Publications by authors named "Qi Guo"

589 Publications

Aminopeptidase N-targeting nanomolecule-assisted delivery of VEGF siRNA to potentiate antitumour therapy by suppressing tumour revascularization and enhancing radiation response.

J Mater Chem B 2021 Sep 22;9(36):7530-7543. Epub 2021 Sep 22.

Department of Radiology, Tianjin Medical University Second Hospital, No. 23, Pingjiang Road, Hexi District, Tianjin 300211, P. R. China.

Tumour revascularization and the consequent radioresistance activated by the up-regulated angiogenic pathway after radiation exposure remain a major bottleneck for improving the tumouricidal effect of radiotherapy (RT) in hepatocellular carcinoma (HCC). Herein, we show that fabricated aminopeptidase N (ANP/CD13)-targeting Gd-hybridized gold nanomolecules (tGd-GNMs) can efficaciously suppress tumour revascularization and the consequent radioresistance, and then synergize in augmenting the RT response. Both and experiments demonstrate that the targeted delivery of vascular endothelial growth factor (VEGF) siRNA into the tumour site and the generation of an abundance of intratumourally cytotoxic reactive oxygen species (ROS) under X-ray radiation by the tGd-GNMs complex has the capability to down-regulate VEGF gene expression and strengthen the radiation response. Furthermore, the tGd-GNMs complex contributes to excellent active tumour targeting ability, remarkably enhancing tumour contrast in the fluorescence, computed tomography (CT) and magnetic resonance (MR) imaging modalities in real-time with a long imaging time window. Overall, the synthesized tGd-GNMs complex with excellent potentiation of the antitumour ability and real-time multimodal imaging ability represents a promising visualized theranostic nanoplatform for the treatment of HCC.
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http://dx.doi.org/10.1039/d1tb00990gDOI Listing
September 2021

Invasive Blood Pressure Measurement and In-hospital Mortality in Critically Ill Patients With Hypertension.

Front Cardiovasc Med 2021 1;8:720605. Epub 2021 Sep 1.

Department of Cardiology, Sun Yat-sen Memorial Hospital of Sun Yat-sen University, Guangzhou, China.

Invasive blood pressure (IBP) measurement is common in the intensive care unit, although its association with in-hospital mortality in critically ill patients with hypertension is poorly understood. A total of 11,732 critically ill patients with hypertension from the eICU-Collaborative Research Database (eICU-CRD) were enrolled. Patients were divided into 2 groups according to whether they received IBP. The primary outcome in this study was in-hospital mortality. Propensity score matching (PSM) and inverse probability of treatment weighing (IPTW) models were used to balance the confounding covariates. Multivariable logistic regression was used to evaluate the association between IBP measurement and hospital mortality. The IBP group had a higher in-hospital mortality rate than the no IBP group in the primary cohort [238 (8.7%) vs. 581 (6.5%), < 0.001]. In the PSM cohort, the IBP group had a lower in-hospital mortality rate than the no IBP group [187 (8.0%) vs. 241 (10.3%), = 0.006]. IBP measurement was associated with lower in-hospital mortality in the PSM cohort (odds ratio, 0.73, 95% confidence interval, 0.59-0.92) and in the IPTW cohort (odds ratio, 0.81, 95% confidence interval, 0.67-0.99). Sensitivity analyses showed similar results in the subgroups with high body mass index and no sepsis. In conclusion, IBP measurement was associated with lower in-hospital mortality in critically ill patients with hypertension, highlighting the importance of IBP measurement in the intensive care unit.
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http://dx.doi.org/10.3389/fcvm.2021.720605DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8440864PMC
September 2021

Preoperative Short Physical Performance Battery as a predictor of prolonged hospitalization after coronary artery bypass grafting in older patients.

J Int Med Res 2021 Sep;49(9):3000605211044043

Shanghai University of Medicine and Health Sciences Affiliated Zhoupu Hospital, Shanghai, China.

Objective: The study aimed to evaluate the predictive value of the Short Physical Performance Battery (SPPB) and its three components for identifying the requirement for a prolonged hospitalization for coronary artery bypass grafting (CABG) in older patients.

Methods: This prospective, observational study included 425 older patients who consecutively underwent selective CABG surgery. All patients were assessed for the SPPB. We analysed the association of the postoperative length of hospital stay with the SPPB and three components. Receiver operating characteristic curve analysis was performed to determine the validity of the SPPB for predicting older patients with a prolonged hospitalization (>8 days).

Results: The SPPB and its three individual components were independent risk factors for a prolonged postoperative length of hospital stay. Only the SPPB summary score and the 4-m gait speed components showed good discriminative capabilities. An SPPB score cut-off of 9.5 provided the best accuracy for identifying a prolonged hospitalization. A poor physical performance (SPPB <10 score) was related to an increased risk of adverse cardiac and cerebrovascular events within 6 months after discharge.

Conclusions: This study provides evidence for clinical utility of the SPPB score for identifying older patients undergoing CABG who are at risk of prolonged hospitalization.
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http://dx.doi.org/10.1177/03000605211044043DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8451264PMC
September 2021

Recent developments in antifungal lactic acid bacteria: Application, screening methods, separation, purification of antifungal compounds and antifungal mechanisms.

Crit Rev Food Sci Nutr 2021 Sep 15:1-15. Epub 2021 Sep 15.

College of Food Science and Engineering, Northwest A&F University, Yangling, China.

Fungal contamination of food, which causes large economic losses and public health problems, is a global concern. Chemical methods are typically used in the food industry to inhibit the growth of spoilage fungus, but there are several drawbacks of chemical methods. Thus, the development of consumer-friendly and ecologically sustainable biological preservation technology has become a hot spot in food research. As a natural biological control agent, lactic acid bacteria (LAB) is a good choice in food preservation due to its antifungal properties. In order to screen and identify new antifungal LAB and antifungal compounds, this review compares three screening methods (overlay method, agar diffusion method, and microplate inhibition method) of antifungal LAB and summarizes the separation and purification techniques of antifungal compounds. A discussion of the effects of LAB, media, temperature, pH, and incubation period on the antifungal activity of LAB to highlight the antifungal properties of LAB for future studies then follows. Additionally, the antifungal mechanism of LAB is elucidated from three aspects: 1) LAB cells, 2) antifungal compounds, and 3) co-cultivation. Finally, research regarding antifungal LAB in food preservation (fruits, vegetables, grain cereals, bakery products, and dairy products) is summarized, which demonstrates the potential application value of LAB in food.
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http://dx.doi.org/10.1080/10408398.2021.1977610DOI Listing
September 2021

Ultrasound Elastography for the Evaluation of Lymph Nodes.

Front Oncol 2021 17;11:714660. Epub 2021 Aug 17.

Department of Internal Medicine, Hirslanden Clinic, Bern, Switzerland.

The differential diagnosis of lymphadenopathy is important for predicting prognosis, staging, and monitoring the treatment, especially for cancer patients. Conventional computed tomography and magnetic resonance imaging characterize lymph node (LN) with disappointing sensitivity and specificity. Conventional ultrasound with the advantage of high resolution has been widely used for the LN evaluation. Ultrasound elastography (UE) using color map or shear wave velocity can non-invasively demonstrate the stiffness and homogeneity of both the cortex and medulla of LNs and can detect early circumscribed malignant infiltration. There is a need of a review to comprehensively discuss the current knowledge of the applications of various UE techniques in the evaluation of LNs. In this review, we discussed the principles of strain elastography and shear wave-based elastography, and their advantages and limitations in the evaluation of LNs. In addition, we comprehensively introduced the applications of various UE techniques in the differential diagnosis of reactive LNs, lymphoma, metastatic LNs, and other lymphadenopathy. Moreover, the applications of endoscopic UE and endobronchial UE are also discussed, including their use for improving the positive rate of diagnosis of fine-needle aspiration biopsy.
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http://dx.doi.org/10.3389/fonc.2021.714660DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8415874PMC
August 2021

Rapid Internal Control Reference Recombinase-Aided Amplification Assays for EBV and CMV Detection.

Biomed Environ Sci 2021 Aug;34(8):650-655

NHC Key Laboratory of Medical Virology and Viral Diseases, National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing 102206, China;Center for Biosafety Mega-Science, Chinese Academy of Sciences, Wuhan 430071, Hubei China.

Epstein-Barr virus (EBV) and cytomegalovirus (CMV), two of the most prevalent human herpesviruses, cause a wide spectrum of diseases and symptoms and are associated with serious health problem. In this study, we developed an internal control reference recombinase-aided amplification (ICR-RAA) assay for the rapid detection of EBV and CMV within 30 min. The assay had a sensitivity of 5 and 1 copies/test for EBV and CMV, respectively, with no cross reaction with other pathogens. In comparison with those of the commercial quantitative polymerase chain reaction (qPCR), the sensitivity of the EBV and CMV ICR-RAAs using extracted DNA was 93.33% and 84.84%, respectively; the specificity was 98.75% and 100.00%, respectively; and the Kappa values were 0.930 and 0.892 ( < 0.05), respectively. In comparison with those of qPCR, the sensitivity of the EBV and CMV ICR-RAAs using the DNA by thermal lysis was 72.22% and 80.00%, respectively; the specificity was 100.00%; and the Kappa values were 0.764 and 0.878 ( < 0. 05), respectively. Thus, rapid and specific detection of EBV and CMV is possible using ICR-RAA assays.
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http://dx.doi.org/10.3967/bes2021.091DOI Listing
August 2021

Newborn screening with targeted sequencing: a multicenter investigation and a pilot clinical study in China.

J Genet Genomics 2021 Aug 30. Epub 2021 Aug 30.

Beijing Key Laboratory for Genetics of Birth Defects, Beijing Pediatric Research Institute, Beijing 100045, China; MOE Key Laboratory of Major Diseases in Children, Beijing 100045, China; Rare Disease Center, National Center for Children's Health, Beijing 100045, China; Beijing Children's Hospital, Capital Medical University, Beijing 100045, China. Electronic address:

Different newborn screening (NBS) programs have been practiced in many countries since the 1960s. It is of considerable interest whether next-generation sequencing is applicable in NBS. We have developed a panel of 465 causative genes for 596 early-onset, relatively high incidence, and potentially actionable severe inherited diseases in our Newborn Screening with Targeted Sequencing (NESTS) program to screen 11,484 babies in 8 Women and Children's hospitals nationwide in China retrospectively. The positive rate from preliminary screening of NESTS was 7.85% (902/11,484). With 45.89% (414/902) follow-up of preliminary positive cases, the overall clinically confirmative diagnosis rate of monogenic disorders was 12.07% (50/414), estimating an average of 0.95% (7.85% × 12.07%) clinical diagnosis rate, suggesting that monogenic disorders account for a considerable proportion of birth defects. The disease/gene spectrum varied in different regions of China. NESTS was implemented in a hospital by screening 3923 newborns to evaluate its clinical application. The turn-around time of a primary report, including the sequencing period of < 7 days, was within 11 days by our automatic interpretation pipeline. Our results suggest that NESTS is feasible and cost-effective as a first-tier NBS program, which will change the status of current clinical practice of NBS in China.
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http://dx.doi.org/10.1016/j.jgg.2021.08.008DOI Listing
August 2021

[Mechanism of paeonol combined with paeoniflorin against myocardial ischemia injury:based on proteomics].

Zhongguo Zhong Yao Za Zhi 2021 Aug;46(15):3943-3948

Jiangsu University Zhenjiang 212013, China.

The study aims to investigate the effect of the compatibility of paeonol and paeoniflorin(hereinafter referred to as the compatibility) on the expression of myocardial proteins in rats with myocardial ischemia injury and explore the underlying mechanism of the compatibility against myocardial ischemia injury. First, the acute myocardial infarction rat model was established by ligation of the anterior descending branch of the left coronary artery. The model rats were given(ig) paeonol and paeoniflorin. Then protein samples were collected from rat cardiac tissue and quantified by tandem mass tags(TMT) to explore the differential proteins after drug intervention. The experimental results showed that differential proteins mainly involved phagocytosis engulfment, extracellular space, and antigen binding, as well as Kyoto encyclopedia of genes and genomes(KEGG) pathways of complement and coagulation cascades, syste-mic lupus erythematosus, and ribosome. In this study, the target proteins and related signaling pathways identified by differential proteomics may be the biological basis of the compatibility against myocardial ischemia injury in rats.
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http://dx.doi.org/10.19540/j.cnki.cjcmm.20210615.701DOI Listing
August 2021

Task-Specific Tailored Cationic Polymeric Network with High Base-Resistance for Unprecedented TcO Cleanup from Alkaline Nuclear Waste.

ACS Cent Sci 2021 Aug 13;7(8):1441-1450. Epub 2021 Aug 13.

State Key Laboratory of Radiation Medicine and Protection, School for Radiological and Interdisciplinary Sciences (RAD-X), and Collaborative Innovation Center of Radiation Medicine of Jiangsu Higher Education Institutions, Soochow University, Suzhou 215123, China.

Direct removal of TcO from alkaline nuclear waste is desirable because of the nuclear waste management and environmental protection relevant to nuclear energy but is yet to be achieved given that combined features of decent base-resistance and high uptake selectivity toward anions with low charge density have not been integrated into a single anion-exchange material. Herein, we proposed a strategy overcoming these challenges by rationally modifying the imidazolium unit of a cationic polymeric network (SCU-CPN-4) with bulky alkyl groups avoiding its ring-opening reaction induced by OH because of the steric hindrance effect. This significantly improves not only the base-resistance but also the affinity toward TcO as a result of enhanced hydrophobicity, compared to other existing anion-exchange materials. More importantly, SCU-CPN-4 exhibits record high uptake selectivity, fast sorption kinetics, sufficient robustness, and promising reusability for removing TcO from the simulated high-level waste stream at the U.S. Savannah River Site, a typical alkaline nuclear waste, in both batch experiment and dynamic column separation test for the first time.
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http://dx.doi.org/10.1021/acscentsci.1c00847DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8393213PMC
August 2021

A Novel Oxazolidinone, Contezolid (MRX-I), Expresses Activity .

Antimicrob Agents Chemother 2021 Aug 30:AAC0088921. Epub 2021 Aug 30.

Department of Respiratory Medicine, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, China.

An evaluation of the anti- activity expressed by a novel oxazolidinone, contezolid (MRX-I), toward 12 reference strains and 194 clinical isolates was conducted. Contezolid was active against , and comparable to the anti- effects of linezolid both extracellularly and intracellularly. Contezolid did not antagonize the most frequently used anti- drugs nor did pre-exposure to contezolid induce drug resistance. These results provide a novel approach to treating infections.
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http://dx.doi.org/10.1128/AAC.00889-21DOI Listing
August 2021

Interleukin 2 Ameliorates Autoimmune Neuroinflammation by Modulating the Balance of T Helper 17 Cells and Regulatory T Cells in Mouse.

Ann Clin Lab Sci 2021 Jul;51(4):529-534

Department of Hand Surgery, China-Japan Union Hospital, Jilin University, Changchun, Jilin, China

Objective: Multiple sclerosis (MS) is a progressive autoimmune-mediated inflammation of the central nervous system (CNS), and experimental autoimmune encephalomyelitis (EAE) is a suitable model to study the pathogenesis of MS. IL-2 has been considered as both a T cell growth factor and an anti-inflammatory cytokine. In the present study, we investigated the effects of a low dose IL-2 treatment on mouse EAE therapy.

Method: The expression of IL-2 and IL-2 receptor were predicted using public microarray data and verified by real-time PCR and ELISA in mouse EAE model. Mice were injected with Myelin Oligodendrocyte Glycoprotein (35-55)(MOG) subcutaneously to induce EAE model. IL-2 treatment was initiated during 5 consecutive days from day 15 post MOG immunization. Flow cytometry was applied to investigate the proportions of Th17 and Treg cells. ELISA was used to detect the concentrations of IL-17a, IFNr, IL-10 and TGFb.

Results: In this study, we showed that the IL-2 treatment ameliorates the clinical severity of EAE. Flow cytometry results indicated that the therapeutic effect was related to a reduction of Th17 cells and an expansion of Treg cells in the EAE spinal cord. experiments also confirmed the anti-inflammatory effect of IL-2 in EAE-reactivated T cells.

Conclusion: Low-dose IL-2 is a potential therapeutic strategy for EAE and MS.
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July 2021

Identification of Autophagy- and Ferroptosis-Related lncRNAs Functioned through Immune-Related Pathways in Head and Neck Squamous Carcinoma.

Life (Basel) 2021 Aug 16;11(8). Epub 2021 Aug 16.

Department of Geriatrics, Gerontology Institute of Anhui Province, The First Affiliated Hospital, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei 230026, China.

The interplay between autophagy and ferroptosis has been highlighted as an important event to decide cancer cell fate. However, the underlying mechanisms remain largely unclear. In this study, we systematically explored the expression, prognostic value and functional roles of lncRNA in autophagy and ferroptosis. By a set of bioinformatics analyses, we identified 363 autophagy- and ferroptosis-related lncRNAs (AF-lncRNAs) and found 17 of them are dramatically related to the prognosis of head and neck squamous cell carcinoma (HNSC) patients, named as prognosis-related AF-lncRNAs (PAF-lncRNAs). Based on six key PAF-lncRNAs, a risk score model was developed and used to categorize the TCGA-retrieved HNSC patients into two groups (high-risk vs. low-risk). Functional analysis showed the differentially expressed genes (DEGs) between the two groups were mainly enriched in immune-related pathways and regulated by a PAF-lncRNA-directed ceRNA (competitive endogenous RNA) network. Combined with a variety of immune infiltration analyses, we also found a decreased landscape of immune cell infiltration in high-risk groups. Together, by revealing PAF-lncRNAs with tumor prognostic features functioned through immune-related pathways, our work would contribute to show the pathogenesis of a lncRNA-directed interplay among autophagy, ferroptosis and tumor immunity in HNSC and to develop potential prognostic biomarkers and targets for tumor immunotherapy.
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http://dx.doi.org/10.3390/life11080835DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8399325PMC
August 2021

Liquid-Liquid Phase Separation of the Green Mussel Adhesive Protein Pvfp-5 is Regulated by the Post-Translated Dopa Amino Acid.

Adv Mater 2021 Aug 26:e2103828. Epub 2021 Aug 26.

Center for Sustainable Materials (SusMat), School of Materials Science and Engineering, Nanyang Technological University (NTU), 50 Nanyang Avenue, Singapore, 637553, Singapore.

The underwater adhesive prowess of aquatic mussels has been largely attributed to the abundant post-translationally modified amino acid l-3,4-dihydroxyphenylalanine (Dopa) in mussel foot proteins (MFPs) that make up their adhesive threads. More recently, it has been suggested that during thread fabrication, MFPs form intermediate fluidic phases such as liquid crystals or coacervates regulated by a liquid-liquid phase separation (LLPS) process. Here, it is shown that Dopa plays another central role during mussel fiber formation, by enabling LLPS of Pvfp-5β, a main MFP of the green mussel Perna viridis. Using residue-specific substitution of Tyrosine (Tyr) for Dopa during recombinant expression, Dopa-substituted Pvfp-5β is shown to exhibit LLPS under seawater-like conditions, whereas the Tyr-only version forms insoluble aggregates. Combining quantum chemistry calculations and solution NMR, a transient H-bonding network requiring the two hydroxyl groups of Dopa is found to be critical to enable LLPS in Dopa-mutated Pvfp-5β. Overall, the study suggests that Dopa plays an important role in regulating LLPS of MFPs, which may be critical to concentrate the adhesive proteins at the plaque/substrate interface and therefore produce a more robust adhesive. The findings also provide molecular-level lessons to guide biomanufacturing of protein-based materials such as bioadhesives and load-bearing fibers.
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http://dx.doi.org/10.1002/adma.202103828DOI Listing
August 2021

NAT10-Mediated N4-Acetylcytidine of RNA Contributes to Post-transcriptional Regulation of Mouse Oocyte Maturation .

Front Cell Dev Biol 2021 30;9:704341. Epub 2021 Jul 30.

Reproductive Medicine Center, Sixth Affiliated Hospital of Sun Yat-sen University, Guangzhou, China.

N4-acetylcytidine (ac4C), a newly identified epigenetic modification within mRNA, has been characterized as a crucial regulator of mRNA stability and translation efficiency. However, the role of ac4C during oocyte maturation, the process mainly controlled via post-transcriptional mechanisms, has not been explored. N-acetyltransferase 10 (NAT10) is the only known enzyme responsible for ac4C production in mammals and ac4C-binding proteins have not been reported yet. In this study, we have documented decreasing trends of both ac4C and NAT10 expression from immature to mature mouse oocytes. With NAT10 knockdown mediated by small interfering RNA (siRNA) in germinal vesicle (GV)-stage oocytes, ac4C modification was reduced and meiotic maturation was significantly retarded. Specifically, the rate of first polar body extrusion was significantly decreased with NAT10 knockdown (34.6%) compared to control oocytes without transfection (74.6%) and oocytes transfected with negative control siRNA (72.6%) ( < 0.001), while rates of germinal vesicle breakdown (GVBD) were not significantly different ( = 0.6531). RNA immunoprecipitation and high-throughput sequencing using HEK293T cells revealed that the modulated genes were enriched in biological processes associated with nucleosome assembly, chromatin silencing, chromatin modification and cytoskeletal anchoring. In addition, we identified TBL3 as a potential ac4C-binding protein by a bioinformatics algorithm and RNA pulldown with HEK293T cells, which may mediate downstream cellular activities. Taken together, our results suggest that NAT10-mediated ac4C modification is an important regulatory factor during oocyte maturation and TBL3 is a potential ac4C-binding protein.
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http://dx.doi.org/10.3389/fcell.2021.704341DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8363255PMC
July 2021

Global Disease Burden From Acute Glomerulonephritis 1990-2019.

Kidney Int Rep 2021 Aug 5;6(8):2212-2217. Epub 2021 May 5.

Department of Nephrology, The First Affiliated Hospital, Zhejiang University, Hangzhou, China.

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http://dx.doi.org/10.1016/j.ekir.2021.04.038DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8343788PMC
August 2021

Rational design of selective HDAC2 inhibitors for liver cancer treatment: computational insights into the selectivity mechanism through molecular dynamics simulations and QM/MM calculations.

Phys Chem Chem Phys 2021 Aug 9;23(32):17576-17590. Epub 2021 Aug 9.

Key Laboratory of Structure-Based Drug Design & Discovery, Ministry of Education, Shenyang Pharmaceutical University, Shenyang 110016, Liaoning 110016, China.

The rational design of selective histone deacetylase 2 (HDAC2) inhibitors is beneficial for the therapeutic treatment of liver cancer, though HDAC2 is highly homologous to HDAC8, which may lead to undesired side effects due to the pan-inhibition towards HDAC2 and HDAC8. To clarify the structural basis of selective inhibition towards HDAC2 over HDAC8, we utilized multiple in silico strategies, including sequence alignment, structural comparison, molecular docking, molecular dynamics simulations, free energy calculations, alanine scanning mutagenesis, pharmacophore modeling, protein contacts atlas analysis and QM/MM calculations to study the binding patterns of HDAC2/8 selective inhibitors. Through the whole process described above, it is found that although HDAC2 has conserved GLY154 and PHE210 that also exist within HDAC8, namely GLY151 and PHE208, the two isoforms exhibit diverse binding modes towards their inhibitors. Typically, HDAC2 inhibitors interact with the Zn ions through the core chelate group, while HDAC8 inhibitors adopt a bent conformation within the HDAC8 pocket that inclines to be in contact with the Zn ions through the terminal hydroxamic acid group. In summary, our data comprehensively elucidate the selectivity mechanism towards HDAC2 over HDAC8, which would guide the rational design of selective HDAC2 inhibitors for liver cancer treatment.
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http://dx.doi.org/10.1039/d1cp02264dDOI Listing
August 2021

Base editing-coupled survival screening enabled high-sensitive analysis of PAM compatibility and finding of the new possible off-target.

iScience 2021 Jul 24;24(7):102769. Epub 2021 Jun 24.

State Key Laboratory of Microbial Technology, Shandong university, Qingdao 266237, People's Republic of China.

Base editing (BE) is a promising genome engineering tool for modifying DNA or RNA and has been widely used in various microorganisms as well as eukaryotic cells. Despite the proximal protospacer adjacent motif (PAM) is critical to the targeting range and off-target effect of BE, there is still lack of a specific approach to analyze the PAM pattern in BE systems. Here, we developed a base editing-coupled survival screening method. Using dCas9 from (SpdCas9) and its variants xdCas9 3.7 and dCas9 NG as example, their PAM patterns in BE systems were extensively characterized using the NNNN PAM library with high sensitivity. In addition to the typical PAM recognition features, we observed more unique PAMs exhibiting BE activity. These PAM patterns will boost the finding of potential off-target editing event arising from non-canonical PAMs and provide the guidelines for PAM usage in the BE system.
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http://dx.doi.org/10.1016/j.isci.2021.102769DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8324807PMC
July 2021

Long Sleep Duration Associated With Cognitive Impairment in Chinese Community-Dwelling Older Adults.

J Nerv Ment Dis 2021 Jul 30. Epub 2021 Jul 30.

Shanghai University of Medicine and Health Science Affiliated First Rehabilitation Hospital Shanghai University of Traditional Chinese Medicine College of Rehabilitation Sciences, Shanghai University of Medicine and Health Sciences, Shanghai, China.

Abstract: We aimed to examine the association between sleep duration and impaired cognitive function in different cognitive domains in Chinese community-dwelling older adults. A total of 1591 participants (≥60 years) were divided into five groups: ≤6 hours (very short sleep duration), >6 to 7 hours (short sleep duration), ≥7 to 8 hours (moderate sleep duration), >8 to 9 hours (moderately long sleep duration), and >9 hours (long sleep duration), according to sleep duration. Cognitive function was assessed using the Mini-Mental State Examination. Long sleep duration significantly increased the likelihood of cognitive impairment. In addition to attention, long sleep duration was negatively related to poorer global cognition and other cognitive domain functions. With the stratification of age groups, long sleep duration was negatively associated with other cognitive domain functions except delayed recall in older elderly (≥75 years) people, but not in younger elderly (60-74 years) people. Long sleep duration was associated with higher rates of cognitive impairment, poorer global cognition, and declined orientation, memory, language ability, and executive function in Chinese community-dwelling older adults, which was more significant in older elderly people.
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http://dx.doi.org/10.1097/NMD.0000000000001401DOI Listing
July 2021

Y-Box Binding Protein 1 Regulates Angiogenesis in Bladder Cancer via miR-29b-3p-VEGFA Pathway.

J Oncol 2021 1;2021:9913015. Epub 2021 Jul 1.

Institute of Urology, Lanzhou University Second Hospital, Key Laboratory of Urological Diseases in Gansu Province, Gansu Nephro-Urological Clinical Center, Lanzhou 730030, Gansu, China.

Angiogenesis plays a vital role in the development of bladder cancer (BC). The Y-box-binding protein 1 (YB-1) is a well-known oncoprotein which is closely related to angiogenesis of tumors, but the relationship and mechanism of YB-1 and angiogenesis in BC remain unclear. Based on 56 clinical BC specimens, this study found that high expression of YB-1 samples demonstrated a higher expression of vascular endothelial growth factor A (VEGFA) than those of YB-1 low expression. Subsequently, the expression of YB-1 and miR-29b-3p was regulated in the BC cell lines where we noted that YB-1 promoted VEGFA expression by downregulating the expression of miR- 29b-3p. The ability of BC cells to induce angiogenesis decreased after YB-1 was knocked down. Moreover, the in vivo study further confirmed that YB-1 promotes angiogenesis in BC. Our findings enhance the understanding of how YB-1 promotes angiogenesis in BC and provide evidence for YB-1 as a therapeutic target of BC. Moreover, this may provide new inspiration for miRNAs replacement therapies.
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http://dx.doi.org/10.1155/2021/9913015DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8270724PMC
July 2021

Association Between Physical Performance and Cognitive Function in Chinese Community-Dwelling Older Adults: Serial Mediation of Malnutrition and Depression.

Clin Interv Aging 2021 12;16:1327-1335. Epub 2021 Jul 12.

Department of Rehabilitation Medicine, Shanghai University of Medicine and Health Sciences, Shanghai, People's Republic of China.

Purpose: We aimed to propose a serial mediational model to further analyze the relationship between poor physical performance, malnutrition, depression and cognitive impairment in Chinese community-dwelling older adults.

Patients And Methods: This study consisted of 1386 community-dwelling Chinese older adults aged 65 years and older in Shanghai, China. Mild cognitive impairment (MCI) was assessed by the Mini-Mental State Examination (MMSE) and Instrumental Activities Of Daily Living (IADL). Physical performance was assessed by short physical performance battery (SPPB). Malnutrition was defined with the Mini Nutritional Assessment (MNA). Depressive symptoms were evaluated by the 30-item Geriatric Depression Scale (GDS). Serial multiple mediator models were used.

Results: The mean age of the final analysis sample was 73.62±6.14, and 57.6% (n=809) were females. The prevalence of MCI was 14.35% (n=199). Physical performance (p<0.001), nutritional status (p=0.025), and depressive symptoms (p=0.002) were correlated with MCI. The serial mediational model revealed that MNA and GDS scores significantly mediated association of SPPB and MMSE scores (c'=0.4728, p<0.001). Furthermore, depressive symptoms significantly mediated the association of physical performance and cognition (p=0.0311), while malnutrition had no independent mediating effect between these two factors (p=0.794).

Conclusion: Our study examined the serial multiple mediation roles of nutritional status and depressive symptoms on the relationship between physical performance and cognitive function in community-dwelling Chinese older adults. Older adults who were in poor physical condition tend to have worse nutritional status, more severe depression, and poorer cognitive function.
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http://dx.doi.org/10.2147/CIA.S315892DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8285124PMC
July 2021

Mobility speed predicts new-onset hypertension: a longitudinal study.

Blood Press Monit 2021 Jul 13. Epub 2021 Jul 13.

PT Department, College of Rehabilitation Sciences, Shanghai University of Medicine and Health Sciences Department of Acupuncture, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, China.

Objective: The aim of this study was to investigate whether declining mobility and muscle strength predict new-onset hypertension in suburban-dwelling elderly individuals.

Methods: This study was designed as a longitudinal prospective cohort study. It was comprised of 362 individuals (mean age = 67.8 ± 6.2; 157 men) without hypertension at baseline. At baseline, all participants completed health questionnaires and underwent measurements of mobility [the Timed Up and Go test (TUGT) and 4-m walking test] and muscle strength (grip strength). At 1-year follow-up, we determined the number of participants who had developed new-onset hypertension. We then evaluated the relationship between above metrics and the development of hypertension.

Results: In the present study, 94 (26.0%) participants developed hypertension after 1 year. After adjusting for mixed factors, the TUGT scores [hazard ratio = 1.15; 95% confidence interval (CI), 1.10-1.31; P = 0.030] were positively associated with the development of hypertension, while the 4-m walking test scores (hazard ratio = 0.07; 95% CI, 0.01-0.47; P = 0.007) showed an inverse relationship with hypertension incidence. Grip strength (hazard ratio = 1.03; 95% CI, 0.99-1.06; P = 0.098) was not significantly associated with hypertension incidence.

Conclusion: Our results indicate that people with declining mobility are significantly more likely to develop hypertension. Hence, improving mobility could be protective against hypertension for elderly individuals.
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http://dx.doi.org/10.1097/MBP.0000000000000562DOI Listing
July 2021

Coexisting nutcracker phenomenon and superior mesenteric artery syndrome in a patient with IgA nephropathy: A case report.

Medicine (Baltimore) 2021 Jul;100(28):e26611

Department of Nephrology, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, Shandong, China.

Rationale: Nutcracker and superior mesenteric artery (SMA) syndrome share the same pathogenesis, but the simultaneous occurrence of both diseases is quite rare. A combination of the nutcracker syndrome and IgA nephropathy has previously been reported. Herein, we report what we believe is the first case of coexisting nutcracker and SMA syndrome in a patient with IgA nephropathy.

Patient Concerns: A 15-year-old Chinese boy who was diagnosed with IgA nephropathy at 8 years of age presented with gross hematuria, fatigue, anorexia, nausea, and recurrent abdominal distension for 1 week without any obvious evidence of preceding infection. Laboratory data showed macroscopic hematuria, heavy proteinuria, and relatively normal renal function. Doppler ultrasonography and upper gastrointestinal gastrografin study were performed, respectively. Since his renal function deteriorated after admission, repeated renal biopsy was performed.

Diagnoses: IgA nephropathy with nutcracker phenomenon and SMA syndrome.

Intervention: Immunosuppressive therapy combined with conservative therapy for superior mesenteric artery syndrome.

Outcomes: One month later, his abdomen symptoms such as anorexia and abdominal distension eased a lot with body weight increase of about 3 kg. After 6 months of follow-up, his body weight increased to 57 kg, serum creatinine decreased to 63 μmol/L, and urine microscopy showed 75.5 RBC/high-power field with 0.3 g urine protein per day.

Lessons: Although the association between vascular compression and IgA nephropathy (IgAN) has not been elucidated yet, combination of nutcracker syndrome and SMA syndrome should be considered in patients with IgAN. The combination may increase the complexity of the disease, and renal biopsy should not be hesitated for differential diagnosis.
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http://dx.doi.org/10.1097/MD.0000000000026611DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8284758PMC
July 2021

Mediating effects of lower extremity function on the relationship between night sleep duration and cardiovascular disease risk: a cross-sectional study in elderly Chinese without cardiovascular diseases.

BMJ Open 2021 07 8;11(7):e046015. Epub 2021 Jul 8.

Shanghai University of Traditional Chinese Medicine, Shanghai, China

Objective: The purpose of this study is to investigate the mediating effect of physical performance on the relationship between night sleep duration and risk of cardiovascular disease (CVD) in elderly Chinese without CVD.

Methods: 782 participants without CVD over 65 years (average: 70.82±3.86 years, 448 women) were included in this study. CVD risk was calculated by the Framingham Risk Score and participants were divided into four groups of night sleep duration (in hours): <7 hours, ≥7-8 hours, >8-9 hours and >9 hours. Upper extremity function was measured by grip strength and lower extremity function was measured by the Short Physical Performance Battery (SPPB), consisting of balance, 4 m walk and chair stands tests.

Results: After adjusting for covariates, long night sleep duration (>9 hours) and CVD risk were significantly positively associated compared with moderate night sleep duration (≥7-8 hours) (β=1.152; 95% CI 0.05 to 2.25). SPPB total score (indirect effect ab=-0.122; 95% CI -0.291 to -0.0008) rather than grip strength partially mediated the relationship between long night sleep duration and CVD risk, in which chair stands played a major mediating role (indirect effect ab=-0.171; 95% CI -0.040 to -0.0006), while balance (indirect effect ab=-0.016; 95% CI -0.100 to 0.063) and 4 m walk (indirect effect ab=0.048; 95% CI -0.066 to 0.201) did not.

Conclusions: Lower extremity function, especially lower limb muscle strength, partially mediates a positive association between long night sleep duration and CVD risk in the elderly without CVD. Suitable interventions for physical performance and sleep may minimise the risk of subsequent CVD.
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http://dx.doi.org/10.1136/bmjopen-2020-046015DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8268917PMC
July 2021

Shotgun proteomics of Brassica rapa seed proteins identifies vicilin as a major seed storage protein in the mature seed.

PLoS One 2021 9;16(7):e0253384. Epub 2021 Jul 9.

Southern Cross Plant Science, Faculty of Science and Engineering, Southern Cross University, Lismore, New South Wales, Australia.

Proteins make up a large percentage of the Brassica seed and are second only to the oil in economic importance with uses for both animal and human nutrition. The most abundant proteins reported in the seeds of Brassica are the seed storage proteins cruciferin and napin, belonging to the 12S globulin and 2S albumin families of proteins, respectively. To gain insight into the Brassica rapa seed proteome and to confirm the presence and relative quantity of proteins encoded by candidate seed storage genes in the mature seed, shotgun proteomics was carried out on protein extracts from seeds of B. rapa inbred line R-o-18. Following liquid chromatography tandem mass spectrometry, a total of 34016 spectra were mapped to 323 proteins, where 233 proteins were identified in 3 out of 4 biological replicates by at least 2 unique peptides. 2S albumin like napin seed storage proteins (SSPs), 11/12S globulin like cruciferin SSPs and 7S globulin like vicilin SSPs were identified in the samples, along with other notable proteins including oil body proteins, namely ten oleosins and two oil body-associated proteins. The identification of vicilin like proteins in the mature B. rapa seed represents the first account of these proteins in the Brassicaceae and analysis indicates high conservation of sequence motifs to other 7S vicilin-like allergenic proteins as well as conservation of major allergenic epitopes in the proteins. This study enriches our existing knowledge on rapeseed seed proteins and provides a robust foundation and rational basis for plant bioengineering of seed storage proteins.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0253384PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8270179PMC
July 2021

Biological implications of genetic variations in autism spectrum disorders from genomics studies.

Biosci Rep 2021 Jul;41(7)

Beijing Key Laboratory for Genetics of Birth Defects, Beijing Pediatric Research Institute; MOE Key Laboratory of Major Diseases in Children; Rare Disease Center, National Center for Children's Health, Beijing Children's Hospital, Capital Medical University, Beijing, China.

Autism spectrum disorder (ASD) is a highly heterogeneous neurodevelopmental condition characterized by atypical social interaction and communication together with repetitive behaviors and restricted interests. The prevalence of ASD has been increased these years. Compelling evidence has shown that genetic factors contribute largely to the development of ASD. However, knowledge about its genetic etiology and pathogenesis is limited. Broad applications of genomics studies have revealed the importance of gene mutations at protein-coding regions as well as the interrupted non-coding regions in the development of ASD. In this review, we summarize the current evidence for the known molecular genetic basis and possible pathological mechanisms as well as the risk genes and loci of ASD. Functional studies for the underlying mechanisms are also implicated. The understanding of the genetics and genomics of ASD is important for the genetic diagnosis and intervention for this condition.
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http://dx.doi.org/10.1042/BSR20210593DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8298259PMC
July 2021

Transseptal Puncture in Patients with Septal Occluder Devices during Catheter Ablation of Atrial Fibrillation.

EuroIntervention 2021 07 6. Epub 2021 Jul 6.

Department of Cardiology, Beijing Anzhen Hospital, Capital Medical University, National Clinical Research Center for Cardiovascular Diseases, Beijing, China.

Background: The atrial septal occluder (ASO) becomes a major obstacle to the widespread adoption of atrial fibrillation (AF) catheter ablation in patients with prior atrial septal defects (ASD) closure.

Aims: To describe the "Sequential Technique" of transseptal puncture (TSP) in AF patients with ASO.

Methods: Sixty-four drug-refractory AF patients with ASO who underwent catheter ablation in our center from September 2007 to March 2020 were enrolled.

Results: Puncture through the native septum was acquired in 29 patients (Group A) and through the device in 35 patients (Group B). The mean diameter of the occluder was significantly larger in Group B than in Group A (31.6 ± 4.6 mm vs. 22.8 ± 3.5 mm, P <0.001). The mean time of TSP (24.9 ± 8.8 vs. 5.8 ± 2.1min, P <0.001), total fluoroscopy time (23.7 ± 10.9 vs. 7.5 ± 4.4 min, P <0.001), and total procedure time (172.7 ± 58.3 vs. 123.4 ± 43.8 min, P =0.001) of Group B were significantly longer than that of Group A. In group B, 21 patients got the external sheath crossed the device by reshaping the needle and adjusting the puncture angle and position (Group B1), 12 patients got the external sheath crossed the device with assistance of the balloon dilation (Group B2). No patient had thrombus, periprocedural interatrial shunt and procedural complications.

Conclusions: TSP and AF ablation in patients with ASO are feasible and safe. The "Sequential Technique" could be safely used in patients with ASO.
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http://dx.doi.org/10.4244/EIJ-D-21-00340DOI Listing
July 2021

Adsorption Mechanism of Patulin from Apple Juice by Inactivated Lactic Acid Bacteria Isolated from Kefir Grains.

Toxins (Basel) 2021 06 22;13(7). Epub 2021 Jun 22.

College of Food Science and Engineering, Northwest A&F University, Yangling 712100, China.

In the food industry, microbiological safety is a major concern. Mycotoxin patulin represents a potential health hazard, as it is heat-resistant and may develop at any stage during the food chain, especially in apple-based products, leading to severe effects on human health, poor quality products, and profit reductions. The target of the study was to identify and characterize an excellent adsorbent to remove patulin from apple juice efficiently and to assess its adsorption mechanism. To prevent juice fermentation and/or contamination, autoclaving was involved to inactivate bacteria before the adsorption process. The HPLC (high-performance liquid chromatography) outcome proved that all isolated strains from kefir grains could reduce patulin from apple juice. A high removal of 93% was found for juice having a 4.6 pH, 15° Brix, and patulin concentration of 100 μg/L by , named JKSP109, which was morphologically the smoothest and biggest of all isolates in terms of cell wall volume and surface area characterized by SEM (Scanning electron microscopy) and TEM (transmission electron microscopy). C=O, OH, C-H, and N-O were the main functional groups engaged in patulin adsorption indicated by FTIR (Fourier transform-infrared). E-nose (electronic nose) was performed to evaluate the aroma quality of the juices. PCA (Principal component analysis) results showed that no significant changes occurred between control and treated juice.
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http://dx.doi.org/10.3390/toxins13070434DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8309945PMC
June 2021

Epsilon-polylysine based magnetic nanospheres as an efficient and recyclable antibacterial agent for Alicyclobacillus acidoterrestris.

Food Chem 2021 Dec 21;364:130382. Epub 2021 Jun 21.

College of Food Science and Engineering, Northwest A & F University, Yangling 712100, China; Laboratory of Quality & Safety Risk Assessment for Agro-products (Yangling), Ministry of Agriculture, Yangling 712100, China; College of Food Science and Technology, Northwest University, Xi'an 710069, China. Electronic address:

In this work, polyacrylic acid modified ferroferric oxide (FeO-PAA) was synthesized via a one-step hydrothermal method. The magnetic nanospheres modified with carboxyl groups were combined with epsilon-polylysine (EPL) via an EDC/NHS coupling reaction to obtain FeO-PAA-EPL nanospheres. FeO-PAA-EPL was employed as an antibacterial agent against Alicyclobacillus acidoterrestris and characterized by XRD, FTIR, XPS, VSM, SEM and TEM techniques. Experimental results showed the minimum inhibition concentration (MIC) of FeO-PAA-EPL against A. acidoterrestris was 1.25 mg mL. Furthermore, A. acidoterrestris treated with FeO-PAA-EPL nanospheres obviously lysed. Morphological analysis of bacteria supported by SEM indicated that the cell membrane of A. acidoterrestris was damaged, revealing that FeO-PAA-EPL is an effective antibacterial agent. Additionally, the nanospheres with excellent magnetism can be simply separated from a reaction system via an external magnet. The construction of magnetic nanospheres with satisfactory antibacterial activity provides an effective and new method to control A. acidoterrestris.
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http://dx.doi.org/10.1016/j.foodchem.2021.130382DOI Listing
December 2021

Metric learning for image-based flower cultivars identification.

Plant Methods 2021 Jun 22;17(1):65. Epub 2021 Jun 22.

College of Agriculture / College of Tree Peony, Henan University of Science and Technology, Luoyang, 471023, China.

Background: The study of plant phenotype by deep learning has received increased interest in recent years, which impressive progress has been made in the fields of plant breeding. Deep learning extremely relies on a large amount of training data to extract and recognize target features in the field of plant phenotype classification and recognition tasks. However, for some flower cultivars identification tasks with a huge number of cultivars, it is difficult for traditional deep learning methods to achieve better recognition results with limited sample data. Thus, a method based on metric learning for flower cultivars identification is proposed to solve this problem.

Results: We added center loss to the classification network to make inter-class samples disperse and intra-class samples compact, the script of ResNet18, ResNet50, and DenseNet121 were used for feature extraction. To evaluate the effectiveness of the proposed method, a public dataset Oxford 102 Flowers dataset and two novel datasets constructed by us are chosen. For the method of joint supervision of center loss and L-softmax loss, the test accuracy rate is 91.88%, 97.34%, and 99.82% across three datasets, respectively. Feature distribution observed by T-distributed stochastic neighbor embedding (T-SNE) verifies the effectiveness of the method presented above.

Conclusions: An efficient metric learning method has been described for flower cultivars identification task, which not only provides high recognition rates but also makes the feature extracted from the recognition network interpretable. This study demonstrated that the proposed method provides new ideas for the application of a small amount of data in the field of identification, and has important reference significance for the flower cultivars identification research.
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http://dx.doi.org/10.1186/s13007-021-00767-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8220695PMC
June 2021

Plasma Proteomics of Renal Function: A Trans-ethnic Meta-analysis and Mendelian Randomization Study.

J Am Soc Nephrol 2021 Jun 16. Epub 2021 Jun 16.

M Prunotto, School of Pharmaceutical Sciences, University of Geneva, Geneva, Switzerland.

Background: Studies on the relationship between renal function and the human plasma proteome have identified several potential biomarkers. However, investigations have been conducted largely in European populations, and causality of the associations between plasma proteins and kidney function has never been addressed.

Methods: A cross-sectional study of 993 plasma proteins among 2,882 participants in four studies of European and admixed ancestries (KORA, INTERVAL, HUNT, QMDiab) identified trans-ethnic associations between eGFR/CKD and proteomic biomarkers. For the replicated associations, two-sample bidirectional Mendelian randomization (MR) was used to investigate potential causal relationships. Publicly available datasets and transcriptomic data from independent studies were used to examine the association between gene expression in kidney tissue and eGFR .

Results: Fifty-seven plasma proteins were associated with eGFR, including one novel protein. Twenty-three of these were additionally associated with CKD. The strongest inferred causal effect was the positive effect of eGFR on testican-2, in line with the known biological role of this protein and the expression of its protein-coding gene (SPOCK2) in renal tissue. We also observed suggestive evidence of an effect of melanoma inhibitory activity (MIA), carbonic anhydrase III, and cystatin-M on eGFR.

Conclusions: In a discovery-replication setting, we identified 57 proteins trans-ethnically associated with eGFR. The revealed causal relationships are an important stepping-stone in establishing testican-2 as a clinically relevant physiological marker of kidney disease progression, and point to additional proteins warranting further investigation.
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http://dx.doi.org/10.1681/ASN.2020071070DOI Listing
June 2021
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