfully constructed and used to detect glucose and hydrogen peroxide (H2O2). The morphologies and structures of the Co3O4 and Co3O4-Ni nanocomposites were characterized via transmission electron microscopy (TEM), scanning electron microscopy (SEM), and X-ray diffraction (XRD). The construction process of the modified electrode was characterized via electrochemical impedance spectroscopy (EIS) and cyclic voltammetry (CV) techniques. Co3O4-NiNPs/GCE shows more excellent electrocatalytic activity for the detection of glucose and H2O2 compared with Co3O4/GCE and NiNPs/GCE. The amperometric i-t method was used for the quantitative analysis of glucose and H2O2. The plots of current difference versus concentration of glucose and H2O2 were linear in the range of 0.3-550 μM and 0.5-89 μM, respectively. The corresponding limits of detection (LODs) were 0.086 μM and 0.23 μM for glucose and H2O2, respectively. This recommended sensor was successfully applied for the quantitative analysis of glucose in fruit and H2O2 in water samples.
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http://dx.doi.org/10.1039/d1ay00495fDOI Listing
April 2021

A Live-attenuated Zika Virus Vaccine with High Production Capacity Confers Effective Protection in Neonatal Mice.

J Virol 2021 Apr 28. Epub 2021 Apr 28.

State Key Laboratories of Respiratory Diseases, Guangdong-Hong Kong-Macao Joint Laboratory of Infectious Respiratory Disease, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, China.

Zika virus (ZIKV) infection during pregnancy has been linked to congenital abnormalities such as microcephaly in infants. An efficacious vaccine is still desirable for preventing the potential recurrence of ZIKV epidemic. Here, we report the generation of an attenuated ZIKV (rGZ02a) that has sharply decreased virulence in mice but grows to high titers in Vero cells, a widely approved cell line for manufacturing human vaccines. Compared to the wild-type ZIKV (GZ02) and a plasmid-launched rGZ02p, rGZ02a has 3 unique amino acid alterations in the envelope (E, S304F), non-structural protein 1 (NS1, R103K), and NS5 (W637R). rGZ02a is more sensitive to type I interferon than GZ02 and rGZ02p, and causes no severe neurological disorders in either wild-type neonatal C57BL/6 mice or type I interferon receptor knock-out ( ) C57BL/6 mice. Immunization with rGZ02a elicits robust inhibitory antibody responses with a certain long-term durability. Neonates born to the immunized dams are effectively protected against ZIKV-caused neurological disorders and brain damage. rGZ02a as a booster vaccine greatly improves the protective immunity primed by Ad2-prME, an adenovirus vectored vaccine expressing ZIKV prM and E proteins. Our results illustrate that rGZ02a-induced maternal immunity can be transferred to the neonates and confer effective protection. Hence, rGZ02a may be developed as an alternative live-attenuated vaccine and warrants a further evaluation.Zika virus (ZIKV), a mosquito-borne flavivirus that has caused global outbreaks since 2013, is associated with severe neurological disorders such as Guillian-Barré syndrome in adults and microcephaly in infants. The ZIKV epidemic has gradually subsided, but a safe and effective vaccine is still desirable to prevent its potential recurrence, especially in endemic countries with competent mosquito vectors. Here, we describe a novel live-attenuated ZIKV, rGZ02a, that carries 3 unique amino acid alterations compared to the wild-type GZ02 and a plasmid-launched rGZ02p. The growth capacity of rGZ02a is comparable to GZ02 in Vero cells, but the pathogenicity is significantly attenuated in two mice models. Immunization with rGZ02a elicits robust inhibitory antibody responses in the dams and effectively protects their offspring against ZIKV disease. Importantly, in a heterologous prime-boost regimen, rGZ02a effectively boosts the protective immunity primed by an adenovirus vectored vaccine. Thus, rGZ02a is a promising candidate for live-attenuated ZIKV vaccine.
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http://dx.doi.org/10.1128/JVI.00383-21DOI Listing
April 2021

An organophotoredox-catalyzed C(sp)-N cross coupling reaction of cyclic aldimines with cyclic aliphatic amines.

Org Biomol Chem 2021 Apr;19(16):3595-3600

College of Chemistry, Zhengzhou University, Zhengzhou, Henan 450052, China. and Henan Key Laboratory of Biomolecular Recognition and Sensing, College of Chemistry and Chemical Engineering, Shangqiu Normal University, Shangqiu, Henan 476000, China.

An organophotocatalyzed C(sp2)-H/N-H cross-dehydrogenative coupling of cyclic aldimines with aliphatic amines has been developed, which represents the first example of visible-light-induced C-H amination of N-sulfonylated imines. This methodology enables the streamline assembly of amine derivatives via radical mediated C-N bond formation. The current protocol features transition-metal-free, mild conditions, good functional group tolerance and good yields.
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http://dx.doi.org/10.1039/d1ob00223fDOI Listing
April 2021

Genomic population structure of Shanghai isolates and identification of genomic features uniquely linked with pathogenicity.

Virulence 2021 Dec;12(1):1258-1270

Department of Laboratory Medicine, Research Center on Aging and Medicine, Fudan University, Shanghai, China.

Severe -linked gastric disorders are especially prevalent in the East Asia region. The ability of to cause different clinical outcomes is thought to be associated with unique sets of its genetic features. However, only few genetic features have been definitively linked to specific gastrointestinal pathologies. Genome heterogeneity of clinical strains from patients with four different gastric disorders was studied to explore the population structure and molecular genomic features and their association with pathogenicity. Population analysis showed that 92.9% of the Shanghai isolates were clustered in the East Asia group. Among 2,866 genes detected in all genomes, 1,146 genes formed the core genome, whereas 209 unique genes were detected in individual disease groups. The unique genes of peptic ulcer and gastric cancer groups represented the inorganic ion transport and metabolism function gene clusters. Sixteen virulence genes were detected with statistically different detection rates among the four disease groups. Furthermore, 127 clustered regularly interspaced short palindromic repeats were found with significantly different rates in the four disease groups. A total of 337 putative genomic islands were identified, and three genomic islands were individually found in more than 10% of strains. The genomic islands included several metabolism-associated genes and many genes with unknown function. In total, 88 sequence types were detected among the 112 Shanghai isolates. Our study provides an essential milestone in the mapping of specific genomic features and their functions to identify factors needed to induce specific gastric disorders in
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http://dx.doi.org/10.1080/21505594.2021.1920762DOI Listing
December 2021

2D Metal-Organic Framework-Based Thin-Film Nanocomposite Membranes for Reverse Osmosis and Organic Solvent Nanofiltration.

ChemSusChem 2021 Apr 25. Epub 2021 Apr 25.

Department of Chemical and Biomolecular Engineering, National University of Singapore, 4 Engineering Drive 4, Singapore, 117585, Singapore.

Metal-organic frameworks (MOFs) are promising candidates for membrane-based liquid separations due to their intrinsic microporosity, but many are limited by their insufficient stability. In this work, a copper-benzoquinoid (Cu-THQ) MOF was synthesized and demonstrated structural stability in water and organic solvents. After incorporation into the polyamide layer, the hydrophilicity of the membranes was enhanced. The resultant thin-film nanocomposite (TFN) membranes broke the permeability-selectivity tradeoff by showing 242 % increase in water permeance and slightly enhanced salt rejection at MOF loading of 0.0192 mg cm . The underlying mechanism was probed by different chemical and morphological characterizations. The membranes also showed improved tolerance to chlorine oxidation. With their excellent stability, the Cu-THQ MOF-based membranes further demonstrated impressive performance in organic solvent nanofiltration involving dimethylformamide.
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http://dx.doi.org/10.1002/cssc.202100335DOI Listing
April 2021

2D Metal-Organic Framework-Based Thin-Film Nanocomposite Membranes for Reverse Osmosis and Organic Solvent Nanofiltration.

ChemSusChem 2021 Apr 25. Epub 2021 Apr 25.

Department of Chemical and Biomolecular Engineering, National University of Singapore, 4 Engineering Drive 4, Singapore, 117585, Singapore.

Metal-organic frameworks (MOFs) are promising candidates for membrane-based liquid separations due to their intrinsic microporosity, but many are limited by their insufficient stability. In this work, a copper-benzoquinoid (Cu-THQ) MOF was synthesized and demonstrated structural stability in water and organic solvents. After incorporation into the polyamide layer, the hydrophilicity of the membranes was enhanced. The resultant thin-film nanocomposite (TFN) membranes broke the permeability-selectivity tradeoff by showing 242 % increase in water permeance and slightly enhanced salt rejection at MOF loading of 0.0192 mg cm . The underlying mechanism was probed by different chemical and morphological characterizations. The membranes also showed improved tolerance to chlorine oxidation. With their excellent stability, the Cu-THQ MOF-based membranes further demonstrated impressive performance in organic solvent nanofiltration involving dimethylformamide.
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http://dx.doi.org/10.1002/cssc.202100335DOI Listing
April 2021

Impact of Subthalamic Deep Brain Stimulation on Hyposmia in Patients With Parkinson's Disease Is Influenced by Constipation and Dysbiosis of Microbiota.

Front Neurol 2021 6;12:653833. Epub 2021 Apr 6.

Department of Neurosurgery, Qilu Hospital of Shandong University, Jinan, China.

Non-motor symptoms in PD usually arise at very early stage and vary during the whole disease progression. Deep brain stimulation (DBS) is considered as a highly efficient treatment option for PD's motor function. However, the effect of DBS on NMS, especially hyposmia, has not been fully understood and the deep connection between different NMS such as hyposmia and constipation is still unknown. The objective of this study was to evaluate the therapeutic effect of DBS on hyposmia in PD patients with or without constipation and find potential factors which might influence the efficacy. A retrospective analysis of 65 PD patients accepted STN-DBS operation in Qilu Hospital during 2019-2020 were conducted to evaluate the exact therapeutic effect of DBS on hyposmia in PD. Sub-group analyses about the relationship between hyposmia and constipation were carried out. Analysis of flora in nasal mucosa was also conducted to evaluate the abundance and variety in different PD groups. Our study showed that DBS had clearly improved olfactory function in Parkinson patients ( = 0.012) and subgroup analysis found that PD patients with constipation have lower olfactory function scores (25.27 ± 3.44 vs. 33.90 ± 6.633, = 0.014) and worse improvement after DBS operation (ΔTDI 12.11 ± 3.2 vs. 8.78 ± 2.91, = 0.0072). Analysis of flora indicated the obvious discrepancy on olfactory function scores and degree of improvement might be related to the abundance and dysbiosis of microbiota. In summary, this article presents a study on PD with hyposmia and constipation after DBS operation, explored the relationship between different NMS and offer a potential explanation on why PD patients with constipation usually have worse olfactory function for the less abundance and variety of microbiota.
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http://dx.doi.org/10.3389/fneur.2021.653833DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8056012PMC
April 2021