Publications by authors named "Pin Wu"

90 Publications

High Drying Temperature Accelerates Sunflower Seed Deterioration by Regulating the Fatty Acid Metabolism, Glycometabolism, and Abscisic Acid/Gibberellin Balance.

Front Plant Sci 2021 28;12:628251. Epub 2021 May 28.

Institute of Crop and Nuclear Technology Utilization, Zhejiang Academy of Agricultural Sciences, Hangzhou, China.

Sunflower seed storage is accompanied by the loss of seed vigor. Seed drying is a key link between seed harvest and seed storage; however, to date, the effect of seed drying on sunflower seed deterioration during storage remains unclear. The present study performed hot air drying for sunflower seeds with an initial moisture content of 30% to examine the manner in which drying temperature (35, 40, 45, 50, and 55°C) affects the drying performance and seed vigor following storage process (6 and 12 months). A drying temperature of 40°C was evidently safe for sunflower seeds, whereas the high drying temperatures (HTD, 45, 50, and 55°C) significantly lowered sunflower seed vigor by regulating the fatty acid metabolism, glycometabolism, and abscisic acid (ABA)/gibberellin (GA) balance. HDT significantly increased the seed damage rate and accelerated sunflower seed deterioration during natural and artificial aging process. Further biochemical analysis indicated that HDT significantly increased lipoxygenase and dioxygenase activities, leading to malonaldehyde and reactive oxygen species over-accumulation during storage. During early seed germination, HDT significantly inhibited fatty acid hydrolysis and glycometabolism by decreasing triacylglycerol lipase, CoA-SH oxidase, and invertase activities. Moreover, HDT remarkably increased ABA levels but reduced GA levels by regulating gene expressions and metabolic enzyme activities during early imbibitions. Cumulatively, the seed drying effect on sunflower seed vigor deterioration during the storage process may be strongly related to fatty acid oxidation and hydrolysis metabolism, toxic substance accumulation, and ABA/GA balance.
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http://dx.doi.org/10.3389/fpls.2021.628251DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8193951PMC
May 2021

Automatic Inverse Design of High-Performance Beam-Steering Metasurfaces via Genetic-type Tree Optimization.

Nano Lett 2021 Jun 10. Epub 2021 Jun 10.

Department of Photonics, National Cheng Kung University, Tainan 70101, Taiwan.

We introduce a genetic-type tree search (GTTS) algorithm combined with unsupervised clustering for the automatic inverse design of high-performance metasurfaces. With the proposed method, we realize highly directive beam-steering metasurfaces via the cooptimization of the amplitude and phase. In comparison with previous topology optimization approaches, the developed GTTS algorithm optimizes the organization of subwavelength nanoantennas and, thus, is applicable to the design of both passive and active metasurfaces. The optimized beam-steering metasurface specifically exhibits a nearly constant directivity when the steering angle varies from 5° to 30°. Furthermore, the optimized nonintuitive reflectance and phase profiles assist in achieving highly directive beam steering when the phase modulation range is <180°, which was previously challenging. Our approach can diminish the requirements of scattering light properties with substantially enhanced angular resolution of beam-steering metasurfaces, which enables the realization of high-performance metasurfaces that will be promising for a wide range of advanced nanophotonic applications.
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http://dx.doi.org/10.1021/acs.nanolett.1c00720DOI Listing
June 2021

A novel risk score predicts prognosis in melanoma: The combination of three tumor-infiltrating immune cells and four immune-related genes.

Clin Immunol 2021 Jul 8;228:108751. Epub 2021 May 8.

Department of Pharmacology and Department of Pathology, School of Basic Medical Sciences, Peking University, Beijing 100191, China; Beijing Key Laboratory of Tumor Systems Biology, Peking University, Beijing 100191, China. Electronic address:

Tumor-infiltrating immune cells (TIICs) and immune-related genes (IRGs) of melanoma are associated with prognosis. However, whether the combination of TIICs and IRGs can be used as prognostic clinical biomarkers are still unknown. Here, we downloaded transcription profile of melanoma from TCGA. Then, three TIICs and four IRGs that associated with the overall survival were used to constructed the Immune Cell Score (ICS) and Immune Gene Score (IGS) respectively. Next, to improve the accuracy of ICS and IGS for melanoma prognostic, we combined the ICS and IGS constructed the Immune Cell and Gene Score (ICGS) model. ICGS had higher accuracy and predictive ability than ICS or IGS. Meanwhile, ICGS model reliability was validated by two independent datasets of melanoma. Functional enrichment and protein-protein interaction network analysis based on ICGS were performed to identify T cell mediated immune and inflammatory response are highly associated with melanoma.
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http://dx.doi.org/10.1016/j.clim.2021.108751DOI Listing
July 2021

CD38 identifies pre-activated CD8+ T cells which can be reinvigorated by anti-PD-1 blockade in human lung cancer.

Cancer Immunol Immunother 2021 May 2. Epub 2021 May 2.

Department of Thoracic Surgery, Second Affiliated Hospital, Zhejiang University School of Medicine, Zhejiang University, Hangzhou, 310009, China.

Background: CD38 has been observed expressing in activated T cells, while the features and functions of CD38+ T cells in human NSCLC are still unclear.

Methods: Here we uncovered the correlation between CD38 expression and survival and immune infiltration levels in tumor of NSCLC. Then, we collected samples from 51 NSCLC patients to study the biological feature and response to anti-PD-1 of tumor-infiltrating CD38+ CD8+ T cells in vitro.

Results: We found CD38 expression correlated with the survival and immune infiltration levels of NSCLC. It is interesting that CD38+ CD8+ T cells enriched in the tumors expressed higher level of cytotoxic molecule, cytokines and PD-1 than CD38- CD8+ T cells. Moreover, PD-1+ subset in tumor-infiltrating CD38+ CD8+ T cells expressed higher level of activated markers than PD-1+ CD38- CD8+ T cells. Next, we found tumor-infiltrating CD38+ CD8+ T cells expressed higher level of CD103, IFN-γ, TNF-α and perforin than CD38- CD8+ T cells when were reactivated in vitro. Finally, we observed that CD38+ CD8+ T cells isolated from tumors could be reinvigorated by anti-PD-1 in vitro.

Conclusions: Our findings demonstrate that CD38 expression defines a subset of CD8+ T cells enriched in tumors of NSCLC which have paradoxical phenotypes and response to anti-PD-1. Our results suggest a pre-priming of these cells is may exist in tumor and consequentially facilitate it acquiring both anti-tumor potency and exhausted phenotype which can be reinvigorated by PD-1 blockade.
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http://dx.doi.org/10.1007/s00262-021-02949-wDOI Listing
May 2021

LncRNA-Fendrr protects against the ubiquitination and degradation of NLRC4 protein through HERC2 to regulate the pyroptosis of microglia.

Mol Med 2021 04 15;27(1):39. Epub 2021 Apr 15.

Department of Anesthesiology, The First Affiliated Hospital, College of Medicine, Zhejiang University, 79 Qingchun Road, Hangzhou, 310003, People's Republic of China.

Objectives: Targeted inhibition of inflammatory response can reduce diabetic cerebral ischemia-reperfusion (I/R) injure. Pyroptosis is characterized by caspase-1 dependence and the release of a large number of pro-inflammatory factors. LncRNA-Fendrr is associated with a variety of diseases, but Fendrr has not been studied in diabetic cerebral I/R. NLR-family CARD-containing protein 4 (NLRC4) regulate the pyroptosis of microglia cells. This study was designed to investigate whether Fendrr is involved in the effects of diabetic cerebral I/R injury.

Methods: The diabetic brain I/R model in mice was constructed. Mouse microglia cell line BV-2 cells were exposed to high glucose followed by hypoxia/reoxygenation (H/R). Fendrr and some pyroptosis-associated proteins were detected by qRT-PCR, western blot or ELISA. HE staining was used to detect pathological changes. Microglia pyroptosis was detected by TUNEL staining. RNA pull-down and RNA Immunoprecipitation were used to detect binding of Fendrr to HERC2 (E3 ubiquitin ligase), and CO-IP detected binding of HERC2 to NLRC4. The ubiquitination of NLRC4 was detected by ubiquitination experiments.

Results: Fendrr was significantly increased in the diabetic cerebral I/R model, and NLRC4 inflammatory complex and pyroptosis mediated inflammatory factors were increased. NLRC4 and inflammatory cytokines associated with pyroptosis were decreased in the high glucose-treated hypoxia/reoxygenation (H/R)-induced microglia after Fendrr knockdown. Fendrr bound to HERC2 protein, and HERC2 bound to NLRC4. Meanwhile, Fendrr could inhibit the ubiquitination of NLRC4, HERC2 promoted the ubiquitination of NLRC4 protein. Moreover, the effect of Fendrr overexpression in the diabetic cerebral I/R model of microglia can be reversed by HERC2 overexpression.

Conclusion: Fendrr can protect against the ubiquitination and degradation of NLRC4 protein through E3 ubiquitin ligase HERC2, thereby accelerating the pyroptosis of microglia.
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http://dx.doi.org/10.1186/s10020-021-00299-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8048261PMC
April 2021

Deoxycytidine Kinase (DCK) Mutations in Human Acute Myeloid Leukemia Resistant to Cytarabine.

Acta Haematol 2021 Feb 24:1-8. Epub 2021 Feb 24.

Translational Medical Research Center, The Affiliated Wuxi No. 2 Peoples Hospital of Nanjing Medical University, Wuxi, China,

Resistance to cytarabine is an important cause of therapy failure in persons with acute myeloid leukemia (AML). Deoxycytidine kinase, encoded by DCK, catalyzes phosphorylation of cytarabine to cytarabine monophosphate, a necessary step for eventual incorporation of cytarabine triphosphate into DNA and for clinical efficacy. Whether DCK mutations make AML cells resistant to cytarabine is controversial. We studied DCK mutations and messenger RNA (mRNA) concentrations in leukemia cells from 10 subjects with AML who received cytarabine-based therapy and relapsed and in 2 artificially induced cytarabine-resistant AML cell lines. DCK mutations were detected in 4 subjects with AML relapsing after achieving a complete remission and receiving high-dose cytarabine postremission therapy. Most mutations were in exons 4-6 and were not present before therapy. DCK was also mutated in cytarabine-resistant but not parental AML cell lines. DCK mRNA concentrations were significantly decreased in cytarabine-resistant K562 and SHI-1 cells compared with cytarabine-sensitive parental cells. Mutation frequency of DCK and mRNA concentration did not correlate with the extent of cytarabine resistance indicating other factors operate. Overexpression of wild-type DCK restored cytarabine sensitivity to previously resistant leukemia cell lines. Our data contribute to the understanding of cytarabine resistance in persons with AML.
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http://dx.doi.org/10.1159/000513696DOI Listing
February 2021

[Effect of acupuncture-moxibustion on negative emotions and plasma tryptophan metabolism in patients with Crohn's disease at active stage].

Zhongguo Zhen Jiu 2021 Jan;41(1):17-22

Shanghai Research Institute of Acupuncture and Meridian, Shanghai University of TCM, Shanghai 200030, China.

Objective: To observe the effect of acupuncture-moxibustion on negative emotions and plasma tryptophan (Trip)-kynurenine (Kyn) metabolism in the patients with Crohn's disease (CD) at the mild and moderate active stage.

Methods: A total of 66 CD patients were randomized into an observation group (33 cases, 1 case dropped off) and a control group (33 cases, 2 cases dropped off). In the observation group, acupuncture was applied in combination with moxibustion. In the control group, the sham-acupuncture was used in combination with sham-moxibustion. In both of the observation group and the control group, acupuncture was applied to Zhongwan (CV 12), Shangjuxu (ST 37), Sanyinjiao (SP 6), Gongsun (SP 4), Hegu (LI 4), Quchi (LI 11), Taixi (KI 3) and Taichong (LR 3), and moxibustion was applied to Tianshu (ST 25) and Zusanli (ST 36). The treatment was given once every two days, 3 times a week, totally for 12 weeks. Separately, before and after treatment, the score of the hospital anxiety-depression scale (HADS) and the score of intestinal core symptoms (degree of abdominal pain and frequency of diarrhea) were observed in the patients of the two groups. The concentration of plasma indoleamine 2,3-dioxygenase 1 (IDO1) and the ratios of Kyn/Trp, QuinA/Kyn, KynA/Kyn and KynA/QuinA were compared between the two groups.

Results: Compared with before treatment, the scores of HADS-A and HADS-D in the observation group and the score of HADS-A in the control group were all reduced after treatment (<0.01, <0.05). The scores of abdominal pain degree in the two groups and score of diarrhea frequency in the observation group were all reduced after treatment (<0.001). After treatment, the reducing ranges of the score of HADS-A and the scores of abdominal pain degree and diarrhea frequency in the observation group were all larger than the control group (<0.01, <0.05). Compared with before treatment, the plasma IDO1 concentration in the two groups and the ratios of plasma Kyn/Trp and QuinA/Kyn in the observation group were all reduced after treatment (<0.001, <0.05, <0.01), the ratios of plasma KynA/Kyn and KynA/QuinA were increased after treatment in the observation group (<0.05, <0.01). After treatment, the changes in IDO1 concentration and the ratios of plasma QuinA/Kyn and KynA/QuinA in the observation were larger than the control group (≤0.01, <0.05). In the observation group, the difference in the ratio of plasma KynA/Kyn before and after treatment was negatively related to the improvement value of HADS-D (=-0.67, <0.05). After treatment, plasma IDO1 concentration was positively related to HADS-A in the observation group ( =0.65, <0.05).

Conclusion: Acupuncture and moxibustion relieve the negative emotions of anxiety and depression in CD patients at mild and moderate active stage, which is probably related to the regulation of plasma Trp-Kyn metabolic pathway.
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http://dx.doi.org/10.13703/j.0255-2930.20200814-k0003DOI Listing
January 2021

Stress-responses of microbial population and activity in activated sludge under long-term ciprofloxacin exposure.

J Environ Manage 2021 Mar 25;281:111896. Epub 2020 Dec 25.

China-UK Low Carbon College, Shanghai Jiao Tong University, Shanghai, 200240, China.

In this study, the effects of ciprofloxacin on activated sludge were evaluated based on the microbial community and metabolic characteristics. The results indicated that the metabolism of chemical oxygen demand (COD) and nitrogen were inhibited with ciprofloxacin at mg/L level compared to the control experiment, and the concentration of ciprofloxacin was slightly decreased. High-throughput sequencing (HTS) results showed that ciprofloxacin greatly shaped the microbial communities in activated sludge, especially for the Nitrospirae phylum and Nitrospira genus. High concentrations of ciprofloxacin stimulated the enrichment of Zoogloea, thus reducing the stability of the activated sludge. Moreover, quinolone resistance proteins in Aeromonas were enriched, which demonstrates their competitive advantage in these enrichment incubations. Finally, the functional profiles were predicted through Tax4Fun, which revealed the adaption to microbes in activated sludge to the ciprofloxacin selective pressure. This work demonstrates the influence of ciprofloxacin on the activated sludge process, and can provide a useful reference for the assessment of the ecological security of ciprofloxacin.
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http://dx.doi.org/10.1016/j.jenvman.2020.111896DOI Listing
March 2021

Intestinal Dysbiosis Correlates With Sirolimus-induced Metabolic Disorders in Mice.

Transplantation 2021 May;105(5):1017-1029

State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.

Background: Long-time use of pharmacological immunosuppressive agents frequently leads to metabolic disorders. Most studies have focused on islet toxicity leading to posttransplantation diabetes mellitus. In contrast, the link between intestinal dysbiosis and immunosuppressive drug-induced metabolic disorders remains unclear.

Methods: We established a mouse model of metabolic abnormality via sirolimus treatment. Fecal microbiota was examined using 16S rRNA gene MiSeq sequencing. Intestinal barrier function was assessed using fluorescein isothiocyanate-dextran assay and mucus immunostaining. Systemic inflammation was determined using a multiplexed fluorescent bead-based immunoassay.

Results: Sirolimus induced dyslipidemia and glucose intolerance in mice in a dose-dependent manner. Interestingly, the clinical-mimicking dose of sirolimus altered the intestinal microbiota community, which was characterized by the enrichment of Proteobacteria, depletion of Akkermansia, and potential function shifts to those involved in lipid metabolism and the immune system. In addition, the clinical-mimicking dose of sirolimus reduced the thickness of the intestinal mucosal layer, increased the intestinal permeability, and enriched the circulating pro-inflammatory factors, including interleukin (IL)-12, IL-6, monocyte chemotactic protein 1, granulocyte-macrophage colony stimulating factor, and IL-1β. Our results showed a close association between intestinal dysbiosis, intestinal barrier failure, systemic inflammation, and metabolic disorders. Furthermore, we demonstrated that oral intervention in the gut microbiota by Lactobacillus rhamnosus HN001 protected against intestinal dysbiosis, especially by depleting the lipopolysaccharide-producing Proteobacteria, and attenuated the sirolimus-induced systemic inflammation, dyslipidemia, and insulin resistance.

Conclusions: Our study demonstrated a potentially causative role of intestinal dysbiosis in sirolimus-induced metabolic disorders, which will provide a novel therapeutic target for transplant recipients.
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http://dx.doi.org/10.1097/TP.0000000000003494DOI Listing
May 2021

Extraordinary Multipole Modes and Ultra-Enhanced Optical Lateral Force by Chirality.

Phys Rev Lett 2020 Jul;125(4):043901

Department of Electrical and Computer Engineering, National University of Singapore, Singapore 117583.

Strong mode coupling and Fano resonances arisen from exceptional interaction between resonant modes in single nanostructures have raised much attention for their advantages in nonlinear optics, sensing, etc. Individual electromagnetic multipole modes such as quadrupoles, octupoles, and their counterparts from mode coupling (toroidal dipole and nonradiating anapole mode) have been well investigated in isolated or coupled nanostructures with access to high Q factors in bound states in the continuum. Albeit the extensive study on ordinary dielectric particles, intriguing aspects of light-matter interactions in single chiral nanostructures is lacking. Here, we unveil that extraordinary multipoles can be simultaneously superpositioned in a chiral nanocylinder, such as two toroidal dipoles with opposite moments, and electric and magnetic sextupoles. The induced optical lateral forces and their scattering cross sections can thus be either significantly enhanced in the presence of those multipoles with high-Q factors, or suppressed by the bound states in the continuum. This work for the first time reveals the complex correlation between multipolar effects, chiral coupling, and optical lateral force, providing a distinct way for advanced optical manipulation.
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http://dx.doi.org/10.1103/PhysRevLett.125.043901DOI Listing
July 2020

Ambiguous roles and potential therapeutic strategies of innate lymphoid cells in different types of tumor.

Oncol Lett 2020 Aug 16;20(2):1513-1525. Epub 2020 Jun 16.

Department of Thoracic Surgery, The Second Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, Zhejiang 310009, P.R. China.

Recent years have witnessed a significant development in the current understanding of innate lymphoid cells (ILCs) and their roles in the innate immune system, where they regulate tissue homeostasis, inflammation, as well as tumor surveillance and tumorigenesis. Based on the limited studies of ILCs in cancer, ILCs may be classified into three subgroups depending on their phenotypic and functional characteristics: Group 1 ILCs, which include natural killer cells and ILC1s; Group 2 ILCs, which only contain ILC2s and Group 3 ILCs, which comprise of LTi cells and ILC3s. Group 1 ILCs predominantly exert antitumor activities, while Group 2 ILCs and Group 3 ILCs are predominantly procarcinogenic in nature. In different types of tumor, each ILC subset behaves differently. Current research is focused on investigating how ILCs may be manipulated and employed as therapeutic strategies for the treatment of cancer. The present review aimed to summarize the characteristics and effects of ILCs in the context of tumor immunology, and provide novel insight into the pro- or anti-tumor activities of ILCs in different types of malignancy, including solid tumors, such as those in the gastrointestinal tract, lung, breast, bladder or prostate, as well as melanoma, further to hematological malignancies, with the aim to highlight potential therapeutic targets for the treatment of cancer.
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http://dx.doi.org/10.3892/ol.2020.11736DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7377136PMC
August 2020

Electro-optically Tunable Multifunctional Metasurfaces.

ACS Nano 2020 Jun 4;14(6):6912-6920. Epub 2020 Jun 4.

Department of Photonics, National Cheng Kung University, Tainan 70101, Taiwan.

Shaping the flow of light at the nanoscale has been a grand challenge for nanophotonics over decades. It is now widely recognized that metasurfaces represent a chip-scale nanophotonics array technology capable of comprehensively controlling the wavefront of light appropriately configuring subwavelength antenna elements. Here, we demonstrate a reconfigurable metasurface that is multifunctional, .., notionally capable of providing diverse optical functions in the telecommunication wavelength regime, using a single compact, lightweight, electronically controlled array with no moving parts. By electro-optical control of the phase of the scattered light from each identical individual metasurface element in an array, we demonstrate a single prototype multifunctional programmable metasurface that is capable of both dynamic beam steering and reconfigurable light focusing. Reconfigurable multifunctional metasurfaces with arrays of tunable optical antennas thus can perform arbitrary optical functions by programmable array-level control of scattered light phase, amplitude, and polarization, similar to dynamic and programmable memories in electronics.
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http://dx.doi.org/10.1021/acsnano.0c01269DOI Listing
June 2020

Experimental Study of Somatic Variants of Osteosarcoma by Whole-Exome Sequencing.

Med Sci Monit 2020 Mar 20;26:e920826. Epub 2020 Mar 20.

Department of Bone and Soft Tissue Oncology, Affiliated Cancer Hospital of Zhengzhou University, Zhengzhou, Henan, China (mainland).

BACKGROUND This study aimed to investigate the role of gene mutation site distribution, biological function, pathway enrichment, and gene association analysis in the occurrence, development, and migration of osteosarcoma. MATERIAL AND METHODS Somatic mutation screening was performed using the whole-exome sequencing of osteosarcoma samples, and the distribution of mutations was demonstrated by Circos diagrams. Metascape was used to analyze the GO and KEGG signal pathway enrichment of the genes harboring protein coding alterations, and GeneMANIA was used to analyze the interaction of mutated genes. RESULTS The results showed that the protein coding alterations were found throughout the whole genome in 3 osteosarcoma samples. A large number of identical or related biological processes and pathways were found in osteosarcoma samples. The GeneMANIA analysis of the 10 mutations shared by 3 samples showed that the target gene minichromosome maintenance complex component 4 (MCM4) and 3 lateral genes were most functional, and were all related to DNA replication. The analysis of GO and KEGG signal pathway enrichment showed that the mutated genes were involved mainly in tumor-related metabolic pathways. Three mutated genes were involved in the cell process, and 2 mutated genes were involved in the metabolic process. Known driver gene mutations were also observed in the samples. CONCLUSIONS The gene analysis confirmed that patients with osteosarcoma had a wide range of common gene mutations related to each other, which are involved in tumor-related metabolic pathways. These findings provide a basis for further gene-targeted therapy and pathway research.
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http://dx.doi.org/10.12659/MSM.920826DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7106971PMC
March 2020

Phylogenetic Tree Inference: A Top-Down Approach to Track Tumor Evolution.

Front Genet 2019 7;10:1371. Epub 2020 Feb 7.

School of Life Science and Technology, ShanghaiTech University, Shanghai, China.

Recently, an increasing number of studies sequence multiple biopsies of primary tumors, and even paired metastatic tumors to understand heterogeneity and the evolutionary trajectory of cancer progression. Although several algorithms are available to infer the phylogeny, most tools rely on accurate measurements of mutation allele frequencies from deep sequencing, which is often hard to achieve for clinical samples (especially FFPE samples). In this study, we present a novel and easy-to-use method, PTI (Phylogenetic Tree Inference), which use an iterative top-down approach to infer the phylogenetic tree structure of multiple tumor biopsies from same patient using just the presence or absence of somatic mutations without their allele frequencies. Therefore PTI can be used in a wide range of cases even when allele frequency data is not available. Comparison with existing state-of-the-art methods, such as LICHeE, Treeomics, and BAMSE, shows that PTI achieves similar or slightly better performance within a short run time. Moreover, this method is generally applicable to infer phylogeny for any other data sets (such as epigenetics) with a similar zero and one feature-by-sample matrix.
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http://dx.doi.org/10.3389/fgene.2019.01371DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7020887PMC
February 2020

CD8 T Cells Form the Predominant Subset of NKG2A Cells in Human Lung Cancer.

Front Immunol 2019 17;10:3002. Epub 2020 Jan 17.

Department of Thoracic Surgery, Second Affiliated Hospital, Zhejiang University School of Medicine, Zhejiang University, Hangzhou, China.

NKG2A is an inhibitory receptor of both T cells and natural killer (NK) cells. Persistent activation promotes T cells and NK cells to express NKG2A and results in the progression of chronic infection and cancer. However, the characteristics and subsets of NKG2A lymphocytes in human lung cancer are still unclear. Here, we used the Tumor Immune Estimation Resource database and immune profiling of paired biospecimens to uncover the correlation between NKG2A expression and immune infiltration levels in human cancer as well as the characteristics of NKG2A lymphocytes in human lung cancer. We found that KLRC1 expression was especially correlated with CD8 T-cell infiltration levels in 34 types of human cancer through the Tumor Immune Estimation Resource database. Moreover, NKG2A CD8 T cells were the predominant subset of NKG2A lymphocytes in human lung cancer. In contrast, the NKG2A NK cells were decreased in tumors compared with the paired normal lung tissue. Tumor-infiltrating NKG2A CD8 T cells expressed tissue-resident memory T cell (T cell) and exhausted T-cell markers. Cytokines and cytotoxic molecules secreted by tumor-infiltrating NKG2A CD8 T cells were significantly lower than those secreted by NKG2A CD8 T cells . When stimulated with T-cell receptor activator, tumor-infiltrating NKG2A CD8 T cells could secrete large amounts of granzyme B. Our findings demonstrate that tumor-infiltrating NKG2A CD8 T cells form the predominant subset of NKG2A cells in human lung cancer and suggest that targeting NKG2A CD8 T cells is a promising approach for future anti-lung cancer immunotherapy.
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http://dx.doi.org/10.3389/fimmu.2019.03002DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6979261PMC
December 2020

Epidural anesthesia for emergency cesarean section in a woman with Fontan circulation: A case report.

Medicine (Baltimore) 2020 Jan;99(4):e18986

Department of Anesthesia, First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, PR China.

Rationale: Anesthetic management of pregnant women with Fontan circulation remains challenging. There are few reports that describe the anesthetic management of cesarean section after Fontan surgery. Here, we present a case of successful epidural anesthesia in a woman with Fontan circulation who required emergency cesarean section.

Patient Concerns: A 29-year-old woman at gestational week 28 was scheduled for emergency cesarean section because of fetal distress. Her past medical history was significant for congenital transposition of the great arteries that had been treated by Fontan surgery 26 years earlier. Her postoperative course had been uneventful and she had reached a near normal level of activity with no arrhythmias or thrombotic complications. On presentation, her oxygen saturation was approximately 84% and she had digital clubbing. Arterial blood gas analysis showed a PCO2 of 35 mmHg, PO2 of 55.5 mmHg, and hemoglobin of 16.3 g/dL. Her blood coagulation parameters were within normal limits except for a high fibrinogen concentration (4.55 g/L).

Diagnosis: The diagnosis was pregnancy requiring emergency cesarean section because of fetal distress.

Interventions: Before anesthesia, a radial artery line was established for continuous measurement of blood pressure. An air pressure pump was placed on the patient's lower limbs and a low-dose dobutamine infusion was started. Next, epidural anesthesia was successfully performed at L2-3. Five milliliters of 2% lidocaine followed by 10 mL of 0.75% ropivacaine were injected. Dobutamine was infused to maintain a target blood pressure of 100-120/60-70 mmHg.

Outcomes: The procedure was uneventful with the patient maintaining a stable heart rate of 80 to 90 beats/min and an oxygen saturation of 90% to 94%. A male infant weighing 840 g was delivered. The Apgar score was 9 at 1 and 5 minutes. The patient was transferred to the intensive care unit for 20 hours of monitoring and discharged 9 days later. The neonate was discharged after 2 months of specialist neonatal treatment.

Lessons: Epidural anesthesia may be used in women with Fontan circulation undergoing emergency cesarean section. Knowledge of the physiology of the heart lesion and that of pregnancy are critical to the outcome.
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http://dx.doi.org/10.1097/MD.0000000000018986DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7004742PMC
January 2020

[Coexisting Mutations in IDH1/2-Mutated Acute Myeloid Leukemia].

Zhongguo Shi Yan Xue Ye Xue Za Zhi 2019 Oct;27(5):1440-1448

Department of Hematology, Changzhou Municipal Second People's Hospital Affiliated to Nanjing Medical University, Changzhou 213003, Jiangsu Province, China.

Objective: To explore the coexisting mutations in IDH-mutated acute myeloid leukemia(AML) and its relation with partial clinical parametrs.

Methods: The exon 4 mutation of IDH1/2 gene was screened by using genome DNA-PCR combined with sanger sequencing, 51 targeted gene mutations in the patients with IDH1/2 mutation were detected by using high throughput DNA sequencing combined with sanger sequencing.

Results: Among 358 patients, the IDH1/2 mutation was found in 46 cases including IDH1 mutation in 35 cases and IDH2 mutation in 11 cases, 97.87%(45/46) patients with IDH1/2 mutation simultaneously carried other gene mutations including 8(17.8%) cases with mutation of double gene, 17(37.8%) cases with mutation of 3 genes and 20(44.4%) cases with mutation of ≥ 4 genes. The mutation frequency of each patient averaged 3.52 times. In mutation of accompanied genes, the common genes were NPM1(n=29, 63.0%), next DNMT3A(n=25, 54.3%), FLT3-ITD(n=7, 15.2%), TET2(n=5, 10.9%) and NRAS(n=5, 10.9%). The average WBC level of patients with NPM1 mutation in IDH1 mutation group was higher than that of patients in wild type group(P<0.05). The complete remission (CR) rate of patients with DNMT3A mutation was significant lower than that of patients with wild type (30% vs 80%, P<0.01). The presence of ≥ 4 mutations was found to be significantly associated with higher white blood level than that in the patients with double mutations(P<0.05).

Conclusion: More than 95% AML patients with IDH1/2 mutation commonly show additional mutations. The number and the type of IDH coexisting mutations have certain effect on the clinical features and CR rate.
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http://dx.doi.org/10.19746/j.cnki.issn.1009-2137.2019.05.014DOI Listing
October 2019

Combined Ectopic Variation of the Right Upper Pulmonary Vein and Bronchus.

Ann Thorac Surg 2020 05 12;109(5):e353-e355. Epub 2019 Sep 12.

Department of Thoracic Surgery, Second Affiliated Hospital, Zhejiang University, Hangzhou, China. Electronic address:

Ectopia of the right upper pulmonary vein (RUV) is rare and sometimes combined with tracheal bronchus. Such anomalies can affect surgical procedures. We report the case of a 66-year-old woman with lung cancer in which preoperative three-dimensional computed tomography reconstruction and intraoperative images displayed a combined ectopic variation of the RUV and bronchus. The RUV was absent from the anterior hilum, but instead was present in the superior and posterior hilum dispersedly. In addition, the right upper lobe bronchus was ectopic to the lower edge of the "bronchus intermedius." Based on this discovery, video-assisted thoracoscopic lobectomy was successfully performed.
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http://dx.doi.org/10.1016/j.athoracsur.2019.07.081DOI Listing
May 2020

Dynamic beam steering with all-dielectric electro-optic III-V multiple-quantum-well metasurfaces.

Nat Commun 2019 Aug 13;10(1):3654. Epub 2019 Aug 13.

Thomas J. Watson Laboratory of Applied Physics, California Institute of Technology, Pasadena, CA, 91125, USA.

Tunable metasurfaces enable dynamical control of the key constitutive properties of light at a subwavelength scale. To date, electrically tunable metasurfaces at near-infrared wavelengths have been realized using free carrier modulation, and switching of thermo-optical, liquid crystal and phase change media. However, the highest performance and lowest loss discrete optoelectronic modulators exploit the electro-optic effect in multiple-quantum-well heterostructures. Here, we report an all-dielectric active metasurface based on electro-optically tunable III-V multiple-quantum-wells patterned into subwavelength elements that each supports a hybrid Mie-guided mode resonance. The quantum-confined Stark effect actively modulates this volumetric hybrid resonance, and we observe a relative reflectance modulation of 270% and a phase shift from 0° to ~70°. Additionally, we demonstrate beam steering by applying an electrical bias to each element to actively change the metasurface period, an approach that can also realize tunable metalenses, active polarizers, and flat spatial light modulators.
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http://dx.doi.org/10.1038/s41467-019-11598-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6692380PMC
August 2019

[Effect of PI3K/mTOR Signal Pathway Inhibitor XL765 on Human Leukemic KG-1 Cells].

Zhongguo Shi Yan Xue Ye Xue Za Zhi 2019 Jun;27(3):729-734

Department of Hematology, the First Affiliated Hospital of Soochow University, Jiangsu Institute of Hematology, Key Laboratory of Thrombosis and Hemostasis, Suzhou 215006, Jiangsu Province, China,E-mail:

Objective: To explore the effect and possible mechanism of PI3K/mTOR inhibitor XL765 on KG-1 cells in vitro.

Methods: The effect of XL765 on cell proliferation was detected by CCK-8 assay. The colony formation test (200 cells were plated in a plate for 9 days) was used to detect the effect of XL765 on the colony forming ability of KG-1 cells. The apoptosis was assessed by flow cytometry with Annexin V-FITC/PI double staining. Quantitative real-time polymerase chain reaction (q-PCR) was used to detect the expression of cell apoptosis-related genes BCL-2, BAX and caspase-3, Western blot was performed to detect the expression levels of BCL-2, BAX, Caspase-3, and the phosphorylation change of p-PI3K, p-AKT and p-S6K.

Results: XL765 effectively inhibited the proliferation and the colony formation of KG-1 cells (P=0.0002). XL765 (150 nmol/L) induced KG-1 cell apoptosis (31.87±1.376%), very statistically significant different from (3.533±0.4179% ) in the control group (P<0.01). Treatment with 150 nmol/L XL765 could in a significantly increase the expression levels of BAX and active caspase-3, and decreases expression level of the BCL-2 (P<0.01). In accordance with these results, the Western blot further confirmed the expression decrease of BCL-2 protein along with the increase BAX and cleaved caspase-3 activity. XL765 statistically significantly down-regulated the phosphorylation levels of PI3K, AKT and S6K.

Conclusion: PI3K/mTOR inhibitor XL765 substantially suppresses KG-1 cell proliferation and induces apoptosis by inhibiting the activation of PI3K-AKT-mTOR signaling pathway, and regulating the apoptosis-related proteins.
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http://dx.doi.org/10.19746/j.cnki.issn.1009-2137.2019.03.014DOI Listing
June 2019

Phase Modulation with Electrically Tunable Vanadium Dioxide Phase-Change Metasurfaces.

Nano Lett 2019 06 4;19(6):3961-3968. Epub 2019 Jun 4.

We report a dynamically tunable reflectarray metasurface that continuously modulates the phase of reflected light in the near-infrared wavelength range under active electrical control of the phase transition from semiconducting to semimetallic states. We integrate a vanadium dioxide (VO) active layer into the dielectric gap of antenna elements in a reflectarray metasurface, which undergoes an insulator-to-metal transition upon resistive heating of the metallic patch antenna. The induced phase transition in the VO film strongly perturbs the magnetic dipole resonance supported by the metasurface. By carefully controlling the volume fractions of coexisting metallic and dielectric regions of the VO film, we observe a continuous shift of the phase of the reflected light, with a maximal achievable phase shift as high as 250°. We also observe a reflectance modulation of 23.5% as well as a spectral shift of the resonance position by 175 nm. The metasurface phase modulation is fairly broadband, yielding large phase shifts at multiple operation wavelengths.
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http://dx.doi.org/10.1021/acs.nanolett.9b01246DOI Listing
June 2019

Responses to Dasatinib as a Second- and Third-Line Tyrosine Kinase Inhibitor in Chronic Phase Chronic Myeloid Leukaemia Patients.

Acta Haematol 2019 16;142(2):79-86. Epub 2019 May 16.

Institute of Blood and Marrow Transplantation, Collaborative Innovation Center of Haematology, Soochow University, Suzhou, China,

We retrospectively evaluated the efficacy and safety of dasatinib among 48 Chinese patients with chronic phase chronic myeloid leukaemia. The proportions of patients achieving the optimal molecular responses at 3, 6, and 12 months, a major molecular response (MMR) rate and a complete cytogenetic response (CCyR) rate were 87.0, 87.0, 72.2, 45.8, and 72.7% for patients with dasatinib as second-line therapy, and 34.8, 34.8, 33.3, 20.8, and 46.2% as third-line therapy, respectively. A BCR-ABL1 transcript level on the International Scale (BCR-ABL1IS) of ≤10% at the initiation of -dasatinib treatment was found to be associated with a higher probability of achieving MMR. Among patients with a -BCR-ABL1IS higher than 10% at initiation of dasatinib treatment, dasatinib showed better performance as a second-line therapy than as a third-line therapy. The patients who achieved an optimal molecular response at 3 months had a superior cumulative incidence of MMR and CCyR compared with patients who failed to achieve such a response. Dasatinib induced considerable responses as a second-line treatment, especially in patients with a BCR-ABL1IS ≤10% at initiation of treatment, whereas the efficacy was limited in patients receiving third-line therapy with a BCR-ABL1IS >10% at the initiation of treatment.
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http://dx.doi.org/10.1159/000495335DOI Listing
February 2020

Antibiotics-mediated intestinal microbiome perturbation aggravates tacrolimus-induced glucose disorders in mice.

Front Med 2019 Aug 2;13(4):471-481. Epub 2019 May 2.

National Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310003, China.

Both immunosuppressants and antibiotics (ABX) are indispensable for transplant patients. However, the former increases the risk of new-onset diabetes, whereas the latter impacts intestinal microbiota (IM). It is still unclear whether and how the interaction between immunosuppressants and ABX alters the IM and thus leads to glucose metabolism disorders. This study examined the alterations of glucose and lipid metabolism and IM in mice exposed to tacrolimus (TAC) with or without ABX. We found that ABX further aggravated TAC-induced glucose tolerance and increased insulin secretion. Combined treatment resulted in exacerbated lipid accumulation in the liver. TAC-altered microbial community was further amplified by ABX administration, as characterized by reductions in phylum Firmicutes, family Lachnospiraceae, and genus Coprococcus. Analyses based on the metagenomic profiles revealed that ABX augmented the effect of TAC on microbial metabolic function mostly related to lipid metabolism. The altered components of gut microbiome and predicted microbial functional profiles showed significant correlation with hepatic lipid accumulation and glucose disorders. In conclusion, ABX aggravated the effect of TAC on the microbiome and its metabolic capacities, which might contribute to hepatic lipid accumulation and glucose disorders. These findings suggest that the ABX-altered microbiome can amplify the diabetogenic effect of TAC and could be a novel therapeutic target for patients.
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http://dx.doi.org/10.1007/s11684-019-0686-8DOI Listing
August 2019

5-Hydroxytryptamine1a receptors on tumour cells induce immune evasion in lung adenocarcinoma patients with depression via autophagy/pSTAT3.

Eur J Cancer 2019 06 19;114:8-24. Epub 2019 Apr 19.

Department of Oncology, XiangYang Central Hospital, Hubei University of Arts and Science, XiangYang 441021, China. Electronic address:

Background: Cancer patients frequently suffer from fatigue and depression. Dysregulation of the immune system, tumour recurrence and metastasis are more common in cancer patients with depression. 5-Hydroxytryptamine (5-HT), a neurotransmitter, contributes to immune evasion in lung adenocarcinoma patients by activating 5-HTRs, but the mechanism for this phenomenon is still unclear. In this study, we examined the function of 5-HT1a receptors (5-HT1aRs) in immune evasion in a mouse model and in samples from lung adenocarcinomas patients.

Experimental Design: Sixty-four human lung adenocarcinoma patients with depression and 64 lung adenocarcinoma patients without depression were recruited for this study. The expression of 5-HT receptors on lung adenocarcinoma cells from tumour tissues were detected by using immunohistochemistry (IHC) and fluorescence-activated cell sorting (FACS). The depression models were established in vitro and in vivo. The effects of immunosuppression were evaluated by testing the function of cytotoxic lymphocyte (CTLs) and Tregs, measuring tumour weight or volume, assessing the survival of mice and staining of tissues by IHC. Changes in the expression of immunoregulatory factor genes were assessed to elucidate the mechanism of immune evasion induced by the 5- hydroxytryptamine receptor (HTRs).

Results: Higher levels of 5-HT, increased expression of 5-HT1Rs and decreased overall survival were observed in lung adenocarcinomas patients with depression compared with those without depression. Moreover, 5-HT1aR, a critical factor for increasing the number of CD4CD25Foxp3 Treg cells and decreasing the ratio of Th1/Th2 cells, which suggested immune system dysregulation. In addition, expression of 5-HT1aR on tumour cells was also negatively associated with CTL activity in both peripheral blood and tumour infiltrating lymphocytes. In a depressive state, 5-HT1aR activates p-signal transducer and activator of transcription 3 (STAT3) and autophagy, and programmed death ligand-1, a downstream gene of autophagy/p-STAT3 signalling, mediates an immunosuppressive environment. Moreover, in both the mouse model and lung adenocarcinoma patients, the activation of 5HT1aR and the elevated tumour autophagy/p-STAT3 axis were associated with reduced overall survival.

Conclusions: The 5-HT1aR/autophagy/p-STAT3 axis influences both tumour cells and immune cells, resulting in immunosuppression in lung adenocarcinomas patients with depression.
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http://dx.doi.org/10.1016/j.ejca.2019.03.017DOI Listing
June 2019

Achromatic metalens array for full-colour light-field imaging.

Nat Nanotechnol 2019 03 21;14(3):227-231. Epub 2019 Jan 21.

Department of Physics, National Taiwan University, Taipei, Taiwan.

A light-field camera captures both the intensity and the direction of incoming light. This enables a user to refocus pictures and afterwards reconstruct information on the depth of field. Research on light-field imaging can be divided into two components: acquisition and rendering. Microlens arrays have been used for acquisition, but obtaining broadband achromatic images with no spherical aberration remains challenging. Here, we describe a metalens array made of gallium nitride (GaN) nanoantennas that can be used to capture light-field information and demonstrate a full-colour light-field camera devoid of chromatic aberration. The metalens array contains an array of 60 × 60 metalenses with diameters of 21.65 μm. The camera has a diffraction-limited resolution of 1.95 μm under white light illumination. The depth of every object in the scene can be reconstructed slice by slice from a series of rendered images with different depths of focus. Full-colour, achromatic light-field cameras could find applications in a variety of fields such as robotic vision, self-driving vehicles and virtual and augmented reality.
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http://dx.doi.org/10.1038/s41565-018-0347-0DOI Listing
March 2019

Second Harmonic Light Manipulation with Vertical Split Ring Resonators.

Adv Mater 2019 Feb 14;31(7):e1806479. Epub 2018 Dec 14.

Research Center for Applied Sciences, Academia Sinica, Taipei, 11529, Taiwan.

The second harmonic generation (SHG) of vertical and planar split-ring resonators (SRRs) that are broken centro-symmetry configurations at the interface of metal surface and air is investigated. Strong interactions, better electromagnetic field confinements, and less leakage into the substrate for vertical SRRs are found. Experimental results show a 2.6-fold enhancement of SHG nonlinearity, which is in good agreement with simulations and calculations. Demonstrations of 3D metastructures and vertical SRRs with strong SHG nonlinearity majorly result from magnetic dipole and electric quadrupole clearly provides potential applications for photonics and sensing.
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http://dx.doi.org/10.1002/adma.201806479DOI Listing
February 2019

Smoker and non-smoker lung adenocarcinoma is characterized by distinct tumor immune microenvironments.

Oncoimmunology 2018;7(10):e1494677. Epub 2018 Jul 30.

Department of Respiratory Medicine, Sir Run Run Shaw Hospital and Institute of Translational Medicine, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China.

Tobacco smoking causes DNA damages in epithelial cells and immune dysfunction in the lung, which collectively contribute to lung carcinogenesis and progression. However, potential mechanisms by which tumor-infiltrating immune cells contribute to lung cancer survival and their differential contributions in ever-smokers and never-smokers are not well studied. Here, we performed integrative analysis of 11 lung cancer gene-expression datasets, including 1,111 lung adenocarcinomas and 200 adjacent normal lung samples. Distinct pathways were altered in lung carcinogenesis in ever-smokers and never-smokers. Never-smoker patients had a better outcome than ever-smoker patients. We characterized compositional patterns of 21 types of immune cells in lung adenocarcinomas and revealed the complex association between immune cell composition and clinical outcomes. Interestingly, we found two subsets of immune cells, mast cells and CD4 memory T cells, which had completely opposite associations with outcomes in resting and activated status. We further discovered that several chemokines and their associated receptors (e.g., CXCL11-CX3CR1 axis) were selectively altered in lung tumors in response to cigarette smoking and their abundances showed stronger correlation with fractions of these immune subsets in ever-smokers than never-smokers. The status switched from the resting to activated forms in mast cells and CD4 memory T cells might manifest some important processes induced by cigarette smoking during tumor development and progression. Our findings suggested that aberrant activation of mast cells and CD4+ memory T cells plays crucial roles in cigarette smoking-induced immune dysfunction in the lung, which contributes to tumor development and progression.
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http://dx.doi.org/10.1080/2162402X.2018.1494677DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6169585PMC
July 2018

CD8 Resident Memory T Cells and Viral Infection.

Front Immunol 2018 19;9:2093. Epub 2018 Sep 19.

Department of Infectious Diseases, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.

Tissue-resident memory T (Trm) cells are a subset of recently identified memory T cells that mainly reside and serve as sentinels in non-lymphoid peripheral tissues. Unlike the well-characterized circulating central memory T (Tcm) cells and effector memory T (Tem) cells, Trm cells persist in the tissues, do not recirculate into blood, and offer immediate protection against pathogens upon reinfection. In this review, we focus on CD8 Trm cells and briefly introduce their characteristics, development, maintenance, and function during viral infection. We also discuss some unresolved problems, such as how CD8 Trm cells adapt to the local tissue microenvironment, how Trm cells interact with other immune cells during their development and maintenance, and the mechanisms by which CD8 Trm cells confer immune protection. We believe that a better understanding of these problems is of great clinical and therapeutic value and may contribute to more effective vaccination and treatments against viral infection.
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http://dx.doi.org/10.3389/fimmu.2018.02093DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6156262PMC
September 2019

Reduced complexity of uniportal video-assisted thoracoscopic left upper sleeve lobectomy.

J Thorac Dis 2018 Jun;10(6):3791-3796

Department of Thoracic Surgery, 2nd Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310009, China.

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http://dx.doi.org/10.21037/jtd.2018.05.97DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6051779PMC
June 2018

γδ T Cells: Crosstalk Between Microbiota, Chronic Inflammation, and Colorectal Cancer.

Front Immunol 2018 26;9:1483. Epub 2018 Jun 26.

Cancer Institute (Key Laboratory of Cancer Prevention and Intervention, National Ministry of Education), The Second Affiliated Hospital, Zhejiang University School of Medicine, Zhejiang University, Hangzhou, China.

Increasing evidence suggests that intestinal microbiota dysbiosis and chronic inflammation contribute to colorectal cancer (CRC) development. γδ T cells represent a major innate immune cell population in the intestinal epithelium that is involved in the maintenance of gut homeostasis, inflammation regulation, and carcinogenesis. The important contributions of γδ T cells are (i) to perform a protective role in the context of barrier damage and pathogenic microorganism translocation; (ii) to exert either pro- or anti-inflammatory effects at different inflammatory stages; and (iii) to boost the crosstalk between immune cells and tumor microenvironment, inducing a cascade of suppressive immune responses. Understanding the crucial role of γδ T cells would enable us to manipulate these cells during the CRC sequence and improve the efficacy of tumor therapy.
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http://dx.doi.org/10.3389/fimmu.2018.01483DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6028700PMC
June 2018