Publications by authors named "Xi Chen"

5,059 Publications

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Highly Sensitive Ultrastable Electrochemical Sensor Enabled by Proton-Coupled Electron Transfer.

Nano Lett 2021 Jun 14. Epub 2021 Jun 14.

Department of Earth and Environmental Engineering, Columbia University, New York, New York 10027, United States.

Electrochemical sensors are critical to artificial intelligence by virtue of capability of mimicking human skin to report sensing signals. But their practical applications are restricted by low sensitivity and limited cycling stability, which result from piezoionic mechanism with insufficient sensing response. Here, we report a highly sensitive ultrastable sensor based on proton-coupled electron transfer, which is different from piezoionic mechanism. The sensor gives a high sensing signal output of 117 mV, which is 16 times higher than that of counterpart device (7 mV). It delivers excellent working stability with performance retention as high as 99.13% over 10 000 bending cycles in air, exceeding that of the best-known sensors reported previously. The flexible sensor displays high sensitivity in detecting real-time signals of human activities with large and subtle deformations, including wrist bending, moving speed, pulse wave and voice vibration. Smart functions, such as braille language and handwriting recognitions, are demonstrated for artificial intelligence.
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http://dx.doi.org/10.1021/acs.nanolett.1c01692DOI Listing
June 2021

First-generation species-selective chemical probes for fluorescence imaging of human senescence-associated β-galactosidase.

Chem Sci 2020 Jun 17;11(28):7292-7301. Epub 2020 Jun 17.

State Key Laboratory of Bioreactor Engineering, Shanghai Key Laboratory of New Drug Design, School of Pharmacy, East China University of Science and Technology Shanghai 200237 China

Human senescence-associated β-galactosidase (SA-β-gal), the most widely used biomarker of aging, is a valuable tool for assessing the extent of cell 'healthy aging' and potentially predicting the health life span of an individual. Human SA-β-gal is an endogenous lysosomal enzyme expressed from , the catalytic domain of which is very different from that of β-gal, a bacterial enzyme encoded by . However, existing chemical probes for this marker still lack the ability to distinguish human SA-β-gal from β-gal of other species, such as bacterial β-gal, which can yield false positive signals. Here, we show a molecular design strategy to construct fluorescent probes with the above ability with the aid of structure-based steric hindrance adjustment catering to different enzyme pockets. The resulting probes normally work as traditional SA-β-gal probes, but they are unique in their powerful ability to distinguish human SA-β-gal from β-gal, thus achieving species-selective visualization of human SA-β-gal for the first time. NIR-emitting fluorescent probe as their representative further displays excellent species-selective recognition performance in biological systems, which has been herein verified by testing in senescent cells, in -transfected cells and in -β-gal-contaminated tissue sections of mice. Because of our probes, it was also discovered that SA-β-gal content in mice increased gradually with age and SA-β-gal accumulated most in the kidneys among the main organs of naturally aging mice, suggesting that the kidneys are the organs with the most severe aging during natural aging.
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http://dx.doi.org/10.1039/d0sc01234cDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8159415PMC
June 2020

Interleukin-20 Acts as a Promotor of Osteoclastogenesis and Orthodontic Tooth Movement.

Stem Cells Int 2021 26;2021:5539962. Epub 2021 May 26.

Hospital of Stomatology, Guanghua School of Stomatology, Sun Yat-sen University, Guangzhou, China.

Objectives: Bones constitute organs that are engaged in constant self-remodelling. Osteoblast and osteoclast homeostasis during remodelling contribute to overall skeletal status. Orthodontics is a clinical discipline that involves the investigation and implementation of moving teeth through the bone. The application of mechanical force to the teeth causes an imbalance between osteogenesis and osteogenesis in alveolar bone, leading to tooth movement. Osteoimmunology comprises the crosstalk between the immune and skeletal systems that regulate osteoclast-osteoblast homeostasis. Interleukin- (IL-) 20, an IL-10 family member, is regarded as a proinflammatory factor for autoimmune diseases and has been implicated in bone loss disease. However, the mechanism by which IL-20 regulates osteoclast differentiation and osteoclastogenesis activation remains unclear. This study investigated the effects of IL-20 on osteoclast differentiation in a rat model; it explored the underlying molecular mechanism in vitro and the specific effects on orthodontic tooth movement in vivo.

Methods: For in vitro analyses, primary rat bone marrow-derived macrophages (BMMs) were prepared from Sprague-Dawley rats for osteoclast induction. After BMMs had been treated with combinations of recombinant IL-20 protein, siRNA, and plasmids, the expression levels of osteoclast-specific factors and signalling pathway proteins were detected through real-time polymerase chain reaction, western blotting, and immunofluorescence staining. For in vivo analyses, IL-20 was injected into the rat intraperitoneal cavity after the establishment of a rat orthodontic tooth movement (OTM) model. OTM distance was detected by Micro-CT and HE staining; the expression levels of protein were detected through immunofluorescence staining.

Results: In vitro analyses showed that a low concentration of IL-20 promoted preosteoclast proliferation and osteoclastogenesis. However, a high concentration of IL-20 inhibited BMM proliferation and osteoclastogenesis. IL-20 knockdown decreased the expression of osteoclast specific-markers, while IL-20 overexpression increased the expression of osteoclast specific-markers. Furthermore, IL-20 regulated osteoclast differentiation through the OPG/RANKL/RANK pathway. Overexpression of IL-20 could significantly upregulate RANKL-mediated osteoclast differentiation and osteoclast specific-marker expression; moreover, RANKL/NF-B/NFATc1 acted as downstream signalling molecule for IL-20. In vivo analysis showed that OTM speed was significantly increased after intraperitoneal injection of IL-20; additionally, mechanical stress sensing proteins were markedly activated.

Conclusions: IL-20 augments osteoclastogenesis and osteoclast-mediated bone erosion through the RANKL/NF-B/NFATc1 signalling pathway. IL-20 inhibition can effectively reduce osteoclast differentiation and diminish bone resorption. Furthermore, IL-20 can accelerate orthodontic tooth movement and activate mechanical stress sensing proteins.
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http://dx.doi.org/10.1155/2021/5539962DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8172288PMC
May 2021

Negative Emotion Arousal and Altruism Promoting of Online Public Stigmatization on COVID-19 Pandemic.

Front Psychol 2021 26;12:652140. Epub 2021 May 26.

School of Business Administration and Tourism Management, Yunnan University, Kunming, China.

The outbreak of COVID-19 is a public health crisis that has had a profound impact on society. Stigma is a common phenomenon in the prevalence and spread of infectious diseases. In the crisis caused by the pandemic, widespread public stigma has influenced social groups. This study explores the negative emotions arousal effect from online public stigmatization during the COVID-19 pandemic and the impact on social cooperation. We constructed a model based on the literature and tested it on a sample of 313 participants from the group being stigmatized. The results demonstrate: (1) relevance and stigma perception promote negative emotions, including anxiety, anger, and grief; (2) the arousal of anger and grief leads to a rise in the altruistic tendency within the stigmatized group; and (3) stigmatization-induced negative emotions have a complete mediating effect between perceived relevance and altruistic tendency, as well as perceived stigma and altruistic tendency. For a country and nation, external stigma will promote the group becoming more united and mutual help. One wish to pass the buck but end up helping others unintentionally. We should not simply blame others, including countries, regions, and groups under the outbreak of COVID-19, and everyone should be cautious with the words and actions in the Internet public sphere.
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http://dx.doi.org/10.3389/fpsyg.2021.652140DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8187574PMC
May 2021

Biomolecular recognition of the glycan neoantigen CA19-9 by distinct antibodies.

J Mol Biol 2021 Jun 10:167099. Epub 2021 Jun 10.

Department of Chemical and Structural Biology, Weizmann Institute of Science, 76100 Rehovot, Israel. Electronic address:

Glycans decorate the cell surface, secreted glycoproteins and glycolipids, and altered glycans are often found in cancers. Despite their high diagnostic and therapeutic potential, however, glycans are polar and flexible molecules that are quite challenging for the development and design of high-affinity binding antibodies. To understand the mechanisms by which glycan neoantigens are specifically recognized by antibodies, we analyze the biomolecular recognition of the tumor-associated carbohydrate antigen CA19-9 by two distinct antibodies using X-ray crystallography. Despite the potential plasticity of glycans and the very different antigen-binding surfaces presented by the antibodies, both structures reveal an essentially identical extended CA19-9 conformer, suggesting that this conformer's stability selects the antibodies. Starting from the bound structure of one of the antibodies, we use the AbLIFT computational algorithm to design a variant with seven core mutations in the variable domain's light-heavy chain interface that exhibits tenfold improved affinity for CA19-9. The results reveal strategies used by antibodies to specifically recognize glycan antigens and show how automated antibody-optimization methods may be used to enhance the clinical potential of existing antibodies.
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http://dx.doi.org/10.1016/j.jmb.2021.167099DOI Listing
June 2021

Identification of Differentially Expressed Plasma lncRNAs As Potential Biomarkers for Breast Cancer.

Clin Breast Cancer 2021 May 18. Epub 2021 May 18.

Department of Clinical Laboratory, The Affiliated Hospital of Qingdao University, Qingdao University, Qingdao, China. Electronic address:

Background: Breast cancer is the most common malignant tumor in women and is not easy to diagnose. Increasing evidence has underscored that long non-coding RNAs (lncRNAs) play important regulatory roles in the occurrence and progression of many cancers, including breast cancer. We aimed to identify lncRNAs in plasma as potential biomarkers for breast cancer.

Patients And Methods: We analyzed the Gene Expression Omnibus (GEO) datasets GSE22820, GSE42568, and GSE65194 to identify the common differential genes between cancer tissues and adjacent tissues. Then 14 lncRNAs were identified among the common differential genes and validated by using real-time quantitative polymerase chain reaction in 92 patients with breast cancer and 100 healthy controls. Receiver operating characteristic (ROC) curves were constructed to evaluate their diagnostic value for breast cancer.

Results: Integrated analysis of the GEO datasets identified three significantly upregulated and 11 downregulated lncRNAs in breast cancer tissues. Compared with healthy controls, MIAT was significantly upregulated in breast cancer patient plasma, and LINC00968 and LINC01140 were significantly downregulated. ROC curve analysis suggested that these three lncRNAs can discriminate breast cancer from healthy individual with high specificity and sensitivity.

Conclusion: This research identified three differentially expressed lncRNAs in breast cancer patient plasma. Our data suggest that these three lncRNAs can be used as potential diagnostic biomarkers of breast cancer.
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http://dx.doi.org/10.1016/j.clbc.2021.05.003DOI Listing
May 2021

New concept in swine wastewater treatment: development of a self-sustaining synergetic microalgae-bacteria symbiosis (ABS) system to achieve environmental sustainability.

J Hazard Mater 2021 Jun 3;418:126264. Epub 2021 Jun 3.

State Key Laboratory of Urban Water Resource and Environment, School of Environment, Harbin Institute of Technology, Harbin 150090, PR China. Electronic address:

Much attention has been paid to developing methods capable of synchronous removal of pollutants from swine wastewater. Due to the natural symbiotic interactions between microalgae and bacteria, the microalgae-bacteria symbiosis (ABS) system has been found to have potential for treating wastewater. However, the corresponding biological mechanisms in the ABS system and the role of dynamic microbial community evolution in pollutant removal systems remain poorly understood. Therefore, we investigate the potential of an ABS system for pollutant removal applications and analyze the bacterial consortium symbiotically combined with Chlorella sp. MA1 and Coelastrella sp. KE4. The NH-N and PO-P removal efficiencies were significantly increased from 12.79% to 99.52% and 35.66% to 96.06% due to biotic interactions between the microalgae and bacteria. The abundance of bacterial taxa and genes related to oxidative stress, cell growth and nitrogen transfer were found to increase in response to photosynthesis, respiration and NH-N uptake. Furthermore, pathogen inactivation was induced via microalgae, co-driven by microbial succession under high dissolved oxygen conditions. In this microalgae-enhanced ABS system, the interactions between microalgae and bacteria are established for pathogens elimination and nitrogen cycling, verifying that the ABS system is an effective and environmentally sustainable swine wastewater treatment method.
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http://dx.doi.org/10.1016/j.jhazmat.2021.126264DOI Listing
June 2021

Chemoenzymatic modular assembly of O-GalNAc glycans for functional glycomics.

Nat Commun 2021 06 11;12(1):3573. Epub 2021 Jun 11.

Department of Chemistry, Georgia State University, Atlanta, GA, 30303, USA.

O-GalNAc glycans (or mucin O-glycans) play pivotal roles in diverse biological and pathological processes, including tumor growth and progression. Structurally defined O-GalNAc glycans are essential for functional studies but synthetic challenges and their inherent structural diversity and complexity have limited access to these compounds. Herein, we report an efficient and robust chemoenzymatic modular assembly (CEMA) strategy to construct structurally diverse O-GalNAc glycans. The key to this strategy is the convergent assembly of O-GalNAc cores 1-4 and 6 from three chemical building blocks, followed by enzymatic diversification of the cores by 13 well-tailored enzyme modules. A total of 83 O-GalNAc glycans presenting various natural glycan epitopes are obtained and used to generate a unique synthetic mucin O-glycan microarray. Binding specificities of glycan-binding proteins (GBPs) including plant lectins and selected anti-glycan antibodies towards these O-GalNAc glycans are revealed by this microarray, promoting their applicability in functional O-glycomics. Serum samples from colorectal cancer patients and healthy controls are assayed using the array reveal higher bindings towards less common cores 3, 4, and 6 than abundant cores 1 and 2, providing insights into O-GalNAc glycan structure-activity relationships.
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http://dx.doi.org/10.1038/s41467-021-23428-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8196059PMC
June 2021

Fluorescence Anisotropy Decays and Microscale-Volume Viscometry Reveal the Compaction of Ribosome-Bound Nascent Proteins.

J Phys Chem B 2021 Jun 10. Epub 2021 Jun 10.

Department of Chemistry, University of Wisconsin-Madison, Madison, Wisconsin 53706, United States.

This work introduces a technology that combines fluorescence anisotropy decay with microscale-volume viscometry to investigate the compaction and dynamics of ribosome-bound nascent proteins. Protein folding in the cell, especially when nascent chains emerge from the ribosomal tunnel, is poorly understood. Previous investigations based on fluorescence anisotropy decay determined that a portion of the ribosome-bound nascent protein apomyoglobin (apoMb) forms a compact structure. This work, however, could not assess the size of the compact region. The combination of fluorescence anisotropy with microscale-volume viscometry, presented here, enables identifying the size of compact nascent-chain subdomains using a single fluorophore label. Our results demonstrate that the compact region of nascent apoMb contains 57-83 amino acids and lacks residues corresponding to the two native C-terminal helices. These amino acids are necessary for fully burying the nonpolar residues in the native structure, yet they are not available for folding before ribosome release. Therefore, apoMb requires a significant degree of post-translational folding for the generation of its native structure. In summary, the combination of fluorescence anisotropy decay and microscale-volume viscometry is a powerful approach to determine the size of independently tumbling compact regions of biomolecules. This technology is of general applicability to compact macromolecules linked to larger frameworks.
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http://dx.doi.org/10.1021/acs.jpcb.1c04473DOI Listing
June 2021

Surfactant protein A modulates the activities of the JAK/STAT pathway in suppressing Th1 and Th17 polarization in murine OVA-induced allergic asthma.

Lab Invest 2021 Jun 9. Epub 2021 Jun 9.

Department of Respirology Medicine, Xinhua Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, 200092, China.

Asthma is an allergic inflammatory lung disease affecting nearly 300 million people worldwide. To better understand asthma, new regulators must be identified. We conducted a study to investigate the effect and mechanisms of action of surfactant protein A (SPA) in OVA-induced asthmatic mice. Treatment with SPA delayed the onset of asthma, decreased its severity, as well as notably suppressed pro-inflammatory cytokine production. Furthermore, SPA-treated mice possessed more leukocytes; more CD4 T cells infiltrated the spleen in the SPA-treated mice than in the control mice, and there were decreased percentages of Th1 and Th17 cells in vivo. In addition, expression levels of the T-bet (Th1 transcription factor) and RORγt (Th17 transcription factor) genes were significantly downregulated by SPA treatment. Moreover, SPA reduced the production and mRNA expression of pro-inflammatory cytokine mRNAs in activated T cells in vivo. Mechanistically, SPA could inhibit STAT1/4 and STAT3 phosphorylation, resulting in the differentiation of Th1 and suppression of Th17 cells, respectively. In the presence of CD3/CD28 expression, STAT1/4 and STAT3 were activated but suppressed by SPA, which was responsible for the augmentation of Th1 and Th17 differentiation. This result showed that SPA can effectively modulate the JAK/STAT pathway by suppressing Th1 and Th17 differentiation, thus preventing asthma. The present study reveals the novel immunomodulatory activity of SPA and highlights the importance of further investigating the effects of SPA on asthma.
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http://dx.doi.org/10.1038/s41374-021-00618-1DOI Listing
June 2021

SNP discovery of gene and their associations with growth traits in goats.

Anim Biotechnol 2021 Jun 9:1-7. Epub 2021 Jun 9.

Institute of Cellular and Molecular Biology, Jiangsu Normal University, Xuzhou, China.

AMPK plays an important role in regulating the metabolism of carbohydrate, lipid and protein in an organism, and is considered to be a key regulator of cellular energy homeostasis. In recent years, attention has been drawn to AMPK subunit polymorphisms and their association with economical traits of domestic animals and fowls. PRKAB1 encodes the β1 regulatory subunit of AMPK, and it has been reported that PRKAB1 may be applied in breeding programs of meat-type chicken. To date, the polymorphism of goat PRKAB1 gene and its associations remain unknown. In this paper, the polymorphism of gene was detected in 316 goats of three breeds. A total of four novel single nucleotide polymorphisms (SNPs) of PRKAB1 gene were revealed by sequence analysis. Among them, three were in the coding region (285 C > A, 297 C > A, 309 C > T), and they were all synonymous. One was in the intron (229 A > G). The associations between polymorphic loci and the growth traits of Xuhuai and Haimen goats were analyzed, and significant associations were found in body length index and trunk index ( < 0.05) for Xuhuai breed, while no significant associations in Haimen breed. Our results provide useful information for the improvement and breeding of Chinese native goats.
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http://dx.doi.org/10.1080/10495398.2021.1920426DOI Listing
June 2021

[Quantitative Analysis on Immunophenotype of CD34 Myeloid Precursor Cells in Myelodysplastic Syndrome and Its Correlation with Clinical Features].

Zhongguo Shi Yan Xue Ye Xue Za Zhi 2021 Jun;29(3):832-839

Department of Hematology, Second Hospital of Shanxi Medical University, Taiyuan 030001, Shanxi Province, China,E-mail:

Objective: To investigate the quantitative expression of immunophenotype of CD34 myeloid precursor cells in myelodysplastic syndrome (MDS) patients and its correlation with clinical characteristics, and understand the effect of quantitative expression of CD7 and CD117 on the prognosis of low-risk MDS patients.

Methods: Multi-parameter flow cytometry (FCM) was used to detect the proportion and mean fluorescence intensity (MFI) of each antigen of bone marrow CD34 myeloid precursor cells in 79 MDS patients. The correlation between the expression level of each immune marker and clinical characteristics was compared. The effects of quantitative expressions of CD7 and CD117 on the overall survival rate of low-risk patients were explored.

Results: Bone marrow blast cell proportion (P<0.01), RBC level (P<0.01), and Hb level (P<0.05) of high-risk MDS patients were higher, while EPO level (P<0.05) was lower than those of low-risk patients. The proportion of CD34 blast cells (P<0.01), the proportion of CD117 (P<0.05) and the MFI of CD7 (P<0.05) were higher in high-risk patients than those in low-risk patients, but the MFI of CD123 was lower (P<0.05). In high-risk MDS patients, CD15/CD34 (MFI) and CD19/CD34 (MFI) positively correlated with the proportion of total T cells (r=0.458; r=0.505), while CD19/CD34 (%) and CD19/CD34 (MFI) negatively correlated with WBC levels (r=-0.469; r=-0.503). In low-risk MDS patients, CD34 (%) positively correlated with bone marrow erythrocyte proportion, PLT level and neutrophil level (r=0.426; r=0.486; r=0.495), but negatively correlated with LDH level (r=-0.421); WT1 expression level was positively correlated with CD10/CD34 (%), CD10/CD34 (MFI) and CD117/CD34 (MFI) (r=0.745; r=0.800; r=0.434), while negatively correlated with CD11b/CD34 (%)(r=-0.457); CD19/CD34 (%) and CD71/CD34 (MFI) negatively correlated with NK cell proportion (r=-0.786; r=-0.514); CD10/CD34 (%) positively correlated with Th/Ts, while CD7/CD34 (MFI) negatively correlated with the proportion of Th cells (r=0.738; r=-0.513); HLADR/CD34 (%) and HLADR/CD34 (MFI) negatively correlated with PLT level (r=-0.461; r=-0.445), while HLADR/CD34 (MFI) positively correlated with bone marrow NAP fraction (r=0.552). The quantitative expression of CD7 and CD117 had no significant effect on the overall survival rate of low-risk MDS patients.

Conclusion: The immunophenotype of CD34 myeloid precursor cell in different risk groups in MDS patients is related to clinical characteristics. Bone marrow cell morphology, clinical and laboratory features and immunophenotype will be of great significance to the diagnosis, clinical classification and prognosis evaluation of MDS patients.
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http://dx.doi.org/10.19746/j.cnki.issn.1009-2137.2021.03.028DOI Listing
June 2021

Capture of ambient air CO from municipal wastewater mineralization by using an ion-exchange membrane.

Sci Total Environ 2021 May 29;790:148136. Epub 2021 May 29.

Earth Engineering Center, Center for Advanced Materials for Energy and Environment, Department of Earth and Environmental Engineering, Columbia University, New York, NY 10027, USA.

The capture of ambient air CO from synthetic urban wastewater mineralization reaction was studied. An ion exchange membrane was used as sorbent, which adsorbs CO when dry and releases it when wet. The UV/HO degradation process was chosen to convert Total Organic Carbon (TOC) to carbon dioxide due to its advantages of convenience and fast kinetics over the conventional biological treatment that is usually used in urban wastewater treatment plants. In the first phase, experiments combining UV-C light and HO were carried out to select the optimal values of the following parameters: pH, the dose of HO and temperature. In the second stage, the CO emission into the air from the degradation of organic compounds present in wastewater during UV/HO process in the absence or presence of ion exchange membranes was evaluated. The effects of parameters such as temperature or air humidity were studied. A qualitative study of desorption was carried out to check the viability of reuse CO captured in the membrane. Finally, a similar CO adsorption capacity after five cycles of adsorption and regeneration of the membranes was observed, being percentage loss of around 4%.
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http://dx.doi.org/10.1016/j.scitotenv.2021.148136DOI Listing
May 2021

H3K36 methyltransferase NSD1 regulates chondrocyte differentiation for skeletal development and fracture repair.

Bone Res 2021 Jun 7;9(1):30. Epub 2021 Jun 7.

Shanghai Institute of Microsurgery on Extremities, and Department of Orthopedic Surgery, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, China.

Chondrocyte differentiation is a critical process for endochondral ossification, which is responsible for long bone development and fracture repair. Considerable progress has been made in understanding the transcriptional control of chondrocyte differentiation; however, epigenetic regulation of chondrocyte differentiation remains to be further studied. NSD1 is a H3K36 (histone H3 at lysine 36) methyltransferase. Here, we showed that mice with Nsd1 deficiency in Prx1 mesenchymal progenitors but not in Col2 chondrocytes showed impaired skeletal growth and fracture healing accompanied by decreased chondrogenic differentiation. Via combined RNA sequencing (RNA-seq) and chromatin immunoprecipitation sequencing (ChIP-seq) analysis, we identified sex determining region Y box 9 (Sox9), the key transcription factor of chondrogenic differentiation, as a functional target gene of NSD1. Mechanistically, NSD1 regulates Sox9 expression by modulating H3K36me1 and H3K36me2 levels in the Sox9 promoter region, constituting a novel epigenetic regulatory mechanism of chondrogenesis. Moreover, we found that NSD1 can directly activate the expression of hypoxia-inducible factor 1α (HIF1α), which plays a vital role in chondrogenic differentiation through its regulation of Sox9 expression. Collectively, the results of our study reveal crucial roles of NSD1 in regulating chondrogenic differentiation, skeletal growth, and fracture repair and expand our understanding of the function of epigenetic regulation in chondrogenesis and skeletal biology.
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http://dx.doi.org/10.1038/s41413-021-00148-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8185073PMC
June 2021

Significant Enhancement of the Polarization Holographic Performance of Photopolymeric Materials by Introducing Graphene Oxide.

ACS Appl Mater Interfaces 2021 Jun 7;13(23):27500-27512. Epub 2021 Jun 7.

Information Photonics Research Center, Key Laboratory of Opto-Electronic Science and Technology for Medicine of Ministry of Education, Fujian Provincial Key Laboratory of Photonics Technology, Fujian Provincial Engineering Technology Research Center of Photoelectric Sensing Application, Fujian Normal University, Fuzhou 350117, China.

Relying on various defects and functional oxygen-containing groups on the basal planes, graphene oxide (GO) is commonly unitized for intimate mixing with a polymer matrix to fabricate high-performance nanocomposite polymeric materials with the characteristics of graphene. Herein, by introducing GO nanosheets in a phenanthraquinone-doped polymethyl methacrylate (PQ/PMMA) photopolymer, we demonstrate that the polarization holographic diffraction efficiency of nanocomposite materials can be dramatically enhanced up to nearly 10 times and the photosensitivity can also be enhanced by more than 3 times. Experimental observations reveal that the incorporation of GO nanosheets serves as a polymerization initiator not only to promote the polymerization of MMA monomers and induce the drafting behavior of the PMMA polymer on its surface but also to effectively modulate the molecular weight of the PQ/PMMA photopolymer by adjusting the doping concentration of GO nanosheets. The current study, for the first time, demonstrates that the modulation of molecular weight for PQ/PMMA photopolymers here exerts a significant impact on their holography performance. In addition, due to the strong physisorption of PQ photosensitizers onto GO nanosheets, the aggregation of PQ around GO-graft-PMMA also facilitates the formation of GO-graft-PMMA/PQ and is beneficial to the enhancement of holographic performance. The emergence of GO-graft-PMMA/PQ nanocomposite materials here is expected to fulfill the requirement of high-performance polarization-sensitive materials in the field of polarization holographic data storage and provide a facile but effective nanocomposite doping strategy to modulate the holographic performance of photopolymers from micro- and mesoscopic levels.
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http://dx.doi.org/10.1021/acsami.1c07390DOI Listing
June 2021

YY1-mediated reticulocalbin-2 upregulation promotes the hepatocellular carcinoma progression via activating MYC signaling.

Am J Cancer Res 2021 15;11(5):2238-2251. Epub 2021 May 15.

Department of Hepatobiliary and Pancreatic Surgery, Zhongnan Hospital of Wuhan University Wuhan 430071, Hubei, People's Republic of China.

Hepatocellular carcinoma (HCC) is a common digestive tumor with high fatality worldwide. Previous studies have shown that Reticulocalbin-2 (RCN2) was a crucial factor for HCC proliferation, but invasion and migration mechanism of RCN2 contributing to HCC is poorly investigated. In this study, we estimated the RCN2 expression in both patient tissues and cell lines by polymerase chain reaction (PCR) and western blotting (WB), as well as the clinical information of HCC patients from public databases. Biological function induced by RCN2 in and was also researched through multiple functional experiments. Upstream and downstream signal of RCN2 was identified by bioinformatics. We found that up-regulated RCN2 was related to poorer prognosis in HCC patients and attached significance to HCC proliferation, invasion and migration. Luciferase reporter assay and chromatin immunoprecipitation validated that YY1 as the upstream transcription factor of RCN2, facilitating the expression of RCN2. Gene set enrichment analysis indicated that HCC progression induced by RCN2 might be related to MYC signaling. Furthermore, we demonstrated RCN2 reduced proteasomal degradation of MYC and lead to HCC progression. The effects of overexpressed RCN2 in HCC were attenuated by MYC silencing. In conclusion, our study highlighted the vital role of RCN2 in tumor progression and the potential benefit for the treatment of HCC.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8167676PMC
May 2021

PredTAD: A machine learning framework that models 3D chromatin organization alterations leading to oncogene dysregulation in breast cancer cell lines.

Comput Struct Biotechnol J 2021 7;19:2870-2880. Epub 2021 May 7.

School of Biomedical Informatics, University of Texas Health Science Center, Houston, TX 77054, USA.

Topologically associating domains, or TADs, play important roles in genome organization and gene regulation; however, they are often altered in diseases. High-throughput chromatin conformation capturing assays, such as Hi-C, can capture domains of increased interactions, and TADs and boundaries can be identified using well-established analytical tools. However, generating Hi-C data is expensive. In our study, we addressed the relationship between multi-omics data and higher-order chromatin structures using a newly developed machine-learning model called PredTAD. Our tool uses already-available and cost-effective datatypes such as transcription factor and histone modification ChIPseq data. Specifically, PredTAD utilizes both epigenetic and genetic features as well as neighboring information to classify the entire human genome as boundary or non-boundary regions. Our tool can predict boundary changes between normal and breast cancer genomes. Among the most important features for predicting boundary alterations were CTCF, subunits of cohesin (RAD21 and SMC3), and chromosome number, suggesting their roles in conserved and dynamic boundaries formation. Upon further analysis, we observed that genes near altered TAD boundaries were found to be involved in several important breast cancer signaling pathways such as Ras, Jak-STAT, and estrogen signaling pathways. We also discovered a TAD boundary alteration that contributes to RET oncogene overexpression. PredTAD can also successfully predict TAD boundary changes in other conditions and diseases. In conclusion, our newly developed machine learning tool allowed for a more complete understanding of the dynamic 3D chromatin structures involved in signaling pathway activation, altered gene expression, and disease state in breast cancer cells.
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http://dx.doi.org/10.1016/j.csbj.2021.05.013DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8142020PMC
May 2021

Effects of Hsp90 Inhibitor Ganetespib on Inhibition of Azole-Resistant .

Front Microbiol 2021 20;12:680382. Epub 2021 May 20.

School of Pharmacy, Second Military Medical University, Shanghai, China.

is the most common fungal pathogen. Recently, drug resistance of is increasingly severe. Hsp90 is a promising antifungal target to overcome this problem. To evaluate the effects of Hsp90 inhibitor ganetespib on the inhibition of azole-resistant , the microdilution checkerboard method was used to measure the synergistic efficacy of ganetespib. The XTT/menadione reduction assay, microscopic observation, and Rh6G efflux assay were established to investigate the effects of ganetespib on azole-resistant biofilm formation, filamentation, and efflux pump. Real-time RT-PCR analysis was employed to clarify the mechanism of antagonizing drug resistance. The antifungal efficacy of ganetespib was determined by the infectious model of azole-resistant . Ganetespib showed an excellent synergistic antifungal activity and significantly inhibited the fungal biofilm formation, whereas it had no inhibitory effect on fungal hypha formation. Expression of azole-targeting enzyme gene and efflux pump genes , and was significantly down-regulated when ganetespib was used in combination with FLC. In a mouse model infected with FLC-resistant , the combination of ganetespib and FLC effectively reversed the FLC resistance and significantly decreased the kidney fungal load of mouse.
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http://dx.doi.org/10.3389/fmicb.2021.680382DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8174564PMC
May 2021

Multifaceted Therapy of Nanocatalysts in Neurological Diseases.

J Biomed Nanotechnol 2021 May;17(5):711-743

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

With the development of enzymes immobilization technology and the discover of nanozymes, catalytic therapy exhibited tremendous potential for neurological diseases therapy. In especial, since the discovery of Fe₃O₄ nanoparticles possessing intrinsic peroxidase-like activity, various nanozymes have been developed and recently started to explore for neurological diseases therapy, such as Alzheimer's disease, Parkinson's disease and stroke. By combining the catalytic activities with other properties (such as optical, thermal, electrical, and magnetic properties) of nanomaterials, the multifunctional nanozymes would not only alleviate oxidative and nitrosative stress on the basis of multienzymes-mimicking activity, but also exert positive effects on immunization, inflammation, autophagy, protein aggregation, which provides the foundation for multifaceted treatments. This review will summarize various types of nanocatalysts and further provides a valuable discussion on multifaceted treatment by nanozymes for neurological diseases, which is anticipated to provide an easily accessible guide to the key opportunities and current challenges of the nanozymes-mediated treatments for neurological diseases.
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http://dx.doi.org/10.1166/jbn.2021.3063DOI Listing
May 2021

Risk of Immune-related Adverse Events in Melanoma Patients With Preexisting Autoimmune Disease Treated With Immune Checkpoint Inhibitors: A Population-based Study Using SEER-Medicare Data.

Am J Clin Oncol 2021 Jun 3. Epub 2021 Jun 3.

Division of Urological Surgery and Center for Surgery and Public Health, Brigham and Women's Hospital, Harvard Medical School Lank Center for Genitourinary Oncology, Dana-Farber/Brigham and Women's Cancer Center, Harvard Medical School, Boston, MA Department of Urology and Neurourology, Marien Hospital Herne, Ruhr-University Bochum, Herne, Germany.

Objective: The objective of this study was to examine the risk of immune-related adverse events (irAEs) in patients with a preexisting autoimmune disease (pAID) presenting with a cutaneous melanoma receiving an immune checkpoint inhibitor (ICI) therapy.

Methods: Data from the Surveillance, Epidemiology, and End Results cancer registries and linked Medicare claims between January 2010 and December 2015 was used to identify patients diagnosed with cutaneous melanoma who had pAID or received ICI or both. Patients were then stratified into 3 groups: ICI+pAID, non-ICI+pAID, and ICI+non-pAID. Inverse probability of treatment weighted Cox proportional hazards regression models were fitted to assess the risk of cardiac, pulmonary, endocrine, and neurological irAE.

Results: In total, 3704 individuals were included in the analysis. The majority of patients consisted of non-ICI+pAID patients (N=2706/73.1%), while 106 (2.9%) patients and 892 (24.1%) were classified as ICI+pAID and ICI+non-pAID, respectively. The risk of irAE was higher in the ICI+pAID group compared with the non-ICI+pAID and ICI+non-pAID, respectively (non-ICI: cardiac: hazard ratio [HR]=3.59, 95% confidence interval [CI]: 2.83-4.55; pulmonary: HR=3.94, 95% CI: 3.23-4.81; endocrine: HR=1.72, 95% CI: 1.53-1.93; neurological: HR=3.88, 95% CI: 2.30-6.57/non-pAID: cardiac: HR=3.83, 95% CI: 3.39-4.32; pulmonary: HR=2.08, 95% CI: 1.87-2.32; endocrine: HR=1.23, 95% CI: 1.14-1.32; neurological: HR=3.77, 95% CI: 2.75-5.18).

Conclusions: Patients with a pAID face a significantly higher risk of irAEs. Further research examining the clinical impact of these events on the patients' oncological outcome and quality of life is urgently needed given our findings of significantly worse rates of adverse events.
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http://dx.doi.org/10.1097/COC.0000000000000840DOI Listing
June 2021

Cervical Ossification of Ligamentum Flavum: Elaborating an Underappreciated but Occasional Contributor to Myeloradiculopathy in Aging Population Based on Synthesis of Individual Participant Data.

Clin Interv Aging 2021 24;16:897-908. Epub 2021 May 24.

Peking University Third Hospital, Department of Orthopaedics, Beijing, 100191, People's Republic of China.

Purpose: Cervical ossification of ligamentum flavum (COLF) is a rare clinical entity which can occasionally contribute to severe myeloradiculopathy. Many orthopedists are unfamiliar with or underestimate this pathology. Therefore, a comprehensive research is obligatory to reappraise the epidemiological, radiological, clinical and histopathological characteristics of COLF-myeloradiculopathy based on synthesis of individual patient data.

Methods: Following Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, PubMed, EMBASE, Scopus and Web of Science databases were searched for studies discussing COLF-myeloradiculopathy from the inception to December 2020.

Results: A total of 94 cases from 54 studies were identified. The annual publications demonstrated a steady increase, and most reports were from Japan and China. The mean age was 58.76±13.39 years and nearly 60% of cases occurred in the 55-64 and 65-74 years age group. The male-female ratio was 1.4:1. Most cases belonged to East Asian population (60.64%). COLF predominately appeared in the lower cervical and cervicothoracic spine (76.60%) and mainly affected C4-5 (23.29%) and C5-6 (21.23%). Single-segment type ossification accounted for 62.76 and 45.45% of ossification lesions distributed bilaterally. The majority of COLF (81.1%) were spontaneous, and motor disturbance (76.4%), spinal ataxia (62.5%) and sensory disturbance (58.9%) were the most common manifestations. Histopathologically, it's a metaplastic process of endochondral ossification with the formation of mature lamellar bone which was distinguished from calcification of ligamentum flavum. About 21.28% of concurrent COLF and COPLL cases were identified as a separated group, with unique characteristics.

Conclusion: COLF is an underappreciated but potentially growing pathogeny of myeloradiculopathy in aging population, though its distinct epidemiological, radiological, clinical and histopathological features are not fully supported by current evidence. However, our findings will provide several referential data for future researches to shed light on COLF.
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http://dx.doi.org/10.2147/CIA.S313357DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8163622PMC
June 2021

Functionalized Silver Nanocapsules with Improved Antibacterial Activity Using Silica Shells Modified with Quaternary Ammonium Polyethyleneimine as a Bacterial Cell-Targeting Agent.

J Agric Food Chem 2021 Jun 2;69(23):6485-6494. Epub 2021 Jun 2.

College of Plant Protection, China Agricultural University, Beijing 100193, China.

Silver nanoparticles (AgNPs) have remarkable and broad-spectrum antibacterial activities against Gram-positive (G+) and Gram-negative bacteria (G-). However, the negative surface potential of AgNPs limits their antibacterial activities due to the electrostatic repulsion with the negatively charged bacterial cell membrane. To address the limitation, AgNPs were loaded in the mesoporous silica nanoparticles by preparing silver core-mesoporous silica shell nanocapsules ([email protected]), and then, a cationic antibacterial polymer, quaternary ammonium polyethyleneimine (QPEI), was used to modify [email protected] for improving their surface potential and antibacterial activities. The results showed that the obtained [email protected] exhibited a high positive surface potential (+39.6 mV) and a strong electrostatic attraction with . cells in coculture, resulting in an excellent bacterial cell-targeting effect. At the same concentration, [email protected] exhibited less silver content (reducing the silver content of [email protected] by 19%), higher antibacterial activities, and longer effective duration against subsp. (G+) and . (G-) than [email protected] and QPEI alone. The excellent bacterial cell-targeting effect and synergistic antibacterial action combined with QPEI accounted for the significantly enhanced antibacterial activities of [email protected] Therefore, using a cationic antibacterial polymer to confer the bacterial cell-targeting effect and synergistic antibacterial action would be extended to other antimicrobial materials.
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http://dx.doi.org/10.1021/acs.jafc.1c01930DOI Listing
June 2021

Chinese Propolis Suppressed Pancreatic Cancer Panc-1 Cells Proliferation and Migration via Hippo-YAP Pathway.

Molecules 2021 May 10;26(9). Epub 2021 May 10.

College of Animal Sciences, Zhejiang University, Hangzhou 310058, China.

Pancreatic cancer is one of the most malignant cancers with high mortality. Therefore, it is of great urgency to develop new agents that could improve the prognosis of Pancreatic cancer patients. Chinese propolis (CP), a flavonoid-rich beehive product, has been reported to have an anticancer effect. In this study, we applied CP to the human Pancreatic cancer cell line Panc-1 to verify its impact on tumor development. CP induced apoptosis in Panc-1 cells from 12.5 µg/mL in a time- and dose-dependent manner with an IC value of approximately 50 µg/mL. Apoptosis rate induced by CP was examined by Annexing FITC/PI assay. We found that 48 h treatment with 50 µg/mL CP resulted in 34.25 ± 3.81% apoptotic cells, as compared to 9.13 ± 1.76% in the control group. We further discovered that the Panc-1 cells tended to be arrested at G2/M phase after CP treatment, which is considered to contribute to the anti-proliferation effect of CP. Furthermore, our results demonstrated that CP suppressed Panc-1 cell migration by regulating epithelial-mesenchymal transition (EMT). Interestingly, the Hippo pathway was activated in Panc-1 cells after CP treatment, serving as a mechanism for the anti-pancreatic cancer effect of CP. These findings provide a possibility of beehive products as an alternative treatment for pancreatic cancer.
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http://dx.doi.org/10.3390/molecules26092803DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8126155PMC
May 2021

Dietary Derived Propionate Regulates Pathogenic Fibroblast Function and Ameliorates Experimental Arthritis and Inflammatory Tissue Priming.

Nutrients 2021 May 13;13(5). Epub 2021 May 13.

Department of Internal Medicine 3-Rheumatology and Immunology, Friedrich-Alexander Universität Erlangen-Nürnberg (FAU), Universitätsklinikum Erlangen, 91054 Erlangen, Germany.

Short-chain fatty acids are gut-bacteria-derived metabolites that execute important regulatory functions on adaptive immune responses, yet their influence on inflammation driven by innate immunity remains understudied. Here, we show that propionate treatment in drinking water or upon local application into the joint reduced experimental arthritis and lowered inflammatory tissue priming mediated by synovial fibroblasts. On a cellular level, incubation of synovial fibroblasts with propionate or a physiological mixture of short-chain fatty acids interfered with production of inflammatory mediators and migration and induced immune-regulatory fibroblast senescence. Our study suggests that propionate mediates its alleviating effect on arthritis by direct abrogation of local arthritogenic fibroblast function.
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http://dx.doi.org/10.3390/nu13051643DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8152983PMC
May 2021

Sorghum Phenolic Compounds Are Associated with Cell Growth Inhibition through Cell Cycle Arrest and Apoptosis in Human Hepatocarcinoma and Colorectal Adenocarcinoma Cells.

Foods 2021 May 1;10(5). Epub 2021 May 1.

Department of Food Nutrition Dietetics and Health, Kansas State University, Manhattan, KS 66506, USA.

Phenolic compounds in some specialty sorghums have been associated with cancer prevention. However, direct evidence and the underlying mechanisms for this are mostly unknown. In this study, phenolics were extracted from 13 selected sorghum accessions with black pericarp while F10000 hybrid with white pericarp was used as a control, and cell growth inhibition was studied in hepatocarcinoma HepG2 and colorectal adenocarcinoma Caco-2 cells. Total phenolic contents of the 13 high phenolic grains, as determined by Folin-Ciocalteu, were 30-64 mg GAE/g DW in the phenolic extracts of various accessions compared with the control F10000 at 2 mg GAE/g DW. Treatment of HepG2 with the extracted phenolics at 0-200 μM GAE up to 72 h resulted in a dose- and time-dependent reduction in cell numbers. The values of IC varied from 85 to 221 mg DW/mL while the control of F10000 was 1275 mg DW/mL. The underlying mechanisms were further examined using the highest phenolic content of PI329694 and the lowest IC of PI570481, resulting in a non-cytotoxic decrease in cell number that was significantly correlated with increased cell cycle arrest at G2/M and apoptotic cells in both HepG2 and Caco-2 cells. Taken together, these results indicated, for the first time, that inhibition of either HepG2 or Caco-2 cell growth by phenolic extracts from 13 selected sorghum accessions was due to cytostatic and apoptotic but not cytotoxic mechanisms, suggesting some specialty sorghums are a valuable, functional food, providing sustainable phenolics for potential cancer prevention.
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http://dx.doi.org/10.3390/foods10050993DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8147257PMC
May 2021

Immune Landscape of Gastric Carcinoma Tumor Microenvironment Identifies a Peritoneal Relapse Relevant Immune Signature.

Front Immunol 2021 13;12:651033. Epub 2021 May 13.

Department of Medical Oncology, The First Hospital of China Medical University, Shenyang, China.

Background: Gastric cancer (GC) still represents the third leading cause of cancer-related death worldwide. Peritoneal relapse (PR) is the most frequent metastasis occurring among patients with advanced gastric cancer. Increasingly more evidence have clarified the tumor immune microenvironment (TIME) may predict survival and have clinical significance in GC. However, tumor-transcriptomics based immune signatures derived from immune profiling have not been established for predicting the peritoneal recurrence of the advanced GC.

Methods: In this study, we depict the immune landscape of GC by using transcriptome profiling and clinical characteristics retrieved from GSE62254 of Gene Expression Omnibus (GEO). Immune cell infiltration score was evaluated single-sample gene set enrichment (ssGSEA) analysis algorithm. The least absolute shrinkage and selection operator (LASSO) Cox regression algorithm was used to select the valuable immune cells and construct the final model for the prediction of PR. The receiver operating characteristic (ROC) curve and the Kaplan-Meier curve were used to check the accuracy of PRIs. Gene Set Enrichment Analysis (GSEA) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis were performed to explore the molecular pathways associated with PRIs.

Results: A peritoneal recurrence related immune score (PRIs) with 10 immune cells was constructed. Compared to the low-PRIs group, the high-PRIs group had a greater risk. The upregulation of the focal adhesion signaling was observed in the high-PRIs subtype by GSEA and KEGG. Multivariate analysis found that both in the internal training cohort and the internal validation cohort, PRIs was a stable and independent predictor for PR. A nomogram that integrated clinicopathological features and PRIs to predict peritoneal relapse was constructed. Subgroup analysis indicated that the PRIs could obviously distinguish peritoneal recurrence in different molecular subtypes, pathological stages and Lauren subtypes, in which PRIs of Epithelial-Mesenchymal Transitions (EMT) subtype, III-IV stage and diffuse subtype are higher respectively.

Conclusion: Overall, we performed a comprehensive evaluation of the immune landscape of GC and constructed a predictive PR model based on the immune cell infiltration. The PRIs represents novel promising feature of predicting peritoneal recurrence of GC and sheds light on the improvement of the personalized management of GC patients after surgery.
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http://dx.doi.org/10.3389/fimmu.2021.651033DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8155484PMC
May 2021

Basil Polysaccharide Reverses Development of Experimental Model of Sepsis-Induced Secondary Staphylococcus aureus Pneumonia.

Mediators Inflamm 2021 18;2021:5596339. Epub 2021 May 18.

Department of Critical Care Medicine, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China.

Background: Basil polysaccharide (BPS) represents a main active ingredient extracted from basil (Ocimum basilicum L.), which can regulate secondary bacterial pneumonia development in the process of sepsis-mediated immunosuppression.

Methods: In this study, a dual model of sepsis-induced secondary pneumonia with cecal ligation and puncture and intratracheal instillation of or was constructed.

Results: The results indicated that BPS-treated mice undergoing CLP showed resistance to secondary pneumonia. Compared with the IgG-treated group, BPS-treated mice exhibited better survival rate along with a higher bacterial clearance rate. Additionally, BPS treatment attenuated cell apoptosis, enhanced lymphocyte and macrophage recruitment to the lung, promoted pulmonary cytokine production, and significantly enhanced CC receptor ligand 4 (CCL4). Notably, recombinant CCL4 protein could enhance the protective effect on -induced secondary pulmonary infection of septic mice, which indicated that BPS-induced CCL4 partially mediated resistance to secondary bacterial pneumonia. In addition, BPS priming markedly promoted the phagocytosis of alveolar macrophages while killing , which was related to the enhanced p38MAPK signal transduction pathway activation. Moreover, BPS also played a protective role in sepsis-induced secondary pneumonia by inducing Treg cell differentiation.

Conclusions: Collectively, these results shed novel lights on the BPS treatment mechanism in sepsis-induced secondary pneumonia in mice.
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http://dx.doi.org/10.1155/2021/5596339DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8149242PMC
May 2021

Human gut-microbiome interplay: Analysis of clinical studies for the emerging roles of diagnostic microbiology in inflammation, oncogenesis and cancer management.

Infect Genet Evol 2021 May 28;93:104946. Epub 2021 May 28.

Department of Oncology, Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing 210028, PR China; Jiangsu Province Academy of Traditional Chinese Medicine, Nanjing 210028, PR China. Electronic address:

Microorganisms have been known to coexist in various parts of human body including the gut. The interactions between microbes and the surrounding tissues of the host are critical for fine fettle of the gut. The incidence of such microorganisms tends to vary among specific type of cancer affected individuals. Such microbial communities of specific tumor sites in cancer affected individuals could plausibly be used as prognostic and/or diagnostic markers for tumors associated with that specific site. Microorganisms of intestinal and non-intestinal origins including Helicobacter pylori can target several organs, act as carcinogens and promote cancer. It is interesting to note that diets causing inflammation can also increase the cancer risk. Yet, dietary supplementation with prebiotics and probiotics can reduce the incidence of cancer. Therefore, both diet and microbial community of the gut have dual roles of prevention and oncogenesis. Hence, this review intends to summarize certain important details related to gut microbiome and cancer.
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http://dx.doi.org/10.1016/j.meegid.2021.104946DOI Listing
May 2021

Polar in-plane surface orientation of a ferroelectric nematic liquid crystal: Polar monodomains and twisted state electro-optics.

Proc Natl Acad Sci U S A 2021 Jun;118(22)

Department of Physics, University of Colorado, Boulder, CO 80309;

We show that surface interactions can vectorially structure the three-dimensional polarization field of a ferroelectric fluid. The contact between a ferroelectric nematic liquid crystal and a surface with in-plane polarity generates a preferred in-plane orientation of the polarization field at that interface. This is a route to the formation of fluid or glassy monodomains of high polarization without the need for electric field poling. For example, unidirectional buffing of polyimide films on planar surfaces to give quadrupolar in-plane anisotropy also induces macroscopic in-plane polar order at the surfaces, enabling the formation of a variety of azimuthal polar director structures in the cell interior, including uniform and twisted states. In a π-twist cell, obtained with antiparallel, unidirectional buffing on opposing surfaces, we demonstrate three distinct modes of ferroelectric nematic electro-optic response: intrinsic, viscosity-limited, field-induced molecular reorientation; field-induced motion of domain walls separating twisted states of opposite chirality; and propagation of polarization reorientation solitons from the cell plates to the cell center upon field reversal. Chirally doped ferroelectric nematics in antiparallel-rubbed cells produce Grandjean textures of helical twist that can be unwound via field-induced polar surface reorientation transitions. Fields required are in the 3-V/mm range, indicating an in-plane polar anchoring energy of ∼3 × 10 J/m.
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http://dx.doi.org/10.1073/pnas.2104092118DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8179187PMC
June 2021

Three-dimensional ATUM-SEM reconstruction and analysis of hepatic endoplasmic reticulum‒organelle interactions.

J Mol Cell Biol 2021 May 28. Epub 2021 May 28.

National Laboratory of Pattern Recognition, Institute of Automation, Chinese Academy of Sciences, Beijing 100190, China.

The endoplasmic reticulum (ER) is a contiguous and complicated membrane network in eukaryotic cells, and membrane contact sites (MCSs) between the ER and other organelles perform vital cellular functions, including lipid homeostasis, metabolite exchange, calcium level regulation, and organelle division. Here, we establish a whole pipeline to reconstruct all ER, mitochondria, lipid droplets, lysosomes, peroxisomes, and nuclei by automated tape-collecting ultramicrotome scanning electron microscopy (ATUM-SEM) and deep learning techniques, which generates an unprecedented 3D model for mapping liver samples. Furthermore, the morphology of various organelles and the MCSs between the ER and other organelles are systematically analyzed. We found that the ER presents with predominantly flat cisternae and is knitted tightly all throughout the intracellular space and around other organelles. In addition, the ER has a smaller volume-to-membrane surface area ratio than other organelles, which suggests that the ER could be more suited for functions that require a large membrane surface area. Our data also indicate that ER‒mitochondria contacts are particularly abundant, especially for branched mitochondria. Our study provides 3D reconstructions of various organelles in liver samples together with important fundamental information for biochemical and functional studies in the liver.
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http://dx.doi.org/10.1093/jmcb/mjab032DOI Listing
May 2021