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High quality-factor (Q) optical resonators are a key component for ultra-narrow linewidth lasers, frequency stabilization, precision spectroscopy and quantum applications. Integration in a photonic waveguide platform is key to reducing cost, size, power and sensitivity to environmental disturbances. However, to date, the Q of all-waveguide resonators has been relegated to below 260 Million. Here, we report a Si3N4 resonator with 422 Million intrinsic and 3.4 Billion absorption-limited Qs. The resonator has 453 kHz intrinsic, 906 kHz loaded, and 57 kHz absorption-limited linewidths and the corresponding 0.060 dB m−1 loss is the lowest reported to date for waveguides with deposited oxide upper cladding. These results are achieved through a careful reduction of scattering and absorption losses that we simulate, quantify and correlate to measurements. This advancement in waveguide resonator technology paves the way to all-waveguide Billion Q cavities for applications including nonlinear optics, atomic clocks, quantum photonics and high-capacity fiber communications.

Zhiru Xiu,1 Yiquan Li,1 Jinbo Fang,1 Jicheng Han,1 Shanzhi Li,1 Yaru Li,1,2 Xia Yang,1 Gaojie Song,3 Yue Li,1 Ningyi Jin,1,4,5 Yilong Zhu,1 Guangze Zhu,1 Lili Sun,6 Xiao Li1,4,7 1Academician Workstation of Jilin Province, Changchun University of Chinese Medicine, Changchun, People’s Republic of China; 2Medical College, Yanbian University, Yanji, People’s Republic of China; 3Medical College, Jiujiang· University, Jiujiang, People’s Republic of China; 4Changchun Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Changchun, People’s Republic of China; 5Jiangsu Co-Innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou, People’s Republic of China; 6Department of Head and Neck Surgery, Tumor Hospital of Jilin Province, Changchun, People’s Republic of China; 7College of Life Sciences, Shandong Normal University, Jinan, People’s Republic of ChinaCorrespondence: Lili Sun; Xiao Li, Boshuo Road, 1035, Jingyue Economic & Technological Development Zone, Changchun, Jilin, 130122, People’s Republic of China, Tel +86-431-86985923, Fax +86-431-87985861, Email skylee6226@163.com; linjiaxiaoya@163.comObjective: To explore the effects of Esculetin on liver cancer and explore potential mechanisms of Esculetin-inducing cells death.Methods: Esculetin’s effects on the proliferation, migration and apoptosis of HUH7 and HCCLM3 cells were detected by using CCK8, crystal violet staining, wound healing, TranswellTM and Annexin V-FITC/PI. Flow cytometry, fluorescence staining, Western blot, T-AOC, DPPH radical scavenging assay, hydroxyl radical’s inhibitory capability and GSH test were used to examine the esculetin’s effects on the ROS level, the oxidation-related substances and proteins’ expression in hepatoma cells. In vivo experiment was performed by xenograft model. Ferrostatin-1 was used to determine the death way of hepatoma cells induced by esculetin. Live cell probe, Western blot, Fe2+ content, MDA, HE staining, Prussian blue staining and immunohistochemistry were used to examine the ferritinophagy-related phenomenon induced by esculetin in hepatoma cells. The relationship between esculetin and NCOA4-mediated ferritinophagy was confirmed through gene silence and overexpression, immunofluorescence staining and Western blot.Results: Esculetin suppressed the proliferation, migration and apoptosis of HUH7 and HCCLM3 cells significantly, influenced the oxidative stress level, altered the autophagy and iron metabolism levels in cells, and produced a ferritinophagy-related phenomena. Esculetin increased the levels of cellular lipid peroxidation and reactive oxygen species. In vivo, esculetin could decrease tumour volume, promote LC3 and NCOA4 expressions, suppresse hydroxyl radical‘s inhibiting capacity and GSH, increase Fe2+ and MDA levels, decrease antioxidant proteins expression in tumour tissue. In addition, Esculetin could also increase the iron deposition of tumour tissues, promote ferritinophagy, and induce tumours’ ferroptosis.Conclusion: Esculetin has an inhibitory effect on liver cancer in vivo and in vitro through triggering NCOA4 pathway-mediation ferritinophagy.Keywords: esculetin, ferritinophagy, liver cancer, anti-tumour, NCOA4

Jing Wang,1 Shuting Zuo,1 Yan Zhang,1 Shanzhi Li,2 Ying Shi,1 Tonghua Du,1 Jicheng Han,2 Ningyi Jin,2– 4 Yiquan Li,2 Xiao Li2,3 1Department of Breast Surgery, The Second Hospital of Jilin University, Changchun, 130000, People’s Republic of China; 2Academician Workstation of Jilin Province, Changchun University of Chinese Medicine, Changchun, 130117, People’s Republic of China; 3Changchun Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Changchun, 130122, People’s Republic of China; 4Jiangsu Co-innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou, 225009, People’s Republic of ChinaCorrespondence: Yiquan Li; Xiao Li, Academician Workstation of Jilin Province, Changchun University of Chinese Medicine, Liuying West Road, 666, Jingyue Economic & Technological Development Zone, Changchun, People’s Republic of China, Tel +86-431-86985923, Fax +86-431-87985861, Email 905381255@qq.com; 1077614276@qq.comPurpose: Oncolytic virus therapy has gradually become an integral approach in cancer treatment. We explored the therapeutic effects of the combination of a dual cancer-selective anti-tumor recombinant adenovirus (Ad-Apoptin-hTERTp-E1a) and cyclophosphamide on breast cancer cells.Methods: The inhibition of MCF-7 and MDA-MB-231 breast cancer cells by Ad-Apoptin-hTERTp-E1a (Ad-VT), cyclophosphamide, and Ad-VT + Cyclophosphamide was investigated using the CCK-8 assay. The combination index (CI) was calculated using CalcuSyn software to determine the best combination based on the inhibition rates of the different treatment combinations. The CCK-8 assay and crystal violet staining were used to detect the cytotoxicity of the combined Ad-VT and cyclophosphamide in breast cancer cells and breast epithelial cells. Subsequently, Hoechst staining, annexin V flow cytometry, and JC-1 staining were used to analyze the inhibitory pathway of Ad-VT plus cyclophosphamide on breast cancer cells. Cell migration and invasion of breast cancer cells were assessed using the cell-scratch and Transwell assays. The anti-tumor effects of different treatment groups in a tumor-bearing nude mouse model also were analyzed.Results: The treatment combination of Ad-VT (40 MOI) and cyclophosphamide (400 μM) significantly inhibited MCF-7 and MDA-MB-231 cells and reduced the toxicity of cyclophosphamide in normal cells. Ad-VT primarily induced breast cancer cell apoptosis through the endogenous apoptotic pathway. Apoptosis was significantly increased after treatment with Ad-VT plus cyclophosphamide. The combination significantly inhibited the migration and invasion of MCF-7 and MDA-MB-231 cells. The in vivo experiments demonstrated that exposure to Ad-VT plus cyclophosphamide significantly inhibited tumor growth and extended the survival time of the nude mice.Conclusion: Ad-VT plus cyclophosphamide reduced toxicity and exhibited increased efficacy in treating breast cancer cells.Keywords: cyclophosphamide, recombinant adenovirus, breast cancer, synergy, toxicity

Accurately predicting the lifetime of complex, nonlinear systems such as lithium-ion batteries is critical for accelerating technology development. However, diverse aging mechanisms, significant device variability and dynamic operating conditions have remained major challenges. We generate a comprehensive dataset consisting of 124 commercial lithium iron phosphate/graphite cells cycled under fast-charging conditions, with widely varying cycle lives ranging from 150 to 2,300 cycles. Using discharge voltage curves from early cycles yet to exhibit capacity degradation, we apply machine-learning tools to both predict and classify cells by cycle life. Our best models achieve 9.1% test error for quantitatively predicting cycle life using the first 100 cycles (exhibiting a median increase of 0.2% from initial capacity) and 4.9% test error using the first 5 cycles for classifying cycle life into two groups. This work highlights the promise of combining deliberate data generation with data-driven modelling to predict the behaviour of complex dynamical systems.

Yu Tian,1,2,* Lei Zhang,3,* Nenghao Jin,1,2,* Zhiyi Wan,3 Henghui Zhang,4,5 Haizhong Zhang,2 Lei Zhang2 1Department of Stomatology, Medical School of Chinese PLA, Beijing, People’s Republic of China; 2Department of Stomatology, The First Medical Center, Chinese PLA General Hospital, Beijing, People’s Republic of China; 3Department of Medicine, Genecast Biotechnology Co., Ltd, Wuxi, Jiangsu, People’s Republic of China; 4Biomedical Innovation Center, Beijing Shijitan Hospital, Capital Medical University, Beijing, People’s Republic of China; 5Ninth School of Clinical Medicine, Peking University, Beijing, China; School of Oncology, Capital Medical University, Beijing, People’s Republic of China*These authors contributed equally to this workCorrespondence: Haizhong Zhang; Lei Zhang, Department of Stomatology, The First Medical Center, Chinese PLA General Hospital, No. 28, Fuxing Road, Beijing, People’s Republic of China, Tel/Fax +86 1066938316, Email zhang126301@126.com; okdental@163.comAbstract: Immune checkpoint inhibitors (ICIs) pembrolizumab and nivolumab have been approved for the treatment of head and neck squamous cell carcinoma (HNSCC) and used in neoadjuvant immunotherapy in clinical trials. However, combination of ICIs with targeted therapy and chemotherapy was rarely used in pre-surgical HNSCC patients. Herein, we encountered three cases of patients with oral squamous cell carcinoma (OSCC) who all had good responses to neoadjuvant immunotherapy (anti-PD-1 inhibitors) combined with nimotuzumab (anti-EGFR monoclonal antibody) plus paclitaxel. Both Case 1 and Case 2 underwent the same neoadjuvant therapeutic combination (nivolumab, nimotuzumab and paclitaxel) and exhibited a marked tumor shrinkage even complete disappearance by radiological evaluation. Moreover, pathological response was observed in post-surgical tissues of Case 1. Additionally, Case 3 with tongue squamous cell carcinoma also had satisfactory tumor regression (complete healing of his tongue ulcer upon treatment) after receiving similar neoadjuvant therapy with sintilimab (another PD-1 inhibitor), nimotuzumab and paclitaxel. We characterized their potential causes behind favorable treatment outcomes. While there were differences in driver mutations and tumor mutation burden (TMB) identified in pre-treatment tumor tissues among the three patients, numerous CD68+ (macrophages) infiltrates were common for all the cases. Of note, the majority (> 80%) of the total macrophages were molecularly defined as PD-L1-positive macrophages. Given the high expression of PD-L1 in macrophages is associated with better immunotherapy outcomes, we propose that the high proportion of CD68+PD-L1+ cells in total macrophages alone could serve as a promising biomarker for neoadjuvant immunotherapy in combination with other therapies in HNSCC.Keywords: head and neck squamous cell carcinoma, oral squamous cell carcinoma, neoadjuvant immunotherapy, PD-L1, CD68, macrophage

In this work, ZnO-CuO core-shell hybrid nanospheres with well-crystalline wurzite ZnO core and monoclinic CuO shell were successfully synthesized through a two-stage solution process. The as-prepared nanocomposites were carefully characterized by X-ray diffraction (XRD), transmission electron microscopy (TEM), high-resolution transmission electron microscopy (HRTEM), and UV/Vis diffuse reflection spectroscopy (DRS). Compared with bare ZnO cores, the ZnO-CuO core-shell 0-dimensional nanocomposites had greatly enhanced absorption strength and dramatically broadened optical response ranging from near-ultraviolet to visible light, which was probably attributed to heterojunction between n-ZnO core and p-CuO shell and defects originated from synthetic procedure. The as-synthesized p-CuO/n-ZnO core-shell hybrid structure may lead to tantalizing applications including solar energy materials, LED and optical sensor.

Yong Tao,1 Danping Yuan,1 Hongshuang Pang,1 Hongbiao Wu,1 Dongfang Liu,1 Ningning Jin,1 Ningning Wu,1 Jianming Qiu,2 Yuepeng Cao11Department of Colorectal Surgery, Ningbo City First Hospital, Ningbo, Zhejiang, 86-315000, People’s Republic of China; 2Department of Colorectal Surgery, Hangzhou Third People’s Hospital, Hangzhou, 86-310009, People’s Republic of ChinaBackground: Inflammatory cellular response is implicated in the pathogenesis of colorectal cancer (CRC). Nevertheless, the dynamic effects of inflammatory index coNLR (neutrophil-to-lymphocyte ratio)-PLR (platelet-to-lymphocyte ratio) during chemotherapy remain elusive.Methods: The baseline clinical data and laboratory parameters of 480 CRC patients who received palliative resection of primary tumors and FOLFOX-based chemotherapy from January 2007 to January 2013 were retrospectively analyzed. Receiver operating characteristic curves were plotted to obtain the predictive NLR and PLR values, and to calculate the coNLR-PLR score. The Kaplan–Meier method was used to estimate the rates of recurrence-free survival (RFS) and overall survival (OS), and the Cox proportional hazards model was employed for analysis.Results: The dynamic cut-off values of NLR during four periods of chemotherapy were 3.029, 2.466, 2.102 and 1.795, respectively, and those of PLR were 216.438, 187.572, 169.027 and 174.368, respectively. A higher coNLR-PLR was significantly associated with lower rates of RFS and OS (P

Differentiated services can ensure that traffic on some codepoints receives higher quality of service (QoS) than traffic on other codepoints, but without additional mechanisms it cannot target any particular QoS. Congestion-based pricing has been suggested as a method to target QoS in other network architectures. Here, we investigate whether congestion-based pricing can be used to control aggregate traffic into each codepoint by motivating users to choose the codepoints appropriate for each application.We first ask what information needs to be exchanged; we assert that both price and QoS information must be available for users to make decisions. We then ask how effective congestion- based pricing in diffServ can be; we find that it is feasible only for networks with sufficiently high bandwidth to guarantee that QoS can be quickly measured.

In this paper, the recently proposed patch antenna with switchable slot (PASS) concept is implemented to design a novel reconfigurable antenna with both frequency and polarization diversities. Using only one switch and a single patch, the antenna operates at 4.20 GHz with right-handed circular polarization and at 4.55 GHz with left-handed circular polarization. The fabricated antenna has both an acceptable return loss and a broadside axial ratio (AR) lower than 2 dB at each operation frequency. The frequency and polarization diversities of this design could potentially improve the reliability of wireless communication systems.

This paper presents a novel evolutionary optimization methodology for multiband and wide-band patch antenna designs. The particle swarm optimization (PSO) and the finite-difference time-domain (FDTD) are combined to achieve the optimum antenna satisfying a certain design criterion. The antenna geometric parameters are extracted to be optimized by PSO, and a fitness function is evaluated by FDTD simulations to represent the performance of each candidate design. The optimization process is implemented on parallel clusters to reduce the computational time introduced by full-wave analysis. Two examples are investigated in the paper: first, the design of rectangular patch antennas is presented as a test of the parallel PSO/FDTD algorithm. The optimizer is then applied to design E-shaped patch antennas. It is observed that by using different fitness functions, both dual-frequency and wideband antennas with desired performance are obtained by the optimization. The optimized E-shaped patch antennas are analyzed, fabricated, and measured to validate the robustness of the algorithm. The measured less than - 18 dB return loss (for dual-frequency antenna) and 30.5% bandwidth (for wide-band antenna) exhibit the prospect of the parallel PSO/FDTD algorithm in practical patch antenna designs.

Hongming Zhang, Runzhe Chen, Jian Cheng, Nan Jin, Baoan Chen Department of Hematology and Oncology (Key Department of Jiangsu Medicine), Zhongda Hospital, Medical School, Southeast University, Nanjing, Jiangsu Province, People’s Republic of China Purpose: The aim of this systematic review was to evaluate the efficacy and safety of extracorporeal photopheresis (ECP) treatment in patients with steroid-refractory acute graft-versus-host disease (SR-aGVHD).Methods: An electronic search was carried out on the MEDLINE, EMBASE, Science Citation Index (SCI), and Cochrane Library databases. We included prospective clinical trials in SR-aGVHD treated by ECP. The main endpoints consisted of mortality, exacerbation, or response.Results: Only seven studies involving 121 patients met the inclusion criteria for further review. Our analysis showed positive results of ECP for aGVHD. The overall response rate (ORR) was 0.71 and the complete response rate (CRR) was 0.71. The efficacy of ECP for skin aGVHD, liver aGVHD, and gut aGVHD were 0.86, 0.60, and 0.68, respectively. However, no sufficient evidence verifies the exact benefit in this review, because the number of patients enrolled in trials is limited and publish bias exists.Conclusion: ECP is an effective therapy for skin, liver, and gut aGVHD, and large double-blind clinical trials are required to prove the outcome of this meta-analysis. Keywords: extracorporeal photopheresis, steroid-refractory acute graft-versus-host disease, allogeneic hematopoietic stem cell transplantation

Run-Zhe Chen,* Gang Zhao,* Nan Jin, Bao-An Chen, Jia-Hua Ding Department of Hematology and Oncology, Key Department of Jiangsu Medicine, Zhongda Hospital, Medical School, Southeast University, Nanjing, Jiangsu Province, People’s Republic of China *These authors contributed equally to this work Abstract: Superselective arterial embolization is a common therapeutic procedure for cases of visceral hemorrhage. However, until now, it has not been applied in the treatment of gastrointestinal (GI) hemorrhage caused by acute graft-versus-host disease (GVHD) after allogeneic hematopoietic stem cell transplantation. We describe a case presenting with persistent GI bleeding associated with acute GVHD successfully treated by superselective arterial embolization of the superior mesenteric artery with gelatin sponge after noneffective conventional management. This case will help guide hematologists to deal with a similar situation in the future. Keywords: gastrointestinal bleeding, acute graft-versus-host disease, allo-hematopoietic stem cell transplantation, arterial embolization

Little is known about the morphological structure and photosynthetic physiology of Phoebe bournei (P. bournei) of different age classes in different light environments in a natural forest. There are four light intensity levels under the natural forest of P. bournei in Taijiang county, Guizhou Province, China, with 10% of the total light being weak light (WL), 30-40% being medium low light (LL), 50-60% being medium light (ML) and 80-100% being high light (HL) respectively. Our results are as follows: (1) Under high light (HL), the occurrence of younger seedlings and saplings is less frequent, especially P. bournei of age I was not observed in HL light intensity. (2) In the same age class and different light intensity classes: The leaf area of the same age class increases gradually with decreasing light intensity, except for the first age class; The specific leaf area (SLA), chlorophyll a (Chl a) and chlorophyll b (Chl b) increase gradually with decreasing light intensity; The thickness of palisade tissue and leaves decreases with decreasing light intensity; (3) In the same light intensity class and different age level classes. Palisade tissue thickness, spongy tissue thickness and leaf thickness gradually increases with the increase of age grade; Chl a and Chl b decreased with increasing light age. With the current study of the change of morphological and photosynthetic physiological characteristics of P. bournei of different ages with the light environment, we aim at providing theoretical basis and technical guidance for the management and protection of P. bournei natural forests and the formulation of technical measures for plantation cultivation. [ABSTRACT FROM AUTHOR]

Jian Cheng1,*, Ying Zhou1,*, Baoan Chen1, Jun Wang1, Guohua Xia1, Nan Jin1, Jiahua Ding1, Chong Gao1, Gouming Chen2, Yushan Miao2, Weilan Li2, Ziling Liu3, Xuemei Wang11Department of Hematology, Zhongda Hospital, Medical School, Southeast University, Nanjing, People’s Republic of China; 2Department of Pharmacy, Zhongda Hospital, Medical College, Southeast University, Nanjing, People’s Republic of China; 3The First Hospital of Jilin University, Changchun, Jilin, People’s Republic of China *These authors have contributed equally to this workObjective: To investigate the effect of magnetic nanoparticles (MNPs) of Fe3O4 combined with cyclosporin A (CsA) on acute graft-versus-host disease (aGVHD) after allogeneic hematopoietic stem cell transplantation (allo-HSCT) in murine models.Methods: BALB/c mice preconditioned with total-body irradiation generated aGVHD and then were followed with allo-HSCT from allogeneic C57BL/6. Recipient mice were randomly divided into five groups and then given different supportive care and followed up. The physical signs and median survival time (MST) were recorded, peripheral blood cell counts were assessed, and histological changes of the main tissues were evaluated with hematoxylin-eosin staining. Furthermore, fluorescence polarization immunoassay was used to monitor the concentration of CsA.Results: The irradiated-only mice developed typical aGVHD, and the typical signs of aGVHD in the skin, liver, and intestine were observed by histopathological examination. Both CsA alone and in combination with Fe3O4 MNPs significantly prolonged the MST of recipient mice compared with both the control and the Fe3O4 MNPs groups. Notably, a combination of CsA with Fe3O4 MNPs can elevate the peripheral white blood cells and alleviate the symptoms of GVHD and the pathological damage after allo-HSCT. In addition, the concentration of CsA was higher in plasma, heart, liver, and spleen of recipient mice with supporting care of the combination of CsA with Fe3O4 MNPs than with CsA alone.Conclusion: Taken together, Fe3O4MNPs may be used as a carrier of immunosuppressive agents to alleviate GVHD after allo-HSCT in murine models.Keywords: allogenetic stem cell transplantation, mice, HSCT

Jun Wang1, Baoan Chen1, Nan Jin1, Guohua Xia2, Yue Chen1, Ying Zhou1, Xiaohui Cai1,2, Jiahua Ding1, Xiaomao Li3, Xuemei Wang41Department of Hematology, Zhongda Hospital, 2Department of Medical Laboratory, Medical School, Southeast University, Nanjing, People's Republic of China; 3Department of Physics, University of Saarland, Saarbruecken, Germany; 4National Key Laboratory of Bioelectronics (Chien-Shiung Wu Laboratory), Southeast University, Nanjing, People’s Republic of ChinaAbstract: The aim of this article is to study the changes inhibited T lymphocytes and cytokines related to the cellular immunity in ICR (imprinting control region) mice fed with Fe3O4 magnetic nanoparticles (Fe3O4-MNPs). The Fe3O4-MNPs were synthesized, and their characteristics such as particle size, zeta potential, and X-ray diffraction patterns were measured and determined. All ICR mice were sacrificed after being exposed to 0, 300, 600, and 1200 mg/kg of Fe3O4-MNPs by single gastric administration for 14 days. Splenocytes proliferation was indicated with stimulate index by MTT assay; release of cytokines in the serum of ICR mice was detected by enzyme-linked immunosorbent assay, and the phenotypic analyses of T-lymphocyte subsets were performed using flow cytometry. Our results indicated that there were no significant differences in splenocyte proliferation and release of cytokines between exposed and control groups. Furthermore, there was no significant difference in the proportions of T-lymphocyte subsets in the low-dose Fe3O4-MNPs group when compared to the control group, but the proportions of CD3+CD4+ and CD3+CD8+ T-lymphocyte subsets both in the medium- and high-dose Fe3O4-MNPs groups were higher than those in the control group. It is concluded that a high dose of Fe3O4-MNPs, to some extent, could influence in vivo immune function of normal ICR mice.Keywords: Fe3O4, magnetic nanoparticles, splenocyte proliferation, release of cytokines, T-lymphocyte subsets, ICR mice