Publications by authors named "Shuang Yang"

572 Publications

The interplay of protein engineering and glycoengineering to fine-tune antibody glycosylation and its impact on effector functions.

Biotechnol Bioeng 2021 Oct 13. Epub 2021 Oct 13.

Department of Chemical and Biomolecular Engineering, Johns Hopkins University, Baltimore, MD, 21218, USA.

The N-glycan pattern of an IgG antibody, attached at a conserved site within the Fc region, is a critical antibody quality attribute whose structural variability can also impact antibody function. For tailoring the Fc glycoprofile, glycoengineering in cell lines as well as Fc amino acid mutations have been applied. Multiple glycoengineered CHO cell lines were generated, including defucosylated (FUT8KO), α-2,6-sialylated (ST6KI) and defucosylated α-2,6-sialylated (FUT8KOST6KI), expressing either a wild-type anti-CD20 IgG (WT) or phenylalanine to alanine (F241A) mutant. MALDI-TOF MS characterization of antibody N-glycans revealed that the F241A mutation significantly increased galactosylation and sialylation content and glycan branching. Furthermore, overexpression of recombinant human α-2,6-sialyltransferase resulted in a predominance of α-2,6-sialylation rather than α-2,3-sialylation for both wild-type and heavily sialylated F241A antibody N-glycans. Interestingly, knocking out α-1,6-fucosyltransferase (FUT8KO), which removed core fucose, lowered the content of N-glycans with terminal Gal and increased levels of terminal GlcNAc and Man5 groups on WT antibody. Further complement-dependent cytotoxicity (CDC) analysis revealed that, regardless of the production cells, WT antibody samples have higher cytotoxic CDC activity with more exposed Gal residues compared to their individual F241A mutants. However, the FUT8KO WT antibody, with a large fraction of bi-GlcNAc structures (G0), displayed the lowest CDC activity of all WT antibody samples. Furthermore, for the F241A mutants, a higher CDC activity was observed for α-2,6- compared to α-2,3-sialylation. Antibody-dependent cellular cytotoxicity (ADCC) analysis revealed that the defucosylated WT and F241A mutants showed enhanced in vitro ADCC performance compared to their fucosylated counterparts, with the defucosylated WT antibodies displaying the highest overall ADCC activity, regardless of sialic acid substitution. Moreover, the FcγRIIIA receptor binding by antibodies did not always correspond directly with ADCC result. This study demonstrates that glycoengineering and protein engineering can both promote and inhibit antibody effector functions and represent practical approaches for varying glycan composition and functionalities during antibody development. This article is protected by copyright. All rights reserved.
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http://dx.doi.org/10.1002/bit.27953DOI Listing
October 2021

A Linkage-specific Sialic Acid Labeling Strategy Reveals Different Site-specific Glycosylation Patterns in SARS-CoV-2 Spike Protein Produced in CHO and HEK Cell Substrates.

Front Chem 2021 24;9:735558. Epub 2021 Sep 24.

Laboratory of Bacterial Polysaccharides, Division of Bacterial, Parasitic and Allergenic Products, Center for Biologics Evaluation and Research, Food and Drug Administration, Baltimore, MD, United States.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus utilizes the extensively glycosylated spike (S) protein protruding from the viral envelope to bind to angiotensin-converting enzyme-related carboxypeptidase (ACE2) as its primary receptor to mediate host-cell entry. Currently, the main recombinant S protein production hosts are Chinese hamster ovary (CHO) and human embryonic kidney (HEK) cells. In this study, a recombinant S protein truncated at the transmembrane domain and engineered to express a C-terminal trimerization motif was transiently produced in CHO and HEK cell suspensions. To further evaluate the sialic acid linkages presenting on S protein, a two-step amidation process, employing dimethylamine and ammonium hydroxide reactions in a solid support system, was developed to differentially modify the sialic acid linkages on the glycans and glycopeptides from the S protein. The process also adds a charge to Asp and Glu which aids in ionization. We used MALDI-TOF and LC-MS/MS with electron-transfer/higher-energy collision dissociation (EThcD) fragmentation to determine global and site-specific N-linked glycosylation patterns. We identified 21 and 19 out of the 22 predicted N-glycosites of the SARS-CoV-2 S proteins produced in CHO and HEK, respectively. It was found that the N-glycosite at 1,158 position (N1158) and at 122, 282 and 1,158 positions (N122, N282 and N1158) were absent on S from CHO and HEK cells, respectively. The structural mapping of glycans of recombinant human S proteins reveals that CHO-Spike exhibits more complex and higher sialylation (α2,3-linked) content while HEK-Spike exhibits more high-mannose and a small amount of α2,3- and α2,6-linked sialic acids. The N74 site represents the most abundant glycosite on both spike proteins. The relatively higher amount of high-mannose abundant sites (N17, N234, N343, N616, N709, N717, N801, and N1134) on HEK-Spike suggests that glycan-shielding may differ among the two constructs. HEK-Spike can also provide different host immune system interaction profiles based on known immune system active lectins. Collectively, these data underscore the importance of characterizing the site-specific glycosylation of recombinant human spike proteins from HEK and CHO cells in order to better understand the impact of the production host on this complex and important protein used in research, diagnostics and vaccines.
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http://dx.doi.org/10.3389/fchem.2021.735558DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8497748PMC
September 2021

ZmCTLP1 is required for the maintenance of lipid homeostasis and the basal endosperm transfer layer in maize kernels.

New Phytol 2021 Sep 24. Epub 2021 Sep 24.

State Key Laboratory of Plant Physiology and Biochemistry and National Maize Improvement Center, Department of Plant Genetics and Breeding, China Agricultural University, Beijing, 100193, China.

Maize kernel weight is influenced by the unloading of nutrients from the maternal placenta and their passage through the transfer tissue of the basal endosperm transfer layer (BETL) and the basal intermediate zone (BIZ) to the upper part of the endosperm. Here, we show that Small kernel 10 (Smk10) encodes a choline transporter-like protein 1 (ZmCTLP1) that facilitates choline uptake and is located in the trans-Golgi network (TGN). Its loss of function results in reduced choline content, leading to smaller kernels with a lower starch content. Mutation of ZmCTLP1 disrupts membrane lipid homeostasis and the normal development of wall in-growths. Expression levels of Mn1 and ZmSWEET4c, two kernel filling-related genes, are downregulated in the smk10, which is likely to be one of the major causes of incompletely differentiated transfer cells. Mutation of ZmCTLP1 also reduces the number of plasmodesmata (PD) in transfer cells, indicating that the smk10 mutant is impaired in PD formation. Intriguingly, we also observed premature cell death in the BETL and BIZ of the smk10 mutant. Together, our results suggest that ZmCTLP1-mediated choline transport affects kernel development, highlighting its important role in lipid homeostasis, wall in-growth formation and PD development in transfer cells.
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http://dx.doi.org/10.1111/nph.17754DOI Listing
September 2021

Stoichiometry of Carbon, Nitrogen and Phosphorus in Shrub Organs Linked Closely With Mycorrhizal Strategy in Northern China.

Front Plant Sci 2021 7;12:687347. Epub 2021 Sep 7.

College of Agriculture, Henan University of Science and Technology, Luoyang, China.

Mycorrhizal strategies include mycorrhizal statuses and mycorrhizal types, which are important reflections of the functional characteristics of ecosystems. The stoichiometry of carbon, nitrogen, and phosphorus in plant organs is an important part of ecosystem functions, which has an important impact on the nutrient cycle of the ecosystem. The concentration of carbon, nitrogen, and phosphorus played a crucial role in ecosystem functioning and dynamics. The purpose of this study is to provide theoretical basis and data support for improving the properties of global terrestrial ecosystems by exploring the impact of mycorrhizal strategies on the stoichiometry of C, N, and P in different shrub organs. In this study, stoichiometric patterns of carbon (C), nitrogen (N) and phosphorus (P) in different shrub organs under different mycorrhizal status or types were analyzed at 725 samples across Northern China. Results showed that in different mycorrhizal status, the highest carbon concentration in shrub organs appeared in the facultatively mycorrhizal (FM) mycorrhizal status, and the highest nitrogen concentration appeared in the Non-mycorrhizal (NM) mycorrhizal status. Under different mycorrhizal types, the nitrogen concentration in the shrub organs under the arbuscular mycorrhiza (AM) mycorrhizal type was the highest, and the phosphorus concentration under the ecto-mycorrhiza (ECM) mycorrhizal type was the highest. In the OM or FM mycorrhizal status, the concentrations of C, N, and P in the stems and leaves increase with the increase of the concentrations of C, N, and P in the roots. In the NM mycorrhizal status, the N concentration in the stems and leaves increases with the increase of the N concentration in the roots. Under AM, AM+ECM, and ECM mycorrhizal type, the concentrations of C, N, and P are closely related in roots, stems and leaves. The content of plant nutrients in different organs is closely related. It turned out that mycorrhizal statuses or types are able to alter the allocation of C, N, and P in different organs, and the relationships of C, N, and P among different organs are able to present different trend with the varying of mycorrhizal statuses or types.
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http://dx.doi.org/10.3389/fpls.2021.687347DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8453024PMC
September 2021

Capecitabine Can Induce T Cell Apoptosis: A Potential Immunosuppressive Agent With Anti-Cancer Effect.

Front Immunol 2021 7;12:737849. Epub 2021 Sep 7.

Organ Transplant Department, Tianjin First Central Hospital, School of Medicine, Nankai University, Tianjin, China.

Capecitabine (CAP) is now widely used in the comprehensive treatment of digestive system tumors. Some clinical observations have shown that CAP may have immunosuppressive effects, but there is still a lack of clear experimental verification. In this study, different doses of CAP were administered to normal mice by gavage. Our results confirmed that CAP did not cause myelosuppression in bone marrow tissue; CAP selectively reduced the proportion of T cells and the concentration of related pro-inflammatory cytokines, while it increased the concentration of anti-inflammatory cytokines. Thymidylate phosphorylase (TP) is the key enzyme for the transformation of CAP ; this study confirmed that T cells express TP, but the bone marrow tissue lacks TP expression, which explains the selectivity in pharmacodynamic effects of CAP. In addition, it was confirmed that CAP can induce T cell apoptosis and experiments showed that CAP-induced T cell apoptosis was related to TP expression, endoplasmic reticulum stress (ERS) induction, reactive oxygen species (ROS) production, and mitochondria-mediated apoptosis activation. Therefore, this study confirmed that the differential expression of TP in cells and tissues explains why CAP avoids the toxic effects of myelosuppression while inducing T cell apoptosis to exert the immunosuppressive effect. Therefore, CAP may become an immunosuppressive agent with a simultaneous anti-cancer effect, which is worthy of further studies.
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http://dx.doi.org/10.3389/fimmu.2021.737849DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8452994PMC
September 2021

Multifunctional Ca-Zn-Si-based micro-nano spheres with anti-infective, anti-inflammatory, and dentin regenerative properties for pulp capping application.

J Mater Chem B 2021 Oct 13;9(39):8289-8299. Epub 2021 Oct 13.

Affiliated Stomatology Hospital of Guangzhou Medical University, Guangzhou Key Laboratory of Basic and Applied Research of Oral Regenerative Medicine, Guangzhou, Guangdong 510182, China.

While pulp capping using a variety of materials has been applied clinically to preserve the health and vitality of the dental pulp and induce dentin repair no material meets all the anti-infection, anti-inflammation, and promoting pulp tissue regeneration criteria. Micro-nano materials of bioactive glasses (BG) with the biocompatibility and osteogenesis-promoting properties were developed for this study using Zn-doped bioactive glass (BGz) micro-nano spheres for dental pulp capping to control infection and inflammation and promote tissue regeneration. Of three key findings, the co-culture of showed that the BGz had an excellent antibacterial effect, and after being stimulated with BGz , macrophages showed a significant decrease of pro-inflammatory M1 markers compared with the undoped BG group. It is also noted that the conditioned medium derived from BGz-stimulated macrophages could significantly promote mineralized dentin formation of dental pulp cells (DPCs). In rats, acute pulp restoration experiments proved that BGz used as a pulp capping agent had excellent dentin regenerative properties. This work may provide a novel strategy to promote osteo/dentinogenic differentiation through regulating early inflammation, with potential applications in pulp capping.
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http://dx.doi.org/10.1039/d1tb01517fDOI Listing
October 2021

Expression and significance of miR-30d-5p and SOCS1 in patients with recurrent implantation failure during implantation window.

Reprod Biol Endocrinol 2021 Sep 8;19(1):138. Epub 2021 Sep 8.

Reproductive Medical Center, Department of Obstetrics and Gynecology, Xiangya Hospital, Central South University, Changsha, 410008, Hunan, China.

Background: Poor endometrial receptivity is a major factor that leads to recurrent implantation failure. However, the traditional method cannot accurately evaluate endometrial receptivity. Various studies have indicated that microRNAs (miRNAs) are involved in multiple processes of embryo implantation, but the role of miRNAs in endometrial receptivity in patients with recurrent implantation failure (RIF) remains elusive. In the present study, we investigated the presence of pinopodes and the roles of miR-30d-5p, suppressor of cytokine signalling 1 (SOCS1) and the leukaemia inhibitory factor (LIF) pathway in women with a history of RIF during the implantation window.

Methods: Endometrial tissue samples were collected between January 2018 to June 2019 from two groups of women who underwent in vitro fertilisation and embryo transfer (IVF-ET) or frozen ET. The RIF group included 20 women who underwent ≥ 3 ETs, including a total of ≥ 4 good-quality embryos, without pregnancy, whereas the control group included 10 women who had given birth at least once in the past year. An endometrial biopsy was performed during the implantation window (LH + 7). The development of pinopodes in the endometrial biopsy samples from all groups was evaluated using scanning electron microscopy (SEM). Quantitative reverse transcription-polymerase chain reaction and western blotting were used to investigate the expression levels of miR-30d-5p, SOCS1, and the LIF pathway.

Results: The presence of developed pinopodes decreased in patients with RIF on LH + 7. The expression level of miR-30d-5p decreased in the endometria during the implantation window of patients with RIF, whereas the mRNA and protein levels of SOCS1 were significantly higher in the RIF group than in the control group. Furthermore, a negative correlation was observed between the expression of miR-30d-5p and SOCS1 (r = 0.8362). In addition, a significant decrease in LIF and p-STAT3 expression was observed during the implantation window in patients with RIF.

Conclusions: MiR-30d-5p and SOCS1 may be potential biomarkers for endometrial receptivity. Changes in pinopode development and abnormal expression of miR-30d-5p, SOCS1 and LIF pathway in the endometrium could be the reasons for implantation failure.
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http://dx.doi.org/10.1186/s12958-021-00820-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8425163PMC
September 2021

Synthesis, crystal structures, anticancer activities and molecular docking studies of novel thiazolidinone Cu(II) and Fe(III) complexes targeting lysosomes: special emphasis on their binding to DNA/BSA.

Dalton Trans 2021 Oct 5;50(38):13387-13398. Epub 2021 Oct 5.

College of Chemistry, Nankai University, Tianjin 300071, P. R. China.

Novel [CuLCl]Cl·HO (1) and [FeLCl]Cl·MeOH·CHCl·HO (2) complexes of ()-'-(()-3-methyl-4-oxothiazolidin-2-ylidene)picolinohydrazonamide (L) as antitumor agents were designed and synthesized in order to explore DNA and serum albumin interaction. X-ray diffraction revealed that both 1 and 2 were a triclinic crystal system with 1̄ space group, which consisted of a positive electric main unit, a negative chloride ion and some solvent molecules. The complexes with DNA and bovine serum albumin (BSA) were studied by fluorescence and electronic absorption spectrometry. The results indicated that there was moderate intercalative binding mode between the complexes and DNA with values of 2.40 × 10 M (1) and 6.49 × 10 M (2). Agarose gel electrophoresis experiment showed that both 1 and 2 exhibited obvious DNA cleavage activity an oxidative DNA damage pathway, and the cleavage activities of 1 were stronger than those of 2. Cytotoxicity assay showed that 1 had a more effective antitumor activity than 2. The two complexes were bound to BSA by a high affinity and quenched the fluorescence of BSA through a static mechanism. The thermodynamic parameters suggested that hydrophobic interactions played a key role in the binding process. The binding energy xpscore of 1 and 2 were -10.529 kcal mol and -10.826 kcal mol by docking studies, and this suggested that the binding process was spontaneous. Complex 1 displayed a lysosome-specific targeting behavior with a Pearson coefficient value of 0.82 by confocal laser scanning microscopy (CLSM), and accumulated in the lysosomes, followed by the disruption of lysosomal integrity.
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http://dx.doi.org/10.1039/d1dt02180jDOI Listing
October 2021

PHF6 and JAK3 mutations cooperate to drive T-cell acute lymphoblastic leukemia progression.

Leukemia 2021 Aug 31. Epub 2021 Aug 31.

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

T-cell acute lymphoblastic leukemia (T-ALL) is a malignant hematologic disease caused by gene mutations in T-cell progenitors. As an important epigenetic regulator, PHF6 mutations frequently coexist with JAK3 mutations in T-ALL patients. However, the role(s) of PHF6 mutations in JAK3-driven leukemia remain unclear. Here, the cooperation between JAK3 activation and PHF6 inactivation is examined in leukemia patients and in mice models. We found that the average survival time is shorter in patients with JAK/STAT and PHF6 comutation than that in other patients, suggesting a potential role of PHF6 in leukemia progression. We subsequently found that Phf6 deficiency promotes JAK3-induced T-ALL progression in mice by inhibiting the Bai1-Mdm2-P53 signaling pathway, which is independent of the JAK3/STAT5 signaling pathway. Furthermore, combination therapy with a JAK3 inhibitor (tofacitinib) and a MDM2 inhibitor (idasanutlin) reduces the Phf6 KO and JAK3 leukemia burden in vivo. Taken together, our study suggests that combined treatment with JAK3 and MDM2 inhibitors may potentially increase the drug benefit for T-ALL patients with PHF6 and JAK3 comutation.
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http://dx.doi.org/10.1038/s41375-021-01392-1DOI Listing
August 2021

Effects of Polysaccharides on Immunity and the Gut Microbiota in Cyclophosphamide-Induced Immunosuppressed Mice.

Front Microbiol 2021 6;12:701566. Epub 2021 Aug 6.

School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing, China.

The mechanism of immunoregulation by polysaccharides (LBPs) was assessed by studying the effect of LBP on the immunity and the gut microbiota. LBP isolated and purified in this study was composed of nine monosaccharides, with an w 1,207 kDa. LBP showed immunomodulatory activity in cyclophosphamide (Cy)-treated mice by restoring the damaged immune organs and adjusting the T lymphocyte subsets. We also found that LBP increased the diversity of the gut microbiota and the relative abundances of bacteria, such as , , , and so on, which were positively associated with immune traits. In addition, Caco2 cells model was used to explore the intestinal absorption of LBP. Results showed that LBP was hardly absorbed in the intestine, which suggesting that most LBP may interact with gut microbiota. These findings suggest that the immune response induced by LBP is associated with the regulation of the gut microbiota.
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http://dx.doi.org/10.3389/fmicb.2021.701566DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8377584PMC
August 2021

Design, synthesis and biological evaluation of sphingosine-1-phosphate receptor 2 antagonists as potent 5-FU-resistance reversal agents for the treatment of colorectal cancer.

Eur J Med Chem 2021 Aug 12;225:113775. Epub 2021 Aug 12.

Laboratory for Marine Drugs and Bioproducts of Qingdao National Laboratory for Marine Science and Technology, Key Laboratory of Marine Drugs, Ministry of Education, School of Medicine and Pharmacy, Ocean University of China, Qingdao, 266003, China. Electronic address:

5-Fluorouracil (5-FU) and its prodrugs are the essential clinical drugs for colorectal cancer (CRC) treatment. However, the drug resistance of 5-FU has caused high mortality of CRC patients. Thus, it is urgent to develop reversal agents of 5-FU resistance. Sphingosine-1-phosphate receptor 2 (S1PR2) was proved to be a potential target for reversing 5-FU resistance, but the activity of known S1PR2 antagonists JTE-013 were weak in 5-FU-resistant cell lines. To develop more potent S1PR2 antagonists to treat 5-FU-resistant cancer, a series of JTE-013 derivatives were designed and synthesized. The most promising compound 40 could markedly reverse the resistance in 5-FU-resistant HCT116 cells and 5-FU-resistant SW620 cells via inhibiting the expression of dihydropyrimidine dehydrogenase (DPD). The key was that compound 40 with improved pharmacokinetic properties significantly increased the inhibitory rate of 5-FU in the SW620/5-FU cells xenograft model with no observable toxicity by inhibiting the expression of DPD in tumor and liver tissues. Altogether, these results suggest that compound 40 may be a promising drug candidate to reverse 5-FU resistance in the treatment of CRC.
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http://dx.doi.org/10.1016/j.ejmech.2021.113775DOI Listing
August 2021

Mediating the Local Oxygen-Bridge Interactions of Oxysalt/Perovskite Interface for Defect Passivation of Perovskite Photovoltaics.

Nanomicro Lett 2021 Aug 17;13(1):177. Epub 2021 Aug 17.

Key Laboratory for Ultrafine Materials of Ministry of Education, Shanghai Engineering Research Center of Hierarchical Nanomaterials, School of Materials Science and Engineering, East China University of Science and Technology, Shanghai, 200237, People's Republic of China.

Passivation, as a classical surface treatment technique, has been widely accepted in start-of-the-art perovskite solar cells (PSCs) that can effectively modulate the electronic and chemical property of defective perovskite surface. The discovery of inorganic passivation compounds, such as oxysalts, has largely advanced the efficiency and lifetime of PSCs on account of its favorable electrical property and remarkable inherent stability, but a lack of deep understanding of how its local configuration affects the passivation effectiveness is a huge impediment for future interfacial molecular engineering. Here, we demonstrate the central-atom-dependent-passivation of oxysalt on perovskite surface, in which the central atoms of oxyacid anions dominate the interfacial oxygen-bridge strength. We revealed that the balance of local interactions between the central atoms of oxyacid anions (e.g., N, C, S, P, Si) and the metal cations on perovskite surface (e.g., Pb) generally determines the bond formation at oxysalt/perovskite interface, which can be understood by the bond order conservation principle. Silicate with less electronegative Si central atoms provides strong O-Pb motif and improved passivation effect, delivering a champion efficiency of 17.26% for CsPbIBr solar cells. Our strategy is also universally effective in improving the device performance of several commonly used perovskite compositions.
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http://dx.doi.org/10.1007/s40820-021-00683-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8371073PMC
August 2021

Preserved C-reactive protein responses to blood stream infections following tocilizumab treatment for COVID-19.

J Infect 2021 Aug 14. Epub 2021 Aug 14.

Department of Infection, Royal Free London NHS Trust, London, United Kingdom; Division of Infection & Immunity, University College London, United Kingdom. Electronic address:

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http://dx.doi.org/10.1016/j.jinf.2021.08.017DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8363426PMC
August 2021

Chinese herbal medicine for symptoms of depression and anxiety in chronic obstructive pulmonary disease: A systematic review and meta-analysis.

Complement Ther Clin Pract 2021 Aug 4;45:101470. Epub 2021 Aug 4.

Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, China; Department of Respiratory and Critical Medicine, Jiangsu Province Hospital of Chinese Medicine, Nanjing, China. Electronic address:

Objectives: To evaluate the efficacy and safety of Chinese herbal medicine (CHM) on symptoms of depression and anxiety complicated by chronic obstructive pulmonary disease (COPD).

Methods: Literature from 8 electronic medical databases were searched for meta-analysis using RevMan (version 5.3) and Stata (version 12.0) software. The GRADE Pro Guideline Development Tool and TSA Viewer (version.0.9.5.10 beta) were adopted to evaluate the certainty and conclusiveness of the evidence.

Results: 26 studies involving 2529 participants were identified. CHM demonstrated significant lower scores on the Hamilton Depression Rating Scale, Self-Rating Depression Scale, Hamilton Anxiety Rating Scale, and Self-Rating Anxiety Scale compared to the control group without CHM. Moreover, CHM showed favorable safety.

Conclusions: The evidence verified the efficacy and safety of CHM on relieving depression and anxiety in COPD. However, further large-scale and rigorously designed studies are urgently warranted to strengthen the evidence.
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http://dx.doi.org/10.1016/j.ctcp.2021.101470DOI Listing
August 2021

[Effect of Huangqi decoction on delaying renal cell apoptosis induced by C ion irradiation in rats and its mechanism].

Zhongguo Ying Yong Sheng Li Xue Za Zhi 2021 May;37(3):318-323

School of Basic Medicine of Gansu University of Traditional Chinese Medicine (TCM), Lanzhou 730000.

To investigate the molecular protective mechanisms of Huangqi decoction inhibiting the apoptosis of renal cells in the C radiation brain model rats. Fifty Wistar rats were randomly divided into five groups: normal control group, radiation alone model group, Huangqi decoction (high-dose, middle-dose and low-dose ) groups. The normal control group and the radiation alone group were treated with saline10 ml/(kg·d) by gavage, the Huangqi decoction treatment groups were treated with Huangqi decoction at the doses of 4.5, 9 and 18 g/(kg·d) by gavage respectively. After 7 d, except mice in normal control group, the brain of the rats in radiation alone model group, high-dose, middle-dose and low-dose Huangqi decoction group were radiated by 4 Gy C ion once. The rats were killed by the femoral artery after irradiation 7 d. The pathomorphism changes of renal tissue were observed by HE, the IL-6 level in serum was detected by ELISA, the gene expressions of Bcl-2, Bax and caspase-3 in renal tissue were assessed by RT-PCR, and the protein expressions of Bcl-2, Bax, caspase-3 and NF-κB in renal tissue were analyzed by immunehistochemical staining. Compared with normal control group, the body weight and kidney index were decreased significantly, the expression of Bcl-2 in renal tissue was decreased significantly, the serum content of IL-6 was increased obviously, and the expressions of Bax, caspase-3 and NF-κB in renal tissue were increased significantly in the radiation alone model group (<0.01). The mesangial cells proliferated obviously, interstitial vessels of renal tubules were dilated and congested obviously, the lumen of renal tubules was narrow and irregular in the radiation alone model group. As compared with the radiation alone model group, the body weight and the kidney index were increased obviously in high-dose Huangqi decoction group, the gene and protein expressions of Bcl-2 in renal tissue were increased significantly in Huangqi decoction intervention group(<0.05 or <0.01). whereas, the protein expressions of Bax and caspase-3 in renal tissue were decreased significantly in middle-dose and high-dose Huangqi decoction group, the serum content of IL-6 was decreased obviously, the gene expressions of Bax and caspase-3 in renal tissue were decreased significantly and the protein expression of NF-κB in renal tissue was decreased significantly in Huangqi decoction intervention group(<0.05 or <0.01). The proliferation of mesangial cells was improved and the contour of renal tubules was clear in high-dose huangqi decoction group. High-dose of huangqi decoction has protective effect on kidney in rats induced by C radiation brain, the mechanism may be related to the regulation of Bcl-2/NF-κB signal pathway.
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http://dx.doi.org/10.12047/j.cjap.6079.2021.023DOI Listing
May 2021

Trends in Total and Out-of-pocket Payments for Insulin Among Privately Insured U.S. Adults With Diabetes From 2005 to 2018.

Diabetes Care 2021 Aug 4. Epub 2021 Aug 4.

Division of Diabetes Translation, Centers for Disease Control and Prevention, Atlanta, GA

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http://dx.doi.org/10.2337/dc20-2529DOI Listing
August 2021

Surgical repair of subaortic stenosis resection: 10 years of single-center experience in 65 patients.

J Card Surg 2021 Oct 2;36(10):3593-3598. Epub 2021 Aug 2.

Department of Pediatric Cardiac Center, Beijing Anzhen Hospital, Capital Medical University, Beijing, China.

Background: Subaortic stenosis (SAS) was a rare congenital heart disease of left ventricular outflow tract (LVOT), ranging from "isolated" lesions to "tunnel" or "diffuse" lesions. We conducted a retrospective study to describe the characteristics of patients with different lesions and analyze the risk factors for reoperation.

Methods: In this study, we examined a single-center retrospective cohort of SAS patients undergoing resection from 2010 to 2019. Patients were classified as simple lesion group (n = 37) or complex lesion group (n = 28). Demographics, perioperative findings, and clinical data were analyzed.

Results: The surgical effect of the two groups was significantly lower than that before the operation (p < .05). The median age at operation was 6 (3-11.8) years. There was no operative mortality. In complex lesion group, cardiopulmonary bypass time (CPB time), aortic cross-clamping time (ACC time), mechanical ventilation time, and intensive care unit (ICU) stay time were longer. The median follow-up period was 2.8 years (range: 1-3.8), with two late death. Six patients (9.2%) required reoperation due to restenosis or severe aortic insufficiency. The freedom from reoperation rates at 5 years was 66.7% for simple lesion but only 52.3% for complex lesion (p = .036).

Conclusions: Although the lesions include many forms, SAS resection was still satisfactory. However, the reoperation after initial surgical treatment was not infrequent, especially in patients with complex lesion.
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http://dx.doi.org/10.1111/jocs.15886DOI Listing
October 2021

Differentially Expressed Circular Non-coding RNAs in Atherosclerotic Aortic Vessels and Their Potential Functions in Endothelial Injury.

Front Cardiovasc Med 2021 7;8:657544. Epub 2021 Jul 7.

Department of Pharmacology (State-Province Key Laboratories of Biomedicine-Pharmaceutics; Key Laboratory of Cardiovascular Medicine Research, Ministry of Education), College of Pharmacy, Harbin Medical University, Harbin, China.

Circular non-coding RNA (circRNA) has a variety of biological functions. However, the expression profile and potential effects of circRNA on atherosclerosis (AS) and vascular endothelial injury have not been fully elucidated. This study aims to identify the differentially expressed circRNAs in atherosclerotic aortic vessels and predict their potential functions in endothelial injury. ApoE-/- mice were fed with high-fat diet for 12 weeks to induce AS. Atherosclerotic plaques were evaluated by H&E and Masson staining and immunohistochemistry; differentially expressed circRNAs were detected by Arraystar Circular RNA Microarray and verified by RT-PCR; the potential target mircoRNAs of circRNAs were predicted by miRanda, Tarbase, Targetscan and their expression changes were verified by RT-PCR; the potential target genes of mircoRNAs were predicted by Targetscan and verified by Western blot; the signaling pathways that they might annotate or regulate and their potential functions in vascular endothelial injury were predicted by gene enrichment analysis. Fifty two circRNAs were up-regulated more than twice and 47 circRNAs were down-regulated more than 1.5 times in AS aortic vessels. Mmmu_circRNA_36781 and 37699 were up-regulated both in AS aortic vessels and HO-treated mouse aortic endothelial cells (MAECs). The expression of miR-30d-3p and miR-140-3p, the target microRNA of circRNA_37699 and circRNA_36781, were downregulated both in AS vessels and HO-treated MAECs. On the contrary, MKK6 and TP53RK, the potential target gene of miR-140-3p and miR-30d-3p, were upregulated both in AS aortic roots and HO-treated MAECs. Besides, gene enrichment analysis showed that MAPK and PI3K-AKT signaling pathway were the most potential signaling pathways regulated by the differentially expressed circRNAs in atherosclerosis. Mmu_circRNA_36781 (circRNA ABCA1) and 37699 (circRNA KHDRBS1) were significantly up-regulated in AS aortic vessels and HO-treated MAECs. They have potential regulatory effects on atherosclerosis and vascular endothelial injury by targeting miR-30d-3p-TP53RK and miR-140-3p-MKK6 axis and their downstream signaling pathways.
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http://dx.doi.org/10.3389/fcvm.2021.657544DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8294331PMC
July 2021

Comparing the downstream costs and healthcare utilization associated with the use of low-dose computed tomography (LDCT) in lung cancer screening in patients with and without alzheimer's disease and related dementias (ADRD).

Curr Med Res Opin 2021 Oct 26;37(10):1731-1737. Epub 2021 Jul 26.

Department of Pharmaceutical Outcomes and Policy, College of Pharmacy, University of Florida, Gainesville, FL, USA.

Objective: This study aims to compare the downstream costs and healthcare utilization associated with using low-dose computed tomography (LDCT) for lung cancer screening in patients with and without Alzheimer's disease and related dementias (ADRD).

Methods: Based on data from IBM MarketScan Commercial Claims Databases (2014-2018), we have identified four study cohorts: ADRD and non-ADRD patients who went through LDCT screening; ADRD and non-ADRD patients without LDCT screening. Annually healthcare utilization and cost were grouped into outpatient, inpatient, and pharmacy. We used difference-in-differences (DID) models to estimate the downstream healthcare utilization and cost associated with LDCT screening in both ADRD and non-ADRD population. We used a difference-in-difference-in-differences (DDD) model to explore whether LDCT screening was associated with higher downstream cost and healthcare utilization in ADRD population than non-ADRD population.

Result: Compared to individuals without LDCT screening, LDCT screening was associated with increased outpatient visits (2.1, 95% CI 0.7, 3.4) and outpatient cost ($2301.0, 95% CI 296.2, 4305.8) in the ADRD population and increased outpatient visits (0.6, 95% CI 0.1, 1.1) in the non-ADRD population within 1 year after screening. Compared with the non-ADRD population, LDCT screening was found to be associated with an additional 1.5 (95% CI 0.2, 2.8) outpatient visits, 0.7 (95% CI 0.1, 1.3) days of inpatient stays, and $4,960.4 (95% CI 532.7, 9388.0) in overall healthcare costs within 1-year after LDCT in the ADRD population (all  < .5).

Conclusion: The downstream cost and healthcare utilization associated with LDCT screening were found to be higher in the ADRD population compared to the average population.
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http://dx.doi.org/10.1080/03007995.2021.1953972DOI Listing
October 2021

Toxic chromium treatment induce amino-assisted electrostatic adsorption for the synthesis of highly dispersed chromium catalyst.

J Hazard Mater 2021 Sep 19;417:126155. Epub 2021 May 19.

Faculty of Environmental Science and Engineering, Kunming University of Science and Technology, Kunming 650500, PR China; The Innovation Team for Volatile Organic Compounds Pollutants Control and Resource Utilization of Yunnan Province, Kunming 650500, PR China. Electronic address:

Removal of toxic Cr (VI) from aqueous solutions using silicon-based adsorbents has been widely investigated. Meanwhile, contradictory between highly dispersed active Cr species and high Cr loading over commercial Cr-based catalyst was inevitable. In this work, amino-assisted electrostatic adsorption from toxic Cr (VI) treatment was developed to prepare highly dispersed Cr oxides catalysts supported on MCM-41. The Cr loading was as high as 15 wt%, and structure characters of the catalysts were well-reserved. As a result, electrostatic adsorption and subsequent complexation from negatively charged Cr (VI) species and positively charged ammonium groups made a positive contribution to the appearance of highly dispersed mono Cr species, which gave rise to improved non-oxidative propane dehydrogenation (PDH) activity. In contrast, the agglomeration of Cr species and lower PDH activity were observed on the sample synthesized using the traditional wet impregnation method. Besides, the transformation of Cr (VI) to active Cr (III) sites over the catalyst was proved by the designed in-situ H-TPR, ex-situ UV-vis and Raman spectra results. This procedure reflects a new avenue of green chemistry, which can recycle waste Cr adsorbents as efficient PDH catalysts.
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http://dx.doi.org/10.1016/j.jhazmat.2021.126155DOI Listing
September 2021

CPEB1 enhances erastin-induced ferroptosis in gastric cancer cells by suppressing twist1 expression.

IUBMB Life 2021 09 12;73(9):1180-1190. Epub 2021 Jul 12.

Department of Biochemistry and Molecular Biology, Harbin Medical University, Harbin, Heilongjiang, China.

The induction of ferroptosis is considered a new strategy for cancer treatment. Cytoplasmic polyadenylation element binding protein 1 (CPEB1) is a post-transcriptional regulatory factor, whose low expression has been reported to link to the enhanced metastasis and angiogenesis of gastric cancer (GC). In this study, to explore the role of CPEB1 in ferroptosis, GC cells with overexpressed or silenced CPEB1 expression were treated with erastin, a classic ferroptosis inducer. The results showed that erastin dose-dependently decreased the viability of four GC cell lines (AGS, SNU-1, Hs-746 T, and HGC-27), suggesting that ferroptosis could be triggered in these GC cells. Interestingly, HGC-27 cells overexpressing CPEB1 were more sensitive to erastin, generated more lipid reactive oxygen species (ROS) and malondialdehyde (MDA), and their glutathione peroxidase 4 (Gpx4) expression and GSH content were reduced. Contrarily, CPEB1-silenced AGS cells were more resistant to erastin. Mechanically, we demonstrated that CPEB1 overexpression reduced the expression of twist1, an inhibitor of activating transcription factor 4 (ATF4), thereby activating the ATF4/ChaC Glutathione Specific Gamma-Glutamylcyclotransferase 1 (CHAC1) pathway (CHAC1, a molecule known to induce GSH degradation). Furthermore, re-expression of twist1 in GC cells impaired the effects of CPEB1 overexpression in presence of erastin. Additionally, similar to the in vitro results, the growth-inhibiting effects of erastin on GC xenografted tumors were also augmented by CPEB1 overexpression in vivo. Collectively, we demonstrate that CPEB1 facilitates erastin-induced ferroptosis by inhibiting twist1.
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http://dx.doi.org/10.1002/iub.2525DOI Listing
September 2021

Simultaneous determination of chito-oligosaccharides in rat plasma by the LC-MS/MS method: application to a pharmacokinetic study.

Anal Methods 2021 07;13(29):3242-3248

School of Medicine and Pharmacy, Ocean University of China, 5 Yushan Road, Qingdao 266003, People's Republic of China. and Laboratory for Marine Drugs and Bioproducts of Qingdao National Laboratory for Marine Science and Technology, Qingdao 266003, People's Republic of China and Key Laboratory of Glycoscience & Glycotechnology of Shandong Province, Qingdao 266003, People's Republic of China and Key Laboratory of Marine Drugs, Ministry of Education of China, Qingdao 266003, People's Republic of China.

A simple and sensitive method for the simultaneous determination of chito-oligosaccharides (COSs) with degrees of polymerization (DPs) from 2 to 7 was developed and used for COS quantification in rat plasma. Samples were separated on a Waters XBridge Amide column (3.5 μm, 2.1 × 150 mm) by isometric elution with 10 mM aqueous ammonium acetate (pH = 9) in acetonitrile and 10 mM aqueous ammonium acetate (pH = 9) (v/v, 50 : 50) employing multiple reaction monitoring (MRM) detection. Analytes and internal standards (IS) were extracted from rat plasma by protein precipitation with acetonitrile. The assay was linear over a concentration range of 20-10 000 ng mL-1 for COS2-7. The intra-day and inter-day precision of the investigated components exhibited an RSD within 15%, and the accuracy (RE%) ranged from -7.3% to 7.6%. The extraction recoveries of the six constituents were determined to be between 82.5% and 94.3%. No significant matrix effects for COS2-7 were observed in rat plasma. COS in plasma remained stable for 24 h at room temperature (short-term), after freeze-thaw cycles, and 30 days in a -40 °C freezer. In comparison to reported COS quantitation methods, this method is simple, sensitive and cost-effective and could be used for the simultaneous quantitation of COS2-7. This method meets the Food and Drug Administration guidelines and had been successfully applied to the analysis of pharmacokinetic samples collected from rats.
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http://dx.doi.org/10.1039/d1ay00772fDOI Listing
July 2021

Impact of Expressing Cells on Glycosylation and Glycan of the SARS-CoV-2 Spike Glycoprotein.

ACS Omega 2021 Jun 11;6(24):15988-15999. Epub 2021 Jun 11.

Center for Clinical Mass Spectrometry, Department of Pharmaceutical Analysis, Soochow University, Suzhou, Jiangsu 215123, China.

The spike glycoprotein of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the first point of contact for the virus to recognize and bind to host receptors, is the focus of biomedical research seeking to effectively prevent and treat coronavirus disease (COVID-19). The mass production of spike glycoproteins is usually carried out in different cell systems. Studies have been shown that different expression cell systems alter protein glycosylation of hemagglutinin and neuraminidase in the influenza virus. However, it is not clear whether the cellular system affects the spike protein glycosylation. In this work, we investigated the effect of an expression system on the glycosylation of the spike glycoprotein and its receptor-binding domain. We found that there are significant differences in the glycosylation and glycans attached at each glycosite of the spike glycoprotein obtained from different expression cells. Since glycosylation at the binding site and adjacent amino acids affects the interaction between the spike glycoprotein and the host cell receptor, we recognize that caution should be taken when selecting an expression system to develop inhibitors, antibodies, and vaccines.
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http://dx.doi.org/10.1021/acsomega.1c01785DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8204757PMC
June 2021

Glycoengineering of Aspergillus nidulans to produce precursors for humanized N-glycan structures.

Metab Eng 2021 09 24;67:153-163. Epub 2021 Jun 24.

Department of Biotechnology and Biomedicine, Technical University of Denmark, Søltofts Plads, Building 223, 2800 kgs, Lyngby, Denmark. Electronic address:

Filamentous fungi secrete protein with a very high efficiency, and this potential can be exploited advantageously to produce therapeutic proteins at low costs. A significant barrier to this goal is posed by the fact that fungal N-glycosylation varies substantially from that of humans. Inappropriate N-glycosylation of therapeutics results in reduced product quality, including poor efficacy, decreased serum half-life, and undesirable immune reactions. One solution to this problem is to reprogram the glycosylation pathway of filamentous fungi to decorate proteins with glycans that match, or can be remodeled into, those that are accepted by humans. In yeast, deletion of ALG3 leads to the accumulation of ManGlcNAc glycan structures that can act as a precursor for remodeling. However, in Aspergilli, deletion of the ALG3 homolog algC leads to an N-glycan pool where the majority of the structures contain more hexose residues than the ManGlcNAc species that can serve as substrates for humanized glycan structures. Hence, additional strain optimization is required. In this report, we have used gene deletions in combination with enzymatic and chemical glycan treatments to investigate N-glycosylation in the model fungus Aspergillus nidulans. In vitro analyses showed that only some of the N-glycan structures produced by a mutant A. nidulans strain, which is devoid of any of the known ER mannose transferases, can be trimmed into desirable ManGlcNAc glycan structures, as substantial amounts of glycan structures appear to be capped by glucose residues. In agreement with this view, deletion of the ALG6 homolog algF, which encodes the putative α-1,3- glucosyltransferase that adds the first glucose residue to the growing ER glycan structure, dramatically reduces the amounts of HexHexNAc structures. Similarly, these structures are also sensitive to overexpression of the genes encoding the heterodimeric α-glucosidase II complex. Without the glucose caps, a new set of large N-glycan structures was formed. Formation of this set is mostly, perhaps entirely, due to mannosylation, as overexpression of the gene encoding mannosidase activity led to their elimination. Based on our new insights into the N-glycan processing in A. nidulans, an A. nidulans mutant strain was constructed in which more than 70% of the glycoforms appear to be ManGlcNAc species, which may serve as precursors for further engineering in order to create more complex human-like N-glycan structures.
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http://dx.doi.org/10.1016/j.ymben.2021.06.001DOI Listing
September 2021

Access to enantioenriched compounds bearing challenging tetrasubstituted stereocenters via kinetic resolution of auxiliary adjacent alcohols.

Nat Commun 2021 06 18;12(1):3735. Epub 2021 Jun 18.

State Key Laboratory of Structural Chemistry, and Key Laboratory of Coal to Ethylene Glycol and Its Related Technology, Center for Excellence in Molecular Synthesis, Fujian Institute of Research on the Structure of Matter, University of Chinese Academy of Sciences, Fuzhou, China.

Contemporary asymmetric catalysis faces huge challenges when prochiral substrates bear electronically and sterically unbiased substituents and when substrates show low reactivities. One of the inherent limitations of chiral catalysts and ligands is their incapability in recognizing prochiral substrates bearing similar groups. This has rendered many enantiopure substances bearing several similar substituents inaccessible. Here we report the rationale, scope, and applications of the strategy of kinetic resolution of auxiliary adjacent alcohols (KRA*) that can be used to solve the above troubles. Using this method, a large variety of optically enriched tertiary alcohols, epoxides, esters, ketones, hydroxy ketones, epoxy ketones, β-ketoesters, and tetrasubstituted methane analogs with two, three, and four spatially and electronically similar groups can be readily obtained (totally 96 examples). At the current stage, the strategy serves as the optimal solution that can complement the inability caused by direct asymmetric catalysis in getting chiral molecules with challenging fully substituted stereocenters.
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http://dx.doi.org/10.1038/s41467-021-23990-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8213810PMC
June 2021

Correction to: CDK4/6 inhibition blocks cancer metastasis through a USP51-ZEB1-dependent deubiquitination mechanism.

Signal Transduct Target Ther 2020 Jun 19;5(1):103. Epub 2020 Jun 19.

Tianjin Key Laboratory of Tumor Microenvironment and Neurovascular Regulation, Medical College of Nankai University, Tianjin, 300071, China.

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http://dx.doi.org/10.1038/s41392-020-00212-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7305231PMC
June 2020

Removal of perfluorooctanoic acid (PFOA) from aqueous solution by amino-functionalized graphene oxide (AGO) aerogels: Influencing factors, kinetics, isotherms, and thermodynamic studies.

Sci Total Environ 2021 Aug 20;783:147041. Epub 2021 Apr 20.

Department of Laboratory Medicine and Pathology, University of Alberta, Edmonton T6G 2G3, Canada. Electronic address:

Perfluorooctanoic acid (PFOA) is an emerging organic pollutant that has become ubiquitous in waterways and is difficult to be removed from wastewater using traditional treatment methods. In this study, amino-functionalized graphene oxide (AGO) aerogels were prepared as a potential remediation tool for water contaminated by PFOA. The structure of the prepared absorbent material was characterized by Fourier transform infrared spectroscopy, Raman spectroscopy, scanning electron microscope, and X-ray diffraction. The use of various adsorption times, temperatures, solution pH, and absorbent amount were investigated to determine optimum conditions for PFOA adsorption. Adsorption kinetics and thermodynamics of the absorbent were analyzed as well. AGO aerogels exhibited a high adsorption capacity of PFOA (1575 mg∙g) and high removal efficiency (99.95%) in a solution containing 10 mg PFOA L, likely due to the interconnected porous microstructures and amino groups of the AGO aerogels. The adsorption kinetics and isotherm of PFOA were well-fitted using pseudo-second-order and the Freundlich modelling. The adsorption mechanism of PFOA onto AGO aerogels followed spontaneous, exothermic, and physical processes. This study shows the potential of this material to remove PFOA from PFOA-contaminated waters effectively by providing insight into the understanding of the adsorption mechanisms of PFOA onto AGO aerogels.
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http://dx.doi.org/10.1016/j.scitotenv.2021.147041DOI Listing
August 2021

cRGD peptide-conjugated polyethylenimine-based lipid nanoparticle for intracellular delivery of siRNA in hepatocarcinoma therapy.

Drug Deliv 2021 Dec;28(1):995-1006

School of Pharmacy, Shanxi Medical University, Taiyuan, China.

The effective delivery system plays an important role in the application of siRNA in the antitumor study. However, until now, researches on the delivery systems targeting hepatocarcinoma cells are still being explored. Here we designed and prepared a novel siRNA delivery system, cRGD-PSH-NP, which was based on a modified polyethyleneimine (PSH) and DSPE-PEG-cRGD. cRGD-PSH-NP loaded with survivin siRNA (cRGD-PSH-NP/S) was composed of egg phosphatidylcholine, cationic PSH, PEGylated lipids, survivin siRNA, and cRGD peptide as a targeting ligand. The formulations of cRGD-PSH-NP/S were optimized and characterized. investigations showed excellent gene silencing and antitumor activity compared with the unmodified nanoparticles in HepG2 cells. antitumor efficacy of cRGD-PSH-NP/S exhibited potent tumor inhibition (74.71%) in HepG2-bearing nude mice without inducing toxicity. These data suggested further research of cRGD-PSH-NP/S in hepatocarcinoma therapy.
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http://dx.doi.org/10.1080/10717544.2021.1928794DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8168781PMC
December 2021

Recent advances in understanding the adaptive evolution of metabolic genes and traits.

Curr Opin Clin Nutr Metab Care 2021 07;24(4):308-314

Department of Genetics, Franklin College of Arts and Sciences.

Purpose Of Review: This review summarizes the recent advances in understanding the adaptive evolution of metabolic genes and traits, providing insights into gene-diet interactions in human evolution and health.

Recent Findings: The rapid accumulation of ancient DNA across time and geography illuminates unprecedented details of some well-established examples of genetic adaptation to diet, such as the LCT and FADS genes. Novel cases of thrifty genes were identified, especially a microRNA at the LCT locus that controls energy expenditure and glucose homeostasis, connecting the historical adaptation to present-day metabolic disorders. A new example of gene-diet-microbiota interactions was established among the AMY1 copy number, starchy diets, and resistant-starch-digesting Ruminococcus. The explosion of genome-wide association studies in large cohorts unravels the present-day health implications of historically adaptive genetic variants. It also enables studies into the polygenic adaptation of metabolic traits, revealing intriguing adaptive signals for increased bone mineral density, blood pressure, and risk of type 2 diabetes, but decreased body mass index and HbA1c.

Summary: The rapid accumulation of ancient and modern DNA has fueled the characterization of novel and existing cases of genetic adaptation. However, transferring these evolutionary insights into genome-informed precision nutrition requires extensive mechanistic studies and genotype-aware clinical trials.
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http://dx.doi.org/10.1097/MCO.0000000000000770DOI Listing
July 2021

The absorption of glycosaminoglycans of different molecular weight obtained from : an and study.

Food Funct 2021 Jun;12(12):5551-5562

Key Laboratory of Marine Drugs, Ministry of Education of China, School of Medicine and Pharmacy, Ocean University of China, Qingdao, Shandong Province 266003, People's Republic of China. and Laboratory of Marine Drugs and Bioproducts, Pilot National Laboratory for Marine Science and Technology, Qingdao, Shandong Province 266237, People's Republic of China.

The purpose of this study was to investigate the absorption and transport of glycosaminoglycan from Apostichopus japonicus (AHG) and its depolymerized derivatives (DAHG-1, DAHG-2, DAHG-3). The AHG and depolymerized AHGs (DAHGs) were characterized by high-performance gel permeation chromatography (HPGPC), Raman spectroscopy and atomic force microscopy (AFM). The results showed that there was no significant difference of an AHG primary structure and functional groups during the depolymerization. Meanwhile, AFM observation showed that AHG and DAHGs possessed linear structures. In this study, a rapid and sensitive liquid chromatographic post-column derivatization method was used to investigate the absorption of AHG and DAHGs with the Caco-2 cell model, the M cell model and the intestinal recirculating perfusion. It was found that AHG and DAHGs can be absorbed in the intestine, and their transport involved endocytosis.
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http://dx.doi.org/10.1039/d1fo00624jDOI Listing
June 2021
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