Publications by authors named "Kai Yang"

1,327 Publications

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Antimicrobial and Bioactive Silk Peptide Hybrid Hydrogel with a Heterogeneous Double Network Formed by Orthogonal Assembly.

ACS Biomater Sci Eng 2021 Dec 3. Epub 2021 Dec 3.

Institute for Frontier Materials, Deakin University, Geelong, Victoria 3200, Australia.

Hydrogels mimic the natural extracellular matrix in terms of their nanofibrous structure and large water content. However, the lack of a combination of properties including sufficient heterogeneity in the gel structure, intrinsic antimicrobial activity, and bioactivity limits the efficiency of hydrogels for tissue engineering applications. In this work, a hydrogel with a combination of these properties was fabricated by hybridizing silk fibroin with a low-molecular-weight peptide gelator. It was observed that silk fibroin and the peptide gelator assembled orthogonally in sequence. While the morphology of silk fibroin nanofibrils was not affected by the peptide gelator, silk fibroin promoted the formation of wider nanoribbons of the peptide gelator by modulating its nucleation and growth. Orthogonal assembly maintained the antimicrobial activity of the peptide gelator and the excellent biocompatibility of silk fibroin in the hybrid gel. The hybrid gel also demonstrated improved interactions with cells, an indicator of a higher bioactivity, possibly due to the heterogeneous double network structure.
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http://dx.doi.org/10.1021/acsbiomaterials.1c01228DOI Listing
December 2021

An Oxidative Stress-Related Gene Pair (/), Competitive Endogenous RNAs, and Immune-Infiltration Patterns Potentially Regulate Intervertebral Disc Degeneration Development.

Front Immunol 2021 9;12:765382. Epub 2021 Nov 9.

Department of Orthopaedics, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China.

Oxidative stress (OS) irreversibly affects the pathogenesis of intervertebral disc degeneration (IDD). Certain non-coding RNAs act as competitive endogenous RNAs (ceRNAs) that regulate IDD progression. Analyzing the signatures of oxidative stress-related gene (OSRG) pairs and regulatory ceRNA mechanisms and immune-infiltration patterns associated with IDD may enable researchers to distinguish IDD and reveal the underlying mechanisms. In this study, OSRGs were downloaded and identified using the Gene Expression Omnibus database. Functional-enrichment analysis revealed the involvement of oxidative stress-related pathways and processes, and a ceRNA network was generated. Differentially expressed oxidative stress-related genes (De-OSRGs) were used to construct De-OSRG pairs, which were screened, and candidate De-OSRG pairs were identified. Immune cell-related gene pairs were selected immune-infiltration analysis. A potential long non-coding RNA-microRNA-mRNA axis was determined, and clinical values were assessed. Eighteen De-OSRGs were identified that were primarily related to intricate signal-transduction pathways, apoptosis-related biological processes, and multiple kinase-related molecular functions. A ceRNA network consisting of 653 long non-coding RNA-microRNA links and 42 mRNA-miRNA links was constructed. Three candidate De-OSRG pairs were screened out from 13 De-OSRG pairs. The abundances of resting memory CD4 T cells, resting dendritic cells, and CD8 T cells differed between the control and IDD groups. CD8 T cell infiltration correlated negatively with cyclin B1 () expression and positively with protein kinase D1 () expression. - was the only pair that was differentially expressed in IDD, was correlated with CD8 T cells, and displayed better predictive accuracy compared to individual genes. The -- and -- axes may regulate IDD. Our findings indicate that the OSRG pair -, which regulates oxidative stress during IDD development, is a robust signature for identifying IDD. This OSRG pair and increased infiltration of CD8 T cells, which play important roles in IDD, were functionally associated. Thus, the OSRG pair - is promising target for treating IDD.
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http://dx.doi.org/10.3389/fimmu.2021.765382DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8630707PMC
November 2021

Hair Growth Promoting Effects of 650 nm Red Light Stimulation on Human Hair Follicles and Study of Its Mechanisms via RNA Sequencing Transcriptome Analysis.

Ann Dermatol 2021 Dec 4;33(6):553-561. Epub 2021 Nov 4.

Department of Dermatology, Jing'an District Central Hospital, Shanghai, China.

Background: Androgenetic alopecia (AGA) leads to thinning of scalp hair and affects 60%~70% of the adult population worldwide. Developing more effective treatments and studying its mechanism are of great significance. Previous clinical studies have revealed that hair growth is stimulated by 650-nm red light.

Objective: This study aimed to explore the effect and mechanism of 650-nm red light on the treatment of AGA by using hair follicle culture.

Methods: Human hair follicles were obtained from hair transplant patients with AGA. Hair follicles were cultured in Williams E medium and treated with or without 650-nm red light. Real-time RT-PCR and immunofluorescence staining were used to detect the expression level of genes and proteins in hair follicles, respectively. RNA-sequencing analysis was carried out to reveal the distinct gene signatures upon 650 nm treatment.

Results: Low-level 650 nm red light promoted the proliferation of human hair follicles in the experimental cultured-tissue model. Consistently, 650 nm red light significantly delayed the transition of hair cycle from anagen to catagen . RNA-seq analysis and gene clustering for the differentially expressed genes suggests that leukocyte transendothelial migration, metabolism, adherens junction and other biological process maybe involved in stimulation of hair follicles by 650-nm red light treatment.

Conclusion: The effect of 650-nm red light on hair follicles and the transcriptome set which implicates the role of red light in promoting hair growth and reversing of miniaturization process of AGA were identified.
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http://dx.doi.org/10.5021/ad.2021.33.6.553DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8577899PMC
December 2021

Biomaterial-mediated internal radioisotope therapy.

Mater Horiz 2021 May 12;8(5):1348-1366. Epub 2021 Jan 12.

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

Radiation therapy (RT), including external beam radiotherapy (EBRT) and internal radioisotope therapy (RIT), has been an indispensable strategy for cancer therapy in clinical practice in recent years. Ionized atoms and free radicals emitted from the nucleus of radioisotopes can cleave a single strand of DNA, inducing the apoptosis of cancer cells. Thus far, nuclides used for RIT could be classified into three main types containing alpha (α), beta (β), and Auger particle emitters. In order to enhance the bioavailability and reduce the physiological toxicity of radioisotopes, various biomaterials have been utilized as multifunctional nanocarriers, including targeting molecules, macromolecular monoclonal antibodies, peptides, inorganic nanomaterials, and organic and polymeric nanomaterials. Therapeutic radioisotopes have been labeled onto these nanocarriers via different methods (chelating, chemical doping, encapsulating, displacement) to inhibit or kill cancer cells. With the continuous development of research in this respect, more promising biomaterials as well as novel therapeutic strategies have emerged to achieve the high-performance RIT of cancer. In this review article, we summarize recent advances in biomaterial-mediated RIT of cancer and provide guidance for non-experts to understand nuclear medicine and to conduct cancer radiotherapy.
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http://dx.doi.org/10.1039/d0mh01761bDOI Listing
May 2021

Natural ingredients from Chinese materia medica for pulmonary hypertension.

Chin J Nat Med 2021 Nov;19(11):801-814

State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangdong Key Laboratory of Vascular Disease, Guangdong-Hong Kong-Macao Joint Laboratory of Respiratory Infectious Disease, Guangzhou Institute of Respiratory Health, the First Affiliated Hospital of Guangzhou Medical University, Guangzhou 510000, China. Electronic address:

Pulmonary hypertension (PH) is a severe pathophysiological condition characterized by pulmonary artery remodeling and continuous increases in pulmonary artery pressure, which may eventually develop to right heart failure and death. Although newly discovered and incredible treatment strategies in recent years have improved the prognosis of PH, limited types of effective and economical drugs for PH still makes it as a life-threatening disease. Some drugs from Chinese materia medica (CMM) have been traditionally applied in the treatment of lung diseases. Accumulating evidence suggests active pharmaceutical ingredients (APIs) derived from those medicines brings promising future for the prevention and treatment of PH. In this review, we summarized the pharmacological effects of APIs derived from CMM which are potent in treating PH, so as to provide new thoughts for initial drug discovery and identification of potential therapeutic strategies in alternative medicine for PH.
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http://dx.doi.org/10.1016/S1875-5364(21)60092-4DOI Listing
November 2021

Real-time monitoring the interfacial dynamic processes at model cell membranes: Taking cell penetrating peptide TAT as an example.

J Colloid Interface Sci 2021 Nov 18. Epub 2021 Nov 18.

Institute of Functional Nano & Soft Materials (FUNSOM), Jiangsu Key Laboratory for Carbon-Based Functional Materials & Devices, Soochow University, Suzhou 215123, Jiangsu, China; Institute of Advanced Materials, Northeast Normal University, 5268 Renmin Street, Changchun 130024, Jilin, China. Electronic address:

A real-time and molecule-level monitoring of the interfacial dynamic interactions between molecules and a cell membrane is of vital importance. Herein, taking TAT, one of the most representative cell penetrating peptides, as an example, a photo-voltage transient technique and a dynamic giant bistratal vesicle (GBV) leakage method were combined with the traditional giant unilamellar vesicle (GUV) leakage assays, to provide a molecule-level understanding of the dynamic membrane interaction process performed in a low ionic strength and neutral pH condition. The photo-voltage test based on supported phospholipid bilayers showed a quick disturbance (<1 min) followed by a continuous reconstruction of the membrane by peptides, leading to a slight destruction (at TAT concentrations lower than 1 μg mL, i.e., 0.64 μM) or strong damage (e.g. at 10 μg mL, i.e., 6.4 μM) of the bilayer structure. The GUV/GBV leakage assays further demonstrated the TAT-induced membrane deformation and transmembrane diffusion of dyes, which occurred in an immediate, linear, and TAT-concentration dependent manner. Moreover, the flux of dye across the substrate-immobilized membranes was approximately three times of that across the substrate-free ones. This work gives information on time and molecular mechanism of the TAT-membrane interactions, demonstrates the different permeabilizing effects of TAT on immobilized and free membranes. Overall, it provides useful strategies to investigate the nano-bio interfacial interactions in a simple, global and real-time way.
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http://dx.doi.org/10.1016/j.jcis.2021.11.076DOI Listing
November 2021

[Genetic analysis of a fetus with mosaicism of structural aberration of Y chromosome].

Zhonghua Yi Xue Yi Chuan Xue Za Zhi 2021 Dec;38(12):1250-1253

Langfang Maternal and Child Health Care Hospital, Hebei 065000, China.

Objective: To carry out genetic analysis and parental tracing for a fetus with an inconclusive chromosomal karyotype.

Methods: The fetus and its parents were subjected to combined chromosomal karyotyping, chromosomal microarray analysis (CMA), fluorescence in situ hybridization (FISH) and multiplex PCR testing for Y chromosome microdeletions.

Results: The fetus was found to have a karyotype of 45,X[18]/46,X,+mar[72]. CMA revealed that the fetus has carried a 2.6 Mb duplication at Yp11.32p11.31 and a 44.5 Mb deletion at Yq11.21q12. Interphase FISH of amniocytes confirmed the chromosomal mosaicism in the fetus, which has derived from Y chromosome. Multiplex PCR revealed deletion of AZFb and AZFc regions on the Y chromosome. No karyotypic abnormality was found with either parent at 400-band level.

Conclusion: Combined genetic analysis has delineated the aberrant karyotype in the fetus, which has facilitated prediction of its clinical phenotype and genetic counseling.
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http://dx.doi.org/10.3760/cma.j.cn511374-20201209-00861DOI Listing
December 2021

Radiation exposure in 101 non-coronary fluoroscopically guided interventional procedures: reference levels of air kerma at the reference point and air kerma-area product.

Br J Radiol 2021 Nov 26:20211108. Epub 2021 Nov 26.

Department of Radiology, Massachusetts General Hospital, Boston, Massachusetts, USA.

Objectives: To present the median value and 75 percentile of air kerma at the reference point (K), air kerma-area product (KAP), and fluoroscopic time for a large number of fluoroscopically-guided interventional (FGI) procedures.

Methods: This retrospective study included the consecutive non-coronary FGI procedures from a Radiology department between May 2016 and October 2018 at a large tertiary care hospital in the U.S. An in-house developed, semi-automated software, integrated with a dictation system, was used to record patient examination information, including K, KAP and fluoroscopic time. The included patient procedures were categorized into procedure types. A software package R (version 3.5.1, R Foundation) was used to calculate procedure-specific quartiles of radiation exposure.

Results: Based on analysis of 24,911 FGI cases, median value and 75 percentile are presented for each of K, KAP and fluoroscopic time for 101 procedures that can act as benchmark for comparison for dose optimization studies.

Conclusion: This study provides reference levels (50 and 75 percentiles) for a comprehensive list of FGI procedures, reflecting an overall picture of the latest FGI studies for diagnosis, targeted minimally invasive intervention, and therapeutic treatment.

Advances In Knowledge: This study provides reference levels (50 and 75 percentiles) for the largest number of fluoroscopically-guided interventional procedures reported to-date (101 procedures), in terms of air kerma at the reference point, air kerma-area product, and fluoroscopic time, among which these quartiles for ≥50 procedures are presented for the first time.
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http://dx.doi.org/10.1259/bjr.20211108DOI Listing
November 2021

iTRAQ and RNA-seq analyses provide an insight into mechanisms of recalcitrance in a medicinal plant Panax notoginseng seeds during the after-ripening process.

Funct Plant Biol 2021 Nov 26. Epub 2021 Nov 26.

Panax notoginseng (Burk) F.H. Chen is an important economic and medicinal plant from the family of Araliaceae, and its seed is characterised by the recalcitrance and after-ripening process. However, the molecular mechanism on the dehydration sensitivity is not clear in recalcitrant seeds. In the present study, isobaric tag for relative and absolute quantification (iTRAQ) and RNA-seq were used to analyse the proteomic and transcriptomic changes in seeds of P. notoginseng in days after-ripening (DAR). A total of 454 differentially expressed proteins (DEPs) and 12000 differentially expressed genes (DEGs) were obtained. The activity of enzymes related to antioxidant system were significantly increased, and the late embryogenesis abundant (LEA) protein family and most members of glutathione metabolism enzymes have been downregulated during the after-ripening process. The lack or inadequate accumulation of LEA proteins in the embryo and the low activity of antioxidant defense in glutathione metabolism might be the key factors leading to the dehydration sensitivity in recalcitrant seeds of P. notoginseng. In addition, the increased activity of elycolysis (EMP), citric acid cycle (TCA) and pentose phosphate pathway (PPP) pathways might be one of important signals to complete the after-ripening process. Overall, our study might provide a new insight into the molecular mechanism on dehydration sensitivity of recalcitrant seeds.
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http://dx.doi.org/10.1071/FP21197DOI Listing
November 2021

Quantitative Proteomics Analysis of Differentially Expressed Proteins in Serum of Former Uranium Miners by Isobaric Tags for the Relative and Absolute Quantitation.

Dose Response 2021 Oct-Dec;19(4):15593258211056190. Epub 2021 Nov 19.

China Institute for Radiation Protection, Taiyuan, China.

The carcinogenicity of radon has been convincingly documented through epidemiological studies of underground miners. However, there is a lack of early warning indicators for radon radiation damage. In this study, mixed serum samples of 3 groups were collected from 27 underground uranium miners and seven aboveground miners according to the radiation exposure dose. The differentially expressed proteins in the serum were identified using the isobaric tags for the relative and absolute quantitation (iTRAQ)-based method. Some differentially expressed proteins were validated by enzyme-linked immunosorbent assay (ELISA) in 84 underground and 32 aboveground miners. A total of 25 co-differentially expressed proteins in 2 underground miner groups were screened, of which 9 were downregulated and 13 were upregulated. Biological process analysis of these proteins using Metascape showed that 5 GO terms were enriched, such as negative regulation of very-low-density lipoprotein particle clearance, endocytosis, and regulated exocytosis. The results of the ELISA for the expression levels of GCN1, CIP2A, and IGHV1-24 in the serum of 116 miners' serum showed that the levels of GCN1 and CIP2A were consistent with the iTRAQ results. In conclusion, APOC1, APOC2, APOC3, ORM1, ORM2, ANTXR1, GCN1, and CIP2A may be potential early markers of radon radiation damage.
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http://dx.doi.org/10.1177/15593258211056190DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8606944PMC
November 2021

Biophysical Impact of Lipid A Modification Caused by Mobile Colistin Resistance Gene on Bacterial Outer Membranes.

J Phys Chem Lett 2021 Nov 24:11629-11635. Epub 2021 Nov 24.

Center for Soft Condensed Matter Physics and Interdisciplinary Research & School of Physical Science and Technology, Soochow University, Suzhou, Jiangsu 215006, China.

Expression of mobile colistin resistance gene results in the addition of phosphoethanolamine (pEtN) to the lipid A headgroup in the bacterial outer membrane (OM) of Gram-negative bacteria, increasing the resistance to the last-line polymyxins. However, the potential biological consequences of such modification remain unclear. Using coarse-grained molecular simulations with quantitative lipidomics models, we discovered pEtN modification of the lipid A headgroup caused substantial changes to the morphology and physicochemical properties of the OM. Single-lipid level structural and energetic analyses revealed that this modification resulted in lipid A-pEtN adopting an abnormally twisted and slanted conformation with a closer packing state because of strengthened inter-lipid attraction. The consequent accumulation of lipid A-pEtN produced a negative curvature of the OM and altered the membrane's tension, fluidity, and rigidity. Our results provide a key mechanistic connection between expression and biophysical changes in the bacterial OM.
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http://dx.doi.org/10.1021/acs.jpclett.1c03295DOI Listing
November 2021

The amino acids of Autographa californica multiple nucleopolyhedrovirus P48 critical for the association with Ac93 are important for the nuclear egress of nucleocapsids and efficient formation of intranuclear microvesicles.

Virus Res 2021 Nov 21;308:198644. Epub 2021 Nov 21.

State Key Laboratory of Biocontrol and School of Life Sciences, Sun Yat-sen University, Guangzhou 510275, China.

Autographa californica multiple nucleopolyhedrovirus (AcMNPV) undergoes a biphasic life cycle with the production of two physically and functionally distinct virions: budded virions (BVs) and occlusion-derived virions (ODVs). Nuclear egress of nucleocapsids and intranuclear microvesicle formation are critical for the morphogenesis of BVs and ODVs, respectively, but the mechanisms and details of these two processes remain unknown. Our previous studies have shown that AcMNPV p48 (ac103) gene is essential for the nuclear egress of nucleocapsids and efficient formation of intranuclear microvesicles, and protein P48 associates with Ac93, which is also involved in the above processes in virion morphogenesis. In this study, we present evidence that alanine substitution for residues N318, V319, C320, R321, and I323 of P48 disrupted the association with Ac93. Moreover, mutation of these residues blocked the nuclear egress of nucleocapsids and efficient formation of intranuclear microvesicles, and subsequent BV formation, as well as ODV envelopment and embedding of ODVs into polyhedra. These results suggested that the association between P48 and Ac93 may be important for both BV and ODV morphogenesis.
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http://dx.doi.org/10.1016/j.virusres.2021.198644DOI Listing
November 2021

Discarded masks as hotspots of antibiotic resistance genes during COVID-19 pandemic.

J Hazard Mater 2021 Nov 15:127774. Epub 2021 Nov 15.

Key Laboratory of Urban Environment and Health, Institute of Urban Environment, Chinese Academy of Sciences, 1799 Jimei Road, Xiamen 361021, China; University of Chinese Academy of Sciences, 19A Yuquan Road, Beijing 100049, China.

The demand for facial masks remains high. However, little is known about discarded masks as a potential refuge for contaminants and to facilitate enrichment and spread of antibiotic resistance genes (ARG) in the environment. We address this issue by conducting an in-situ time-series experiment to investigate the dynamic changes of ARGs, bacteria and protozoa associated with discarded masks. Masks were incubated in an estuary for 30 days. The relative abundance of ARGs in masks increased after day 7 but levelled off after 14 days. The absolute abundance of ARGs at 30 days was 1.29 × 10 and 1.07 × 10 copies for carbon and surgical masks, respectively. According to normalized stochasticity ratio analysis, the assembly of bacterial and protistan communities was determined by stochastic (NST = 62%) and deterministic (NST = 40%) processes respectively. A network analysis highlighted potential interactions between bacteria and protozoa, which was further confirmed by culture-dependent assays, that showed masks shelter and enrich microbial communities. An antibiotic susceptibility test suggested that antibiotic resistant pathogens co-exist within protozoa. This study provides an insight into the spread of ARGs through discarded masks and highlights the importance of managing discarded masks with the potential ecological risk of mask contamination.
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http://dx.doi.org/10.1016/j.jhazmat.2021.127774DOI Listing
November 2021

A comprehensive texture feature analysis framework of renal cell carcinoma: pathological, prognostic, and genomic evaluation based on CT images.

Eur Radiol 2021 Nov 20. Epub 2021 Nov 20.

Department of Urology, The Third Affiliated Hospital of Shenzhen University (Luohu Hospital Group), Shenzhen, 518001, China.

Objectives: We tried to realize accurate pathological classification, assessment of prognosis, and genomic molecular typing of renal cell carcinoma by CT texture feature analysis. To determine whether CT texture features can perform accurate pathological classification and evaluation of prognosis and genomic characteristics in renal cell carcinoma.

Methods: Patients with renal cell carcinoma from five open-source cohorts were analyzed retrospectively in this study. These data were randomly split to train and test machine learning algorithms to segment the lesion, predict the histological subtype, tumor stage, and pathological grade. Dice coefficient and performance metrics such as accuracy and AUC were calculated to evaluate the segmentation and classification model. Quantitative decomposition of the predictive model was conducted to explore the contribution of each feature. Besides, survival analysis and the statistical correlation between CT texture features, pathological, and genomic signatures were investigated.

Results: A total of 569 enhanced CT images of 443 patients (mean age 59.4, 278 males) were included in the analysis. In the segmentation task, the mean dice coefficient was 0.96 for the kidney and 0.88 for the cancer region. For classification of histologic subtype, tumor stage, and pathological grade, the model was on a par with radiologists and the AUC was 0.83 [Formula: see text] 0.1, 0.80 [Formula: see text] 0.1, and 0.77 [Formula: see text] 0.1 at 95% confidence intervals, respectively. Moreover, specific quantitative CT features related to clinical prognosis were identified. A strong statistical correlation (R = 0.83) between the feature crosses and genomic characteristics was shown. The structural equation modeling confirmed significant associations between CT features, pathological (β =  - 0.75), and molecular subtype (β =  - 0.30).

Conclusions: The framework illustrates high performance in the pathological classification of renal cell carcinoma. Prognosis and genomic characteristics can be inferred by quantitative image analysis.

Key Points: • The analytical framework exhibits high-performance pathological classification of renal cell carcinoma and is on a par with human radiologists. • Quantitative decomposition of the predictive model shows that specific texture features contribute to histologic subtype and tumor stage classification. • Structural equation modeling shows the associations of genomic characteristics to CT texture features. Overall survival and molecular characteristics can be inferred by quantitative CT texture analysis in renal cell carcinoma.
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http://dx.doi.org/10.1007/s00330-021-08353-3DOI Listing
November 2021

Metabolic and biophysical study of the MFN2 mutant causing Hereditary Motor and Sensory Neuropathy (HMSN).

Am J Transl Res 2021 15;13(10):11501-11512. Epub 2021 Oct 15.

Prenatal Diagnosis Center, Beijing Obstetrics and Gynecology Hospital, Capital Medical University Beijing, China.

Charcot-Marie-Tooth (CMT) 2A disease, a genetic axonal nervous lesion, results from pathogenic variation, and this gene plays a pivotal role in mitochondrial dynamics and calcium signaling. However, the underlying mechanism linking MFN2 defect to progressive dying-back of peripheral nerves is still unclear. The present work focused on analyzing one CMT2A patient from multiple perspectives. Clinical and pathologic evaluation was initially conducted on the recruited case. Subsequently, Sanger sequencing and whole-exome sequencing (WES) were performed for genetic detection. To reveal the cell metabolic alteration caused by the identified variant, this study also established and transfected plasmid vectors in HEK293 cells and analyzed cell metabolites through liquid chromatography in combination with quadrupole time-of-flight tandem mass spectrometry (UPLC Q-TOF MS). Additionally, we completed structural modeling and molecular dynamic (MD) simulation to investigate the intramolecular impact of the variant. According to our results, the clinical and neuropathologic manifestations of the proband matched with the diagnosis of CMT. The causative variant : c.638T>C: (p.Ile213Thr) was identified through genetic analysis. Moreover, metabolic pathway enrichment results demonstrated that this variant significantly affected the metabolism of sphingolipids and glycerophospholipids. MD analysis indicated that this variant crippled the binding ability of MFN2 to GTP. Taken together, our study deduced preliminary clues for the underlying mechanism by which mutant MFN2 affects cell metabolism and provided a novel perspective to understand the cellular and molecular impacts of MFN2 variants.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8581889PMC
October 2021

Expert consensus on the clinical application of recombinant adenovirus human p53 for head and neck cancers.

Int J Oral Sci 2021 Nov 16;13(1):38. Epub 2021 Nov 16.

State Key Laboratory of Oral Diseases & National Clinical Research Center for Oral Diseases & Department of Head and Neck Oncology, West China Hospital of Stomatology, Sichuan University, Chengdu, China.

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http://dx.doi.org/10.1038/s41368-021-00145-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8595718PMC
November 2021

Correlation between left ventricular fractal dimension and impaired strain assessed by cardiac MRI feature tracking in patients with left ventricular noncompaction and normal left ventricular ejection fraction.

Eur Radiol 2021 Nov 15. Epub 2021 Nov 15.

MR Center, Fuwai Hospital, Stata Key Laboratory of Cardiovascular Disease, National Center for Cardiovascular Diseases of China, Chinese Academy of Medical Sciences and Peking Union Medical College, No. 167, Beilishi Road, Xicheng District, Beijing, 100037, China.

Objectives: To investigate the correlation between the extent of excessive trabeculation assessed by fractal dimension (FD) and myocardial contractility assessed by cardiac MRI feature tracking in patients with left ventricular noncompaction (LVNC) and normal left ventricular ejection fraction (LVEF).

Methods: Forty-one LVNC patients with normal LVEF (≥ 50%) and 41 healthy controls were retrospectively included. All patients fulfilled three available diagnostic criteria on MRI. Cardiac MRI feature tracking was performed on cine images to determine left ventricular (LV) peak strains in three directions: global radial strain (GRS), global circumferential strain (GCS), and global longitudinal strain (GLS). The complexity of excessive trabeculation was quantified by fractal analysis on short-axis cine stacks.

Results: Compared with controls, patients with LVNC had impaired GRS, GCS, and GLS (all p < 0.05). The global, maximal, and regional FD values of the LVNC population were all significantly higher than those of the controls (all p < 0.05). Global FD was positively correlated with the end-diastolic volume index, end-systolic volume index, and stroke volume index (r = 0.483, 0.505, and 0.335, respectively, all p < 0.05), but negatively correlated with GRS and GCS (r =  - 0.458 and 0.508, respectively, both p < 0.001). Moreover, apical FD was also weakly associated with LVEF and GLS (r =  - 0.249 and 0.252, respectively, both p < 0.05).

Conclusion: In patients with LVNC, LV systolic dysfunction was detected early by cardiac MRI feature tracking despite the presence of normal LVEF and was associated with excessive trabecular complexity assessed by FD.

Key Points: • Left ventricular global strain was already impaired in patients with extremely prominent excessive trabeculation but normal left ventricular ejection fraction. • An increased fractal dimension was associated with impaired deformation in left ventricular noncompaction.
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http://dx.doi.org/10.1007/s00330-021-08346-2DOI Listing
November 2021

[Repair of eyelid and periocular soft tissue defects with Pacman flap].

Zhongguo Xiu Fu Chong Jian Wai Ke Za Zhi 2021 Nov;35(11):1463-1466

Department of Plastic and Reconstructive Surgery, Peking University People's Hospital, Beijing, 100044, P.R.China.

Objective: To explore the effectiveness and safety of Pacman flap for repair of eyelid and periocular soft tissue defects.

Methods: The clinical data of 12 patients who underwent repair of eyelid and periocular soft tissue defects with Pacman flap between April 2015 and September 2020 was retrospectively reviewed. There were 5 males and 7 females, aged from 18 to 87 years, with a median age of 63 years. The disease duration ranged from 6 months to 50 years, with a median time of 3 years. The defect was located on the lateral eyelid in 5 cases, inferior eyelid in 3 cases, inferior and medial eyelid in 2 cases, inferior and lateral eyelid in 2 cases, and lateral eyebrow in 1 case. Pathological diagnosis included 4 cases of basal cell carcinoma, 4 cases of squamous cell carcinoma, 1 case of junction nevus, 1 case of intradermal nevus, 1 case of seborrheic keratosis, and 1 case of keratoacanthoma. The size of defects ranged from 1.4 cm×1.2 cm to 5.5 cm×5.0 cm. According to the skin mobility and toughness around the defects, Pacman flaps with the size of 1.6 cm×1.4 cm to 10.0 cm×6.0 cm were designed and advanced to repair the defects.

Results: All flaps survived completely with no necrosis. One patient had infection, and another patient had partial wound dehiscence, but the wounds healed after dressing change without further debridement. Other patients all recovered successfully. The follow-up time ranged from4 to 51 months, with a median time of 12 months. No recurrence and metastasis occurred, and the scars were invisible without deformity of eyelid and brow. All patients were satisfied with the aesthetic and functional outcomes of the eyes.

Conclusion: Pacman flap is a simple and feasible technique for repair of eyelid and periocular soft tissue defects, with satisfactory effectiveness.
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http://dx.doi.org/10.7507/1002-1892.202106066DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8586763PMC
November 2021

Coordination Polymer-Coated CaCO Reinforces Radiotherapy by Reprogramming the Immunosuppressive Metabolic Microenvironment.

Adv Mater 2021 Nov 12:e2106520. Epub 2021 Nov 12.

Institute of Functional Nano & Soft Materials (FUNSOM), Jiangsu Key Laboratory for Carbon-Based Functional Materials & Devices, Soochow University, 199 Ren'ai Road, Suzhou, Jiangsu, 215123, China.

Radiotherapy is widely exploited for the treatment of a large range of cancers in clinic, but its therapeutic effectiveness is seriously crippled by the tumor immunosuppression, mainly driven by the altered metabolism of cancer cells. Here, a pH-responsive nanomedicine is prepared by coating calcium carbonate (CaCO ) nanoparticles with 4-phenylimidazole (4PI), an inhibitor against indoleamine 2,3-dioxygenase 1 (IDO-1), together with zinc ions via the coordination reaction, aiming at reinforcing the treatment outcome of radiotherapy. The obtained pH-responsive nanomedicine, coined as acidity-IDO1-modulation nanoparticles (AIM NPs), is able to instantly neutralize protons, and release 4PI to suppress the IDO1-mediated production of kynurenine (Kyn) upon tumor accumulation. As a result, treatment with AIM NPs can remarkably enhance the therapeutic efficacy of radiotherapy against both murine CT26 and 4T1 tumors by eliciting potent antitumor immunity. Furthermore, it is shown that such combination treatment can effectively suppress the growth of untreated distant tumors via the abscopal effect, and result in immune memory responses to reject rechallenged tumors. This work highlights a novel strategy of simultaneous tumor acidity neutralization and IDO1 inhibition to potentiate radiotherapy, with great promises to suppress tumor metastasis and recurrence by eliciting robust antitumor immunity.
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http://dx.doi.org/10.1002/adma.202106520DOI Listing
November 2021

Four types of global spine sagittal alignment and compensation mechanism in adult patients with lumbar degenerative disease.

J Orthop Sci 2021 Nov 9. Epub 2021 Nov 9.

Department of Orthopedics, Xuanwu Hospital, Capital Medical University, No. 45 Changchun Street, Xicheng District, Beijing, China; National Clinical Research Center for Geriatric Diseases, Beijing, China. Electronic address:

Background: The objective of this study was to describe and classify common variations and compensation mechanisms in the sagittal alignment of the spine with lumbar degenerative disease.

Methods: A total of 230 patients over 18 years old who underwent whole-spine X-rays to evaluate lower back pain were enrolled in this study. C7 slope, pelvic tilt (PT), sacral slope (SS), pelvic incidence (PI), thoracic kyphosis (TK), lumbar lordosis (LL), cervical lordosis (CL), thoracolumbar kyphosis (TLK), and sagittal vertical axis (SVA) were measured. Patients were divided into Group A (balance without compensation), B (balance with compensation), C (unbalance with compensation), and D (unbalance without compensation) according to spinopelvic balance and thoracic compensation.

Results: Group A had the largest LL, smallest PT, largest SS, and best clinical parameters of the four groups (p < 0.001, p < 0.001, p < 0.001, p < 0.001). The age increased gradually from Group B to Group D. Group B had an increased TK compared with Group A (p < 0.001). Group C had an increased TK compared with Group A (p < 0.001). Group D had an increased C7 slope compared with Group A (p = 0.022).

Conclusions: This classification is shown four different regional and global alignments of the spine. Compensation took place to keep the balance of the spine. Classification types were consistent with age, compensation abilities, and clinical parameters. This classification potentially represents a valuable tool for comprehensive analysis of lumbar degenerative before surgical treatment considering sagittal balance.
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http://dx.doi.org/10.1016/j.jos.2021.09.006DOI Listing
November 2021

Red blood cell distribution width-standard deviation but not red blood cell distribution width-coefficient of variation as a potential index for the diagnosis of iron-deficiency anemia in mid-pregnancy women.

Open Life Sci 2021 6;16(1):1213-1218. Epub 2021 Nov 6.

Department of Medical Technology, Anhui Medical College, Hefei, Anhui Province, 230601, People's Republic of China.

The aim of this study was to compare the diagnostic values of red blood cell distribution width-coefficient of variation (RDW-CV) and red blood cell distribution width-standard deviation (RDW-SD) in mid-pregnancy women with iron deficiency anemia (IDA). To obtain the results, 115 mid-pregnancy women with IDA, defined as the IDA group, and 142 healthy mid-pregnancy women, selected as the control group, were enrolled in this study. Hematological parameters and ferritin concentrations in the serum were analyzed. The efficiency of RDW-CV and RDW-SD to distinguish IDA from mid-pregnancy women was evaluated using receiver operating characteristic (ROC) curves. The RDW-SD value in the IDA group was significantly higher than that in the control group ( < 0.05), while the RDW-CV value did not differ between them ( = 0.84). Significantly negative correlations were found between RDW-CV ( = -0.297, = 0.001), RDW-SD ( = -0.404, = 0.000), and serum ferritin in the IDA group but not in the control group. For the diagnosis of IDA, RDW-CV and RDW-SD produced areas under the ROC curves of 0.58 and 0.84. To conclude, our results suggest that RDW-SD, but not RDW-CV, can be used as a diagnostic index of IDA for mid-pregnancy women.
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http://dx.doi.org/10.1515/biol-2021-0120DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8572805PMC
November 2021

Efficacy and safety of a parylene-coated occluder for atrial septal defect: a prospective, multi-center, randomized controlled clinical trial.

Chin Med J (Engl) 2021 Nov 10;134(22):2685-2691. Epub 2021 Nov 10.

Center of Structural Heart Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing 100037, China.

Background: Nitinol-containing devices are widely used in clinical practice. However, there are concerns about nickel release after nitinol-containing device implantation. This study aimed to compare the efficacy and safety of a parylene-coated occluder vs. a traditional nitinol-containing device for atrial septal defect (ASD).

Methods: One-hundred-and-eight patients with ASD were prospectively enrolled and randomly assigned to either the trial group to receive a parylene-coated occluder (n = 54) or the control group to receive a traditional occluder (n = 54). The plugging success rate at 6 months after device implantation and the pre- and post-implantation serum nickel levels were compared between the two groups. A non-inferiority design was used to prove that the therapeutic effect of the parylene-coated device was non-inferior to that of the traditional device. The Cochran-Mantel-Haenszel chi-squared test with adjustment for central effects was used for the comparison between groups.

Results: At 6 months after implantation, successful ASD closure was achieved in 52 of 53 patients (98.11%) in both the trial and control groups (95% confidence interval (CI): [-4.90, 5.16]) based on per-protocol set analysis. The absolute value of the lower limit of the 95% CI was 4.90%, which was less than the specified non-inferiority margin of 8%. No deaths or severe complications occurred during 6 months of follow-up. The serum nickel levels were significantly increased at 2 weeks and reached the maximum value at 1 month after implantation in the control group (P < 0.05 vs. baseline). In the trial group, there was no significant difference in the serum nickel level before vs. after device implantation (P > 0.05).

Conclusions: The efficacy of a parylene-coated ASD occluder is non-inferior to that of a traditional uncoated ASD occluder. The parylene-coated occluder prevents nickel release after device implantation and may be an alternative for ASD, especially in patients with a nickel allergy.
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http://dx.doi.org/10.1097/CM9.0000000000001865DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8631379PMC
November 2021

Fixation effects of different types of cannulated screws on vertical femoral neck fracture: A finite element analysis and experimental study.

Med Eng Phys 2021 Nov 30;97:32-39. Epub 2021 Sep 30.

Biomechanical Laboratory of Orthopedic Surgery Department, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, 200233, PR China. Electronic address:

Femoral neck fractures (FNFs) in young patients usually result from high-energy violence, and the vertical transcervical type is typically challenging for its instability. FNFs are commonly treated with three cannulated screws (CS), but the role of screws type on fixation effects (FE) is unclear. The purpose of this study was to evaluate the FE of ten types of CS with different diameters, lengths, depths, and pitches of thread via finite element analysis which was validated by a biomechanical test. Ten vertical FNF models were grouped, fixed by ten types of CS, respectively, all in a parallel, inverted triangular configuration. Their FE were scored comprehensively from six aspects via an entropy evaluation method, as higher scores showed better results. For partial-thread screws, thread length and thread shape factor (TSF) are determinative factors on stability of FNF only if thread depth is not too thick, and they have less cut-out risk, better compression effects and better detached resistance of fracture than full-thread screws, whereas full-thread screws appear to have better shear and shortening resistance. A combination of two superior partial-thread screws and one inferior full-thread screw for vertical FNF may get optimal biomechanical outcomes. The type of cannulated screw is important to consider when treating vertical FNF.
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http://dx.doi.org/10.1016/j.medengphy.2021.09.007DOI Listing
November 2021

The impact of metro-based underground logistics system on city logistics performance under COVID-19 epidemic: A case study of Wuhan, China.

Transp Policy (Oxf) 2022 Feb 30;116:81-95. Epub 2021 Oct 30.

School of Defense Engineering, Army Engineering University of PLA, Nanjing, 210007, China.

The global outbreak of COVID-19 has further exposed deficiencies in city logistics based on human and ground roads, such as poor emergency response capacity and high risk of infection during transportation. Metro-based underground logistics system (M-ULS) may be an innovative approach to deal with this city-level disaster due to its efficient operation, contactless and driverless characteristics. However, the market evolution process and the quantitative calculation framework of comprehensive benefits after the application of M-ULS are still unclear, which has become a problem of mutual restriction with the extensive application of M-ULS. This paper attempts to use the system dynamics method, based on the real-world simulation, to analyze the quantitative relationship between the M-ULS implementation and the city logistics performance under epidemic outbreaks. Wuhan city in China was selected as the empirical background, and five simulation scenarios were set under different implementation strategies of M-ULS in response to the epidemic. Six variables were selected to measure city logistics performance and M-ULS operation status, including demand fill-rate, unit delivery time, total deprivation cost, total transportation cost, total number of susceptible people, and utilization rate of M-ULS. The results show that M-ULS is effective in improving the performance of city logistics and responding to the epidemic. The delivery time and transportation cost have a strong impact on the market share of M-ULS. Finally, a set of incentive policies was designed to promote the adoption of M-ULS. The findings not only provide a method for evaluating the overall performance of M-ULS, but also provide a unique perspective for promoting the implementation of M-ULS and responding to the transportation challenges brought by the epidemic.
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http://dx.doi.org/10.1016/j.tranpol.2021.10.020DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8556189PMC
February 2022

Chromosome doubling influences the morphological, physiological, biochemical and genetic traits related to essential oil biosynthesis of peppermint (Mentha piperita) under salinity stress.

J Plant Res 2021 Nov 2. Epub 2021 Nov 2.

Shandong Province Key Laboratory of Applied Microbiology, Ecology Institute of Shandong Academy of Sciences, Qilu University of Technology, No. 28789, Jingshi East Road, Jinan City, 250103, Shandong Province, China.

Peppermint (Mentha piperita L.) is an important medicinal aromatic plant. In this study, the morphology, physiology, biochemistry and gene expression of chromosomes doubling peppermint (D1 lines) were analyzed. The analysis showed that D1 lines had larger, thicker and darker leaves, and stronger roots when planted in the pots, but delayed growth in the field condition. Under NaCl stress, the D1 lines increased cell oxidative defense through more active antioxidant enzymes and decreased the oxidative damages of cell membrane, leading to a significantly greater survival rate and photosynthesis intensity than WT lines. The size and density of glandular trichomes of D1 lines was larger, which contributed to its higher essential oil yield. In addition, chromosome doubling reduced the inhibition of NaCl stress on essential oil yield and quality, through changing the expression of genes in the oil biosynthesis pathway. The traits of chromosome doubling peppermint provide new technical and theoretical evidence for peppermint germplasm improvement.
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http://dx.doi.org/10.1007/s10265-021-01347-8DOI Listing
November 2021
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