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Comprehensive Summary: Near‐infrared (NIR)‐absorbing polymerized small molecule acceptors (PSMAs) based on a Y‐series backbone (such as PY‐IT) have been widely developed to fabricate efficient all‐polymer solar cells (all‐PSCs). However, medium‐bandgap PSMAs are often overlooked, while they as the third component can be expected to boost power conversion efficiencies (PCEs) of all‐PSCs, mainly due to their up‐shifted lowest unoccupied molecular orbital (LUMO) energy level, complimentary absorption, and diverse intermolecular interaction compared to the NIR‐absorbing host acceptor. Herein, an IDIC‐series medium‐bandgap PSMA (P‐ITTC) is developed and introduced as the third component into D18/PY‐IT host, which can not only form complementary absorption and cascade energy level, but also finely optimize active layer morphology. Therefore, compared to the D18/PY‐IT based parental all‐PSCs, the ternary all‐PSCs based on D18/PY‐IT:P‐ITTC obtain an increased exciton dissociation, charge transport, carrier lifetime, as well as suppressed charge recombination and energy loss. As a result, the ternary all‐PSCs achieve a high PCE of 17.64% with a photovoltage of 0.96 V, both of which are among the top values in layer‐by‐layer typed all‐PSCs. This work provides a method for the design and selection of the medium‐bandgap third component to fabricate efficient all‐PSCs. [ABSTRACT FROM AUTHOR]

Summary: To better meet the evolving requirements of industrialized building system, this paper introduces a novel approach by proposing the utilization of a plate‐reinforced composite (PRC) coupling beam, which incorporates a steel bar truss deck as a substitute for the conventional reinforced concrete (RC) slab. In order to study the effect of different types of RC slabs on the performance of PRC coupling beams, the low‐cyclic reversed loading test was carried out on three PRC coupling beams. The differences of failure modes, load bearing capacity, stiffness degradation, and energy dissipation capacity of each coupling beam are analyzed. The finite element software ABAQUS is used to analyze the stress distribution in the concrete, steel plate, and reinforcement skeleton of the novel coupling beam. The results show that the incorporation of a steel bar truss deck in PRC coupling beams with a small span‐to‐depth ratio can effectively enhance their shear bearing capacity and energy dissipation capacity. The inclusion of a slab significantly enhances the load‐bearing capacity of the coupling beam, while the utilization of a steel bar truss deck in PRC coupling beams greatly improves their overall bearing capacity. The PRC coupling beams featuring a steel bar truss deck exhibit superior load capacity compared to those with conventional RC slabs. The cumulative energy dissipation at the damage point in PRC beams with a steel bar truss deck is 1.39 times greater than that of the coupling beam without slabs and 1.18 times higher than that of the coupling beam with traditional RC slabs. [ABSTRACT FROM AUTHOR]

Propionate metabolism is important in the development of diabetes, and fibrosis plays an important role in diabetic nephropathy (DN). However, there are no studies on biomarkers related to fibrosis and propionate metabolism in DN. Hence, the current research is aimed at evaluating biomarkers associated with fibrosis and propionate metabolism and to explore their effect on DN progression. The GSE96804 (DN : control = 41 : 20) and GSE104948 (DN : control = 7 : 18) DN‐related datasets and 924 propionate metabolism‐related genes (PMRGs) and 656 fibrosis‐related genes (FRGs) were acquired from the public database. First, DN differentially expressed genes (DN‐DEGs) between the DN and control samples were sifted out via differential expression analysis. The PMRG scores of the DN samples were calculated based on PMRGs. The samples were divided into the high and low PMRG score groups according to the median scores. The PM‐DEGs between the two groups were screened out. Second, the intersection of DN‐DEGs, PM‐DEGs, and FRGs was taken to yield intersected genes. Random forest (RF) and recursive feature elimination (RFE) analyses of the intersected genes were performed to sift out biomarkers. Then, single gene set enrichment analysis was conducted. Finally, immunoinfiltrative analysis was performed, and the transcription factor (TF)–microRNA (miRNA)–mRNA regulatory network and the drug–gene interaction network were constructed. There were 2633 DN‐DEGs between the DN and control samples and 515 PM‐DEGs between the high and low PMRG score groups. In total, 10 intersected genes were gained after taking the intersection of DN‐DEGs, PM‐DEGs, and FRGs. Seven biomarkers, namely, SLC37A4, ACOX2, GPD1, angiotensin‐converting enzyme 2 (ACE2), SLC9A3, AGT, and PLG, were acquired via RF and RFE analyses, and they were found to be involved in various mechanisms such as glomerulus development, fatty acid metabolism, and peroxisome. The seven biomarkers were positively correlated with neutrophils. Moreover, 8 TFs, 60 miRNAs, and 7 mRNAs formed the TF–miRNA–mRNA regulatory network, including USF1‐hsa‐mir‐1296‐5p‐AGT and HIF1A‐hsa‐mir‐449a‐5p‐ACE2. The drug–gene network contained UROKINASE–PLG, ATENOLOL–AGT, and other interaction relationship pairs. Via bioinformatic analyses, the risk of fibrosis and propionate metabolism‐related biomarkers in DN were explored, thereby providing novel ideas for research related to DN diagnosis and treatment. [ABSTRACT FROM AUTHOR]

Background and Aim: Nonalcoholic fatty liver disease (NAFLD) and advanced hepatic fibrosis (AHF) have been associated with sarcopenia. However, modifiers of this association have been less studied. Methods: This study used data from the NHANES database 2011–2014 of the USA. Adults aged 18 years or older, had complete information of handgrip strength test and NAFLD and AHF status were eligible for inclusion. NAFLD was defined using the Fatty Liver Index (FLI). AHF was defined using the NAFLD fibrosis score (NFS). Univariate and multivariate logistic regression were performed to determine the associations between the study variables and prevalent NAFLD and AHF. Results: A total of 19 931 participants were selected from the 2011–2014 NHANES database. The multivariate analysis showed that stronger grip strength was significantly and independently associated with decreased odds for NAFLD (tertile 2: adjusted odd ratio [aOR]: 0.41, 95% confidence interval [CI]: 0.29–0.59; tertile 3: aOR: 0.11, 95% CI: 0.05–0.24) and AHF (tertile 2: aOR: 0.66, 95% CI: 0.46–0.94; tertile 3: aOR: 0.28, 95% CI: 0.12–0.63). In stratified analyses, strongest grip strength was significantly associated with reduced odds for NAFLD regardless of age, body mass index, and having diabetes or not. Strongest grip strength was associated with reduced odds for NAFLD in individuals who had moderate to ideal physical activity (aOR: 0.31). Conclusions: Grip strength has an inverse association with prevalent NAFLD and AHF in the US population, which appears to be modified by physical activity level. Future prospective cohort studies are needed to clarify the role of physical activity in modifying the risks. [ABSTRACT FROM AUTHOR]

In this paper, a new sparsity‐optimised Farrow structure variable fractional delay (SFS‐VFD) filter is proposed to address the aperture effect in wideband array. Our method is based on coefficient (anti‐)symmetry and optimises the number and orders of its sub‐filters, greatly reducing the non‐zero coefficients. The established cost function is formulated as a parametric minimisation problem with multiple regularisation constraints, and solved by the modified three‐block alternating direction multiplier method (MTB‐ADMM), which is improved by introducing core variable correction items to ensure stable and fast convergence. Experimental results show that the SFS‐VFD filter reduces the complexity of the system by decreasing the use of multipliers and adders while ensuring high delay accuracy. In wideband array, the SFS‐VFD filter effectively corrects the aperture effect and achieves precise beam pointing. [ABSTRACT FROM AUTHOR]

Mesenchymal stromal/stem cells (MSCs) have emerged as a promising approach against myocardial infarction. Due to hostile hyperinflammation, however, poor retention of transplanted cells seriously impedes their clinical applications. Proinflammatory M1 macrophages, which rely on glycolysis as their main energy source, aggravate hyperinflammatory response and cardiac injury in ischemic region. Here, we showed that the administration of an inhibitor of glycolysis, 2‐deoxy‐d‐glucose (2‐DG), blocked the hyperinflammatory response within the ischemic myocardium and subsequently extended effective retention of transplanted MSCs. Mechanistically, 2‐DG blocked the proinflammatory polarization of macrophages and suppressed the production of inflammatory cytokines. Selective macrophage depletion abrogated this curative effect. Finally, to avoid potential organ toxicity caused by systemic inhibition of glycolysis, we developed a novel chitosan/gelatin‐based 2‐DG patch that directly adhered to the infarcted region and facilitated MSC‐mediated cardiac healing with undetectable side effects. This study pioneered the application of an immunometabolic patch in MSC‐based therapy and provided insights into the therapeutic mechanism and advantages of this innovative biomaterial. [ABSTRACT FROM AUTHOR]

Background and Objective. Tuberculosis (TB) is a major threat to human health, especially in developing countries. Its susceptibility and progression depend on interactions between mycobacterium tuberculosis, host immune system, and genetic and environmental factors. Up to now, many studies have presented the association between TB susceptibility and host genetic polymorphisms, but never regarding CD59 gene, which is an essential complement regulator. This study investigated the relationship between multiple CD59 single nucleotide polymorphisms (SNPs) and susceptibility to TB among Chinese patients. Methods. A case–control study was conducted to investigate the SNPs at CD59 rs1047581, rs7046, rs2231460, rs184251026, rs41275164, rs831633, rs704700, rs41275166, and rs10768024 by sequence-specific primer-polymerase chain reaction (SSP-PCR) in 900 tuberculosis patients and 1,534 controls. Results. The minor allele frequencies at rs2231460, rs184251026, rs41275164, and rs41275166 were extremely low both in the Cases (0.00%–0.61%) and in the Controls (0.07%–0.43%), comparatively at rs1047581, rs7046, rs831633, rs704700, and rs10768024 were notably higher both in the Cases (8.23%–48.39%) and in the Controls (8.57%–47.16%). Among the nine SNPs, only homozygous CC genotype at rs10768024 showed a significant protective effect against TB than homozygous TT genotype (OR(95% CI) = 0.59(0.38, 0.91), χ2 = 5.779, P = 0.016), and homozygous TT and heterozygous CT genotypes showed a significant risk of TB infection in the recessive model (OR(95% CI) = 1.68(1.10, 2.56), χ2 = 5.769, P = 0.016). Further analysis verified that rs10768024 CC genotype independently related to TB susceptibility (OR(95% CI) = 0.60(0.39, 0.91), Wald χ2 = 5.664, P = 0.017) in multivariate logistic regression analysis, and its genetic mutation was independent of the other SNPs (r2 = 0.00–0.20) in haplotype analysis. Conclusions. The first investigation of the CD59 gene and susceptibility to TB suggests a significant risk with homozygous TT and heterozygous CT genotypes at rs10768024 loci. The homozygous CC mutation at rs10768024 loci showed a significant protection against TB susceptibility. [ABSTRACT FROM AUTHOR]

As a green and sustainable strategy, the electrocatalytic N2 reduction reaction (NRR) has been considered the best potential approach to replace the traditional Haber‐Bosch process under ambient conditions. The key is to exploit efficient and low‐cost electrocatalysts according to the current situation. Herein, a series of Molybdenum (Mo) doped CeO2 nanorods (NR) catalysts were successfully fabricated via a hydrothermal reaction coupled with high temperature calcination. The nanorod structures were not altered after Mo atom doping. The obtained 5 %‐Mo‐CeO2 nanorods act as a superior electrocatalyst in neutral electrolytes of 0.1 M Na2SO4. Such electrocatalyst significantly enhances NRR performance with an NH3 yield of 10.9 μg h−1 mg−1cat at −0.45 V vs reversible hydrogen electrode (RHE) and a Faradaic efficiency (FE) of 26.5 % at −0.25 V vs RHE. That outcome is 4 times higher than that of CeO2 nanorods (2.6 μg h−1 mg−1cat; 4.9 %). Meanwhile, density functional theory (DFT) calculation shows the characteristics after Mo doping: the band gap value lowers, the density of states increases, electrons are more easily excited, and N2 molecules are more easily adsorbed, thereby enhancing the activity of the electrocatalytic NRR. [ABSTRACT FROM AUTHOR]

Earring porphyrins bearing a 1,3‐di(pyrid‐2‐yl)phenylene ear or a 2,5‐di(pyrid‐2‐yl)pyrrole ear were synthesized by Suzuki‐Miyaura cross coupling reactions. Upon treatment with Pd(OAc)2 and Ni(OAc)2 ⋅ 4H2O, these earring porphyrins gave the corresponding PdII and NiII complexes with distorted coordination geometries, indicating their abilities to serve as a divalent ligand. Owing to non‐conjugated properties, these complexes show larger HOMO‐LUMO gaps as compared with the parent earring porphyrin bearing a tripyrrin ear. [ABSTRACT FROM AUTHOR]

Objective. To systematically evaluate the correlation between the positive rate of sputum bacterial culture and the results of drug sensitivity test and the severity of the disease and its clinical significance, so as to provide evidence-based medicine for clinical application. Methods. PubMed, Embase, ScienceDirect, Cochrane Library, China Knowledge Network Database (CNKI), China VIP Database, Wanfang Database, and China Biomedical Literature Database (CBM) online database were used. The retrieval time limit was from the establishment of the database to the present. Data for all included studies were extracted by two independent researchers, and the risk of bias for the quality of each included study was assessed by the Cochrane Handbook 5.1.0 criteria. RevMan5.4 statistical software was used to analyze the collected data by meta. Results. In the end, 6 RCT articles were included. Overall, 613 samples were included in 6 RCT studies. The correlation between the positive rate of sputum bacterial culture in inpatients and the severity of the disease was meta-analyzed. The heterogeneity test results showed that Chi2 = 177.20, df = 3, P < 0.00001, and I2 = 98%, indicating that there was obvious heterogeneity among the included research data. It was considered that there was a correlation between the positive rate of sputum bacterial culture and the severity of the disease. The correlation between the results of the drug sensitivity test of inpatients and the severity of the disease was evaluated. The results of the heterogeneity test showed that Chi2 = 0.00, df = 1, P = 1 > 0.05, and I2 = 0%, indicating that there was no heterogeneity among the included research data. In addition, the combined effect of WMD was analyzed by the fixed effect model. The combined effect dose WMD test was Z = 6.58 (P < 0.00001). It was considered that there was a correlation between the results of the drug sensitivity test and the severity of the disease. Conclusion. There is a correlation between positive sputum culture and drug sensitivity test results and the severity of the disease in hospitalized patients. In clinical practice, for hospitalized patients, the positive sputum bacterial culture rate and drug sensitivity test results can be used to guide the appropriate use of antibiotics. Due to the low input from the literature, more studies with higher methodological quality and longer follow-up are needed for further validation. [ABSTRACT FROM AUTHOR]

High-viscosity modified asphalt (HVA) is widely used as the binder for permeable asphalt pavement, and hydrated lime (HL) attracts a strong technical interest as an effective moisture additive in asphalt for a long time. However, the application of HL in HVA has been rarely studied. The present study evaluates the influence of HL on the high-temperature rheological properties of HVA and selects the optimum HL content and fineness. The asphalt mortars of HVA and HL of different contents and fineness were prepared. Temperature scanning (DSR-TS), multiple stress creep recovery (MSCR) by using a dynamic shear rheometer, and scanning electron microscope (SEM) tests were carried out to evaluate the high-temperature rheological properties and microstructure morphology characteristics of the asphalt mortars. Based on the DSR-TS and MSCR tests, the results showed that high-temperature performance together with the ability to deformation resistance of HVA was improved apparently with the increase of the HL content. When the HL content is above 1.2, the stress sensitivity of HVA is lower. The SEM results clearly showed that the uniformity of asphalt mortars could be effectively guaranteed when the HL content was 1.2 and the fineness was 800 mesh. The HL fineness has little effect on the high-temperature performance of HVA. In summary, taking into account the high-temperature performance and microstructure of HVA with HL, the optimum HL content and fineness could be finally determined. [ABSTRACT FROM AUTHOR]

Summary: Plants use their innate immune system to defend against phytopathogens. As a part of this, pattern triggered‐immunity is activated via pattern recognition receptor (PRR) detection of pathogen‐associated molecular patterns (PAMPs). Although an increasing number of PAMPs have been identified, the PRRs for their recognition remain largely unknown.In the present study, we report a receptor‐like protein RE02 (Response to VmE02) in Nicotiana benthamiana, which mediates the perception of VmE02, a PAMP previously identified from the phytopathogenic fungus Valsa mali, using virus‐induced gene silencing (VIGS), co‐immunoprecipitation, pull‐down and microscale thermophoresis assays.We show that silencing of RE02 markedly attenuated VmE02‐triggred cell death and immune responses. RE02 specifically interacted with VmE02 in vivo and in vitro, and it displayed a high affinity for VmE02. Formation of a complex with the receptor‐like kinases SOBIR1 and BAK1 was essential for RE02 to perceive VmE02. Moreover, RE02‐silenced plants exhibited enhanced susceptibility to both the oomycete Phytophthora capsici and the fungus Sclerotinia sclerotiorum, while overexpression of RE02 increased plant resistance to these pathogens.Together, our results indicate that the PAMP VmE02 and the receptor‐like protein RE02 represent a new ligand–receptor pair in plant immunity, and that RE02 represents a promising target for engineering disease resistance. [ABSTRACT FROM AUTHOR]

Objective: Insulo‐opercular seizures are characterized by diverse semiology, related to the insula's multiple functional roles and extensive connectivity. We aimed to identify semiologic subgroups and correlate these with insulo‐opercular subregions based on connectional architecture. Methods: We retrospectively collected a large series of 37 patients with insulo‐opercular seizures explored by stereoelectroencephalography (SEEG) from three epilepsy centers. A new human brain atlas (Brainnetome Atlas, BNA) based on both anatomic and functional connections was employed to segment insulo‐opercular cortex. Semiology and SEEG changes were carefully reviewed and quantified. Principal component analysis and cluster analysis were used to correlate semiologic characteristics with insulo‐opercular subregions. Results: Four main semiologic subgroups were identified, organized along an anteroventral to posterodorsal axis based on BNA. Group 1 was characterized by epigastric sensation and/or integrated gestural motor behaviors with or without feelings of fear or rage, involving the anteroventral insular regions and mesial temporal lobes. Group 2 was characterized by auditory sensations and symmetric proximal/axial tonic signs involving the posteroventral temporal operculum. The characteristics of group 3 were orofacial and laryngeal signs, involving the intermediate insulo‐opercular regions. The features of group 4 were somatosensory signs followed by nonintegrated gestural motor behaviors and/or asymmetric tonic signs involving the posterodorsal insulo‐opercular regions with propagation to the mesial frontal lobes. Thus anteroventral seizure organizations predominantly showed limbic system semiology, whereas more posterodorsal regions were associated with semiology involving mainly the sensorimotor system. Subjective symptoms proved to be particularly discriminating factors. Significance: Insulo‐opercular seizures can be categorized in terms of clinical semiology and correlate with connectional architecture subregions along an anteroventral‐posterodorsal axis in line with the cytoarchitectonic gradient rather than the gyral anatomy of the insula cortex. This provides new insights into facilitating differential diagnosis and presurgical localization but also highlights the importance of considering connectional architecture in determining neural correlates of complex semiologic patterns. [ABSTRACT FROM AUTHOR]

Proteolipid protein 2 (PLP2) is an integral ion channel membrane protein of the endoplasmic reticulum. The protein has been shown to be highly expressed in many cancer types, but its importance in glioma progression is poorly understood. Using publicly available datasets (Rembrandt, TCGA and CGGA), we found that the expression of PLP2 was significantly higher in high‐grade gliomas than in low‐grade gliomas. We confirmed these results at the protein level through IHC staining of high‐grade (n = 56) and low‐grade glioma biopsies (n = 16). Kaplan‐Meier analysis demonstrated that increased PLP2 expression was associated with poorer patient survival. In functional experiments, siRNA and shRNA PLP2 knockdown induced ER stress and increased apoptosis and autophagy in U87 and U251 glioma cell lines. Inhibition of autophagy with chloroquine augmented apoptotic cell death in U87‐ and U251‐siPLP2 cells. Finally, intracranial xenografts derived from U87‐ and U251‐shPLP2 cells revealed that loss of PLP2 reduced glioma growth in vivo. Our results therefore indicate that increased PLP2 expression promotes GBM growth and that PLP2 represents a potential future therapeutic target. [ABSTRACT FROM AUTHOR]

Excessive activation of pro‐inflammatory M1 macrophages following acute myocardial infarction (MI) aggravates adverse cardiac remodelling and heart dysfunction. There are two break points in the tricarboxylic acid cycle of M1 macrophages, and aspartate‐arginosuccinate shunt compensates them. Aminooxyacetic acid (AOAA) is an inhibitor of aspartate aminotransferase in the aspartate‐arginosuccinate shunt. Previous studies showed that manipulating macrophage metabolism may control macrophage polarization and inflammatory response. In this study, we aimed to clarify the effects of AOAA on macrophage metabolism and polarization and heart function after MI. In vitro, AOAA inhibited lactic acid and glycolysis and enhanced ATP levels in classically activated M1 macrophages. Besides, AOAA restrained pro‐inflammatory M1 macrophages and promoted anti‐inflammatory M2 phenotype. In vivo, MI mice were treated with AOAA or saline for three consecutive days. Remarkably, AOAA administration effectively inhibited the proportion of M1 macrophages and boosted M2‐like phenotype, which subsequently attenuated infarct size as well as improved post‐MI cardiac function. Additionally, AOAA attenuated NLRP3‐Caspase1/IL‐1β activation and decreased the release of IL‐6 and TNF‐α pro‐inflammatory cytokines and reciprocally increased IL‐10 anti‐inflammatory cytokine level in both ischaemic myocardium and M1 macrophages. In conclusion, short‐term AOAA treatment significantly improves cardiac function in mice with MI by balancing macrophage polarization through modulating macrophage metabolism and inhibiting NLRP3‐Caspase1/IL‐1β pathway. [ABSTRACT FROM AUTHOR]

Background: Antituberculosis drug‐induced liver injury (ATDILI) is increasing globally and, hence, it is crucial to predict its risk in the clinical management of antituberculosis therapy. As a major antioxidant, superoxide dismutase (SOD) is mainly responsible for providing defence against oxidative stress, which is involved in ATDILI. The present study aimed to investigate the associations between polymorphisms in SOD genes, including Cu/ZnSOD (SOD1), mitochondrial manganese SOD (MnSOD or SOD2) and extracellular SOD (SOD3), as well as the susceptibility to ATDILI in a Chinese Han population. Methods: In total, 1060 Chinese Han subjects highly suspected to have tuberculosis (TB) were prospectively enrolled from West China Hospital of Sichuan University. Overall, 746 subjects comprising 118 ATDILI and 628 ATD‐tolerant TB patients were eligible and were genotyped for seven single‐nucleotide polymorphisms in three SOD genes (SOD1: rs4816407 and rs1041740; SOD2: rs4880; SOD3: rs699473, rs2536512, rs2855262 and rs8192290). Results: Logistic regression analysis showed that none of the seven genetic variants in the three SOD genes were significantly associated with susceptibility to ATDILI in the Chinese Han population after Bonferroni correction, except for a potential association for the SOD2 rs4880 A>G (G allele, p = 0.190, odds ratio = 1.53, 95% confidence interval = 1.05–2.23; GG genotype, p = 0.155). Conclusions: The promising application of single‐nucleotide polymorphisms in the SOD1, SOD2 and SOD3 genes as genetic markers for ATDILI is challenged, and further studies are needed with larger sample sizes and different ethnicities, especially for SOD2 rs4880. [ABSTRACT FROM AUTHOR]

Aim: Although peripheral low‐grade inflammation and brain‐derived neurotrophic factor (BDNF) levels have been implicated in schizophrenia (SCZ), the interactions between them remain to be fully revealed. We aimed to compare BDNF and cytokines in patients with SCZ and healthy controls (HC). Additionally, we aimed to investigate the association between peripheral levels of cytokines and BDNF in patients with SCZ. Methods: Plasma levels of BDNF, interferon gamma, interleukin (IL)‐10, IL‐12, IL‐1, IL‐6, IL‐8, tumor necrosis factor alpha, macrophage migration inhibitory factor, IL‐1 receptor antagonist (IL‐1Ra), and CD40 Ligand were compared in 45 SCZ patients and 38 HC using Luminex technology. Results: Compared to HC, patients had significantly higher IL‐1Ra levels (P = 0.031). We found a strong positive association between BDNF and CD40 Ligand in the patient group (rho = 0.858, P < 0.001) as well as in the HC group (rho = 0.822, P < 0.001), respectively. Furthermore, there was a negative association between BDNF and tumor necrosis factor alpha in patients (rho = −0.429, P = 0.030) as well as in HC (rho = −0.649, P < 0.001). Conclusion: These results suggest that the cytokine IL‐1Ra may play a role in SCZ pathophysiology. Additionally, the interaction between cytokines and BDNF levels further indicated the diverse actions of these cytokines. [ABSTRACT FROM AUTHOR]

Abstract: Background: Matrine, a traditional Chinese medicine, has recently been shown to have antitumor properties in diverse cancer cells. Here, we explored the effect of matrine on human glioblastoma multiforme (GBM) cells. Methods: Glioblastoma multiforme cell lines were treated with matrine to assess proliferation and viability using EdU and CCK8 assays. SA‐β‐gal assays were used to evaluate cellular senescence, and a cytokine array and ELISA assay were used to screen for secreted cytokines altered in GBM cells after matrine treatment. Immunohistochemistry and Western blot analysis were performed to evaluate protein levels in matrine‐treated cell lines and in samples obtained from orthotopic xenografts. Specific activators of AKT and IGF1 were used to identify the pathways mediating the effect. Results: Matrine potently inhibited growth of GBM cell lines in vitro. Based on in situ assays, growth arrest induced by matrine was primarily achieved through induction of cellular senescence. Matrine treatment led to decreased expression of proteins involved in promoting cell growth, IGF1, PI3K, and pAKT. Exposure of cells to a small molecule activating AKT (SC79) and recombinant IGF1 led to a reduced number of senescent SA‐β‐gal‐positive cells in the presence of matrine. Finally, matrine inhibited growth of orthotopic xenografts established from luciferase‐stable‐U251 or luciferase‐stable‐P3 cells and prolonged overall survival in mice. Conclusions: These results indicated that matrine arrested cell growth through inhibition of IGF1/PI3K/AKT signaling. Matrine warrants further investigation as a potential therapy in the treatment of patients with GBM. [ABSTRACT FROM AUTHOR]

Abstract: The gas‐solid flow in a cylindrical spouted bed with a pair of spherical longitudinal vortex generators (LVGs) was numerically investigated by a two‐fluid model with kinetic theory for granular flow. Simulations and analyses were conducted on five types of spouted beds: a conventional spouted bed without disturbance units as well as spouted beds with a pair of LVGs in which the radius of spheres installed on the LVGs had four different dimensions. Results of the computational fluid dynamics demonstrate that the fountain height decreases with larger radius, and the influence range of the longitudinal vortex increases with the greater radius, both for the gas phase and particle phase. The turbulent kinetic energy of the gas phase along the radial and axial directions in the spouted bed was also promoted significantly by the longitudinal vortex and increased with larger radius, which is due to the higher LVG volume. [ABSTRACT FROM AUTHOR]

Background and Aims Recent genome-wide association studies have shown associations between variants in loci (4q28.1, 6p21.32, 6p21.1, 6q16.1, 10q22.1 and 10q22.3) and chronic obstructive pulmonary disease (COPD) or smoking behaviors. The objective of this study was to look for associations between 16 single nucleotide polymorphisms (SNP) at these six loci and COPD susceptibility in Hainan region. Methods A case-control cohort was composed of 200 COPD cases and 401 controls that were genotyped and analyzed statistically. Odds ratios (OR) and 95% confidence intervals (CIs) were computed by chi-square (χ2) test and genetic models by unconditional logistic regression. Results After Hardy-Weinberg equilibrium (HWE) P value screening, we excluded the SNP rs12220777 with P < 0.001. By χ2 test only rs9296092 which located on 6p21.32 was provided the strongest evidence of an increasing risk of COPD with an OR of 3.28 (95% CI = 1.03 - 2.32; P = 0.003) between cases and controls. By genetic models analysis, we not only found rs9296092 increased COPD risk, but also found in the over-dominant model the genotype 'C/T' (OR = 0.55; 95% CI = 0.33 - 0.93; P = 0.023) of rs950063 was proved to be associated with decreased COPD risk. Conclusions This study is the first to provide evidence of importance of rs9296092 and rs950063 for risk of COPD in Hainan Province. Further studies are needed to characterize the functional sequences that cause COPD. [ABSTRACT FROM AUTHOR]

Casting-type calcifications and a histopathological picture with cancer-filled duct-like structures have been presented as breast cancer with neoductgenesis. We correlated mammographic features and histopathological neoductgenesis with prognosis in a DCIS cohort with long follow-up. Mammographic features were classified into seven groups according to Tabár. Histopathological neoductgenesis was defined by concentration of ducts, lymphocyte infiltration, and periductal fibrosis. Endpoints were ipsilateral (IBE) in situ and invasive events. Casting-type calcifications and neoductgenesis were both related to high nuclear grade, ER- and PR-negativity, and HER2 overexpression but not to each other. Casting-type calcifications and neoductgenesis were both related to a nonsignificant lower risk of invasive IBE, HR 0.38 (0.13–1.08) and 0.82 (0.29–2.27), respectively, and the HR of an in situ IBE was 0.90 (0.41–1.95) and 1.60 (0.75–3.39), respectively. Casting-type calcifications could not be related to a worse prognosis in DCIS. We cannot explain why a more aggressive phenotype of DCIS did not correspond to a worse prognosis. Further studies on how the progression from in situ to invasive carcinoma is driven are needed. [ABSTRACT FROM AUTHOR]

The steady natural convection in a rectangular cavity filled with a heat-generating porous medium was numerically investigated using a thermal non-equilibrium model for the heat transfer between the fluid and solid phases. All of the walls of the enclosure are adiabatic, except for the left wall, which is partially heated and cooled by a spatial sinusoidal temperature profile. The results show that the temperature fields near the left wall and the local Nusselt number of the left wall vary periodically because of the sinusoidal boundary condition. There exists an optimal fluctuant parameter of N ( N = 3) to maximize the heat transfer rate of the fluid phase in the square enclosure. The periodicity parameter N has a significant influence on the value of the average Nusselt number of the fluid phase when the Darcy and Rayleigh numbers increase. [ABSTRACT FROM AUTHOR]

Epidemiologic studies have shown that the treatment of diabetics with metformin reduced the risk of cancer-related mortality. Here, we investigated the chemopreventive effects of metformin on dimethylhydrazine (DMH)-induced colorectal carcinogenesis in diabetic SD rats following metformin treatment and the effect on Warburg effect involved in this process. Diabetic rat models were induced with high-fat feeding in combination with a low dose of Streptozotocin (STZ) and then induce colorectal cancer with a low dose of DMH. The formation of colorectal Aberrant crypt foci (ACF) and the incidence, number and size of the tumor were measured. The proliferation indices of colonic tissues were determined through Proliferating cell nuclear antigen (PCNA) immunostaining. Then detect the expression of PK and IDH in colonic tissues using immunohistochemistry and Western blot. The enzyme activities of HK and PDH in colonic tissues were measured. The growth and expression of PK and IDH and activity of HK and PDH in cell lines LoVo and HT-29 were measured after metformin treatment. The results showed that metformin treatment significantly inhibited the formation of ACF and tumors. The proliferation index of colonic tissues was significantly decreased following metformin treatment. In addition, metformin inhibited cell growth and decreased the imbalance in the expression of the enzymes involved in glycolysis and the TCA cycle. These findings suggested that metformin might produce a synergistic colon cancer-preventative effect in diabetic patients through the regulation of the enzymes expression involved in glucose metabolism. [ABSTRACT FROM AUTHOR]

Abstract: Ductal carcinoma in situ (DCIS) is a non-invasive form of breast cancer where cells restricted to the ducts exhibit an atypical phenotype. Some DCIS lesions are believed to rapidly transit to invasive ductal carcinomas (IDCs), while others remain unchanged. Existing classification systems for DCIS fail to identify those lesions that transit to IDC. We studied gene expression patterns of 31 pure DCIS, 36 pure invasive cancers and 42 cases of mixed diagnosis (invasive cancer with an in situ component) using Agilent Whole Human Genome Oligo Microarrays 44k. Six normal breast tissue samples were also included as controls. qRT-PCR was used for validation. All DCIS and invasive samples could be classified into the “intrinsic” molecular subtypes defined for invasive breast cancer. Hierarchical clustering establishes that samples group by intrinsic subtype, and not by diagnosis. We observed heterogeneity in the transcriptomes among DCIS of high histological grade and identified a distinct subgroup containing seven of the 31 DCIS samples with gene expression characteristics more similar to advanced tumours. A set of genes independent of grade, ER-status and HER2-status was identified by logistic regression that univariately classified a sample as belonging to this distinct DCIS subgroup. qRT-PCR of single markers clearly separated this DCIS subgroup from the other DCIS, and contains samples from several histopathological and intrinsic molecular subtypes. The genes that differentiate between these two types of DCIS suggest several processes related to the re-organisation of the microenvironment. This raises interesting possibilities for identification of DCIS lesions both with and without invasive characteristics, which potentially could be used in clinical assessment of a woman’s risk of progression, and lead to improved management that would avoid the current over- and under-treatment of patients. [ABSTRACT FROM AUTHOR]

Abstract: In breast cancer, previous studies have suggested that somatic TP53 mutations are likely to be an early event. However, there are controversies regarding the cellular origin and linear course of breast cancer. The purpose of this study was to investigate tumor evolution in breast cancer by analyzing TP53 mutation status in tumors from various stages of the disease. The entire coding sequence of TP53 was sequenced in a cohort of pure ductal carcinoma in situ (DCIS), pure invasive cancer (≤15mm) and mixed lesions (i.e. invasive cancer with an in situ component). Of 118 tumor samples, 19 were found to harbor a TP53 mutation; 5 (15.6%) of the pure DCIS, 4 (10.5%) of the pure invasive cancers and 10 (20.8%) of the mixed lesions. In the mixed lesions, both the invasive and the DCIS components showed the same mutation in all 5 cases where the two components were successfully microdissected. Presence of the same mutation in both DCIS and invasive components from the same tumor indicates same cellular origin. The role of mutant TP53 in the progression of breast cancer is less clear and may vary between subtypes. [Copyright &y& Elsevier]