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Metastatic castration-resistant prostate cancer (PC) is the final stage of PC that acquires resistance to androgen deprivation therapies (ADT). Despite progresses in understanding of disease mechanisms, the specific contribution of the metastatic microenvironment to ADT resistance remains largely unknown. The current study identified that the macrophage is the major microenvironmental component of bone-metastatic PC in patients. Using a novel in vivo model, we demonstrated that macrophages were critical for enzalutamide resistance through induction of a wound-healing–like response of ECM–receptor gene expression. Mechanistically, macrophages drove resistance through cytokine activin A that induced fibronectin (FN1)-integrin alpha 5 (ITGA5)–tyrosine kinase Src (SRC) signaling cascade in PC cells. This novel mechanism was strongly supported by bioinformatics analysis of patient transcriptomics datasets. Furthermore, macrophage depletion or SRC inhibition using a novel specific inhibitor significantly inhibited resistant growth. Together, our findings elucidated a novel mechanism of macrophage-induced anti-androgen resistance of metastatic PC and a promising therapeutic approach to treat this deadly disease.

RATIONALE AND OBJECTIVES Skeletal muscle mass measurement is the most important element for diagnosing sarcopenia. MRI has an excellent soft-tissue contrast, which can non-invasively assess abdominal skeletal muscle area (SMA) as well as CT. This study aimed to assess the validity and reliability of abdominal SMA measurement by comparing CT and MRI based on the fat image of IDEAL-IQ sequence at the lumbar level mid-L3. MATERIALS AND METHODS CT and MRI images of 32 patients diagnosed with various kidney diseases were used to analyze intra-observer variability among abdominal SMA measurements. This was done to evaluate the correlation of SMA between CT and fat images of MRI. SMA images were segmented using Materialise Mimics software before quantification. Interobserver reliability and validation of measurements was evaluated by two independent investigators. Abdominal SMA reproducibility and correlation between CT and MRI were then assessed using the intraclass correlation coefficient (ICC), coefficient of variation (CV), Bland-Altman plot, and Pearson's correlation coefficient respectively. RESULTS The interobserver reliability of MRI was excellent. The CV value was 2.82% while the ICC values ranged between 0.996 and 0.999. Validity was high (CV was 1.7% and ICC ranged between 0.986 and 0.996) for measurements by MRI and CT. Bland Altman analysis revealed an average difference of 2.2% between MRI and CT. The Pearson's correlation coefficient was 0.995 (p < 0.0001). This result revealed that there was a strong correlation between the two technologies. CONCLUSION MRI exhibited good interobserver reliability and excellent agreement with CT for quantification of abdominal SMA.

BackgroundGiant cell tumors of the mobile spine invasion of the adjacent vertebrae are an ignored imaging finding.MethodsNine patients with giant cell tumors of the mobile spine with invasion of the adjacent vertebrae confirmed by pathology were enrolled. Eight patients had pure giant cell tumors (GCTs), while one patient also had an aneurysmal bone cyst. All patients underwent conventional computed tomography, three-dimensional reconstruction, and conventional magnetic resonance imaging, while seven patients also underwent post-contrast magnetic resonance imaging.ResultsAll patients showed GCTs of the mobile spine that arose from the vertebral body and extended to the vertebral arch. The tumors showed soft-tissue attenuation with no evidence of a mineralized matrix. Pathological fracture was seen in five patients. The margin of the original tumor showed partial sclerosis in four patients and involved an adjacent vertebral body with a sclerotic rim in two patients. The tumors showed a homogeneous and similar signal intensity to the normal spinal cord on T1WI (T1-weighted image) in five patients. The cystic area of the tumors was hyperintense on T2WI in the remaining four patients, while one patient showed hemorrhage that was hyperintense on T1WI. The solid components of the GCTs show marked enhancement in all cases, while the cystic area of the tumors was observed without enhancement on contrast-enhanced images in four patients. Bone destruction of the adjacent vertebral body showed a homogeneous signal on T1WI and T2WI and marked enhancement on contrast-enhanced images.ConclusionsGiant cell tumors of the mobile spine with invasion into adjacent vertebrae are an unusual imaging finding. Radiologists should be familiar with this imaging characteristic.

BACKGROUND Multiple myeloma is a malignant hematological disease characterized by proliferation of monoclonal plasma cells mainly in the bone marrow. Extraosseous epidural plasmacytoma associated with myeloma arises from lymphoid tissue in the epidural space without focal vertebral involvement, and is rare. CASE SUMMARY A 52-year-old woman was diagnosed with kappa subtype nonsecretory multiple myeloma and presented with bilateral arm weakness 11 mo after completing multiple courses of chemotherapy. Spinal magnetic resonance imaging (MRI) showed a posterior C7–T3 epidural mass with spinal cord compression. After five courses of chemotherapy, follow-up MRI showed resolution of cord compression. A 54-year-old man presented with paraplegia 15 mo after a diagnosis of IgD kappa subtype multiple myeloma and completing multiple courses of chemotherapy. He underwent Th11 and L1 laminectomies for tumor resection because MRI showed an epidural mass causing cord compression. His-topathologic examination was consistent with IgD multiple myeloma. The patients have currently survived for 33 mo and 19 mo, respectively. CONCLUSION Isolated extraosseous epidural plasmacytoma associated with multiple myeloma without bony involvement is difficult to diagnose by imaging. Definitive diagnosis requires pathological and immunohistochemical examination.

Based on localized surface plasmon resonance (LSPR) enhanced quantum dot (QD) emission in a sandwich assay of “capture PCT antibody/PCT/detection PCT antibody labelled with QD” on a gold nanoarray chip, a fully automated point-of-care (POC) system for quick quantitative analysis of procalcitonin (PCT) for sepsis diagnostics was developed. The core technology of the system is to design and fabricate gold nanostructures that can generate plasmonics at resonant wavelength coincident with excitation wavelength of the fluorescent dyes. Gold nanopillar arrays at the size of 140 nm square and 320 nm pitch were found to be good candidates for the desired dye emission. Gold nanochip fabricated by e-beam lithography or nanoimprinting was integrated into a microfluidic chip, with analyte sampling and bioassay reagent flow controlled by LabVIEW program. To detect QD emission of the bioassay from the chip, a CCD camera and a laser source controlled by LabVIEW were incorporated to form a user-friendly and fully-automated POC system for on-site detection of PCT in clinics. Upon detection, the microfluidic chip is inserted into the POC system, where the processes of blood sample loading, detection antibody recognition, fluorescent dye labelling, fluorescent detection, and data analysis are conducted automatically in the device within 30 min at a test sensitivity of 0.5 ng/ml, which fulfills the clinical needs for diagnosis of sepsis through PCT biomarker.

Ginsenoside Rg3 is a steroidal saponin isolated from Panax ginseng. Previous studies have shown that Rg3 treatment downregulates the activity of rapamycin complex 1 (mTORC1) activity and inhibits the growth of cancer cells. However, the inhibitory effect of Rg3 on cancer cells is associated with high concentrations of Rg3 that are difficult to achieve in vivo. The human cervix adenocarcinoma HeLa cells were treated with Rg3. The protein levels of AMP-activated protein kinase alpha (AMPKα), protein kinase B(Akt), ribosomal S6 protein(S6), and Erk were determined by immunoblotting analyses. We used a fluorescent probe to detect reactive oxygen species (ROS) production in living cells. The oxygen consumption rate (OCR) was examined by the Seahorse Extracellular Flux Analyzer. The content of adenosine triphosphate (ATP) was measured by ATPlite kit and Mitotracker was applied to detect the mitochondria. We showed that at lower concentrations, Rg3 activates mTORC1 independent of AKT and AMP-activated protein kinase (AMPK). Rg3 promotes mitochondrial biogenesis and function, increases the oxygen consumption of mitochondria and the content of ATP. This effect is in contrast to that of high concentrations of Rg3, which inhibits cell growth. These findings demonstrate a pro-growth activity of Rg3 that acts through mTORC1 and mitochondrial biogenesis and suggest a dose-dependent effect of Rg3 on tumor cell growth., Graphical Abstract Ginsenoside Rg3 promotes cell growth through activation of mTORC1 and increasing mitochondrial biogenesis.

BackgroundCisplatin-based chemotherapy was previously considered as the standard adjuvant therapy for improved overall survival (OS) in patients with non-small cell lung cancer (NSCLC) after surgery. However, the benefit was limited due to high risks of recurrence and adverse events. In the present study, the efficacy of adjuvant epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) for EGFR-mutant patients after surgery was investigated using the latest updated data.MethodsThis meta-analysis included a comprehensive range of relevant studies identified from database searches. Disease-free survival (DFS) and OS with hazard ratios (HRs) were calculated using random-effect or fixed-effect models. Subgroup analysis was also performed.ResultsA total of seven randomized clinical trials were included in the meta-analysis and involved 1,283 NSCLC patients harboring EGFR mutations. In resected EGFR-mutant NSCLC patients, adjuvant EGFR-TKIs were significantly better than chemotherapy in terms of DFS (HR: 0.41; 95%CI: 0.24–0.70, P = 0.001), without showing any benefit in OS (HR: 0.72; 95%CI: 0.37–1.41, P = 0.336). No significant difference in DFS was observed between patients with EGFR exon 19 deletion and those with L858R mutation. Resected EGFR-mutant NSCLC patients treated with osimertinib experienced improved DFS and a lower risk of brain recurrence than those treated with gefitinib or erlotinib. Adjuvant EGFR-TKIs reduced the risk of bone and lung relapse, without decreasing the risk of local recurrence and liver relapse.ConclusionThis meta-analysis shows that adjuvant EGFR-TKI therapy could significantly prolong DFS in patients with resected EGFR-mutant NSCLC. Treatment with osimertinib showed improved DFS with a lower risk of brain recurrence than treatment with gefitinib or erlotinib for resected disease.

Cell proliferation and differentiation require signalling pathways that enforce appropriate and timely gene expression. We find that Tor2, the catalytic subunit of the TORC1 complex in fission yeast, targets a conserved nuclear RNA elimination network, particularly the serine and proline-rich protein Pir1, to control gene expression through RNA decay and facultative heterochro-matin assembly. Phosphorylation by Tor2 protects Pir1 from degradation by the ubiquitin-proteasome system involving the polyubiquitin Ubi4 stress-response protein and the Cul4–Ddb1 E3 ligase. This pathway suppresses widespread and untimely gene expression and is critical for sustaining cell proliferation. Moreover, we find that the dynamic nature of Tor2-mediated control of RNA elimination machinery defines gene expression patterns that coordinate fundamental chromosomal events dur-ing gametogenesis, such as meiotic double-strand-break formation and chromosome segregation. These findings have impor-tant implications for understanding how the TOR signalling pathway reprogrammes gene expression patterns and contributes to diseases such as cancer.

Background: Cisplatin (DDP) is the firs-line chemotherapeutic agent for the treatment of NSCLC. However, DDP resistance limits their usage to maximize the antineoplastic effect. The aims of this study were to investigate whether cordycepin (Cor) could reverse multidrug resistance (MDR) in NSCLC and to explore the underlying mechanisms.Methods: Cell proliferation and apoptosis were analyzed in NSCLC cell lines in vitro and in vivo, parental and DDP-resistant A549 cells, treated with DDP alone or combination with Cor. Proteins of different signaling pathways were investigated between DDP-sensistive and -insensitive A549 cell lines by GO terms and KEGG analysis, and perturbations of the MAPK and PI3K-AKT signaling pathways were evaluated by western blot. Results: Our data showed that Cor enhanced DDP inhibition of cell proliferation and promotion of apoptosis markedly compared to DDP alone group in both A549 and A549DDP. The synergic actions were associated with activation of AMPK and inhibition of AKT, mTOR and downstream P709S6K, S6 phosphorylation in the AKT pathway.Conclusion: Cor/DDP combination has synergistic effect on inhibiting proliferation and promoting apoptosis of NSCLC cells in the presence or absence of DDP resistance.

Cisplatin (DDP) is the first-line chemotherapeutic agent against lung cancer. However, the therapeutic effect of DDP loses over time due to the acquired drug resistance in non-small cell lung cancer (NSCLC) cells. In recent years, the role of the traditional Chinese medicine (TCM) cordycepin (Cor) in cancer treatment has been attracting attention. However, the effects of Cor on DDP resistance in NSCLC are unclear. In the present study, we aimed to investigate the effects of Cor in combination with DDP on cell proliferation and apoptosis in NSCLC and explore possible underlying mechanisms. The cell proliferation and apoptosis were analyzed in NSCLC parental (A549) and DDP-resistant (A549DDP) cells treated with DDP alone or in combination with Cor both in vitro and in vivo. Different genes and signaling pathways were investigated between DDP-sensitive and DDP-resistant A549 cells by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis. The perturbations of the MAPK and PI3K-AKT signaling pathways were evaluated by Western blot analysis. Our data showed that Cor markedly enhanced DDP inhibition on cell proliferation and promotion of apoptosis compared to the DDP-alone group in both A549 and A549DDP cells. The synergic actions were associated with activation of AMPK; inhibition of AKT, mTOR, and downstream P709S6K; and S6 phosphorylation in the AKT pathway compared with DDP alone. Collectively, combination of Cor and DDP has a synergistic effect in inhibiting proliferation and promoting apoptosis of NSCLC cells in the presence or absence of DDP resistance. The antitumor activity is associated with activation of AMPK and inhibition of the AKT pathway to enhance DDP inhibition on NSCLC. Our results suggested that Cor in combination with DDP could be an additional therapeutic option for the treatment of DDP-resistant NSCLC.

Background Limited treatment strategies are available for squamous-cell lung cancer (SQLC) patients. Few studies have addressed whether immune-related genes (IRGs) or the tumor immune microenvironment can predict the prognosis for SQLC patients. Our study aimed to construct a signature predict prognosis for SQLC patients based on IRGs. Methods We constructed and validated a signature from SQLC patients in The Cancer Genome Atlas (TCGA) using bioinformatics analysis. The underlying mechanisms of the signature were also explored with immune cells and mutation profiles. Results A total of 464 eligible SQLC patients from TCGA dataset were enrolled and were randomly divided into the training cohort (n = 232) and the testing cohort (n = 232). Eight differentially expressed IRGs were identified and applied to construct the immune signature in the training cohort. The signature showed a significant difference in overall survival (OS) between low-risk and high-risk cohorts (P < 0.001), with an area under the curve of 0.76. The predictive capability was verified with the testing and total cohorts. Multivariate analysis revealed that the 8-IRG signature served as an independent prognostic factor for OS in SQLC patients. Naive B cells, resting memory CD4 T cells, follicular helper T cells, and M2 macrophages were found to significantly associate with OS. There was no statistical difference in terms of tumor mutational burden between the high-risk and low-risk cohorts. Conclusion Our study constructed and validated an 8-IRG signature prognostic model that predicts clinical outcomes for SQLC patients. However, this signature model needs further validation with a larger number of patients.

Macroautophagy (autophagy) is driven by the coordinated actions of core autophagy-related (Atg) proteins. Atg8, the core Atg protein generally considered acting most downstream, has recently been shown to interact with other core Atg proteins via their Atg8-family-interacting motifs (AIMs). However, the extent, functional consequence, and evolutionary conservation of such interactions remain inadequately understood. Here, we show that, in the fission yeast Schizosaccharomyces pombe, Atg38, a subunit of the phosphatidylinositol 3-kinase (PtdIns3K) complex I, interacts with Atg8 via an AIM, which is highly conserved in Atg38 proteins of fission yeast species, but not conserved in Atg38 proteins of other species. This interaction recruits Atg38 to Atg8 on the phagophore assembly site (PAS) and consequently enhances PAS accumulation of the PtdIns3K complex I and Atg proteins acting downstream of the PtdIns3K complex I, including Atg8. The disruption of the Atg38-Atg8 interaction leads to the reduction of autophagosome size and autophagic flux. Remarkably, the loss of this interaction can be compensated by an artificial Atg14-Atg8 interaction. Our findings demonstrate that the Atg38-Atg8 interaction in fission yeast establishes a positive feedback loop between Atg8 and the PtdIns3K complex I to promote efficient autophagosome formation, underscore the prevalence and diversity of AIM-mediated connections within the autophagic machinery, and reveal unforeseen flexibility of such connections. Abbreviations: AIM: Atg8-family-interacting motif; AP-MS: affinity purification coupled with mass spectrometry; Atg: autophagy-related; FLIP: fluorescence loss in photobleaching; PAS: phagophore assembly site; PB: piggyBac; PE: phosphatidylethanolamine; PtdIns3K: phosphatidylinositol 3-kinase; PtdIns3P: phosphatidylinositol 3-phosphate.

A novel fast adaptive-gain complementary filter algorithm is developed for Unmanned Aerial Vehicle (UAV) attitude estimation. This approach provides an accurate, robust and simple method for attitude estimation with minimised attitude errors and reduced computation. UAV attitude data retrieved from accelerometer data is transformed to the solution of a linearly discrete dynamic system. A novel complementary filter is designed to fuse accelerometer and gyroscope data, with a self-adjusted gain to achieve a good performance in accuracy. The performance of the proposed algorithm is compared with an Adaptive-gain Complementary Filter (ACF) and Extended Kalman Filtering (EKF). Simulation and experimental results show that the accuracy of the proposed filter has the same performance as an EKF in high dynamic operating conditions. Therefore, the proposed algorithm can balance accuracy and time consumption, and it has a better price/performance ratio in engineering applications.

In this paper, a novel symbiosis approach is introduced to predict the on-wafer vector calibration drift error, hence the consistency of S-parameter measurement data, especially in mm-wave frequency band, will be greatly improved. This approach is based on the assumption that the calibration condition of measurement bench is symbiosis with the observable measurement parameters. The paper start with the analyzing of the drift error of a real on-wafer measurement system, then established a symbiosis drift model using support vector regression method to extract the model parameters. Experimental test examples are presented, revealing that this novel methodology provides a very efficient way to predict drift error and prolong the stability of on-wafer measurement system at mm-wave frequencies.

Objective: Compound traditional Chinese medicine (CTCM) with the application of compatibility from multiple active ingredients with multiple-specific targets can achieve a synergistic effect on cancer therapy. This study is aimed to observe the compatibility effects of Aidi injection on the treatment of hepatocellular carcinoma and to explore the mechanism of CTCM. Methods: Aidi injection is a clinical compound prescription containing Mylabris, Ginseng, Astragalus, and Acanthopanax, which can inhibit tumor growth and induce apoptosis. In this study, the anticancer activity of Aidi injection, as well as its disassembled and combined compositions, had been evaluated by varying levels of polyamine biomarkers on human hepatoma Hep-G2 cells detected using ultrahigh-performance liquid chromatography-tandem mass spectrometry. Results: According to the different variations in polyamine levels, it was revealed that Mylabris and Ginseng had an antitumor effect, while Astragalus acted as an assistant and Acanthopanax had weak anticancer activity. The increased level of polyamines in Hep-G2 cells had been found in HL-7702 cells. On combining Mylabris and Ginseng, polyamine levels went close to the normal level, which was even more marked when Astragalus was added. Aidi injection acted like the combination of Mylabris, Ginseng, and Astragalus. Conclusions: This study established a quantitative evaluation of the compatibility effects of Aidi injection based on polyamine biomarkers and evaluated the consistency of its anticancer effect, providing a manner to research the efficacy evaluation of CTCM. Moreover, the correlation between polyamine metabolism and anticancer activity can be used in anticancer drug screening.

We investigated methods for accelerating the e-beam writing by minimizing the exposure time of the resist. We write on positive resist ZEP of 400nm thick, keep a high voltage of 100kV to maintain the high resolution of each dot, and a low dot map of 20k to reduce the number of the dots. We vary the current, dose and resist development time, to write 510, 210, 120 or 60nm sized nanosquare or nanoslit arrays. The time durations for resist exposure and beam settling for each kind of patterns are calculated separately, and quality and deformation of each pattern are analyzed by scanning electron microscope images. The 510 to 120nm sized patterns written by 0.8nA with 178C/cm2 dose and 3min development yield comparable quality to the ones written by 0.2nA with 320C/cm2 and 30s development, while the exposure time is reduced to 14%. Because e-beam writing time for one-dimensional nanoslits mainly spends on resist exposure, this acceleration is more prominent for nanoslits than two-dimensional nanosquares. Acceleration of e-beam lithography by minimized resist exposure for large scale nanofabricationDisplay Omitted E-beam lithography is accelerated by minimizing the exposure time of the resist.Nanosquare or nanoslit arrays are written at different current, dose and development time.Time saving by reduced resist exposure time is more effective to nanoslit than nanosquare array.Exposure time can be reduced to 1/7 (at 0.8nA and 178C/cm2), while still get good patterns.

Heavy metals and metalloids such as cadmium [Cd(II)] and arsenic [As(III)] are widespread environmental toxicants responsible for multiple adverse health effects in humans. However, the molecular mechanisms underlying metal-induced cytotoxicity and carcinogenesis, as well as the detoxification and tolerance pathways, are incompletely understood. Here, we use global fitness profiling by barcode sequencing to quantitatively survey the Schizosaccharomyces pombe haploid deletome for genes that confer tolerance of cadmium or arsenic. We identified 106 genes required for cadmium resistance and 110 genes required for arsenic resistance, with a highly significant overlap of 36 genes. A subset of these 36 genes account for almost all proteins required for incorporating sulfur into the cysteine-rich glutathione and phytochelatin peptides that chelate cadmium and arsenic. A requirement for Mms19 is explained by its role in directing iron–sulfur cluster assembly into sulfite reductase as opposed to promoting DNA repair, as DNA damage response genes were not enriched among those required for cadmium or arsenic tolerance. Ubiquinone, siroheme, and pyridoxal 5′-phosphate biosynthesis were also identified as critical for Cd/As tolerance. Arsenic-specific pathways included prefoldin-mediated assembly of unfolded proteins and protein targeting to the peroxisome, whereas cadmium-specific pathways included plasma membrane and vacuolar transporters, as well as Spt–Ada–Gcn5-acetyltransferase (SAGA) transcriptional coactivator that controls expression of key genes required for cadmium tolerance. Notable differences are apparent with corresponding screens in the budding yeast Saccharomyces cerevisiae, underscoring the utility of analyzing toxic metal defense mechanisms in both organisms.

Summary In eukaryotes, heterochromatin is generally located at the nuclear periphery. This study investigates the biological significance of perinuclear positioning for heterochromatin maintenance and gene silencing. We identify the nuclear rim protein Amo1NUPL2 as a factor required for the propagation of heterochromatin at endogenous and ectopic sites in the fission yeast genome. Amo1 associates with the Rix1PELP1-containing RNA processing complex RIXC and with the histone chaperone complex FACT. RIXC, which binds to heterochromatin protein Swi6HP1 across silenced chromosomal domains and to surrounding boundary elements, connects heterochromatin with Amo1 at the nuclear periphery. In turn, the Amo1-enriched subdomain is critical for Swi6 association with FACT that precludes histone turnover to promote gene silencing and preserve epigenetic stability of heterochromatin. In addition to uncovering conserved factors required for perinuclear positioning of heterochromatin, these analyses elucidate a mechanism by which a peripheral subdomain enforces stable gene repression and maintains heterochromatin in a heritable manner.

Oxidative stress and neuroinflammation are important in the pathogenesis of ageing and age‑related neurodegenerative diseases, including Alzheimer's disease. NADPH oxidase 2 (NOX2) is a major source of reactive oxygen species (ROS) in the brain. The nucleotide‑binding oligomerisation domain (NOD)‑like receptor protein 1 (NLRP1) inflammasome is responsible for the formation of pro‑inflammatory molecules in neurons. Whether the NOX2‑NLRP1 inflammasome signalling pathway is involved in neuronal ageing and age‑related damage remains to be elucidated. Ginsenoside Rg1 (Rg1) is a steroidal saponin found in ginseng. In the present study, the primary hippocampal neurons were treated with H2O2 (200 µM) and Rg1 (1, 5 and 10 µM) for 24 h to investigate the protective effects and mechanisms of Rg1 on H2O2‑induced hippocampal neuron damage, which mimics age‑related damage. The results showed that H2O2 treatment significantly increased ROS production and upregulated the expression of NOX2 and the NLRP1 inflammasome, and led to neuronal senescence and damage to hippocampal neurons. Rg1 decreased ROS production, reducing the expression of NOX2 and the NLRP1 inflammasome in H2O2‑treated hippocampal neurons. Furthermore, Rg1 and tempol treatment significantly decreased neuronal apoptosis and the expression of β‑galactosidase, and alleviated the neuronal senescence and damage induced by H2O2. The present study indicates that Rg1 may reduce NOX2‑mediated ROS generation, inhibit NLRP1 inflammasome activation, and inhibit neuronal senescence and damage.

A lumped-element model for ON-chip interconnects is proposed in this paper. The effect of current return path of interconnects is analyzed. An efficient analytical parameter extraction method for the model is proposed. The inductor $L_{g}$ was adopted in the shunt branch of this model to characterize the induced time-varying magnetic field. Thus, the bandwidth of the model is extended over the resonance frequency. A group of interconnects with different structures were fabricated in a 0.18- $\mu \text{m}$ CMOS process to investigate the effects of current return path. The good agreement of $S$ -parameters between the model and measurements suggests that the proposed model can accurately predict the performance of interconnect in a wide frequency band up to 80 GHz, even over the resonance frequency.

Melt electrospinning is a novel technology in the field of 1D micro/nanostructure fabrication. Decreasing the diameter and promoting surface morphology of melt fiber are the key for the application of melt electrospinning technology. Heated sheath gas is introduced to build up melt electrospinning direct-write technology, and then orderly micro/nanofibers can be direct-written. The heated sheath gas provided a good way to increase the temperature of melt jet, by which solidification can be slowed. With the help of heated sheath gas, the diameter of melt fiber can be decreased. The affects of process parameters on the diameter of melt electrospinning fiber was investigated, the diameter of melt electrospinning fiber increased with the increasing of temperature of spinneret and feed rate, but decreased with the increasing of voltage and distance between spinneret and collector. Heated sheath gas is an excellent method to promote the application of melt electrospinning.

Electrohydrodynamic Direct-Writing (EDW) provides a simple and rapid way to print micro/nanostructures from viscoelastic solution, which meets the demand in the development of all-printed organic electronics. Overlapped printing of different functional materials to build up multi-layer devices displays excellent advantages in the flexible electron. The 3D multi-layer devices as well as flat interconnection can be fabricated on the flexible substrate directly via EDW technology. The technology of EDW utilized stable charged jet to print orderly conductive and insulator micro/nanostructure. Silver ink is used to print conductor connection, and polyvinylpyrrolidone (PVP) solution is used to fabricate insulator layer. Multi-layer interconnection can be printed layer by layer on the polyimide (PI) flexible insulator substrate. The resistance of top and bottom conductor connection was 6.1Ω and 5.9Ω, respectively. The insulator layer demonstrated excellent insulation characteristics between the bottom and top silver interconnection.

As a novel and simple non-contact fabrication method, electrohydrodynamic direct-write (EDW) has been regarded as one of the most potential technologies for large scale manufacturing of flexible and organic electronics. An inducing tip was introduced into the EDW apparatus. The enhanced electrical field between spinneret and inducing tip provided an excellent way to restrict the motion of charged jet, by which the stabilization of EDW jet can be promoted and the disturbances can also be overcome. Charged jet is deposited layer by layer to construct three dimension structure between spinneret and collector. The three dimension structure grows directly to the spinneret by the guidance and restriction of focused electric field. With the help of X-Y motion stage, the motion track of collector can be controlled by the host computer to fabricate designed pattern. The inducing tip provides a good way to increase the stability and deposition accurate of EDW charged jet.

Correlations are concerned for modeling of CMOS devices and circuits variability when using back propagation of variations (BPV) methodology in the paper. Strong reverse correlations are observed and investigated between variation parameters, particularly for threshold voltage (VT), total gate capacitance (Cgg) and trans-conductance (gm), on gate voltage dependence due to random dopant fluctuation (RDF) in nanometer MOSFETs. These correlations are verified both in theoretical and simulation approaches. Based on these correlations, a simple and accurate analytical model for capturing fT variability is proposed. The model is in good agreement with HSPICE Monte Carlo simulations in different design decisions such as effective width length ratios, source voltages and doping concentrations. Results show the estimation errors are not more than −2.33% and 1.30% for NMOS and PMOS, respectively. Furthermore, our analysis of the correlation and analytical formula are still effective for the continued scaling CMOS technology.

To review the clinical details and further treatments for recurrent spinal giant cell tumors (SGCT), and to analyze the risk factors of recurrence and shed new light on the treatment options and prognosis of recurrent SGCT.A retrospective analysis of recurrent SGCT between April 2003 and January 2014 was performed. A total of 10 patients comprising 3 men and 7 women with a mean age of 28.9 years (range, 21-40 years) were included in the study. All complete clinical data, radiographs, CT, MRI, scans and pathological data were reviewed. The tumor locations and the regions involved were evaluated by CT and MRI. The blood supply of the tumors was evaluated by enhanced CT and MRI. The mean follow-up was 81.3 months (range, 35.7-172.1 months).All patients had Enneking stage 3 tumors; 9 (90%) of them had different extents of spinal canal involvement in the primary time period. All patients underwent intralesional resection during their first surgery. Only 1 patient received local adjuvant treatments; no patient underwent selective arterial embolization or used denosumab at that time. Only 1 patient underwent adjuvant radiotherapy postoperatively, and another patient used bisphosphonates. After recurrence, 1 patient was cured using denosumab, and 2 patients' disease was controlled through use of other medical treatments or adjuvant treatments. There were 3 repeated recurrences and 7 repeated surgical procedures were performed in 5 patients. There were 6 intralesional excisions and 1 decompression surgery. The mean relapse-free time after the first surgery was 32.3 months (range, 10.5-62.6 months). The overall mean relapse-free time was 40.2 months (range, 10.5-157 months). No distant metastasis was found in our series. At the final follow-up, 4 patients were disease free, 3 patients' disease was under control, 2 has progressive disease aggravation, while 1 patient died as a result of progression of disease 133.9 months after first surgery.Intralesional excision for recurrent spinal giant cell tumors is an effective option that may have satisfactory prognosis. However, the excision and the inactivation of the lesion should be carried out carefully and thoroughly without missing any corners. Early diagnosis of recurrence may be associated with better prognosis. Adjuvant treatments perioperatively and systemic medical treatments can decrease recurrence rates and can have therapeutic effects in the recurrent SGCT.

Rhabdomyosarcoma (RMS) is the most common type of soft-tissue sarcoma in children. Immunotherapy has been proposed as a treatment for this deadly tumor. In the present study, the cytotoxicity of ex vivo expanded γδ T cells on RMS cell lines was evaluated and the molecular interactions involved were investigated. γδ T cells were expanded in vitro using peripheral blood mononuclear cells from 5 healthy donors and were stimulated with zoledronic acid (Zol) and interleukin 2. RMS cell lines RD and A-673 were used as target cells. The cytotoxicity of the γδ T cells against RMS was assessed in vitro and in vivo. γδ T cells were cytotoxic to RMS cells. Importantly, Zol markedly increased their cytotoxic potential. RMS cells treated with Zol-stimulated γδ T cells to produce interferon γ. γδ T cell-mediated cytotoxicity was primarily through the T cell receptor-dependent signaling pathway in blocking studies. Transfer of γδ T cells together with Zol into nude mice induced the regression of RD tumor xenotransplants. The results of the present study provide the rationale for the clinical evaluation of γδ T cells in RMS.

Biosensor and microfluidic chip based point-of-care (POC) testing offers many advantages over centralized laboratory testing, such as small sample and reagent volumes required, rapid detection and on-site analysis. In Temasek Polytechnic Microelectronics Center, we are focusing on developing biosensor and microfluidic chip based POC systems for immunological detection of diseases, such as Sepsis and Urinary Tract Infection (UTI). The systems integrate several elements: (1) biosensor, (2) microfluidic chip, (3) pumps and valves for fluid delivery, (4) signal detection components, and (5) a computer for controlling the fluidics, logging and data analysis. A POC system for quantitative analysis of procalcitonin (PCT) was developed based on a plasmonic biosensing chip. The plasmonic biosensing chip with gold nanopillar array structure was fabricated by high fidelity nanoimprinting technology. The chip was integrated into a microfluidic device to channel reagents over the nanopillar array. A robust sandwich bioassay of capture antibody / PCT / detection antibody labelled with quantum dot (QD) was established on the chip. To detect the QD emission from the chip, a CCD-based fluorescence detection system was built, which uses a laser beam as light source and an air-cooled CCD camera as detector. A compact circular multi-purpose holder for receiving the microfluidic device was designed with reduced tubing length and optimized valves and reservoirs configuration. With incorporation of the control cum switching software program, this POC system is user friendly and provides a desirable on-site yet sensitive detection of PCT at 1ng/ml for clinical practice. Another POC system integrated with dielectrophoresis on-chip concentration module was developed for UTI detection. A sandwiched immunoassay was developed on microfabricated interdigitated electrode (IDE) biosensor chip for UTI E.Coli detection. Dielectrophoresis (DEP) technology was successfully used to concentration E.Coli and increased the local concentration of bacteria for more than 1000 folds. The DEP-enhanced microfluidic immunoassay can detect E.Coli at the concentration level of 105 CFU/ml.

This paper firstly introduces the construction status of Intangible Cultural Heritage Resources, and discusses the importance in combination with “Internet +”. Mainly analyzes the platform’s construction and Service of Intangible Cultural Heritage Resources. Finally discusses the main problems that to be paid attention to and solved.

Point-of-care devices are highly desired not only in developing countries, but also in developed countries for the medical detection for remote/rural areas and home use. Compared with conventional bulky immunosystem widely used in central laboratories and hospitals, point-of-care device is usually cost-effective for each test, with small footprint and light weight, and however tends to suffer low sensitivity and inaccurate quantification. So some signal amplification mechanisms are required for the development of a reliable point-of-care device with high sensitivity for clinical use, such as early-stage cancer detections. In this book chapter, we introduce in detail for the development of point-of-care devices based on gold nanoarray generated plasmonics, i.e., localized surface plasmon resonance (LSPR). We have demonstrated that the gold nanoarray sensing chip can be fabricated in a cost-effective way by combining the nickel mold fabrication and nanoimprinting, and the sensing chip can be used to detect the clinical related biomarkers either by direct one-step assay through the LSPR absorption peak shift detected using a portable optical spectroscopy, with example given for cardiac troponin I (cTnI); or by a sandwich assay with its fluorescent label signal amplified by LSPR to achieve higher sensitivity, which can be detected on a commercial microscope or home-developed fully automated point-of-care device, as exemplified by prostate specific antigen (PSA) detection for prostate cancer, thrombin detection for blood clots, and procalcitonin (PCT) detection for sepsis. The advantage of the gold nanoarray LSPR-based point-of-care device is that the sensing area can be as small as the light beam, the sensing chip can be sealed in a microfluidic channel and use a little amount of the analyte and bio-reagent, and the optical signal can be detected by images to facilitate the future multichannel detections with little additional cost. Our fully automated point-of-care device detects the PCT with only 50 μL of analyte, and provides the data with 30 min at a test cost of less than 10 US dollars. Our experiments also demonstrated that both kinds of point-of-care devices are with enough sensitivity for clinical use.

It is increasingly apparent that cancer development depends not only on genetic alterations, but also on epigenetic changes involving histone modifications. GASC1, member of the histone demethylases affecting heterochromatin formation and transcriptional repression, has been found to be dysregulation in many types of cancers including breast cancer, prostate cancer, metastatic lung sarcomatoid carcinoma, and leukemia. In this study, we examined the expression of GASC1 and certain GASC1-targeted genes (KLF4, MYC, SOX2, PPARG, MDM2, and NANOG) and identified a three-gene prognostic signature (PPARG, MDM2, and NANOG), using risk scores based on immunohistochemical analyses of 149 tumor specimens from patients with esophageal squamous cell carcinoma (ESCC). The presence of a high-risk three-gene signature in the ESCC tumors was significantly associated with decreased overall survival (OS) of the patients. We validated the predictive value of the three-gene signature in a second independent cohort of 101 patients with ESCC in order to determine whether it had predictive value. The results were similar to those in 149 patients. According to multivariate Cox proportional hazards analyses, the predictive model of a three-gene signature was an independent predictor for OS (p = 0.005 in cohort 1, p = 0.025 in cohort 2). In addition, ROC analysis indicated that the predictive ability of the three-gene model was more robust than that of a single biomarker. Therefore, our three-gene signature is closely associated with OS among patients with ESCC and may serve as a predictor for the poor prognosis of ESCC patients. What's new? Epigenetic alterations that involve modifications to histones are thought to play critical roles in cancer, with effects on processes ranging from tumor development to metastasis. The present investigation focused on the expression of the histone demethylase GASC1 and its gene targets in tumors from patients with esophageal squamous cell carcinoma (ESCC). Using risk scores from immunohistochemical analyses, the authors developed a three-gene prognostic signature involving the genes PPARG, MDM2, and NANOG. The signature was associated with a reduction in overall survival of ESCC patients, suggesting that it is predictive for poor prognosis in ESCC.

A new secondary metabolite, named altertoxin IV (1), together with altertoxin II (2), was isolated from the fermentation broth of Alternaria tenuissima, an endophytic fungal strain residing in the stem of Tribulus terrestris L. The structure of new compound 1 was established by HR-ESI-MS, multinuclear NMR spectroscopy, and single crystal X-ray diffraction method. In their in vitro bioassay, compound 2 exhibited moderate cytotoxic activity against PC-3 cell lines with an IC50 value of 14.28 μM.

Background: Colorectal cancer (CRC) remains one of the leading contributors to cancer-related mortality and morbidity worldwide. Traditional Chinese medicines have been widely employed to treat various types of cancer in China. This investigation aims to determine the association between Chinese herbal medicine (CHM) therapy and survival outcomes in CRC patients with liver-limited metastases. Methods: A retrospective cohort study was performed among patients with colorectal liver metastases at the First Affiliated Hospital of Guangzhou University of Chinese Medicine in Guangzhou, China. Data from a series of consecutive patients were collected via an electronic medical record system or telephone follow-up. We defined high exposure as a period of CHM therapy lasting more than 6 months. The primary outcome was overall survival. Results: The study included the data of 191 patients from January 2008 to December 2017; 126 patients (65.97%) met the inclusion criteria of high exposure to CHM. Multivariate analyses revealed that high exposure to CHM was associated with better overall survival (hazard ratio = 0.444, 95% confidence interval = [0.213, 0.926], P = .030). The association was further confirmed by a subgroup exploratory analysis. Conclusion: Long-term CHM therapy is correlated with improved survival outcomes in CRC patients with liver-limited metastases.

One new polyhydroxylated steroid, caerulsteroid A (1), along with nine known analogues (2-10), was isolated from the gorgonian coral Anthogorgia caerulea collected from the South China Sea. The structure of the new compound was elucidated by 1-D and 2-D NMR, and mass spectrometry. The absolute configuration of 1 was assigned on the basis of the absolute configurations of the related congeners 2 and 3, which were determined by application of the modified Mosher's method. The isolated compounds were assayed for their cytotoxicity, antimicrobial activity and lethality towards brine shrimp Artemia salina.

The effect of the addition of stearic acid on properties of wheat, mung bean and potato starches were studied. Soluble amylose content in three kinds of starches was significantly reduced. Both λmax values and the 630/520 nm ratio were decreased. Stearic acid added starches showed a significantly higher pasting temperature, breakdown and setback compared to the native starches as measured by RVA. Texture properties analysis showed that hardness of wheat and mung bean starches significantly decreased, while that of potato starch significantly increased after the addition of stearic acid. Diffraction peaks of wheat, mung bean and potato starches appeared at 22° which indicated that complex formation by X-ray diffraction

Jumonji AT-rich interactive domain 1B (JARID1B) and PHD finger protein 2 (PHF2), members of the histone demethylases, have been found to be involved in many types of tumors. However, the expression and prognostic significance of JARID1B and PHF2 in esophageal squamous cell carcinoma (ESCC) still remains unclear. In this study, JARID1B and PHF2 expression were detected on tissue microarrays of ESCC samples in 120 cases using immunohistochemical staining. Our results showed that JARID1B and PHF2 were overexpressed in ESCCs. In addition, a significant correlation was observed between JARID1B nuclear expression level and histological grade (P=0.003). Kaplan-Meier survival analysis showed a tendency that high cytoplasmic expression of JARID1B and PHF2 was associated with decreased overall survival of ESCC patients, whereas JARID1B high expression in the nucleus was associated with high overall survival, although there was no statistical significance. Overall, our data suggest that JARID1B and PHF2 are overexpressed in ESCC and that they may play crucial roles in the course of ESCC initiation and/or progression.

Autophagy cargos include not only soluble cytosolic materials but also bulky organelles, such as ER and mitochondria. In budding yeast, two proteins that contain the PX domain and the BAR domain, Atg20 and Atg24 (also known as Snx42 and Snx4, respectively) are required for organelle autophagy and contribute to general autophagy in a way that can be masked by compensatory mechanisms. It remains unclear why these proteins are important for organelle autophagy. Here, we show that in a distantly related fungal organism, the fission yeast Schizosaccharomyces pombe, autophagy of ER and mitochondria is induced by nitrogen starvation and is promoted by three Atg20- and Atg24-family proteins – Atg20, Atg24 and SPBC1711.11 (named here as Atg24b). These proteins localize at the pre-autophagosomal structure, or phagophore assembly site (PAS), during starvation. S. pombe Atg24 forms a homo-oligomer and acts redundantly with Atg20 and Atg24b, and the latter two proteins can form a hetero-oligomer. The organelle autophagy defect caused by the loss of these proteins is associated with a reduction of autophagosome size and a decrease in Atg8 accumulation at the PAS. These results provide new insights into the autophagic function of Atg20- and Atg24-family proteins.