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Coptotermes (Blattodea: Isoptera: Rhinotermitidae) is an economically important genus. There are many problematic taxa within the genus because of small differences between different species and large variations within the same species with respect to morphology. Coptotermes species, especially those in China, are in need of careful monographic revisions. In this paper, type specimens of 14 Coptotermes species were reexamined. Their relationship was preliminarily studied with statistical methods. The phylogenetic relationships among the 21 species that are recorded in China were investigated based on soldier morphological characters. The cladistic analysis inferred that Chinese Coptotermes species are divided into two main clades and there were some species closely related to C. formosanus Shiraki and C. gestroi (Wasmann), respectively. Based on a comparison of measurement data of the closely related species C. cochlearus Xia and He and C. gestroi in the cladogram, we propose that C. cochlearus is a new synonym of C. gestroi. In the situation where it is difficult to obtain more molecular data of Chinese Coptotermes species, the present work serves as a basis for further revisionary work on Coptotermes.

The intracellular bacterial pathogen Legionella pneumophila uses hundreds of effector proteins to manipulate multiple processes of the host cells to establish a replicative niche known as Legionella -containing vacuole (LCV). Biogenesis of the LCV has been known to depend on host small guanosine triphosphatases (GTPases), but whether bacterial effector GTPases are also involved remains unknown. Here, we show that an ankyrin repeat containing effector LegA15 localizes directly in host lipid droplets (LDs), leading to Golgi apparatus fragmentation of the host cells by hijacking the host vesicular transport factor p115. LegA15 is a GTPase with a unique catalytic mechanism, unlike any eukaryotic small GTPases. Moreover, the effector LegA15 co-opts p115 to modulate homeostasis of the host LDs in its GTPase-dependent manner. Together, our data reveal that an atypical GTPase effector regulates the host LDs through impeding the vesicle secretion system of the host cells for intracellular life cycle of Legionella .

The intracellular bacterial pathogen

A three-hidden-layer neural network with super approximation power is introduced. This network is built with the floor function ( ⌊ x ⌋ ), the exponential function ( 2 x ), the step function ( 1 x ≥ 0 ), or their compositions as the activation function in each neuron and hence we call such networks as Floor-Exponential-Step (FLES) networks. For any width hyper-parameter N ∈ N + , it is shown that FLES networks with width max { d , N } and three hidden layers can uniformly approximate a Holder continuous function f on [ 0 , 1 ] d with an exponential approximation rate 3 λ ( 2 d ) α 2 − α N , where α ∈ ( 0 , 1 ] and λ > 0 are the Holder order and constant, respectively. More generally for an arbitrary continuous function f on [ 0 , 1 ] d with a modulus of continuity ω f ( ⋅ ) , the constructive approximation rate is 2 ω f ( 2 d ) 2 − N + ω f ( 2 d 2 − N ) . Moreover, we extend such a result to general bounded continuous functions on a bounded set E ⊆ R d . As a consequence, this new class of networks overcomes the curse of dimensionality in approximation power when the variation of ω f ( r ) as r → 0 is moderate (e.g., ω f ( r ) ≲ r α for Holder continuous functions), since the major term to be concerned in our approximation rate is essentially d times a function of N independent of d within the modulus of continuity. Finally, we extend our analysis to derive similar approximation results in the L p -norm for p ∈ [ 1 , ∞ ) via replacing Floor-Exponential-Step activation functions by continuous activation functions.

[Image: see text] Protein aggregation is associated with a large number of human protein-misfolding diseases, yet FDA-approved drugs are currently not available. Amylin amyloid and plaque depositions in the pancreas are hallmark features of type 2 diabetes. Moreover, these amyloid deposits are implicated in the pathogenesis of diabetic complications such as neurodegeneration. We recently discovered that catechols and redox-related quinones/anthraquinones represent a broad class of protein aggregation inhibitors. Further screening of a targeted library of natural compounds in complementary medicine that were enriched with catechol-containing compounds identified rosmarinic acid (RA) as a potent inhibitor of amylin aggregation (estimated inhibitory concentration IC(50) = 200–300 nM). Structure–function relationship analysis of RA showed the additive effects of the two catechol-containing components of the RA molecule. We further showed that RA does not reverse fibrillation back to monomeric amylin but rather lead to nontoxic, remodeled protein aggregates. RA has significant ex vivo efficacy in reducing human amylin oligomer levels in HIP rat sera as well as in sera from diabetic patients. In vivo efficacy studies of RA treatment with the diabetic HIP rat model demonstrated significant reduction in amyloid islet deposition and strong mitigation of diabetic pathology. Our work provides new in vitro molecular mechanisms and in vivo efficacy insights for a model nutraceutical agent against type 2 diabetes and other aging-related protein-misfolding diseases.

An improved successive over-relaxation iterative method is proposed for coupled Lyapunov matrix equations (CLMEs) from continuous-time Markovian jump linear systems. The improved algorithm accelerates the convergence rate and converges to the unique positive definite solution of a CLME. The illustrative examples show that the method is effective and more efficient.

A series of novel thienopyridine derivatives were designed and synthesized as P2Y

Chemoresistance has been a major challenge in the treatment of patients with breast cancer. The diverse omics platforms and small sample sizes reported in the current studies of chemoresistance in breast cancer limit the consensus regarding the underlying molecular mechanisms of chemoresistance and the applicability of these study findings. Therefore, we built two transcriptome datasets for patients with chemotherapy-resistant breast cancers—one comprising paired transcriptome samples from 40 patients before and after chemotherapy and the second including unpaired samples from 690 patients before and 45 patients after chemotherapy. Subsequent conventional pathway analysis and new subpathway analysis using these cohorts uncovered 56 overlapping upregulated genes (false discovery rate [FDR], 0.018) and 36 downregulated genes (FDR, 0.016). Pathway analysis revealed the activation of several pathways in the chemotherapy-resistant tumors, including those of drug metabolism, MAPK, ErbB, calcium, cGMP-PKG, sphingolipid, and PI3K-Akt, as well as those activated by Cushing’s syndrome, human papillomavirus (HPV) infection, and proteoglycans in cancers, and subpathway analysis identified the activation of several more, including fluid shear stress, Wnt, FoxO, ECM-receptor interaction, RAS signaling, Rap1, mTOR focal adhesion, and cellular senescence (FDR < 0.20). Among these pathways, those associated with Cushing’s syndrome, HPV infection, proteoglycans in cancer, fluid shear stress, and focal adhesion have not yet been reported in breast cancer chemoresistance. Pathway and subpathway analysis of a subset of triple-negative breast cancers from the two cohorts revealed activation of the identical chemoresistance pathways.

The Publisher regrets that this article is an accidental duplication of an article that has already been published in [Toxicology Letters, 339C (2021) 88–96], https://doi.org/10.1016/j.toxlet.2020.11.022. The duplicate article has therefore been withdrawn. The full Elsevier Policy on Article Withdrawal can be found at https://www.elsevier.com/about/our-business/policies/article-withdrawal

Background: With prior preclinical and clinical knowledge, an effective and efficient cancer drug combinatory trial design could be expected, which will significantly accelerate the translation. However, our internal survey results suggested that some knowledge and data sources were underused or underestimated by researchers. One primary reason is that knowledge of drug combinations is scattered in many distinct databases. Moreover, some essential information, such as MTD and DLT was missed in current databases. Drug Combo (https://drugcombo.shinyapps.io/DrugCombo/) is the first knowledge base that integrates drug toxicity and PK data that may help design an efficient Phase I trial. It is a unique informatics resource that manually curated MTD and DLT are well organized in the knowledgebase. Methods: Drug Combo integrates various publicly available PK and toxicity knowledge for individual drugs and drug combinations (Table 1). More importantly, it is the unique knowledgebase with MTD and DLT. An expert team manually curated MTD and DLT data from publicly available publications. Some standard healthcare terminologies, e.g., Rx-Norm and MedDRA were applied for concept normalization at the back end. We implemented a User-Centered Design process in the user interface (UI).The UI layout will be simple, consistent, purposeful, comprehensive, easy to navigate and informative with readable or scannable typography. A summary view was provided to inform users of some essential information, e.g., MTD, and Overlapping toxicities. The user can find the details in the “Detail Tab”. Results: Currently, Drug Combo integrates pharmacological, pharmacokinetics, and toxicity data. Especially, MTD and DLT data from more than 1,600 published Phase I trials results are exclusive in Drug Combo. Conclusions: Drug Combo is the first knowledge base that provides expert-curated MTD and DLT information. It could help design an effective and efficient drug combination phase 1 trial. Current knowledge type in Drug Combo Type Source Drug Names DrugBank, RxNorm Target DrugBank, Manual curation Associated Condition RxNorm, Drug Labels PK profiles DrugBank Adverse Drug Event Drug Label, FAERS MTD Manual curation DLT Manual curation DDI DrugBank, Manual curation Citation Format: Lei Wang, Shijun Zhang, Lai Wei, Yuxi Zhu, Dwight Owen, Lang Li. Drug Combo: A unique resource for efficient phase 1 trial design with manually curated MTD and DLT [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 6573.

The aim of this retrospective study was to demonstrate that irAEs, specifically gastrointestinal and pulmonary, examined through International Classification of Disease (ICD) data leads to underrepresentation of true irAEs and overrepresentation of false irAEs, thereby concluding that ICD claims data are a poor approach to electronic health record (EHR) data mining for irAEs in immunotherapy clinical research. This retrospective analysis was conducted in 1,063 cancer patients who received ICIs between 2011 and 2017. We identified irAEs by manual review of medical records to determine the incidence of each of our endpoints, namely colitis, hepatitis, pneumonitis, other irAE, or no irAE. We then performed a secondary analysis utilizing ICD claims data alone using a broad range of symptom and disease-specific ICD codes representative of irAEs. 16% (n = 174/1,063) of the total study population was initially found to have either pneumonitis 3% (n = 37), colitis 7% (n = 81) or hepatitis 5% (n = 56) on manual review. Of these patients, 46% (n = 80/174) did not have ICD code evidence in the EHR reflecting their irAE. Of the total patients not found to have any irAEs during manual review, 61% (n = 459/748) of patients had ICD codes suggestive of possible irAE, yet were not identified as having an irAE during manual review. Examining gastrointestinal and pulmonary irAEs through the International Classification of Disease (ICD) data leads to underrepresentation of true irAEs and overrepresentation of false irAEs.

Hepatocellular carcinoma (HCC) has been known as the second common leading cancer worldwide, as it responds poorly to both chemotherapy and medication. Triptolide (TP), a diterpenoid triepoxide, is a promising treatment agent for its effective anticancer effect on multiple cancers including HCC. However, its clinical application has been limited owing to its severe systemic toxicities, low solubility, and fast elimination in the body. Therefore, to overcome the above obstacles, photo-activatable liposomes (LP) integrated with both photosensitizer Ce6 and chemotherapeutic drug TP (TP/Ce6-LP) was designed in the pursuit of controlled drug release and synergetic photodynamic therapy in HCC therapy. The TP encapsulated in liposomes accumulated to the tumor site due to the enhanced permeability and retention (EPR) effect. Under laser irradiation, the photosensitizer Ce6 generated reactive oxygen species (ROS) and further oxidized the unsaturated phospholipids. In this way, the liposomes were destroyed to release TP. TP/Ce6-LP with NIR laser irradiation (TP/Ce6-LP+L) showed the best anti-tumor effect both in vitro and in vivo on a patient derived tumor xenograft of HCC (PDXHCC). TP/Ce6-LP significantly reduced the side effects of TP. Furthermore, TP/Ce6-LP+L induced apoptosis through a caspase-3/PARP signaling pathway. Overall, TP/Ce6-LP+L is a novel potential treatment option in halting HCC progression with attenuated toxicity., Graphical abstract Photo-activatable liposomes incorporating Ce6 and triptolide (TP/Ce6-LP) for hepatocellular carcinoma (HCC) therapy were designed. Photodynamic therapy (PDT) and TP possibly induced cell apoptosis via a caspase-3/PARP signaling pathway in PDXHCC model.Image 1

Traditional Chinese Medicine often use the prescription composed of herbs to cure the disease, which requires doctors with the rich professional knowledge and experience. It is much expected that the prescription can be generated automatically to assist doctors in prescribing using such as machine learning on the tongue images. However, it is confronted with two challenges. First, there is not a larger tongue image database available for machine learning. Second, there is no such machine learning method available for generating prescription according to the given tongue image. This paper begins with constructing a larger tongue image database, where each image corresponds to a prescription. It then uses auto-encoder to extract features for the tongue image, on which the recommendation neural network is proposed to recommend herbs for the prescription. Finally, a new prescription generation method is proposed to select optimal herbs from the recommended herbs to form the final prescription. Experimental results on our constructed databases validate the effectiveness and the superior performance of the proposed methods.

NLRP3 inflammasome has recently attracted much attention as a potentially druggable target to develop potential therapeutics for inflammatory and neurodegenerative disorders. In our continuing studies, structure–activity relationship studies were conducted based on a newly identified NLRP3 inhibitor, YQ-II-128, from our laboratory to understand the structural features and improve aqueous solubility. The results revealed that steric interactions at the propoxyl and amide domain of YQ-II-128 are important for the observed inhibitory potency on the NLRP3 inflammasome. The results also identified the amide domain to incorporate polar moieties to improve solubility and potentially pharmacokinetic properties. As a result, analog 10 was identified as a selective NLRP3 inhibitor with comparable potency while significantly improved aqueous solubility. Collectively, these findings strongly encourage further optmization of 10 to develop analogs with improved pharmacokinetic properties as potential NLRP3-targted therapeutics.

In recent years, the research on the physical properties of two-dimensional (2D) materials has attracted much attention. In this paper, the magnetic and ferroelectric (FE) properties of semi-hydrogenated graphene, silylene and germanene X2H (X = C, Si, and Ge) under strain are systematically investigated. The results have shown that X2H is a magnetic FE semiconductor with ferromagnetic (FM) and FE structures, both perpendicular to the plane, a large energy gap, and a high polarization reversal barrier. It is found that both the polarization reversal barrier and the magnitude of FE polarization gradually decrease, but the FM state remains the same, upon gradually increasing the tensile strain. As the tensile strain is increased to 19%, the barriers of the Si2H and Ge2H monolayer films to flip a single valence bond are decreased to 1.123 eV and 0.768 eV, respectively, and the systems still maintain semiconductor characteristics. When the strain is increased to 20%, the films begin to show metallicity in the plane of films, but still have the polarity perpendicular to the plane because of the anisotropy of the band structure. These research results suggest that the magnetoelectric properties of Si2H and Ge2H monolayer films provide the possibility for achieving a new generation of information storage materials.

To explore a low–cost functional phase alternative material for thick film resistors, the thermal behavior, sintering and electrical properties of LaCo0·4Ni0.6-yZnyO3 (y = 0.00–0.08, LCNZ) ceramics were investigated through experiments and density functional theory calculations. Results of simultaneous thermal analysis, thermomechanical analysis, scanning electron microscopy, and DC four–probe method indicated that substitution of Ni-ion by Zn–ion could lower the phase formation and densification temperatures of LCNZ, as well as increase the resistivity and decrease the temperature coefficient of resistance (TCR). The resistivity of 0.94 mΩ cm (y = 0.00) and 1.03 mΩ cm (y = 0.02), as well as TCR value of −312.79 ppm/°C (for y = 0.00) and −872.82 ppm/°C (for y = 0.02) could be achieved as the LCNZ ceramics sintered at 1200 °C. The variations of octahedral bond population, electron density around oxygens, and partial density of states near the Fermi level firmly supported the results of experiments.

Aims. Abundant evidences in traditional Chinese medicine (TCM) supported the therapeutic value of herbal medicine Yinchen in hepatocellular carcinoma (HCC), but the underlying mechanism remains to be investigated. Main Methods. The intersection of immune gene set, module genes, HCC-associated genes, and target genes of Yinchen was employed for further analyses. The module genes were identified by weighted gene coexpression network analysis, and the other three gene sets were obtained from public databases. Subsequently, we further explored the clinical value and immunoregulation of the hub gene of intersection. The relevant pathways related to hub gene expression were investigated by gene set enrichment analysis. Finally, the interaction of active compounds and target genes was validated by molecular docking. Key Findings. Thirteen active compounds and 90 target genes of Yinchen were included. After constructing the network among Yinchen, target genes, and HCC, BIRC5 was identified as the hub gene. Significant difference was found between the high-expressed group and the low-expressed group in survival and stage. Different immune subtypes also presented significant difference in BIRC5 expression. Moreover, NK cell and T cell (CD4+ effector memory and CD4+ memory resting) were negatively correlated with BIRC5 expression, while CTLA4 and LAG3 were positively correlated. The results of molecular docking further validated a good binding activity of quercetin-BIRC5 interaction. Significance. In summary, our research identified for the first time a novel underlying association among herbal medicine Yinchen, BIRC5, immunotherapy, and HCC. We speculated that Yinchen may target the immune checkpoints (CTLA4 and LAG3) and activate the immune cells by suppressing BIRC5.

Background: The ecology and evolution of phoretic mites and termites have not been well studied. In particular, it is unknown whether the specific relationship between mites and termites is commensal or parasitic. High phoretic mite densities have often been found to occur in weak termite colonies, suggesting that the relationship is closer to that of parasitism than commensalism. Results: To examine this, Coptotermes formosanus was used as a carrier, and Acarus farris as the phoretic mite. We used video recordings to observe termite social immunity behaviors and bioassay to examine termite fitness. Our results showed that the attachment of the mite on the termite can enhance termite social immunity behaviors like alarm vibration and grooming frequency while decreasing the duration of individual grooming episodes in phoretic mites. Further, A. farris phoresy led to a 22.91% reduction in termite abdomen volume and a 3.31-fold increase in termite mortality. Conclusions: Phoretic behavior hastened termites’ death, and helped propagate the population of mites feeding on dead termites. Frequent social behaviors may cost termites energy, and thus provides a case for phoresy being a precursor to parasitism. The specific relationship between A. farris and C. formosanus is closer to parasitism than to commensalism.

Background subtraction of videos has been a fundamental research topic in computer vision in the past decades. To alleviate the computation burden and enhance the efficiency, background subtraction from online compressive measurements has recently attracted much attention. However, current methods still have limitations. First, they are all based on matrix modeling, which breaks the spatial structure within video frames. Second, they generally ignore the complex disturbance within the background, which reduces the efficiency of the low-rank assumption. To alleviate this issue, we propose a tensor-based online compressive video reconstruction and background subtraction method, abbreviated as NIOTenRPCA, by explicitly modeling the background disturbance in different frames as nonidentical but correlated noise. By virtue of such sophisticated modeling, the proposed method can well adapt to complex video scenes and, thus, perform more robustly. Extensive experiments on a series of real-world video datasets have demonstrated the effectiveness of the proposed method compared with the existing state of the arts. The code of our method is released on the website: https://github.com/crystalzina/NIOTenRPCA.

To analyse spermatic vein parameters and post-varicocelectomy diagnostic ultrasound methods by comparing pre- and post-operative ultrasound parameters and semen quality in patients undergoing varicocelectomy. Ultrasound and semen analyses were performed within 1 week before surgery and 3 months after surgery in 125 patients who underwent varicocelectomy for infertility. Patients were divided into three groups according to the post-operative internal diameter of the spermatic vein and reflux: recovery, dilatation, and reflux. Changes in semen quality before and after surgery were compared between groups. Sperm concentration, motility, and morphology were significantly improved (p 0.05); however, semen volume did not improve (p 0.05) in patients in the recovery and dilatation groups compared to those in patients before surgery. Sperm concentration, motility, and semen volume did not improve in patients in the reflux group compared with those in patients before surgery (p 0.05). Logistic regression analysis revealed that the internal diameter of the spermatic vein and reflux duration were risk factors for post-operative spermatic vein dilatation without reflux. Ultrasonography after varicocelectomy should primarily be used to observe reflux, and should not be used as a diagnostic criterion for varicocele based on the internal diameter of the spermatic vein alone.

Astrocyte aerobic glycolysis provides vital trophic support for central nervous system neurons. However, whether and how astrocytic metabolic dysregulation contributes to neuronal dysfunction in intellectual disability (ID) remain unclear. Here, we demonstrate a causal role for an ID-associated SNX27 mutation (R198W) in cognitive deficits involving reshaping astrocytic metabolism. We generated SNX27

NLRP3 inflammasome dysregulation has been observed in many human diseases including neurodegenerative disorders. Thus, development of small molecule inhibitors targeting this protein complex represents a promising strategy to achieve disease intervention. In our continuing efforts to develop NLRP3 inhibitors, a recently identified lead inhibitor, YQ128, was further modified and optimized. The structure-activity relationship studies of this lead compound suggested its flexibility for structural modifications while the sulfonamide and benzyl moiety demonstrated being important for selectivity. Additionally, the systematic SAR studies also provided insights for designing NLRC4 and AIM2 inflammasome inhibitors. A new lead inhibitor, 19, was identified with improved potency (IC(50): 0.12 ± 0.01 μM) and binding affinity (K(D): 84 nM). Further characterization of this lead compound using wild type and nlrp3(−/−) mice confirmed its in vivo selective target engagement. PET studies using a radiotracer based on the structure of 19 also demonstrated its improved brain penetration compared to previous lead compounds. These results strongly encourage further testing of 19 in disease models.

Background. mTORC1 signal pathway plays a role in the initiation and progression of hepatocellular carcinoma (HCC), but no relevant gene signature was developed. This research aimed to explore the potential correlation between the mTORC1 signal pathway and HCC and establish the related gene signature. Methods. HCC cases were retrieved from The Cancer Genome Atlas (TCGA), International Cancer Genome Consortium (ICGC), and Gene Expression Omnibus (GEO) databases. The genes included in mTORC1-associated signature were selected by performing univariate and multivariate Cox regression analyses and lasso regression analysis. The protein expression level of included genes was verified by The Human Protein Altas. Then, the signature was verified by survival analysis and multiple receiver operating characteristic (ROC) curve. Moreover, the correlation between signature and immune cells infiltration was investigated. Furthermore, a nomogram was established and evaluated by C-index and calibration plot. Results. The signature was established with the six genes (ETF1, GSR, SKAP2, HSPD1, CACYBP, and PNP). Three genes (ETF1, GSR, and HSPD1) have verified their protein expression level in HCC. Under the grouping from signature, patients in the high-risk group showed worse survival than those in the low-risk group in both three datasets. The signature was found to be significantly associated with the infiltration of B cells, CD4+ T-cells, CD8+ T-cells, dendritic cells, macrophages, and neutrophils. The univariate and multivariate Cox regression analysis indicated that mTORC1-related signature could be the potential independent prognostic factor in HCC. Finally, the nomogram involving age, gender, stage, and signature has been established and verified. Conclusion. The mTORC1-associated gene signature established and validated in our research could be used as a potential prognostic factor in HCC.

Retinal dehydrogenase 5 (RDH5) is an important enzyme in the visual cycle. Several studies have reported that the RDH family may play crucial roles in tumor prognosis. However, the role of RDH5 in tumor prognosis is still unclear. We examined the mRNA level of RDH5 by using q-PCR in hepatocellular carcinoma (HCC) and adjacent non-cancerous tissues. The proliferation rate of HCC cells was detected by MTS assay, and the invasive ability was examined by transwell and scratch wound assays. The YAP protein localization and expression were visualized by immunofluorescence in two different cell lines. CpG islands in the promoter region were predicted by using the methprimer database. Clinical characteristics of a patient cohort data came from The Cancer Genome Atlas database. RDH5 was significantly downregulated in hepatocellular carcinoma tissues, and low RDH5 expression was associated with metastasis and poor patient prognosis. Functional assays revealed that the RDH5 promoter is methylated in HCC cell lines. Moreover, overexpressing RDH5 can suppress metastasis by reversing the epithelial-mesenchymal transition (EMT) process, and RDH5 also inhibits cell proliferation in HCC cell lines. Furthermore, suppressing RDH5 can activate the Hippo/YAP signaling pathway and promote the nuclear translocation of YAP. Clinical data demonstrated that RDH5 is an independent prognostic factor in HCC. In our study, we provided the first evidence that RDH5 plays a crucial role in suppressing proliferation and metastasis, and the RDH5 promoter is methylated in hepatocellular carcinoma. And as an important regulator, RDH5 can suppress the Hippo/YAP signaling pathway. Taken together, it revealed that RDH5 might be a potential therapeutic target in HCC patients.

The effect of Ni substitution on the thermal behavior, crystal structure, densification, and electrical properties of La0.5Sr0.5Co1–yNiyO3-δ (y = 0.00–0.08) (LSCN) ceramics was discussed based on experimental measurements and theoretical calculations to search for a ruthenium–free and lead–free conductive oxide for thick film resistors. Ceramics were synthesized by the solid–state reaction, and calculations were performed with first–principle density functional theory (DFT). Results showed that the replacement of Ni ion to Co ion could help decrease the densification temperature and enhance the densification level and improve the conductivity of LSCN. Theoretical calculations, including the crystal structure, bond population, total energy, and density of states (DOS), supported the experimental results well. The maximum conductivity of 3155 S/cm was achieved as y = 0.04 was sintered at 1200 °C, and the peak temperature coefficient of resistance (TCR) of 2405.7 ppm/°C occurred at y = 0.06.

Background Studies have demonstrated that the roots of Averrhoa carambola L. (Oxalidaceae), a traditional Chinese medicine, can be used to treat diabetes and diabetes-related diseases. Nevertheless, the potential beneficial effects and mechanism of benzoquinone isolated from the roots of Averrhoa carambola L. (BACR) on diabetes remain unclear. Methods Diabetic Kunming mice were injected with STZ (120 mgkg-1) in the tail vein. Fasting blood glucose (FBG) and the change of body weight were measured after oral administration of BACR (120, 60, 30 mg/kg/d) every week. The levels of the total cholesterol (TC), triglyceride (TG), free fatty acids (FFA), glucosylated hemoglobin (GHb), fasting insulin (FINS), tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) were measured. The histological examination of pancreatic tissues and the TLR4/NF-κB pathway was analyzed by RT-PCR, immunohistochemistry and Western blot. Results The study found that clearly the BACR obviously reduced the blood glucose, serum lipids, GHb and FINS. In addition, BACR treatment markedly reduced the release of inflammatory factors, including IL-6 and TNF-α, and down-regulated the expression of the TLR4/NF-κB pathway. Conclusion BACR has potential benefits for the treatment of diabetes by ameliorating metabolic functions and attenuating the inflammatory response via inhibition of the activation of theTLR4/NF-κB pathway.

This paper quantitatively characterizes the approximation power of deep feed-forward neural networks (FNNs) in terms of the number of neurons. It is shown by construction that ReLU FNNs with width $\mathcal{O}\big(\max\{d\lfloor N^{1/d}\rfloor,\, N+1\}\big)$ and depth $\mathcal{O}(L)$ can approximate an arbitrary H\"older continuous function of order $\alpha\in (0,1]$ on $[0,1]^d$ with a nearly tight approximation rate $\mathcal{O}\big(\sqrt{d} N^{-2\alpha/d}L^{-2\alpha/d}\big)$ measured in $L^p$-norm for any $N,L\in \mathbb{N}^+$ and $p\in[1,\infty]$. More generally for an arbitrary continuous function $f$ on $[0,1]^d$ with a modulus of continuity $\omega_f(\cdot)$, the constructive approximation rate is $\mathcal{O}\big(\sqrt{d}\,\omega_f( N^{-2/d}L^{-2/d})\big)$. We also extend our analysis to $f$ on irregular domains or those localized in an $\varepsilon$-neighborhood of a $d_{\mathcal{M}}$-dimensional smooth manifold $\mathcal{M}\subseteq [0,1]^d$ with $d_{\mathcal{M}}\ll d$. Especially, in the case of an essentially low-dimensional domain, we show an approximation rate $\mathcal{O}\big(\omega_f(\tfrac{\varepsilon}{1-\delta}\sqrt{\tfrac{d}{d_\delta}}+\varepsilon)+\sqrt{d}\,\omega_f(\tfrac{\sqrt{d}}{(1-\delta)\sqrt{d_\delta}}N^{-2/d_\delta}L^{-2/d_\delta})\big)$ for ReLU FNNs to approximate $f$ in the $\varepsilon$-neighborhood, where $d_\delta=\mathcal{O}\big(d_{\mathcal{M}}\tfrac{\ln (d/\delta)}{\delta^2}\big)$ for any $\delta\in(0,1)$ as a relative error for a projection to approximate an isometry when projecting $\mathcal{M}$ to a $d_{\delta}$-dimensional domain.

Depressive disorder (DD) is the leading cause of disability worldwide and is the most prevalent mood disorder. Accumulative evidence from epidemiological studies has shown that DD is a risk factor for cancer. However, the role and molecular mechanism of DD in hepatocellular carcinoma (HCC) are still unknown. In this study, 30 mice were randomly divided into two groups: the HCC group and the HCC-DD group. The DD mouse model of HCC was established by induction with reserpine every other day and with monthly doses of diethylnitrosamine (DEN). All of the molecular studies were based on primary cell culture, and the effects of DD on HCC cell proliferation and migration and cancer stem cell (CSC) self-renewal were determined by colony formation, wound healing, and sphere culture assays. We found that the CSC markers ABCG2 and CD133 were upregulated in HCC-DD primary cells compared with HCC primary cells. Moreover, HCC-DD primary cells were more aggressive in terms of metastasis and self-renewal than HCC primary cells. Further study revealed that DD promoted tumor growth and metastasis by activating the AKT signaling pathway followed by an increased ABCG2 expression. Taken together, our novel findings indicate that DD promotes proliferation, self-renewal, and metastasis by upregulating ABCG2 in the AKT pathway.

China has a large number of gas stations, with which thousands of workers are associated. There is abundant online literature documenting the various occupational health risks these workers face. However, this literature has many flaws to address, and it falls short of suggesting measures to manage these risks. This study strives to fill that gap, and aims to improve the occupational health of gas station workers through comprehensive risk management and performance analysis. To this end, a reasonable volume of reliable data, i.e., 208 completed questionnaires, were analyzed through current statistical routines, viz., fuzzy Analytical Hierarchy Process (AHP) and Importance Performance Analysis (IPA). These methods were employed to hierarchically organize the main factors and sub-factors of physical risk management, chemical risk management, biological risk management, physiological risk management and psychological risk management according to their appraised importance, and screen out the risk management stratagem for priority improvement. Research findings reveal that chemical risk and biological risk response schemes have the lowest performance, and need to be prioritized for improvement. Furthermore, this study argues that we can safeguard the occupational health of gas station workers through appropriate risk management strategies. It also elaborates on implications, limitations and future research directions.

The rapid development of the Internet of Things (IoT) has accelerated the integration of science and technology with life, enabling the public to start enjoying the convenience brought by intelligent living. However, there are multiple resource-constrained sensing devices in IoT, which are always facing various external or internal attacks, making it difficult to ensure the secure transmission of sensitive data in IoT. Therefore, to address the problem of data transmission in resource-constrained devices in IoT, we propose a new certificateless hybrid signcryption scheme for IoT. It is a novel scheme that satisfies confidentiality and unforgeability, showing higher computational efficiency and lower overhead of transmission. To prove that it satisfies the efficent transmission of IoT, we conduct simulation experiments, and the experimental results show that our proposed scheme has higher efficiency than the existing schemes.

Cadmium (Cd) and fluorine (F) often coexist in environment and are toxic to organisms; however, their combined effects on plants are still not well documented. In this study, the co-effects of Cd and F on germination, biomass, photosynthesis, and nutrients uptake of lettuce were carried out in hydroponic culture. The results showed that the seed germination and seedling biomass decreased with an increase in Cd and F supplementation. The root morphology verified these effects as excess combined Cd and F diminished the root tips and surface area of lettuce, while single Cd and F inhibited the growth by decreasing root length and average diameter, respectively. These effects were also consistence with a reduction in photosynthesis which was mainly regulated by reducing the quantum yield of PS II, electron transport activity, stomatal conductance, intercellular CO

The discovery of drug–drug interactions (DDIs) that have a translational impact among in vitro pharmacokinetics (PK), in vivo PK and clinical outcomes depends largely on the quality of the annotated corpus available for text mining. We have developed a new DDI corpus based on an annotation scheme that builds upon and extends previous ones, where an abstract is fragmented and each fragment is then annotated along eight dimensions, namely, focus, polarity, certainty, evidence, directionality, study type, interaction type and mechanism. The guideline for defining these dimensions has undergone refinement during the annotation process. Our DDI corpus comprises 900 positive DDI abstracts and 750 that are not directly relevant to DDI. The abstracts in corpus are separated into eight categories of DDI or non-DDI evidence: DDI with pharmacokinetic (PK) mechanism, in vivo DDI PK, DDI clinical, drug–nutrition interaction, single drug, not drug related, in vitro pharmacodynamic (PD) and case report. Seven annotators, three annotators with drug–interaction research experience and four annotators with less drug–interaction research experience independently annotated the DDI corpus, where two researchers independently annotated each abstract. After two rounds of annotations with additional training in between, agreement improved from (0.79, 0.96, 0.86, 0.70, 0.91, 0.65, 0.78, 0.90) to (0.93, 0.99, 0.96, 0.94, 0.95, 0.93, 0.96, 0.97) for focus, certainty, evidence, study type, interaction type, mechanisms, polarity and direction, respectively. The novice-level annotators improved from 0.83 to 0.96, while the expert-level annotators stayed in high performance with some improvement, from 0.90 to 0.96. In summary, we achieved 96% agreement among each pair of annotators with regard to the eight dimensions. The annotated corpus is now available to the community for inclusion in their text-mining pipelines. Database URL https://github.com/zha204/DDI-Corpus-Database/tree/master/DDI%20corpus