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Stigmaeopsis (Acari: Tetranychidae) species with social behaviors are difficult to be identified by morphological characteristics. The lack of nucleic acid resources as well as difficulties in sample acquisition have hindered phylogenetic studies and comparative mitochondrial genome analyses. In this study, we sequenced and annotated the mitochondrial genomes of Stigmaeopsis nanjingensis (Ma & Yuan, 1980) and S. continentalisSaito & Lin, 2018 using Illumina platform and homologous structures. The new resources integrated with public representative species under the family Tetranychidae to support the comparative and phylogenetic analysis. We obtained 37 mitochondrial genes from S. nanjingensis and S. continentalis, respectively. In phylogenetic results, all species of family Tetranychidae are well-clustered and divided into three clades. Genes and relative synonymous codon usage showed strong AT bias within Tetranychidae. Atp8 was the most variable gene and cox1 was the most conserved gene among 14 spider mite species verified by nucleotide content and bias, genes pairwise identities and the nucleotide diversities. [ABSTRACT FROM AUTHOR]

Intracranial aneurysm (IA) is a common cerebrovascular disease. Immune system disorders and endothelial dysfunction are essential mechanisms of its pathogenesis. This study aims to explore the therapeutic effect and mechanism of Geniposide (Gen) on IA, which has a protective impact on endothelial cells and cardiovascular and cerebrovascular diseases. IA mouse models were administered intraperitoneal injections of geniposide for 2 weeks following elastase injection into the right basal ganglia of the brain for intervention. The efficacy of Gen in treating IA was evaluated through pathological testing and transcriptome sequencing analysis of Willis ring vascular tissue. The primary mechanism of action was linked to the expression of GSK3β in Th17 cells. The percentage of splenic Th17 cell differentiation in IA mice was significantly inhibited by Gen. GSK3β/STAT3, and other pathway protein expression levels were also significantly inhibited by Gen. Additionally, TNF‐α and IL‐23 cytokine contents were significantly downregulated after Gen treatment. These results indicated that Gen significantly inhibited the percentage of Th17 cell differentiation, an effect that was reversed upon overexpression of the GSK3B gene. Furthermore, Gen‐treated, Th17 differentiation‐inducing cell‐conditioned medium significantly up‐regulated the expression of tight junction proteins ZO‐1, Occludin, and Claudin‐5 in murine aortic endothelial cells. Administering the GSK3β inhibitor Tideglusib to IA mice alleviated the severity of IA disease pathology and up‐regulated aortic tight junction protein expression. In conclusion, Gen inhibits Th17 cell differentiation through GSK3β, which reduces endothelial cell injury and up‐regulates tight junction protein expression. [ABSTRACT FROM AUTHOR]

Neoseiulus californicus is a key natural predator of spider mites and small arthropod pests. Although vitellogenin (Vg) and vitellogenin receptor (VgR) genes are important regulators of oocyte maturation, egg formation, and embryonic development in spider mites and ticks, their role in phytoseiid mites is less understood. Investigating the reproductive mechanism of predatory mites is crucial for understanding their reproduction and evolution. In this study, three Vg genes and one VgR gene were identified, cloned, and characterized in N. californicus. Vg1, Vg2, Vg3, and VgR mRNAs were 6066, 5728, 4515, and 5331 bp long, encoding proteins comprising 1851, 1849, 1471, and 1722 amino acids, respectively. Temporal expression analysis revealed elevated Vg1, Vg2, and VgR levels in fertilized female adult mites, whereas Vg3 exhibited peak expression during the developmental stage. RNA interference–mediated suppression of Vg1 and Vg2 resulted in 14.66% and 11.59% decreases in fecundity, respectively. Vg1 silencing notably reduced egg hatching rate and female offspring ratio. In contrast, Vg3 and VgR silencing had no significant impact on fecundity and egg hatching rate. These findings provide insights into the regulatory roles of Vg and VgR in predatory mite reproduction, offering a theoretical foundation for understanding their evolution and reproductive strategies. [ABSTRACT FROM AUTHOR]

Background and purpose: Calmodulin (CaM) levels exhibit significant elevation in the brain tissue of rodent and cell line models infected with prion, as well as in the cerebrospinal fluid (CSF) samples from patients diagnosed with sporadic Creutzfeldt-Jakob disease (sCJD). However, the status of CSF CaM in patients with genetic prion diseases (gPrDs) remains unclear. This study aims to assess the characteristics of CSF CaM in Chinese patients presenting four subtypes of gPrDs. Methods: A total of 103 CSF samples from patients diagnosed with T188KgCJD, E200K-gCJD, D178N-FFI, P102L-GSS were included in this study, along with 40 CSF samples from patients with non-prion diseases (non-PrDs). The presence of CSF CaM and 14-3-3 proteins was assessed using Western blots analysis, while levels of CSF 14-3-3 and total tau were measured using enzymelinked immunosorbent assays (ELISAs). Statistical methods including multivariate logistic regression were employed to evaluate the association between CSF CaM positivity and relevant clinical, laboratory, and genetic factors. Results: The positive rates of CSF CaM were significantly higher in cases of T188K-gCJD (77.1%), E200K-gCJD (86.0%), and P102-GSS (90.9%) compared to non-PrD cases (22.5%). In contrast, CSF CaM positivity was slightly elevated in D178N-FFI (34.3%). CSF CaM positivity was remarkably high in patients who tested positive for CSF 14-3-3 by Western blot and exhibited high levels of total tau (≥1400 pg/ml) as measures by ELISA. Multivariate logistic regression analysis confirmed a significant association between CSF CaM positivity and specific mutations in PRNP, as well as with CSF 14-3-3 positivity. Furthermore, the diagnostic performance of CaM surpassed that of 14-3-3 and tau when analyzing CSF samples from T188K-gCJD and E200K-gCJD patients. Conclusion: Western blot analysis reveals significant variations in the positivity of CSF CaM among the four genotypes of gPrD cases, demonstrating a positive correlation with 14-3-3 positivity and elevated tau levels in CSF. [ABSTRACT FROM AUTHOR]

Objectives: Histological transformation to small cell lung cancer (SCLC) has been identified as a mechanism of TKIs resistance in EGFR-mutant non-small cell lung cancer (NSCLC). We aim to explore the prevalence of transformation in EGFR-wildtype NSCLC and the mechanism of SCLC transformation, which are rarely understood. Methods: We reviewed 1474 NSCLC patients to investigate the NSCLC-to-SCLC transformed cases and the basic clinical characteristics, driver gene status and disease course of them. To explore the potential functional genes in SCLC transformation, we obtained pre- and post-transformation specimens and subjected them to a multigene NGS panel involving 416 cancer-related genes. To validate the putative gene function, we established knocked-out models by CRISPR-Cas 9 in HCC827 and A549-TP53-/- cells and investigated the effects on tumor growth, drug sensitivity and neuroendocrine phenotype in vitro and in vivo. We also detected the expression level of protein and mRNA to explore the molecular mechanism involved. Results: We firstly reported an incidence rate of 9.73% (11/113) of SCLC transformation in EGFR-wildtype NSCLC and demonstrated that SCLC transformation is irrespective of EGFR mutation status (P = 0.16). We sequenced 8 paired tumors and identified a series of mutant genes specially in transformed SCLC such as SMAD4, RICTOR and RET. We firstly demonstrated that SMAD4 deficiency can accelerate SCLC transition by inducing neuroendocrine phenotype regardless of RB1 status in TP53-deficient NSCLC cells. Further mechanical experiments identified the SMAD4 can regulate ASCL1 transcription competitively with Myc in NSCLC cells and Myc inhibitor acts as a potential subsequent treatment agent. Conclusions: Transformation to SCLC is irrespective of EFGR status and can be accelerated by SMAD4 in non-small cell lung cancer. Myc inhibitor acts as a potential therapeutic drug for SMAD4-mediated resistant lung cancer. 9vNWjpNbo9djtsBQF6k7BH Video Abstract [ABSTRACT FROM AUTHOR]

We obtained TiNiSn-based half-Heusler HfxTi1−xNiSn0.97Sb0.03 bulks with 85%–96% relative densities via 5-min microwave synthesis and 20-min microwave sintering in sealed vacuum. The phase composition and microstructure of samples were characterized by X-ray diffractometer (XRD) and scanning electron microscopy (SEM). Thermoelectric (TE) properties were measured, i.e., Seebeck coefficient (S), electrical resistivity (ρ), and thermal conductivity (κ) through Seebeck coefficient/resistance analysis system (S/RAs) and laser flash thermal analyzer (LFT). The results show that the nearly single phase exists after microwave sintering. The grain sizes and the number of grain boundaries decrease with increase in Hf-doping amount due to an increase in point defects. The matrix grains for Hf0.1Ti0.9NiSn0.97Sb0.03 are ~ 10 μm. The nanoscle pores and precipitates are present as second phases in matrix grain. The real composition for Hf0.1Ti0.9NiSn0.97Sb0.03 matrix grain is Hf3.51Ti28.76Ni34.76Sn31.55Sb1.43. The variation trends of electrical resistivity, Seebeck coefficient, power factor, and thermal conductivity were analyzed in detail. The maximum figure of merit (ZT) of 0.46 is obtained for Hf0.1Ti0.9NiSnSn0.97Sb0.03 at 723 K. The innovation route exhibits advantages for predation of TE bulks when compared to the conventional methods, especially in terms of efficiency while it still maintains TE performance. [ABSTRACT FROM AUTHOR]

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Objective: Tertiary lymphoid structures (TLSs) provide sites for antigen presentation and activation of lymphocytes, promoting their infiltration; thus, enhancing specific immune responses. The aim of this comparative cross‐sectional study was to reveal the characteristics and influence of TLSs in oral lichen planus (OLP) and oral epithelial dysplasia (OED) with lichenoid features. Methods: Clinical information and samples of 51 OLP and 19 OED with lichenoid features were collected. Immunohistochemistry was performed, and the structures where CD20+ B cells and CD3+ T cells aggregated with peripheral lymph node addressin positive (PNAd+) vessels were defined as TLSs. The results and clinical information were analysed. Result: TLS were found in 44 (86.3%) patients with OLP and 19 (100%) patients with OED. The TLS score was higher in OED group (p = 0.023), accompanied by an increased number of PNAd+ vessels. The TLS was significantly correlated with PNAd+ vessels (p = 0.027), CD20+ B (p < 0.001) and CD208+ dendritic cells (p = 0.001). Foxp3+ Treg cells but not CD8+ T cells infiltrated more severely in OED (p = 0.003) and increased when TLS score was high (p = 0.002). Conclusions: This study revealed the widespread development of TLSs in the OLP and OED. The presence of TLSs showed a close relationship with dysplasia and may increase malignant potency by over‐inducing Treg cells. [ABSTRACT FROM AUTHOR]

Surface charging commonly appears on dielectrics in vacuum in the presence of electron bombardment, seriously aggravating the superficial withstand strength of assorted devices. Nonetheless, a pre-conditioning technique is introduced in this paper capitalizing on surface charges to play an opposite role, enhancing flashover strength and suppressing the multipactor which is frequently found over vacuum insulator. A theoretical study is first performed, incorporated with particle-in-cell simulation to show the critical condition for a single-surface multipactor to initiate. Therewith, it is proven that a negative charge accretion in cathode adjacency can prevent the multipactor from commencing with efficiency. Subsequently, an analytical model is constructed to expatiate multipactor expansion with pre-set surface charges getting involved, illustrating an upper bound of its propagation velocity, influenced by pre-conditioning. Corresponding experiments are also conducted to corroborate previous conclusions, presenting both a deflected electron trajectory and an improved flashover threshold. In the end, a brief discussion is given on a possible method to generate desired surface charge distribution in practical applications. [ABSTRACT FROM AUTHOR]

Our general purpose was to examine the effect of condensed Fuzheng extract (CFE) on the alleviation of immunosuppression. A mouse model of immunosuppression was established by intraperitoneal injection of CTX. A healthy control group received no CTX and no CFE; different intragastric doses of CFE were administered to three groups of mice for 28 days (4500, 2250, or 1125 mg/kg/day); a negative control received CTX alone, and a positive control received CTX and levamisole hydrochloride. We evaluated the effects of CFE on the immune system organs, cells, and molecules by comparing the different groups. CFE significantly improved immune system organs (spleen and thymus indices and histology), stimulated immune cell activities (number of white blood cells and lymphocytes, phagocytosis of mononuclear phagocytes, proliferation of splenic lymphocytes, antibody formation, and NK cell activity), and increased the levels of immunoglobulins (IgA, IgG, and IgM) and cytokines (IL‐2 and IFN‐γ). Thus CFE effectively alleviated CTX‐mediated immunosuppression and oxidative stress and enhanced the immunological functions of mice. [ABSTRACT FROM AUTHOR]

Objectives: The relationship between fertility history and human health has long fascinated scholars; however, whether there is a link between number of children and cognitive function in older adults remains unclear. We investigated the associations between parity and the timing of first and last births with the cognitive function of older adults over 65. Methods: The mini‐mental state examination (MMSE) was selected as a tool to measure cognitive function. We analyzed data on 5847 older adults in rural and urban communities in China from the 2018 Chinese Longitudinal Healthy Longevity Survey using ordinary least squares. To further explore the transmission mechanism, we also conducted a mediating effect analysis. Results: We found a negative association between number of children and cognitive function in older adults. Compared with older adults with four children, the MMSE scores of older adults with more than five children decreased significantly, and the score of older adults with zero to three children increased. Further, a late age at first birth (≥35) and a late age at last birth (≥35) were negatively associated with cognitive function. We also found that the associations between parity and cognition might be partly explained by variations in health. Conclusion: Our analyses provided evidence from China to support the link between fertility history and cognitive function that has been observed in previous international studies: We suggest that high parity (≥5) is negatively associated with cognitive function. [ABSTRACT FROM AUTHOR]

MOFs with adequate free nitrogen sites have potential applications in dye adsorption and formic acid dehydrogenation. Here, we successfully synthesized a novel 3-D MOF 1 ([(CH3)2NH2][Cd(L)DMA]·0.5DMA·1.5H2O) with a special two-fold interpenetrating framework through a simple solvothermal reaction between CdCl2·1.5H2O and a nitrogen-rich triangular tricarboxylate-based linker (H3L, 4,4′,4′′-s-triazine-2,4,6-tribenzoic acid). After removing the guest molecules of dimethylacetamide (DMA) and H2O, including the coordinated DMA from 1 by vacuum activation at 423 K, a compound named 1′ with a formula of [(CH3)2NH2][Cd(L)] and a similar interpenetrating framework structure was obtained. In comparison with compound 1, the total void volume of 1′ is nearly doubled, and thus may provide higher potential for the adsorption of other guest molecules. Notably, the pyridine N atoms located in the middle of the triangular tricarboxylate-based linker are not involved in the coordination with Cd2+, and are all uniformly dispersed throughout the whole framework of the 3-D MOFs. Due to its unique structural features, the 3-D MOF 1′ could effectively adsorb the cationic dye MB+ for recycling purposes. The rapid adsorption rate (0.7 × 10−2 g mg−1 min−1) and the relatively high capacity (900 mg g−1) for MB+ demonstrate the potential of 1′ in dye adsorption. In addition, 1′ may also be used as an effective support to immobilize PdAu NPs via the double-solvent method. The resultant catalyst Pd0.8Au0.2/1′ exhibits decent catalytic activity for the dehydrogenation of formic acid with a TOF value of 1854 h−1 at 333 K. The existence of a large void volume and accessible pyridine N atoms provide a suitable environment for achieving a high dispersion of PdAu NPs, thereby leading to the formation of a catalytically active and stable supported noble-metal NP catalyst for H2 generation from formic acid decomposition. [ABSTRACT FROM AUTHOR]

Owing to high speeds and heavy loads, the wheels of trains and locomotives undergo gradual but significant damage. Conventionally, these damaged wheels are repaired using the rotatory repair method; however, this approach results in large amounts of material waste. To address this issue, in this study, laser cladding remanufacturing technology was employed to repair a damaged wheel. The contact stress and creep characteristics of the cladded wheel were determined using Simpack, a dynamic simulation software program. The existing damage function model, which is based on the wear number, was modified, and this modified model was used to perform damage assessments for the remanufactured wheel. Furthermore, a life evaluation model for wheels remanufactured using this laser cladding technology was established. The service life of the cladded wheel calculated using this model was in good agreement with the design life of the wheel. [ABSTRACT FROM AUTHOR]

Background: Cancer-associated fibroblasts (CAFs), the most abundant cells in the tumor microenvironment, have prominent roles in the development of solid tumors as stromal targets. However, the underlying mechanism of CAFs' function in oral squamous cell carcinoma (OSCC) development remains unclear. Here, we investigated the role of lysyl oxidase (LOX) expression in CAFs in tumor stromal remodeling and the mechanism of its effect on OSCC progression.Methods: Multiple immunohistochemistry (IHC) staining was performed to detect the correlation of CAFs and LOX in the stroma of OSCC specimens, as well as the correlation with clinicopathological parameters and prognosis. The expression of LOX in CAFs were detected by RT-qPCR and western blot. The effects of LOX in CAFs on the biological characteristics of OSCC cell line were investigated using CCK-8, wound-healing and transwell assay. CAFs were co-cultured with type I collagen in vitro, and collagen contraction test, microstructure observation and rheometer were used to detect the effect of CAFs on remodeling collagen matrix. Then, collagen with different stiffness were established to investigate the effect of matrix stiffness on the progression of OSCC. Moreover, we used focal adhesion kinase (FAK) phosphorylation inhibitors to explored whether the increase in matrix stiffness promote the progression of OSCC through activating FAK phosphorylation pathway.Results: LOX was colocalized with CAFs in the stroma of OSCC tissues, and its expression was significantly related to the degree of malignant differentiation and poor prognosis in OSCC. LOX was highly expressed in CAFs, and its knockdown impaired the proliferation, migration, invasion and EMT process of OSCC cells. The expression of LOX in CAFs can catalyze collagen crosslinking and increase matrix stiffness. Furthermore, CAFs-derived LOX-mediated increase in collagen stiffness induced morphological changes and promoted invasion and EMT process in OSCC cells by activating FAK phosphorylation pathway.Conclusions: Our findings suggest that CAFs highly express LOX in the stroma of OSCC and can remodel the matrix collagen microenvironment, and the increase in matrix stiffness mediated by CAFs-derived LOX promotes OSCC development through FAK phosphorylation pathway. Thus, LOX may be a potential target for the early diagnosis and therapeutic treatment of OSCC. [ABSTRACT FROM AUTHOR]

Distance-based fares have been applied widely in practice using automatic fare collection technology. This paper proposes an optimization model for the distance-based transit fare structure. A bilevel model was formulated to obtain the optimal fare functions with the aim of minimizing the Gini coefficient of the entire transit system. Passengers' travel behavior is modeled by a stochastic transit assignment problem in the lower level. Considering the inherent complexity of the bilevel model, a heuristic algorithm, namely the artificial bee colony algorithm, is applied, which is incorporated with a method of successive averages to solve the transit assignment subproblem. The results show that the Euclidean distance-based fare has better performance in terms of social equity, but it is less equitable for passengers with middistance trips. [ABSTRACT FROM AUTHOR]

This research was designed to analyze the composition of immune cells in obesity and identify novel and potent drugs for obesity management by epigenetic and transcriptomic conjoint analysis. DNA methylation data set (GSE166611) and mRNA expression microarray (GSE18897) were obtained from the Gene Expression Omnibus database. A total of 72 objects (35 obese samples and 37 controls) were included in the study. Immune cell composition analysis, drug repositioning, and gene set enrichment analysis (GSEA) were performed using CIBERSORT, connectivity map (CMap), and GSEA tools. Besides, we performed a single-cell RNA-seq of the immune cells from whole blood samples obtained from one obese patient and one healthy control. mRNA levels of drug target genes were analyzed by qPCR assay in blood samples from six patients and six healthy controls. Immune cell composition analysis found that CD8 + T cells and NK cells were significantly lower in the obese group. 11 drugs/compounds are considered to possess obesity-control potential, such as atorvastatin. Moreover, the expression of drug targets (STAT3, MCL1, PMAIP1, SOD2, FOX O 3, FOS, FKBP5) in obese patients were higher than those in controls. In conclusion, immune cells are potential therapeutic targets for obesity. Our results also contribute to accelerate research on drug development of obesity. [ABSTRACT FROM AUTHOR]

Due to the population-based and iterative-based characteristics of evolutionary computation (EC) algorithms, parallel techniques have been widely used to speed up the EC algorithms. However, the parallelism usually performs in the population level where multiple populations (or subpopulations) run in parallel or in the individual level where the individuals are distributed to multiple resources. That is, different populations or different individuals can be executed simultaneously to reduce running time. However, the research into generation-level parallelism for EC algorithms has seldom been reported. In this article, we propose a new paradigm of the parallel EC algorithm by making the first attempt to parallelize the algorithm in the generation level. This idea is inspired by the industrial pipeline technique. Specifically, a kind of EC algorithm called local version particle swarm optimization (PSO) is adopted to implement a pipeline-based parallel PSO (PPPSO, i.e., P3SO). Due to the generation-level parallelism in P3SO, when some particles still perform their evolutionary operations in the current generation, some other particles can simultaneously go to the next generation to carry out the new evolutionary operations, or even go to further next generation(s). The experimental results show that the problem-solving ability of P3SO is not affected while the evolutionary speed has been substantially accelerated in a significant fashion. Therefore, generation-level parallelism is possible in EC algorithms and may have significant potential applications in time-consumption optimization problems. [ABSTRACT FROM AUTHOR]

We design and develop a high-performance magnetic shielding system for a long baseline fountain-type atom interferometer. The shielding system is achieved by a combination of passive shielding using permalloy and active compensation with coils. An 11.4 m-long three-layer cylindrical shield is completed by the process of welding, local annealing, and entire annealing. The active compensations compress the residual magnetic field to 8.0 nT max-to-min and the corresponding gradient below 30 nT/m over 10 m along the axial direction in which external compensation, internal compensation, and constant magnetic field (C-field) compensation reduce the inhomogeneities to 25.0, 12.6, and 1.7 nT (standard deviation) sequentially. We estimate that this system could reduce the systematic error of the quadratic Zeeman shift to the 10−13 level for the weak equivalence principle test with a simultaneous 85Rb–87Rb dual-species atom interferometer. [ABSTRACT FROM AUTHOR]

To investigate the attenuating effects of fermented Hylocereus undulatus peels (FHP) on lipopolysaccharide (LPS)-induced inflammation in RAW264.7 cells, and the mechanisms of attenuation, Hylocereus undulatus peels were fermented using Lactobacillus casei CICC20280. A methyl-thiazolyl-tetrazolium reduction assay was used to determine FHP cytotoxicity at different concentrations (50, 100, 200, 400 and 800 µg/mL). The following groups were included: a control group, an LPS-induced inflammation model group, and five groups treated with LPS and different concentrations of FHP. Nitric oxide (NO), reactive oxygen species (ROS), and cytokines (TNF-α, IL-1β, IL-6, and IL-10) in cell culture supernatants were quantitated using various molecular analysis techniques, including Griess, DCFH-DA fluorescence, and ELISA assays. RT-PCR was used to detect expression of NF-κB pathway components (TLR4/MyD88/NF-κB) and pro-inflammatory factors. FHP at concentrations of ≤400 µg/mL is non-toxic to RAW264.7 cells. FHP significantly decreases (p<0.05) concentrations of pro-inflammatory factors including NO, ROS, TNF-α, IL-1β and IL-6, by an average of 76.40%, and increases the concentration of the anti-inflammatory factor IL-10, by an average of 173.72%, in a dose-dependent manner, compared to the LPS-induced inflammation model group. Expression levels of TLR4, MyD88, NF-κB and TNF-α, IL-1β, IL-6 were significantly down-regulated (p<0.01) by FHP. In summary, FHP displays readily detectable attenuating effects on LPS-induced inflammation in RAW264.7 cells, probably by inhibiting secretion of pro-inflammatory mediators and increasing levels of anti-inflammatory factors, via a mechanism possibly associated with an NF-κB pathway. [ABSTRACT FROM AUTHOR]

Resistance to tumor‐necrosis‐factor‐related apoptosis‐inducing ligand (TRAIL) of cancer cell remains a key obstacle for clinical cancer therapies. To overcome TRAIL resistance, this study identifies curcumol as a novel safe sensitizer from a food‐source compound library, which exhibits synergistic lethal effects in combination with TRAIL on non‐small cell lung cancer (NSCLC). SILAC‐based cellular thermal shift profiling identifies NRH:quinone oxidoreductase 2 (NQO2) as the key target of curcumol. Mechanistically, curcumol directly targets NQO2 to cause reactive oxygen species (ROS) generation, which triggers endoplasmic reticulum (ER) stress‐C/EBP homologous protein (CHOP) death receptor (DR5) signaling, sensitizing NSCLC cell to TRAIL‐induced apoptosis. Molecular docking analysis and surface plasmon resonance assay demonstrate that Phe178 in NQO2 is a critical site for curcumol binding. Mutation of Phe178 completely abolishes the function of NQO2 and augments the TRAIL sensitization. This study characterizes the functional role of NQO2 in TRAIL resistance and the sensitizing function of curcumol by directly targeting NQO2, highlighting the potential of using curcumol as an NQO2 inhibitor for clinical treatment of TRAIL‐resistant cancers. [ABSTRACT FROM AUTHOR]

Oleanolic acid (OA) is a pentacyclic triterpenoid compound with extensive biological effects, such as anti-inflammatory and anticancer activities. However, the application of OA in chemotherapy is hampered by its poor solubility and severe adverse effects. To solve the problems, we developed a self-assembled nanoparticle platform based on amphiphilic oleanolic acid polyprodrug, poly[oligo(ethylene glycol) methyl ether methacrylate]-b-poly[oleanolic acid methacrylate] (POEGMA-b-POAMA), encapsulating 10-hydroxycamptothecin (HCPT) to achieve efficient cancer therapy. The polyprodrug was prepared via reversible addition-fragmentation chain transfer polymerization (RAFT), and could self-assemble to prepare POEGMA-b-POAMA/HCPT nanoparticles (NPs). The obtained nanoparticles exhibited appropriate particle size, excellent drug stability, good drug loading capacity, and high drug loading efficiency. In vitro drug release indicated that the drug release was prolonged to 132 h. The POEGMA-b-POAMA/HCPT NPs enhanced cell cytotoxicity in 4T1 cells and MCF-7 cells and could be efficiently uptaken by 4T1 cells. Furthermore, in vivo antitumor efficiency showed that the POEGMA-b-POAMA/HCPT NPs had great antitumor efficiency with considerably low adverse effects in the treatment of the 4T1 mouse breast tumor xenograft tumor. Therefore, POEGMA-b-POAMA/HCPT NPs provide great potential as a platform for drug delivery applications. [ABSTRACT FROM AUTHOR]

Purpose: To investigate the efficacy and safety of flurbiprofen axetil in postoperative analgesia in upper abdominal surgery. Methods: This was a multicenter, randomized, positive drug parallel controlled double-blind clinical study. Patients undergoing upper abdominal surgery were randomly divided to receive flurbiprofen axetil or tramadol. The VAS pain scores at rest and on coughing (pulmonary function training) were assessed immediately before drug usage (T1) to evaluate the efficacy of postoperative analgesia. Repeat assessment of the VAS was performed after T1. The timing of the recovery of the gastrointestinal function and the preoperative and postoperative IL-6, cortisol, and blood glucose levels were recorded as secondary endpoints. Vital signs and the occurrence of adverse reactions were evaluated for the assessment of safety. Results: A total of 240 patients were enrolled in the current study; 119 used flurbiprofen axetil for postoperative analgesia. The VAS scores at rest and on coughing did not differ between the two groups to a statistically significant extent (P > 0.05). However, the reduction of the VAS score at rest in the flurbiprofen axetil group was greater than that in the tramadol group at 4–24 h after T1. The reduction of the VAS score on coughing at 8 h after T1 was greater in the flurbiprofen axetil group. The incidence of adverse reactions was significantly lower in the flurbiprofen axetil group, with only one adverse reaction recorded. In contrast, 18 adverse reactions were reported in the tramadol group. Conclusion: Flurbiprofen axetil showed superior efficacy to tramadol in early postoperative analgesia after upper abdominal surgery. Flurbiprofen axetil was associated with a significantly lower incidence of adverse reactions in comparison to tramadol. [ABSTRACT FROM AUTHOR]

Rationale, aims, and objectives: Acute postoperative pain can result in immune dysfunction, which can be partly mitigated by efficient pain management. Opioids that have been widely applied to analgesia have been shown to suppress immune function, which has a negative impact on the treatment of patients with cancer. This study investigated the effects of perioperative fentanyl analgesia alone or in combination with parecoxib sodium on postoperative pain, immune function, and prognosis in patients undergoing hepatectomy of hepatocellular carcinoma (HCC). Methods: A total of 80 patients scheduled for hepatectomy between October 2013 and August 2014 were included. Patients were randomly divided into two groups (n = 40) and allocated to receive parecoxibsodium 40 mg (group P) or placebo (group C) 30 minutes before induction of anaesthesia, followed by 40 mg every 12 hours for 48 hours after the operation. All patients had access to patient‐controlled analgesia with intravenous fentanylpostoperatively. Venous blood samples were collected at the following time points: 30 minutes before induction of anaesthesia (T0), the end of the surgery (T1), 24 hours after surgery (T2), and 72 hours after surgery (T3). The percentages of CD3+, CD4+, CD8+, CD4+/CD8+ T cells, and CD3+CD16+CD56+ (NK) cells at these time points were quantified by flow cytometry (FCM).Visual analogue scale (VAS) scores, total fentanyl consumption, and adverse effects were recorded. The prognostic differences in overall survival (OS) and disease‐free survival (DFS) between the two groups was also investigated. Results: For both groups, the percentages of CD3+, CD4+ T cells, and the ratio of CD4+/CD8+ significantly decreased at T1 and T2 (P <.05). The percentages of CD3+ T cells were significantly lower in group C than that in group P at T2 (P <.05). In group C, the amount of CD3+ T cells was lower at T3 compared with T0 (P <.05). The percentages of NK cells significantly decreased at T1 in both groups (P <.05). The percentages of NK in group P were recovered nearly to baseline (T0) at T2, which was higher than that of group C (P <.05). In group C, the percentages of NK cells have not recovered nearly to baseline at T3 compared with T0 (P <.05). VAS scores at rest and on cough in group P were significantly lower than those in group C at 2, 6, 12, and 24 hours after operation (P <.05), and there were no significant differences in VAS scores between the two groups at 48 hours after surgery (P >.05). There were no significant differences regarding the incidence of adverse effects between the two groups (P >.05). Kaplan‐Meier analysis indicated that the DFS time in group P was significantly longer than in group C (19.0 months, 95% confidence interval [CI], 9.8–28.2 vs 14.0 months, 95% CI, 8.1–19.9; P <.05). There was no significant difference in OS time (36.0 months, 95% CI, 13.4–58.9 vs 14.0 months, 95% CI, 10.6–25.4; P >.05) between two groups. Conclusions: The present study indicated that perioperative analgesia of parecoxib sodium combined with patient‐controlled analgesic fentanyl resulted in better preserved immune function with enhancement of the analgesic efficacy to fentanyl alone of HCC patients undergoing hepatectomy and helped postpone postoperative tumour recurrence. [ABSTRACT FROM AUTHOR]

Aims: Our previous study indicated that chronic stress caused autophagy impairment and subsequent neuron apoptosis in hippocampus. However, the mechanism underlying the stress‐induced damage to neurons is unclear. In present work, we investigated whether stress‐level glucocorticoids (GCs) GCs promoted PC12 cell damage via AMPK/mTOR signaling‐mediated autophagy. Methods: Chronic stress‐induced PC12 cell injury model was built by treatment with high level corticosterone (CORT). Cell injury was evaluated by flow cytometry assay and transmission electron microscopy observation. Results: Autophagy flux was measured based on the changes in LC3‐II and P62 protein expressions, and the color alteration of mCherry‐GFP‐LC3‐II transfection. Our results showed that CORT not only increased cell injury and apoptosis, but also dysregulated AMPK/mTOR signaling‐mediated autophagy flux, as indicated by the upregulated expression of LC3‐II and P62 proteins, and the lowered ration of autolysosomes to autophagosomes. Mechanistically, our results demonstrated that autophagy activation by AMPK activator metformin or mTOR inhibitor rapamycin obviously promotes cell survival and autophagy flux, improved mitochondrial ultrastructure, and reduced expression of Cyt‐C and caspase‐3 in CORT‐induced PC12 cells. Conclusion: These results indicate that high CORT triggers PC12 cell damage through disrupting AMPK/mTOR‐mediated autophagy flux. Targeting this signaling may be a promising approach to protect against high CORT and chronic stress‐induced neuronal impairment. [ABSTRACT FROM AUTHOR]

By studying the gravity relationships among cities within the region, the economic relationships among cities can be explored, which is the basis for reasonably dividing the urban groups within the city circle and achieving the coordinated development. Based on the theory of urban gravity model, this paper introduces the theory of psychological distance and improves the urban gravity model based on the urban competitiveness and vector-based gravity model. Taking Chengdu city circle as an example, this paper expounds the current situation and economic connection of Chengdu city cycle's gravity pattern. The results show that the improved gravity model can objectively reflect the current conditions of relative gravity among cities. The city circle of Chengdu clearly presents the economic pattern of "overdominance". The urban competitiveness and gravity of Chengdu are far beyond the average level. The economic connection of the whole city is too scattered and the regional development is not balanced, which need to be improved in the future development. [ABSTRACT FROM AUTHOR]

A type of carboxymethyl cellulose/chitosan composite sponge that is able to indicate pH changes was prepared and characterized. This sponge, dyed with the natural dye cyanine, showed a rather rapid response by changing from blue to green as the solution pH changed from 4 to 8. This visible color change indicated that the sponge could be a pH sensor with high sensitivity. The carboxymethyl cellulose/chitosan composite sponges exhibited a good air permeability and high porosity because the sponge's pores were all open and interconnected. The porosity, the moisture vapor transmission rate, and the water vapor permeability all increased as the chitosan content increased. The chitosan microparticles added in carboxymethyl cellulose reinforced the composite sponge and improved its antibacterial activity. The cyanine dyed carboxymethyl cellulose/chitosan sponges have substantial potential as wound-healing monitors. [ABSTRACT FROM AUTHOR]

Poly(L‐lactic acid)/poly(D‐lactic acid) (PLLA/PDLA) blended with plasticizer poly(ethylene glycol) and nucleation agent TMC‐306 as‐spun fibers were prepared by melt spinning. The posttreatment was applied by hot drawing at 70°C and then heat‐treating at different temperatures for 30 minutes. In the process of hot drawing, orientation induced the further formation of the sc crystals and increased the degree of crystallinity of drawn fibers. When the hot drawing ratio reached 3 times, the properties of the fibers were relatively better. The highly oriented fibers containing pure sc crystals with high crystallinity were obtained by heat‐treating at a temperature above the melting point of α crystals. The posttreated PLLA/PDLA fibers with poly(ethylene glycol) and TMC‐306 (LDTP) obtained by hot drawing to 3 times at 70°C and then annealing at 170°C for 30 minutes exhibited the best antioxidative degradation and heat resistance properties. The initial decomposition temperature (T5%) and heat resistance of posttreated LDTP fiber were about 94°C and 20°C higher than those of the commercial PLLA fiber, respectively. [ABSTRACT FROM AUTHOR]

Transition-metal-free α-arylation of α-nitroketones with diaryliodonium salts has been realized for the first time. As an application of this methodology, a concise synthesis of the clinical drug tiletamine was also achieved via a three-step procedure from 2-nitrocyclohexanone without the isolation of intermediates. [ABSTRACT FROM AUTHOR]

Municipal solid waste incinerator (MSWI) fly ash contains large amounts of arsenic and antimony. This study focuses on the incorporation and evaporation of arsenic and antimony when MSWI fly ash added to clinker raw meal. Thermal analysis was used to simulate the “single incorporation” of arsenic and antimony into clinker with HSC. Statistical analysis was acquired by cement industrial monitoring data to determine the effect of total chloride, arsenic and antimony input on the incorporation or evaporation of arsenic or antimony. A simplified mass balance model was used to evaluate the effect of cement kiln dust (CKD) recirculation on the “multiple incorporation” of arsenic and antimony in clinker and the evaporation of arsenic and antimony in waste CKD. The results indicated that arsenic and antimony was largely incorporated into the clinker as Ca2(AsO4)2(s), even in the presence of chlorides. Moreover, CKD recirculation promoted arsenic and antimony incorporation into clinker. [ABSTRACT FROM AUTHOR]

In this study, the effects of surfactants on the hydrodynamic characteristics of bubbles in shear-thinning fluids at low Reynolds number (Re<50) are investigated. The bubble terminal velocity and drag coefficient of bubble in clean and contaminated carboxymethylcellulose (CMC) solutions are obtained using a high-speed camera for examining differences. The results show that the existence of surfactant could reduce the terminal velocity of bubble at small volume (0.25wt% CMC: <100 mm3; 0.50wt% CMC: <110 mm3), attributed to stiffening the bubble interface. However, this negative effect decreases and finally disappears with increasing bubble volume. The drag coefficient curves of the bubble in contaminated CMC solution exhibit behavior similar to that exhibited by a solid sphere at Re<10, indicating that internal circulation flow is absent at the bubble interface as compared to that in clean CMC solution. However, for 10Re to 16/Re in contaminated CMC solution is observed, which is easy at low SDS concentrations and high CMC concentrations. [ABSTRACT FROM AUTHOR]

Purpose: The tumor suppressor candidate 3 (TUSC3) has been considered to be closely associated with the occurrence, development and invasion of various malignant tumors. However, the expression of TUSC3 in hepatocellular carcinoma (HCC) tissues remains ambiguous. The purpose of this research was to investigate the expression of TUSC3 in HCC tissues and analyze the relationship between TUSC3 levels and clinicopathological characteristics and prognosis of HCC patients. Materials and methods: Immunohistochemistry was used to detect the expression of TUSC3 in HCC and the corresponding para-cancerous tissues from 92 samples of HCC patients. mRNA and protein expression levels of TUSC3 were evaluated by quantitative real-time polymerase chain reaction (qRT-PCR) and Western blot assays in 25 paired HCC and corresponding adjacent nontumor tissues. Furthermore, statistical analysis was applied to evaluate the correlation between TUSC3 level and the clinicopathological features and prognosis of HCC patients. Results: Immunohistochemical assay indicated that the expression of TUSC3 was significantly lower in HCC tissues when compared with the corresponding para-cancerous tissues (χ2=11.512, P=0.001). The analysis of clinicopathological characteristics showed that low expression of TUSC3 in HCC tissues was significantly associated with Edmondson grade, Barcelona Clinic Liver Cancer stage and tumor size (P=0.008, 0.009 and 0.020, respectively). Univariate analysis showed that the expression of TUSC3 was strongly correlated with overall survival (OS) and disease-free survival (DFS) after radical surgery in HCC patients (P<0.001, P<0.001, respectively). Multivariate analysis revealed that the TUSC3 level was an independent risk factor for OS and DFS in HCC patients (P=0.001, P<0.001, respectively). Results of qRT-PCR and Western blot assays indicated that the level of TUSC3 in HCC tissues was significantly lower than that in the corresponding adjacent noncancerous tissues (P<0.01, P<0.001). Conclusion: The expression of TUSC3 in HCC was significantly downregulated and was correlated with tumor progression and prognosis, which could be used as an independent predictor of prognosis in HCC patients. [ABSTRACT FROM AUTHOR]

We present a novel anisotropic Spherical Gaussian (ASG) function, built upon the Bingham distribution [Bingham 1974], which is much more effective and efficient in representing anisotropic spherical functions than Spherical Gaussians (SGs). In addition to retaining many desired properties of SGs, ASGs are also rotationally invariant and capable of representing all-frequency signals. To further strengthen the properties of ASGs, we have derived approximate closed-form solutions for their integral, product and convolution operators, whose errors are nearly negligible, as validated by quantitative analysis. Supported by all these operators, ASGs can be adapted in existing SG-based applications to enhance their scalability in handling anisotropic effects. To demonstrate the accuracy and efficiency of ASGs in practice, we have applied ASGs in two important SG-based rendering applications and the experimental results clearly reveal the merits of ASGs. [ABSTRACT FROM AUTHOR]

Three new triterpenoid alkaloids, namely buxmicrophyllines P-R (1-3), were isolated from the twigs and leaves of Buxus microphylla. Their structures were elucidated on the basis of NMR and MS spectroscopic analyses. Structurally, compounds 1-3 belong to the 9,10-cycloartane type alkaloids. In addition, compound 3 exhibited moderate cytotoxic activities in vitro against HL-60, SMMC-7221, A-549, MCF-7, and SW480 cell lines (with IC50 values ranging from 4.51 to 15.58 μM). [ABSTRACT FROM AUTHOR]

The behavior of single bubble rising in quiescent shear-thinning fluids was investigated numerically by level set method. A number of bubbles in a large range of Reynolds number and Eotvos number were investigated including spherical, oblate and spherical. The bubble shape and drag coefficient were compared with experimental results. It is observed that the simulated results show good conformity to experimental results over a wide range of Reynolds number. In addition, the detailed flow field based on the reference coordinate system moving with the bubble is obtained, and the relationship among flow field, bubble shape and velocity is discussed. [ABSTRACT FROM AUTHOR]

We present a novel anisotropic Spherical Gaussian (ASG) function, built upon the Bingham distribution [Bingham 1974], which is much more effective and efficient in representing anisotropic spherical functions than Spherical Gaussians (SGs). In addition to retaining many desired properties of SGs, ASGs are also rotationally invariant and capable of representing all-frequency signals. To further strengthen the properties of ASGs, we have derived approximate closed-form solutions for their integral, product and convolution operators, whose errors are nearly negligible, as validated by quantitative analysis. Supported by all these operators, ASGs can be adapted in existing SG-based applications to enhance their scalability in handling anisotropic effects. To demonstrate the accuracy and efficiency of ASGs in practice, we have applied ASGs in two important SG-based rendering applications and the experimental results clearly reveal the merits of ASGs. [ABSTRACT FROM AUTHOR]