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Immunotherapy can enhance primary tumor efficacy, restrict distant growth, and combat lung metastasis. Unfortunately, it remains challenging to effectively activate the immune response. Here, tertiary butyl, methoxy, and triphenylamine (TPA) were utilized as electron donors to develop multifunctional photosensitizers (PSs). CNTPA-TPA, featuring TPA as the donor (D) and cyano as the acceptor (A), excelled in reactive oxygen species (ROS) generation due to its smaller singlet-triplet energy gap (ΔE S-T) and larger spin-orbit coupling constant (SOC). Additionally, cyano groups reacted with glutamate (Glu) and glutathione (GSH), reducing intracellular GSH levels. This not only enhanced PDT efficacy but also triggered redox dyshomeostasis-mediated ferroptosis. The positive effects of photodynamic therapy (PDT) and ferroptosis promoted immunogenic cell death (ICD) and immune activation. By further combining anti-programmed cell death protein ligand-1 (anti-PD-L1) antibody, the powerful treatments of ferroptosis-assisted photodynamic immunotherapy significantly eradicated the primary tumors, inhibited the growth of distant tumors, and suppressed lung metastasis. In this study, a three-pronged approach was realized by single-component CNTPA-TPA, which simultaneously served as metal-free ferroptosis inducers, type-I photosensitizers, and immunologic adjuvants for near-infrared fluorescence imaging (NIR FLI)-guided multimodal phototheranostics of tumor. (1) CNTPA-TPA shared the smallest singlet-triplet energy gap and the largest spin-orbit coupling constant, which boosted intersystem crossing for efficient type-I photodynamic therapy (PDT); (2) Special reactions between cyano groups with glutamate and glutathione in mild conditions restricted the biosynthesis of intracellular GSH. GSH-depletion efficiently induced glutathione peroxidase 4 inactivation and lipid peroxide, resulting in ferroptosis of tumor cells; (3) The combination treatments of ferroptosis-assisted photodynamic immunotherapy induced by single-component CNTPA-TPA with the participation of anti-PD-L1 antibody resulted in increased T-cell infiltration and profound suppression of both primary and distant tumor growth, as well as lung metastasis. [Display omitted] [ABSTRACT FROM AUTHOR]

Deep neural networks (DNNs) have shown high accuracy in fault diagnosis, but they struggle to effectively capture changes over time in multivariate time-series data and suffer from resource consumption issues. Spike deep belief networks (spike-DBNs) address these limitations by capturing the change in time-varying signals and reducing resource consumption, but they sacrifice accuracy. To overcome these limitations, we propose integrating an event-driven approach into spike-DBNs through the Latency-Rate coding method and the reward-STDP learning rule. The encoding method enhances the event representation capability, while the learning rule focuses on the global behavior of spiking neurons triggered by events. Our proposed method not only maintains low resource consumption but also improves the fault diagnosis ability of spike-DBNs. We conducted a series of experiments to verify our model's performance, and the results demonstrate that our proposed method improves the accuracy of fault classification of manipulators and reduces learning time by nearly 76% compared to spike-CNN under the same conditions. • An event-driven spike-DBN is proposed for fault diagnosis. • The event-driven spike-DBN is based on evt-Siegert neuron model. • The core of evt-Siegert is Latency-Rate encoding. • An event-driven reward-STDP learning algorithm is developed for network training. • The proposed method is demonstrated via UCI execution failures dataset. [ABSTRACT FROM AUTHOR]

Spiking neural networks (SNNs) are regarded as effective models for processing spatio-temporal information. However, their inherent complexity of temporal coding makes it an arduous task to put forward an effective supervised learning algorithm, which still puzzles researchers in this area. In this paper, we propose a Recursive Least Squares-Based Learning Rule (RLSBLR) for SNN to generate the desired spatio-temporal spike train. During the learning process of our method, the weight update is driven by the cost function defined by the difference between the membrane potential and the firing threshold. The amount of weight modification depends not only on the impact of the current error function, but also on the previous error functions which are evaluated by current weights. In order to improve the learning performance, we integrate a modified synaptic delay learning to the proposed RLSBLR. We conduct experiments in different settings, such as spiking lengths, number of inputs, firing rates, noises and learning parameters, to thoroughly investigate the performance of this learning algorithm. The proposed RLSBLR is compared with competitive algorithms of Perceptron-Based Spiking Neuron Learning Rule (PBSNLR) and Remote Supervised Method (ReSuMe). Experimental results demonstrate that the proposed RLSBLR can achieve higher learning accuracy, higher efficiency and better robustness against different types of noise. In addition, we apply the proposed RLSBLR to open source database TIDIGITS, and the results show that our algorithm has a good practical application performance. [ABSTRACT FROM AUTHOR]

The aim of this study was to explore the ototoxicity of toluene in the early development of zebrafish embryos/larvae. Zebrafish were utilized to explore the ototoxicity of toluene. Locomotion analysis, immunofluorescence, and qPCR were used to understand the phenotypes and molecular mechanisms of toluene ototoxicity. The results demonstrated that at 2 mmol/L, toluene induced zebrafish larvae death at 120 hours post fertilization (hpf) at a rate of 25.79% and inhibited the rate of hatching at 72 hpf. Furthermore, toluene exposure inhibited the distance travelled and average swimming velocity of zebrafish larvae while increasing the frequency of movements. As shown by fluorescence staining of hair cells, toluene inhibited the formation of lateral line neuromasts and middle line 1 (Ml 1) neuromasts in 3 days post fertilization larvae in a concentration-dependent manner. Toluene altered the expression level of genes involved in ear development/function in zebrafish, among which the mRNA levels of cd164l2, tekt3, and pcsk5a were upregulated, while the level of otofb was downregulated, according to the qPCR results. This study indicated that toluene may affect the development of both the inner ear and lateral line systems in zebrafish, while the lateral line system may be more sensitive to toluene than the inner ear. [ABSTRACT FROM AUTHOR]

We have shown before that HDAC3 was involved in the pathogenesis of ovarian cancer; however, the specific mechanism of HDAC3 on the pathogenesis of ovarian cancer has not been thoroughly studied. To explore the related proteins in the mechanism of HDAC3 on ovarian cancer. The transcriptome profiles were identified in ovarian carcinoma cells with HDAC3 knockdown or overexpression. Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and western blot analysis were used to verify transfection efficiency. Immunofluorescence staining were performed to detect the expression levels of HDAC3 and RNF144B in tissues. Cell proliferation, apoptosis, migration and invasion were confirmed by cell counting Kit-8 (CCK-8), terminal deoxynucleotidyl transferase (TUNEL) and transwell assay, respectively. The protein expression of p53, p21, Bax and Bcl-2 was confirmed by western blot, and CoIP assay was used to validate RNF144B/P21/P53 interaction. Meanwhile, the protein synthesis inhibitor cycloheximide (CHX) was performed to treat cells to probe p21 stability. Finally, we established an in vivo tumor model to explore the effects of HDAC3 and RNF144B on tumor growth. Microarray results showed that among the overlapping genes in the two profiles (HDAC3 knockdown and overexpression), RNF144B was decreased or increased in ovarian carcinoma cells with HDAC3 knockdown or overexpression, HDAC3 overexpression promoted RNF144B expression, and HDAC3 knockdown hindered RNF144B levels. The levels of HDAC3 and RNF144B in malignant ovarian cancer were significantly higher than those in normal ovarian tissue and benign ovarian cancer tissue. RNF144B promoted cell proliferation, migration and invasion, and inhibited cell apoptosis. In addition, overexpression of HDAC3 or RNF144B inhibited p53/p21/Bax expression and promoted Bcl-2 expression. Knockout of HDAC3 or RNF144B has the opposite effect, and RNF144B interacted with p21 and regulated the p21/p53 complex degradation, and finally in vivo experiments proved that HDAC3 and RNF144B promoted tumor growth. RNF144B-mediated p21 degradation regulated by HDAC3 contributed to enhancing ovarian cancer growth and metastasis. • RNF144B-mediated p21 degradation regulated by HDAC3 contributed to enhancing ovarian cancer growth and metastasis. • The levels of HDAC3 and RNF144B in malignant ovarian cancer were significantly higher than those in normal ovarian tissue and benign ovarian cancer tissue. • RNF144B promoted cell proliferation, migration and invasion, and inhibited cell apoptosis. [ABSTRACT FROM AUTHOR]

Abstract The flexible binderless films composed of cobalt selenide grains attached on carbon nanofibers (denoted as CoSe 2 /CNFs) are prepared by electrospinning to enhance the electronic conductivity, Na-ions diffusion and alleviate volume variation during charge/discharge process for high performance sodium-ion batteries (SIBs). The binderless and flexible CoSe 2 /CNFs electrode can obtain a high reversible capacity of 430 mAh g−1 after 400 cycles at a current density of 200 mA g−1, an exceptional rate capability of 224 mAh g−1 at 15 A g−1, even a capacity of 370 mAh g−1 at 2 A g−1 after 1000 cycles. The superior electrochemical performance can be ascribed to the synergistic effects of the homogeneous distribution of CoSe 2 grains attached to the carbon nanofibers and the high electronic conductivity framework of 3D interconnecting carbon nanofibers, which can alleviate the volume variation during charge-discharge process and sustain the high electrical conductivity and fast Na-ions diffusion throughout the electrode. This binderless flexible CoSe 2 /CNFs nanocomposite electrode may hold great application promising for high cycling performance SIBs. Graphical abstract The flexible binder-free film of CoSe 2 grains attached carbon nanofibers (CoSe 2 /CNFs) was prepared by electrospun. As a sodium ion battery (SIB) anode, it delivers a high reversible capacity of 370 mAh g−1 after 1000 cycles at 2 A g−1 and a high rate capability of 224 mAh g−1 at 15 A g−1. fx1 Highlights • The CoSe 2 grains attached on CNFs form a 3-D interwoven network. • The flexible full cells are fabricated using CoSe 2 /C electrodes, which deliver the capacity of 370 mAh g−1. • The superior performance is ascribed to enhanced conductivity, Na-ion diffusion and alleviation of volume variation. [ABSTRACT FROM AUTHOR]

It is crucial to represent the semantic information of a document in sentiment classification. Various semantic information representation models have been proposed, however existing approaches have their setbacks. Notable weaknesses among these are: (1) tradition VSM methods, completely ignore the semantic information; (2) averaging word embedding methods, cannot depict the synthetical semantic meaning of the given document; (3) neural network methods, require complex structure and are notoriously difficult to be trained. To overcome these limitations, we introduce a simple but novel method which we call bag of meta-words (BoMW). In our method, the semantic information of the document is indicated by a meta-words vector in which every single meta-word element denotes particular semantic information. Especially, these meta-words are extracted from pre-trained word embeddings through two different but complemental models, naive interval meta-words (NIM) and feature combination meta-words (FCM). In general, our new model BoMW is as simple as traditional VSM model but it can capture the synthetical semantic meanings of the document. Numerous experiments on two benchmarks (IMDB dataset and Pang’s dataset) are carried out to verify the effectiveness of the proposed method, and the results show that the performance of our method can exceed the traditional VSM methods and methods using pre-trained word embedding. [ABSTRACT FROM AUTHOR]

Abstract Anchored stabilizing pile is a typical earthquake-resistant structure in reinforced slope with advantages of safety, reliability and low cost. It demonstrated excellent seismic performance during the 2008 Great Wenchuan earthquake. However, due to the complexity of the structural system, the coupling relationship between soil, pile, and anchor cable is not well understood at present. This paper developed an analytical model in modeling the dynamic responses of the pile, anchor cable and soil slope system based on Winkler elastic foundation beam theory. The seismic design of the anchored sheet pile wall can then be carried out. An experimental shake-table test was conducted to validate the proposed analytical model. Through the test, the displacements of the pile, axial force of the anchor cable, and earth pressure along the pile derived from the analytical model were validated by the test results. It shows that the proposed analytical model is suitable for the practical application and can provide theoretical basis for dynamic response analysis and seismic design of anchored sheet pile wall. Highlights • An analytical model of anchored sheet pile wall under ground motion is derived. • Analytical solutions of dynamic interaction between pile, anchor cable and slope can be obtained. • Seismic design of anchored sheet pile wall can be carried out through the analytical model. • The accuracy and reliability of the proposed analytical model are validated by the shake-table test. [ABSTRACT FROM AUTHOR]

Neighborhood-based collaborative filtering is a method of high significance among recommender systems, with advantages of simplicity and justifiability. However, recently it is receiving less popularity due to its low prediction accuracy in contrast with model-based collaborative filtering systems, but model-based methods also suffer from a drawback worthy of attention that is they cannot effectively explain the reason behind their estimation. In order to develop a system with both high accuracy and justifiability, we propose a novel neighborhood-based collaborative filtering method inspired by the natural mechanism of attention. Our method can adaptively find neighborhood items to the prediction in user history without any pre-defined function with respect item correlations. Then the estimation are made based on these relationships. Experiments on several benchmarks are carried out to verify the performance of the proposed method, and the result shows that our method beats all previous state-of-the-art methods on MovieLens 10M and Netflix in addition to being able to justify the prediction obtained. [ABSTRACT FROM AUTHOR]

The emergence and spread of antibiotic resistance has posed a major threat to both human health and environmental ecosystem. Although the disinfection has been proved to be efficient to control the occurrence of pathogens, little effort is dedicated to revealing potential impacts of disinfection on transmission of antibiotic resistance genes (ARGs), particularly for free-living ARGs in final disinfected effluent of urban wastewater treatment plants (UWWTP). Here, we investigated the effects of chlorine disinfection on the occurrence and concentration of both extracellular ARGs (eARGs) and intracellular ARGs (iARGs) in a full-scale UWWTP over a year. We reported that the concentrations of both eARGs and iARGs would be increased by the disinfection with chlorine dioxide (ClO 2 ). Specifically, chlorination preferentially increased the abundances of eARGs against macrolide ( ermB ), tetracycline ( tetA, tetB and tetC ), sulfonamide ( sul1, sul2 and sul3 ), β -lactam ( ampC ), aminoglycosides ( aph(2’)-Id ), rifampicin ( katG ) and vancomycin ( vanA ) up to 3.8 folds. Similarly, the abundances of iARGs were also increased up to 7.8 folds after chlorination. In terms of correlation analyses, the abundance of Escherichia coli before chlorination showed a strong positive correlation with the total eARG concentration, while lower temperature and higher ammonium concentration were assumed to be associated with the concentration of iARGs. This study suggests the chlorine disinfection could increase the abundances of both iARGs and eARGs, thereby posing risk of the dissemination of antibiotic resistance in environments. [ABSTRACT FROM AUTHOR]

Purpose: Evidence that asymptomatic third molars (M3s) negatively affect their adjacent second molars (A-M2s) is limited. The present study evaluated the association between visible M3s (V-M3s) of various clinical status with the periodontal pathologic features of their A-M2s.Patients and Methods: Subjects with at least 1 quadrant having intact first and second molars, either with V-M3s and symptom free or without adjacent V-M3s, were enrolled in the present cross-sectional investigation. Periodontal parameters, including plaque index (PLI), bleeding on probing (BOP), probing pocket depth (PPD), and at least 1 site with a PPD of 5 mm or more (PPD5+), obtained from M2s were analyzed according to the presence or absence of V-M3s or the status of the M3s. The χ2 test or t test was used to compare the mean PLI, PPD, BOP percentage, and PPD5+ percentage. The association of PPD5+ with V-M3 status was assessed using a multivariable logistic regression model (quadrant-based analysis), and variances were adjusted for clustered observations within subjects.Results: In total, 572 subjects were enrolled in the study, and 423 had at least 1 V-M3. At the in-quadrant level, the presence of a V-M3 significantly increased M2 pathologic parameters, including PLI, PPD, BOP, and PPD5+. When analyzed using a multivariate logistic regression model, impacted M3s and normally erupted M3s significantly elevated the risk of PPD5+ on their A-M2s (odds ratio 3.20 and 1.67, respectively). Other factors associated with an increased odds of PPD5+ were mandibular region and older age. Finally, the patient-matched comparison showed that the percentage of BOP and PPD5+ on M2s increased when V-M3s were present.Conclusions: Irrespective of their status, the presence of V-M3s is a risk factor for the development of periodontal pathologic features in their A-M2s. Although the prophylactic removal of asymptomatic V-M3s remains controversial, medical decisions should be made as early as possible, because, ideally, extraction should be performed before symptom onset. [ABSTRACT FROM AUTHOR]

Purpose: Most previous studies of the effect of third molars (M3s) on the health of adjacent second molars (A-M2s) have focused on impacted M3s (I-M3s). The purpose of this study was to investigate whether nonimpacted M3 (N-M3s) could affect the periodontal status of A-M2s.Patients and Methods: In this cross-sectional study, patients (≥18 years) who had at least 1 quadrant with intact first and second molars and a nonimpacted or absent M3 were enrolled in this study. The periodontal measurements of M2 (6 sites) in the examined quadrants included the gingival index (GI), plaque index (PLI), probing pocket depth (PPD), clinical attachment level (CAL), gingival recession, and bleeding on probing (BOP). The mean GI, PLI, PPD, CAL, and BOP proportion and the proportion with at least 1 site with a PPD of at least 5 mm (PPD5+) were compared using the t test or χ2 test. The association of PPD5+ (percentage) or BOP (percentage) with the presence of N-M3s was assessed using a 2-level logistic regression model (quadrant-based analysis).Results: One hundred thirty-five patients (43.7% men; 40.6 ± 11.5 yr old) were enrolled in this study. Patients who had at least 1 quadrant with 3 intact molars and an N-M3 were enrolled in group A (105 patients), and patients who had at least 1 quadrant with intact first and second molars without an M3 were enrolled in group B (30 patients). The periodontal parameters (ie, GI, PLI, PPD, CAL, BOP, and PPD5+) were markedly greater in group A. When other factors associated with periodontal disease were controlled, N-M3s were associated with the PPD5+ (odds ratio = 6.7) and BOP (odds ratio = 4.0) of the A-M2s. Other factors positively associated with A-M2 PPD5+ were location on the mandible, age older than 35 years, and smoking.Conclusions: The presence of N-M3s is a potential risk factor for the development of periodontitis in A-M2s. [ABSTRACT FROM AUTHOR]

The spiking neural networks (SNNs) are the third generation of artificial neural networks, which have made great achievements in the field of pattern recognition. However, the existing supervised training methods of SNNs are not efficient enough to meet the real-time requirement in most cases. To address this issue, the normalized perceptron based learning rule (NPBLR) is proposed in this paper for the supervised training of the multi-layer SNNs. Different from traditional methods, our algorithm only trains the selected misclassified time points and the target ones, employing the perceptron based neuron. Furthermore, the weight modification in our algorithm is normalized by a voltage based function, which is more efficient than the traditional time based method because the firing time is calculated by the voltage value. Superior to the traditional multi-layer algorithm ignoring the time accumulation of spikes, our algorithm defines the spiking activity of the postsynaptic neuron as the rate accumulation function of all presynaptic neurons in a specific time-frame. By these strategies, our algorithm overcomes some difficulties in the training of SNNs, e.g., the inefficient and no-fire problems. Comprehensive simulations are conducted both in single and multi-layer networks to investigate the learning performance of our algorithm, whose results demonstrate that our algorithm possesses higher learning efficiency and stronger parameter robustness than traditional algorithms. [ABSTRACT FROM AUTHOR]

With a similar capability of processing spikes as biological neural systems, networks of spiking neurons are expected to achieve a performance similar to that of living brains. Despite the achievement of spiking neuron based applications, most of them assume noise-free condition for learning and testing. This assumption, though fairly general, ignores the fact that noise widely exists in spiking neural networks (SNNs) and the neural response can be significantly disturbed by noise. Therefore, how to deal with noise is an important issue in the applications of SNNs. Here, by analyzing strategies employed to make spiking neurons robust to noise, also inspired by biological neurons, we propose a strategy that train spiking neurons with a dynamic firing threshold named noise-threshold. The noise-threshold can be applied by the existing supervised learning methods to improve the noise tolerance of them. Experimental results show that, with a combination of noise-threshold, the anti-noise capability of the existing supervised learning methods improves significantly, and the trained neuron can precisely and reliably reproduce target sequences of spikes even under highly noisy conditions. More importantly, the SNNs-based computational model equipped with a noise-threshold is more robust and can achieve a good performance even with different types of noise. Therefore, the noise-threshold is significant to practical applications and theoretical researches of SNNs. [ABSTRACT FROM AUTHOR]

Kidney renal clear cell carcinoma (KIRC, ccRCC) is one of the most common and aggressive subtypes of urinary system cancer. Cancer-associated fibroblasts (CAFs) in the tumor microenvironment (TME) exacerbate the malignant phenotype of KIRC. It is necessary to explore further how KIRC induces normal fibroblasts (NFs) into CAFs. The transcriptome data of KIRC was obtained from The Cancer Genome Atlas (TCGA), and the hub-genes and their corresponding functions in the co-expression module were obtained through differential analysis, enrichment analysis, and weighted correlation network analysis (WGCNA) analysis. RT-PCR, western-blot, and Elisa assays were used to detect the expression of CXCL5 (C-X-C Motif Chemokine Ligand 5) in KIRC cells and medium. Western-blot and immunofluorescence were used to demonstrate the transformation of NFs to CAF-like cells and relevant pathways. Human umbilical vein endothelial cells (huvec) were seeded within collagen gel to represent the neo-vascular network. Transwell, scrape, colony formation, and CCK-8 assays were performed to reveal the feedback effect of KIRC cells. Bioinformatics analysis showed that CXCL5 was a core gene in differential expression genes (DEGs) and was associated with extracellular matrix (ECM), which was associated with CAFs. KIRC-derived CXCL5 promoted the conversion of NFs to CAF-like cells. It included morphological and corresponding molecular marker changes. Activation of the JAK/STAT3 pathway was involved in this process. Corresponding, CAFs cells could secrete vascular endothelial growth factor (VEGF), which induced angiogenesis. CXCL5 promoted KIRC invasion and proliferation. Our research suggested that KIRC-derived CXCL5 could induce NFs to become CAFs-like cells that promote angiogenesis in the TME. The positive feedback of CXCL5 promoted its own invasive growth. The intercellular communication with CXCL5 as the core might be the critical node in the occurrence and development of KIRC. [ABSTRACT FROM AUTHOR]

Summary Intracellular membrane fusion is mediated by dynamic assembly and disassembly of soluble N-ethylmaleimide-sensitive factor (NSF) attachment protein (SNAP) receptors (SNAREs). α-SNAP guides NSF to disassemble SNARE complexes after membrane fusion. Recent experiments showed that α-SNAP also dramatically enhances SNARE assembly and membrane fusion. How α-SNAP is involved in these opposing activities is not known. Here, we examine the effect of α-SNAP on the stepwise assembly of the synaptic SNARE complex using optical tweezers. We found that α-SNAP destabilized the linker domain (LD) of the SNARE complex but stabilized its C-terminal domain (CTD) through a conformational selection mechanism. In contrast, α-SNAP minimally affected assembly of the SNARE N-terminal domain (NTD), indicating that α-SNAP barely bound the partially assembled trans -SNARE complex. Thus, α-SNAP recognizes the folded CTD for SNARE disassembly with NSF and subtly modulates membrane fusion by altering the stabilities of the SNARE CTD and LD. [ABSTRACT FROM AUTHOR]

The Yanshan Movement and the destruction of the North China Craton are two important geological events of the late Mesozoic in the central and eastern China. There are, however, still uncertainties about their initial timing, development, and intrinsic relationship. Late Mesozoic (Jurassic–Cretaceous) basin filling processes are crucial to understanding these questions. The Ningwu–Jingle Basin and the Hunyuan Basin, are situated in the north-central part of the North China Craton, have a complete late Mesozoic sedimentary strata. Their late Mesozoic sedimentary filling characteristics and key geochronology indicate the development of the North China Craton and its tectonic setting in different evolution stages. Our new sedimentary, geochronological and geochemical data of the volcanic rocks combined with the previously published results on Mesozoic sedimentary, deformation and magmatism in the North China Craton indicate a temporal and spatial migration of the tectonic movement. In the study, we divide the late Mesozoic tectonic evolution of the area into several stages using the sedimentary sequences and zircon U–Pb isotope dating, and discuss the intrinsic relationship between the Yanshan Movement and the destruction of the North China Craton. Our conclusions are as follows. (1) Extensional tectonics were probably dominated in the northern North China Craton from the Early Jurassic to the early Middle Jurassic, and continued until 168 Ma. (2) The Yanshan Movement took place between 168 Ma and 152 Ma, involving into an intensive compressional stage at 161–159 Ma with a peak stage at 159–152 Ma. (3) Late Mesozoic tectonic regime change took place in the northern North China Craton between 152 and 113 Ma, with a transitional stage from compression to extension at 152–130 Ma and a peak extensional stage at 130–113 Ma. The compressional tectonic regime became an extensional tectonic regime during the late Late Jurassic and Early Cretaceous, indicating the initiation and development of the destruction of the North China Craton. [ABSTRACT FROM AUTHOR]

In an effort to develop potent anti-cancer chemopreventive agents, a novel series of bisindole derivatives bearing oxime moiety were synthesized. Structures of all compounds were characterized by NMR and HRMS. Anti-proliferative activities for all of these compounds were investigated by the method of MTT assay on 7 human cancer lines and the normal cell lines (HUVEC). Most of them showed a noteworthy anti-cancer activity in vitro , the half maximal inhibitory concentration (IC 50 ) value is 4.31 μM of 4e against T24. The results from Hoechst 33258 and acridine orange/propidium iodide staining as well as annexinV-FITC assays provided evidence for an apoptotic cell death. The further mechanisms of compound 4e -induced apoptosis in T24 cells demonstrated that compound 4e induced the productions of ROS, and altered anti- and pro-apoptotic proteins, leading to mitochondrial dysfunction and activations of caspase-9 and caspase-3 for causing cell apoptosis. Moreover, the cell cycle analysis and western-blot analysis indicated that compound 4e effectively arrested T24 cells in G1 stage and possibly has an effect on cell cycle regulatory proteins particularly cyclin D1. [ABSTRACT FROM AUTHOR]

Objective To describe the baseline data of cancers in the Jinchang Cohort, this paper examined trends in cancer mortality among adults investigated in Jinchang, Gansu province from 2001 to 2010. Methods Mortality data were collected from company departments through administrative documents, death certificates, etc. Trend analyses of cancer mortality were performed on the basis of 925 cancer deaths between 2001 and 2010. Results The crude mortality rate of cancer continuously increased from 161.86 per 100,000 in 2001 to 315.32 per 100,000 in 2010, with an average increase of 7.69% per year in the Jinchang Cohort (16.41% in females compared to 6.04% in males), but the age-standardized mortality rate increased only in females. Thirteen leading cancers accounted for 92.10% of all cancer deaths. The five leading causes of cancer mortality in males were lung, gastric, liver, esophageal, and colorectal cancer, whereas those in females were lung, liver, gastric, breast, and esophageal cancer. Conclusion The overall cancer mortality rate increased from 2001 to 2010 in the Jinchang Cohort, with greater rate of increase in females than in males. Lung, breast, and gastric cancer, in that order, were the leading causes of increased cancer mortality in females. [ABSTRACT FROM AUTHOR]