Publications by authors named "Yuan Zhou"

1,101 Publications

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Suppresses Cell Proliferation and Apoptosis via Regulation of SIRT1/PGC-1α/NRF2 Axis in Pancreatic Cancer.

Cell J 2021 Jul 26;23(2):199-210. Epub 2021 May 26.

Department of Gastrointestinal Surgery, The Central Hospital of Hengyang City, Hengyang 421001, P.R.China.Email:

Objective: Our study aimed to investigate function and mechanism of in proliferation and apoptosis of pancreatic cancer (PC) cells by regulating NAD+-dependent histone deacetylase sirtulin 1 (SIRT1).

Materials And Methods: This experimental study included two PC cell lines AsPC-1 and PANC-1 in which expression levels of and were manipulated. The level of was detected by reverse transcription quantitative polymerase chain reaction (RT-qPCR) method. Expression levels of SIRT1, BCL-2, BAX, cleaved CASPASE-8/9/3, PARP, PGC-1α, NRF2, eNOS and iNOS were examined via RT-qPCR and western blotting, respectively. The binding sites of on the SIRT1 were examined via dual-luciferase assay. Cell proliferation and apoptosis were examined by MTT assay, colony formation assay, Annexin-V/PI staining and TUNEL assay. The oxidative metabolic changes were monitored by reactive oxygen species (ROS), malondialdehyde (MDA) and superoxide dismutase (SOD) detection.

Results: could specifically target the 3'-UTR of and reduce its expression in PC cells. Either elevated expression of or partial loss of SIRT1 inhibited cell proliferation and induced cell apoptosis. Accumulation of BAX and cleaved CASPASE-8/9/3, inhibition of PGC-1α/NRF2 pathway, increase oxidative stress and reduction of BCL-2 as well as uncleaved PARP were found in the presence of or the absence of . Overexpression of could reduce anti-proliferative and pro-apoptotic effects of .

Conclusion: Overall, this study concluded that -dependent inhibition displays anti-proliferative and proapoptotic roles in PC cells via PGC-1α/NRF2 pathway, which highlights as a potential target for PC treatment.
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http://dx.doi.org/10.22074/cellj.2021.7038DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8181315PMC
July 2021

A novel risk-scoring system conducing to chemotherapy decision for patients with pancreatic ductal adenocarcinoma after pancreatectomy.

J Cancer 2021 27;12(14):4433-4442. Epub 2021 May 27.

Department of General Visceral and Thoracic Surgery, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.

Chemotherapy is suggested to use in all stages of pancreatic cancer. Is it reasonable to recommend chemotherapy for all PDAC patients? It is necessary to distinguish low-risk PDAC patients underwent pancreatectomy, who may not lose survival time due to missed chemotherapy and not need to endure pain, nausea, tiredness, drowsiness, and breath shortness caused by chemotherapy. Nomograms were constructed with basis from the multivariate Cox regression analysis. X-tile software was utilized to perform risk stratification. Survival curves were used to display the effect of chemotherapy in different risk-stratification. All of the significant variables were used to create the nomograms for overall survival (OS). The total risk score of each patient was calculated by summing the scores related to each variable. X-tile software was utilized to classify patients into high-risk (score >283), median-risk (197
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http://dx.doi.org/10.7150/jca.57768DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8176415PMC
May 2021

Cimifugin relieves pruritus in psoriasis by inhibiting TRPV4.

Cell Calcium 2021 May 25;97:102429. Epub 2021 May 25.

School of Medicine & Holistic Integrative Medicine, Nanjing University of Chinese Medicine, Nanjing, 210023 China. Electronic address:

Psoriasis is an immune-mediated chronic inflammatory skin disease characterized by erythema, scales, and infiltration of the skin, which causes deleterious effects on patient quality of life. TRP channel played important roles in the generation and conductance of itch signal . According to our results, psoriasis induced itch was TRPV4 dependent, and TRPV4 expression in both epidermis and DRG were up-regulated in psoriasis. Thus, TRPV4 is an attractive candidate for treating psoriasis induced itch. Cimifugin is a common compound in antipruritic Chinese medicine. In our study, GSK1016790A, a TRPV4 channel specific agonist, induced acute itch was inhibited by cimifugin in a dose-dependent manner. Furthermore, cimifugin treatment reduced the scratching behavior and reversed the TRPV4 up-regulation induced by psoriasis. In particular, cimifugin decreased GSK1016790A induced calcium response both in HaCaT cells and DRG neurons. Importantly, in TRPV4 transfected HEK293 cells, GSK101 induced calcium response was also significantly inhibited by cimifugin pretreatment. Consistent with our calcium imaging result, cimifugin pretreatment also inhibited GSK101 induced inward currents. Our study delineated a new role of TRPV4 in psoriasis and emphasized the antipruritic effect of cimifugin, which opened a new avenue to itch management in psoriasis.
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http://dx.doi.org/10.1016/j.ceca.2021.102429DOI Listing
May 2021

Natural discoidal lipoproteins with tiny modification for tumor extracellular dissociation in antitumor chemoimmunotherapy.

Biomaterials 2021 May 29;275:120859. Epub 2021 May 29.

State Key Laboratory of Natural Medicines, Department of Pharmaceutics, China Pharmaceutical University, Nanjing, 210009, China; NMPA Key Laboratory for Research and Evaluation of Pharmaceutical Preparations and Excipients, Nanjing, 210009, China. Electronic address:

Appealing cancer immunotherapy requires synchronous presentation of tumor antigens and immunoadjuvant. Herein, a "one-step" modification strategy is proposed to tinily remould endogenous discoidal high density lipoprotein (dHDL) for tumor-homing and site-specific chemoimmunotherapy. For molecular targeting therapy, lipophilic immunoadjuvant CpG oligodeoxynucleotides is conjugated to facilitate HDL-surface anchoring; and GC nucleotides provide enough reservoir for completion of doxorubicin (Dox) "sandwich". After administration, the tiny size (~30 nm) of disc nanodrug can maneuver deeply into tumors for receptor binding and in situ structural collapse. The intracellular concentrated CpG-Dox induce potent immunogenic cell death from burst Dox liberation at acidic pH. In turn, the released antigens and CpG motifs are simultaneously recognized by dendritic cells for antigen presentation and antitumor T cell responses. Combination chemoimmunotherapy with discoidal nanodrugs performed highest tumor weight inhibitory of 93.2% and extend the median survival time at a safe level. Collectively, this study suggests that the minimalist revolution of natural dHDL particulates may provide a biomimicry nanoplatform for site-specific amplified chemoimmunotherapy.
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http://dx.doi.org/10.1016/j.biomaterials.2021.120859DOI Listing
May 2021

Potential of fecal microbiota for detection and postoperative surveillance of colorectal cancer.

BMC Microbiol 2021 May 27;21(1):156. Epub 2021 May 27.

Clinical laboratory of BGI Health, BGI-Shenzhen, Shenzhen, 518083, China.

Background: Colorectal cancer (CRC) is one of the most common cancers. In recent studies, the gut microbiota has been reported to be potentially involved in aggravating or favoring CRC development. However, little is known about the microbiota composition in CRC patients after treatment. In this study, we explored the fecal microbiota composition to obtain a periscopic view of gut microbial communities. We analyzed microbial 16S rRNA genes from 107 fecal samples of Chinese individuals from three groups, including 33 normal controls (NC), 38 CRC patients (Fa), and 36 CRC post-surgery patients (Fb).

Results: Species richness and diversity were decreased in the Fa and Fb groups compared with that of the NC group. Partial least squares discrimination analysis showed clustering of samples according to disease with an obvious separation between the Fa and NC, and Fb and NC groups, as well as a partial separation between the Fa and Fb groups. Based on linear discriminant analysis effect size analysis and a receiver operating characteristic model, Fusobacterium was suggested as a potential biomarker for CRC screening. Additionally, we found that surgery greatly reduced the bacterial diversity of microbiota in CRC patients. Some commensal beneficial bacteria of the intestinal canal, such as Faecalibacterium and Prevotella, were decreased, whereas the drug-resistant Enterococcus was visibly increased in CRC post-surgery group. Meanwhile, we observed a declining tendency of Fusobacterium in the majority of follow-up CRC patients who were still alive approximately 3 y after surgery. We also observed that beneficial bacteria dramatically decreased in CRC patients that recidivated or died after surgery. This revealed that important bacteria might be associated with prognosis.

Conclusions: The fecal bacterial diversity was diminished in CRC patients compared with that in NC. Enrichment and depletion of several bacterial strains associated with carcinomas and inflammation were detected in CRC samples. Fusobacterium might be a potential biomarker for early screening of CRC in Chinese or Asian populations. In summary, this study indicated that fecal microbiome-based approaches could be a feasible method for detecting CRC and monitoring prognosis post-surgery.
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http://dx.doi.org/10.1186/s12866-021-02182-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8157663PMC
May 2021

CryoEM and AI reveal a structure of SARS-CoV-2 Nsp2, a multifunctional protein involved in key host processes.

Res Sq 2021 May 19. Epub 2021 May 19.

The SARS-CoV-2 protein Nsp2 has been implicated in a wide range of viral processes, but its exact functions, and the structural basis of those functions, remain unknown. Here, we report an atomic model for full-length Nsp2 obtained by combining cryo-electron microscopy with deep learning-based structure prediction from AlphaFold2. The resulting structure reveals a highly-conserved zinc ion-binding site, suggesting a role for Nsp2 in RNA binding. Mapping emerging mutations from variants of SARS-CoV-2 on the resulting structure shows potential host-Nsp2 interaction regions. Using structural analysis together with affinity tagged purification mass spectrometry experiments, we identify Nsp2 mutants that are unable to interact with the actin-nucleation-promoting WASH protein complex or with GIGYF2, an inhibitor of translation initiation and modulator of ribosome-associated quality control. Our work suggests a potential role of Nsp2 in linking viral transcription within the viral replication-transcription complexes (RTC) to the translation initiation of the viral message. Collectively, the structure reported here, combined with mutant interaction mapping, provides a foundation for functional studies of this evolutionary conserved coronavirus protein and may assist future drug design.
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http://dx.doi.org/10.21203/rs.3.rs-515215/v1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8142659PMC
May 2021

Correction to: Nrf2 is required to maintain the self-renewal of glioma stem cells.

BMC Cancer 2021 May 21;21(1):582. Epub 2021 May 21.

Department of Neurosurgery in Jinling Hospital, Neurosurgical Institution of People's Liberation Army of China, No. 305, East Zhongshan Road, Nanjing, 210002, Jiangsu, China.

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http://dx.doi.org/10.1186/s12885-021-08338-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8139154PMC
May 2021

Roles of exosomes in cancer chemotherapy resistance, progression, metastasis and immunity, and their clinical applications (Review).

Int J Oncol 2021 Jul 20;59(1). Epub 2021 May 20.

Department of Hematology, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, Anhui 230001, P.R. China.

Exosomes are a type of vesicle that are secreted by cells, with a diameter of 40‑100 nm, and that appear as a cystic shape under an electron microscope. Exosome cargo includes a variety of biologically active substances such as non‑coding RNA, lipids and small molecule proteins. Exosomes can be taken up by neighboring cells upon secretion or by distant cells within the circulatory system, affecting gene expression of the recipient cells. The present review discusses the formation and secretion of exosomes, and how they can remodel the tumor microenvironment, enhancing cancer cell chemotherapy resistance and tumor progression. Exosome‑mediated induction of tumor metastasis is also highlighted. More importantly, the review discusses the manner in which exosomes can change the metabolism of cancer cells and the immune system, which may help to devise novel therapeutic approaches for cancer treatment. With the development of nanotechnology, exosomes can also be used as biomarkers and for the delivery of chemical drugs, serving as a tool to diagnose and treat cancer.
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http://dx.doi.org/10.3892/ijo.2021.5224DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8143748PMC
July 2021

CryoEM and AI reveal a structure of SARS-CoV-2 Nsp2, a multifunctional protein involved in key host processes.

bioRxiv 2021 May 11. Epub 2021 May 11.

The SARS-CoV-2 protein Nsp2 has been implicated in a wide range of viral processes, but its exact functions, and the structural basis of those functions, remain unknown. Here, we report an atomic model for full-length Nsp2 obtained by combining cryo-electron microscopy with deep learning-based structure prediction from AlphaFold2. The resulting structure reveals a highly-conserved zinc ion-binding site, suggesting a role for Nsp2 in RNA binding. Mapping emerging mutations from variants of SARS-CoV-2 on the resulting structure shows potential host-Nsp2 interaction regions. Using structural analysis together with affinity tagged purification mass spectrometry experiments, we identify Nsp2 mutants that are unable to interact with the actin-nucleation-promoting WASH protein complex or with GIGYF2, an inhibitor of translation initiation and modulator of ribosome-associated quality control. Our work suggests a potential role of Nsp2 in linking viral transcription within the viral replication-transcription complexes (RTC) to the translation initiation of the viral message. Collectively, the structure reported here, combined with mutant interaction mapping, provides a foundation for functional studies of this evolutionary conserved coronavirus protein and may assist future drug design.
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http://dx.doi.org/10.1101/2021.05.10.443524DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8132225PMC
May 2021

Inhibitory affinity modulation of FcγRIIA ligand binding by glycosphingolipids by inside-out signaling.

Cell Rep 2021 May;35(7):109142

Department of Pathology, Brigham and Women's Hospital & Harvard Medical School, Boston, MA 02115, USA. Electronic address:

The interaction of the human FcγRIIA with immune complexes (ICs) promotes neutrophil activation and thus must be tightly controlled to avoid damage to healthy tissue. Here, we demonstrate that a fungal-derived soluble β-1,3/1,6-glucan binds to the glycosphingolipid long-chain lactosylceramide (LacCer) to reduce FcγRIIA-mediated recruitment to immobilized ICs under flow, a process requiring high-affinity FcγRIIA-immunoglobulin G (IgG) interactions. The inhibition requires Lyn phosphorylation of SHP-1 phosphatase and the FcγRIIA immunotyrosine-activating motif. β-glucan reduces the effective 2D affinity of FcγRIIA for IgG via Lyn and SHP-1 and, in vivo, inhibits FcγRIIA-mediated neutrophil recruitment to intravascular IgG deposited in the kidney glomeruli in a glycosphingolipid- and Lyn-dependent manner. In contrast, β-glucan did not affect FcγR functions that bypass FcγR affinity for IgG. In summary, we have identified a pathway for modulating the 2D affinity of FcγRIIA for ligand that relies on LacCer-Lyn-SHP-1-mediated inhibitory signaling triggered by β-glucan, a previously described activator of innate immunity.
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http://dx.doi.org/10.1016/j.celrep.2021.109142DOI Listing
May 2021

Design, Synthesis, and Antifungal Activity of 2,6-Dimethyl-4-aminopyrimidine Hydrazones as PDHc-E1 Inhibitors with a Novel Binding Mode.

J Agric Food Chem 2021 Jun 19;69(21):5804-5817. Epub 2021 May 19.

Key Laboratory of Pesticide and Chemical Biology of Ministry of Education, College of Chemistry, Central China Normal University, 152 Luoyu Road, Wuhan 430079, P. R. China.

A series of novel 2,6-dimethyl-4-aminopyrimidine hydrazones were rationally designed and synthesized as pyruvate dehydrogenase complex E1 (PDHc-E1) inhibitors. Compounds strongly inhibited () PDHc-E1 (IC values 0.94-15.80 μM). As revealed by molecular docking, site-directed mutagenesis, enzymatic, and inhibition kinetic analyses, compounds competitively inhibited PDHc-E1 and bound in a "straight" pattern at the PDHc-E1 active site, which is a new binding mode. In antifungal assays, most compounds at 50 μg/mL showed more than 80% inhibition against the mycelial growth of six tested phytopathogenic fungi, including , , , and. Notably, and were 1.8-380 fold more potent against than the commercial fungicides captan and chlorothalonil. , and controlled the growth of comparably to the commercial fungicide tebuconazole. Thus, and have potential commercial value for the control of peach brown rot caused by .
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http://dx.doi.org/10.1021/acs.jafc.0c07701DOI Listing
June 2021

The chloroplast-associated protein degradation pathway controls chromoplast development and fruit ripening in tomato.

Nat Plants 2021 May 18;7(5):655-666. Epub 2021 May 18.

Department of Plant Sciences, University of Oxford, Oxford, UK.

The maturation of green fleshy fruit to become colourful and flavoursome is an important strategy for plant reproduction and dispersal. In tomato (Solanum lycopersicum) and many other species, fruit ripening is intimately linked to the biogenesis of chromoplasts, the plastids that are abundant in ripe fruit and specialized for the accumulation of carotenoid pigments. Chromoplasts develop from pre-existing chloroplasts in the fruit, but the mechanisms underlying this transition are poorly understood. Here, we reveal a role for the chloroplast-associated protein degradation (CHLORAD) proteolytic pathway in chromoplast differentiation. Knockdown of the plastid ubiquitin E3 ligase SP1, or its homologue SPL2, delays tomato fruit ripening, whereas overexpression of SP1 accelerates ripening, as judged by colour changes. We demonstrate that SP1 triggers broader effects on fruit ripening, including fruit softening, and gene expression and metabolism changes, by promoting the chloroplast-to-chromoplast transition. Moreover, we show that tomato SP1 and SPL2 regulate leaf senescence, revealing conserved functions of CHLORAD in plants. We conclude that SP1 homologues control plastid transitions during fruit ripening and leaf senescence by enabling reconfiguration of the plastid protein import machinery to effect proteome reorganization. The work highlights the critical role of chromoplasts in fruit ripening, and provides a theoretical basis for engineering crop improvements.
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http://dx.doi.org/10.1038/s41477-021-00916-yDOI Listing
May 2021

Exploiting Operation Importance for Differentiable Neural Architecture Search.

IEEE Trans Neural Netw Learn Syst 2021 May 17;PP. Epub 2021 May 17.

Recently, differentiable neural architecture search (NAS) methods have made significant progress in reducing the computational costs of NASs. Existing methods search for the best architecture by choosing candidate operations with higher architecture weights. However, architecture weights cannot accurately reflect the importance of each operation, that is, the operation with the highest weight might not be related to the best performance. To circumvent this deficiency, we propose a novel indicator that can fully represent the operation importance and, thus, serve as an effective metric to guide the model search. Based on this indicator, we further develop a NAS scheme for ``exploiting operation importance for effective NAS'' (EoiNAS). More precisely, we propose a high-order Markov chain-based strategy to slim the search space to further improve search efficiency and accuracy. To evaluate the effectiveness of the proposed EoiNAS, we applied our method to two tasks: image classification and semantic segmentation. Extensive experiments on both tasks provided strong evidence that our method is capable of discovering high-performance architectures while guaranteeing the requisite efficiency during searching.
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http://dx.doi.org/10.1109/TNNLS.2021.3072950DOI Listing
May 2021

High-dynamic-resolution optical edge detection based on liquid crystal diffractive moiré lenses with a tunable focal length.

Opt Lett 2021 May;46(10):2549-2552

In this Letter, we experimentally demonstrate liquid crystal-based moiré lenses with a wide and tunable focal length by direct-writing photoalignment. Our moiré lenses, which consist of two cascaded diffractive optical elements, have a large range of refractive power between $\pm 0.85\;{{\rm m}^{- 1}}$ at 532 nm and a mutual rotation between $\pm 90^\circ$ with high diffraction efficiency ($\gt\!{75}\%$). Based on the as-designed moiré lenses, we propose high-dynamic-resolution optical edge detection without any axial shift or substitution of components. The minimum edge width is 13.2 µm and can be adjusted within 100 µm by mutual rotation of this device, which has great potential to be used in adaptive and compact optical systems.
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http://dx.doi.org/10.1364/OL.425427DOI Listing
May 2021

Low-cost compressive sensing imaging based on spectrum-encoded time-stretch structure.

Opt Express 2021 May;29(10):14931-14940

A low-cost compressive sensing imaging (CSI) system based on spectrum-encoded time-stretch (SETS) structure involving cascaded Mach-Zehnder Interferometers (MZIs) for spectral domain random mixing (also known as the optical random pattern generator) is proposed and experimentally demonstrated. A proof-of-principle simulation and experiment is performed. A mode-locked laser with a repetition rate of 50MHz and low-cost cascaded MZIs as the key devices enable fast CSI system. Data compression ratio from 6% to 25% are obtained using proposed CSI based SETS system. The proposed design solves the big data issue in the traditional time-stretch system. It has great potential in fast dynamic phenomena with low-cost and easy-access components.
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http://dx.doi.org/10.1364/OE.421055DOI Listing
May 2021

PD-1 suppresses TCR-CD8 cooperativity during T-cell antigen recognition.

Nat Commun 2021 05 12;12(1):2746. Epub 2021 May 12.

Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology, Atlanta, GA, USA.

Despite the clinical success of blocking its interactions, how PD-1 inhibits T-cell activation is incompletely understood, as exemplified by its potency far exceeding what might be predicted from its affinity for PD-1 ligand-1 (PD-L1). This may be partially attributed to PD-1's targeting the proximal signaling of the T-cell receptor (TCR) and co-stimulatory receptor CD28 via activating Src homology region 2 domain-containing phosphatases (SHPs). Here, we report PD-1 signaling regulates the initial TCR antigen recognition manifested in a smaller spreading area, fewer molecular bonds formed, and shorter bond lifetime of T cell interaction with peptide-major histocompatibility complex (pMHC) in the presence than absence of PD-L1 in a manner dependent on SHPs and Leukocyte C-terminal Src kinase. Our results identify a PD-1 inhibitory mechanism that disrupts the cooperative TCR-pMHC-CD8 trimolecular interaction, which prevents CD8 from augmenting antigen recognition, explaining PD-1's potent inhibitory function and its value as a target for clinical intervention.
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http://dx.doi.org/10.1038/s41467-021-22965-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8115078PMC
May 2021

Neoadjuvant radiotherapy for locoregional Siewert type II gastroesophageal junction adenocarcinoma: A propensity scores matching analysis.

PLoS One 2021 12;16(5):e0251555. Epub 2021 May 12.

Department of General Surgery, Xiangya Hospital, Central South University, Changsha, China.

Objective: To analyze the effect of neoadjuvant radiotherapy (nRT) on prognosis in patients with locoregional Siewert type II gastroesophageal junction adenocarcinoma (GEA).

Method: All patients pathologically diagnosed as Siewert type II GEA between 2004 and 2015 were retrieved from the Surveillance, Epidemiology and Final Results (SEER) database. We analyzed the impact of different treatment regimens on the prognosis in each stage. Survival analysis was performed by Kaplan-Meier (K-M) method. Multivariate Cox model and propensity score matching was further used to verify the results.

Results: 4,160 patients were included in this study. The efficacy of nRT was superior to that of adjuvant radiotherapy (aRT) (p = 0.048), which was the same as that of surgery combined with chemotherapy (p = 0.836), but inferior to the overall survival (OS) of surgical treatment alone (p<0.001) in T1-2N0M0 patients. Patients receiving nRT had distinctly better survival than those receiving surgical treatment alone (p = 0.008), but had similar survival compared with patients treated with aRT (p = 0.989) or surgery combined with chemotherapy (p = 0.205) in the T3N0/T1-3N+M0 subgroup. The efficacy of nRT is clearly stronger than that of surgical therapy alone (p<0.001), surgery combined with chemotherapy (p<0.001), and aRT (p = 0.008) in patients with T4 stage. The survival analysis results were consistent before and after propensity score matching.

Conclusion: In these carefully selected patients, the present study made the following recommendations: nRT can improve the prognosis of patients with T3N0M0/T1-3N+M0 and T4 Siewert type II GEA, and it seems to be a better treatment for T4 patients. Surgery alone seems to be sufficient, and nRT is not conducive to prolonging the survival of Siewert II GEA patients with T1-2N0M0 stage. Of course, further prospective trials are needed to verify this conclusion.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0251555PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8115852PMC
May 2021

Characteristics of biofilm-induced degradation at resin-dentin interfaces using multiple combinations of adhesives and resins.

Dent Mater 2021 May 5. Epub 2021 May 5.

Laboratory of Molecular and Preventive Dentistry, Department of Preventive Dentistry, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, 639 Zhizaoju Road, Huangpu District, Shanghai 200011, China. Electronic address:

Objective: We aimed to evaluate morphological, mechanical and chemical characteristics at resin-dentin interfaces using multiple combinations of adhesives and resins after a short-term biofilm-induced degradation.

Methods: Cervical cavities were prepared in bovine incisors, treated by Clearfil SE Bond 2 (SE) or FL-Bond II (FL), restored by Clearfil Majesty ES Flow (ES) or Beautifil Flow Plus (BFP) and grouped into SE-ES, SE-BFP, FL-ES and FL-BFP. After biofilm challenge, interfacial gaps and dentin wall lesions were examined by optical coherence tomography (OCT). Gap depth (GD), gap pattern scale (GPS) and dentin wall lesion depth (WLD) were evaluated from confocal laser scanning microscope. Microhardness of dentin lesions was measured with a Vickers microhardness tester. Chemical elements in resins and dentin wall lesions were analyzed by scanning electron microscopy and energy dispersive X-ray spectrometry (SEM/EDS). Morphological structures of interfacial gaps were observed by SEM.

Results: OCT could detect adhesive-dentin-bonded and adhesive-dentin-debonded gaps. SE-containing groups showed significantly lower GPS than FL-containing groups. FL-BFP showed significantly lower WLD than FL-ES. Microhardness of dentin wall lesions was higher than that of outer lesions and they showed significant differences in FL-BFP. SE-BFP showed a lower GPS curve and higher intensities of Ca and P in the upper half of dentin wall lesions than other groups. From SEM, microgaps between filler and matrix, break and loss of matrix, separation of adhesive matrix with hybrid layer occurred at interfacial gaps.

Significance: The morphological, mechanical and chemical characteristics of resin-dentin interfacial degradation depend on the component and chemistry of restorative materials.
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http://dx.doi.org/10.1016/j.dental.2021.04.007DOI Listing
May 2021

Ultrafast Flame-Induced Pyrolysis of Poly(dimethylsiloxane) Foam Materials toward Exceptional Superhydrophobic Surfaces and Reliable Mechanical Robustness.

ACS Appl Mater Interfaces 2021 May 6;13(19):23161-23172. Epub 2021 May 6.

Key Laboratory of Organosilicon Chemistry and Material Technology of MoE, College of Material, Chemistry and Chemical Engineering, Hangzhou Normal University, Hangzhou 311121, P. R. China.

Superhydrophobic surfaces are imperative in flexible polymer foams for diverse applications; however, traditional surface coatings on soft skeletons are often fragile and can hardly endure severe deformation, making them unstable and highly susceptible to cyclic loadings. Therefore, it remains a great challenge to balance their mutual exclusiveness of mechanical robustness and surface water repellency on flexible substrates. Herein, we describe how robust superhydrophobic surfaces on soft poly(dimethylsiloxane) (PDMS) foams can be achieved using an extremely simple, ultrafast, and environmentally friendly flame scanning strategy. The ultrafast flame treatment (1-3 s) of PDMS foams produces microwavy and nanosilica rough structures bonded on the soft skeletons, forming robust superhydrophobic surfaces (i.e., water contact angles (WCAs) > 155° and water sliding angles (WSAs) < 5°). The rough surface can be effectively tailored by simply altering the flame scanning speed (2.5-15.0 cm/s) to adjust the thermal pyrolysis of the PDMS molecules. The optimized surfaces display reliable mechanical robustness and excellent water repellency even after 100 cycles of compression of 60% strain, stretching of 100% strain, and bending of 90° and hostile environmental conditions (including acid/salt/alkali conditions, high/low temperatures, UV aging, and harsh cyclic abrasion). Moreover, such flame-induced superhydrophobic surfaces are easily peeled off from ice and can be healable even after severe abrasion cycles. Clearly, the flame scanning strategy provides a facile and versatile approach for fabricating mechanically robust and surface superhydrophobic PDMS foam materials for applications in complex conditions.
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http://dx.doi.org/10.1021/acsami.1c03272DOI Listing
May 2021

RO4929097 regulates RANKL-induced osteoclast formation and LPS-mediated bone resorption.

Aging (Albany NY) 2021 05 2;13(9):12526-12536. Epub 2021 May 2.

Department of Orthopaedics, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.

To investigate the suppressive function of RO4929097, a potent -secretase inhibitor, on RANKL-induced osteoclastogenesis. The cytotoxicity of RO4929097 was evaluated. The suppressive effect and possible molecular mechanism of RO4929097 on RANKL-induced osteoclastogenesis was evaluated both and . The IC50 of RO4929097 was 2.93 μM. Treatment with different doses of RO4929097 (100 nM, 200 nM, and 400 nM) effectively reduced osteoclast formation (number and resorption area) in a dose-dependent manner. The qPCR results revealed that RO4929097 attenuates RANKL-induced osteoclast formation and NFATc1 protein expression. The experiments demonstrated that RO4929097 had an inhibitory effect on LPS-induced bone resorption. Our experiments showed that RO4929097 can potently inhibit osteoclastogenesis and bone resorption by down-regulating the Notch/MAPK/JNK/Akt-mediated reduction of NFATc1. In accordance with these observations, RO4929097 attenuated LPS-induced osteolysis in mice. In conclusion, our findings indicate that Notch may represent a potential therapeutic target for the treatment of osteolytic diseases.
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http://dx.doi.org/10.18632/aging.202926DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8148457PMC
May 2021

Electro-optically tunable microring laser monolithically integrated on lithium niobate on insulator.

Opt Lett 2021 May;46(9):2127-2130

We demonstrate monolithic integration of an electro-optically (EO) tunable microring laser on lithium niobate on insulator (LNOI) platform. The device is fabricated by photolithography assisted chemo-mechanical etching, and the pump laser is evanescently coupled into the erbium (${\rm{E}}{{\rm{r}}^{3 +}}$)-doped lithium niobate (LN) microring laser using an undoped LN waveguide mounted above the microring. The quality factor of the LN microring resonator is measured as high as ${1.54} \times {{1}}{{{0}}^5}$ at the wavelength of 1542 nm. Lasing action can be observed at a pump power threshold below 3.5 mW using a 980 nm continuous-wave pump laser. Finally, tuning of the laser wavelength is achieved by varying the electric voltage on the microelectrodes fabricated in the vicinity of a microring waveguide, showing an EO coefficient of 0.33 pm/V.
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http://dx.doi.org/10.1364/OL.424996DOI Listing
May 2021

Role of HEART score in evaluating clinical outcomes among emergency department patients with different ethnicities.

J Int Med Res 2021 Apr;49(4):3000605211010638

Department of Emergency Medicine, JPS Health Network, 1500 S. Main St., Fort Worth, TX, USA.

Objective: We aimed to examine the role of the HEART (history, EKG, age, risk factors, and troponin) score in the evaluation of six clinical outcomes among three groups of patients in the emergency department (ED).

Methods: We performed a retrospective observational study among three ED patient groups including White, Black, and Hispanic patients. ED providers used the HEART score to assess the need for patient hospital admission and for emergent cardiac imaging tests (CITs). HEART scores were measured using classification accuracy rates. Performance accuracies were measured in terms of HEART score in relation to four clinical outcomes (positive findings of CITs, ED returns, hospital readmissions, and 30-day major adverse cardiac events [MACE]).

Results: A high classification accuracy rate (87%) was found for use of the HEART score to determine hospital admission. HEART scores showed moderate accuracy (area under the receiver operating characteristic curve 0.66-0.78) in predicting results of emergent CITs, 30-day hospital readmissions, and 30-day MACE outcomes.

Conclusions: Providers adhered to use of the HEART score to determine hospital admission. The HEART score may be associated with emergent CIT findings, 30-day hospital readmissions, and 30-day MACE outcomes, with no differences among White, Black, and Hispanic patient populations.
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http://dx.doi.org/10.1177/03000605211010638DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8113935PMC
April 2021

Palladium(II)-catalyzed aerobic oxidative O-H/C-H isocyanide insertion: facile access to pyrrolo[2,1-][1,4]benzoxazine derivatives.

Org Biomol Chem 2021 May;19(19):4364-4368

Sichuan Research Center for Drug Precision Industrial Technology, West China School of Pharmacy, Sichuan University, Chengdu, 610041, China. and Engineering Center of Catalysis and synthesis for Chiral Molecules, Department of chemistry, Fudan University, Shanghai, 200433, China. [email protected] fudan.edu.cn.

Palladium-catalyzed aerobic oxidative cyclizations of substituted 2-(1H-pyrrol-1-yl)phenols with isocyanides via an O-H/C-H insertion cascade have been developed. This strategy provides facile access to pyrrolo[2,1-c][1,4]benzoxazine derivatives in good to excellent yields under an O2 atmosphere. The notable features of this protocol include its mild reaction conditions, atom-economy, and broad functional group tolerance.
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http://dx.doi.org/10.1039/d1ob00393cDOI Listing
May 2021

Single-cell transcriptome and genome analyses of pituitary neuroendocrine tumors.

Neuro Oncol 2021 Apr 28. Epub 2021 Apr 28.

Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing, 100070, China.

Background: Pituitary neuroendocrine tumors (PitNETs) are the second most common intracranial tumor. We lacked a comprehensive understanding of the pathogenesis and heterogeneity of these tumors.

Methods: We performed high-precision single-cell RNA sequencing for 2,679 individual cells obtained from 23 surgically resected samples of the major subtypes of PitNETs from 21 patients. We also performed single-cell multi-omics sequencing for 238 cells from 5 patients.

Results: Unsupervised clustering analysis distinguished all tumor subtypes, which was in accordance with the classification based on immunohistochemistry and provided additional information. We identified three normal endocrine cell types: somatotrophs, lactotrophs and gonadotrophs. Comparisons of tumor and matched normal cells showed that differentially expressed genes of gonadotroph tumors were predominantly downregulated, while those of somatotroph and lactrotroph tumors were mainly upregulated. We identified novel tumor-related genes, such as AMIGO2, ZFP36, BTG1 and DLG5. Tumors expressing multiple hormone genes showed little transcriptomic heterogeneity. Furthermore, single-cell multi-omics analysis demonstrated that the tumor shad a relatively uniform pattern of genome with slight heterogeneity in copy number variations.

Conclusions: Our single-cell transcriptome and single-cell multi-omics analyses provide novel insights into the characteristics and heterogeneity of these complex neoplasms for the identification of biomarkers and therapeutic targets.
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http://dx.doi.org/10.1093/neuonc/noab102DOI Listing
April 2021

JAK/STAT pathway promotes the progression of diabetic kidney disease via autophagy in podocytes.

Eur J Pharmacol 2021 Jul 24;902:174121. Epub 2021 Apr 24.

Department of Clinical Pharmacy, The Second Aliated Hospital, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, PR China. Electronic address:

Diabetic kidney disease (DKD) is one of the major microvascular complications of diabetes and an important cause of end-stage renal disease. Previous studies have shown that the damage to podocyte autophagy is related to the pathogenesis of DKD, and this damage is closely mediated by the Janus kinase (JAK)/signal transductors and the transcription (STAT) signaling pathway. Here, the underlying molecular mechanism of the JAK/STAT signaling pathway regulating podocyte autophagy was investigated. In the present study, compared to controls, DKD mice showed glomerular hypertrophy, increased kidney weight/weight ratio, and increased urinary protein levels, as well as decreased desmin and synaptopodin expression. Meanwhile, levels of triglyceride, total cholesterol, reduced glutathione, and malondialdehyde were also increased in the serum of DKD mice. Further, a lower number of autophagosomes, reduced expression of MAP1LC3 (LC3) in glomeruli, and increased expression of JAK/STAT pathway-related proteins, namely JAK1, JAK2, STAT1, STAT3, STAT5, and STAT6, were observed in DKD mice. In the in vitro experiments, we observed impaired autophagy, enhanced apoptosis, and activated JAK/STAT pathway in podocytes under high glucose conditions. Studies using ruxolitinib inhibitors have showed that suppression of the JAK/STAT pathway in podocytes subjected to high glucose could increase autophagic flux and autophagy-related protein expression. Taken together, the present study demonstrates that high glucose inhibits autophagy by activating the JAK/STAT pathway in mice and podocytes, thereby preventing the efficient removal of damaged proteins and organelles from the body to prevent apoptosis, and ultimately aggravating the progression of podocyte injury and DKD.
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http://dx.doi.org/10.1016/j.ejphar.2021.174121DOI Listing
July 2021

Integration of evidence across human and model organism studies: A meeting report.

Genes Brain Behav 2021 Apr 23:e12738. Epub 2021 Apr 23.

Department of Psychiatry, Yale University School of Medicine, West Haven, Connecticut, USA.

The National Institute on Drug Abuse and Joint Institute for Biological Sciences at the Oak Ridge National Laboratory hosted a meeting attended by a diverse group of scientists with expertise in substance use disorders (SUDs), computational biology, and FAIR (Findability, Accessibility, Interoperability, and Reusability) data sharing. The meeting's objective was to discuss and evaluate better strategies to integrate genetic, epigenetic, and 'omics data across human and model organisms to achieve deeper mechanistic insight into SUDs. Specific topics were to (a) evaluate the current state of substance use genetics and genomics research and fundamental gaps, (b) identify opportunities and challenges of integration and sharing across species and data types, (c) identify current tools and resources for integration of genetic, epigenetic, and phenotypic data, (d) discuss steps and impediment related to data integration, and (e) outline future steps to support more effective collaboration-particularly between animal model research communities and human genetics and clinical research teams. This review summarizes key facets of this catalytic discussion with a focus on new opportunities and gaps in resources and knowledge on SUDs.
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http://dx.doi.org/10.1111/gbb.12738DOI Listing
April 2021

Ratiometric Fluorescent DNA Nanostructure for Mitochondrial ATP Imaging in Living Cells Based on Hybridization Chain Reaction.

Anal Chem 2021 05 22;93(17):6715-6722. Epub 2021 Apr 22.

State Key Laboratory of Chemo/Biosensing and Chemometrics, College of Chemistry and Chemical Engineering, Key Laboratory for Bio-Nanotechnology and Molecular Engineering of Hunan Province, Hunan University, Changsha 410082, China.

For intracellular molecular detection, the appropriate probes should include the abilities to enter target cells noninvasively, target specific sites, and then respond to the analytes reliably. Herein, a ratiometric fluorescent DNA nanostructure (RFDN) was designed for mitochondrial adenosine triphosphate (ATP) imaging in living cells. The DNA nanostructure was constructed by continuous hybridization of two hairpin DNA strands (HS1-Cy3 and HS2-Cy5) under the initiation of the trigger. HS1-Cy3 and HS2-Cy5 contained split aptamer fragments of ATP and are labeled with a fluorescent donor (Cy3) and acceptor (Cy5), respectively. The RFDN integrated multiple split aptamer fragments and increased the local concentration of sensing probes. The binding of ATP to aptamer fragments on the RFDN shortened the distance between Cy3 and Cy5, resulting in obvious ratiometric signals (fluorescence resonance energy transfer). The RFDN showed good biocompatibility and can be internalized into cells in a caveolin-dependent endocytosis pathway. The co-localization imaging results indicated that the DNA nanostructure could target the mitochondria Cy3 and Cy5. Moreover, the confocal imaging results showed that the intracellular ATP changes stimulated by drugs in living cells could be indicated by the RFDN. In this way, the RFDN is expected to be a simple, flexible, and general platform for chemo/biosensing in living cells.
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http://dx.doi.org/10.1021/acs.analchem.1c00176DOI Listing
May 2021

Utilising multi-large omics data to elucidate biological mechanisms within multiple sclerosis genetic susceptibility loci.

Mult Scler 2021 Apr 19:13524585211004422. Epub 2021 Apr 19.

Menzies Institute for Medical Research, University of Tasmania, Hobart, TAS, Australia.

Background: Genome-wide association studies (GWAS) have succeeded in identifying over 200 susceptibility loci for multiple sclerosis (MS). However, the potential functional variants and the mechanisms by which these loci affect MS risk remain largely unexplained.

Objectives: We used summary data-based Mendelian randomisation to prioritise risk genes and infer potential biological mechanisms for MS risk loci.

Methods: The data used consisted of DNA methylation ( = 1980) QTL (mQTL) and gene expression ( = 31,684) QTL (eQTL) derived from whole blood as well as MS GWAS summary statistics (14,802 cases, 26,703 controls). The findings were further evaluated using data derived from independent brain mQTL ( = 1160) and eQTL ( = 1194).

Results: In whole blood, we identified two independent genomic loci (lincRNA: and ) with consistent genome-wide significant pleiotropic associations across different omics layers. In brain tissue, a similar effect for the locus was observed but not for , indicating a potential tissue-specific effect for the locus.

Conclusion: We provide in silico evidence for the putative biological mechanisms by which the identified DNA methylation sites and target genes are functionally relevant to MS development in different tissues. Future research targeting these genes and DNA methylation sites will determine their roles in the pathophysiology of MS.
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http://dx.doi.org/10.1177/13524585211004422DOI Listing
April 2021

Has the increase in the regional nodes evaluated improved survival rates for patients with locoregional colon cancer?

J Cancer 2021 5;12(9):2513-2525. Epub 2021 Mar 5.

Department of General Surgery, Xiangya Hospital, Central South University, Changsha, China.

The guidelines for colon cancer surgery have been evolving over the past three decades. The advances in colectomy have focused mainly on the number of regional nodes evaluated (RNE). Data in this retrospective analysis were extracted from the Surveillance, Epidemiology, and End Results (SEER) linked database. Rapid growth of RNE (the median rising from 10 (6-16) to 17 (13-23)) occurred from 2000 to 2009. The rate of colon cancer patients with positive lymph nodes following colectomy was greatly decreasing only in the group with RNE greater than 12 after 2000. Patients with T4 and/or N+ cannot obtain survival benefit from the increasing trend of RNE. The apparent survival benefit for T1-3N0 patients may result from augmented false negatives in patients from previous periods. The golden period of surgical development in colon cancer, using RNE as an alternative indicator, occurred in the first decade of the 21st century. Although a more extensive lymph node evaluation is able to reduce the risk of underestimated staging, the increase of RNE does not provide survival benefits for locoregional colon cancer. A proper reduction in the scope of lymph node dissection may be reasonable in radical surgery for colon cancer.
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http://dx.doi.org/10.7150/jca.52352DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8040710PMC
March 2021

The impact of COVID-19 on body-dissatisfied female university students.

Int J Eat Disord 2021 Apr 13. Epub 2021 Apr 13.

College of Education Psychology & Social Work, Flinders University, Adelaide, South Australia, Australia.

Objective: This study investigated the impact of COVID-19 on young women's disordered eating and their responses to online interventions to reduce disordered eating.

Method: University students at risk of developing an eating disorder (N = 100) were randomly assigned to either receiving an online intervention to reduce disordered eating or not. Forty-one participants entered the study from September 2019 to March 2020 (pre-COVID) and 59 after physical distancing was introduced due to COVID pandemic (during COVID). Online assessments were conducted at baseline and 1-week follow up.

Results: There was a significant increase in weight concerns, disordered eating, and negative affect among participants entering the trial during COVID compared to pre-COVID. The increases in the first two variables remained when adjusting for baseline negative affect. No significant interactions between time, condition and COVID status were observed.

Discussion: Young women experienced increased levels of disordered eating after the onset of COVID. While no interactions with COVID were detected, changes to within-group effect sizes for disordered eating more than doubled for both online interventions and assessment from pre-COVID to during COVID, suggesting any attention to issues related to disordered eating in the context of reduced social contact may be beneficial.
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http://dx.doi.org/10.1002/eat.23521DOI Listing
April 2021