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- ArticleLin SJ, Hwang WJ, Lee WH.Sensors (Basel). 2012;12(5):6244-68.This paper presents a novel hardware architecture for principal component analysis. The architecture is based on the Generalized Hebbian Algorithm (GHA) because of its simplicity and effectiveness. The architecture is separated into three portions: the weight vector updating unit, the principal computation unit and the memory unit. In the weight vector updating unit, the computation of different synaptic weight vectors shares the same circuit for reducing the area costs. To show the effectiveness of the circuit, a texture classification system based on the proposed architecture is physically implemented by Field Programmable Gate Array (FPGA). It is embedded in a System-On-Programmable-Chip (SOPC) platform for performance measurement. Experimental results show that the proposed architecture is an efficient design for attaining both high speed performance and low area costs.
- ArticleJin J, Zhao Q.Theranostics. 2020;10(14):6231-6244.During the last few decades, cell-based anti-tumor immunotherapy emerged and it has provided us with a large amount of knowledge. Upon chemokines recognition, immune cells undergo rapid trafficking and activation in disease milieu, with immune cells chemotaxis being accompanied by activation of diverse intercellular signal transduction pathways. The outcome of chemokines-mediated immune cells chemotaxis interacts with the cue of mammalian target of rapamycin (mTOR) in the tumor microenvironment (TME). Indeed, the mTOR cascade in immune cells involves migration and infiltration. In this review, we summarize the available mTOR-related chemokines, as well as the characterized upstream regulators and downstream targets in immune cells chemotaxis and assign potential underlying mechanisms in each evaluated chemokine. Specifically, we focus on the involvement of mTOR in chemokine-mediated immune related cells in the balance between tumor immunity and malignancy.
- ArticleWang L, Dong Z, Wang D, Zhang F, Jin J.Nano Lett. 2013;13(12):6244-50.High-capacity electrochemical active material-based electrodes for lithium ion batteries (LIBs), such as sulfur (S), always face the collapse of the electrode due to the big volume change during insertion of the lithium (Li) ion and therefore shorten the cycle life of the cells. Herein, a series of design from the viewpoint of both individual components and the entire cathode in lithium-sulfur (Li-S) cell was introduced aiming at addressing the issues of poor conductivity, leakage of intermediate polysulphides, and large volumetric expansion upon insertion of the Li ion. In the designed electrode, polydopamine (PD)-coated S nanosheets (NSs) were used as active materials, carboxylic acid functionalized multiwall carbon nanotube (MWCNT-COOH) as conductive additives, and poly(acrylic acid) (PAA) as binders. Far different from the traditional hydrogen bond and/or van der Waals force linked electrodes, stronger covalent bonds formed by cross-linking of PD/MWCNT-COOH and PD/PAA into amide bonds, respectively, were built throughout the whole electrode to firmly integrate all of the individual components in the electrode together. As a result, the cathode demonstrated excellent cyclic performance with a charge capacity of 640 mAh/g after 500 cycles at a current density of 1 A/g. Besides, the charge capacity decay after 500 cycles is as small as 0.021% per cycle, which represents the best capacity retention so far.
- ArticleKhatri A, Trinh R, Zhao W, Podsadecki T, Menon R.Antimicrob Agents Chemother. 2016 10;60(10):6244-51.The direct-acting antiviral regimen of 25 mg ombitasvir-150 mg paritaprevir-100 mg ritonavir once daily (QD) plus 250 mg dasabuvir twice daily (BID) is approved for the treatment of hepatitis C virus genotype 1 infection, including patients coinfected with human immunodeficiency virus. This study was performed to evaluate the pharmacokinetic, safety, and tolerability effects of coadministering the regimen of 3 direct-acting antivirals with two antiretroviral therapies (dolutegravir or abacavir plus lamivudine). Healthy volunteers (n = 24) enrolled in this phase I, single-center, open-label, multiple-dose study received 50 mg dolutegravir QD for 7 days or 300 mg abacavir plus 300 mg lamivudine QD for 4 days, the 3-direct-acting-antiviral regimen for 14 days, followed by the 3-direct-acting-antiviral regimen with dolutegravir or abacavir plus lamivudine for 10 days. Pharmacokinetic parameters were calculated to compare combination therapy with 3-direct-acting-antiviral or antiretroviral therapy alone, and safety/tolerability were assessed throughout the study. Coadministration of the 3-direct-acting-antiviral regimen increased the geometric mean maximum plasma concentration (Cmax) and the area under the curve (AUC) of dolutegravir by 22% (central value ratio [90% confidence intervals], 1.219 [1.153, 1.288]) and 38% (1.380 [1.295, 1.469]), respectively. Abacavir geometric mean Cmax and AUC values decreased by 13% (0.873 [0.777, 0.979]) and 6% (0.943 [0.901, 0.986]), while those for lamivudine decreased by 22% (0.778 [0.719, 0.842]) and 12% (0.876 [0.821, 0.934]). For the 3-direct-acting-antiviral regimen, geometric mean Cmax and AUC during coadministration were within 18% of measurements made during administration of the 3-direct-acting-antiviral regimen alone, although trough concentrations for paritaprevir were 34% (0.664 [0.585, 0.754]) and 27% (0.729 [0.627, 0.847]) lower with dolutegravir and abacavir-lamivudine, respectively. All study treatments were generally well tolerated, with no evidence of increased rates of adverse events during combination administration. These data indicate that the 3-direct-acting-antiviral regimen can be administered with dolutegravir or abacavir plus lamivudine without dose adjustment.
- ArticleXia X, Wang S, Ni B, Xing S, Cao H, Zhang Z, Yu F, Zhao E, Zhao G.Oncogene. 2020 09;39(39):6231-6244.Hypoxic tumor microenvironment(TME) is a universal feature in solid carcinoma and is associated with unfavorable prognosis. Tumor-derived exosomes are now significantly implicating in mediating cellular communication and interactions in TME. The aim of this study was to identify exosomal miR-301a-3p involved in gastric cancer(GC) progression and metastasis. Here, we found hypoxia promote GC exosomes release and miR-301a-3p expression in an HIF-1α-dependent manner. In hypoxic TME, enriched miR-301a-3p could be transmitted between GC cells via exosomes and then contributed to inhibit HIF-1α degradation through targeting PHD3, that were capable to hydroxylate HIF-1α subunits to ubiquitinate degradation. This synergistical positive feedback loop between HIF-1α and miR-301a-3p facilitated GC proliferation, invasion, migration, and epithelial-mesenchymal transition. In clinical samples, we further discovered circulating exosomal miR-301a-3p in serum was positively related with peritoneal metastasis. Collectively, these data indicate that GC cells could generate miR-301a-3p-rich exosomes in the hypoxic TME, which then help to HIF-1α accumulation and promote GC malignant behaviors and metastasis. Exosomal miR-301a-3p/HIF-1α signaling axis may serve as a promising predictor and potential therapeutic target of GC with metastasis.
- ArticleZhang D, Zhou C, Sun Z, Wu LZ, Tung CH, Zhang T.Nanoscale. 2012 Oct 21;4(20):6244-55.Recent advances in wet chemical synthesis of magnetically recyclable nanocatalysts (MRNCs), a versatile integration of high catalytic activity and facile recovery, have led to a dramatic expansion of their potential applications. This review focuses on the recent work in the development of metal and metal oxide based MRNCs for catalytic conversion of organic compounds in solution phase. This will be discussed in detail, according to the two main synthesis methods of MRNCs as classified by us. The two methods are: template-assisted synthetic strategy and direct synthetic strategy. And the template-assisted synthesis is further divided into three subcategories, synthetic strategies assisted by hard-, soft-, and mixed hard-soft coupling layers. At the end, we outline future trends and perspectives in these research areas.
- ArticlePfanzelt S, Albach DC, von Hagen KB.PeerJ. 2019;7:e6244.Astelia pumila (G.Forst.) Gaudich. (Asteliaceae, Asparagales) is a major element of West Patagonian cushion peat bog vegetation. With the aim to identify appropriate chloroplast markers for the use in a phylogeographic study, the complete chloroplast genomes of five A. pumila accessions from almost the entire geographical range of the species were assembled and screened for variable positions. The chloroplast genome sequence was obtained via a mapping approach, using Eustrephus latifolius (Asparagaceae) as a reference. The chloroplast genome of A. pumila varies in length from 158,215 bp to 158,221 bp, containing a large single copy region of 85,981-85,983 bp, a small single copy region of 18,182-18,186 bp and two inverted repeats of 27,026 bp. Genome annotation predicted a total of 113 genes, including 30 tRNA and four rRNA genes. Sequence comparisons revealed a very low degree of intraspecific genetic variability, as only 37 variable sites (18 indels, 18 single nucleotide polymorphisms, one 3-bp mutation)-most of them autapomorphies-were found among the five assembled chloroplast genomes. A Maximum Likelihood analysis, based on whole chloroplast genome sequences of several Asparagales accessions representing six of the currently recognized 14 families (sensu APG IV), confirmed the phylogenetic position of A. pumila. The chloroplast genome of A. pumila is the first to be reported for a member of the astelioid clade (14 genera with c. 215 species), a basally branching group within Asparagales.
- ArticleKimishima A, Umihara H, Mizoguchi A, Yokoshima S, Fukuyama T.Org Lett. 2014 Dec 05;16(23):6244-7.Our novel synthetic route to (-)-oxycodone, a semisynthetic opioid analgesic, features a palladium-catalyzed direct intramolecular arylation of an aryl bromide, oxidative dearomatization of a dihydrophenanthrenol, formation of a benzylic quaternary carbon by an intramolecular Michael addition of a malonate moiety, and construction of the morphinan skeleton via a Hofmann rearrangement/lactamization cascade.
- ArticleMohammed KAS, Hussein HM, Elshamly AMS.Sci Rep. 2024 03 15;14(1):6244.In recent decades, numerous studies have examined the effects of climate change on the responses of plants. These studies have primarily examined the effects of solitary stress on plants, neglecting the simultaneous effects of mixed stress, which are anticipated to transpire frequently as a result of the extreme climatic fluctuations. Therefore, this study investigated the impact of applied chitosan on boosting the resistance responses of peanuts to alkali and mixed drought-alkali stresses. Peanuts were grown in mid-alkaline soil and irrigated with full irrigation water requirements (100%IR), represented alkali condition (100% IR × alkali soil) and stress conditions (70% IR × alkali soil-represented mixed drought-alkali conditions). Additionally, the plants were either untreated or treated with foliar chitosan. The study evaluated various plant physio-chemical characteristics, including element contents (leaves and roots), seed yield, and irrigation water use efficiency (IWUE). Plants that experienced solitary alkali stress were found to be more vulnerable. However, chitosan applications were effective for reducing (soil pH and sodium absorption), alongside promoting examined physio-chemical measurements, yield traits, and IWUE. Importantly, when chitosan was applied under alkali conditions, the accumulations of (phosphorus, calcium, iron, manganese, zinc, and copper) in leaves and roots were maximized. Under mixed drought-alkali stresses, the results revealed a reduction in yield, reaching about 5.1 and 5.8% lower than under (100% IR × alkali), in the first and second seasons, respectively. Interestingly, treated plants under mixed drought-alkali stresses with chitosan recorded highest values of relative water content, proline, yield, IWUE, and nutrient uptake of (nitrogen, potassium, and magnesium) as well as the lowest sodium content in leaves and roots. Enhances the accumulation of (N, K, and Mg) instead of (phosphorus, calcium, iron, manganese, zinc, and copper) was the primary plant response to chitosan applications, which averted severe damage caused by mixed drought-alkali conditions, over time. These findings provide a framework of the nutrient homeostasis changes induced by chitosan under mixed stresses. Based on the findings, it is recommended under mixed drought-alkali conditions to treat plants with chitosan. This approach offers a promising perspective for achieving optimal yield with reduced water usage.
- ArticleSun Z, Zhang H, Zhao Y, Huang C, Tao R, Liu Z, Wu Z.Langmuir. 2011 May 17;27(10):6244-51.A universal strategy was developed for the preparation of high-temperature-stable carbon nanotube (CNT) -supported metal nanocatalysts by encapsulation with a mesoporous silica coating. Specifically, we first showed the design of one novel catalyst, Pt(@)CNT/SiO(2), with a controllable mesoporous silica coating in the range 11-39 nm containing pores ≈3 nm in diameter. The hollow porous silica shell offers a physical barrier to separate Pt nanoparticles from contact with each other, and at the same time the access of reactant species to Pt was not much affected. As a result, the catalyst showed high thermal stability against metal particle agglomeration or sintering even after being subjected to harsh treatments up to 500 °C. In addition, degradation in catalytic activity was minimized for the hydrogenation of nitrobenzene over the catalyst treated at 300 °C for 2 h. The scheme was also extended to coat porous silica onto the surfaces of CuRu(@)CNT and the resultant catalyst thereby can be reusable at least four times without loss of activity for the hydrogenolysis of glycerol. These results suggest that the as-prepared nanostructured CNT-supported catalysts may find promising applications, especially in those processes requiring rigorous conditions.
- ArticleFan SY, Yang Q, Li SP, Fristoe TS, Cadotte MW, Essl F, Kreft H, Pergl J, Pyšek P, Weigelt P, Kartesz J, Nishino M, Wieringa JJ, van Kleunen M.Nat Commun. 2023 10 12;14(1):6244.Darwin's naturalization conundrum describes two seemingly contradictory hypotheses regarding whether alien species closely or distantly related to native species should be more likely to naturalize in regional floras. Both expectations have accumulated empirical support, and whether such apparent inconsistency can be reconciled at the global scale is unclear. Here, using 219,520 native and 9,531 naturalized alien plant species across 487 globally distributed regions, we found a latitudinal gradient in Darwin's naturalization conundrum. Naturalized alien plant species are more closely related to native species at higher latitudes than they are at lower latitudes, indicating a greater influence of preadaptation in harsher climates. Human landscape modification resulted in even steeper latitudinal clines by selecting aliens distantly related to natives in warmer and drier regions. Our results demonstrate that joint consideration of climatic and anthropogenic conditions is critical to reconciling Darwin's naturalization conundrum.
- ArticleHerzog R, Mediano PAM, Rosas FE, Lodder P, Carhart-Harris R, Perl YS, Tagliazucchi E, Cofre R.Sci Rep. 2023 04 17;13(1):6244.Psychedelic drugs, including lysergic acid diethylamide (LSD) and other agonists of the serotonin 2A receptor (5HT2A-R), induce drastic changes in subjective experience, and provide a unique opportunity to study the neurobiological basis of consciousness. One of the most notable neurophysiological signatures of psychedelics, increased entropy in spontaneous neural activity, is thought to be of relevance to the psychedelic experience, mediating both acute alterations in consciousness and long-term effects. However, no clear mechanistic explanation for this entropy increase has been put forward so far. We sought to do this here by building upon a recent whole-brain model of serotonergic neuromodulation, to study the entropic effects of 5HT2A-R activation. Our results reproduce the overall entropy increase observed in previous experiments in vivo, providing the first model-based explanation for this phenomenon. We also found that entropy changes were not uniform across the brain: entropy increased in all regions, but the larger effect were localised in visuo-occipital regions. Interestingly, at the whole-brain level, this reconfiguration was not well explained by 5HT2A-R density, but related closely to the topological properties of the brain's anatomical connectivity. These results help us understand the mechanisms underlying the psychedelic state and, more generally, the pharmacological modulation of whole-brain activity.
- ArticleHuang C, Yu QP, Ding Z, Zhou Z, Shi X.Cancer Med. 2023 03;12(5):6244-6259.BACKGROUND: This study aims to determine the independent prognostic predictors of cancer-specific survival (CSS) in patients with primary Ewing sarcoma (ES) that underwent chemotherapy and create a novel prognostic nomogram and risk stratification system.
METHODS: Demographic and clinicopathologic characteristics related to patients with primary ES that underwent chemotherapy between 2000 and 2018 were extracted from the Surveillance, Epidemiology, and End Results (SEER) database. CSS was the primary endpoint of this study. First, independent prognostic predictors of CSS identified from univariate and multivariate Cox regression analyses were used to construct a prognostic nomogram for predicting 1-, 3-, and 5-year CSS of patients with primary ES that underwent chemotherapy. Then, calibration curves and receiver operating characteristic (ROC) curves were used to evaluate the nomogram's prediction accuracy, while decision curve analysis (DCA) was used to evaluate the nomogram's clinical utility. Finally, a mortality risk stratification system was constructed for this subpopulation.
RESULTS: A total of 393 patients were included in this study. Age, tumor size, bone metastasis, and surgery were independent prognostic predictors of CSS. The calibration curves, ROC, and DCA showed that the nomogram had excellent discrimination and clinical value, with the 1-, 3-, and 5-year AUCs higher than 0.700. Moreover, the mortality risk stratification system could effectively divide all patients into three risk subgroups and achieve targeted patient management.
CONCLUSIONS: Based on the SEER database, a novel prognostic nomogram for predicting 1-, 3-, and 5- year CSS in patients with primary ES that underwent chemotherapy has been constructed and validated. The nomogram showed relatively good performance, which could be used in clinical practice to assist clinicians in individualized treatment strategies. - ArticleWu ZJ, Xu H, Wang R, Bu LJ, Ning J, Hao JQ, Sun GP, Ma T.J Cancer. 2019;10(25):6244-6251.Background: To investigate the prognostic significance of the cumulative score based on preoperative fibrinogen and pre-albumin (FP score) in patients with gastric cancer after radical gastrectomy. Methods: Baseline characteristics, preoperative fibrinogen and pre-albumin levels were retrospectively reviewed in patients who underwent radical gastrectomy. The optimal cut-off values for fibrinogen and pre-albumin were defined as 4.0 g/L and 230.0 mg/L, respectively. Patients with elevated fibrinogen (≥ 4.0 g/L) and decreased pre-albumin (< 230.0 mg/L) levels were allocated an FP score of 2, those with only one of these two abnormalities were assigned a score of 1, and those with neither of the two abnormalities were allocated a score of 0. The prognostic value was examined by univariate and multivariate regression analyses. Results: The preoperative FP score was significantly correlated with age, tumor size, fibrinogen level, pre-albumin level and white blood cell count. No significant differences based on sex, tumor location, degree of differentiation, depth of invasion, lymph node status, tumor-node-metastasis (TNM) stage or adjuvant chemotherapy were identified between the groups. In addition, univariate survival analysis revealed that a high preoperative FP score was significantly associated with unfavorable disease-free survival (DFS) [hazard ratio (HR), 1.482; 95% confidence interval (CI), 1.222-1.796; P < 0.001] and overall survival (OS) (HR, 1.623; 95% CI, 1.315-2.002; P < 0.001). Moreover, after adjusting for other factors, a high preoperative FP score remained an independent predictor for impaired DFS (HR, 1.434; 95% CI, 1.177-1.747; P < 0.001) and OS (HR, 1.413; 95% CI, 1.136-1.758; P = 0.002) in multivariate Cox regression analysis. Conclusions: The preoperative FP score significantly predicts long-term survival for gastric cancer patients who have undergone radical gastrectomy.
- ArticleZhou K, Xu H, Lu S, Jiang S, Hou G, Deng X, He M, Zhu Y.Nat Commun. 2022 10 21;13(1):6244.The nucleus accumbens (NAc) is critical in mediating reward seeking and is also involved in negative emotion processing, but the cellular and circuitry mechanisms underlying such opposing behaviors remain elusive. Here, using the recently developed AAV1-mediated anterograde transsynaptic tagging technique in mice, we show that NAc neurons receiving basolateral amygdala inputs (NAcBLA) promote positive reinforcement via disinhibiting dopamine neurons in the ventral tegmental area (VTA). In contrast, NAc neurons receiving paraventricular thalamic inputs (NAcPVT) innervate GABAergic neurons in the lateral hypothalamus (LH) and mediate aversion. Silencing the synaptic output of NAcBLA neurons impairs reward seeking behavior, while silencing of NAcPVT or NAcPVT→LH pathway abolishes aversive symptoms of opiate withdrawal. Our results elucidate the afferent-specific circuit architecture of the NAc in controlling reward and aversion.
- ArticleRashidi A, Ebadi M, Rehman TU, Elhusseini H, Halaweish H, Holtan SG, Ramamoorthy S, Weisdorf DJ, Khoruts A, Staley C.Sci Rep. 2022 04 15;12(1):6244.Neutropenic fever (NF) is a common complication of chemotherapy in patients with cancer which often prolongs hospitalization and worsens the quality of life. Although an empiric antimicrobial approach is used to prevent and treat NF, a clear etiology cannot be found in most cases. Emerging data suggest an altered microbiota-host crosstalk leading to NF. We profiled the serum metabolome and gut microbiome in longitudinal samples before and after NF in patients with acute myeloid leukemia, a prototype setting with a high incidence of NF. We identified a circulating metabolomic shift after NF, with a minimal signature containing 18 metabolites, 13 of which were associated with the gut microbiota. Among these metabolites were markers of intestinal epithelial health and bacterial metabolites of dietary tryptophan with known anti-inflammatory and gut-protective effects. The level of these metabolites decreased after NF, in parallel with biologically consistent changes in the abundance of mucolytic and butyrogenic bacteria with known effects on the intestinal epithelium. Together, our findings indicate a metabolomic shift with NF which is primarily characterized by a loss of microbiota-derived protective metabolites rather than an increase in detrimental metabolites. This analysis suggests that the current antimicrobial approach to NF may need a revision to protect the commensal microbiota.
- ArticlePhulwale BV, Mishra SK, Nečas M, Mazal C.J Org Chem. 2016 08 05;81(15):6244-52.A series of macrocycles consisting of 9,10-substituted phenanthrenes connected by butadiynylene linkers in positions 3 and 6 has been described as well as their transformation into the corresponding phenanthrylene-thienylene macrocycles. Structure and properties of the macrocycles, such as self-association in solution and optical and electrochemical properties, were studied and reported in a comparative manner with respect to the effects of the different sizes and shapes of the macrocycles and the character and length of their side chains.
- ArticlePozner R, Lifshitz E, Peskin U.Nano Lett. 2014 Nov 12;14(11):6244-9.Colloidal quantum dots (CQDs) are free-standing nanostructures with chemically tunable electronic properties. This combination of properties offers intriguing new possibilities for nanoelectromechanical devices that were not explored yet. In this work, we consider a new scanning tunneling microscopy setup for measuring ligand-mediated effective interdot forces and for inducing motion of individual CQDs within an array. Theoretical analysis of a double quantum dot structure within this setup reveals for the first time voltage-induced interdot recoil and dissociation with pronounced changes in the current. Considering realistic microscopic parameters, our approach enables correlating the onset of mechanical motion under bias voltage with the effective ligand-mediated binding forces.
- ArticleMoreno-Clavijo E, Moreno-Vargas AJ, Kieffer R, Sigstam T, Carmona AT, Robina I.Org Lett. 2011 Dec 02;13(23):6244-7.The high strain of bicyclic systems drives retro-condensation reactions on bridgehead substituted bicyclo[2.2.1]hept-2-enes giving rise to orthogonally functionalized cyclopentene, 2,5-dihydrofuran, and 3-pyrroline scaffolds. Retro-Dieckman reactions were easily carried out on 3-tosyl-(7-carba/7-oxa/7-aza)bicyclo[2.2.1]hept-5-en-2-ones. Retro-aldol reactions of N-Boc-3-tosyl-7-azabicyclo[2.2.1]hept-5-en-2-ol and functionalized N-Boc-3-tosyl-7-azabicyclo[2.2.1]heptan-2-ols yield functionalized pyrrolidine scaffolds stereoselectively. The same reaction does not work with corresponding norbornene and 7-oxanorbornene derivatives.
- ArticleGautom T, Dheeman D, Levy C, Butterfield T, Alvarez Gonzalez G, Le Roy P, Caiger L, Fisher K, Johannissen L, Dixon N.Nat Commun. 2021 10 29;12(1):6244.Biological degradation of Polyethylene terephthalate (PET) plastic and assimilation of the corresponding monomers ethylene glycol and terephthalate (TPA) into central metabolism offers an attractive route for bio-based molecular recycling and bioremediation applications. A key step is the cellular uptake of the non-permeable TPA into bacterial cells which has been shown to be dependent upon the presence of the key tphC gene. However, little is known from a biochemical and structural perspective about the encoded solute binding protein, TphC. Here, we report the biochemical and structural characterisation of TphC in both open and TPA-bound closed conformations. This analysis demonstrates the narrow ligand specificity of TphC towards aromatic para-substituted dicarboxylates, such as TPA and closely related analogues. Further phylogenetic and genomic context analysis of the tph genes reveals homologous operons as a genetic resource for future biotechnological and metabolic engineering efforts towards circular plastic bio-economy solutions.