Publications by authors named "Qing Meng"

323 Publications

The Molecular Mechanism of Yellow Mushroom () Response to Strong Ultraviolet Radiation on the Qinghai-Tibet Plateau.

Front Microbiol 2022 20;13:918491. Epub 2022 Jun 20.

Test Station for Grassland Improvement, Xining, China.

The Qinghai-Tibet Plateau (QTP) is the highest plateau in the world, and its ultraviolet (UV) radiation is much greater than that of other regions in the world. Yellow mushroom () is a unique and widely distributed edible fungus on the QTP. However, the molecular mechanism of response to strong UV radiation remains unclear. Herein, we reported the 205 environmental adaptation and information processing genes from genome of . In addition, we assembled the RNA sequence of UV-affected at different growth stages. The results showed that in response to strong UV radiation, a total of 11,871 significantly different genes were identified, of which 4,444 genes in the vegetative mycelium (VM) stage were significantly different from the young fruiting bodies (YFB) stage, and only 2,431 genes in the YFB stage were significantly different from fruiting bodies (FB) stage. A total of 225 differentially expressed genes (DEGs) were found to be involved in environmental signal transduction, biochemical reaction preparation and stress response pathway, pigment metabolism pathway, and growth cycle regulation, so as to sense UV radiation, promote repair damage, regulate intracellular homeostasis, and reduce oxidative damage of UV radiation. On the basis of these results, a molecular regulation model was proposed for the response of to strong UV radiation. These results revealed the molecular mechanism of adaptation of adapting to strong UV radiation, and provided novel insights into mechanisms of fungi adapting to extreme environmental conditions on the QTP; the production the riboflavin pigment of the endemic fungi (Yellow mushroom) in the QTP was one of the response to extreme environment of the strong UV radiation.
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http://dx.doi.org/10.3389/fmicb.2022.918491DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9251379PMC
June 2022

Temporal metabolite responsiveness of microbiota in the tea plant phyllosphere promotes continuous suppression of fungal pathogens.

J Adv Res 2022 07 18;39:49-60. Epub 2021 Oct 18.

College of Agriculture and Biotechnology, Zhejiang University, Hangzhou 310058, China; Key Laboratory of Biology of Crop Pathogens and Insects of Zhejiang Province, Key Laboratory of Molecular Biology of Crop Pathogens and Insects, Ministry of Agriculture, Zhejiang University, Hangzhou 310058, China. Electronic address:

Introduction: A broad spectrum of rhizosphere bacteria and fungi were shown to play a central role for health, fitness and productivity of their host plants. However, implications of host metabolism on microbiota assembly in the phyllosphere and potential consequences for holobiont functioning were sparsely addressed. Previous observations indicated that tea plants might reduce disease occurrence in various forests located in their proximity; the underlying mechanisms and potential implications of the phyllosphere microbiota remained elusive.

Objectives: This study aimed atdeciphering microbiome assembly in the tea plant phyllosphere throughout shoot development as well as elucidating potential implications of host metabolites in this process. The main focus was to explore hidden interconnections between the homeostasis of the phyllosphere microbiome and resistance to fungal pathogens.

Methods: Profiling of host metabolites and microbiome analyses based on high-throughput sequencing were integrated to identify drivers of microbiome assembly throughout shoot development in the phyllosphere of tea plants. This was complemented by tracking of beneficial microorganisms in all compartments of the plant. Synthetic assemblages (SynAss), bioassays and field surveys were implemented to verify functioning of the phyllosphere microbiota.

Results: Theophylline and epigallocatechin gallate, two prevalent metabolites at the early and late shoot development stage respectively, were identified as the main drivers of microbial community assembly. Flavobacterium and Myriangium were distinct microbial responders at the early stage, while Parabacteroides and Mortierella were more enriched at the late stage. Reconstructed, stage-specific SynAss suppressed various tree phytopathogens by 13.0%-69.3% in vitro and reduced disease incidence by 8.24%-41.3% in vivo.

Conclusion: The findings indicate that a functional phyllosphere microbiota was assembled along with development-specific metabolites in tea plants, which continuously suppressed prevalent fungal pathogens. The insights gained into the temporally resolved metabolite response of the tea plant microbiota could provide novel solutions for disease management.
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http://dx.doi.org/10.1016/j.jare.2021.10.003DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9263646PMC
July 2022

Quantitative Trait Locus Mapping and Identification of Candidate Genes Controlling Bolting in Spinach ( L.).

Front Plant Sci 2022 30;13:850810. Epub 2022 Mar 30.

Institute of Vegetables and Flowers, Chinese Academy of Agricultural Sciences, Beijing, China.

Spinach is a typical light-sensitive plant. Long days can induce early bolting, thereby influencing the regional adaptation, quality, and vegetative yield of spinach. However, the genes and genetic mechanisms underlying this trait in spinach remain unclear. In this study, a major quantitative trait locus (QTL) BT1.1, was mapped on chromosome 1 using a BC population (BC) derived from 12S3 (late-bolting recurrent lines) and 12S4 (early bolting lines) with specific-locus amplified fragment (SLAF) markers and Kompetitive Allele Specific PCR (KASP) markers. The BT1.1 locus was further confirmed and narrowed down to 0.56 Mb by using a large BC (BC) population and an F population using the above KASP markers and the other 20 KASP markers. Within this region, two putative genes, namely, and 14, were of interest due to their relationship with flower regulatory pathways. For 14, we found multiple variations in the promoter, and the expression pattern was consistent with bolting stages. 14 was therefore assumed to the best candidate gene for bolting. Overall, our results provide a basis for understanding the molecular mechanisms of bolting in spinach and contribute to the breeding of diverse spinach germplasms for adaptation to different regions.
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http://dx.doi.org/10.3389/fpls.2022.850810DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9006512PMC
March 2022

Construction of a paclitaxel-related competitive endogenous RNA network and identification of a potential regulatory axis in pancreatic cancer.

Transl Oncol 2022 Jun 9;20:101419. Epub 2022 Apr 9.

Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, No. 270 Dong'An Road, Shanghai 200032, China; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China; Shanghai Pancreatic Cancer Institute, No. 270 Dong'An Road, Shanghai 200032, China; Pancreatic Cancer Institute, Fudan University, Shanghai, China. Electronic address:

Background: Increasing numbers of studies have elucidated the role of competitive endogenous RNA (ceRNA) networks in carcinogenesis. However, the potential role of the paclitaxel-related ceRNA network in the innate mechanism and prognosis of pancreatic cancer has not been identified.

Methods: Comprehensive bioinformatics analyses were performed to identify drug-related miRNAs (DRmiRNAs), drug-related mRNAs (DRmRNAs) and drug-related lncRNAs (DRlncRNAs) and construct a ceRNA network. The ssGSEA and CIBERSORT algorithms were utilized for immune cell infiltration analysis. Additionally, we validated our paclitaxel-related ceRNA regulatory axis at the gene expression level; functional experiments were conducted to explore the biological functions of the key genes.

Results: A total of 182 mRNAs, 13 miRNAs, and 53 lncRNAs were confirmed in the paclitaxel-related ceRNA network. In total, 6 mRNAs, 4 miRNAs, and 6 lncRNAs were identified to establish a risk signature and exhibited optimal prognostic effects. The mRNA signature can predict the abundance of immune cell infiltration and the sensitivity of different chemotherapeutic drugs and may also have a guiding effect in immune checkpoint therapy. A potential PART1/hsa-mir-21/SCRN1 axis was confirmed according to the ceRNA theory and was verified by qPCR. The results indicated that PART1 knockdown markedly increased hsa-mir-21 expression but inhibited SCRN1 expression, weakening the proliferation and migration abilities.

Conclusions: We hypothesized that the paclitaxel-related ceRNA network strongly influences the innate mechanism, prognosis, and immune infiltration of pancreatic cancer. Our risk signatures can accurately predict survival outcomes and provide a clinical basis.
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http://dx.doi.org/10.1016/j.tranon.2022.101419DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9018166PMC
June 2022

Nowhere to Hide: Online Rumor Detection Based on Retweeting Graph Neural Networks.

IEEE Trans Neural Netw Learn Syst 2022 Apr 6;PP. Epub 2022 Apr 6.

Online rumor detection is crucial for a healthier online environment. Traditional methods mainly rely on content understanding. However, these contents can be easily adjusted to avoid such supervision and are insufficient to improve the detection result. Compared with the content, information propagation patterns are more informative to support further performance promotion. Unfortunately, learning the propagation patterns is difficult, since the retweeting tree is more topologically complicated than linear sequences or binary trees. In light of this, we propose a novel rumor detection framework based on structure-aware retweeting graph neural networks. To capture the propagation patterns, we first design a novel conversion method to transform the complex retweeting tree as more tractable binary tree without losing the reconstruction information. Then, we serialize the retweeting tree as a corpus of meta-tree paths, where each meta-tree can preserve a basic substructure. A deep neural network is then designed to integrate all meta-trees and to generate the global structural embeddings. Furthermore, we propose to integrate content, users, and propagation patterns to enhance more reliable performance. To this end, we propose a novel self-attention-based retweeting neural network to learn individual features from both content and users. We then fuse the node-level features with our global structural embeddings via a mutual attention unit. In this way, we can generate more comprehensive representations for rumor detection. Extensive evaluations on two real-world datasets show remarkable superiorities of our model compared with existing methods.
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http://dx.doi.org/10.1109/TNNLS.2022.3161697DOI Listing
April 2022

Transcriptome analysis in the spleen of Northern Snakehead (Channa argus) challenged with Nocardia seriolae.

Genomics 2022 Apr 2;114(3):110357. Epub 2022 Apr 2.

College of Animal Science and Technology, Shandong Agricultural University, Taian, China. Electronic address:

Northern snakehead (Channa argus) is an indigenous fish species and is one of popularly cultured snakeheads in China and other Asian countries. Unfortunately, Nocardia seriolae infections have caused considerable losses in the snakehead aquaculture industry. However, the infectivity and the immune response induced by N. seriolae in snakehead are unclear. In order to better understand the immune response of Northern snakehead in a series of time points after N. seriolae challenge, we conducted the transcriptomic comparison in snakehead spleen at 48, 96, and 144 h after the challenge of N. seriola against their control counterparts. Gene annotation and pathway analysis of differentially expressed genes (DEGs) were carried out to understand the functions of the DEGs. Additionally, protein-protein interaction networks were conducted to obtain the interaction relationships of immune-related DEGs. These results revealed the expression changes of multiple DEGs and signaling pathways involved in immunity during N. seriolae infection, which will facilitate our comprehensive understanding of the mechanisms involved in the immune response to bacterial infection in the northern snakehead.
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http://dx.doi.org/10.1016/j.ygeno.2022.110357DOI Listing
April 2022

C-Terminal Domains of Spider Silk Proteins Having Divergent Structures but Conserved Functional Roles.

Biomacromolecules 2022 04 21;23(4):1643-1651. Epub 2022 Mar 21.

Department of Biological Sciences, National University of Singapore, 14 Science Drive 4, Singapore 117543.

Spider silk is self-assembled from silk proteins or spidroins. C-terminal domains (CTDs) of various types of spidroins are relatively conserved in amino acid sequences and are suggested to adopt similar structures and perform similar functional roles in spidroin storage and silk formation. Here, we solved the structure of the CTD from a capture-spiral silk protein (CTD) and characterized its stability and fibril formation in the presence and absence of a reducing agent at different pH values. CTD adopts a dimeric structure with 8 helices, but the CTDs of other types of spidroins exist in a domain-swapped dimeric structure with 10 helices. Despite the structural differences, CTD is pH-responsive in stability and fibril formation, similar to the CTDs from minor and major ampullate spidroins. Thus, the functional role of CTDs in silk fiber formation seems conserved. Comparing wild-type CTD and its mutants, we found that the pH-responsive behavior results from the protonation of H76, which is conserved from different spider species. In addition, the fibril formation rate of CTD correlates with its instability, suggesting that structural changes are involved in fibril formation.
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http://dx.doi.org/10.1021/acs.biomac.1c01513DOI Listing
April 2022

SPHK Inhibitors and Zoledronic Acid Suppress Osteoclastogenesis and Wear Particle-Induced Osteolysis.

Front Pharmacol 2021 14;12:794429. Epub 2022 Feb 14.

Department of Joint Surgery, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China.

Inflammatory osteolysis induced by wear particles is the major cause of prosthetic loosening after artificial joint replacement, and its prevention and treatment are difficult worldwide. Our previous study confirmed that sphingosine kinases (SPHKs) are important mediators regulating the wear particle-induced macrophage inflammatory response. However, it is unclear whether SPHKs can modulate chronic inflammation and alleviate osteolysis. Zoledronic acid (ZA), an imidazole-containing bisphosphonate, directly affects osteoclasts and prevents bone mineral-related diseases. However, the effects of SPHK inhibitors and ZA used to treat periprosthetic osteolysis are unknown. We applied tartrate-resistant acid phosphatase (TRAP) staining to evaluate bone destruction in the interface membranes of patients with aseptic loosening and a control group. A murine calvarial osteolysis model was used to examine the preventative effect of SPHK inhibitors and ZA on osteolysis. Micro-CT scanning, immunohistochemistry (IHC), and histomorphometric analysis were conducted to determine the variations in inflammatory osteolysis. The effects of different drug concentrations on cell viability were evaluated using the Cell Counting Kit-8 (CCK-8) assay. Real-time quantitative polymerase chain reaction (RT-qPCR) analysis was performed to confirm the reduced expression of osteoclast-specific genes after drug and titanium treatment. The osteoclast formation and functions of the drugs were analyzed using TRAP staining and . The effect of SPHKs/S1P-TRAF2-BECN1 signaling pathways was verified via RT-qPCR and tissue IHC. In this study, we found that SPHK inhibitors (ABC294640 and FTY720) combined with ZA decreased the degree of inflammatory osteolysis . However, ABC294640 and ZA suppressed osteoclast differentiation and osteoclast-specific genes . SPHKs regulate the inflammatory osteolysis induced by wear particles by increasing the expression of SPHKs/S1P-TRAF2-BECN1. Our study revealed that wear particles could induce inflammatory osteolysis by upregulating SPHKs/S1P-TRAF2-BECN1 and SPHK inhibitors/ZA inhibit osteoclastogenesis in vitro and prevent inflammatory osteolysis in vivo, suggesting that SPHK inhibitors and ZA can be a new perspective and scientific basis for the prevention and treatment of prosthesis loosening.
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http://dx.doi.org/10.3389/fphar.2021.794429DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8883393PMC
February 2022

Electroencephalographic Evidence for Individual Neural Inertia in Mice That Decreases With Time.

Front Syst Neurosci 2021 14;15:787612. Epub 2022 Jan 14.

Department of Anesthesiology and Critical Care, University of Pennsylvania, Philadelphia, PA, United States.

Previous studies have demonstrated that the brain has an intrinsic resistance to changes in arousal state. This resistance is most easily measured at the population level in the setting of general anesthesia and has been termed neural inertia. To date, no study has attempted to determine neural inertia in individuals. We hypothesize that individuals with markedly increased or decreased neural inertia might be at increased risk for complications related to state transitions, from awareness under anesthesia, to delayed emergence or confusion/impairment after emergence. Hence, an improved theoretical and practical understanding of neural inertia may have the potential to identify individuals at increased risk for these complications. This study was designed to explicitly measure neural inertia in individuals and empirically test the stochastic model of neural inertia using spectral analysis of the murine EEG. EEG was measured after induction of and emergence from isoflurane administered near the EC dose for loss of righting in genetically inbred mice on a timescale that minimizes pharmacokinetic confounds. Neural inertia was assessed by employing classifiers constructed using linear discriminant or supervised machine learning methods to determine if features of EEG spectra reliably demonstrate path dependence at steady-state anesthesia. We also report the existence of neural inertia at the individual level, as well as the population level, and that neural inertia decreases over time, providing direct empirical evidence supporting the predictions of the stochastic model of neural inertia.
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http://dx.doi.org/10.3389/fnsys.2021.787612DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8794956PMC
January 2022

Gospel of malignant Glioma: Oncolytic virus therapy.

Gene 2022 Apr 28;818:146217. Epub 2022 Jan 28.

Department of Neurosurgery, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, China. Electronic address:

Glioma accounts for nearly 80% of all intracranial malignant tumors. It is a major challenge to society as it is causes to impaired brain function in many patients. Currently, gliomas are mainly treated with surgery, postoperative radiotherapy, and chemotherapy. However, the curative effects of these treatments are not satisfactory. Oncolytic virus (OV) is a novel treatment which works by activating the immune functions and inducing apoptosis of tumor cells. The OV propagates indefinitely in the host cell, eventually leading to the death of host cell. Subsequently, a large number of antigens and signal molecules are released which exert antitumor immunity. Several preclinical and clinical studies have shown that G207, DNX2401, Zika and other viruses have important roles in malignant tumors. For example, these viruses can reduce the growth of tumor cells without causing severe complications. However, the known OVs have not been clearly classified. Herein, we divided OVs into neurotropic and non-neurophilic OVs based on whether the OVs are naturally neurotropic or not. The therapeutic effects of each group were compared. Finally, challenges encountered in the clinical application of OVs in the treatment of malignant gliomas were summarized.
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http://dx.doi.org/10.1016/j.gene.2022.146217DOI Listing
April 2022

Identification and expression analysis of the ZRT, IRT-like protein (ZIP) gene family in Camellia sinensis (L.) O. Kuntze.

Plant Physiol Biochem 2022 Feb 12;172:87-100. Epub 2022 Jan 12.

College of Food Science, Southwest University, Chongqing, 400715, China. Electronic address:

The ZRT, IRT-like protein (ZIP) family plays an essential role in the homeostasis of zinc and iron in plants. However, studies on this family are mainly limited to model species. Here, 12 CsZIPs were identified and investigated the function in Camellia sinensis, being named CsZIP1-12 and divided into four different groups based on phylogenetic relationships. These CsZIPs contained 2-9 TMDs and other conserved motifs for ZIP proteins. And CsZIPs were located in cell membrane, excepting for CsZIP4 and CsZIP6. The expression of CsZIPs were different in varieties and organs of tea plants. They were involved in the response process of abiotic stresses, such as NaCl, drought, cold and exogenous Me-JA. In addition, 31 types of promoter elements were identified in the CsZIPs, including core promoters, light responsiveness, stress responsive and other elements. The CsZIP1, CsZIP2, CsZIP4, CsZIP5, CsZIP6, CsZIP11 and CsZIP12 could be induced by zinc deficiency and 50 μM Zn treatment, but CsZIP7 and CsZIP8 were up regulated by 300 μM Zn. Heterogeneous complementation analysis showed that CsZIP1, CsZIP2, CsZIP7 and CsZIP8 could complement the Zn sensitivity of △zrc1cot1 yeast double mutant. There was a positive correlation between the expression of CsZIPs and secondary metabolites in tea plant. Together, our analysis of CsZIPs could provide comprehensive insights on the structure and function of this protein family in the regulation of zinc and ion homeostasis in the tea plant.
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http://dx.doi.org/10.1016/j.plaphy.2022.01.008DOI Listing
February 2022

TIMP-2 regulates 5-Fu resistance via the ERK/MAPK signaling pathway in colorectal cancer.

Aging (Albany NY) 2022 01 12;14(1):297-315. Epub 2022 Jan 12.

Department of Colorectal Surgery, Sir Run Run Shaw Hospital of Zhejiang University, Hangzhou, China.

5-Fluorouracil (5-Fu) is the first-line chemotherapeutic option for colorectal cancer. However, its efficacy is inhibited by drug resistance. Cytokines play an important role in tumor drug resistance, even though their mechanisms are largely unknown. Using a cytokine array, we established that tissue inhibitor metalloproteinase 2 (TIMP-2) is highly expressed in 5-Fu resistant colorectal cancer patients. Analysis of samples from 84 patients showed that elevated TIMP-2 expression levels in colorectal patients were correlated with poor prognostic outcomes. In a 5-Fu-resistant patient-derived xenograft (PDX) model, TIMP-2 was also found to be highly expressed. We established an autocrine mechanism through which elevated TIMP-2 protein levels sustained colorectal cancer cell resistance to 5-Fu by constitutively activating the ERK/MAPK signaling pathway. Inhibition of TIMP-2 using an anti-TIMP-2 antibody or ERK/MAPK inhibition by U0126 suppressed TIMP-2 mediated 5-Fu-resistance in CRC patients. In conclusion, a novel TIMP-2-ERK/MAPK mediated 5-Fu resistance mechanism is involved in colorectal cancer. Therefore, targeting TIMP-2 or ERK/MAPK may provide a new strategy to overcome 5-Fu resistance in colorectal cancer chemotherapy.
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http://dx.doi.org/10.18632/aging.203793DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8791226PMC
January 2022

Elastase Inhibitor Cyclotheonellazole A: Total Synthesis and In Vivo Biological Evaluation for Acute Lung Injury.

J Med Chem 2022 02 10;65(4):2971-2987. Epub 2022 Jan 10.

State Key Laboratory of Medicinal Chemical Biology, College of Pharmacy, Nankai University, Tianjin 300353, People's Republic of China.

Acute lung injury/acute respiratory distress syndrome (ALI/ARDS) is one of the most common complications in COVID-19. Elastase has been recognized as an important target to prevent ALI/ARDS in the patient of COVID-19. Cyclotheonellazole A (CTL-A) is a natural macrocyclic peptide reported to be a potent elastase inhibitor. Herein, we completed the first total synthesis of CTL-A in 24 linear steps. The key reactions include three-component MAC reactions and two late-stage oxidations. We also provided seven CTL-A analogues and elucidated preliminary structure-activity relationships. The ALI mouse model further suggested that CTL-A alleviated acute lung injury with reductions in lung edema and pathological deterioration, which is better than sivelestat, one approved elastase inhibitor. The activity of CTL-A against elastase, along with its cellular safety and well-established synthetic route, warrants further investigation of CTL-A as a candidate against COVID-19 pathogeneses.
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http://dx.doi.org/10.1021/acs.jmedchem.1c01583DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8936052PMC
February 2022

The novel aciniform silk protein (AcSp2-v2) reveals the unique repetitive domain with high acid and thermal stability and self-assembly capability.

Int J Biol Macromol 2022 Mar 30;202:91-101. Epub 2021 Dec 30.

Institute of Biological Sciences and Biotechnology, Donghua University, Shanghai 201620, China. Electronic address:

Orb-weaving spiders spin a mechanically and functionally diverse range of silk fibers, each composed of one or more specific silk proteins. Of all silk types, wrapping silk combines high strength and extensibility and is made of multiple aciniform silk proteins (AcSp) that can be grouped into two AcSp types (AcSp1 and AcSp2) according to their distinct repetitive regions. Here, we present a novel and complete AcSp gene from orb weaving spider Araneus ventricosus. Phylogenetic analysis of the terminal regions of spidroins reveals that the new silk protein and the published A. ventricosus AcSp2 together form a subclade, indicating that this protein is a member of AcSp2 subclass and therefore named AcSp2 variant 2 (AcSp2-v2). The repetitive region of A. ventricosus AcSp2-v2 contains 24 cysteine residues, which is the first time that cysteine has been found in repetitive regions of spidroins. Moreover, the discovery of the ability of AcSp2-v2 repetitive domain to self-assemble into silk fibers expands the repertoire of known self-assembling sequences.
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http://dx.doi.org/10.1016/j.ijbiomac.2021.12.088DOI Listing
March 2022

Molecular Characteristics of Isolated From Chinese Children With Different Diseases.

Front Microbiol 2021 9;12:722225. Epub 2021 Dec 9.

Microbiology Laboratory, National Center for Children's Health, Beijing Pediatric Research Institute, Beijing Children's Hospital, Capital Medical University, Beijing, China.

is a bacterial pathogen that causes a wide spectrum of clinical diseases exclusively in humans. The distribution of type, antibiotic resistance and virulence gene expression for varies temporally and geographically, resulting in distinct disease spectra. In this study, we analyzed antibiotic resistance and resistance gene expression patterns among isolates from pediatric patients in China and investigated the relationship between virulence gene expression, type, and disease categories. Forty-two representative 1.0 and 12.0 strains ( = 20 and = 22, respectively) isolated from patients with scarlet fever or obstructive sleep apnea-hypopnea syndrome were subjected to whole-genome sequencing and phylogenetic analysis. These strains were further analyzed for susceptibility to vancomycin. We found a high rate and degree of resistance to macrolides and tetracycline in these strains, which mainly expressed and . The disease category correlated with type but not superantigens. The distribution of and virulence genes were associated with type. Previously reported important prophages, such as φHKU16.vir, φHKU488.vir, Φ5005.1, Φ5005.2, and Φ5005.3 encoding streptococcal toxin, and integrative conjugative elements (ICEs) such as ICE-emm12 and ICE-HKU397 encoding macrolide and tetracycline resistance were found present amongst 1 or 12 clones from Shenzhen, China.
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http://dx.doi.org/10.3389/fmicb.2021.722225DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8696671PMC
December 2021

Customized Flagelliform Spidroins Form Spider Silk-like Fibers at pH 8.0 with Outstanding Tensile Strength.

ACS Biomater Sci Eng 2022 01 15;8(1):119-127. Epub 2021 Dec 15.

Department of Biosciences and Nutrition, Karolinska Institutet, 14157 Huddinge, Sweden.

Spider flagelliform silk shows the best extensibility among various types of silk, but its biomimetic preparation has not been much studied. Herein, five customized flagelliform spidroins (FlSps: S and NTD-Sn-CTD, = 1-4), in which the repetitive region (S) and N-/C- terminal domains (NTD and CTD) are from the same spidroin and spider species, were produced recombinantly. The recombinant spidroins with terminal domains were able to form silk-like fibers with diameters of ∼5 μm by manual pulling at pH 8.0, where the secondary structure transformation occurred. The silk-like fibers from NTD-S4-CTD showed the highest tensile strength (∼250 MPa), while those ones with 1-3 S broke at a similar stress (∼180 MPa), suggesting that increasing the amounts of the repetitive region can improve the tensile strength, but a certain threshold might need to be reached. This study shows successful preparation of flagelliform silk-like fibers with good mechanical properties, providing general insights into efficient biomimetic preparations of spider silks.
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http://dx.doi.org/10.1021/acsbiomaterials.1c01354DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8753598PMC
January 2022

Black Tea Alleviates Particulate Matter-Induced Lung Injury via the Gut-Lung Axis in Mice.

J Agric Food Chem 2021 Dec 14;69(50):15362-15373. Epub 2021 Dec 14.

Institute of Tea Science, Zhejiang University, Hangzhou 310058, China.

Black tea, as the most consumed kind of tea, is shown to have beneficial effects on human health. However, its impact on particulate matter (PM) induced lung injury and the mechanisms involved have been sparsely addressed. Here, we show that PM-exposed mice exhibited oxidative stress and inflammation in the lungs, which was significantly alleviated by a daily intake of black tea infusion (TI) in a concentration-dependent manner. Interestingly, both the ethanol-soluble fraction (ES) and the ethanol precipitate fraction (EP) exhibited better effects than those of TI; moreover, EP tended to have stronger protection than ES in some indicators, implying that EP played a dominant role in the prevention effects. Furthermore, fecal microbiota transplantation (FMT) revealed that the gut microbiota was differentially reshaped by TI and its fractions were able to directly alleviate the injury induced by PMs. These results indicate that daily intake of black tea and its fractions, especially EP, may alleviate particulate matter-induced lung injury via the gut-lung axis in mice. In addition, the could be the core gut microbe contributing to the protection of EP and thus should be further studied in the future.
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http://dx.doi.org/10.1021/acs.jafc.1c06796DOI Listing
December 2021

Improvement of Astragalin on Spermatogenesis in Oligoasthenozoospermia Mouse Induced by Cyclophosphamide.

Reprod Sci 2022 06 30;29(6):1738-1748. Epub 2021 Nov 30.

Department of Obstetrics and Gynecology, Key Laboratory for Gynecologic Oncology Gansu Province, The First Hospital of Lanzhou University, Lanzhou, China.

More than 40% of infertile men are diagnosed with oligoasthenozoospermia and the incidence is still rising, but the effective treatments are not been found until now. Astragalin, one of the main active ingredients in traditional Chinese medicine, may be effective in the treatment of oligoasthenozoospermia. This study investigated the pharmacological effects of astragalin for treatment of oligoasthenozoospermia in male mice, induced by cyclophosphamide (CTX). Male mice were intraperitoneally injected by CTX (50 mg/kg), and astragalin (30 mg/kg) was given via oral gavage once daily. RNA-seq analysis highlighted astragalin upregulated gene expression of anti-apoptosis (AKT1and BCL2-XL), cell proliferation (ETV1, MAPKAPK2, and RPS6KA5) and synthesis of testosterone (STAR, CYP11A1, and PRKACB), but downregulated gene expression of cell apoptosis (BAD, BCL-2, CASPASE9, and CASPASE3) in mouse testis. Astragalin also significantly reversed the reduction in body weight, reproductive organs index, and sperm parameters (sperm concentration, viability, and motility) induced by CTX, and restored testicular abnormal histopathologic morphology induced by CTX. Furthermore, astragalin dramatically rescued the gene expression related to spermatogenesis (AKT1, BCL-2, CASPASE9, CASPASE3, MAPKAPK2, RPS6KA5, STAR, and PRKACB), and increased the level of testosterone by improving related proteins (STAR, CYP11A1, PRKACB) for oligoasthenozoospermia induced by CTX. In conclusion, astragalin may be a potential beneficial agent for oligoasthenozoospermia by increasing the testosterone levels in testis.
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http://dx.doi.org/10.1007/s43032-021-00808-8DOI Listing
June 2022

A word of caution on using tumor biomarker reference change values to guide medical decisions and the need for alternatives.

Clin Chem Lab Med 2022 03 15;60(4):553-555. Epub 2021 Oct 15.

Institute of Laboratory Medicine, Munich Biomarker Research Center, Deutsches Herzzentrum München, Technische Universität Munchen, Munich, Germany.

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http://dx.doi.org/10.1515/cclm-2021-0933DOI Listing
March 2022

Characteristics of electrospun membranes in different spidroin/PCL ratios.

Biomed Mater 2021 10 13;16(6). Epub 2021 Oct 13.

Institute of Biological Sciences and Biotechnology, Donghua University, Shanghai 201620, People's Republic of China.

Spider silk is a protein fiber with the highest strength and elasticity known in nature, even higher than that of silkworm silk. It was a biological and technical reserve material with great potential. However, the low yield of natural spider silk limits the application of spider silk, and the development of genetic engineering provides opportunities for the mass production of spider silk. We constructed a mini-recombinant spidroin NRC based on spider silk gene fromand successfully expressed it through Prokaryotic expression that provide a high production for application using electrospinning, which is a mature technique to produce micro-nano scale fibers as thin as natural spider silks. By blending the purified and lyophilized NRC with polycaprolactone (PCL) in different mass ratio for electrospinning, different electrospun membranes were obtained, and then characterized in terms of morphology, chemical structure, mechanical and Schwann cell proliferation. Compared the difference between polycaprolactone (PCL) and NRC, the fiber diameter decreased from 1.0779 μm to 0.5785 μm, water contact angel decreased from 104.1 ± 2° to 56.9 ± 5°, and elongation decreased from 240.97 ± 89% to 37.76 ± 13%, while tensile strength increased from 1.74 ± 1.2 MPa to 3.18 ± 0.9 MPa and Young's Module increased from 3.05 ± 1.6 MPa to 16.54 ± 6.7 MPa. In this study, we obtained a thinner fiber, hydrophilicity and high strengthen electrospinning spidroin contained membrane, which can also promote Schwann cell proliferation and adhesion.
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http://dx.doi.org/10.1088/1748-605X/ac2ab7DOI Listing
October 2021

Transcriptome Analysis and Expression Profiling of Molecular Responses to Cd Toxicity in .

Mycobiology 2021 10;49(4):421-433. Epub 2021 Jul 10.

College of Eco-Environmental Engineering, Qinghai University, Qinghai, China.

is a genus of fungi with the ability to concentrate Cd both in the fruit-body and mycelium. However, the molecular mechanisms conferring resistance to Cd stress in are unknown. Here, RNA-based transcriptomic sequencing was used to identify the genes and pathways involved in Cd tolerance in . 7444 differentially expressed genes (DEGs) were identified by cultivating in media containing 0.15, 0.90, or 1.50 mg/L Cd. The DEGs were divided into six sub-clusters based on their global expression profiles. GO enrichment analysis indicated that numerous DEGs were associated with catalytic activity, cell cycle control, and the ribosome. KEGG enrichment analysis showed that the main pathways under Cd stress were MAPK signaling, oxidative phosphorylation, pyruvate metabolism, and propanoate metabolism. In addition, several DEGs encoding ion transporters, enzymatic/non-enzymatic antioxidants, and transcription factors were identified. Based on these results, a preliminary gene regulatory network was firstly proposed to illustrate the molecular mechanisms of Cd detoxification in . These results provide valuable insights into the Cd tolerance mechanism of and constitute a robust foundation for further studies on detoxification mechanisms in macrofungi that could potentially lead to the development of new and improved fungal bioremediation strategies.
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http://dx.doi.org/10.1080/12298093.2021.1937882DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8409932PMC
July 2021

Rapid, robust, and sustainable antibody responses to mRNA COVID-19 vaccine in convalescent COVID-19 individuals.

JCI Insight 2021 10 22;6(20). Epub 2021 Oct 22.

Department of Pathology and Laboratory Medicine, Weill Cornell Medicine, New York, New York, USA.

Longitudinal studies are needed to evaluate the SARS-CoV-2 mRNA vaccine antibody response under real-world conditions. This longitudinal study investigated the quantity and quality of SARS-CoV-2 antibody response in 846 specimens from 350 patients, comparing BNT162b2-vaccinated individuals (19 previously diagnosed with COVID-19, termed RecoVax; and 49 never diagnosed, termed NaiveVax) with 122 hospitalized unvaccinated (HospNoVax) and 160 outpatient unvaccinated (OutPtNoVax) COVID-19 patients. NaiveVax experienced delay in generating SARS-CoV-2 total antibodies (TAb) and surrogate neutralizing antibodies (SNAb) after the first vaccine dose (D1) but rapid increase in antibody levels after the second dose (D2). However, these never reached RecoVax's robust levels. In fact, NaiveVax TAb and SNAb levels decreased 4 weeks after D2. For the most part, RecoVax TAb persisted, after reaching maximal levels 2 weeks after D2, but SNAb decreased significantly about 6 months after D1. Although NaiveVax avidity lagged behind that of RecoVax for most of the follow-up periods, NaiveVax did reach similar avidity by about 6 months after D1. These data suggest that 1 vaccine dose elicits maximal antibody response in RecoVax and may be sufficient. Also, despite decreasing levels in TAb and SNAb over time, long-term avidity may be a measure worth evaluating and possibly correlating to vaccine efficacy.
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http://dx.doi.org/10.1172/jci.insight.151477DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8564891PMC
October 2021

AACC Practical Recommendations for Implementing and Interpreting SARS-CoV-2 Emergency Use Authorization and Laboratory-Developed Test Serologic Testing in Clinical Laboratories.

Clin Chem 2021 09;67(9):1188-1200

LifeLabs Medical Laboratories, Toronto, ON, Canada.

Background: The clinical laboratory continues to play a critical role in managing the coronavirus pandemic. Numerous US Food and Drug Administration emergency use authorization (EUA) and laboratory-developed test (LDT) serologic assays have become available. The performance characteristics of these assays and their clinical utility continue to be defined in real time during this pandemic. The AACC convened a panel of experts from clinical chemistry, microbiology, and immunology laboratories; the in vitro diagnostics industry; and regulatory agencies to provide practical recommendations for implementation and interpretation of these serologic tests in clinical laboratories.

Content: The currently available EUA serologic tests and platforms, information on assay design, antibody classes including neutralizing antibodies, and the humoral immune responses to SARS-CoV-2 are discussed. Verification and validation of EUA and LDT assays are described, along with a quality management approach. Four indications for serologic testing are outlined. Recommendations for result interpretation, reporting comments, and the role of orthogonal testing are also presented.

Summary: This document aims to provide a comprehensive reference for laboratory professionals and healthcare workers to appropriately implement SARS-CoV-2 serologic assays in the clinical laboratory and to interpret test results during this pandemic. Given the more frequent occurrence of outbreaks associated with either vector-borne or respiratory pathogens, this document will be a useful resource in planning for similar scenarios in the future.
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http://dx.doi.org/10.1093/clinchem/hvab051DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8083777PMC
September 2021

Are Arterial Blood Samples Acceptable for Chemistry Testing in Laboratory Practice?

Authors:
Qing H Meng

J Appl Lab Med 2021 09;6(5):1380-1383

Department of Laboratory Medicine, Division of Pathology and Laboratory Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.

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http://dx.doi.org/10.1093/jalm/jfab060DOI Listing
September 2021

Assessment of Prognostic Value of High-Sensitivity Cardiac Troponin T for Early Prediction of Chemoradiation Therapy-Induced Cardiotoxicity in Patients with Non-Small Cell Lung Cancer: A Secondary Analysis of a Prospective Randomized Trial.

Int J Radiat Oncol Biol Phys 2021 11 21;111(4):907-916. Epub 2021 Jul 21.

Departments of Radiation Oncology. Electronic address:

Purpose: Cardiotoxicities induced by cancer therapy can negatively affect quality of life and survival. We investigated whether high-sensitivity cardiac troponin T (hs-cTnT) levels could serve as biomarker for early detection of cardiac adverse events (CAEs) after chemoradiation therapy (CRT) for non-small cell lung cancer (NSCLC).

Methods And Materials: This study included 225 patients who received concurrent platinum and taxane-doublet chemotherapy with thoracic radiation therapy to a total dose of 60 to 74 Gy for NSCLC. All patients were evaluated for CAEs; 190 patients also had serial hs-cTnT measurements.

Results: Grade ≥3 CAEs occurred in 24 patients (11%) at a median interval of 9 months after CRT. Pretreatment hs-cTnT levels were higher in men, in patients aged ≥64 years, and in patients with pre-existing heart disease or poor performance status (P < .05). hs-cTnT levels increased at 4 weeks during CRT (P < .05) and decreased after completion of CRT but did not return to pretreatment levels (P = .002). The change (Δ) in hs-cTnT levels during CRT correlated with mean heart dose (P = .0004), the heart volumes receiving 5 to 55 Gy (P < .05), and tumor location (P = .006). Risks of severe CAEs and mortality were significantly increased if the pretreatment hs-cTnT was >10 ng/L or the Δ during CRT was ≥5 ng/L.

Conclusions: Elevation of hs-cTnT during CRT was radiation heart dose-dependent, and high hs-cTnT levels during the course of CRT were associated with CAEs and mortality. Routine monitoring of hs-cTnT could identify patients who are at high risk of CRT-induced CAEs early to guide modifications of cancer therapy and possible interventions to mitigate cardiotoxicity.
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http://dx.doi.org/10.1016/j.ijrobp.2021.07.035DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8530972PMC
November 2021

Fusobacterium nucleatum secretes amyloid-like FadA to enhance pathogenicity.

EMBO Rep 2021 07 29;22(7):e52891. Epub 2021 Jun 29.

Section of Oral, Diagnostic and Rehabilitation Sciences, Division of Periodontics, College of Dental Medicine, Columbia University Irving Medical Center, New York, NY, USA.

Fusobacterium nucleatum (Fn) is a Gram-negative oral commensal, prevalent in various human diseases. It is unknown how this common commensal converts to a rampant pathogen. We report that Fn secretes an adhesin (FadA) with amyloid properties via a Fap2-like autotransporter to enhance its virulence. The extracellular FadA binds Congo Red, Thioflavin-T, and antibodies raised against human amyloid β42. Fn produces amyloid-like FadA under stress and disease conditions, but not in healthy sites or tissues. It functions as a scaffold for biofilm formation, confers acid tolerance, and mediates Fn binding to host cells. Furthermore, amyloid-like FadA induces periodontal bone loss and promotes CRC progression in mice, with virulence attenuated by amyloid-binding compounds. The uncleaved signal peptide of FadA is required for the formation and stability of mature amyloid FadA fibrils. We propose a model in which hydrophobic signal peptides serve as "hooks" to crosslink neighboring FadA filaments to form a stable amyloid-like structure. Our study provides a potential mechanistic link between periodontal disease and CRC and suggests anti-amyloid therapies as possible interventions for Fn-mediated disease processes.
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http://dx.doi.org/10.15252/embr.202152891DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8406402PMC
July 2021

Circular RNA circRHOBTB3 represses metastasis by regulating the HuR-mediated mRNA stability of PTBP1 in colorectal cancer.

Theranostics 2021 1;11(15):7507-7526. Epub 2021 Jun 1.

Department of Colorectal Surgery, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, 310058 Hangzhou, China.

Tumor metastasis of colorectal cancer (CRC) is the main cause of death in most patients and the major difficulty in comprehensive CRC treatment. Circular RNAs (circRNAs) affect many biological functions in solid tumors. However, their mechanisms in CRC metastasis remain unclear. RNA sequencing (RNA-seq) and quantitative real-time PCR were performed to screen differentially expressed circRNAs between CRC tissues and adjacent normal tissues. CCK-8, cell migration and wound healing assays were performed to determine the functions of circRHOBTB3 in cell proliferation and metastasis. RNA pulldown and RNA immunoprecipitation assays were performed to verify the interaction between circRHOBTB3 and the HuR (ELAVL1) protein. Further RNA-seq and rescue experiments were applied to search for the downstream target. We also conducted a mouse xenograft model to elucidate the effect of circRHOBTB3 on cancer metastasis . We identified circRHOBTB3 which is markedly downregulated in CRC tissues and cell lines. Furthermore, lower circRHOBTB3 levels were significantly associated with advanced clinical stages and greater risk of metastases. Overexpression of circRHOBTB3 suppresses tumor metastasis in CRC cells. Mechanistically, circRHOBTB3 binds to HuR, which is a ubiquitously expressed and functional RNA-binding protein (RBP) in CRC development, and promotes β-Trcp1-mediated ubiquitination of HuR. Normally, HuR binds to the 3'UTR of target mRNAs to facilitate their stabilization, whereas the interaction between circRHOBTB3 and HuR degrades HuR to reduce the expression level of the downstream target PTBP1. Furthermore, overexpressed circRHOBTB3 suppresses lung metastases , and this effect can be partly reversed by PTBP1 overexpression. In addition, the transcription of circRHOBTB3 can be improved by both FUS and ADARB2 in CRC cells. Our findings indicate that circRHOBTB3 exerts suppressive effects on CRC aggressiveness through the HuR/PTBP1 axis.
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http://dx.doi.org/10.7150/thno.59546DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8210600PMC
July 2021

Delayed elimination communication on the prevalence of children's bladder and bowel dysfunction.

Sci Rep 2021 06 11;11(1):12366. Epub 2021 Jun 11.

Pediatric Urodynamic Center and Department of Urology, First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, China.

To determine the prevalence of bladder and bowel dysfunction (BBD) and its relationship with delayed elimination communication (EC) in children. A cross-sectional study was carried out in kindergartens and primary schools in mainland China. A total of 10,166 children ranging from 4 to 10 years old were included. A total of 10,166 valid questionnaires were collected, and 409 children were diagnosed with BBD. The overall prevalence was 4.02% (409/10,166) and decreased with age, from 6.19% at age 4 to 1.96% at age 10. With the prolonged use of disposable diapers (DDs), the commencement of usage of EC in a child was significantly put off or delayed by parents, and the prevalence of BBD amongst these children increased (P < 0.001). The prevalence of BBD among children who stopped using DDs within the first 12 months and after more than 24 months was 2.79% and 4.38% respectively. Additionally, the prevalence among children who started EC within 12 months after birth and those who never engaged in EC was 1.36% and 15.71% respectively. Early introduction of EC and weaning of DD usage has a positive correlation with lower prevalence of BBD in children in China.
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http://dx.doi.org/10.1038/s41598-021-91704-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8196082PMC
June 2021

An Oligonucleotide-Distortion-Responsive Organic Transistor for Platinum-Drug-Induced DNA-Damage Detection.

Adv Mater 2021 Jun 13;33(25):e2100489. Epub 2021 May 13.

Beijing National Laboratory for Molecular Sciences, CAS Key Laboratory of Organic Solids, Institute of Chemistry, Chinese Academy of Sciences, Beijing, 100190, China.

Organic transistor with DNA-damage evaluation ability can open up novel opportunities for bioelectronic devices. Even though trace amounts of drugs can cause cumulative gene damage in vivo, the extremely low occurrence proportion makes them hardly transduced into detectable electric signals. Here, an ultrasensitive DNA-damage sensor based on an oligonucleotide-distortion-responsive organic transistor (DROT) is reported by creating controllable conformation change of double-stranded DNA on the surface of organic semiconductors. In combination with interfacial charge redistribution and efficient signal amplification, the DROT provides an ultrasensitive single-site DNA-damage response with 20.5 s even upon 1 × 10 m cisplatin. The high generalizability of this DROT to three generations of classical platinum drugs and gene-relevant DNA damage is demonstrated. A biochip is further designed for intelligent damage analysis in complex environments, which holds the potential for high-throughput biotoxicity evaluation and drug screening in the future.
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http://dx.doi.org/10.1002/adma.202100489DOI Listing
June 2021

[CT and Magnetic Resonance Imaging Findings of the Intracranial Extra-cerebral Chondroma:A Case Report].

Zhongguo Yi Xue Ke Xue Yuan Xue Bao 2021 Apr;43(2):300-304

Department of Radiology,Hainan Hospital of Chinese PLA General Hospital,Sanya,Hainan 572013,China.

Intracranial intradural chondroma is a rare disorder,the imaging findings of which have been rarely reported.The current study reported a case of intracranial extra-cerebral chondroma and described the detailed CT and magnetic resonance imaging findings,which would provide valuable imaging evidence for the diagnosis of intracranial extra-cerebral chondroma.
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http://dx.doi.org/10.3881/j.issn.1000-503X.12506DOI Listing
April 2021
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