Publications by authors named "He Xiao"

609 Publications

Based on Plasma Metabonomics and Network Pharmacology Exploring the Therapeutic Mechanism of on Type 2 Diabetes.

Front Pharmacol 2021 28;12:674379. Epub 2021 May 28.

National Pharmaceutical Engineering Center for Solid Preparation in Chinese Herbal Medicine, Nanchang, China.

(GP) is a perennial herbal medicine and food homologous plant, which has been reported to have a good hypoglycemic effect. However, its active components and underlying mechanism of action are not clear. Here, we aimed to confirm the effects of GP on type 2 diabetes (T2DM) from several different aspects. We used UPLC/Q-TOF MS to analyze the metabolic patterns, which included blood samples of clinical subjects and / mice to screen for serum metabolic markers and metabolic pathways. We also used network pharmacology to study GP targets in the treatment of T2DM. Data from endogenous metabolites in plasma showed that two common pathways, including glycerol phosphate metabolism and retinol metabolism, were identified in plasma samples of the groups. Finally, Western blot analysis was used to verify the expression of proteins in the PI3K/AKT and AGE-RAGE signaling pathways. The protein expression of AKT, eNOS, iNS, and MAPK was significantly upregulated, and the expression of caspase-8 and caspase-3 was significantly downregulated. Thus, our findings indicated that GP could alleviate insulin resistance by regulating biometabolic markers and key proteins in the PI3K/AKT and AGE-RAGE signaling pathways to treat T2DM.
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http://dx.doi.org/10.3389/fphar.2021.674379DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8192979PMC
May 2021

Comparative toxicity of rod-shaped nano-CeO2 and nano-CePO4 to lettuce.

Metallomics 2021 Jun 8. Epub 2021 Jun 8.

Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety, Institute of High Energy Physics, Chinese Academy of Sciences, Beijing 100049, China.

The influence of morphology on the biological effects of nanomaterials (NMs) has not been well understood. In the present study, we compared the phytotoxicity of rod-shaped nano-cerium dioxide (R-CeO2) and nano-cerium phosphate (R-CePO4) to lettuce plants. The results showed that R-CeO2 significantly inhibited the root elongation of lettuce, induced oxidative damages, and caused cell death, while R-CePO4 was nontoxic to lettuce. The different distribution and speciation of Ce in plant tissues were determined by transmission electron microscopy (TEM) and X-ray absorption near edge spectroscopy (XANES) combined with linear combination fitting (LCF). The results showed that in the R-CeO2 group, part of Ce was transformed from Ce(IV) to Ce(III), while only Ce(III) was present in the R-CePO4 group. When interacting with plants, R-CeO2 is easier to be dissolved and transformed than R-CePO4, which might be the reason for their different phytotoxicity. Although they are both Ce-based NMs and have the same morphology, the toxicity of R-CeO2 seems to come from the released Ce3+ ions rather than its shape. This research emphasizes the importance of chemical composition and reactivity of nanomaterials to their toxicological effects.
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http://dx.doi.org/10.1093/mtomcs/mfab033DOI Listing
June 2021

miR-204-5p inhibits inflammation of synovial fibroblasts in osteoarthritis by suppressing FOXC1.

Authors:
Xiao He Lili Deng

J Orthop Sci 2021 May 24. Epub 2021 May 24.

Pediatric Intensive Care Unit, Chenzhou No. 1 People's Hospital, Chenzhou, Hunan, 423000, PR China.

Background: The paper is aimed at uncovering the mechanism of miR-204-5p in regulating inflammatory responses of human osteoarthritic synovial fibroblasts (SFs).

Methods: IL-1β-induced osteoarthritic SFs were established as an osteoarthritis (OA) cell model. The osteoarthritic SFs were accordingly transfected with mimics-miR-204-5p, inhibitors-miR-204-5 or FOXC1 siRNA. MTT tested the vitality of osteoarthritic SFs by analyzing the cell optical density. The expressions of miR-204-5p, FOXC1, TNF-α, IL-6, PGE2, MMP-1, MMP-13 and COX-2 in osteoarthritic SFs were measured by qRT-PCR, Western blotting and/or ELISA. The binding of miR-204-5p to FOXC1 was verified through luciferase reporter assay. The regulatory effect of miR-204-5p on FOXC1 was also tested in normal SFs.

Results: miR-204-5p was under-expressed and FOXC1 was over-expressed in osteoarthritic SFs. The expressions of FOXC1, TNF-α, IL-6, PGE2, MMP-1, MMP-13 and COX-2 were up-regulated in IL-1β-treated SFs. Up-regulation of miR-204-5p or down-regulation of FOXC1 suppressed the inflammatory responses of osteoarthritic SFs. miR-204-5p negatively regulated FOXC1 by being a sponge in osteoarthritic SFs as well as in normal SFs.

Conclusion: miR-204-5p down-regulates FOXC1 to ameliorate inflammation of SFs in OA.
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http://dx.doi.org/10.1016/j.jos.2021.03.014DOI Listing
May 2021

CBX7 suppresses urinary bladder cancer progression via modulating AKR1B10-ERK signaling.

Cell Death Dis 2021 May 25;12(6):537. Epub 2021 May 25.

Department of Laboratory Animal Science, Fudan University, 200032, Shanghai, China.

The chromobox (CBX) proteins mediate epigenetic gene silencing and have been implicated in the cancer development. By analyzing eight CBX family members in TCGA dataset, we found that chromobox 7 (CBX7) was the most strikingly downregulated CBX family member in urinary bladder cancer (UBC), as compared to normal tissues. Though dysregulation of CBX7 has been reported in multiple cancers, its specific role and clinical relevance in UBC remain unclear. Herein, we found that frequent downregulation of CBX7 in UBC specimens, which was due to its promoter hypermethylation, was correlated with poor prognosis. The ectopic expression of CBX7 suppressed UBC cell proliferation, migration, invasion, and cancer stemness, whereas CBX7 depletion promoted cancer cell aggressiveness. Importantly, CBX7 overexpression in UBC cells inhibited tumorigenicity, whereas CBX7 depletion promoted the tumor development, indicating its tumor-suppressive role in UBC. Using RNA-seq and chromosome immunoprecipitation (ChIP) assays, we identified aldo-keto reductase family 1 member 10 (AKR1B10) as a novel downstream target of CBX7, which was negatively modulated by CBX7 in a PRC1-dependent manner and involved in stimulating ERK signaling. Consistently, AKR1B10 overexpression induced cancer cell aggressiveness, whereas suppression of AKR1B10 by siRNA or its small molecular inhibitor, oleanolic acid, reversed the CBX7 deficiency-induced cellular effects. AKR1B10 overexpression was negatively associated with CBX7 downregulation and predicted poor clinical outcomes in UBC patients. Taken together, our results indicate that CBX7 functions as a tumor suppressor to downregulate AKR1B10 and further inactivates ERK signaling. This CBX7/AKR1B10/ERK signaling axis may provide a new therapeutic strategy against UBC.
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http://dx.doi.org/10.1038/s41419-021-03819-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8149849PMC
May 2021

Atmospheric Kinetics: Bimolecular Reactions of Carbonyl Oxide by a Triple-Level Strategy.

J Am Chem Soc 2021 Jun 24;143(22):8402-8413. Epub 2021 May 24.

Department of Chemistry, Chemical Theory Center, and Supercomputing Institute, University of Minnesota, Minneapolis, Minnesota 55455-0431, United States.

Criegee intermediates in the atmosphere serve as oxidizing agents to initiate aerosol formation, which are particularly important for atmospheric modeling, and understanding their kinetics is one of the current outstanding challenges in climate change modeling. Because experimental kinetics are still limited, we must rely on theory for the complete picture, but obtaining absolute rates from theory is a formidable task. Here, we report the bimolecular reaction kinetics of carbonyl oxide with ammonia, hydrogen sulfide, formaldehyde, and water dimer by designing a triple-level strategy that combines (i) benchmark results close to the complete-basis limit of coupled-cluster theory with the single, double, triple, and quadruple excitations (CCSDTQ/CBS), (ii) a new hybrid meta density functional (M06CR) specifically optimized for reactions of Criegee intermediates, and (iii) variational transition-state theory with both variable rection coordinates and optimized reaction paths, with multidimensional tunneling, and with pressure effects. For (i) we have found that quadruple excitations are required to obtain quantitative reaction barriers, and we designed new composite methods and strategies to reach CCSDTQ/CBS accuracy. The present findings show that (i) the CHOO + HCHO reaction can make an important contribution to the sink of HCHO under wide atmospheric conditions in the gas phase and that (ii) CHOO + (HO) dominates over the CHOO + HO reaction below 10 km.
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http://dx.doi.org/10.1021/jacs.1c02029DOI Listing
June 2021

Neuroprotective effects of aucubin on hydrogen peroxide-induced toxicity in human neuroblastoma SH-SY5Y cells via the Nrf2/HO-1 pathway.

Phytomedicine 2021 Jul 18;87:153577. Epub 2021 Apr 18.

Biomedicine Key Laboratory of Shaanxi Province, School of Pharmacy, Northwest University, Xi'an, P.R. China; Key Laboratory of Resource Biology and Biotechnology in Western China (Northwest University), Ministry of Education, Xi'an, P.R. China. Electronic address:

Background: When redox balance is lost in the brain, oxidative stress can cause serious damage that leads to neuronal loss, in congruence with neurodegenerative diseases. Aucubin (AU) is an iridoid glycoside and that is one of the active constituents of Eucommia ulmoides, has many pharmacological effects such as anti-inflammation, anti-liver fibrosis, and anti-atherosclerosis.

Purpose: The present study aimed to evaluate the inhibitory effects of AU on cell oxidative stress against hydrogen peroxide (HO)-induced injury in SH-SY5Y cells in vitro.

Methods: SH-SY5Y cells were simultaneously treated with AU and HO for 24 h. Cell viability was measured by CCK-8. Additionally, mitochondrial membrane depolarization, reactive oxygen species (ROS) generation, and cell apoptosis were measured by flow cytometry.

Results: The results showed that AU can significantly increase the HO-induced cell viability and the mitochondrial membrane potential, decrease the ROS generation, malondialdehyde (MDA), and increase glutathione (GSH) contents and the superoxide dismutase (SOD) activity. We also found that HO stimulated the production of nitric oxide (NO), which could be reduced by treatment with AU through inhibiting the inducible nitric oxide synthase (iNOS) protein expression. In HO-induced SH-SY5Y cells, the levels of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6) and interleukin-1β (IL-1β) content and cell apoptosis were significantly reduced by AU treatment through nuclear factor E2-related factor 2/hemo oxygenase-1 (Nrf2/HO-1) activation, inhibiting the expression of p-NF-κB/NF-κB and down-regulating MAPK and Bcl-2/Bax pathways.

Conclusion: These results indicate that AU can reduce inflammation and oxidative stress through the NF-κB, Nrf2/HO-1, and MAPK pathways.
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http://dx.doi.org/10.1016/j.phymed.2021.153577DOI Listing
July 2021

Nanoparticles Determination by Laser Ablation Inductively Coupled Plasma Mass Spectrometry.

J Nanosci Nanotechnol 2021 11;21(11):5436-5442

CAS Key Lab for Biomedical Effects of Nanomaterials and Nanosafety, CAS-HKU Joint Laboratory of Metallomics on Health & Environment, Institute of High Energy Physics, Chinese Academy of Sciences, Beijing 100049, China.

Quantitatively studying the biodistribution and transformation of nanomaterials is of great importance for nanotoxicological evaluation. Recently, laser ablation inductively coupled plasma mass spectrometry has been employed to distinguish nanoparticles (NPs) with their dissolved ions in biological samples. The principle of the proposal is based on a hypothesis that the intact NPs sampled by laser ablation will generate discrete sharp pulses of signals in ICP-MS measurement, being totally different from the continuous, relatively lower signals generated by ions. However, it is still a controversy whether NPs could maintain their intactness during the laser ablation. This work found a way to exactly determine the number of NPs sampled for each LA-ICP-MS measurement. It made possible to reveal the signal profile of a single NP in LA-ICP-MS analysis. The results suggest that AuNR, AgNP and TIO₂ NP were broken into much smaller secondary NPs during the laser ablation, therefore generating continuous signals in the analyzer. There was a certain probability that the fragmentation of large-sized NP or multiple NPs by laser ablation was not sufficient, leaving some NPs unbroken or some secondary NPs with relatively large sizes to generate discrete pulses of signals in the analyzer. When the intactness of NPs during laser ablation cannot be assured, it is impossible to determine the attribution of mass spectrum signals. These findings compromise the reliability of distinguishing NPs from their dissolved ions by LA-ICP-MS.
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http://dx.doi.org/10.1166/jnn.2021.19476DOI Listing
November 2021

DeepBSP-a Machine Learning Method for Accurate Prediction of Protein-Ligand Docking Structures.

J Chem Inf Model 2021 May 12;61(5):2231-2240. Epub 2021 May 12.

Shanghai Engineering Research Center of Molecular Therapeutics and New Drug Development, School of Chemistry and Molecular Engineering, East China Normal University, Shanghai 200062, China.

In recent years, machine-learning-based scoring functions have significantly improved the scoring power. However, many of these methods do not perform well in distinguishing the native structure from docked decoy poses due to the lack of decoy structural information in their training data. Here, we developed a machine-learning model, named DeepBSP, that can directly predict the root mean square deviation (rmsd) of a ligand docking pose with reference to its native binding pose. Unlike the binding affinity, the rmsd between the docking poses with reference to their native structures can be straightforwardly determined. By training on a generated data set with 11,925 native complexes and more than 165,000 docked poses, our model shows excellent docking power on our test set and also on the CASF-2016 docking decoy set compared to other major scoring functions. Thus, by combining molecular dockings that generate many poses with the application of DeepBSP, one can more accurately predict the best binding pose that is closest to the native complex structure. This DeepBSP model shall be very useful in picking out poses close to their natives from many poses generated from a dock application.
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http://dx.doi.org/10.1021/acs.jcim.1c00334DOI Listing
May 2021

Nanocellulose-derived carbon/g-CN heterojunction with a hybrid electron transfer pathway for highly photocatalytic hydrogen peroxide production.

J Colloid Interface Sci 2021 Oct 24;599:507-518. Epub 2021 Apr 24.

College of Material Engineering, Fujian Agriculture and Forestry University, Fuzhou 350108, China.

Using oxygen reduction for the photocatalytic production of hydrogen peroxide (HO) has been considered a green and sustainable route. In the present study, to achieve high efficiency, graphitic carbon nitride (g-CN) was obtained using thermal polymerization from a bi-component precursor and was then assembled with cellulose nanofibers. It was found that a small quantity of cellulose nanofibers that generates carbon fibers upon pyrolysis greatly improves the photocatalytic activity compared with that of g-CN alone. The well-defined carbon/g-CN heterojunction-type material exhibits as high as 1.10 mmol Lh of photo-production of HO under visible light, which is 4.2 times higher than that yielded by pristine g-CN from a single precursor. A comprehensive characterization of the photocatalyst enables us to delineate the effect of the carbon nanofiber with respect to porosity, electron-hole separation, band gap regulation, and especially the electron transfer pathway. Our results demonstrate that nanocellulose-derived carbon, when precisely assembled with other functional material such as a photocatalyst, is a promising promoter of their activity.
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http://dx.doi.org/10.1016/j.jcis.2021.04.111DOI Listing
October 2021

Drug-guided screening for pancreatic lipase inhibitors in functional foods.

Food Funct 2021 May 29;12(10):4644-4653. Epub 2021 Apr 29.

Shanghai Engineering Research Center of Molecular Therapeutics and New Drug Development, School of Chemistry and Molecular Engineering, East China Normal University, Shanghai 200062, China.

Chronic diseases, such as obesity, cause great harm to human health. Conventional drugs have promising therapeutic effects but also cause significant side effects. Functional foods are an excellent therapeutic alternative to pharmaceuticals, as they have fewer side effects. However, screening for active ingredients in natural foods is difficult. In this study, a novel pancreatic lipase inhibitor screening strategy, guided by the drug molecule orlistat, was combined with experimental verification. Twenty compounds from natural foods were evaluated based on the characteristics of orlistat interaction with pancreatic lipase. The characteristics of 13 molecules were comparable to those of orlistat. The pancreatic lipase inhibition rates of curcumin and sinensetin were 82.42 ± 0.50% and 81.07 ± 2.05%, respectively, and their IC values were 0.971 mM and 0.526 mM, respectively; both the inhibition rates as well as IC values were similar to those of orlistat. Curcumin and sinensetin prevented weight gain in mice by 69.17% and 52.29%, respectively, compared to orlistat. Curcumin and sinensetin did not cause significant organ damage in vivo, but significantly reduced the contents of triglycerides and cholesterol in blood and lipids in the liver, protecting liver function. Furthermore, 57 328 molecules in the Chinese Natural Product Database library were screened, and 20 potentially active molecules, found to be highly efficient in our study, were selected. Thus, we successfully established an efficient and accurate strategy for screening active ingredients in natural foods under the guidance of a drug molecule, providing valuable insights for functional food development.
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http://dx.doi.org/10.1039/d0fo03366aDOI Listing
May 2021

Electrosynthesized CuO/graphene by a four-electrode electrolysis system for the oxygen reduction reaction to hydrogen peroxide.

Chem Commun (Camb) 2021 Apr;57(34):4118-4121

Key Laboratory of Magnetic Molecules & Magnetic Information Materials Ministry of Education, The School of Chemical and Material Science, Shanxi Normal University, Linfen, 041004, China.

Here a facile four-electrode electrolysis system is firstly applied to synthesize a CuOx/graphene hybrid. The exfoliation of graphite via high electrolytic voltage and dissolution of copper via low electrolytic voltage are achieved simultaneously. CuOx/G with the highest content of CuOx shows superior electrocatalytic activity for oxygen reduction to hydrogen peroxide.
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http://dx.doi.org/10.1039/d1cc00386kDOI Listing
April 2021

Analysis of the binding modes of the first- and second-generation antiandrogens with respect to F876L mutation.

Chem Biol Drug Des 2021 Apr 27. Epub 2021 Apr 27.

Shanghai Engineering Research Center of Molecular Therapeutics and New Drug Development, Shanghai Key Laboratory of Green Chemistry and Chemical Process, School of Chemistry and Molecular Engineering, East China Normal University, Shanghai, China.

Androgen receptor (AR) is an important target for the treatment of prostate cancer, and mutations in the AR have an important impact on the resistance of existing drugs. In this work, we performed molecular dynamics simulations of the existing marketed antiandrogens flutamide, nilutamide, bicalutamide, enzalutamide, apalutamide, darolutamide, and its main metabolite ORM15341 in complex with the wild-type and F876L mutant AR. We calculated the residue-specific binding free energy contribution of the wild-type and mutant ARs with the AS-IE method and analyzed the hotspot residues and the binding free energy contributions of specific residues before and after the mutation. In addition, we analyzed the total binding obtained by adding residue binding energy contributions and compared the results with experimental values. The obtained residue-specific binding information should be very helpful in understanding the mechanism of drug resistance with respect to specific mutations and in the design of new generation drugs against possible new mutations.
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http://dx.doi.org/10.1111/cbdd.13848DOI Listing
April 2021

Platelet MHC Class I Mediates CD8+ T Cell Suppression During Sepsis.

Blood 2021 Apr 25. Epub 2021 Apr 25.

Department of Medicine, Division of General Internal Medicine, University of Utah School of Medicine, Salt Lake City, United States.

Circulating platelets interact with leukocytes to modulate host immune and thrombotic responses. In sepsis, platelet-leukocyte interactions are increased, and have been associated with adverse clinical events, including increased platelet-T cell interactions. Sepsis is associated with reduced CD8+ T cell numbers and functional responses, but whether platelets regulate CD8+ T cell responses during sepsis remains unknown. In our current study, we systemically evaluated platelet antigen internalization and presentation through major histocompatibility complex class I (MHC-I) and their effects on antigen specific CD8+ T cells in sepsis in vivo and ex vivo. We discovered that both human and murine platelets internalize and proteolyze exogenous antigens, generating peptides that are loaded onto MHC-I. The expression of platelet MHC-I, but not platelet MHC-II, is significantly increased in human and murine platelets during sepsis and in human megakaryocytes stimulated with agonists generated systemically during sepsis (e.g., IFN-g and LPS). Upregulation of platelet MHC-I during sepsis increases antigen cross-presentation and interactions with CD8+ T cells in an antigen-specific manner. Using a platelet lineage specific MHC-I deficient mouse strain (B2mf/f--Pf4Cre), we demonstrate that platelet MHC-I regulates antigen-specific CD8+ T cell proliferation in vitro, as well as the number and functional responses of CD8+ T cells in vivo during sepsis. Loss of platelet MHC-I reduced sepsis-associated mortality in mice in an antigen specific setting. These data identify a new mechanism by which platelets, through MHC-I, process and cross-present antigens, engage antigen specific CD8+ T cells, and regulate CD8+ T cell number, functional responses, and outcomes during sepsis.
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http://dx.doi.org/10.1182/blood.2020008958DOI Listing
April 2021

Exploration of an Efficient Simultaneous Molecular Detection Method of HIV, HCV, and Syphilis from a Single Dried Blood Spot.

Biomed Environ Sci 2021 Apr;34(4):257-264

National HIV Reference Laboratory, National Center for AIDS/STD Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing 102206, China.

Objective: The aim of the present study was to evaluate the performance of the simultaneous detection of HIV-1 RNA, HIV-1 DNA, and HCV RNA using one dried blood spot (DBS) as an alternative sample to plasma.

Method: A total of 571 paired DBS/plasma samples were collected from men who have sex with men (MSM) and injection drug users (IDUs), and serological and molecular assays were performed. Using plasma results as the reference standard, the performance of DBS tests for HIV-1 RNA, HIV-1 DNA, and HCV RNA was evaluated. Pearson's correlation coefficients and Bland-Altman analysis were performed to assess the correlation and concordance between DBS and plasma.

Results: Among paired plasma/DBS samples with detectable HIV-1 RNA and HCV RNA, five samples (5/32) were not detectable in DBS, while measurable HIV-1 RNA levels were present in plasma (1.44 to 3.99 log copies/mL). There were two samples (2/94) with undetectable HCV RNA in DBS, while measurable HCV RNA levels were present in plasma (-5 to 5.99 log copies/mL). The correlation between HIV-1 RNA light chain variable region (VL) values obtained from plasma and DBS showed that = 0.683 ( < 0.01), = 27 and = 0.612 ( < 0.01), = 89 in HCV RNA. Bland-Altman analysis revealed that in HIV-1 RNA, the mean (± SD) difference between HIV-1 RNA in plasma and DBS was 1.00 ± 1.01 log copies/mL, and all samples were within ± 1.96 SD (-0.97 to 2.97 log copies/mL) for DBS. The mean difference (± SD) in HCV RNA was 0.15 ± 1.08 log copies/mL, and 94.38% (84/89) were within ± 1.96 SD (-1.96 to 2.67 log copies/mL). Overall, HIV-1 RNA and HCV RNA levels obtained from a DBS were lower than those obtained from plasma. HIV-1 DNA in a DBS showed concordant results with HIV-1 RNA in plasma. HIV-1 DNA RT-PCR using a DBS showed acceptable performance.

Conclusion: The performance of the simultaneous detection of HIV-1 RNA, HIV-1 DNA, and HCV RNA using one DBS was acceptable. DBS, as an alternative sample to plasma, may be a viable option for the simultaneous detection of HIV-1 RNA, HIV-1 DNA, and HCV RNA in resource-limited settings or for individuals living in areas that are difficult to access.
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http://dx.doi.org/10.3967/bes2021.034DOI Listing
April 2021

Structural dependence of electrosynthesized cobalt phosphide/black phosphorus pre-catalyst for oxygen evolution in alkaline media.

Nanoscale 2021 Apr 13;13(15):7381-7388. Epub 2021 Apr 13.

Key Laboratory of Magnetic Molecules & Magnetic Information Materials, Ministry of Education, The School of Chemical and Material Science, Shanxi Normal University, Linfen 041004, China.

The integration of black phosphorus (BP) with metal phosphides is known to produce high-performance electrocatalysts for oxygen evolution reduction (OER), although increased stability and prevention of the degradation of their lone pairs would be desirable improvements. In this work, cobalt phosphide (CoP)/BP heterostructures were electrochemically synthesized with a two-electrode system, where cobalt ions were generated in situ at a Co anode, and non-aggregated BP nanosheets (NSs) were exfoliated from the bulky BP cathode. With an electrolysis voltage of 30 V, the CoP/BP heterostructure exhibited a superior and stable OER performance (e.g., an overpotential of 300 mV at 10 mA cm, which is 41 mV lower than that obtained with a RuO catalyst). The CoO formed in situ during the OER catalysis and remaining CoP synergistically contributed to the enhanced OER performance. The present strategy provides a new electrosynthetic method to prepare stable BP electrocatalysts and also further expands their electrochemical applications.
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http://dx.doi.org/10.1039/d1nr00062dDOI Listing
April 2021

[Extensor digitorum communis split approach combined with loop-plate technique for treatment of ulnar coronoid fracture in terrible triad of elbow].

Zhongguo Xiu Fu Chong Jian Wai Ke Za Zhi 2021 Apr;35(4):420-425

Department of Orthopaedic Trauma, Honghui Hospital Affiliated to Xi'an Jiaotong University, Xi'an Shaanxi, 710054, P.R.China.

Objective: To explore the effectivenesss of simple lateral extensor digitorum communis (EDC) split approach combined with loop-plate fixation in the treatment of ulnar coronoid fracture in terrible triad of elbow (TTE).

Methods: The clinical data of 60 patients with TTE who met the selection criteria between January 2015 and May 2018 were retrospectively analyzed. There were 48 males and 12 females, aged from 18 to 60 years (mean, 37.4 years). All the patients were closed fractures. Injury causes included fall injury in 28 cases, falling from height in 20 cases, and traffic accident injury in 12 cases. All patients had no vascular and nerve injury, and the time from injury to operation was 1-14 days, with an average of 4.8 days. The height and size of the fracture of the coronal process were measured by CT and accurate classifications were made. All the 60 patients were treated with simple lateral EDC split approach combined with loop-plate to fix the ulnar coronoid fracture; 20 patients of radial head fracture were fixed with hollow screw, 32 patients with mini-plate fixation, 8 patients with radial head prosthesis replacement; 16 patients with suture and 44 patients with suture anchor to reconstruct lateral collateral ligament complex; 10 patients with residual instability of elbow joint were fixed with hinge external fixator, and others were fixed with adjustable tension brace after operation. Postoperative imaging examination was performed to evaluate fracture healing and complications, such as loosening or breakage of internal fixator, osteoarthritis, and heterotopic ossification, etc. During follow-up, the range of motion (ROM) of the elbow joint was recorded, including elbow flexion, extension, and forearm pronation, supination. Mayo elbow function score system (MEPS) was used to evaluate elbow joint function at last follow-up.

Results: All patients were followed up 16-24 months (mean, 20.2 months). All incisions healed by first intention after operation, and no complications such as vascular nerve injury, elbow joint instability, internal fixation failure, and infection occurred; the fracture healing time was 9-17 weeks (mean, 11.7 weeks). Four cases developed elbow stiffness after operation, and all underwent elbow joint lysis with internal fixator removal within 12-15 months after operation; 10 cases developed heterotopic ossification without special treatment. At last follow-up, the ROM of elbow flexion ranged from 85° to 135° (mean, 116°), the ROM of elbow extension ranged from 0° to 20° (mean, 11°), the ROM of forearm pronation ranged from 55° to 75° (mean, 70°), and the ROM of forearm supination ranged from 60° to 90° (mean, 83°). The MEPS score ranged from 55 to 100 (mean, 86.1); the effectiveness were excellent in 40 patients, good in 10 patients, fair in 6 patients, and poor in 4 patients, with an excellent and good rate of 83.3%.

Conclusion: The simple lateral EDC split approach is fully exposed, and the loop-plate can fix the ulnar coronoid fractures firmly and stably, which can restore the stability of the elbow joint, and the effectiveness is satisfactory.
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http://dx.doi.org/10.7507/1002-1892.202010081DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8171629PMC
April 2021

Ablation of Mto1 in zebrafish exhibited hypertrophic cardiomyopathy manifested by mitochondrion RNA maturation deficiency.

Nucleic Acids Res 2021 05;49(8):4689-4704

Division of Medical Genetics and Genomics, The Children's Hospital, Zhejiang University School of Medicine and National Clinical Research Center for Child Health, Hangzhou, Zhejiang 310058, China.

Deficient maturations of mitochondrial transcripts are linked to clinical abnormalities but their pathophysiology remains elusive. Previous investigations showed that pathogenic variants in MTO1 for the biosynthesis of τm5U of tRNAGlu, tRNAGln, tRNALys, tRNATrp and tRNALeu(UUR) were associated with hypertrophic cardiomyopathy (HCM). Using mto1 knock-out(KO) zebrafish generated by CRISPR/Cas9 system, we demonstrated the pleiotropic effects of Mto1 deficiency on mitochondrial RNA maturations. The perturbed structure and stability of tRNAs caused by mto1 deletion were evidenced by conformation changes and sensitivity to S1-mediated digestion of tRNAGln, tRNALys, tRNATrp and tRNALeu(UUR). Notably, mto1KO zebrafish exhibited the global decreases in the aminoacylation of mitochondrial tRNAs with the taurine modification. Strikingly, ablated mto1 mediated the expression of MTPAP and caused the altered polyadenylation of cox1, cox3, and nd1 mRNAs. Immunoprecipitation assay indicated the interaction of MTO1 with MTPAP related to mRNA polyadenylation. These alterations impaired mitochondrial translation and reduced activities of oxidative phosphorylation complexes. These mitochondria dysfunctions caused heart development defects and hypertrophy of cardiomyocytes and myocardial fiber disarray in ventricles. These cardiac defects in the mto1KO zebrafish recapitulated the clinical phenotypes in HCM patients carrying the MTO1 mutation(s). Our findings highlighted the critical role of MTO1 in mitochondrial transcript maturation and their pathological consequences in hypertrophic cardiomyopathy.
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http://dx.doi.org/10.1093/nar/gkab228DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8096277PMC
May 2021

Ropivacaine inhibits proliferation, migration, and invasion while inducing apoptosis of glioma cells by regulating the SNHG16/miR-424-5p axis.

Open Life Sci 2020 31;15(1):988-999. Epub 2020 Dec 31.

Department of Anesthesiology, Ruijin Maternal and Child Health Hospital, Ruijin, Jiangxi, 342500, China.

Background: Regional anesthesia has anti-proliferative and pro-apoptotic effects in various cancers. Therefore, the purpose of this study was to investigate the effects of ropivacaine on the proliferation, migration, invasion, and apoptosis of glioma cells .

Methods: Under ropivacaine stimulation conditions, proliferation, apoptosis, migration, and invasion of glioma cells were determined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2-tetrazol-3-ium bromide (MTT), flow cytometry, and transwell assays, respectively. Western blot assay was employed to measure the protein expression levels in glioma cells. The expression levels of small nucleolar RNA host gene 16 (SNHG16) and miR-424-5p were assessed by reverse transcription-quantitative polymerase chain reaction (RT-qPCR). The interaction relationship between SNHG16 and miR-424-5p was predicted and confirmed using a bioinformatics database and dual-luciferase reporter, RNA immunoprecipitation (RIP) and RNA pull-down assays.

Results: After treatment with ropivacaine, proliferation, migration, and invasion were repressed while apoptosis was enhanced in glioma cells in a dose-depended manner. In addition, ropivacaine impeded SNHG16 expression in glioma cells. Importantly, overexpression of SNHG16 abolished the ropivacaine-induced effects on glioma cells. Analogously, knockdown of miR-424-5p counteracted the function of ropivacaine in glioma cells. We also found that SNHG16 bound to miR-424-5p and negatively regulated miR-424-5p expression in glioma cells. The rescue experiments indicated that ropivacaine might regulate glioma progression by targeting the SNHG16/miR-424-5p axis.

Conclusion: Our findings revealed the anti-tumor effects of ropivacaine in glioma by targeting the SNHG16/miR-424-5p axis. These data might extend the understanding of regulatory mechanisms by which ropivacaine could suppress glioma development.
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http://dx.doi.org/10.1515/biol-2020-0108DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7874551PMC
December 2020

Directional Proton Transfer in the Reaction of the Simplest Criegee Intermediate with Water Involving the Formation of Transient HO.

J Phys Chem Lett 2021 Apr 30;12(13):3379-3386. Epub 2021 Mar 30.

Shanghai Engineering Research Center of Molecular Therapeutics and New Drug Development, School of Chemistry and Molecular Engineering, East China Normal University, Shanghai, 200062, China.

The reaction of Criegee intermediates with water vapor has been widely known as a key Criegee reaction in the troposphere. Herein, we investigated the reaction of the smallest Criegee intermediate, CHOO, with a water cluster through fragment-based molecular dynamics simulations at the MP2/aug-cc-pVDZ level. Our results show that the CHOO-water reaction could occur not only at the air/water interface but also inside the water cluster. Moreover, more than one reactive water molecules are required for the CHOO-water reaction, which is always initiated from the Criegee carbon atom and ends at the terminal Criegee oxygen atom via a directional proton transfer process. The observed reaction pathways include the loop-structure-mediated and stepwise mechanisms, and the latter involves the formation of transient HO. The lifetime of transient HO is on the order of a few picoseconds, which may impact the atmospheric budget of the other trace gases in the actual atmosphere.
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http://dx.doi.org/10.1021/acs.jpclett.1c00448DOI Listing
April 2021

Ab initio determination of crystal stability of di-p-tolyl disulfide.

Sci Rep 2021 Mar 29;11(1):7076. Epub 2021 Mar 29.

Key Laboratory for Thin Film and Microfabrication of Ministry of Education, Department of Micro/Nano-Electronics, Shanghai Jiao Tong University, Shanghai, 200240, China.

With the rapid growth of energy demand and the depletion of existing energy resources, the new materials with superior performances, low costs and environmental friendliness for energy production and storage are explored. Di-p-tolyl disulfide (p-TolS) is a typical lubricating material, which has been applied in the field of energy storage. The conformational properties and phase transformations of p-TolS have been studied by pioneers, but their polymorphs and the polymorphism induced crystal structure changes require further analysis. In this study, we perform the crystal structural screening, prediction and optimization of p-TolS crystal with quantum mechanical calculations, i.e., density functional theory (DFT) and second-order Møller-Plesset perturbation (MP2) methods. A series of crystal structures with different molecular arrangements are generated based on the crystal structure screening. As compared to long-established lattice energy calculation, we take an advantage of using more accurate technique, which is Gibbs free energy calculation. It considers the effects of entropy and temperature to predict the crystal structures and energy landscape. By comparing the Gibbs free energies between predicted and experimental structures, we found that phase α is the most stable structure for p-TolS crystal at ambient temperature and standard atmospheric pressure. Furthermore, we provide an efficient method to discriminate different polymorphs that are otherwise difficult to be identified based on the Raman/IR spectra. The proposed work enable us to evaluate the quality of various crystal polymorphs rapidly.
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http://dx.doi.org/10.1038/s41598-021-86519-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8007795PMC
March 2021

Structural, Functional, and Molecular Imaging of Autism Spectrum Disorder.

Neurosci Bull 2021 Mar 29. Epub 2021 Mar 29.

Department of Nuclear Medicine and Medical PET Center, The Second Hospital of Zhejiang University School of Medicine, Hangzhou, 310009, China.

Autism spectrum disorder (ASD) is a heterogeneous neurodevelopmental disorder associated with both genetic and environmental risks. Neuroimaging approaches have been widely employed to parse the neurophysiological mechanisms underlying ASD, and provide critical insights into the anatomical, functional, and neurochemical changes. We reviewed recent advances in neuroimaging studies that focused on ASD by using magnetic resonance imaging (MRI), positron emission tomography (PET), or single-positron emission tomography (SPECT). Longitudinal structural MRI has delineated an abnormal developmental trajectory of ASD that is associated with cascading neurobiological processes, and functional MRI has pointed to disrupted functional neural networks. Meanwhile, PET and SPECT imaging have revealed that metabolic and neurotransmitter abnormalities may contribute to shaping the aberrant neural circuits of ASD. Future large-scale, multi-center, multimodal investigations are essential to elucidate the neurophysiological underpinnings of ASD, and facilitate the development of novel diagnostic biomarkers and better-targeted therapy.
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http://dx.doi.org/10.1007/s12264-021-00673-0DOI Listing
March 2021

Computational Analysis of Residue-Specific Binding Free Energies of Androgen Receptor to Ligands.

Front Mol Biosci 2021 12;8:646524. Epub 2021 Mar 12.

Shanghai Engineering Research Center of Molecular Therapeutics and New Drug Development, Shanghai Key Laboratory of Green Chemistry and Chemical Process, School of Chemistry and Molecular Engineering, East China Normal University, Shanghai, China.

Androgen receptor (AR) is an important therapeutic target for the treatment of diseases such as prostate cancer, hypogonadism, muscle wasting, etc. In this study, the complex structures of the AR ligand-binding domain (LBD) with fifteen ligands were analyzed by molecular dynamics simulations combined with the alanine-scanning-interaction-entropy method (ASIE). The quantitative free energy contributions of the pocket residues were obtained and hotspot residues are quantitatively identified. Our calculation shows that that these hotspot residues are predominantly hydrophobic and their interactions with binding ligands are mainly van der Waals interactions. The total binding free energies obtained by summing over binding contributions by individual residues are in good correlation with the experimental binding data. The current quantitative analysis of binding mechanism of AR to ligands provides important insight on the design of future inhibitors.
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http://dx.doi.org/10.3389/fmolb.2021.646524DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7994597PMC
March 2021

Circular RNAs: Their Role in the Pathogenesis and Orchestration of Breast Cancer.

Front Cell Dev Biol 2021 11;9:647736. Epub 2021 Mar 11.

Department of Plastic Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

As one of the most frequently occurring malignancies in women, breast cancer (BC) is still an enormous threat to women all over the world. The high mortality rates in BC patients are associated with BC recurrence, metastatic progression to distant organs, and therapeutic resistance. Circular RNAs (circRNAs), belonging to the non-coding RNAs (ncRNAs), are connected end to end to form covalently closed single-chain circular molecules. CircRNAs are widely found in different species and a variety of human cells, with the features of diversity, evolutionary conservation, stability, and specificity. CircRNAs are emerging important participators in multiple diseases, including cardiovascular disease, inflammation, and cancer. Recent studies have shown that circRNAs are involved in BC progress by regulating gene expression at the transcriptional or post-transcriptional level binding to miRNAs then inhibiting their function, suggesting that circRNAs may be potential targets for early diagnosis, treatment, and prognosis of BC. Herein, in this article, we have reviewed and summarized the current studies about the biogenesis, features, and functions of circRNAs. More importantly, we emphatically elucidate the pivotal functions and mechanisms of circRNAs in BC growth, metastasis, diagnosis, and drug resistance. Deciphering the complex networks, especially the circRNA-miRNA target gene axis, will endow huge potentials in developing therapeutic strategies for combating BC.
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http://dx.doi.org/10.3389/fcell.2021.647736DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7991790PMC
March 2021

Design and simulation of a secondary resource recycling system: A case study of lead-acid batteries.

Waste Manag 2021 May 18;126:78-88. Epub 2021 Mar 18.

School of Economics and Management, Nanchang University, Nanchang 330031, PR China.

The recycling of secondary resources is complicated as consumers, recyclers and governments are all involved in this process. In developing countries, compared to legal recyclers, illegal recyclers not only have cost advantages but also create serious pollution. Inappropriate management policies may cause disorder in the recycling market or inefficient fiscal management. This paper takes China's lead-acid batteries (LABs) from 2000 to 2015 as an example to construct a model of a secondary resource recovery system based on heterogeneous groups and analyzes the environmental and economic impacts of used LAB recycling. By simulating the implementation of different tax cuts, subsidies and regulatory policies by the government in each year, we observe the overall environmental impact of the recycling industry. This study finds that when the total amount of government expenditures is limited, the optimal policy combination emphasizes tax reduction and subsidy policies during the growth period of the recycling industry and uses more funds for supervision in the mature period. Under the balance of fiscal revenues and expenditures, the optimal policy combination can reduce the number of illegal recycling companies and waste lead emissions from the recycling market by 97.9% and 45.8%, respectively. Compared to research conducted using mathematical models and system dynamics models, this result is more in line with the actual situation, and the content is more intuitive. The government needs to adopt different policy combinations in different periods according to the state of the recycling market so that the recycling of secondary resources can achieve the optimal effect.
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http://dx.doi.org/10.1016/j.wasman.2020.12.038DOI Listing
May 2021

[Pollution Characteristics and Health Risk Assessment of Heavy Metals in the Water of Lijiang River Basin].

Huan Jing Ke Xue 2021 Apr;42(4):1714-1723

College of Environment Science and Engineering, Guilin University of Technology, Guilin 541004, China.

In order to clarify the pollution levels of heavy metals in the drinking water sources of the Lijiang River Basin, surface water samples were collected from 62 sites throughout the Lijiang River during May 2019. Heavy metals, including As, Cd, Cr, Mn, Cu, Zn, Hg, Co, and Sb, in the water samples were analysed. Health risk assessments associated with these nine heavy metals were conducted using the health risk assessment model from the US EPA. The results indicated that the order of the average concentrations of heavy metals in the water samples were Mn > Zn > As > Cr > Cu > Sb > Co > Cd > Hg. No heavy metals exceeded the limit values of the drinking water health standards in China (GB 5749-2006), and the concentrations were lower than the limitations of Grade Ⅰ level in the environmental quality standards for surface water (GB 3838-2002). According to the spatial distribution, the high contents areas of As, Cr, Zn, and Sb were predominantly distributed downstream of the Lijiang River, while the high contents areas of Cd, Cu, Hg, Co, and Mn were mostly distributed in the upper reaches. Multivariate analysis indicated that Cd, Mn, Cu, and Co were primarily from agricultural production; Cr, Zn, and Sb were mainly from tourism transportation; As was predominantly from the weathering of rock parent material and soil erosion; Hg was mainly from the improper disposal of domestic garbage and atmospheric deposition. The results of the health risk assessment indicated that children were more susceptible to the threat of heavy metal pollution than adults, and the average annual risk of carcinogenic heavy metals to human health through drinking water ingestion were higher than those of non-carcinogenic metals. The maximum personal average annual health risk of Cr was higher than the maximum allowance levels recommended by the International Commission on Radiological Protection (5×10 a). The average annual risk of non-carcinogenic heavy metals (10-10 a) decreased in the order of Co > Cu > Hg > Zn > Sb > Mn, which were far below the maximum allowance levels recommended by the ICRP.
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http://dx.doi.org/10.13227/j.hjkx.202008068DOI Listing
April 2021

Oral delivery of antioxidant enzymes for effective treatment of inflammatory disease.

Biomaterials 2021 04 9;271:120753. Epub 2021 Mar 9.

Chongqing Key Laboratory of Natural Product Synthesis and Drug Research, Chongqing University, Chongqing, 401331, China. Electronic address:

Oral administration of protein is very challenging for therapeutic applications due to its instability and easy degradation in the gastrointestinal tract. Herein, we reported an approach to encapsulate native anti-inflammatory proteins in wind chimes like cyclodextrin (WCC) for efficient oral protein delivery. The amphiphilic WCC can self-assemble into nanoparticles in aqueous solution and achieve superior encapsulation of two antioxidant enzymes such as superoxide dismutase (SOD) and catalase (CAT) by simply mixing with protein solution, avoiding any extra cumbersome steps that might inactivate protein. WCC nanovehicles can effectively protect enzyme activity and enhance their intracellular delivery. SOD and CAT co-loaded WCC nanoparticles (SC/WCC) can integrate the synergistic effect of SOD and CAT for enhancing the removal of reactive oxygen species (ROS), effectively inhibit the inflammatory response by reducing the secretion of proinflammatory factors and protect cells from ROS-induced oxidative damage. In the mouse colitis model, SC/WCC administered orally was able to efficiently accumulate in the inflamed colon, significantly inhibited the expression of proinflammatory mediators and notably alleviated the symptoms related to colitis. Therefore, we believe that the strategies we described here may provide a convenient and powerful platform for the treatment of other inflammatory diseases.
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http://dx.doi.org/10.1016/j.biomaterials.2021.120753DOI Listing
April 2021

A Wetting-Enabled-Transfer (WET) Strategy for Precise Surface Patterning of Organohydrogels.

Adv Mater 2021 Apr 12;33(16):e2008557. Epub 2021 Mar 12.

CAS Key Laboratory of Bio-inspired Materials and Interfacial Science, CAS Center for Excellence in Nanoscience, Technical Institute of Physics and Chemistry, Chinese Academy of Sciences, Beijing, 100190, P. R. China.

The ability to manipulate water and oil phases in a designable manner is of great significance in widespread fields from art paintings to materials science. However, achieving precise and stable surface patterns for two immiscible phases of water and oil remains a challenge. Herein, a general wetting-enabled-transfer (WET) strategy is reported to construct discretionary shape-defined surface patterns of organohydrogels along with their monolithic formation either from flat to curved surfaces or from the microscale to the macroscale. Locally differentiated wettability induces hydrophilic monomers and hydrophobic monomers from an emulsion system onto the wettability-matching regions of the prepatterned substrates, subsequently forming corresponding hydrogel and organogel patterns on the organohydrogel surface after in situ photopolymerization. The precision of the surface patterns can be controlled by optimizing the gel monomers, emulsion droplet size, and surface chemical composition of the prepatterned substrates. This finding may provide a feasible strategy for precisely patterning functional materials from two-immiscible-phase systems.
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http://dx.doi.org/10.1002/adma.202008557DOI Listing
April 2021

APE1 may influence CD4+ naïve T cells on recurrence free survival in early stage NSCLC.

BMC Cancer 2021 Mar 6;21(1):233. Epub 2021 Mar 6.

Cancer Center, Daping Hospital, Army Medical University (Third Military Medical University), No. 10 Changjiang Zhi Rd., Yuzhong Dist, Chongqing, 400042, China.

Background: It was demonstrated that multifunctional protein APE1 (Apurinic/apyrimidinic endonuclease 1) is closely related to tumor immune microenvironment in a number of investigations, Meanwhile, the abundance of tumor infiltrating lymphocytes (TILs) has been shown as a prognosis indicator in some researches. However, it remains unclear whether APE1 is involved in the process of TILs affecting the prognosis of patients. To this end, we investigated the associations between APE1 and TILs in non-small cell lung cancer (NSCLC) and explored whether APE1 would influence the associations of CD4 T cells infiltration with the prognosis of patients.

Methods: Genome-wide expression datasets were obtained from the Gene Expression Omnibus (GEO) public database under accession number GSE68465, GSE30219, GSE31210 and GSE50081. MCPcounter and CIBERSORT analysis was conducted to evaluate the abundance of TILs in 1006 NSCLC patients of GEO database. Spearman correlation tests were used to evaluate correlations between abundance of various TILs and APE1 expression. RFS (recurrence free survival) was estimated using the Kaplan-Meier method and the Cox proportional-hazards model. The expression level of APE1 and tumor-infiltrating CD4 T cells was evaluated by immunohistochemistry (IHC).

Results: The results showed that the abundance of CD4 naïve T cells was negatively associated with the APE1 expression. CD4 naïve T cells infiltration was a favorable prognostic factor for RFS, however, there was no effect of CD4 T cells infiltration on RFS in patients with high APE1 expression. Subsequently, it was further confirmed that CD4 T cells infiltration was negatively associated with the APE1 expression level in 108 NSCLC tissue samples; high CD4 T cells infiltration was associated with longer RFS in low APE1 expression group but not in APE1 high expression group.

Conclusion: These results suggested that APE1 may affect the relationship between CD4 T cells infiltration and prognosis in NSCLC. This study provides new insights into predictors of outcome in patients with NSCLC, and suggests that combining immunotherapy and APE1-targeted therapy may be a promising treatment for NSCLC.
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http://dx.doi.org/10.1186/s12885-021-07950-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7937314PMC
March 2021

[Metabonomics study of Shouhui Tongbian Capsules in slow transit constipation based on UPLC-ESI-QE-Orbitrap-MS].

Zhongguo Zhong Yao Za Zhi 2021 Feb;46(3):532-538

Center for New Drug Pharmacology, Lunan Pharmaceutical Group Co., Ltd. Linyi 276006, China State Key Laboratory of Generic Manufacture Technology of Chinese Traditional Medicine Linyi 276006 China Linyi Key Laboratory for Immunopharmacology and Immunotoxicology of Natural Medicine Linyi 276006, China.

The effect of Shouhui Tongbian Capsules(SHTB) on the endogenous metabolites of colon tissue in mice with slow transit constipation was analyzed by metabolomics methods to explore its mechanism in the treatment of constipation. ICR mice were randomly divided into normal group, model group and SHTB group according to the body weight. The mice were given diphenoxylate to establish the slow transit constipation model. Mouse carbon ink pushing rate, first defecation time and the number of defecation particles in 12 h were observed. The mouse colon tissue was separated and the mucous cells were detected by Periodic acid Schiff and Alcian blue(AB-PAS) staining. Ultra-high-performance liquid chromatography electrospray ionization orbitrap tandem mass spectrometry(UPLC-ESI-Orbitrap-MS/MS) technology was used to characterize the differences in tissue metabolism to screen out the potential different metabolites and possible metabolic pathways in colon tissue. The results indicated that SHTB could significantly shorten the first defecation time and the number of defecations, and increase the number of intestinal peristalsis and mucous cells in the colonic mucosa compared to the model mice. Metabolomics results showed that, compared with the normal group, a total of 17 potential biomarkers, including L-kynurenine, N6,N6,N6-trimethyl-L-lysine, L-formylkynurenine, N6-acetyl-L-lysine, L-phenylalanine, phenylacetaldehyde, xanthoxin, thymidine, glycyl-L-leucine, cystathionine,(R)-1-aminopropan-2-ol, deoxycytidine, gamma-glutamyl-gamma-aminobutyraldehyde, D-galactose, L-arginine, L-proline and pyruvate, were found and identified in colon tissue. Treated with SHTB, these metabolic differences tended to return to normal levels. Therefore, it could be made a conclusion that the therapeutic effect of SHTB on chronic transit constipation may be related to regulating phenylalanine metabolism, phenylalanine, tyrosine and tryptophan biosynthesis, arginine and proline metabolism, cysteine and methionine metabolism, tyrosine metabolism, arginine biosynthesis, pyruvate metabolism, glycolysis, pyrimidine metabolism, tricarboxylic acid cycle and galactose metabolism.
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http://dx.doi.org/10.19540/j.cnki.cjcmm.20201116.401DOI Listing
February 2021

Risk Factors of Elbow Stiffness After Open Reduction and Internal Fixation of the Terrible Triad of the Elbow Joint.

Orthop Surg 2021 Apr 22;13(2):530-536. Epub 2021 Feb 22.

Department of Orthopaedic Surgery, Hong Hui Hospital, Xi'an Jiaotong University, Xi'an, China.

Objective: To analyze the risk factors of elbow stiffness following open reduction and internal fixation of the terrible triad of the elbow joint.

Methods: A retrospective study was conducted of 100 patients with the terrible triad of the elbow joint, who had been treated at our hospital from January 2015 to December 2018. All patients were treated with a loop plate to repair the ulnar coronoid process. According to the severity of the injury, the radial head was either fixed or replaced, and the lateral collateral ligament was repaired with an anchor. According to the range of motion of the elbow during the last follow-up, the patients were divided into two groups. The stiffness group (displayed extension-flexion or pronation-supination <100°) consisted of 30 patients. The second group, named the non-stiffness group (exhibited extension-flexion and pronation-supination ≥100°), consisted of 70 patients. Related risk factors included age, gender, smoking, diabetes, whether the fracture is on the dominant side, mechanism of injury, fracture classification, time from injury to surgery, configuration of internal fixation of the radial head, postoperative immobilization time, and use of anti-heterotopic ossification drugs (oral indomethacin). Both t-test and chi squared test were used to analyze any significant differences. Only the variables with a P < 0.05 in the tests were retested into a logistic multiple regression in order to screen risk factors of elbow stiffness.

Results: All patients were followed up for 12-48 months (average, 25.7 months), and all patients exhibited bone healing. Multivariate regression analysis showed that high-energy injury (OR = 3.068, 95% CI 1.134-8.295, P = 0.027), time from injury to surgery > 1 week (OR = 2.714, 95% CI 1.029-7.159, P = 0.044), and postoperative immobilization time (OR = 3.237, 95% CI 1.176-8.908, P = 0.023) were independent risk factors of elbow stiffness after surgery for the terrible triad of the elbow.

Conclusion: High-energy injury, the time from injury to surgery > 1 week, and postoperative joint immobilization time > 2 weeks are the independent risk factors of elbow stiffness after surgery of the terrible triad of the elbow, which should be treated carefully in clinical treatment.
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http://dx.doi.org/10.1111/os.12879DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7957406PMC
April 2021