Publications by authors named "Xin Yi"

638 Publications

Bacterial volatile-mediated suppression of root-knot nematode (Meloidogyne incognita).

Plant Dis 2021 Nov 29. Epub 2021 Nov 29.

Institute of Microbiology Chinese Academy of Sciences, 85387, State Key Laboratory of Mycology, Beijing, Beijing, China.

Root-knot nematodes (Meloidogyne spp.) are obligate plant parasites that cause severe economic losses to agricultural crops worldwide. Due to serious health and environmental concerns related to the use of chemical nematicides, the development of efficient alternatives is of great importance. Biological control through exploiting the potential of rhizosphere microorganisms is currently accepted as an important approach for pest management in sustainable agriculture. In our research, during screening of rhizosphere bacteria against the root-knot nematodes Meloidogyne incognita, Ochrobactrum pseudogrignonense strain NC1 from the rhizosphere of healthy tomatoes showed strong nematode inhibition. A volatile nematicidal assay showed that the cell-free fermentation filtrate in the first-row wells of 12-well tissue culture plates caused M. incognita juvenile mortality in the second-row wells. Gas chromatography-mass spectrometry (GC-MS) analysis revealed that dimethyl disulfide (DMDS) and benzaldehyde were the main volatile compounds produced by strain NC1. The nematicidal activity of these compounds indicated that the LC50 against the M. incognita juveniles in the second-row wells and the fourth-row wells were 23.4 μmol/mL and 30.7 μmol/mL for DMDS and 4.7 μmol/mL and 15.2 μmol/mL for benzaldehyde, respectively. A greenhouse trial using O. pseudogrignonense strain NC1 provided management efficiencies of root-knot nematodes of 88 to 100% compared with the untreated control. This study demonstrated that nematode-induced root-gall suppression mediated by the bacterial volatiles DMDS and benzaldehyde presents a new opportunity for root-knot nematode management.
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http://dx.doi.org/10.1094/PDIS-06-21-1139-REDOI Listing
November 2021

KIAA1522 is a new biomarker of promoting the tumorigenesis and distant metastasis of colorectal carcinoma.

Cell Signal 2021 Nov 23:110202. Epub 2021 Nov 23.

Department of General Surgery, Qilu Hospital, Cheeloo College of Medicine, Shandong University, 107 Wenhua Road, Jinan, Shandong 250012, China. Electronic address:

Purpose: Our research was absorbed into exploring the expression, clinicopathological value, biological significance and signaling pathway of KIAA1522 in colorectal carcinoma and its distant metastasis.

Materials And Methods: The expression of KIAA1522 and survival analysis in colorectal carcinoma (CRC) were assessed using GEPIA databases. Then we evaluated the expression of KIAA1522 immunohistochemically in tissue samples of 57 patients with colorectal carcinoma liver metastasis (CRLM). The correlations between the expression of KIAA1522, clinical significance and prognosis of these 57 patients with CRLM were analyzed. The migration and invasion of KIAA1522 were explored by western blotting, CCK-8, colony formation, flow cytometry, wound healing assays and transwell invasion in vitro and tail vein injection models in vivo. Then, transcriptome sequencing and gene set enrichment analysis was performed to identify the signaling pathways involved, while western blotting analysis and immunohistochemistry (IHC) were used to identify the expression of key genes in Notch signaling.

Results: KIAA1522 was overexpressed in CRLM tissues and colon cancer cell lines, and the expression of KIAA1522 in metastatic sites was positively correlated with that in primary sites. In addition, the overexpression of KIAA1522 is associated with poor clinicopathological features. Survival analysis showed that the overexpression of KIAA1522 predicted a low overall survival rate in patients with CRLM. Functional studies suggested that KIAA1522 promotes the proliferation, invasion and migration of colon carcinoma in vitro. KIAA1522 could promote distant metastasis of CRC in vivo. Moreover, KIAA1522 upregulated the Notch signaling pathway in colorectal cancer cell lines in vitro and lung metastatic nodes in vivo.

Conclusion: In conclusion, it is suggested that the upregulation of KIAA1522 might promote the tumorigenicity and metastasis of colorectal carcinoma through Notch signaling pathway. KIAA1522 plays a carcinogenic role in the metastasis of colorectal carcinoma and might serve as a new molecular target for the treatment.
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http://dx.doi.org/10.1016/j.cellsig.2021.110202DOI Listing
November 2021

Polycyclic Aromatic Carbon: A Key Fraction Determining the Light Absorption Properties of Methanol-Soluble Brown Carbon of Open Biomass Burning Aerosols.

Environ Sci Technol 2021 Nov 22. Epub 2021 Nov 22.

State Key Laboratory of Organic Geochemistry and Guangdong-Hongkong-Macao Joint Laboratory for Environmental Pollution and Control, Guangzhou Institute of Geochemistry, Chinese Academy of Sciences, Guangzhou 510640, P. R. China.

The composition and radiative forcing of light-absorbing brown carbon (BrC) aerosol remain poorly understood. Polycyclic aromatics (PAs) are BrC chromophores with fused benzene rings. Understanding the occurrence and significance of PAs in BrC is challenging due to a lack of standards for many PAs. In this study, we quantified polycyclic aromatic carbon (PAC), defined as the carbon of fused benzene rings, based on molecular markers (benzene polycarboxylic acids, BPCAs). Open biomass burning aerosols (OBBAs) of 22 rainforest plants were successively extracted with water and methanol for the analysis of water- and methanol-soluble PAC (WPAC and MPAC, respectively). PAC is an important fraction of water- and methanol-soluble organic carbon (WSOC and MSOC, respectively). WPAC/WSOC ranged from 0.03 to 0.18, and MPAC/MSOC was even higher (range: 0.16-0.80). The priority polycyclic aromatic hydrocarbons contributed less than 1% of MPAC. The mass absorption efficiency (MAE) of MSOC showed a strong linear correlation with MPAC/MSOC ( = 0.60-0.95, < 0.01). The absorption Ångström exponent (AAE) of methanol-soluble BrC showed a strong linear correlation with the degree of aromatic condensation of MPAC, which was described by the average number of carboxylic groups of BPCA ( = -0.79, < 0.01). This result suggested that PAC was a key fraction determining the light absorption properties (i.e., light absorptivity and wavelength dependence) of methanol-soluble BrC in OBBAs.
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http://dx.doi.org/10.1021/acs.est.1c06460DOI Listing
November 2021

Generation of two multipotent mesenchymal progenitor cell lines capable of osteogenic, mature osteocyte, adipogenic, and chondrogenic differentiation.

Sci Rep 2021 Nov 19;11(1):22593. Epub 2021 Nov 19.

Indiana Center for Musculoskeletal Health, Indiana University, Indianapolis, IN, 46202, USA.

Mesenchymal progenitors differentiate into several tissues including bone, cartilage, and adipose. Targeting these cells in vivo is challenging, making mesenchymal progenitor cell lines valuable tools to study tissue development. Mesenchymal stem cells (MSCs) can be isolated from humans and animals; however, obtaining homogenous, responsive cells in a reproducible fashion is challenging. As such, we developed two mesenchymal progenitor cell (MPC) lines, MPC1 and MPC2, generated from bone marrow of male C57BL/6 mice. These cells were immortalized using the temperature sensitive large T-antigen, allowing for thermal control of proliferation and differentiation. Both MPC1 and MPC2 cells are capable of osteogenic, adipogenic, and chondrogenic differentiation. Under osteogenic conditions, both lines formed mineralized nodules, and stained for alizarin red and alkaline phosphatase, while expressing osteogenic genes including Sost, Fgf23, and Dmp1. Sost and Dmp1 mRNA levels were drastically reduced with addition of parathyroid hormone, thus recapitulating in vivo responses. MPC cells secreted intact (iFGF23) and C-terminal (cFGF23) forms of the endocrine hormone FGF23, which was upregulated by 1,25 dihydroxy vitamin D (1,25D). Both lines also rapidly entered the adipogenic lineage, expressing adipose markers after 4 days in adipogenic media. MPC cells were also capable of chondrogenic differentiation, displaying increased expression of cartilaginous genes including aggrecan, Sox9, and Comp. With the ability to differentiate into multiple mesenchymal lineages and mimic in vivo responses of key regulatory genes/proteins, MPC cells are a valuable model to study factors that regulate mesenchymal lineage allocation as well as the mechanisms that dictate transcription, protein modification, and secretion of these factors.
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http://dx.doi.org/10.1038/s41598-021-02060-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8605002PMC
November 2021

The endocytic pathway of Pt nanoclusters and their induced apoptosis of A549 and A549/Cis cells through c-Myc/p53 and Bcl-2/caspase-3 signaling pathways.

Biomed Pharmacother 2021 Dec 28;144:112360. Epub 2021 Oct 28.

Henan Key Laboratory for Helicobacter pylori & Microbiota and GI Cancer, Marshall Medical Research Center, The Fifth Affiliated Hospital of Zhengzhou University, No. 3 Kangfuqian Street, Erqi District, Zhengzhou 450052, China.

In recent years, multifunctional platinum nanoclusters (Pt-NCs) as new Pt-based anti-cancer drugs exhibit a promising therapeutic efficiency for several cancer diseases, especially for human pulmonary carcinoma. However, the endocytosis behaviors (like uptake pathway, etc.) and induced apoptosis mechanism of Pt-NCs for drug-resistant non-small cell lung cancer (NSCLC), are still inconclusive. In this research, we explored the endocytic pathway of Pt-NCs in both typical NSCLC A549 cells and cisplatin-resistant A549/Cis cells through qualitative confocal laser scanning microscope (CLSM) measurement and quantitative flow cytometry (FCM) and inductive coupled plasma-optical emission spectroscopy (ICP-OES) analysis, by the means of introducing the specific inhibitors which impede the classical ways of endocytosis. It was found that Pt-NCs dominatingly entered A549 cells via caveolin-mediated endocytosis as well as A549/Cis cells through micropinocytosis approach. Pt-NCs possessed an excellent inhibitory effect on the cell proliferation, migration and invasion, which the cell activity of A549 cells reduced to 14% and that of A549/Cis cells went down about four fifths. Moreover, Pt-NCs treatment increased caspase-3 protein levels and downregulated the expression of c-Myc and Bcl-2, proving the Pt-NCs-induced apoptosis of NSCLC cells was related to c-Myc/p53 and Bcl-2/caspase-3 signal pathways. These results demonstrate the explicit uptake pathway and apoptotic signaling pathway of Pt-NCs for NSCLC, which provides an in-depth and reasonable theoretical basis for the development of new Pt-NCs-based chemotherapeutics in future clinical practice.
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http://dx.doi.org/10.1016/j.biopha.2021.112360DOI Listing
December 2021

Cultivation and Genomic Characterization of the Bile Bacterial Species From Cholecystitis Patients.

Front Microbiol 2021 1;12:739621. Epub 2021 Nov 1.

Department of Microbiology, College of Basic Medical Sciences, Dalian Medical University, Dalian, China.

The microbes in human bile are closely related to gallbladder health and other potential disorders. Although the bile microbial community has been investigated by recent studies using amplicon or metagenomic sequencing technologies, the genomic information of the microbial species resident in bile is rarely reported. Herein, we isolated 138 bacterial colonies from the fresh bile specimens of four cholecystitis patients using a culturome approach and genomically characterized 35 non-redundant strains using whole-genome shotgun sequencing. The bile bacterial isolates spanned 3 classes, 6 orders, 10 families, and 14 genera, of which the members of , , , and frequently appeared. Genomic analysis identified three species, including sp. D135, sp. D093, and sp. D074, which are not represented in existing reference genome databases. Based on the genome data, the functional capacity between bile and gut isolates was compared. The bile strains encoded 5,488 KEGG orthologs, of which 4.9% were specific to the gut strains, including the enzymes involved in biofilm formation, two-component systems, and quorum-sensing pathways. A total of 472 antibiotic resistance genes (ARGs) were identified from the bile genomes including multidrug resistance proteins (42.6%), fluoroquinolone resistance proteins (12.3%), aminoglycoside resistance proteins (9.1%), and β-lactamase (7.2%). Moreover, experiments showed that some bile bacteria have the capabilities for bile salt deconjugation or biotransformation (of primary bile acids into secondary bile acids). Although the physiological or pathological significance of these bacteria needs further exploration, our works expanded knowledge about the genome, diversity, and function of human bile bacteria.
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http://dx.doi.org/10.3389/fmicb.2021.739621DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8591784PMC
November 2021

Genomic Landscape in Neoplasm-Like Stroma Reveals Distinct Prognostic Subtypes of Pancreatic Ductal Adenocarcinoma.

Front Oncol 2021 18;11:771247. Epub 2021 Oct 18.

Key Laboratory of Tumor Molecular Diagnosis and Individualized Medicine of Zhejiang Province, Zhejiang Provincial People's Hospital, People's Hospital of Hangzhou Medical College, Hangzhou, China.

As a main component of the tumor microenvironment, the stroma is critical in development, progression, and metastasis of pancreatic ductal adenocarcinoma (PDAC). The genomic status and its relationship of neoplastic and stromal components remain unclear in PDAC. We performed targeted sequencing for 1,021 cancer-suspected genes on parallel microdissected stromal and neoplastic components from 50 operable PDAC patients. Clonality analysis of mutations was conducted to reconstruct the evolutionary trajectory, and then molecular subtypes were established. Multi-lineage differentiation potential and mesenchymal transformation of -mutant cell line Panc1 were evaluated using RT-PCR and immunofluorescence staining. In this study, 39 (78.0%) were genomically altered in stroma, with (71.8%), (61.5%), and (23.1%) as the most commonly mutated genes. The majority of stromal mutations (89.8%) were detected in matched neoplastic components. Patients with -mut stroma demonstrated a higher tumor cell fraction (TCF) than did those with wild-type (WT) stroma ( = 0.0371, = 0.0014). In both components, mutants and often occurred as clonal events, and the allele frequencies presented linear correlation in the same specimen. All neoplasm-like stroma (characterized with all or initial neoplastic clones and driver events in stroma) harbored or mutations. Neoplasm-like and -mutant stroma was associated with shorter disease-free survival. It is a new finding for the existence of driver gene mutations in PDAC stroma. These data suggest that genomic features of stromal components may serve as prognostic biomarkers in resectable PDAC and might help to guide a more precise treatment paradigm in therapeutic options.
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http://dx.doi.org/10.3389/fonc.2021.771247DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8558555PMC
October 2021

Bulging-to-Budding Transition of Lipid Droplets Confined within Vesicle Membranes.

Authors:
Meng Wang Xin Yi

Langmuir 2021 Nov 28;37(44):12867-12873. Epub 2021 Oct 28.

Department of Mechanics and Engineering Science, College of Engineering, Peking University, Beijing 100871, China.

Lipid droplets (LDs) are intracellular organelles that act as reservoirs for energy homeostasis and phospholipid balance between supply and consumption. In comparison with extensive studies on LD biogenesis from a biological viewpoint, little is known about the mechanical interaction between LDs and vesicles. Here we perform a systematic theoretical study on the budding and morphological evolution of an artificial LD embedded within the lipid membrane of a pressurized vesicle. It is found that LD bulging and budding depend on the bending rigidity and spontaneous curvature of the vesicle membrane, LD-vesicle interfacial interaction energy strength and size ratio, and osmotic pressure of the vesicle. Beyond critical interfacial interaction strength, the embedded LD undergoes a discontinuous shape transition from a lens-shaped bulge to a spherical protrusion connecting to the nearly spherical vesicle lumen via an infinitesimally small monolayer neck. Moreover, a positive monolayer spontaneous curvature promotes budding transition. As the vesicle becomes smaller, higher cost of the monolayer stretching energy is required for an LD to achieve budding transition. Budding phase diagrams distinguishing the embedded and budding states of the LD-vesicle complex accounting for osmotic pressure and interfacial interaction strength are established with the budding transition boundary displaying a nonmonotonic feature. Our results reveal how embedded LDs overcome soft membrane confinement and protrude, and provide fundamental insights into the clustering of nanoparticles between vesicle monolayers.
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http://dx.doi.org/10.1021/acs.langmuir.1c01835DOI Listing
November 2021

Input associativity underlies fear memory renewal.

Natl Sci Rev 2021 Sep 8;8(9):nwab004. Epub 2021 Jan 8.

Center for Brain Science of Shanghai Children's Medical Center, Shanghai Jiao Tong University School of Medicine, Shanghai 200127, China.

Synaptic associativity, a feature of Hebbian plasticity wherein coactivation of two inputs onto the same neuron produces synergistic actions on postsynaptic activity, is a primary cellular correlate of associative learning. However, whether and how synaptic associativity are implemented into context-dependent relapse of extinguished memory (i.e. fear renewal) is unknown. Here, using an auditory fear conditioning paradigm in mice, we show that fear renewal is determined by the associativity between convergent inputs from the auditory cortex (ACx) and ventral hippocampus (vHPC) onto the lateral amygdala (LA) that reactivate ensembles engaged during learning. Fear renewal enhances synaptic strengths of both ACx to LA and the previously unknown vHPC to LA monosynaptic inputs. While inactivating either of the afferents abolishes fear renewal, optogenetic activation of their input associativity in the LA recapitulates fear renewal. Thus, input associativity underlies fear memory renewal.
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http://dx.doi.org/10.1093/nsr/nwab004DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8433092PMC
September 2021

Membrane-mediated interaction of intercellular cylindrical nanoparticles.

Authors:
Zeming Wu Xin Yi

Phys Rev E 2021 Sep;104(3-1):034403

Department of Mechanics and Engineering Science, College of Engineering, Peking University, Beijing 100871, P. R. China.

Nanoparticles in intercellular gaps, junctions, or seals could have close contact with neighboring cells simultaneously. Understanding the interaction between intercellular nanoparticles and confining cell membranes is of fundamental importance, not only to the unravelling of endocytic mechanisms but also to implications such as controlled drug delivery in tumor tissues. Here we theoretically examine the mechanical behaviors of adhesive cylindrical nanoparticles confined between two lipid membrane patches of finite size. As the size of the particle-membrane contact region or wrapping degree increases, neighboring cylindrical nanoparticles become separated and the nanoparticle distance increases first and then decreases until the particles are fully trapped by adjacent membrane patches. Depending on the nanoparticle size, adhesion energy, membrane bending rigidity and tension, and intermembrane distance, three characteristic particle-membrane interaction phases are determined as no wrapping, partial trapping, and full trapping, and the corresponding interaction phase diagram is established. Further energy comparison indicates that multiple nanoparticles undergoing the two-membrane trapping process do not exhibit cooperative effects. Analytical estimations on the system energy and configurations at equilibrium are performed based on the force balance of the membranes at small deformation and match well with numerical solutions. The results shed light on the mechanical behaviors of multiple nanoparticles in cell junctions or gaps and may have implications for drug delivery in tumor tissues.
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http://dx.doi.org/10.1103/PhysRevE.104.034403DOI Listing
September 2021

Genomic comparison between cerebrospinal fluid and primary tumor revealed the genetic events associated with brain metastasis in lung adenocarcinoma.

Cell Death Dis 2021 10 12;12(10):935. Epub 2021 Oct 12.

Department of Neurosurgery, The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University/Hunan Cancer Hospital, Hunan Province, Changsha, 410013, China.

Lung adenocarcinoma (LUAD) is most common pathological type of lung cancer. LUAD with brain metastases (BMs) usually have poor prognosis. To identify the potential genetic factors associated with BM, a genomic comparison for BM cerebrospinal fluid (CSF) and primary lung tumor samples obtained from 1082 early- and late-stage LUAD patients was performed. We found that single nucleotide variation (SNV) of EGFR was highly enriched in CSF (87% of samples). Compared with the other primary lung tissues, copy number gain of EGFR (27%), CDK4 (11%), PMS2 (11%), MET (10%), IL7R (8%), RICTOR (7%), FLT4 (5%), and FGFR4 (4%), and copy number loss of CDKN2A (28%) and CDKN2B (18%) were remarkably more frequent in CSF samples. CSF had significantly lower tumor mutation burden (TMB) level but more abundant copy number variant. It was also found that the relationships among co-occurrent and mutually exclusive genes were dynamically changing with LUAD development. Additionally, CSF (97% of samples) harbored more abundant targeted drugs related driver and fusion genes. The signature 15 associated with defective DNA mismatch repair (dMMR) was only identified in the CSF group. Cancer associated pathway analysis further revealed that ErbB (95%) and cell cycle (84%) were unique pathways in CSF samples. The tumor evolution analysis showed that CSF carried significantly fewer clusters, but subclonal proportion of EGFR was remarkably increased with tumor progression. Collectively, CSF sequencing showed unique genomic characteristics and the intense copy number instability associated with cell cycle disorder and dMMR might be the crucial genetic factors in BM of LUAD.
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http://dx.doi.org/10.1038/s41419-021-04223-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8511004PMC
October 2021

Overcome Isomer Interference in 1α,25-Dihydroxyvitamin D Quantitation by Liquid Chromatography-Tandem Mass Spectrometry.

J Appl Lab Med 2021 Oct 11. Epub 2021 Oct 11.

Department of Pathology and Genomic Medicine, Houston Methodist Hospital, Houston, TX, USA.

Background: The circulating concentration of 1α,25-dihydroxyvitamin D [1α,25(OH)2D] is very low, and the presence of multiple isomers may lead to inaccurate quantitation if not separated prior to analysis. Antibody-based immunoextraction procedures are sometimes used to remove structurally related isomers of 1α,25(OH)2D prior to an LC-MS/MS analysis. However, immunoextraction increases sample preparation time and cost. In addition, some dihydroxyvitamin D metabolites are not completely removed by immunoextraction.

Method: We developed an HPLC method using a phenyl-hexyl column to investigate interfering isomers of 1α,25(OH)2D.

Result: Using this method, 4-phenyl-1,2,4-triazoline-3,5-dione (PTAD) derivatization product of 1α,25(OH)2D was found to be present as 2 epimers, which were separated chromatographically with an area ratio of 2:1. PTAD derivatized metabolite of 25-hydroxyvitamin D3 [i.e., 4β,25-dihydroxyvitamin D3 (4β,25(OH)2D3)] eluted out between 6R and 6S epimers of derivatized 1α,25(OH)2D3. If not chromatographically resolved, 4β,25(OH)2D can affect 1α,25(OH)2D quantitation. In a method comparison study, it was found that the presence of 4β,25(OH)2D produced positive bias up to 127% on 1α,25(OH)2D3 quantitation.

Conclusion: The LC-MS/MS method we developed without an immunoextraction procedure was able to resolve the major interference peak from 1α,25(OH)2D and achieved reliable quantitation of 1α,25(OH)2D.
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http://dx.doi.org/10.1093/jalm/jfab112DOI Listing
October 2021

De novo design of self-assembly hydrogels based on Fmoc-diphenylalanine providing drug release.

J Mater Chem B 2021 Oct 27;9(41):8686-8693. Epub 2021 Oct 27.

Department of Chemistry, Fudan University, Shanghai 200438, P. R. China.

Short peptides with self-assembled nanostructures are widely applied in the areas of drug delivery systems and biomaterials. In this article, we create a new peptide-based hydrogelator (Fmoc-FFRRVR) based on -fluorenylmethoxycarbonyl-diphenylalanine (Fmoc-FF) through an approach to improve its hydrophilicity. Compared to Fmoc-FF, Fmoc-FFRRVR prefers to form a hydrogel under mild conditions, and the gelation time is only 2 s. Fmoc-FFRRVR self-assembles into organized arrays of β-sheets in nanofibers π-stacking of Fmoc-FF, which are supported by circular dichroism and fluorescence emission spectroscopy. Rheology results confirm that the hydrogel of Fmoc-FFRRVR is elastic, reversible and injectable. The newly discovered hydrogel not only retains some excellent performances of Fmoc-FF, but also can be used as a drug carrier for biomedical applications.
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http://dx.doi.org/10.1039/d1tb01628hDOI Listing
October 2021

A bionic piezoelectric tactile sensor for features recognition of object surface based on machine learning.

Rev Sci Instrum 2021 Sep;92(9):095003

Jilin Insitute of Metrology, Changchun 130103, China.

Based on the tactile mechanism of human fingertips, a bionic tactile sensor fabricated from polyvinylidene fluoride piezoelectric film is proposed, which can identify the surface softness, viscoelasticity, thermal conductivity, and texture roughness of the object. The tactile sensor is mounted on the fingertip of the bionic manipulator, which obtains the surface features by touching and sliding the object. The time-domain features of the output signal are used for preliminarily discriminating the softness, viscoelasticity, and heat conduction of the object. Finally, based on the Back Propagation and the Particle Swarm Optimization-Back Propagation neural network algorithm, the recognition experiment of texture roughness is carried out using the PSO algorithm to improve the BP neural network so that the optimized BP algorithm has a higher convergence accuracy. The results show that the PSO-BP algorithm achieved the highest accuracy of 98% for identifying samples with different roughnesses and the average recognition achieved an accuracy of 94%. The bionic piezoelectric tactile sensor proposed in this paper has a good application development prospect in recognizing the surface features of objects and intelligent robots.
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http://dx.doi.org/10.1063/5.0057236DOI Listing
September 2021

Electrochemical performance of a new all solid-state ultra-low noise electrospray electrode as a marine electric field sensor.

Rev Sci Instrum 2021 Sep;92(9):095002

College of Instrumentation and Electrical Engineering, Jilin University, Changchun 130061, China.

A new type of Ag/AgCl electrode as a marine electric field sensor is prepared using electrospray. The surface of the electrode is porous, and the particle size of AgCl is small and uniform with an average particle size of 1.43 µm, which accelerated the speed of the oxidation-reduction reactions. Therefore, the electrode with large specific surface area has high stability and low noise. The impedance, sensitivity, self-noise, and stability of the electrode are measured to study the electrochemical performance of the electrode. The impedance of the electrode is 7.9 Ω, and the electrode shows resistance characteristics, meaning that the electrode can well receive the weak ocean electric field signals with low signal distortion. The sensitivity experiment result shows that the electrode can well restore the sinusoidal electric field signal of 1 Hz (10 mV). The voltage drift is less than 5 µV/100 h, the self-potential is between -51 and 56 µV, and the self-noise of the electrode is 2.48 nV @ 1 Hz. The AgCl layer on the surface of the electrode is porous and thick, and the particle size of AgCl is small and uniform. This makes the electrode have excellent electrochemical performance. All the experimental results show that the electrode has ultra-low noise and excellent response to low frequency weak electric field signals. The electrode is of great significance to the exploitation of marine resources as the marine electric field sensor.
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http://dx.doi.org/10.1063/5.0056177DOI Listing
September 2021

Genetic and functional analysis reveals contributes to schizophrenia.

iScience 2021 Sep 30;24(9):103063. Epub 2021 Aug 30.

Bio-X Institutes, Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders (Ministry of Education), Shanghai Jiao Tong University, 1954 Huashan Rd., Shanghai 200030, PR China.

, encoding a member of the teneurin protein family, is a risk gene shared by many types of mental diseases and is implicated in neuronal plasticity and signaling. However, the role and the mechanisms of in schizophrenia (SCZ) remain unclear. We identified possible pathogenic mutations in the gene through target sequencing of in 68 SCZ families. We further demonstrated that aberrant expression of leads to lower learning ability, sleep reduction, and increased aggressiveness in animal models. RNA sequencing showed that aberrant expression of was related to stimulus perception and metabolic process, and Gene Ontology enrichment terms were neurogenesis and ATPase activity. This study provides strong evidence that contributes to SCZ, and its functional mutations might be responsible for the impaired neural circuits and behaviors observed in SCZ.
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http://dx.doi.org/10.1016/j.isci.2021.103063DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8449235PMC
September 2021

Regulation of cell quiescence-proliferation balance by Ca2+-CaMKK-Akt signaling.

J Cell Sci 2021 10 21;134(20). Epub 2021 Oct 21.

Department of Molecular, Cellular and Developmental Biology, University of Michigan, Ann Arbor, MI 48109, USA.

Compared with our extensive understanding of the cell cycle, we have limited knowledge of how the cell quiescence-proliferation decision is regulated. Using a zebrafish epithelial model, we report a novel signaling mechanism governing the cell quiescence-proliferation decision. Zebrafish Ca2+-transporting epithelial cells, or ionocytes, maintain high cytoplasmic Ca2+ concentration ([Ca2+]c) due to the expression of Trpv6. Genetic deletion or pharmacological inhibition of Trpv6, or reduction of external Ca2+ concentration, lowered the [Ca2+]c and reactivated these cells. The ionocyte reactivation was attenuated by chelating intracellular Ca2+ and inhibiting calmodulin (CaM), suggesting involvement of a Ca2+ and CaM-dependent mechanism. Long-term imaging studies showed that after an initial decrease, [Ca2+]c gradually returned to the basal levels. There was a concomitant decease in endoplasmic reticulum (ER) Ca2+ levels. Lowering the ER Ca2+ store content or inhibiting ryanodine receptors impaired ionocyte reactivation. Further analyses suggest that CaM-dependent protein kinase kinase (CaMKK) is a key molecular link between Ca2+ and Akt signaling. Genetic deletion or inhibition of CaMKK abolished cell reactivation, which could be rescued by expression of a constitutively active Akt. These results suggest that the quiescence-proliferation decision in zebrafish ionocytes is regulated by Trpv6-mediated Ca2+ and CaMKK-Akt signaling.
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http://dx.doi.org/10.1242/jcs.253807DOI Listing
October 2021

PlantGSAD: a comprehensive gene set annotation database for plant species.

Nucleic Acids Res 2021 Sep 17. Epub 2021 Sep 17.

State Key Laboratory of Plant Physiology and Biochemistry, College of Biological Sciences, China Agricultural University, Beijing 100193, China.

With the accumulation of massive data sets from high-throughput experiments and the rapid emergence of new types of omics data, gene sets have become more diverse and essential for the refinement of gene annotation at multidimensional levels. Accordingly, we collected and defined 236 007 gene sets across different categories for 44 plant species in the Plant Gene Set Annotation Database (PlantGSAD). These gene sets were divided into nine main categories covering many functional subcategories, such as trait ontology, co-expression modules, chromatin states, and liquid-liquid phase separation. The annotations from the collected gene sets covered all of the genes in the Brassicaceae species Arabidopsis and Poaceae species Oryza sativa. Several GSEA tools are implemented in PlantGSAD to improve the efficiency of the analysis, including custom SEA for a flexible strategy based on customized annotations, SEACOMPARE for the cross-comparison of SEA results, and integrated visualization features for ontological analysis that intuitively reflects their parent-child relationships. In summary, PlantGSAD provides numerous gene sets for multiple plant species and highly efficient analysis tools. We believe that PlantGSAD will become a multifunctional analysis platform that can be used to predict and elucidate the functions and mechanisms of genes of interest. PlantGSAD is publicly available at http://systemsbiology.cau.edu.cn/PlantGSEAv2/.
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http://dx.doi.org/10.1093/nar/gkab794DOI Listing
September 2021

Multi-region exome sequencing reveals the intratumoral heterogeneity of surgically resected small cell lung cancer.

Nat Commun 2021 09 14;12(1):5431. Epub 2021 Sep 14.

Department of Medical Oncology, Sun Yat-Sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, China.

Small cell lung cancer (SCLC) is a highly malignant tumor which is eventually refractory to any treatment. Intratumoral heterogeneity (ITH) may contribute to treatment failure. However, the extent of ITH in SCLC is still largely unknown. Here, we subject 120 tumor samples from 40 stage I-III SCLC patients to multi-regional whole-exome sequencing. The most common mutant genes are TP53 (88%) and RB1 (72%). We observe a medium level of mutational heterogeneity (0.30, range 0.0~0.98) and tumor mutational burden (TMB, 10.2 mutations/Mb, range 1.1~51.7). Our SCLC samples also exhibit somatic copy number variation (CNV) across all patients, with an average CNV ITH of 0.49 (range 0.02~0.99). In terms of mutation distribution, ITH, TMB, mutation clusters, and gene signatures, patients with combined SCLC behave roughly the same way as patients with pure SCLC. This condition also exists in smoking patients and patients with EGFR mutations. A higher TMB per cluster is associated with better disease-free survival while single-nucleotide variant ITH is linked to worse overall survival, and therefore these features may be used as prognostic biomarkers for SCLC. Together, these findings demonstrate the intratumoral genetic heterogeneity of surgically resected SCLC and provide insights into resistance to treatment.
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http://dx.doi.org/10.1038/s41467-021-25787-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8440529PMC
September 2021

Insights into angiosperm evolution, floral development and chemical biosynthesis from the Aristolochia fimbriata genome.

Nat Plants 2021 09 2;7(9):1239-1253. Epub 2021 Sep 2.

State Key Laboratory of Systematic and Evolutionary Botany, Institute of Botany, the Chinese Academy of Sciences, Beijing, China.

Aristolochia, a genus in the magnoliid order Piperales, has been famous for centuries for its highly specialized flowers and wide medicinal applications. Here, we present a new, high-quality genome sequence of Aristolochia fimbriata, a species that, similar to Amborella trichopoda, lacks further whole-genome duplications since the origin of extant angiosperms. As such, the A. fimbriata genome is an excellent reference for inferences of angiosperm genome evolution, enabling detection of two novel whole-genome duplications in Piperales and dating of previously reported whole-genome duplications in other magnoliids. Genomic comparisons between A. fimbriata and other angiosperms facilitated the identification of ancient genomic rearrangements suggesting the placement of magnoliids as sister to monocots, whereas phylogenetic inferences based on sequence data we compiled yielded ambiguous relationships. By identifying associated homologues and investigating their evolutionary histories and expression patterns, we revealed highly conserved floral developmental genes and their distinct downstream regulatory network that may contribute to the complex flower morphology in A. fimbriata. Finally, we elucidated the genetic basis underlying the biosynthesis of terpenoids and aristolochic acids in A. fimbriata.
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http://dx.doi.org/10.1038/s41477-021-00990-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8445822PMC
September 2021

Multiomics Analysis Reveals Distinct Immunogenomic Features of Lung Cancer with Ground-Glass Opacity.

Am J Respir Crit Care Med 2021 11;204(10):1180-1192

Department of Thoracic Surgery and.

Ground-glass opacity (GGO)-associated lung cancers are common and radiologically distinct clinical entities known to have an indolent clinical course and superior survival, implying a unique underlying biology. However, the molecular and immune characteristics of GGO-associated lung nodules have not been systemically studied. To provide mechanistic insights for the treatment of these radiologically distinct clinical entities. We initiated a prospective cohort study to collect and characterize pulmonary nodules with GGO components (nonsolid and part-solid nodules) or without GGO components, as precisely quantified by using three-dimensional image reconstruction to delineate the molecular and immune features associated with GGO. Multiomics assessment conducted by using targeted gene panel sequencing, RNA sequencing, TCR (T-cell receptor) sequencing, and circulating tumor DNA detection was performed. GGO-associated lung cancers exhibited a lower tumor mutation burden than solid nodules. Transcriptomic analysis revealed a less active immune environment in GGO components and immune pathways, decreased expression of immune activation markers, and less infiltration of most immune-cell subsets, which was confirmed by using multiplex immunofluorescence. Furthermore, T-cell repertoire sequencing revealed lower T-cell expansion in GGO-associated lung cancers. HLA loss of heterozygosity was significantly less common in lung adenocarcinomas with GGO components than in those without. Circulating tumor DNA analysis suggested that the release of tumor DNA to the peripheral blood was correlated with the tumor size of non-GGO components. Compared with lung cancers presenting with solid lung nodules, GGO-associated lung cancers are characterized by a less active metabolism and a less active immune microenvironment, which may be the mechanisms underlying their indolent clinical course. Clinical trial registered with www.clinicaltrials.gov (NCT03320044).
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http://dx.doi.org/10.1164/rccm.202101-0119OCDOI Listing
November 2021

[Advances in microbial degradation of plastics].

Sheng Wu Gong Cheng Xue Bao 2021 Aug;37(8):2688-2702

State Key Laboratory of Mycology, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, China.

Plastics are widely used in daily life. Due to poor management and disposal, about 80% of plastic wastes were buried in landfills and eventually became land and ocean waste, causing serious environmental pollution. Recycling plastics is a desirable approach, but not applicable for most of the plastic waste. Microbial degradation offers an environmentally friendly way to degrade the plastic wastes, and this review summarizes the potential microbes, enzymes, and the underpinning mechanisms for degrading six most commonly used plastics including polyethylene terephthalate, polyethylene, polyvinyl chloride, polypropylene, polystyrene and polyurethane. The challenges and future perspectives on microbial degradation of plastics were proposed.
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http://dx.doi.org/10.13345/j.cjb.200624DOI Listing
August 2021

Analytical and Clinical Evaluation of the Semiquantitative Elecsys Anti-SARS-CoV-2 Spike Protein Receptor Binding Domain Antibody Assay on the Roche cobas e602 Analyzer.

Am J Clin Pathol 2021 Aug 31. Epub 2021 Aug 31.

Department of Pathology, University of Chicago, Chicago, IL, USA.

Objectives: To analytically and clinically evaluate the semiquantitative Elecsys anti-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike protein antibody (S-Ab) assay on the Roche cobas e602 analyzer.

Methods: The S-Ab assay is a 1-step, double-antigen sandwich electrochemiluminescent immunoassay that semiquantitatively measures total IgG, IgM, and IgA antibodies specific for the receptor binding domain of SARS-CoV-2 spike protein in serum or plasma. The S-Ab assay was evaluated for precision, linearity, interference (by hemoglobin, bilirubin, triglycerides, and biotin), cross-reactivity, and clinical performance, and was compared to the qualitative Elecsys anti-nucleocapsid (N-Ab) immunoassay, a lateral flow device that qualitatively detects S-Ab and N-Ab, and an anti-spike enzyme-linked immunosorbent assay (ELISA).

Results: S-Ab assay is precise, exhibits linearity from 0.4 to 250 U/mL, is unaffected by significant cross-reactivity or interferences, and qualitatively demonstrates greater than 90% concordance with N-Ab assay and lateral flow device. Readouts of S-Ab assay correlate with ELISA, which in turn correlates strongly with SARS-CoV-2 virus neutralization assay, and exhibit 100% sensitivity and specificity for COVID-19 patient samples obtained at or more than 14 days after PCR positivity.

Conclusions: The S-Ab assay is a robust clinical test for qualitative and semiquantitative detection of seropositivity following SARS-CoV-2 infection or spike-encoding mRNA COVID-19 vaccination.
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http://dx.doi.org/10.1093/ajcp/aqab092DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8499855PMC
August 2021

Whole exome and transcriptome sequencing reveal clonal evolution and exhibit immune-related features in metastatic colorectal tumors.

Cell Death Discov 2021 Aug 27;7(1):222. Epub 2021 Aug 27.

Cancer Center, Daping Hospital, Army Medical University (Third Military Medical University), No.10 Changjiang Zhilu, Daping Yuzhong District, 400038, Chongqing, P.R. China.

Liver is the most common site where metastatic lesions of colorectal cancer (CRC) arise. Although researches have shown mutations in driver genes, copy number variations (CNV) and alterations in relevant signaling pathways promoted the tumor evolution and immune escape during colorectal liver metastasis (CLM), the underlying mechanism remains largely elusive. Tumor and matched metastatic tissues were collected from 16 patients diagnosed with colorectal cancer and subjected to whole-exome sequencing (WES) and RNA sequencing (RNA-seq) for studying colorectal cancer clonal evolution and immune escape during CLM. Shared somatic mutations between primary and metastatic tissues with a commonly observed subclonal-clonal (S-C) changing pattern indicated a common clonal origin between two lesions. The recurrent mutations with S-C changing pattern included those in KRAS, SYNE1, CACNA1H, PCLO, FBXL2, and DNAH11. The main CNV events underwent clonal-clonal evolution (20q amplification (amp), 17p deletion (del), 18q del and 8p del), subclonal-clonal evolution (8q amp, 13q amp, 8p del) and metastasis-specific evolution (8q amp) during the process of CLM. In addition, we revealed a potential mechanism of tumor cell immune escape by analyzing human leukocytes antigens (HLA) related clonal neoantigens and immune cell components in CLM. Our study proposed a novel liver metastasis-related evolutionary process in colorectal cancer and emphasized the theory of neo-immune escape in colorectal liver metastasis.
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http://dx.doi.org/10.1038/s41420-021-00607-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8397721PMC
August 2021

Analysis on the Temporal and Spatial Features of the Coupling and Coordination of Industrialization and Agricultural Green Development in China during 1990-2019.

Int J Environ Res Public Health 2021 08 6;18(16). Epub 2021 Aug 6.

Changchun Guoxin Modern Agricultural Science and Technology Development Co., Ltd., Shuangyang District, Changchun 130600, China.

In the past 30 years, China's industrialization level has developed rapidly, and agricultural green development (AGD) is facing severe challenges. The research on the temporal and spatial features of the coupling and coordination of industrialization and agricultural green development is a key issue to promote the sustainable development of agriculture. This paper takes China's industrialization and AGD level as the research object, and uses panel data from 31 provinces in China from 1990 to 2019 to construct an evaluation index system for industrialization and AGD. This paper uses the coupling coordination degree model and spatial autocorrelation analysis method to calculate, test and analyze the temporal and spatial features of the coupling coordination level of industrialization and AGD. The results show that: this paper compares the industrialization and AGD levels during the study period and finds that China's industrialization development level is on the rise as a whole, and the AGD level shows a downward trend first and then rises later. Through the horizontal comparison of different regions, this paper finds that there is a large regional imbalance in the level of industrialization and AGD. The coupling and coordination level of industrialization and AGD has always been primary. From the time point of view, coupling coordination degree shows a trend of first decline and then rise. From a spatial point of view, coupling coordination degree varies greatly among provinces, with the eastern, central and western regions decreasing successively. The level of coupling coordination has obvious positive autocorrelation in spatial distribution, and presents significant spatial agglomeration characteristics in space. The research results can provide a theoretical basis for regionally differentiated governance of the coordinated development of industrialization and AGD, and promote coordinated development.
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http://dx.doi.org/10.3390/ijerph18168320DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8393941PMC
August 2021

Distribution of black carbon and PAHs in sediments of Peninsular Malaysia.

Mar Pollut Bull 2021 Nov 21;172:112871. Epub 2021 Aug 21.

State Key Laboratory of Organic Geochemistry and Guangdong-Hong Kong-Macao Joint Laboratory for Environmental Pollution and Control, Guangzhou Institute of Geochemistry, Chinese Academy of Sciences, Guangzhou 510640, China; CAS Center for Excellence in Deep Earth Science, Guangzhou 510640, China.

Concentrations, sources and interactions between black carbon (BC) and polycyclic aromatic hydrocarbons (PAHs) were investigated in 42 sediment samples collected from riverine, coastal and shelf areas in Peninsular Malaysia. The concentrations of BC measured by benzene polycarboxylic acid (BPCA) method and PAHs showed broad spatial variations between the relatively pristine environment of the East coast and developed environment of the West and South coast ranging from 0.02 to 0.36% dw and 57.7 ng g dw to 19,300 ng g dw, respectively. Among diagnostic ratios of PAHs, the ratios of Ant/(Ant+Phe) and LMW/HMW drew the clearest distinctions between the East coast versus the West and South coast sediments indicating the predominance of petrogenic sources in the former versus pyrogenic sources in the latter. PAHs significantly correlated with BC and total organic carbon (TOC) in the sediments (p < 0.05) having similar correlation coefficients. BC accounted for 6.06 to 30.6% of TOC in sediments.
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http://dx.doi.org/10.1016/j.marpolbul.2021.112871DOI Listing
November 2021

Study on a 3D-Bioprinted Tissue Model of Self-Assembled Nanopeptide Hydrogels Combined With Adipose-Derived Mesenchymal Stem Cells.

Front Bioeng Biotechnol 2021 3;9:663120. Epub 2021 Aug 3.

Department of General Surgery, Qilu Hospital of Shandong University, Jinan, China.

This study aimed to observe the cell growth status and multidirectional differentiation ability in a 3D-bioprinted tissue model of self-assembled nanopeptides and human adipose-derived mesenchymal stem cells (Ad-MSCs). Primary Ad-MSCs were isolated, cultured, and identified by flow cytometry. Tissue models were printed 3D bioprinting technology using a "biological ink" consisting of a mixed solution of self-assembled nanopeptides and Ad-MSCs. Ad-MSCs were induced into osteogenic, adipogenic, and endothelial differentiation and compared with the control groups by staining. The nanopeptide fiber was 10-30 nm in diameter and 200-500 nm in length under the atomic-force microscope. It had the characteristics of nano-scale materials. Flow cytometry showed that the isolated and cultured cells were positive for CD29 (98.51%), CD90 (97.87%), and CD166 (98.32%) but did not express CD31 (1.58%), CD34 (2.42%), CD45 (2.95%), or human leukocyte antigen (HLA)-DR (0.53%), consistent with the immunophenotype of Ad-MSCs. Then, a tissue model was printed using the biological ink, followed by induction of differentiation of Ad-MSCs within the tissue model. Alizarin red S staining showed the formation of calcium nodules in the osteogenesis induction experimental group, and oil red O stained lipid droplets in Ad-MSCs in the adipogenesis induction experimental group, whereas the two control groups were not stained. Ad-MSCs from primary cultures have the characteristics of stem cells. Self-assembled nanopeptide hydrogel is a good tissue engineering material that can serve as an extracellular matrix. Ad-MSCs in the 3D-printed tissue model using a biological ink consisting of a mixed solution of self-assembled nanopeptides and Ad-MSCs grew well and still had strong differentiation ability.
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http://dx.doi.org/10.3389/fbioe.2021.663120DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8369258PMC
August 2021

Effects of Lung Injury on Regional Aeration and Expiratory Time Constants: Insights From Four-Dimensional Computed Tomography Image Registration.

Front Physiol 2021 28;12:707119. Epub 2021 Jul 28.

Department of Radiology, University of Iowa, Iowa City, IA, United States.

: Intratidal changes in regional lung aeration, as assessed with dynamic four-dimensional computed tomography (CT; 4DCT), may indicate the processes of recruitment and derecruitment, thus portending atelectrauma during mechanical ventilation. In this study, we characterized the time constants associated with deaeration during the expiratory phase of pressure-controlled ventilation in pigs before and after acute lung injury using respiratory-gated 4DCT and image registration. : Eleven pigs were mechanically ventilated in pressure-controlled mode under baseline conditions and following an oleic acid model of acute lung injury. Dynamic 4DCT scans were acquired without interrupting ventilation. Automated segmentation of lung parenchyma was obtained by a convolutional neural network. Respiratory structures were aligned using 4D image registration. Exponential regression was performed on the time-varying CT density in each aligned voxel during exhalation, resulting in regional estimates of intratidal aeration change and deaeration time constants. Regressions were also performed for regional and total exhaled gas volume changes. : Normally and poorly aerated lung regions demonstrated the largest median intratidal aeration changes during exhalation, compared to minimal changes within hyper- and non-aerated regions. Following lung injury, median time constants throughout normally aerated regions within each subject were greater than respective values for poorly aerated regions. However, parametric response mapping revealed an association between larger intratidal aeration changes and slower time constants. Lower aeration and faster time constants were observed for the dependent lung regions in the supine position. Regional gas volume changes exhibited faster time constants compared to regional density time constants, as well as better correspondence to total exhaled volume time constants. : Mechanical time constants based on exhaled gas volume underestimate regional aeration time constants. After lung injury, poorly aerated regions experience larger intratidal changes in aeration over shorter time scales compared to normally aerated regions. However, the largest intratidal aeration changes occur over the longest time scales within poorly aerated regions. These dynamic 4DCT imaging data provide supporting evidence for the susceptibility of poorly aerated regions to ventilator-induced lung injury, and for the functional benefits of short exhalation times during mechanical ventilation of injured lungs.
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http://dx.doi.org/10.3389/fphys.2021.707119DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8355819PMC
July 2021

RBM10 Deficiency Is Associated With Increased Immune Activity in Lung Adenocarcinoma.

Front Oncol 2021 21;11:677826. Epub 2021 Jul 21.

Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Thoracic Surgery II, Peking University Cancer Hospital & Institute, Beijing, China.

Introduction: RBM10 is one of the frequently mutated genes in lung adenocarcinoma (LUAD). Previous studies have confirmed that RBM10 could suppress the disease progression and cell proliferation in LUAD, but its loss-of-function mutations are more frequent in early-stage disease and decrease with the advancement of the clinical stage. This is contradictory to its role of tumor suppressor. Here, we conducted a systematic analysis to elucidate whether there was other potential biological significance of RBM10 deficiency during the progression of LUAD.

Materials And Methods: The whole exome sequencing data of 39 tumor samples from early-stage LUADs (GGN cohort) and genomic and transcriptome data of the Cancer Genome Atlas (TCGA) LUAD cohort (TCGA_LUAD cohort) and a Chinese LUAD cohort (CHOICE_ADC cohort) were first obtained. Systematic bioinformatic analyses were then conducted to determine gene expression signature, immune infiltration levels and predicted immunotherapy response. Immunohistochemistry (IHC) was also conducted to validate the result of immune infiltration.

Results: The mutation rate of RBM10 was significantly higher in the GGN cohort than that in the TCGA_LUAD and CHOICE_ADC cohorts. In both TCGA_LUAD and CHOICE_ADC cohorts, multiple immune related pathways were markedly enriched in RBM10 deficient group. Further analyses showed that tumors with RBM10 mutations displayed higher TMB, and LUADs with RBM10 deficiency also showed higher HLA expression levels, including many HLA class I and II molecules. Additionally, many immune cells, including myeloid dendritic cells, macrophages, neutrophils and CD8+T cells, showed higher infiltration levels in LUADs with RBM10 deficiency. Finally, some immune checkpoint molecules, such as PD-L1 and TIM-3, were highly expressed in RBM10 deficient population and the predicted immunotherapy response was calculated through TIDE algorithm, showing that IFNG expression, MSI score and CD8 expression were higher in RBM10 deficient group, while MDSC and M2 macrophage were lower in RBM10 deficient group.

Conclusion: Our study demonstrates that RBM10 deficient LUADs show higher HLA expression and immune cell infiltration, and some immune checkpoint molecules are also highly expressed. In brief, RBM10 deficiency could enhance anti-tumor immunity in LUAD.
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http://dx.doi.org/10.3389/fonc.2021.677826DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8336464PMC
July 2021

Distinguishable Targeting of Non-Small Cell Lung Cancer Using Hyaluronan Functionalized Platinum Nanoclusters and Their Inhibition Behaviors of Proliferation, Invasion, Migration.

ChemistryOpen 2021 09 6;10(9):882-888. Epub 2021 Aug 6.

Department of Respiratory and Critical Care Medicine, The Fifth Affiliation Hospital of Zhengzhou University, No. 3 Kangfuqian Street, Zhengzhou, 450052, China.

Lung cancer is the leading cause of cancer deaths worldwide and most cancer patients receiving conventional chemotherapy suffer from severe side effects due to the non-selective effects of chemotherapeutic drugs on normal cells. Targeted nanomaterials can obtain excellent accumulation at the tumor site through their active or passive targeting mechanisms, thereby reducing the toxicity of the drugs in various ways. In this study, hyaluronic acid (HA) which could specifically bind to CD44 on the surface of tumor cells, was used to modify amine-caged platinum nanoclusters (Pt NCs-NH ) to obtain targeting HA-Pt NCs-NH . Based on the differential expression of CD44 on the surface of three lung cells (non-small cell lung cancer cell H1299, small cell lung cancer cell H446, and embryonic lung fibroblast HFL1), HA-Pt NCs-NH can differentially enter the three cells and achieve their targeting of non-small cell lung cancer cell (NSCLC) cells. Pt NCs significantly inhibited the proliferation, migration and invasion of NSCLC cells and induced their apoptosis in comparison of classical cisplatin and carboplatin, showing a bright future in early diagnosis and treatment of NSCLC.
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http://dx.doi.org/10.1002/open.202100070DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8409085PMC
September 2021
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