Showing papers by "Qiang Liu published in 2021"

Blockchain-Secured Smart Manufacturing in Industry 4.0: A Survey

Abstract: Blockchain is a new generation of secure information technology that is fueling business and industrial innovation. Many studies on key enabling technologies for resource organization and system operation of blockchain-secured smart manufacturing in Industry 4.0 had been conducted. However, the progression and promotion of these blockchain applications have been fundamentally impeded by various issues in scalability, flexibility, and cybersecurity. This survey discusses how blockchain systems can overcome potential cybersecurity barriers to achieving intelligence in Industry 4.0. In this regard, eight cybersecurity issues (CIs) are identified in manufacturing systems. Ten metrics for implementing blockchain applications in the manufacturing system are devised while surveying research in blockchain-secured smart manufacturing. This study reveals how these CIs have been studied in the literature. Based on insights obtained from this analysis, future research directions for blockchain-secured smart manufacturing are presented, which potentially guides research on urgent cybersecurity concerns for achieving intelligence in Industry 4.0.

Pyrotinib plus capecitabine versus lapatinib plus capecitabine for the treatment of HER2-positive metastatic breast cancer (PHOEBE): a multicentre, open-label, randomised, controlled, phase 3 trial

Abstract: Summary Background Despite therapeutic advances in HER2-positive metastatic breast cancer, resistance to trastuzumab inevitably develops In the PHOEBE study, we aimed to assess the efficacy and safety of pyrotinib (an irreversible pan-HER inhibitor) plus capecitabine after previous trastuzumab Methods This is an open-label, randomised, controlled, phase 3 trial done at 29 hospitals in China Patients with pathologically confirmed HER2-positive metastatic breast cancer, aged 18–70 years, who had an Eastern Cooperative Oncology Group performance status of 0 or 1, and had been previously treated with trastuzumab and taxanes were randomly assigned (1:1) to receive oral pyrotinib 400 mg or lapatinib 1250 mg once daily plus oral capecitabine 1000 mg/m2 twice daily on days 1–14 of each 21-day cycle Randomisation was done via a centralised interactive web-response system with a block size of four or six and stratified by hormone receptor status and previous lines of chemotherapy for metastatic disease The primary endpoint was progression-free survival according to masked independent central review Efficacy and safety were assessed in all patients who received at least one dose of the study drugs Results presented here are from a prespecified interim analysis This study is registered with ClinicalTrialsgov, NCT03080805 Findings Between July 31, 2017, and Oct 30, 2018, 267 patients were enrolled and randomly assigned 134 patients received pyrotinib plus capecitabine and 132 received lapatinib plus capecitabine At data cutoff of the interim analysis on March 31, 2019, median progression-free survival was significantly longer with pyrotinib plus capecitabine (12·5 months [95% CI 9·7–not reached]) than with lapatinib plus capecitabine (6·8 months [5·4–8·1]; hazard ratio 0·39 [95% CI 0·27–0·56]; one-sided p Interpretation Pyrotinib plus capecitabine significantly improved progression-free survival compared with that for lapatinib plus capecitabine, with manageable toxicity, and can be considered an alternative treatment option for patients with HER2-positive metastatic breast cancer after trastuzumab and chemotherapy Funding Jiangsu Hengrui Medicine and National Key R&D Program of China Translations For the Chinese translation of the abstract see Supplementary Materials section

Optical meta-waveguides for integrated photonics and beyond.

Abstract: The growing maturity of nanofabrication has ushered massive sophisticated optical structures available on a photonic chip. The integration of subwavelength-structured metasurfaces and metamaterials on the canonical building block of optical waveguides is gradually reshaping the landscape of photonic integrated circuits, giving rise to numerous meta-waveguides with unprecedented strength in controlling guided electromagnetic waves. Here, we review recent advances in meta-structured waveguides that synergize various functional subwavelength photonic architectures with diverse waveguide platforms, such as dielectric or plasmonic waveguides and optical fibers. Foundational results and representative applications are comprehensively summarized. Brief physical models with explicit design tutorials, either physical intuition-based design methods or computer algorithms-based inverse designs, are cataloged as well. We highlight how meta-optics can infuse new degrees of freedom to waveguide-based devices and systems, by enhancing light-matter interaction strength to drastically boost device performance, or offering a versatile designer media for manipulating light in nanoscale to enable novel functionalities. We further discuss current challenges and outline emerging opportunities of this vibrant field for various applications in photonic integrated circuits, biomedical sensing, artificial intelligence and beyond.

Digital twin-driven joint optimisation of packing and storage assignment in large-scale automated high-rise warehouse product-service system

Abstract: Current mass individualisation and service-oriented paradigm calls for high flexibility and agility in the warehouse system to adapt changes in products. This paper proposes a novel digital twin-dr...

Understanding the Global Cancer Statistics 2018: implications for cancer control

Abstract: Cancer incidence and mortality increase rapidly worldwide, making cancer the major cause of death in most regions. Understanding the current cancer burden in different regions is necessary to find out potential risk factors and generate strategies for cancer control. The International Agency for Research on Cancer (IARC) has recently provided a status report about the global burden of cancer by estimating the incidence and mortality for 36 cancers in 185 countries (Bray et al., 2018). In this article, we will summarize the distribution of the major cancer types in different regions and reveal the global cancer pattern. In addition, we will stress the potential risk factors responsible for the increase of cancer burden and the importance of medical allocation for cancer control.

Single-atom Fe with Fe 1 N 3 structure showing superior performances for both hydrogenation and transfer hydrogenation of nitrobenzene

Abstract: The design of non-noble metal heterogeneous catalyst with superior performance for selective hydrogenation or transfer hydrogenation of nitroarenes to amines is significant but challenging. Herein, a single-atom Fe supported by nitrogen-doped carbon (Fe1/N-C) catalyst is reported. The Fe1/N-C sample shows superior performances for the selective hydrogenation and transfer hydrogenation of nitrobenzene to aniline at different temperatures. Density functional theory (DFT) calculations show that the superior catalytic activity for the selective hydrogenation at lower temperatures could be attributed to the effective activation of the reactant and intermediates by the Fe1/N-C. Moreover, the excellent performance of Fe1/N-C for the selective transfer hydrogenation could be attributed to that the reaction energy barrier for dehydrogenation of isopropanol can be overcome by elevated temperatures.

Lung cancer organoids analyzed on microwell arrays predict drug responses of patients within a week.

Abstract: While the potential of patient-derived organoids (PDOs) to predict patients’ responses to anti-cancer treatments has been well recognized, the lengthy time and the low efficiency in establishing PDOs hamper the implementation of PDO-based drug sensitivity tests in clinics. We first adapt a mechanical sample processing method to generate lung cancer organoids (LCOs) from surgically resected and biopsy tumor tissues. The LCOs recapitulate the histological and genetic features of the parental tumors and have the potential to expand indefinitely. By employing an integrated superhydrophobic microwell array chip (InSMAR-chip), we demonstrate hundreds of LCOs, a number that can be generated from most of the samples at passage 0, are sufficient to produce clinically meaningful drug responses within a week. The results prove our one-week drug tests are in good agreement with patient-derived xenografts, genetic mutations of tumors, and clinical outcomes. The LCO model coupled with the microwell device provides a technically feasible means for predicting patient-specific drug responses in clinical settings. The lengthy time in establishing patient-derived organoids(PDOs) hampers the implementation of PDO-based drug sensitivity tests in clinics. Here, the authors show a microwell array-based method to predict patient’s responses to anti-cancer therapies in a week using lung cancer organoids.

Near-Infrared-II Nanoparticles for Cancer Imaging of Immune Checkpoint Programmed Death-Ligand 1 and Photodynamic/Immune Therapy.

Abstract: Development of second near-infrared (NIR-II) nanoparticles (NPs) with high biocompatibility, low toxicity, and high singlet oxygen quantum yield (ΦΔ) to prevent tumor recurrence is highly desirable in molecular imaging and photodynamic/immune combination therapy. Here, theranostic photosensitizer BODIPY (BDP)-I-N-anti-PD-L1 NPs were developed by encapsulating the photosensitizer BDP-I-N with amphipathic poly(styrene-co-chloromethylstyrene)-graft-poly(ethylene glycol) nanocarriers through self-assembly functionalization with programmed cell death-ligand 1 (PD-L1) monoclonal antibody. These NPs exhibit highly intensive luminescence in the NIR-II window (1000-1700 nm) to real-time imaging of immune checkpoint PD-L1, high singlet oxygen quantum yield (ΦΔ = 73%), and an eliminating effect of primary cancers. The NPs also allow for profiling PD-L1 expression as well as accumulating in MC38 tumor and enabling molecular imaging in vivo. Upon an 808 nm laser excitation, the targeted NPs produce an emission wavelength above 1200 nm to image a tumor to a normal tissue signal ratio (T/NT) at an approximate value of 14.1. Moreover, the MC38 tumors in mice are eliminated by combining photodynamic therapy and immunotherapy within 30 days, with no tumor recurrence within a period of 40 days. In addition, the tumors do not grow in the rechallenged mice within 7 days of inoculation. Such a strategy shows a durable immune memory effect against tumor rechallenging without toxic side effects to major organs.

Dalpiciclib or placebo plus fulvestrant in hormone receptor-positive and HER2-negative advanced breast cancer: a randomized, phase 3 trial

Abstract: Blockade of the cyclin-dependent kinase 4 and 6 pathway has been shown to be effective in the treatment of hormone receptor-positive advanced breast cancer (ABC). We report the interim results of DAWNA-1 ( NCT03927456 ), a double-blind, randomized, phase 3 trial of dalpiciclib (a new cyclin-dependent kinase 4 and 6 inhibitor) plus fulvestrant in hormone receptor-positive, HER2-negative ABC with disease progression after endocrine therapy. A total of 361 patients were randomized 2:1 to receive dalpiciclib plus fulvestrant or placebo plus fulvestrant. The study met the primary end point, showing significantly prolonged investigator-assessed progression-free survival with dalpiciclib plus fulvestrant versus placebo plus fulvestrant (median = 15.7, 95% confidence interval (CI) = 11.1–not reached versus 7.2, 95% CI = 5.6–9.2 months; hazard ratio = 0.42, 95% CI = 0.31–0.58; one-sided P < 0.0001 (boundary was P ≤ 0.008)). The most common grade 3 or 4 adverse events with dalpiciclib plus fulvestrant were neutropenia (84.2%) and leukopenia (62.1%). The incidence of serious adverse events was 5.8% with dalpiciclib plus fulvestrant versus 6.7% with placebo plus fulvestrant. Our findings support dalpiciclib plus fulvestrant as a new treatment option for pretreated hormone receptor-positive, HER2-negative ABC. In the multicenter, phase 3 DAWNA-1 trial, the combination of dalpiciclib, a new cyclin-dependent kinase 4 and 6 inhibitor, with fulvestrant, in patients with HR+HER2− advanced breast cancer who progressed or relapsed on endocrine therapy, improved progression-free survival with manageable safety and may represent a new treatment option.

Targeting regulator of G protein signaling 1 in tumor-specific T cells enhances their trafficking to breast cancer.

Abstract: Reduced infiltration of anti-tumor lymphocytes remains a major cause of tumor immune evasion and is correlated with poor cancer survival. Here, we found that upregulation of regulator of G protein signaling (RGS)1 in helper TH1 cells and cytotoxic T lymphocytes (CTLs) reduced their trafficking to and survival in tumors and was associated with shorter survival of patients with breast and lung cancer. RGS1 was upregulated by type II interferon (IFN)-signal transducer and activator of transcription (STAT)1 signaling and impaired trafficking of circulating T cells to tumors by inhibiting calcium influx and suppressing activation of the kinases ERK and AKT. RGS1 knockdown in adoptively transferred tumor-specific CTLs significantly increased their infiltration and survival in breast and lung tumor grafts and effectively inhibited tumor growth in vivo, which was further improved when combined with programmed death ligand (PD-L)1 checkpoint inhibition. Our findings reveal RGS1 is important for tumor immune evasion and suggest that targeting RGS1 may provide a new strategy for tumor immunotherapy.

Notched-Polyoxometalate Strategy to Fabricate Atomically Dispersed Ru Catalysts for Biomass Conversion

Abstract: The development of the synthesis methods of single-atom catalysts (SACs) is of great significance for the study of the specificity of SACs. Herein, we report a strategy to immobilize Ru atom using ...

The IRENA lncRNA converts chemotherapy-polarized tumor-suppressing macrophages to tumor-promoting phenotypes in breast cancer

Abstract: Although chemotherapy can stimulate antitumor immunity by inducing interferon (IFN) response, the functional role of tumor-associated macrophages in this scenario remains unclear. Here, we found that IFN-activated proinflammatory macrophages after neoadjuvant chemotherapy enhanced antitumor immunity but promoted cancer chemoresistance. Mechanistically, IFN induced expression of cytoplasmic long noncoding RNA IFN-responsive nuclear factor-κB activator (IRENA) in macrophages, which triggered nuclear factor-κB signaling via dimerizing protein kinase R and subsequently increased production of protumor inflammatory cytokines. By constructing macrophage-conditional IRENA-knockout mice, we found that targeting IRENA in IFN-activated macrophages abrogated their protumor effects, while retaining their capacity to enhance antitumor immunity. Clinically, IRENA expression in post-chemotherapy macrophages was associated with poor patient survival. These findings indicate that lncRNA can determine the dichotomy of inflammatory cells on cancer progression and antitumor immunity and suggest that targeting IRENA is an effective therapeutic strategy to reversing tumor-promoting inflammation. Song and colleagues report that in breast cancer, chemotherapy induces the IRENA lncRNA, which reprograms tumor suppressive macrophages to protumorigenic phenotypes and promotes chemoresistance.

Experimental and numerical simulation study on polyurea-coated fuel tank subjected to combined action of blast shock waves and fragments

Abstract: Fuel tanks, as core fuel components of many types of mechanical equipment, are highly vulnerable to strong dynamic loads, such as those from explosions and fragments. In this paper, two types of polyurea materials (AMMT-53 and AMMT-55) were designed to enhance the damage resistance of fuel tanks. The mechanical parameters and performance differences of the two polyurea materials were first obtained. On this basis, a series of experiments study on fuel tanks coated with different thicknesses polyurea subjected to a combination of blast waves and fragments were performed. The results showed that these two types of polyurea materials had different protective abilities. The AMMT-53 polyurea could effectively reduce the perforation rate but could not prevent the liquid leakage, while the AMMT-55 polyurea could not significantly reduce the perforation rate, but the self-healing property could effectively prevent the leakage of liquid. The whole process of the shock wave and the fragments acting on the fuel tank was revealed by numerical simulations. From the change of the fragment velocity, the strength of the shock wave in the liquid, and the energy change of the polyurea layer, it was proven that the coated polyurea layers had good protective effects on the fuel tank.

All-silica fiber-optic temperature-depth-salinity sensor based on cascaded EFPIs and FBG for deep sea exploration.

Abstract: Using fusion splicing and hydroxide catalysis bonding (HCB) technology, an all-silica inline fiber-optic sensor with high-pressure survivability, high-resolution salinity measurement capability, and corrosion resistance for deep sea explorations is proposed and experimentally demonstrated. Two extrinsic Fabry-Perot interferometers (EFPIs) and a fiber Bragg grating (FBG) are cascaded in one single-mode fiber (SMF), enabling structural integration of single lead-in fiber and versatility of the sensing probe for temperature, depth, and salinity monitoring. The HCB technology offers a polymer adhesive-free assembly of one open-cavity EFPI for refractive index (RI) (salinity) sensing under normal pressure and temperature (NPT) conditions, showing obvious advantages of strong bonding strength, reliable effectiveness, and no corrosive chemicals requirements. The other EFPI formed by a fused structure is designed for pressure (depth) measurement. The cascading of EFPIs, especially the open-cavity EFPI immersed in water, will result in large light transmission loss and bring challenges to signal interrogation. Graded-index fiber (GIF) micro-collimators and reflective films are added to prevent dramatic degradations of signal intensity and fringe visibility underwater. Thereby, a Fabry-Perot (FP) cavity of several hundreds of microns in length and an open cavity of a thousand microns can be cascaded for underwater applications, effectively enhancing sensitivities and underwater signal readout simultaneously. Results show that the proposed sensor can well operate in the deep-sea pressure range of 0∼2039.43 mH2O, RI range of 1.33239∼1.36885 RIU, and temperature range of 23∼80 °C, with resolutions of 0.033 MPa, 4.16×10−7 RIU, and 0.54 °C, respectively. With the multi-parameter measurement capability, all-silica construction, and inline compact structure, the proposed sensor could be a potential candidate for deep sea exploration.

TFBG-SPR DNA-Biosensor for Renewable Ultra-Trace Detection of Mercury Ions

Abstract: In this article, a tilted fiber Bragg grating (TFBG) plasmonic sensor based on thymine (T) - Hg - thymine (T) (T-Hg-T) base asymmetric pairing and Au nanoparticles (AuNPs), which can be used for highly sensitive and selective ultra-low-concentration Hg2+ detection, has been demonstrated. As is known, TFBG can provide an effective mean to easily excite the surface plasmon resonance (SPR) phenomenon while the fiber is coated with metal layer. By measuring the evolution of spectra, the SPR properties hence the surface perturbation could be detected accurately. To achieve highly sensitive and selective Hg2+ detection, the two specially designed single-strand probe DNAs (ssDNAs) with rich T base that can specifically forming stable T-Hg-T asymmetric pairing are served as a binding element for AuNPs labelled-target DNA conjugates. In the present of Hg2+, these two ssDNAs that modified respectively on the surface of the sensor and the AuNPs will create a double helix T-Hg-T structure between the two DNA oligonucleotides and result in the surface refractive index perturbation amplified by the AuNPs. To overcome the low reusability of the AuNPs based DNA biosensor, by using iodide ions that can form more stable compounds with mercury ions over the T-Hg2+-T structure, a regenerable DNA biosensor that can repeatedly detect mercury ions is developed. The experimental results demonstrate that this sensor shows an excellent ultra-low-concentration and selectivity detection capability for Hg2+ with the limit of detection (LOD) of 3.073 × 10−12 M (3.073 pM) as well as a large dynamic range of 8 order of magnitude from 1.0 × 10−11 M to 1.0 × 10−3 M simultaneously. Thus, the experimental results in various actual sample from ultrapure/tap water to even clinical human serum, also reveal that it has potential application for Hg2+ detection in environmental samples and in clinic biological samples.

Biomarkers of response to camrelizumab combined with apatinib: an analysis from a phase II trial in advanced triple-negative breast cancer patients

Abstract: We recently reported results of a phase II trial that camrelizumab plus apatinib induced an objective response rate (ORR) at 43.3% in advanced triple-negative breast cancer (TNBC). This study presents analysis of potential biomarkers. TILs, CD8+ T cells and PD-1/PD-L1 expression were evaluated in tumor samples by immunohistochemistry. 59 Cytokines/chemokines, growth factors, or checkpoint-related proteins, blood immune cell subpopulations were analyzed in blood samples by multiplexed bead immunoassays or flow cytometry. Correlation between biomarkers and clinical outcomes including ORR, progression-free survival (PFS), and overall survival (OS) was analyzed. 28 Patients had biopsies and blood collected. Baseline TILs were significantly associated with longer PFS (P = 0.035). An increase of tumor-infiltrating CD8+ T cells > 15% during therapy was associated with higher ORR (P = 0.040). Patients with lower baseline plasma levels of HGF or IL-8 were more likely to respond to treatment (P = 0.005 or 0.001, respectively), and showed a longer PFS and OS. Patients with a decrease of IL-8, or an increase of TIM-3 or CD152 during treatment responded more to treatment (P = 0.008, 0.040, or 0.014, respectively). Responders had a higher baseline CD4+ T cells and B cell proportions in blood than non-responders (P = 0.002 and 0.030, respectively). Higher baseline TILs or a greater increase of tumor-infiltrating CD8+ T cells during therapy, lower baseline plasma HGF/IL-8, a decrease of plasma IL-8, an increase of plasma TIM-3/CD152 during therapy, higher baseline CD4+ T cells or B cells proportion in blood are potential biomarkers for combinational anti-angiogenesis and immunotherapy in advanced TNBC patients.

Three-dimensional silk fibroin microsphere-nanofiber scaffolds for vascular tissue engineering

Abstract: A significant limitation in the engineering of artificial small-diameter vascular scaffolds is that the number of endothelial cells (ECs) is not sufficient to generate a confluent coverage of the vascular scaffolds, so that the surfaces of vascular scaffolds form thrombus via platelet adhesion and aggregation. Thrombus decrease relies on three-dimensional (3D) scaffolds to mimic the natural extracellular matrix (ECM) as templates to regulate cell behavior and facilitate tissue maturation. Here, we developed 3D scaffolds consisting of silk fibroin (SF) nanofibers and homogeneous microspheres by electrospinning and microfluidics. The nanofibers with diameters ranging from 250 to 350 ​nm doped with microspheres (2–10 ​μm) formed bridge-shaped structures. ECs were seeded and maintained on the 3D microsphere-nanofiber scaffolds with a mean fiber diameter of 300 ​nm. A 10% higher ratio of cell proliferation on 3D microsphere-nanofiber SF scaffolds was noted as compared to that on microporous and sponge-like SF scaffolds with small surface network fabricated by freeze-drying. Moreover, the gene transcript levels including CD146, VE-C and PECAM-1 were better preserved on 3D microsphere-nanofiber SF scaffolds than those on freeze-dried scaffolds. Thus, the developed 3D microsphere-nanofiber structure may have a myriad of applications in vascular tissue engineering scaffolds and cardiovascular devices.

Bioinformatics reveal macrophages marker genes signature in breast cancer to predict prognosis.

Abstract: Background: Breast cancer is a pivotal cause of global women cancer death. Immunotherapy has become a promising means to cure breast cancer. As constitutes of immune microenvironment of breast cancer, macrophages exert complicated functions in the tumour development and treatment. This study aims to develop a prognostic macrophage marker genes signature (MMGS).Methods: Single cell RNA sequence data analysis was performed to identify macrophage marker genes in breast cancer. TCGA database was used to construct MMGS model as a training cohort, and GSE96058 dataset was used to validate the MMGS as a validation cohort.Results: Genes included in the MMGS model were: SERPINA1, CD74, STX11, ADAM9, CD24, NFKBIA, PGK1. MMGS risk score stratified by overall survival of patients divided them into high- and low-risk groups. And MMGS risk score remained independent prognostic factor in multivariate analysis after adjusting for classical clinical factors in both training and validation cohorts. Besides, hormone receptors negative and human epidermal growth factor receptor 2 (HER2) positive patients had higher risk score. MMGS showed better distinguishing capability between high-risk and low-risk groups in hormone receptor positive and HER2 negative subgroup.Conclusion: MMGS provides a new understanding of immune cell marker genes in breast cancer prognosis and may offer reference for immunotherapy decision for breast cancer patients.