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Abstract In order to fulfill the complex cognitive behaviors in neuromorphic systems with reduced peripheral circuits, the reliable electronic synapses mimicked by single device that achieves diverse long‐term and short‐term plasticity are essential. Phase change random access memory (PCRAM) is of great potential for artificial synapses, which faces, however, difficulty to realize short‐term plasticity due to the long‐lasting resistance drift. This work reports the ruthenium‐doped Ge2Sb2Te5 (RuGST) based PCRAM, demonstrating a series of synaptic behaviors of short‐term potentiation, pair‐pulse facilitation, long‐term depression, and short‐term plasticity in the same single device. The optimized RuGST electronic synapse with the high transformation temperature of hexagonal phase >380°C, the outstanding endurance >108 cycles, the low resistance drift factor of 0.092, as well as the extremely high linearity with correlation coefficients of 0.999 and 0.976 in parts of potentiation and depression. Further investigations also go insight to mechanisms of Ru doping according to thorough microstructure characterization, revealing that Ru dopant is able to enter GST lattices thus changing and stabilizing atomic arrangement of GST. This leads to the short‐term plasticity realized by RuGST PCRAM. Eventually, the proposed RuGST electronic synapses performs a high accuracy of ~94.1% in a task of image recognition of CIFAR‐100 database using ResNet 101. This work promotes the development of PCRAM platforms for large‐scale neuromorphic systems.

Abstract Background Cervical cancer is the fourth most common malignant tumor troubling women worldwide. Whether marital status affects the prognosis of cervical cancer is still unclear. Here, we investigate the prognostic value of marital status in patients with cervical cancer based on the seer database. Material/Methods The demographic and clinical data of patients with cervical cancer were extracted from the Surveillance, Epidemiology, and End Results (SEER) database from 1975 to 2017. Patients were divided into two groups (married and unmarried) according to marital status, and then the clinical characteristics of each group were compared using the chi-square test. Propensity score matching (PSM) was used to reduce differences in baseline characteristics. The overall survival (OS) and cervical cancer-specific survival (CCSS) were assessed by the Kaplan-Meier method, univariate and multivariate Cox regression models, and stratified analysis. Moreover, univariate and multivariate competing risk regression models were performed to calculate hazard ratios (HR) of death risk. Results A total of 21,148 patients were included in this study, including 10,603 married patients and 10,545 unmarried patients. Married patients had better OS(P

This paper investigated the inhibitory effect of Sesamol (Ses) on Pestalotiopsis neglecta. The potential inhibitory mechanisms were explored by observing changes in cell morphology, measuring alterations in cell membrane-related indices, as well as energy metabolism-related indices and changes in enzyme activities related to virulence. The results show that Ses completely inhibited the growth of P. neglecta at 600 μg/mL (minimum inhibitory concentration and minimum fungicidal concentration), with an EC50 of 142 ± 13.22 μg/mL. As observed with scanning electron microscopy (SEM) and transmission electron microscopy (TEM), Ses treatment resulted in the breakage and crumpling of P. neglecta cell membrane and organelle lysis. Ergosterol content and the total lipid in P. neglecta treated with 300 μg/mL Ses was 91.52% and 54% of that in the control groups, respectively. In addition, spores were stained, increased leakage of intracellular constituents at 260 nm, and decreased extracellular pH. This suggests damage to the cell membrane integrity and permeability. Furthermore, Ses decreased the ATP levels and key enzymes in the tricarboxylic acid (TCA) cycle, indicating interference with the fungal energy metabolism. Moreover, the activities of polygalacturonase (PG) and endoglucanase (EG) of P. neglecta treated with 300 μg/mL of Ses were only 28.20% and 29.13% of that in the control groups, respectively, indicating that Ses can reduce the virulence of P. neglecta. In conclusion, our results show that Ses should be considered as a potential plant-derived fungicide due to its ability to disrupt the morphology of P. neglecta, damage cell membrane integrity and permeability in P. neglecta, interfere with energy metabolism, and reduce its virulence, ultimately affecting the fungal growth.

Aims To explore the relationship between vitamin D and obesity and abdominal obesity in women with infertility.Material and methods We screened the data from National Health and Nutrition Examination Survey (NHANES) 2013–2016. A total of 201 infertile women between the ages of 20 and 40 years were included in our study. To estimate the independent association of vitamin D with obesity and abdominal obesity, we used weighted multivariate logistic regression models and cubic spline analyses.Results Among infertile women in the NHANES 2013–2016 database, serum vitamin D levels were significantly and negatively associated with body mass index (ß= −0.96, 95% CI: −1.40, −0.51, p 0.05).Conclusion Our findings suggested that a decreased vitamin D might correspond to a higher prevalence of obesity in infertile women, which reminded us to pay more attention to the supplement of vitamin D in obese infertile women.

Abstract Background Skeletal muscle atrophy is a common condition without a pharmacologic therapy. AGGF1 encodes an angiogenic factor that regulates cell differentiation, proliferation, migration, apoptosis, autophagy and endoplasmic reticulum stress, promotes vasculogenesis and angiogenesis and successfully treats cardiovascular diseases. Here, we report the important role of AGGF1 in the pathogenesis of skeletal muscle atrophy and attenuation of muscle atrophy by AGGF1. Methods In vivo studies were carried out in impaired leg muscles from patients with lumbar disc herniation, two mouse models for skeletal muscle atrophy (denervation and cancer cachexia) and heterozygous Aggf1+/− mice. Mouse muscle atrophy phenotypes were characterized by body weight and myotube cross‐sectional areas (CSA) using H&E staining and immunostaining for dystrophin. Molecular mechanistic studies include co‐immunoprecipitation (Co‐IP), western blotting, quantitative real‐time PCR analysis and immunostaining analysis. Results Heterozygous Aggf1+/− mice showed exacerbated phenotypes of reduced muscle mass, myotube CSA, MyHC (myosin heavy chain) and α‐actin, increased inflammation (macrophage infiltration), apoptosis and fibrosis after denervation and cachexia. Intramuscular and intraperitoneal injection of recombinant AGGF1 protein attenuates atrophy phenotypes in mice with denervation (gastrocnemius weight 81.3 ± 5.7 mg vs. 67.3 ± 5.1 mg for AGGF1 vs. buffer; P

Lead-free bismuth sodium titanate (Bi0.5Na0.5)TiO3 (BNT) and related solid solutions are potential piezoelectric materials for such applications as actuators and transducers if their excellent strain responses and piezoelectric properties can be optimized. In this work, a large strain response of 0.61% is achieved in lead-free (0.94-x%)(Bi0.5Na0.5)TiO3-0.06BaTiO3-x%NaNbO3 (x = 0 –6, BNT-6BT-xNN) ceramics with the composition of x = 3.5 in a pseudo-cubic structure. Coexistence of ferroelectric (FE) and relaxor (RE) domain structures is observed in all the unpoled ceramics and the enhanced strain response is believed to be related to the evolution of the ergodic relaxor (ER) and non-ergodic (NR) states thanks to the substitution of antiferroelectric NN. BNT-6BT-3.5NN is a critical composition near the FE/NR/ER phase boundary close to room temperature (RT) and its high strain response arises from a synergistic combination of a reversible electric-field-induced phase transition and an active domain switching in the mixed NR/ER state. This work provides new insights into the dynamic interplay between mesoscopic domains and macroscopic electrical properties in the BNT-based piezoceramics.

Lead-free piezoelectric sodium bismuth titanate (([Formula: see text][Formula: see text])TiO3, BNT) thin films were epitaxially grown onto (001)-, (110)-, and (111)-oriented Nb:SrTiO3 (STO) single crystal substrates prepared by sol–gel processing. Highly oriented growth in (001), (110), and (111) BNT thin films was obtained in this work benefiting from the lattice match between the BNT film and the STO substrate. The different growth models in thin films with various orientations result in various surface morphologies dependent on the film orientation. The piezoresponse of the BNT thin films was represented exhibiting a strong orientation dependence that (110)>(001)>(111). This is contributed by the various domain switching contribution related to the crystal symmetry and polarization distribution in the three oriented thin films.

Abstract Background Neutrophil CD64 (nCD64) index has been widely studied as an indication of bacteria-infected diseases, but the exact usage of nCD64 index in monitoring infections remains debated. So this study aims to investigate the functionality of nCD64 index in tracking infections’ progression and evaluating antibiotic therapy. Methods 160 participants (36 healthy controls, 34 culture-negative patients, 56 respiratory tract infected patients, and 34 bloodstream infected patients) were recruited and divided into groups. Data on nCD64 index, T lymphocyte subsets, and conventional indicators, including white blood cell count, neutrophil to lymphocyte ratio, procalcitonin, and C-reactive protein, were tested and compared. Results Bacteria-infected patients had significantly higher nCD64 indexes (p

Remodeling the tumor microenvironment through reprogramming tumor-associated macrophages (TAMs) and increasing the immunogenicity of tumors via immunogenic cell death (ICD) have been emerging as promising anticancer immunotherapy strategies. However, the heterogeneous distribution of TAMs in tumor tissues and the heterogeneity of the tumor cells make the immune activation challenging. To overcome these dilemmas, a hybrid bacterium with tumor targeting and penetration, TAM polarization, and photothermal conversion capabilities is developed for improving antitumor immunotherapy in vivo. The hybrid bacteria (B.b@QDs) are prepared by loading Ag2S quantum dots (QDs) on the Bifidobacterium bifidum (B.b) through electrostatic interactions. The hybrid bacteria with hypoxia targeting ability can effectively accumulate and penetrate the tumor tissues, enabling the B.b to fully contact with the TAMs and mediate their polarization toward M1 phenotype to reverse the immunosuppressive tumor microenvironment. It also enables to overcome the intratumoral heterogeneity and obtain abundant tumor-associated antigens by coupling tumor penetration of the B.b with photothermal effect of the QDs, resulting in an enhanced immune effect. This strategy that combines B.b-triggered TAM polarization and QD-induced ICD achieved a remarkable inhibition of tumor growth in orthotopic breast cancer.

The integration of epitaxial complex oxides on semiconductor and flexible substrates is required but challenging. Here, the authors report the highly heterogeneous epitaxy of transferrable BaTiO3-δ membrane with enhanced flexoelectricity on Ge (011).

ABSTRACT 5-Fluorouracil (5-FU), irinotecan (CPT-11), oxaliplatin (L-OHP), and calcium folinate (CF) are widely used chemotherapeutic drugs to treat colorectal cancer. However, chemotherapeutic use is often accompanied by intestinal inflammation and gut microbiota disorder. Changes in gut microbiota may destroy the intestinal barrier, which contributes to the severity of intestinal injury. However, intestinal injury and gut microbiota disorder have yet to be compared among 5-FU, CPT-11, L-OHP, and CF in detail, thereby limiting the development of targeted detoxification therapy after chemotherapy. In this study, a model of chemotherapy-induced intestinal injury in tumor-bearing mice was established by intraperitoneally injecting chemotherapeutic drugs at a clinically equivalent dose. 16S rRNA gene sequencing was used to detect gut microbiota. We found that 5-FU, CPT-11, and l-OHP caused intestinal injury, inflammatory cytokine (gamma interferon [IFN-γ], tumor necrosis factor alpha [TNF-α], interleukin-1β [IL-1β], and IL-6) secretion, and gut microbiota disorder. We established a complex but clear network between the pattern of changes in gut microbiota and degree of intestinal damage induced by different chemotherapeutic drugs. L-OHP caused the most severe damage in the intestine and disorder of the gut microbiota and showed a considerable overlap of the pattern of changes in microbiota with 5-FU and CPT-11. Analysis by Phylogenetic Investigation of Communities by Reconstruction of Unobserved States (PICRUSt v.1.0) showed that the microbiota disorder pattern induced by 5-FU, CPT-11, and L-OHP was related to the NOD-like signaling pathway. Therefore, we detected the protein expression of the NOD/RIP2/NF-κB signaling pathway and found that L-OHP most activated this pathway. Redundancy analysis/canonical correlation analysis (RDA/CCA) revealed that Bifidobacterium, Akkermansia, Allobaculum, Catenibacterium, Mucispirillum, Turicibacter, Helicobacter, Proteus, Escherichia Shigella, Alloprevotealla, Vagococcus, Streptococcus, and “Candidatus Saccharimonas” were highly correlated with the NOD/RIP2/NF-κB signaling pathway and influenced by chemotherapeutic drugs. IMPORTANCE Chemotherapy-induced intestinal injury limits the clinical use of drugs. Intestinal injury involves multiple signaling pathways and gut microbiota disruption. Our results suggested that the degree of intestinal injury caused by different drugs of the first-line colorectal chemotherapy regimen is related to the pattern of changes in microbiota. The activation of the NOD/RIP2/NF-κB signaling pathway was also related to the pattern of changes in microbiota. l-OHP caused the most severe damage to the intestine and showed a considerable overlap of the pattern of changes in microbiota with 5-FU and CPT-11. Thirteen bacterial genera were related to different levels of intestinal injury and correlated with the NOD/RIP2/NF-κB pathway. Here, we established a network of different chemotherapeutic drugs, gut microbiota, and the NOD/RIP2/NF-κB signaling pathway. This study likely provided a new basis for further elucidating the mechanism and clinical treatment of intestinal injury caused by chemotherapy.

Abstract The conditions for sex reversal in vertebrate species have been extensively studied, and the results highlighted numerous key factors involved in sex differentiation. However, the transcriptomes in hypothalamic and pituitary tissues from intersex goats have rarely been studied. The aim of this study was to screen candidate genes and signalling pathways related to sex reversal in Huai goats by analyzing gene expression in hypothalamic and pituitary tissues via transcriptome sequencing and bioinformatics analyses. In total, 612 and 139 differentially expressed genes (DEGs) were identified between the intersex and non‐intersex groups in the hypothalamus and pituitary, respectively. The DEGs in the hypothalamus and pituitary were significantly enriched in 41 and 16 signalling pathways, respectively, including the calcium signalling pathway, neuroactive ligand‐receptor interaction signalling pathway, and oestrogen signalling pathway, which might be related to intersex sex development disorders. A candidate gene from the tachykinin family (TACR1) was significantly enriched in the calcium signalling pathway. Thirty‐one DEGs were shared between these two comparisons and were enriched in several acetyl‐CoA‐related processes and the oestrogen signalling pathway. The results of the real‐time PCR analysis show that the transcriptome sequencing results were reliable. The transcriptome data indicate that the regulation of various physiological systems is involved in intersex goat development. Therefore, these results provide helpful data enhancing our understanding of the molecular mechanisms underlying intersex syndrome in goats.

Two–electron (2e-) oxygen reduction reaction (ORR) shows great promise for on–site electrochemical synthesis of hydrogen peroxide (H2O2). However, it is still a great challenge to design efficient electrocatalysts for H2O2 synthesis. To address this issue, the logical design of the active site by controlling the geometric and electronic structures is urgently desired. Therefore, using density functional theory (DFT) computations, two kinds of hybrid double–atom supported on C2N nanosheet (RuCu@C2N and PdCu@C2N) are screened out and their H2O2 performances are predicted. PdCu@C2N exhibits higher activity for H2O2 synthesis with a lower overpotential of 0.12 V than RuCu@C2N (0.59 V), Ru3Cu(110) facet (0.60 V), and PdCu(110) facet (0.54 V). In aqueous phase, the adsorbed O2 is further stabilized with bulk H2O and the thermodynamic rate–determining step of 2e- ORR change. The activation barrier on PdCu@C2N is 0.43 eV lower than the one on RuCu@C2N with 0.68 eV. PdCu@C2N is near the top of 2e- ORR volcano plot, and exhibits high selectivity of H2O2. This work provides guidelines for designing highly effective hybrid double–atom electrocatalysts (HDACs) for H2O2 synthesis.

Bismuth sodium titanate (Bi0.5Na0.5)TiO3 (BNT)–based thin films have attracted large attention for the production of modern precise micro–devices due to their outstanding strain responses. However, obtaining good electrical properties and low leakage current in BNT-based thin films is still a great challenge. In this work, 0.945(Bi0.5Na0.5)TiO3–0.055BaZrO3 (BNT–5.5BZ) thin films were deposited by the chemical solution deposition (CSD) method and annealed under two different conditions. This work describes a careful research study on the influence of the annealing conditions on the crystalline structure, morphology, and electrical performance of the BNT–5.5BZ thin films. The films exhibited a dense structure and excellent electrical properties following an optimized thermal treatment process. An ultra–high strain response of 1.5% with a low dielectric loss of ~0.03 was obtained in the BNT–5.5BZ thin films after post-annealing in an O2 atmosphere. The results of this work show that the enhanced strain response was mainly due to a reversible field-induced phase transition between the ferroelectric phase and the relaxation state. The post-annealing treatment is an effective method to optimize the electrical properties of BNT–based films, providing many opportunities for the application of ferroelectric devices.

The (001) plate-like BaTiO3 piezoelectric micromaterials are synthesized by topochemical microcrystal conversion technique. BaTiO3 plates with a length of 2~10 μm and thickness of 0.5~1.3 μm are obtained. The dependence of morphology on synthesis conditions is discussed in detail. The crystal symmetry and multiscale domain structures of BaTiO3 plates are systematically investigated by various characterizations. X-ray diffraction (XRD) and Raman spectra analyses demonstrate the tetragonal symmetry of the (001) oriented BaTiO3 plates at room temperature. The domain configurations of the micron BaTiO3 are investigated with a polarized light microscope (PLM) and piezoresponse force microscopy (PFM). The single-crystal-like quality and uniformity are supported by PLM observations. More importantly, the classical 90° banded ferroelectric domains of ~125 nm width are observed for the first time in such BaTiO3 plates. The domain features in the mesoscale BaTiO3 plate are discussed and compared with its bulk counterparts. The results may provide insights into understanding and designing the mesoscale BaTiO3 functional materials.

Lead-free piezoelectric 0.92(K0.445Na0.5Li0.05)NbO3-0.08BaZrO3 (KNLN-BZ) ceramics were prepared via conventional sintering. Single-step, 2-step and 3-step temperature-controlled conditions were designed. The structure and electrical properties of ceramics obtained using different temperature-controlled procedures were systematically studied. It was found that ceramic prepared using the 3-step method with a holding time of 20 h showed the highest electrical properties. The Curie temperature was approximately 286 °C, and the dielectric constant and dielectric loss at room temperature were 1350 and 4.5% at the frequency of 1 kHz, respectively. The highest remanent polarization, piezoelectric strain and piezoelectric coefficient, d33*, were obtained 60 °C, indicating a phase transition between ferroelectric phases. Although the ceramics did not show excellent piezoelectric properties, the 3-step sintering method can be considered an effective method to optimize the electrical performances of KNN-based ceramics. Combined with an appropriate composition, ceramics with excellent electrical properties could be obtained. This study provides a path to enhance the density and electrical properties for KNN-based ceramics with simple composition and potential for industry application.

ObjectiveGestational diabetes mellitus (GDM) is a serious threat to maternal and child health. However, there isn’t a standard predictive model for the disorder in early pregnancy. This study is to investigate the association of blood indexes with GDM and establishes a practical predictive model in early pregnancy for GDM.MethodsThis is a prospective cohort study enrolling 413 pregnant women in the department of Obstetrics and Gynecology in Shanghai General Hospital from July 2020 to April 2021.A total of 116pregnantwomen were diagnosed with GDM during the follow-up. Blood samples were collected at early trimester (gestational weeks 12-16) and second trimester(gestational weeks 24-26 weeks). A predictive nomogram was established based on results of the multivariate logistic model and 5-fold cross validation. We evaluate the nomogram by the area under the receiver operating characteristic curve (AUC), calibration curves and decision curve analysis (DCAs).ResultsSignificant differences were observed between the GDM and normal controls among age, pre-pregnancy BMI, whether the pregnant women with complications, the percentage of B lymphocytes, fasting plasma glucose (FPG), HbA1c, triglyceride and the level of progesterone in early trimester. Risk factors used in nomogram included age, pre-pregnancy BMI, FPG, HbA1c, the level of IgA, the level of triglyceride, the percentage of B lymphocytes, the level of progesterone and TPOAb in early pregnancy. The AUC value was 0.772, 95%CI (0.602,0.942). The calibration curves for the probability of GDM demonstrated acceptable agreement between the predicted outcomes by the nomogram and the observed values. DCA curves showed good positive net benefits in the predictive model.ConclusionsA novel predictive nomogram was developed for GDM in our study, which could do help to patient counseling and management during early pregnancy in clinical practice.

Field effect transistors (FETs) using two-dimensional molybdenum disulfide (MoS2) as the channel material has been considered one of the most potential candidates for future complementary metal-oxide-semiconductor technology with low power consumption. However, the understanding of the correlation between the device performance and material properties, particularly for devices with scaling-down channel lengths, is still insufficient. We report in this paper back-gate FETs with chemical-vapor-deposition grown and transferred MoS2 and Zr doped HfO2 ((Hf,Zr)O2, HZO) high-k dielectric gates with channel lengths ranging from 10 to 30 µm with a step of 5 µm. It has been demonstrated that channels with the length to width ratio of 0.2 lead to the most superior performance of the FETs. The MoS2/HZO hybrid FETs show a stable threshold voltage of ∼1.5 V, current on/off ratio of >104, and field effect mobility in excess of 0.38 cm2 V−1 s−1. The impact of the channel lengths on FET performance is analyzed and discussed in depth. A hysteresis loop has been observed in the Ids − Vgs characteristics of the hybrid FETs, which has been further studied and attributed to the charge effect at the interfaces. The HZO films show a relatively weak ferroelectric orthorhombic phase and thus serve mainly as the high-k dielectric gate. Charge trapping in the HZO layer that might induce hysteresis has been discussed. Our results show that MoS2/HZO hybrid FETs possess great potential in future low power and high-speed integrated circuits, and future work will focus on further improvement of the transistor performances using ferroelectric HZO films and the study of devices with even shorter MoS2 channels.

Environment-friendly lead-free piezoelectric ceramics with great properties and high thermal stability are desired in the industry. In this work, the Sm3+-modified lead-free 0.915(K0.45Na0.5Li0.05)NbO3–0.075BaZrO3–0.01(Bi0.5Na0.5)TiO3 (KNLN-BZ-BNT) ceramics are prepared. The piezoelectric properties are improved with the introduction of Sm3+, and the optimal properties (d33 = 325 pC/N and d33* = 384 pm/V) are achieved in the ceramic modified with 0.3 mol% Sm3+ ions. Meanwhile, this sample shows good thermal stability such that the values of d33* decreased less than 20% when the temperature raised from 30 to 180oC. These results show the Sm3+-modified KNLN-BZ-BNT ceramics are good for further applications even under high temperature.

Scope: To investigate the effect of Qingjie Fuzheng Granule (QFG) on lymphangiogenesis and lymphatic metastasis in colorectal cancer. Methods: The effects of QFG on the expression and secretion of vascular endothelial growth factor-C (VEGF-C) in HCT-116 cells were investigated both in vitro and in vivo. HCT-116 cells were treated with different concentrations (0.2, 0.5, and 1.0 mg/mL) of QFG. The VEGF-C expression level was determined using RT-qPCR and western blotting, and the VEGF-C concentration in supernatant was measured by ELISA. Tumor xenograft models of HCT-116 cells were generated using BALB/c nude mice, and the mice were randomly divided into a control group (gavaged with normal saline) and QFG group (gavaged with 2 g/kg QFG). The effect of QFG on tumor growth was evaluated by comparing the volume and weight of tumors between two groups. Immunohistochemistry (IHC) and RT-qPCR were performed to detect the expression levels of VEGF-C, vascular endothelial growth factor receptor 3 (VEGFR-3), and LYVE-1 (lymphatic vessel endothelial hyaluronan receptor 1). ELISA was performed to measure the concentration of serum VEGF-C. TMT proteomics technology and Reactome pathway analysis were used to explore the mechanism of QFG inhibiting lymphangiogenesis in tumor. The VEGF-C (5 ng/mL)-stimulated human lymphatic endothelial cell (HLEC) model was conducted to evaluate the effect of QFG on lymphangiogenesis in vitro. The model cells were treated with different concentrations (0.2, 0.5, and 1.0 mg/mL) of QFG. Cell viability was then determined using an MTT assay. The cell migration, invasion, and tube-formation ability were analyzed using transwell migration, matrigel invasion and tube formation assays, respectively. The underlying mechanism was uncovered, the levels of VEGFR-3, matrix metalloproteinase 2 (MMP-2), matrix metalloproteinase 9 (MMP-9), p-PI3K/PI3K, p-AKT/AKT and p-mTOR/ mTOR were detected using western blotting. Results: QFG significantly reduced VEGF-C expression and secretion in HCT-116 cells. QFG evidently suppressed in vivo tumor growth and the expression of VEGF-C, VEGFR-3, and LYVE-1. The serum VEGF-C level was also reduced by QFG. Moreover, TMT proteomics technology and Reactome pathway analysis identified 95 differentially expressed protein and multiple enriched pathway about matrix metalloproteinase and extracellular matrix, which is direct associate with lymphangiogenesis. In vitro experiment, QFG inhibited the viability, migration, invasion and tube formation of HLECs. Additionally, QFG reduced the VEGFR-3, MMP-2, MMP-9 expression levels, and the p-PI3K/PI3K, p-AKT/AKT, p-mTOR/ mTOR ratios. Conclusion: QFG can exert its effect on both tumor cells and HLECs, exhibiting ani- lymphangiogenesis in colorectal cancer via the VEGF-C/VEGFR-3 dependent PI3K/AKT pathway pathway.

Acoustic tweezers for microparticle non-contact manipulation have attracted attention in the biomedical engineering field. The key components of acoustic tweezers are piezoelectric materials, which convert electrical energy to mechanical energy. The most widely used piezoelectric materials are lead-based materials. Because of the requirement of environmental protection, lead-free piezoelectric materials have been widely researched in past years. In our previous work, textured lead-free (K, Na)NbO3 (KNN)-based piezoelectric ceramics with high piezoelectric performance were prepared. In addition, the acoustic impedance of the KNN-based ceramics is lower than that of lead-based materials. The low acoustic impedance could improve the transmission efficiency of the mechanical energy between acoustic tweezers and water. In this work, acoustic tweezers were prepared to fill the gap between lead-free piezoelectric materials research and applications. The tweezers achieved 13 MHz center frequency and 89% −6 dB bandwidth. The −6 dB lateral and axial resolution of the tweezers were 195 μm and 114 μm, respectively. Furthermore, the map of acoustic pressure measurement and acoustic radiation calculation for the tweezers supported the trapping behavior for 100 μm diameter polystyrene microspheres. Moreover, the trapping and manipulation of the microspheres was achieved. These results suggest that the KNN-based acoustic tweezers have a great potential for further applications.

Objective The objective was to further investigate apoptosis induction by Babao Dan (BBD), which supports its anti-tumor mechanisms, using two human gastric cancer cell lines (AGS and MGC80-3). Methods After treatment with various BBD concentrations, cell viability and cytotoxic effects were investigated using methyl thiazolyl tetrazolium (MTT) and lactate dehydrogenase (LDH) assays, respectively. The following indicators of cell apoptosis were evaluated: Annexin V-APC staining, caspase-3/-8/-9 activation, and mitochondrial membrane potential loss. Apoptosis-related protein levels (including Bcl-2-associated X protein [Bax], B-cell CLL/lymphoma 2 [Bcl-2], factor associated suicide [Fas], and Fas ligand [FasL]) were determined by western blot. The following multi-pathway factors were also assessed: p-ERK1/2, p-JNK, p-p38, and p-NF-κB. Results The MTT and LDH assays both demonstrated increased BBD cytotoxicity. BBD induced cell apoptosis by stimulating caspase-3/-8/-9 activity and destroying the mitochondrial membrane potential. BBD also regulated key factor expression levels including Bcl-2, Bax, Fas, and FasL and down-regulated protein phosphorylation via the MAPK and NF-κB pathway. Conclusions The possible anti-tumor mechanism is that BBD induces apoptosis via the MAPK and NF-κB signaling pathways.

The lead-free piezoelectric 0.915K0.5Na0.5NbO3-0.075BaZrO3-0.01Bi0.5Na0.5TiO3 (0.915KNN-0.075BZ-0.01BNT) films were prepared by a chemical solution deposition method. The films possess a pure rhomobohedral perovskite phase and a dense surface without crack. The temperature-dependent dielectric properties of the specimens manifest that only phase transition from ferroelectric to paraelectric phase occurred and the Curie temperature is 217 oC. The temperature stability of ferroelectric phase was also supported by the stable piezoelectric properties of the films. These results suggest that the slope of the morphotropic phase boundary (MPB) for the solid solution formed with the KNN and BZ in the films should be vertical. The voltage-induced polarization switching, and a distinct piezo-response suggested that the 0.915 KNN-0.075BZ-0.01BNT films show good piezoelectric properties.