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The results obtained by our simulations can provide effective guidance for the design of nanoparticle-grafted bimodal bidisperse polymer chains and provide a theoretical basis for experimentation and production of polymer nanocomposites with better performance.

This study aims to evaluate the intra-procedural use of a novel ablation confirmation (AC) method, consisting of biomechanical deformable image registration incorporating AI-based auto-segmentation, and its impact on tumor coverage by quantitative three-dimensional minimal ablative margin (MAM) CT-generated assessment.This single-center, randomized, phase II, intent-to-treat trial is enrolling 100 subjects with primary and secondary liver tumors (≤ 3 tumors, 1-5 cm in diameter) undergoing microwave or radiofrequency ablation with a goal of achieving ≥ 5 mm MAM. For the experimental arm, the proposed novel AC method is utilized for ablation applicator(s) placement verification and MAM assessment. For the control arm, the same variables are assessed by visual inspection and anatomical landmarks-based quantitative measurements aided by co-registration of pre- and post-ablation contrast-enhanced CT images. The primary objective is to evaluate the impact of the proposed AC method on the MAM. Secondary objectives are 2-year LTP-free survival, complication rates, quality of life, liver function, other oncological outcomes, and impact of AC method on procedure workflow.The COVER-ALL trial will provide information on the role of a biomechanical deformable image registration-based ablation confirmation method incorporating AI-based auto-segmentation for improving MAM, which might translate in improvements of liver ablation efficacy.The COVER-ALL trial aims to provide information on the role of a novel intra-procedural AC method for improving MAM, which might translate in improvements of liver ablation efficacy.ClinicalTrials.gov identifier: NCT04083378.

We present observational constraints on the galaxy-halo connection, focusing particularly on galaxy assembly bias, from a novel combination of counts-in-cylinders statistics, $P(N_{\rm{CIC}})$, with the standard measurements of the projected two-point correlation function, $w_{\rm{p}}(r_{\rm{p}})$, and number density, $n_{\rm{gal}}$, of galaxies. We measure $n_{\rm{gal}}$, $w_{\rm{p}}(r_{\rm{p}})$ and $P(N_{\rm{CIC}})$ for volume-limited, luminosity-threshold samples of galaxies selected from SDSS DR7, and use them to constrain halo occupation distribution (HOD) models, including a model in which galaxy occupation depends upon a secondary halo property, namely halo concentration. We detect significant positive central assembly bias for the $M_r, 16+5 pages, 9+3 figures, 5+2 tables, Fig. 6 shows the main result. To be submitted to MNRAS, comments welcome

Supplementary Table S1. The primers used for real-time PCR analysis Supplementary Table S2. ABPs obtained from Kyoto Encyclopedia of Genes and Genomes (KEGG) database

S1. The GEPIA website (based on TCGA data) revealed that 48 ABPs were significantly up-regulated in GC tissues. S2. H. pylori induces L-plastin expression in GC cells. S3. Direct contact is required for H. pylori induced L-plastin expression in GC cells. S4. The vacA was not involved in the induction of L-plastin. S5. Decreased expression of L-plastin in presence of U0126 during H. pylori infection. S6. L-plastin expression is increased in GC tissues.

Figure S1. NK cell and T cell numbers in the peripheral blood, non-tumor and tumor tissues of GC patients. Figure S2. Expression of activating and inhibitory receptors on NK cells in the peripheral blood, non-tumor and tumor tissues of GC patients. Figure S3. Expression of CD56 and CD16 on NK cells in the peripheral blood, non-tumor and tumor tissues of GC patients. Figure S4. The expression of HLA-DR on tissue-associated monocytes/macrophages in GC patients. Figure S5. The expression of CD48, PD-L1 and PD-L2 on tissue-associated monocytes/macrophages in GC patients. Figure S6. Co-expression of CD68 and TGF-beta1 in tumors of GC patients. Figure S7. Surface expression levels of TGF-beta1 on tumor-associated monocytes/macrophages in GC patients. Table S1. Clinical characteristics of 65 GC patients. Table S2. Fluorochrome-conjugated antibodies used in flow cytometry. Table S3. Univariate and multivariate analyses of factors associated with survival.

Natural killer (NK) cells are a major component of the host antitumor immune response in human cancer. However, the nature, functional regulation, and clinical relevance of NK cells in gastric cancer remain largely unknown. In this study, we showed that the percentages of NK cells in tumors were significantly decreased, and low percentages of tumor-infiltrating NK cells were positively correlated with poor survival and disease progression. Although the expression of activating and inhibitory receptors on NK cells was shown to be not different between tumor and nontumor tissues, NK cells in tumors had impaired effector functions, characterized by decreased IFNγ, TNFα, and Ki-67 expression. We found that tumor-infiltrating monocytes/macrophages were physically close to NK cells, and their percentages negatively correlated with IFNγ+ and TNFα+ NK-cell percentages. Ex vivo study showed that isolated tumor-associated monocytes/macrophages could impair NK-cell expression of IFNγ, TNFα, and Ki-67. Blockade of TGFβ1 attenuated such monocytes/macrophages-mediated impairment of NK-cell function. Our data suggest that human NK-cell function was impaired by tumor-associated monocytes/macrophages, and that restoring NK-cell function may be an important therapeutic strategy to prevent tumor immune escape in gastric cancer. Cancer Immunol Res; 5(3); 248–56. ©2017 AACR.

Actin cytoskeleton dynamic rearrangement is required for tumor cell metastasis and is a key characteristic of Helicobacter pylori (H. pylori)-infected host cells. Actin cytoskeleton modulation is coordinated by multiple actin-binding proteins (ABP). Through Kyoto encyclopedia of gene and genomes database, GEPIA website, and real-time PCR data, we found that H. pylori infection significantly induced L-plastin, a key ABP, in gastric cancer cells. We further explored the regulation and function of L-plastin in H. pylori–associated gastric cancer and found that, mechanistically, H. pylori infection induced gastric cancer cells to express L-plastin via cagA-activated ERK signaling pathway to mediate SP1 binding to L-plastin promoter. Moreover, this increased L-plastin promoted gastric cancer cell proliferation and migration in vitro and facilitated the growth and metastasis of gastric cancer in vivo. Finally, we detected the expression pattern of L-plastin in gastric cancer tissues, and found that L-plastin was increased in gastric cancer tissues and that this increase of L-plastin positively correlated with cagA+ H. pylori infection status. Overall, our results elucidate a novel mechanism of L-plastin expression induced by H. pylori, and a new function of L-plastin–facilitated growth and metastasis of gastric cancer, and thereby implicating L-plastin as a potential therapeutic target against gastric cancer.Implications:Our results elucidate a novel mechanism of L-plastin expression induced by H. pylori in gastric cancer, and a new function of L-plastin–facilitated gastric cancer growth and metastasis, implicating L-plastin as a potential therapeutic target against gastric cancer.

This article presents a novel permanent magnet assisted flux-controllable machine, namely the hybrid-excited biased-flux machine (HEBFM). The proposed machine can implement flexible flux regulations (i.e., either field weakening or strengthening) by integrating the field current winding with the half consequence permanent magnet (PM) poles in the stator. The topology of the HEBFM can be explored to multi-pole cases, which contributes to improved flexibility for the flux control and winding regulation. Compared to the conventional flux-controllable machines, the proposed machine gains the merits of owning (i) extended flux control range via the modulation of winding factor (i.e., winding factor modulation), (ii) stable and compact structure and (iii) reduced demagnetization risk of permanent magnetics (PMs), (iv) capability of topology exploration. In this paper, operation principle and electromagnetic performance of the proposed machine is analyzed using the finite element method (FEM). Besides, the torque and torque ripple are optimized based on the multi-objective differential evolution (DE) coupled with FEM. Finally, a prototype is manufactured and tested to validate the effectiveness and feasibility of the proposed machine designs.

GGC repeat expansion in the 5′ untranslated region (UTR) of NOTCH2NLC is associated with a broad spectrum of neurological disorders, especially neuronal intranuclear inclusion disease (NIID). Studies have found that GGC repeat expansion in NOTCH2NLC induces the formation of polyglycine (polyG)-containing protein, which is involved in the formation of neuronal intranuclear inclusions. However, the mechanism of neurotoxicity induced by NOTCH2NLC GGC repeats is unclear. Here, we used NIID patient-specific induced pluripotent stem cell (iPSC)-derived 3D cerebral organoids (3DCOs) and cellular models to investigate the pathophysiological mechanisms of NOTCH2NLC GGC repeat expansion. IPSC-derived 3DCOs and cellular models showed the deposition of polyG-containing intranuclear inclusions. The NOTCH2NLC GGC repeats could induce the upregulation of autophagic flux, enhance integrated stress response and activate EIF2α phosphorylation. Bulk RNA sequencing for iPSC-derived neurons and single-cell RNA sequencing (scRNA-seq) for iPSC-derived 3DCOs revealed that NOTCH2NLC GGC repeats may be associated with dysfunctions in ribosome biogenesis and translation. Moreover, NOTCH2NLC GGC repeats could induce the NPM1 nucleoplasm translocation, increase nucleolar stress, impair ribosome biogenesis and induce ribosomal RNA sequestration, suggesting dysfunction of membraneless organelles in the NIID cellular model. Dysfunctions in ribosome biogenesis and phosphorylated EIF2α and the resulting increase in the formation of G3BP1-positive stress granules may together lead to whole-cell translational inhibition, which may eventually cause cell death. Interestingly, scRNA-seq revealed that NOTCH2NLC GGC repeats may be associated with a significantly decreased proportion of immature neurons while 3DCOs were developing. Together, our results underscore the value of patient-specific iPSC-derived 3DCOs in investigating the mechanisms of polyG diseases, especially those caused by repeats in human-specific genes.

For a hundred years the Saint Jacques area has been known to produce rich Oligocene vertebrate fossils, yet only a handful of previous studies have focused on this area. Since 2010, we have conducted 12 field expeditions to Saint Jacques, and here we report findings from our paleontological excavations and stratigraphical investigations. Twenty-two fossiliferous blocks across the area are recognized and a chronostratigraphic framework has been established to aid fossil collection. Fossil-mammal materials have been recovered in situ from 1635 localities and additionally from surface sediments. Fossiliferous blocks in the area are correlated by lithological similarity and lateral tracing. Lithologically, the area is mainly composed of reddish silty mudstone and muddy siltstone, with three distinctive layers of grayish white sandstone. The measured composite stratigraphic column spans 239 meters and are divided into 12 lithostratigraphic units. Contrary to previous knowledge that Saint Jacques contains two Oligocene mammalian assemblages, our preliminary biostratigraphic analysis of small mammals shows that the area documents successive faunal transition from the Eocene to possibly the early Miocene. The hyracodontid perissodactyl Ardynia, the ctenodactyloid rodent Gobiomys, and the basal Glires Gomphos from the bottom litho-units imply the presence of the Eocene–Oligocene boundary, while small mammal assemblage of the top units is similar to Miocene faunas in northern China and Mongolia. Thus, rock strata in Saint Jacques likely span the Eocene through the early Miocene, bracketing an entire Oligocene sequence within. In sum, our re-exploration of Saint Jacques has greatly expanded the chronostratigraphic and taxonomic coverage of the mammalian fossil collection from this area. This long, successive Oligocene sequence makes an important record for studying the Eocene–Oligocene Transition. Further study in this area will contribute to a range of paleontological and paleoenvironmental questions.

Background Previous studies have shown that peripheral immune dysregulation plays a paramount role in Alzheimer’s disease (AD), but whether there is a protective causal relationship between peripheral immunophenotypes and AD risk remains ambiguous. Methods Two-sample Mendelian randomization (MR) was performed using large genome-wide association study (GWAS) genetic data to assess causal effects between peripheral immunophenotypes and AD risk. Results This study identified four regulatory T cell (Treg) immunophenotypes—CD25 + + CD45RA- CD4 not regulatory T cell % T cell or CD4 + T cell; Secreting or Activated & secreting CD4 regulatory T cell % CD4 regulatory T cell; monocyte immunophenotype (HLA DR + + monocyte % monocyte); and dendritic cell (DC) subtype (HLA DR on myeloid Dendritic Cell)—that were protective against AD. Discussion These findings enhance the comprehension of the protective role of peripheral immunity in AD and provide further support for Treg and monocyte as potential targets for immunotherapy in AD.

Background To evaluate the feasibility of a novel approach for predicting hepatocellular carcinoma (HCC) response to drug-eluting beads transarterial chemoembolization (DEB-TACE) using computed tomography hepatic arteriography enhancement mapping (CTHA-EM) method. Methods This three-institution retrospective study included 29 patients with 46 HCCs treated with DEB-TACE between 2017 and 2020. Pre- and posttreatment CTHA-EM images were generated using a prototype deformable registration and subtraction software. Relative tumor enhancement (TPost/pre-RE) defined as the ratio of tumor enhancement to normal liver tissue was calculated to categorize tumor response as residual (TPost-RE > 1) versus non-residual (TPost-RE ≤ 1) enhancement, which was blinded compared to the response assessment on first follow-up imaging using modified RECIST criteria. Additionally, for tumors with residual enhancement, CTHA-EM was evaluated to identify its potential feeding arteries. Results CTHA-EM showed residual enhancement in 18/46 (39.1%) and non-residual enhancement in 28/46 (60.9%) HCCs, with significant differences on TPost-RE (3.05 ± 2.4 versus 0.48 ± 0.23, respectively; p < 0.001). The first follow-up imaging showed non-complete response (partial response or stable disease) in 19/46 (41.3%) and complete response in 27/46 (58.7%) HCCs. CTHA-EM had a response prediction sensitivity of 94.7% (95% CI, 74.0–99.9) and specificity of 100% (95% CI, 87.2–100). Feeding arteries to the residual enhancement areas were demonstrated in all 18 HCCs (20 arteries where DEB-TACE was delivered, 2 newly developed collaterals following DEB-TACE). Conclusion CTHA-EM method was highly accurate in predicting initial HCC response to DEB-TACE and identifying feeding arteries to the areas of residual arterial enhancement.

Fast radio bursts (FRBs) are bright millisecond radio bursts at cosmological distances. Only three FRBs have exhibited extreme activities, such as achieving a peak event rate $\gtrsim 100$ hr$^{-1}$ or being persistently active. Only these three among $\sim 50$ known repeating FRBs have circular polarization. We observed the FRB 20220912A with the Robert C. Byrd Green Bank Telescope (GBT) at L-band on 24 October 2022 and detected 128 bursts in 1.4 hours, corresponding to a burst rate of about 90 hr$^{-1}$, which is the highest yet for FRBs observed by the GBT and makes it the fourth extremely active FRB. The median energy of the bursts is $4.0\times10^{37}$ erg, close to the characteristic energy of FRB 20121102A. The average rotation measure (RM) was $-$0.4 rad m$^{-2}$ with unnoticeable intraday RM change, indicating a likely clean environment, in contrast to the other three extremely active repeating FRBs. Most bursts have nearly 100% linear polarization. Approximately 56% of the bright bursts have circular polarization, the highest such fraction among all FRBs. A downward drift in frequency and polarization angle swings were found in our sample. The discovery and characterization of FRB 20220912A support the view that the downward drift in frequency, polarization angle swings, and circular polarization are intrinsic to radiation physics, which may be shared by active repeaters regardless of the environments.

We report the radio observations of the eclipsing black widow pulsar J1720-0534, a 3.26 ms pulsar in orbit with a low mass companion of mass 0.029 to 0.034 M$_{\odot}$. We obtain the phase-connected timing ephemeris and polarization profile of this millisecond pulsar (MSP) using the Five-hundred-meter Aperture Spherical Radio Telescope (FAST), the Green Bank Telescope (GBT), and the Parkes Telescope. For the first time from such a system, an oscillatory polarisation angle change was observed from a particular eclipse egress with partial depolarization, indicating 10-milliGauss-level reciprocating magnetic fields oscillating in a length scale of 5000 km (assuming an orbital inclination angle of 90 degrees) outside the companion's magnetosphere. The dispersion measure variation observed during the ingresses and egresses shows the rapid raising of the electron density in the shock boundary between the companion's magnetosphere and the surrounding pulsar wind. We suggest that the observed oscillatory magnetic fields originate from the pulsar wind outside the companion's magnetosphere., Comment: 18 pages, 8 figures, 1 table, accepted by RAA

Aim: In response to the COVID-19 pandemic, Regeneron developed the anti-SARS-CoV-2 monoclonal antibody cocktail, REGEN-COV® (RONAPREVE® outside the USA). Drug concentration data was important for determination of dose, so a two-part bioanalytical strategy was implemented to ensure the therapy was rapidly available for use. Results & methodology: Initially, a liquid chromatography-multiple reaction monitoring-mass spectrometry (LC-MRM-MS) assay, was used to analyze early-phase study samples. Subsequently, a validated electrochemiluminescence (ECL) immunoassay was implemented for high throughput sample analysis for all samples. A comparison of drug concentration data from the methods was performed which identified strong linear correlations and for Bland-Altman, small bias. In addition, pharmacokinetic data from both methods produced similar profiles and parameters. Discussion & conclusion: This novel bioanalytical strategy successfully supported swift development of a critical targeted therapy during the COVID-19 public health emergency.

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Obtaining accurately calibrated redshift distributions of photometric samples is one of the great challenges in photometric surveys like LSST, Euclid, HSC, KiDS, and DES. We present an inference methodology that combines the redshift information from the galaxy photometry with constraints from two-point functions, utilizing cross-correlations with spatially overlapping spectroscopic samples, and illustrate the approach on CosmoDC2 simulations. Our likelihood framework is designed to integrate directly into a typical large-scale structure and weak lensing analysis based on two-point functions. We discuss efficient and accurate inference techniques that allow us to scale the method to the large samples of galaxies to be expected in LSST. We consider statistical challenges like the parametrization of redshift systematics, discuss and evaluate techniques to regularize the sample redshift distributions, and investigate techniques that can help to detect and calibrate sources of systematic error using posterior predictive checks. We evaluate and forecast photometric redshift performance using data from the CosmoDC2 simulations, within which we mimic a DESI-like spectroscopic calibration sample for cross-correlations. Using a combination of spatial cross-correlations and photometry, we show that we can provide calibration of the mean of the sample redshift distribution to an accuracy of at least 0.002(1+z), consistent with the LSST-Y1 science requirements for weak lensing and large-scale structure probes., Comment: Updated to match the version accepted by the MNRAS, 23 pages, 9 figures, 2 tables

Many secreted proteins, including cytokines, growth factors and hormones, are crucial in processes like intercellular signaling. Dynamic changes in secreted proteins usually reflect the growth and pathological state of the cells. Many drug targets are secretory proteins. The proteins are also important biomarkers. Conditioned cell culture media are important samples for secretory proteomic studies. Biomass spectrometry-based proteomic analysis enables the systematic study of secretory proteins. The main problem in analyzing secretory proteins in conditioned culture media is the low concentration of these proteins and the presence of serum, amino acids, and additives in culture media that may interfere with the protein analysis. Conventional secretory proteome analysis uses serum-free cell culture to reduce sample complexity, and typically involves protein concentration, purification, and desalting using ultrafiltration, dialysis, lyophilization, and trichloroacetic acid (TCA) or acetone precipitation, followed by enzymatic digestion and mass spectrometry analysis. This analytical process does not allow specific enrichment of secreted proteins. Thus, only a few secreted proteins can be identified. In addition, prolonged serum-free incubation of cells also tends to lead to unexpected changes in their activity status. A bioorthogonal-based enrichment approach can effectively avoid this problem. In recent years, unnatural sugars containing bio-orthologous groups, such as azide groups, have been used to metabolically label glycosylated proteins, enabling cellular imaging or selective enrichment of glycoproteins and their use for proteomic analysis. The strategy is a two-step process. First, azide-based sugar analogues are added to the cell culture medium and introduced to glycoproteins via the intracellular glycan biosynthesis pathway. Second, they are specifically covalently labeled with imaging probes or affinity probes via click chemistry. Since secreted proteins are usually glycoproteins, this glycolytic labeling has been used to label and enrich secreted proteins. N-Azidoacetylgalactosamine (GalNAz), N-azidoacetylglucosamine (GlcNAz), and N-azidoacetylmannosamine (ManNAz) are classical azide-based sugar analogues. Their effects on cytoplasmic membrane proteins have been compared. However, only ManNAz has been used for metabolic labeling of secreted proteins. No other glyco-analogues that label secreted proteins have been reported. Here, the bio-orthogonal chemical biology technology achieved highly selective labeling and enriched secreted proteins. In combination with click chemistry, different sugar analogues were evaluated for metabolic labeling of secreted proteins. HeLa cells were metabolically labeled by ManNAz, GalNAz, and GlcNAz (the three most commonly used commercial sugar analogues). These glycolytic markers can selectively label specific types of glycosylation. For example, ManNAz, an analogue of the biosynthetic precursor of sialic acid, N-acetylmannosamine (ManNAc), can label sialylated N- or O-glycoproteins. GalNAz, an analogue of N-acetylgalactosamine (GalNAc), can replace GalNAc as a core residue of mucin-type O-glycans and thus label O-glycoproteins. In addition, the intracellular metabolic intermediate of GalNAz (pyrophosphate) UDP-GalNAz can be interconverted with UDP-GlcNAz catalyzed by UDP-galactose-4-differential isomerase (GALE) and thus can also label N-glycoproteins and O-GlcNAc glycoproteins instead of GlcNAc. The GlcNAz analogue is commonly used to label nuclear and cytoplasmic glycoproteins with β-O-GlcNAc residues, but can also label N-glycoproteins with mucin-type O-glycoproteins by converting GALE to GalNAz, followed by enrichment using a biotin-alkynyl probe. Label-free quantitative proteomic analysis was performed to evaluate their labeling efficiency. ManNAz-based secretory protein labeling identified 282 secretory proteins, 224 plasma membrane proteins, and 846 N-glycosites. Compared with GalNAz and GlcNAz, the enrichment of secreted proteins was increased 130% and 67.2%, respectively, and the enrichment of plasma membrane proteins was increased 273.3% and 148.7%, respectively. This study provides a useful comparative analysis and new strategies for highly selective enrichment and systematic secretome analysis.

As every-one knows, cadmium contamination poses a significant and permanent threat to people and aquatic life. Therefore, research on how to remove cadmium from wastewater is essential to protect the natural environment. In this study, agricultural and forestry waste straw sprayed with selenium-enriched foliar fertilizer was prepared as biochar, which was altered by calcium chloride (CaCl

Chemotherapy based on cisplatin (CDDP) has been established as the treatment of choice for head and neck squamous cell carcinoma (HNSCC). Malignant tumors respond to microenvironmental alterations through a dynamic balance between mitochondrial fission and fusion. HNSCCs are known to exhibit hypoxic conditions, yet the respective effects and underlying mechanisms of hypoxia on chemosensitivity and mitochondrial dynamics remain to be resolved. The effect of hypoxia on the chemosensitivity of HNCC cells was determined by flow cytometry. Mitochondrial fission factor (Mff) expression was assessed by RT-PCR and Western blotting in hypoxic HNSCC cells, and further verified in primary CDDP-sensitive and CDDP-resistant HSNCC samples. The biological function of Mff was evaluated by loss of function and gain of function analyses, both in vitro and in vivo. We found that hypoxia promoted mitochondrial fission and CDDP sensitivity in HNSCC cells. Importantly, Mff was found to be correlated with chemosensitivity in primary clinical samples under hypoxic conditions. Hypoxia-inducible factor 1α (HIF-1α) was found to markedly increase Mff transcription and to directly bind to Mff. Hypoxia enhanced the release of reactive oxygen species (ROS) and upregulated the expression of Mff via HIF-1α in HNSCC cells. ROS depletion in HNSCC cells attenuated HIF-1α expression, Mff expression and mitochondrial fission. Moreover, Mff knockdown led to suppression of hypoxia-induced mitochondrial fission and to decreased CDDP chemosensitivity in vivo and in vitro. Our findings indicate that hypoxia-induced release of ROS can promote mitochondrial fission and CDDP chemosensitivity via HIF1α/Mff regulation in HNSCC cells, indicating that Mff may serve as a biomarker to predict neoadjuvant chemosensitivity in HNSCC patients and as a target for overcoming chemoresistance.

A hybrid single-input-multiple-output (SIMO) buck converter is recently proposed for high-voltage-step-down and transformerless dc–dc applications. By far, no closed-loop control scheme has been designed for the SIMO buck converter in achieving output current and output voltage control. This article bridges the research gap by proposing a double-integral sliding mode-based hybrid control (DISMHC) to accurately regulate the output current and output voltage of the SIMO buck converter. The DISMHC comprises a double-integral sliding mode control for the first module of the converter and multiple linear control for the remaining modules. Both simulation and experimental results validate that the DISMHC can be implemented in inexpensive digital controllers to regulate the SIMO buck converter with negligible steady-state errors and superior dynamic performance than a proportional-integral-based hybrid control. This, thereby, protects the loads and constituting components of the SIMO buck converter from undesirable overshoots/undershoots and settling time.

A Gram-stain-negative, orange, aerobic, non-motile, rod-shaped marine bacterium, designated as 2V75

The aim of this study was to analyze the impact of using intra-procedural pre-ablation contrast-enhanced CT prior to percutaneous thermal ablation (pre-ablation CECT) of colorectal liver metastases (CLM) on local outcomes.This retrospective analysis of a prospectively collected liver ablation registry included 144 consecutive patients (median age 57 years IQR [49, 65], 60% men) who underwent 173 CT-guided ablation sessions for 250 CLM between October 2015 and March 2020. In addition to oncologic outcomes, technical success was retrospectively evaluated using a biomechanical deformable image registration software for 3D-minimal ablative margin (3D-MAM) quantification. Bayesian regression was used to estimate effects of pre-ablation CECT on residual unablated tumor, 3D-MAM, and local tumor progression-free survival (LTPFS).Pre-ablation CECT was acquired in 71/173 (41%) sessions. Residual unablated tumor was present in one (0.9%) versus nine tumors (6.6%) ablated with versus without using pre-ablation CECT, respectively (p = 0.024). Pre-ablation CECT use decreased the odds of residual disease on first follow-up by 78% (CIPre-ablation CECT is associated with improved immediate outcomes by significantly reducing the incidence of residual unablated tumor and by mitigating the risk of incomplete ablation for larger CLM. We recommend performing baseline intra-procedural pre-ablation CECT as a standard imaging protocol.Level 3 (retrospective cohort study).

Background: Previous investigations have illustrated that lysyl oxidase family enzymes (LOXs) are contributing factors for tumor progression and remodeling immunomicroenvironment. However, it is scarce regarding comprehensive analysis of LOXs in the predictions of prognosis, chemotherapy and immunotherapy in glioma, the highly invasive brain tumor. Our present work aimed to explore the prognostic value, chemotherapeutic drug sensitivity and immunotherapy according to distinct LOXs expressions in glioma through bioinformatics analysis and experimental verification.Methods: We collected gene expression data and clinical characteristics from the public databases including Chinese Glioma Genome Atlas (CGGA)-325, CGGA-693, the Cancer Genome Atlas (TCGA), IMvigor210 and Van Allen 2015 cohorts. The correlations between the clinicopathological factors and differential LOXs expressions were analyzed. The ROC curve and Kaplan-Meier analysis were conducted to evaluate the prediction ability of prognosis. Chemotherapeutic drug sensitivity via distinct LOXs expression levels was predicted using the pRRophetic package. Immune score, immune cell infiltration and immune checkpoint expression levels were also analyzed through diverse algorithms in R software. Finally, mRNA and protein expressions of LOXs were validated in glioma cells (T98G and A172) by real-time quantitative PCR and Western blot, respectively.Results: Our results demonstrated that high levels of LOXs expressions were positively associated with glioma grades, older age and MGMT unmethylated status while elevations of LOXs were negatively correlated with IDH mutation or 1p/19q co-deletion. Furthermore, the glioma patients with low levels of LOXs also exhibited better prognosis. Also, differential LOXs expressions were associated with at least 12 chemotherapeutic drug sensitivity. Besides, it was also found that glioma patients with high LOXs expressions showed higher enrichment scores for immune cell infiltration and increased levels of immune checkpoints, suggesting the critical role of distinct LOXs expression levels for glioma immunotherapy. The predictive roles of LOXs expression in tumor immunotherapy were also validated in two immunotherapy cohorts including IMvigor 210 and Van Allen 2015. Experimental results revealed that expressions of LOX, LOXL1, LOXL2, and LOXL3 were higher in glioma cell lines at mRNA and protein levels.Conclusion: Our findings altogether indicate that LOXs have potent predictive value for prognosis, chemotherapy and immunotherapy in glioma patients.

Percutaneous thermal ablation is a curative-intent locoregional therapy (LRT) for selected patients with unresectable colorectal liver metastasis (CLM). Several factors have been identified that contribute to local tumour control after ablation. However, factors contributing to disease progression outside the ablation zone after ablation are poorly understood.In this retrospective study, using next-generation sequencing, we identified genetic biomarkers associated with different patterns of progression following thermal ablation of CLM.A total of 191 ablation naïve patients between January 2011 and March 2020 were included in the analysis, and 101 had genomic profiling available. Alterations in the TGFβ pathway were associated with increased risk of development of new intrahepatic tumours (hazard ratio [HR], 2.75, 95% confidence interval [95% CI] 1.39-5.45, P = 0.004); and alterations in the Wnt pathway were associated with increased probability of receiving salvage LRT for any intrahepatic progression (HR, 5.8, 95% CI 1.94-19.5, P = 0.003).Our findings indicate that genomic alterations in cancer-related signalling pathways can predict different progression patterns and the likelihood of receiving salvage LRT following percutaneous thermal ablation of CLM.

ObjectiveTo investigate the potential pathogenic mechanism of temporal lobe epilepsy with hippocampal sclerosis (TLE+HS) by analyzing the expression profiles of microRNA/ mRNA/ lncRNA/ DNA methylation in brain tissues.MethodsBrain tissues of six patients with TLE+HS and nine of normal temporal or parietal cortices (NTP) of patients undergoing internal decompression for traumatic brain injury (TBI) were collected. The total RNA was dephosphorylated, labeled, and hybridized to the Agilent Human miRNA Microarray, Release 19.0, 8 × 60K. The cDNA was labeled and hybridized to the Agilent LncRNA+mRNA Human Gene Expression Microarray V3.0,4 × 180K. For methylation detection, the DNA was labeled and hybridized to the Illumina 450K Infinium Methylation BeadChip. The raw data was extracted from hybridized images using Agilent Feature Extraction, and quantile normalization was performed using the Agilent GeneSpring. P-value < 0.05 and absolute fold change >2 were considered the threshold of differential expression data. Data analyses were performed using R and Bioconductor. BrainSpan database was used to screen for signatures that were not differentially expressed in normal human hippocampus and cortex (data from BrainSpan), but differentially expressed in TLE+HS’ hippocampus and NTP’ cortex (data from our cohort). The strategy “Guilt by association” was used to predict the prospective roles of each important hub mRNA, miRNA, or lncRNA.ResultsA significantly negative correlation (r < −0.5) was found between 116 pairs of microRNA/mRNA, differentially expressed in six patients with TLE+HS and nine of NTP. We examined this regulation network’s intersection with target gene prediction results and built a lncRNA-microRNA-Gene regulatory network with structural, and functional significance. Meanwhile, we found that the disorder of FGFR3, hsa-miR-486-5p, and lnc-KCNH5-1 plays a key vital role in developing TLE+HS.

Macrophages are highly enriched in renal cell carcinoma, and the inflammatory cytokines secreted by macrophages are remarkably associated with the survival rate of renal cell carcinoma. However, the relationship between gasdermin D (GSDMD) expression driven by macrophage and the invasion of renal cell carcinoma is not clear.The Caki-2 and 786-O cells were co-cultured with monocytes cells (THP-1) derived macrophages, then the bio function changes of Caki-2 and 786-O cells and epithelial-mesenchymal transition of cancer cells were detected. Also, the role of IL-1β in Caki-2 and 786-O cells and macrophage interaction were investigated. Then, the animal model was used to confirm the role of communication of GSDMD with renal cell carcinoma in the tumor microenvironment.CD68 and GSDMD were overexpressed in human renal cell carcinoma. GSDMD contributed to the secretion of IL‑1β in macrophages and was associated with the proliferation rate of renal cell carcinoma cells. Furthermore, silencing GSDMD elicited renal cell carcinoma cells motility through epithelial-mesenchymal transition change. The in vivo study confirmed that GSDMD promoted tumor progression and GSDMD knockout impaired renal cell carcinoma growth and metastases. Finally, the interactions between macrophages and renal cell carcinoma cells promoted renal cell carcinoma proliferation and metastasis, possibly mediated by IL-1β.To our knowledge, this study showed that the GSDMD expressed by macrophages contributed to renal cell carcinoma cell growth, metastases, and epithelial-mesenchymal transition through regulating GSDMD/IL-1β axis and may be a novel therapeutic target and a potential biomarker for treating and diagnosing renal cell carcinoma.

To evaluate the clinical outcomes of preventive covered stent placement at the gastroduodenal artery stump in patients with angiogram-negative sentinel hemorrhage after pancreaticoduodenectomy. Between July 2006 and September 2018, patients undergoing computed tomography angiography or diagnostic angiography for sentinel hemorrhage after pancreaticoduodenectomy were retrospectively reviewed. Patients having angiogram-negative angiography and undergoing preventive covered stent placement or conservative treatment were included. Clinical outcomes, technique success, and complications were evaluated. A total of 25 patients (mean age 62.5 years) were evaluated, including 15 patients underwent preventive covered stent placement at the gastroduodenal artery stump and 10 patients received conservative treatments. The clinical success rates were 50% (5/10) and 86.7% (13/15) for conservative treatments and covered stent groups, respectively (p = 0.07). In the conservative treatment group, delayed massive hemorrhage occurred in five patients, two of whom died of recurrent bleeding due to gastroduodenal artery pseudoaneurysm within 16 days, and two had intraluminal hemorrhage within 5 days. In the covered stent group, one patient had inferior pancreaticoduodenal artery pseudoaneurysm 1 day after the placement of the covered stent, and one had recurrent bleeding due to duodenal ulcer within 14 days. The 30-day mortality was 40% (4/10) and 0 in the conservative treatment and covered stent groups, respectively (p = 0.02). The difference in the overall survival was nonsignificant between the two groups (p = 0.23). The preventive covered stent placement at the gastroduodenal artery stump is safe and reduces delayed massive hemorrhage and short-term mortality in patients with angiogram-negative sentinel hemorrhage after pancreaticoduodenectomy.

Aims Glioma is a highly invasive brain tumor, which makes prognosis challenging and renders patients resistant to various treatments. Induction of cell death is promising in cancer therapy. Ferroptosis, a recently discovered regulated cell death, can be induced for killing glioma cells. However, the prognostic prediction of ferroptosis‐related genes (FRGs) in glioma remains elusive. Methods The mRNA expression profiles and gene variation and corresponding clinical data of glioma patients and NON‐TUMOR control were downloaded from public databases. Risk score based on a FRGs signature was constructed in REMBRANDT cohort and validated in other datasets including CGGA‐693, CGGA‐325, and TCGA. Results Our results demonstrated that the majority of FRGs was differentially expressed among GBM, LGG, and NON‐TUMOR groups (96.6%). Furthermore, the glioma patients with low‐risk score exhibited a more satisfactory clinical outcome. The better prognosis was also validated in the glioma patients with low‐risk score no matter to which grade they were affiliated. Functional analysis revealed that the high‐risk score group was positively correlated with the enrichment scores for immune checkpoint blockade‐related positive signatures, indicating the critical role of glioma immunotherapy via risk score. Conclusion A novel FRGs‐related risk score can predict prognosis and immunotherapy in glioma patients., A random survival forest model was constructed to obtain the risk score based on 59 ferroptosis genes in glioma patients in REMBRANDT cohort and it was validated in other datasets including CGGA‐325, CGGA‐693, and TCGA cohorts. Finally, a novel ferroptosis‐related risk score can predict prognosis and immunotherapy in glioma patients.

Actin cytoskeleton dynamic rearrangement is required for tumor cell metastasis and is a key characteristic of Helicobacter pylori (H. pylori)-infected host cells. Actin cytoskeleton modulation is coordinated by multiple actin-binding proteins (ABP). Through Kyoto encyclopedia of gene and genomes database, GEPIA website, and real-time PCR data, we found that H. pylori infection significantly induced L-plastin, a key ABP, in gastric cancer cells. We further explored the regulation and function of L-plastin in H. pylori–associated gastric cancer and found that, mechanistically, H. pylori infection induced gastric cancer cells to express L-plastin via cagA-activated ERK signaling pathway to mediate SP1 binding to L-plastin promoter. Moreover, this increased L-plastin promoted gastric cancer cell proliferation and migration in vitro and facilitated the growth and metastasis of gastric cancer in vivo. Finally, we detected the expression pattern of L-plastin in gastric cancer tissues, and found that L-plastin was increased in gastric cancer tissues and that this increase of L-plastin positively correlated with cagA+ H. pylori infection status. Overall, our results elucidate a novel mechanism of L-plastin expression induced by H. pylori, and a new function of L-plastin–facilitated growth and metastasis of gastric cancer, and thereby implicating L-plastin as a potential therapeutic target against gastric cancer. Implications: Our results elucidate a novel mechanism of L-plastin expression induced by H. pylori in gastric cancer, and a new function of L-plastin–facilitated gastric cancer growth and metastasis, implicating L-plastin as a potential therapeutic target against gastric cancer.