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Until the advent of phylogenomics, the atypical morphology of extant representatives of the insect orders Grylloblattodea (ice‐crawlers) and Mantophasmatodea (gladiators) had confounding effects on efforts to resolve their placement within Polyneoptera. This recent research has unequivocally shown that these species‐poor groups are closely related and form the clade Xenonomia. Nonetheless, divergence dates of these groups remain poorly constrained, and their evolutionary history debated, as the few well‐identified fossils, characterized by a suite of morphological features similar to that of extant forms, are comparatively young. Notably, the extant forms of both groups are wingless, whereas most of the pre‐Cretaceous insect fossil record is composed of winged insects, which represents a major shortcoming of the taxonomy. Here, we present new specimens embedded in mid‐Cretaceous amber from Myanmar and belonging to the recently described species Aristovia daniili. The abundant material and pristine preservation allowed a detailed documentation of the morphology of the species, including critical head features. Combined with a morphological data set encompassing all Polyneoptera, these new data unequivocally demonstrate that A. daniili is a winged stem Grylloblattodea. This discovery demonstrates that winglessness was acquired independently in Grylloblattodea and Mantophasmatodea. Concurrently, wing apomorphic traits shared by the new fossil and earlier fossils demonstrate that a large subset of the former "Protorthoptera" assemblage, representing a third of all known insect species in some Permian localities, are genuine representatives of Xenonomia. Data from the fossil record depict a distinctive evolutionary trajectory, with the group being both highly diverse and abundant during the Permian but experiencing a severe decline from the Triassic onwards. [ABSTRACT FROM AUTHOR]

Lung cancer is one of the most common cancers worldwide, with the incidence increasing each year. It is crucial to improve the prognosis of patients who have lung cancer. Non-Small Cell Lung Cancer (NSCLC) accounts for the majority of lung cancer. Though its prognostic significance in NSCLC has not been often documented, Endoplasmic Reticulum (ER) stress has been identified to be implicated in tumour malignant behaviours and resistance to treatment. This work aimed to develop a gene profile linked to ER stress that could be applied to predictive and risk assessment for non-small cell lung cancer. Data from 1014 NSCLC patients were sourced from The Cancer Genome Atlas (TCGA) database, integrating clinical and Ribonucleic Acid (RNA) information. Diverse analytical techniques were utilized to identify ERS-associated genes associated with patients’ prognoses. These techniques included Kaplan-Meier analysis, univariate Cox regression, Least Absolute Shrinkage and Selection Operator regression analysis (LASSO) regression, and Pearson correlation analysis. Using a risk score model obtained from multivariate Cox analysis, a nomogram was created and validated to classify patients into high- and low-risk groups. The study employed the CIBERSORT algorithm and Single-Sample Gene Set Eenrichment Analysis (ssGSEA) to investigate the tumour immune microenvironment. We used the Genomics of Drug Sensitivity in Cancer (GDSC) database and R tools to identify medicines that could be responsive. Four genes – FABP5, C5AR1, CTSL, and LTA4H – were chosen to create the risk model. Overall Survival (OS) was considerably lower (P< 0.05) in the high-risk group. When it came to predictive accuracy, the risk model outperformed clinical considerations. Several medication types that are sensitive to high-risk groups were chosen. Our study has produced a gene signature associated with ER stress that may be employed to forecast the prognosis and therapeutic response of non-small cell lung cancer patients. [ABSTRACT FROM AUTHOR]

Health literacy is associated with mental disorders in adolescents. This study aimed to examine the associations between health literacy, depressive symptoms, and suicide-related outcomes. In terms of participants, 937 middle school students in Shenyang City, China were enrolled between December 2018 and December 2019 to assess health literacy, depressive symptoms and suicide-related outcomes. Multiple logistic regression models were used to examine possible associations. Adequate health literacy was negatively associated with 12-month follow-up depressive symptoms (RR = 0.115, 95 % CI : 0.032–0.411) and suicide-related outcomes (RR = 0.230, 95 % CI : 0.085–0.618) in females. Meanwhile, in females, interpersonal relationship, stress management, and self-actualization were negatively related to depressive symptoms, while physical activities, self-actualization, and health awareness are protective factors for suicide-related outcomes (P < 0.05 for each). Recall and reporting bias might be inevitable for self-reported data, and due to the small sample size, the predictive effect may not be very significant. These findings suggest that adequate health literacy may serve as a critical and independent protective factor for poor long-term mental health outcomes and that the predictive effect is more pronounced in female students. Public health efforts to enhance health literacy levels are required to maintain and improve adolescents' mental health outcomes. • Based on a school cohort, health literacy is a protect factor for depressive symptoms and suicide-related outcomes. • Improving health literacy could be an effective protective strategy for depressive symptoms and suicide-related outcomes. • Health literacy serve as a critical and independent protect factor for long-term poor mental health outcomes. [ABSTRACT FROM AUTHOR]

Insects are the most widely distributed and successful animals on the planet. A large number of insects are capable of flight with functional wings. Wing expansion is an important process for insects to achieve functional wings after eclosion and healthy genital morphology is crucial for adult reproduction. Myofilaments are functional units that constitute sarcomeres and trigger muscle contraction. Here, we identified four myofilament proteins, including Myosin, Paramyosin, Tropomyosin and Troponin T, from the wing pads of nymphs in the American cockroach, Periplaneta americana. RNAi‐mediated knockdown of Myosin, Paramyosin, Tropomyosin and Troponin T in the early stage of final instar nymphs caused a severely curly wing phenotype in the imaginal moult, especially in the Paramyosin and Troponin T knockdown groups, indicating that these myofilament proteins are involved in controlling wing expansion behaviours during the nymph‐adult transition. In addition, the knockdown resulted in abnormal external genitalia, caused ovulation failure, and affected male accessory gland development. Interestingly, the expression of myofilament genes was induced by methoprene, a juvenile hormone (JH) analogue, and decreased by the depletion of the JH receptor gene Met. Altogether, we have determined that myofilament genes play an important role in promoting wing expansion and maintaining adult genitalia morphology, and their expression is induced by JH signalling. Our data reveal a novel mechanism by which wing expansion is regulated by myofilaments and the functions of myofilaments are involved in maintaining genitalia morphology. [ABSTRACT FROM AUTHOR]

Background: Although the promising advancements of current therapeutic approaches is available for the squamous cell carcinoma (SCC) patients, the clinical treatment of SCC still faces many difficulties. The surgical irreparable disfigurement and the postoperative wound infection largely hamper the recovery, and the chemo/radiotherapy leads to toxic side effects. Results: Herein, a novel pH/Hyaluronidase (HAase) dual-stimuli triggered smart nanoprobe FeIIITA@HA has been designed through the biomineralization of Fe3+ and polyphenol tannic acid (TA) under the control of hyaluronic acid (HA) matrix. With the HA residues on the outer surface, FeIIITA@HA nanoprobes can specifically target the SCC cells through the over-expressed CD44, and accumulate in the carcinoma region after intravenously administration. The abundant HAase in carcinoma microenvironment will trigger the degradation of HA molecules, thereby exposing the FeIIITA complex. After ingesting by tumor cells via CD44 mediated endocytosis, the acidic lysosomal condition will further trigger the protonation of TA molecules, finally leading to the Fe3+ release of nanoprobe, and inducing a hybrid ferroptosis/apoptosis of tumor cells through peroxidase activity and glutathione depletion. In addition, Owing to the outstanding T1 magnetic resonance imaging (MRI) performance and phototermal conversion efficiency of nanoprobes, the MRI-guided photothermal therapy (PTT) can be also combined to complement the Fe3+-induced cancer therapy. Meanwhile, it was also found that the nanoprobes can promote the recruitment of CD4+ and CD8+ T cells to inhibit the tumor growth through the cytokines secretion. In addition, the FeIIITA@HA nanoprobes can be eliminated from the body and no obvious adverse side effect can be found in histological analysis, which confirmed the biosafety of them. Conclusion: The current FeIIITA@HA nanoprobe has huge potential in clinical translation in the field of precise diagnosis and intelligent synergistic therapy of superficial SCC. This strategy will promisingly avoid the surgical defects, and reduce the systemic side effect of traditional chemotherapy, paving a new way for the future SCC treatment. [ABSTRACT FROM AUTHOR]

The collembolan Folsomia candida Willem, 1902, is widely distributed throughout the world and has been frequently used as a test organism in soil ecology and ecotoxicology studies. However, it is questioned as an ideal "standard" because of differences in reproductive modes and cryptic genetic diversity between strains from various geographical origins. In this study, we obtained two high‐quality chromosome‐level genomes of F. candida, for a parthenogenetic strain (named FCDK, 219.08 Mb, 25,139 protein‐coding genes) and a sexual strain (named FCSH, 153.09 Mb, 21,609 protein‐coding genes), reannotated the genome of the parthenogenetic strain reported by Faddeeva‐Vakhrusheva et al. in 2017 (named FCBL, 221.7 Mb, 25,980 protein‐coding genes) and conducted comparative genomic analyses of the three strains. High genome similarities between FCDK and FCBL based on synteny, genome architecture, mitochondrial and nuclear gene sequences suggest that they are conspecific. The seven chromosomes of FCDK are each 25%–54% larger than the corresponding chromosomes of FCSH, showing obvious repetitive element expansions and large‐scale inversions and translocations but no whole‐genome duplication. The strain‐specific genes, expanded gene families and genes in nonsyntenic chromosomal regions identified in FCDK are highly related to the broader environmental adaptation of parthenogenetic strains. In addition, FCDK has fewer strain‐specific microRNAs than FCSH, and their mitochondrial and nuclear genes have diverged greatly. In conclusion, FCDK/FCBL and FCSH have accumulated independent genetic changes and evolved into distinct species after 10 million years ago. Our work provides important genomic resources for studying the mechanisms of rapidly cryptic speciation and soil arthropod adaptation to soil ecosystems. [ABSTRACT FROM AUTHOR]

l-Arginine serves as a carbon and nitrogen source and is critical for Mycobacterium tuberculosis (Mtb) survival in the host. Generally, ArgR acts as a repressor regulating arginine biosynthesis by binding to the promoter of the argCJBDFGH gene cluster. In this study, we report that the dormancy regulator DosR is a novel arginine regulator binding to the promoter region of argC (rv1652), which regulates arginine synthesis. Phosphorylation modification promoted DosR binding to a region upstream of the promoter. Cofactors, including arginine and metal ions, had an inhibitory effect on this association. Furthermore, DosR regulatory function relies on the interaction of the 167, 181, 182, and 197 amino acid residues with an inverse complementary sequence. Arginine also binds to DosR and directly affects its DNA-binding ability. Together, the results demonstrate that DosR acts as a novel transcriptional regulator of arginine synthesis in Mycobacterium bovis bacille Calmette-Guerin. [ABSTRACT FROM AUTHOR]

Aquifer storage technology for CO2\documentclass[12pt]{minimal}\usepackage{amsmath}\usepackage{wasysym}\usepackage{amsfonts}\usepackage{amssymb}\usepackage{amsbsy}\usepackage{mathrsfs}\usepackage{upgreek}\setlength{\oddsidemargin}{-69pt}\begin{document}$$\textrm{CO}_2$$\end{document} plays a crucial role in achieving carbon emission reduction. Upon injecting CO2\documentclass[12pt]{minimal}\usepackage{amsmath}\usepackage{wasysym}\usepackage{amsfonts}\usepackage{amssymb}\usepackage{amsbsy}\usepackage{mathrsfs}\usepackage{upgreek}\setlength{\oddsidemargin}{-69pt}\begin{document}$$\textrm{CO}_2$$\end{document} into the saline layer, the complex interaction among CO2\documentclass[12pt]{minimal}\usepackage{amsmath}\usepackage{wasysym}\usepackage{amsfonts}\usepackage{amssymb}\usepackage{amsbsy}\usepackage{mathrsfs}\usepackage{upgreek}\setlength{\oddsidemargin}{-69pt}\begin{document}$$\textrm{CO}_2$$\end{document}, saltwater, and rock initiates a seepage process characterized by multiphase fluid flow. This study quantitatively analyzed the impact of injection flow rate and permeability on principles governing CO2\documentclass[12pt]{minimal}\usepackage{amsmath}\usepackage{wasysym}\usepackage{amsfonts}\usepackage{amssymb}\usepackage{amsbsy}\usepackage{mathrsfs}\usepackage{upgreek}\setlength{\oddsidemargin}{-69pt}\begin{document}$$\textrm{CO}_2$$\end{document} migration in isotropic and anisotropic reservoirs. The findings indicated that in isotropic reservoirs with a permeability of 3×10-15\documentclass[12pt]{minimal}\usepackage{amsmath}\usepackage{wasysym}\usepackage{amsfonts}\usepackage{amssymb}\usepackage{amsbsy}\usepackage{mathrsfs}\usepackage{upgreek}\setlength{\oddsidemargin}{-69pt}\begin{document}$$3\times 10^{-15} $$\end{document} m2\documentclass[12pt]{minimal}\usepackage{amsmath}\usepackage{wasysym}\usepackage{amsfonts}\usepackage{amssymb}\usepackage{amsbsy}\usepackage{mathrsfs}\usepackage{upgreek}\setlength{\oddsidemargin}{-69pt}\begin{document}$$^{2}$$\end{document}, CO2\documentclass[12pt]{minimal}\usepackage{amsmath}\usepackage{wasysym}\usepackage{amsfonts}\usepackage{amssymb}\usepackage{amsbsy}\usepackage{mathrsfs}\usepackage{upgreek}\setlength{\oddsidemargin}{-69pt}\begin{document}$$\textrm{CO}_2$$\end{document} penetrated the cap rock’s top by the 60th year at an injection flow rate q≥0.1\documentclass[12pt]{minimal}\usepackage{amsmath}\usepackage{wasysym}\usepackage{amsfonts}\usepackage{amssymb}\usepackage{amsbsy}\usepackage{mathrsfs}\usepackage{upgreek}\setlength{\oddsidemargin}{-69pt}\begin{document}$$q \ge 0.1$$\end{document} kg/s. As the injection flow rate rose from 0.01 to 0.2 kg/s, the maximum horizontal penetration distance increased by 2.43 times and maximum vertical penetration distance by 1.102 times. The injection flow rate significantly influences the horizontal permeability distance but has a less impact on the vertical permeability distance. Lower permeabilities lead to slower but more persistent CO2\documentclass[12pt]{minimal}\usepackage{amsmath}\usepackage{wasysym}\usepackage{amsfonts}\usepackage{amssymb}\usepackage{amsbsy}\usepackage{mathrsfs}\usepackage{upgreek}\setlength{\oddsidemargin}{-69pt}\begin{document}$$\textrm{CO}_2$$\end{document} migration, resulting in higher saturation at the monitoring point and longer vertical penetration distances. In anisotropic reservoirs, when the ratio of horizontal-to-vertical permeability of the reservoir was expanded from 1 to 100, at an injection flow rate q=0.02\documentclass[12pt]{minimal}\usepackage{amsmath}\usepackage{wasysym}\usepackage{amsfonts}\usepackage{amssymb}\usepackage{amsbsy}\usepackage{mathrsfs}\usepackage{upgreek}\setlength{\oddsidemargin}{-69pt}\begin{document}$$q = 0.02$$\end{document} kg/s, the maximum horizontal penetration distance was increased by 2.125 times. The comprehensive data analysis in this paper will provide important data support and guidance for the application of CO2\documentclass[12pt]{minimal}\usepackage{amsmath}\usepackage{wasysym}\usepackage{amsfonts}\usepackage{amssymb}\usepackage{amsbsy}\usepackage{mathrsfs}\usepackage{upgreek}\setlength{\oddsidemargin}{-69pt}\begin{document}$$\textrm{CO}_2$$\end{document} storage technology. [ABSTRACT FROM AUTHOR]

To satisfy incineration efficiency and nitrogen oxides ultra-low emission requirements, it is of great importance to improve the operational performance of the municipal solid waste incineration (MSWI) process. However, due to the complex and fluctuating composition of municipal solid waste, it is challenging to guarantee optimal operation under changing conditions. To address this issue, a multi-condition operational optimization method based on adaptive knowledge transfer (MCOO-TR) is proposed for the MSWI process. First, an integrated optimization scheme, where different operation conditions are identified based on cluster analysis and expert knowledge, is developed. Second, a surrogate-assisted multi-objective particle swarm optimization algorithm is designed to solve the data-driven optimization problems for optimal operation, where the surrogate model selection mechanism is proposed to cope with multi-condition characteristics. Third, an adaptive knowledge transfer strategy, corresponding to condition identification, is designed aiming to improve optimization efficiency. Finally, the proposed MCOO-TR method is evaluated based on actual industrial data. The experimental results demonstrate that the MCOO-TR method can achieve satisfactory operational performance under changing operation conditions. [ABSTRACT FROM AUTHOR]

Ovarian cancer is a gynecological cancer that has the highest mortality rate and is often resistant to conventional treatments. Therefore, development of new therapies is essential. Metformin (MET), which is the priority drug for treatment of type 2 diabetes, has received increasing attention because of its anti-tumor effects. Here, we examined combined anti-tumor effects of MET and RG7388, the only MDM2 (mouse double minute 2 homolog) antagonist that has entered phase III clinical trials, on ovarian cancer cell lines. We examined effects on proliferation by Cell Counting Kit-8 (CCK-8) and colony formation assays, and effects on apoptosis by flow cytometric analysis and Hoechst staining. Western blotting was used to measure protein expression in cells and tissues treated with MET and/or RG7388. Flow cytometry was used to measure reactive oxygen species (ROS). We also examined the effects of MET and/or RG7388 on inhibition of A2780 cell growth in vivo. The combination of MET and RG7388 significantly increased growth inhibition, apoptosis, and ROS of A2780 and SKOV3 cells compared with either agent alone. Additionally, in vitro and in vivo results showed that MET and/or RG7388 inhibited the phosphoinositide 3-kinase (PI3K)/AKT/mammalian target of rapamycin (mTOR) pathway and their combination had a stronger effect. Our findings suggest that the combination of MET and RG7388 enhances growth inhibition and apoptosis induction of ovarian cancer cells through the PI3K/AKT/mTOR pathway and accumulation of intracellular ROS. • Combination of metformin and an MDM2 antagonist enhanced the inhibition of ovarian cancer cells proliferation. • The combination of metformin and RG7388 significantly promoted the apoptosis of ovarian cancer cells. • Metformin and RG7388 induced ROS accumulation in ovarian cancer cells. • Metformin combined with RG7388 inhibited PI3K/Akt/mTOR pathway. [ABSTRACT FROM AUTHOR]

Macrophages serve as the primary immune cells responsible for the innate immune defense against Mycobacterium tuberculosis (MTB) infection within the host. Specifically, NLRP3, a member of the NLRs family, plays a significant role in conferring resistance against MTB infection. Conversely, MTB evades innate immune killing by impeding the activation of the NLRP3 inflammasome, although the precise mechanism remains uncertain. In this study, we have identified PE12 (Rv1172c), a member of the PE/PPE family proteins, as an extracellular protein of MTB. PE12 interacts with Toll like receptor 4 (TLR4) in macrophages, forming the PE12-TLR4 complex which subsequently inhibits the transcription and expression of NLRP3. As a result, the transcription and secretion of IL-1β are reduced through the PE12-TLR4-NLRP3-IL-1β immune pathway. In vitro and in vivo experiments using a PE12-deficient strain (H37RvΔPE12) demonstrate a weakening of the suppression of the inflammatory response to MTB infection. Our findings highlight the role of the PE12 protein in not only inhibiting the transcription and release of inflammatory cytokines but also mediating the killing of MTB escape macrophages through TLR4 and inducing lung injury in MTB-infected mice. These results provide evidence that PE12 plays a significant role in the inhibition of the host immune response by MTB. • PE12 (Rv1172c), an extracellular protein of MTB, inhibits IL-1β release from macrophages. • PE12 interacts with TLR4 in macrophages to inhibit the expression of NLRP3 and promote the survival of MTB. • PE12 plays a role in the colonization of MTB and is associated with lung damage in mice infected with the bacterium. [ABSTRACT FROM AUTHOR]

The 'south forestflies' (Notonemouridae) are known from the southern hemisphere. However, their successive closest sister-groups all occur in the northern hemisphere, suggesting a north-to-south migration at some stage of their evolution. No reliable fossil remains that would provide age constraints for this event have been identified. According to previously published divergence date estimates, the group arose recently (65-98 Ma), implying a late transcontinental dispersal. Here, we describe a new fossil insect, Paranotonemoura zwicki Cui & Béthoux sp. nov. (Daohugou, China), and revise Paranotonemoura fidelis Sinitshenkova, 1987 comb. nov. (Bakhar, Mongolia), both of Jurassic age (c. 165 Ma). Based on the study of their wing venation pattern and of that of extant 'south forestflies', we demonstrate that the fossils belong to this group, and therefore are its first fossils. Our discovery demonstrates that the lineage is much more ancient than previously estimated. Plausible scenarios on the origin, migration and partial extinction are proposed based on the dispersal abilities of these insects and palaeogeographical reconstructions during the Mesozoic. We assume that the north-to-south migration took place between 220 and 160 Ma. http://zoobank.org/urn:lsid:zoobank.org:pub:66E22602-FE0D-4641-AB14-D8CB129D8F67 [ABSTRACT FROM AUTHOR]

Cultural tourism is one of the directions of urban transformation and development, but there are still problems such as fragmentation of resource development models. Urban repair, as a comprehensive, systematic, and holistic updating project under the guidance of the problem, is an important way to promote the sustainable development of urban cultural tourism by paying attention to the connotative development of the "stock" of urban scale. Based on the analysis of the western urban cultural renaissance concept, this study closely followed the actual situation of cultural tourism development in the old city of China, re-examined the scale, goals and values of the current urban repair research to find breakthroughs for urban repair, put forward basic routes for the renewal of the built-up area, and analyzed the project practice of the Old Town of Jiazhou, with a view to providing a new "repair" model for promoting cultural tourism in small and medium-sized cities in China. [ABSTRACT FROM AUTHOR]

Tuberculosis (TB) is an infectious disease caused by Mycobacterium tuberculosis (Mtb). Mtb can overcome macrophage intracellular killing and lead to persistent infections. The proteases of Mtb are critical virulence factors that participate in immune responses. We determined that Rv3090 is a cell wall–associated protease and a potential pathogenic factor. To characterize the role of Rv3090 in Mtb, recombinant Msg_Rv3090 and Msg_pAIN strains were constructed to infect macrophages and mice. Lactate dehydrogenase assays and flow cytometry results showed that Rv3090 induces late macrophage apoptosis. In vivo infection experiments indicated that Rv3090 could induce hepatocyte and lung cell apoptosis and cause pathological damage to the spleen, livers and lungs. Msg_Rv3090 specifically stimulated the secretion of inflammatory cytokines including TNF-α, IL-6 and IL-1β. Overexpression of Rv3090 significantly promoted the survival of Msg in livers and lungs. Thus, Rv3090 protease triggered late cell apoptosis and contributed to the pathogenicity and dissemination of Mtb. • Rv3090 is a cell-wall associated protein and identified as a protease. • Rv3090 has cytotoxicity and can promote the late apoptosis of macrophages. • Rv3090 promotes pathological damage to organs in mice and the secretion of TNF- α, IL-6 and IL-1 β in mycobacterium. • Rv3090 can promote intracellular survival of mycobacterium in mice. [ABSTRACT FROM AUTHOR]

• Glasses with a molar composition of 70TeO 2 -10GeO 2 -10K 2 O-10Nb 2 O 5 were synthesized by conventional melt-quenching. (another bullet) Different melting temperature leads the glasses to present different colors. • The XRD and DSC curves suggest that the formation of Te metalis not the principal reason for the color-changing. • The experiments and XPS spectra indicate the valence states of niobium is not the principal reason for the color-changing. • The generation of T-Nb 2 O 5 causes the color-changing was proposed based on the transmittance, XPS and Raman spectra. Germano-tellurite niobate glasses have gained significant interest because of their applications in lasers and optical devices. However, germano-tellurite niobate glasses tend to turn brown or dark, which is a major disadvantage for visible optical systems. This work is devoted to exploring the mechanism of this color-changing. Glasses with a molar composition of 70TeO 2 -10GeO 2 -10K 2 O-10Nb 2 O 5 (TGKN) were synthesized by conventional melt-quenching at various melting temperatures. Different melting temperature leads the glasses to present different colors. The precise glass composition was revealed by ICP-OES, and the thermal properties, optical properties, and microstructure of the TGKN glasses were investigated. The XRD patterns and DSC curves suggest that the formation of Te metal is not the principal reason for the color-changing. A novel interpretation that the generation of T-Nb 2 O 5 causes the color-changing was proposed based on the transmittance, XPS and Raman spectra. This work will provide a new perspective on clarifying the effects of melting temperature on color-changing in the germano-tellurite niobate glass. [ABSTRACT FROM AUTHOR]

Rv3291c (MtbLrpA), a transcriptional regulator, belongs to the leucine-responsive regulatory protein (Lrp) family and is thought to play an important role in Mycobacterium tuberculosis persistence. In this study, we verified 17 novel potential binding sites for MtbLrpA by in vitro binding assays on the basis of previous predictions from an in silico analysis and bacterial one-hybrid (BIH) reporter system. Amino acids, such as tyrosine, phenylalanine, tryptophan, and histidine, strongly affect the binding affinity of MtbLrpA, and vitamins, including B1, B3, B6, VC, B7, B9, B12, VA, and VK3, also decrease MtbLrpA binding affinity. This is the first report regarding that an Lrp-like protein can sense vitamins as an environmental signal. Vitamin supplementation to the environment can change the expression level of the target genes, which provides a potential mechanism for tuberculosis supplementary treatment with vitamins. [ABSTRACT FROM AUTHOR]

This paper studies a class of auction-based resource allocation games under a hierarchical structure, such that each supplier is assigned a certain amount of resource from a single provider and allocates it to its buyers with auction mechanisms. To implement the efficient allocations for the underlying hierarchical system, we first design an auction mechanism, for each local system composed of a supplier and its buyers, which inherits the advantages of the progressive second price mechanism. By employing a dynamic algorithm, each local system converges to its own efficient Nash equilibrium, at which the efficient resource allocation is achieved and the bidding prices of all the buyers in this local system are identical with each other. After the local systems reach their own equilibria respectively, the resources assigned to suppliers are readjusted via a dynamic hierarchical algorithm with respect to the bidding prices associated with the implemented equilibria of local systems. By applying the proposed hierarchical process, the formulated hierarchical system can converge to the efficient allocation under certain mild conditions. The developed results in this work are demonstrated with simulations. [ABSTRACT FROM AUTHOR]

The presumed phylogenetic link between extant ice-crawlers (Grylloblattidae = ‘crown-Grylloblattida’) and fossil species of the taxon concept Grylloblattida sensu Storozhenko (2002) is essentially based on postabdominal morphology. However, the fossil data are limited, and the interpretation is open to debate. Here we investigate a sample of a poorly known fossil ‘grylloblattidan’ family, the Bajanzhargalanidae, collected from the Daohugou locality (Middle Jurassic, China). We describe Sinonele fangi gen. nov. , sp. nov. , Sinonele hei gen. nov. , sp. nov. , Sinonele phasmoides gen. nov. , sp. nov. , and Sinonele mini gen. nov. , sp. nov. Thanks to the abundance and exceptional preservation of the material, we could document wing venation intra-specific variability, provide cues to identify male and female individuals, describe and tentatively interpret various body structures of both sexes, and discuss them with a broad pterygotan phylogenetic perspective. The Bajanzhargalanidae exhibit a puzzling combination of postabdominal characters leaving us inconclusive on their affinities, or lack thereof, with crown-Grylloblattida. Our contribution suggests that a substantial effort will be needed to further investigate postabdominal structures from comparatively ancient fossil insects preserved as rock imprints, because of their broad morphological disparity. [ABSTRACT FROM AUTHOR]

Potentially fatal chemotherapy (CT)-related gastrorrhagia and gastric perforation in patients with gastric lymphoma present difficult problems to doctors. We retrospectively analyzed 54 patients with ulcerative gastric diffuse large B-cell lymphoma (G-DLBCL) to compare the safety and efficacy of low-dose pre-phase CT before 4–6 cycles of conventional-dose CT (n= 28) with 4–6 cycles of conventional-dose CT (n= 26) between October 2005 and August 2014. Patients who received low-dose pre-phase before conventional-dose CT showed a lower gastrorrhagia or gastric perforation rate (0% vs. 15.4%,p= 0.047) and higher complete response (CR) rate (78.6% vs. 46.2%,p= 0.023) and 5-year progression-free survival (PFS) rate (63% vs. 31%,p= 0.021) than patients who received conventional-dose CT alone. Our study suggests that low-dose pre-phase therapy before conventional-dose CT provides a safe and effective method for ulcerative G-DLBCL. [ABSTRACT FROM PUBLISHER]

A novel MEMS (Micro Electronic Mechanical System) capacitive accelerometer is presented, which is mainly composed of supporting beam, seismic mass, grid strip capacitances, comb capacitances and electrostatic driver. The damping of grid strip capacitances with variable overlapping area is mainly affected by the slide film air damping, which is small and neglectful, and the damping between comb capacitor is squeeze film air damping. The comb sensing gap can be reduced by electrostatic actuators by which the aspect ratio can reach to 75:1 which greatly depress the limitation of DRIE (Deep reactive ion etching) process on high aspect ratio, and the initial sensing capacitance increases from 2.97 pf to 14.87 pf. The squeeze film damping is reduced from 0.046 Nm/s to 0.0015 Nm/s by designing the comb-shaped grooves on the fixed comb electrodes. The comb initial sensing gap is optimized according to formation factors of system noise, and the noise is reduced from 1.395 μg/√HZ to 0.591 μg/√HZ. The simulation results show that the accelerometer sensitivity achieves 8.40 pf/g, which is two times of the conventional devices. [ABSTRACT FROM AUTHOR]

Intestinal fibrosis is a common complication of inflammatory bowel disease. So far, there is no safe and effective drug for intestinal fibrosis. Pirfenidone is an anti-fibrotic compound available for the treatment of idiopathic pulmonary fibrosis. Here, we explored the anti-proliferative and anti-fibrotic properties of pirfenidone on primary human intestinal fibroblasts (p-hIFs). p-hIFs were cultured in the absence and presence of pirfenidone. Cell proliferation was measured by a real-time cell analyzer (xCELLigence) and BrdU incorporation. Cell motility was monitored by live cell imaging. Cytotoxicity and cell viability were analyzed by Sytox green, Caspase-3 and Water Soluble Tetrazolium Salt-1 (WST-1) assays. Gene expression of fibrosis markers was determined by quantitative reverse transcription PCR (RT-qPCR). The mammalian target of rapamycin (mTOR) signaling was analyzed by Western blotting and type I collagen protein expression additionally by immunofluorescence microscopy. Pirfenidone dose-dependently inhibited p-hIF proliferation and motility, without inducing cell death. Pirfenidone suppressed mRNA levels of genes that contribute to extracellular matrix production, as well as basal and TGF-β1-induced collagen I protein production, which was associated with inhibition of the rapamycin-sensitive mTOR/p70S6K pathway in p-hIFs. Thus, pirfenidone inhibits the proliferation of intestinal fibroblasts and suppresses collagen I production through the TGF-β1/mTOR/p70S6K signaling pathway, which might be a novel and safe anti-fibrotic strategy to treat intestinal fibrosis. [ABSTRACT FROM AUTHOR]

This paper is devoted to the study of the pricing of European options under a non-Gaussian model. This model follows a non-extensive statistical mechanics which can better describe the fractal characteristics of price movement in the financial market. Moreover, we present a simple but precise least-square method for approximation and obtain a closed-form solution of the price of European options. The advantages of this technique are illustrated by numerical simulation, which shows that the least-squares method is better compared with Borland's two methods in 2002 and 2004. [ABSTRACT FROM AUTHOR]

Epithelial cells function as the primary line of defense against invading pathogens. However, bacterial pathogens possess the ability to compromise this barrier and facilitate the transmigration of bacteria. Nonetheless, the specific molecular mechanism employed by Mycobacterium tuberculosis (M.tb) in this process is not fully understood. Here, we investigated the role of Rv2569c in M.tb translocation by assessing its ability to cleave E-cadherin, a crucial component of cell-cell adhesion junctions that are disrupted during bacterial invasion. By utilizing recombinant Rv2569c expressed in Escherichia coli and subsequently purified through affinity chromatography, we demonstrated that Rv2569c exhibited cell wall–associated serine protease activity. Furthermore, Rv2569c was capable of degrading a range of protein substrates, including casein, fibrinogen, fibronectin, and E-cadherin. We also determined that the optimal conditions for the protease activity of Rv2569c occurred at a temperature of 37°C and a pH of 9.0, in the presence of MgCl2. To investigate the function of Rv2569c in M.tb, a deletion mutant of Rv2569c and its complemented strains were generated and used to infect A549 cells and mice. The results of the A549-cell infection experiments revealed that Rv2569c had the ability to cleave E-cadherin and facilitate the transmigration of M.tb through polarized A549 epithelial cell layers. Furthermore, in vivo infection assays demonstrated that Rv2569c could disrupt E-cadherin, enhance the colonization of M.tb, and induce pathological damage in the lungs of C57BL/6 mice. Collectively, these results strongly suggest that M.tb employs the serine protease Rv2569c to disrupt epithelial defenses and facilitate its systemic dissemination by crossing the epithelial barrier. Author summary: Mycobacterium tuberculosis (M.tb) causes tuberculosis (TB), a highly contagious respiratory disease and a leading cause of death worldwide. Following the inhalation of aerosol particles, the bacteria often establish a persistent infection within the lungs, leading to the development of the characteristic pulmonary TB syndrome. Additionally, M.tb can breach alveolar barrier, thereby initiating extrapulmonary TB. The pathogenesis of M.tb heavily relies on systemic dissemination, although the precise underlying mechanism remains incompletely elucidated. The alveolar epithelial barrier, composed of tight junctions and adherens junctions, plays a crucial role in safeguarding against invading pathogens. In this study, we present groundbreaking discoveries pertaining to the extracellular serine protease Rv2569c of M.tb, which facilitates bacterial transmigration through the cleavage of E-cadherin. Furthermore, we ascertain that Rv2569c elicits profound pathological harm and enhances M.tb colonization within murine pulmonary tissues. These findings contribute to a deeper comprehension of the pathogenic mechanisms employed by M.tb and hold potential for informing future strategies aimed at controlling TB infections. [ABSTRACT FROM AUTHOR]

This article explores the involvement of the immune system in neuronal intranuclear inclusion disease (NIID), a progressive neurodegenerative disorder. The study found inflammatory cell infiltrates and eosinophilic intranuclear inclusions in various tissues of NIID patients, suggesting the systemic nature of the disease. Additionally, the presence of ubiquitin-positive intranuclear inclusions and uN2CpolyG protein aggregates in peripheral blood monocyte cells (PBMCs) of NIID patients may serve as potential biomarkers for diagnosis. The study highlights the need for further research to understand the immune system's role in NIID and improve clinical management strategies. [Extracted from the article]

Wing venation is a character system commonly used in the systematics of fossil insects, but the existing documentation for extant forms is often insufficient to allow robust identification of extinct forms. The existing literature suggests that the small stonefly family Styloperlidae Illies, 1966 , for which no fossils have ever been identified, might possess a suite of distinctive traits. In order to assess their relevance, we conducted a comparative analysis based on a set of individuals of Cerconychia livida Klapálek, 1913 , and of singletons belonging to four additional species. Our survey demonstrates that, in forewing, a fusion of the anterior-most branch of AA2 with AA1 occurs, a trait unique to the family. The occurrence of one to several cross-veins in the distal part of the ScP–RA area (both wing pairs), and of a supernumerary sigmoidal cross-vein in the MP–CuA area (hind wing), are also distinctive features, but are not unique to the family. A few other peculiar traits, which relevance remains unclear, are highlighted. Hopefully, our survey will allow close fossil relatives to be identified in the near future. [ABSTRACT FROM AUTHOR]

How transient hyperglycemia contributes to cerebro-vascular disease has been a challenge to study under controlled physiological conditions. We use amplified, ultrashort laser-pulses to physically disrupt brain-venule endothelium at targeted locations. This vessel disruption is performed in conjunction with transient hyperglycemia from a single injection of metabolically active D -glucose into healthy mice. The observed real-time responses to laser-induced disruption include rapid serum extravasation, platelet aggregation, and neutrophil recruitment. Thrombo-inflammation is pharmacologically ameliorated by a platelet inhibitor, by a scavenger of reactive oxygen species, and by a nitric oxide donor. As a control, vessel thrombo-inflammation is significantly reduced in mice injected with metabolically inert L -glucose. Venules in mice with diabetes show a similar response to laser-induced disruption and damage is reduced by restoration of normo-glycemia. Our approach provides a controlled method to probe synergies between transient metabolic and physical vascular perturbations and can reveal new aspects of brain pathophysiology. [ABSTRACT FROM AUTHOR]

Currently, studies of ancient faunal community networks have been based mostly on uniformitarian and functional morphological evidence. As an important source of data, taphonomic evidence offers the opportunity to provide a broader scope for understanding palaeoecology. However, palaeoecological research methods based on taphonomic evidence are relatively rare, especially for body fossils in lacustrine sediments. Such fossil communities are not only affected by complex transportation and selective destruction in the sedimentation process, they also are strongly affected by time averaging. Historically, it has been believed that it is difficult to study lacustrine entombed fauna by a small-scale quadrat survey. Herein, we developed a software, the TaphonomeAnalyst, to study the associational network of lacustrine entombed fauna, or taphocoenosis. TaphonomeAnalyst allows researchers to easily perform exploratory analyses on common abundance profiles from taphocoenosis data. The dataset for these investigations resulted from fieldwork of the latest Middle Jurassic Jiulongshan Formation near Daohugou Village, in Ningcheng County of Inner Mongolia, China, spotlighting the core assemblage of the Yanliao Fauna. Our data included 27,000 fossil specimens of animals from this deposit, the Yanliao Fauna, whose analyses reveal sedimentary environments, taphonomic conditions, and co-occurrence networks of this highly studied assemblage, providing empirically robust and statistically significant evidence for multiple Yanliao habitats. A new method and its companion software to study the associational network of lacustrine entombed fauna, or taphocoenosis. The application allows researchers to easily perform exploratory analyses on common abundance profiles from taphocoenosis data. [ABSTRACT FROM AUTHOR]

Crop nitrogen content inversion based on UAV (Unmanned Aerial Vehicle) hyperspectral data is vital for addressing global food supply challenges. Many studies have estimated nitrogen content via simple linear regression using a single vegetation index, multiple vegetation indices, hyperspectral representation, and simple structural transformation. Utilizing UAV hyperspectral data of the winter wheat canopy and leveraging the benefits of fractional differential processing to enhance spectral details, traditional hyperspectral vegetation indices were established, and characteristic parameters derived from spectral position and canopy area were extracted. Then, winter wheat plant nitrogen content models with different spectral information characteristics were highlighted, optimally selected and verified. Results reveal that when the original canopy spectrum is processed using the fractional differential, the association between hyperspectral reflectance and nitrogen levels in winter wheat plants can be effectively enhanced. Fractional differential spectra represent outstanding effects on refining spectral details. The findings provide valuable insights into the potential of hyperspectral fractional differential spectra to enhance the precision of nitrogen estimation in winter wheat. [ABSTRACT FROM AUTHOR]

In this paper, a hybrid flexible oscillating heat pipe (FOHP), characterized by a hot/cold-end length of about 1.07 m, with the adiabatic section made of fluororubber materials and heating/cooling sections made of micro-grooved copper tubes was designed and fabricated. Deionized water was used as the working fluid at volumetric filling ratios of 50%, 60% and 70%. The thermal performance of FOHP with different structural styles created by the deformation of adiabatic section and changing the spatial arrangement of evaporator and condenser were experimental tested and compared. Results show that the FOHP could function well and exhibited highly spatial flexibility and acceptable heat transfer performance. The bending of adiabatic section partially degrades the start-up and heat transfer characteristics of FOHP, largely depend on the deformation extent. The FOHP provides a promising solution for the thermal management of some spatial complicated energy utilization systems. [ABSTRACT FROM AUTHOR]

Protein degradation occurs during the processing of dry‐cured ham, which has important influences on the flavor and quality of products. The aim of this work was to study the degradation kinetics of myofibrillar proteins (MPs) and sarcoplasmic proteins (SPs) extracted from the biceps femoris muscle during the processing of Xuan'en ham. A relationship between protein degradation and the flavor formation was found. During the processing of Xuan'en ham, MPs and SPs were mainly degraded in the salting stage and incipient fermentation. Accompanied by protein degradation, the content of carbonyl group in SPs increased gradually, but in MPs, it first increased and then decreased. Interconversion between sulfhydryl and disulfide bonds was investigated during this processing. Oxidation, degradation, and thermal effects significantly affected the surface hydrophobicity of proteins. More than one hundred volatile compounds have been identified at each stage of ham preparation. Among them, organic acids were the predominant group, followed by hydrocarbons, aldehydes, alcohols, ketones, and esters. [ABSTRACT FROM AUTHOR]

Idiopathic pulmonary fibrosis (IPF) is a progressive and irreversible interstitial pulmonary disease due to chronic inflammatory responses. The prognosis of IPF is very poor, however, the therapeutic options are very limited. Previously we developed a polymeric micellar drug delivery system of carbon monoxide (CO) that is a pivotal anti-inflammatory gaseous molecule, i.e., SMA/CORM2, which exhibited therapeutic potentials against dextran sulfate sodium (DSS)-induced mouse colitis and acetaminophen (APAP) induced liver injury. Along this line, here we investigate the applicability of SMA/CORM2 on IPF using a bleomycin (BLM)-induced pulmonary fibrosis model. Severe inflammation and the consequent pulmonary fibrosis were triggered by BLM, whereas SMA/CORM2 treatment remarkably suppressed the inflammation progression and ameliorated the formation of fibrosis. CO is the effector molecule of SMA/CORM2, which exerted the therapeutic/protective effect mostly through suppressing the reprogramming of anti-inflammatory macrophages as revealed by the decreased expressions of CD206 and arginase-1 that were remarkably upregulated by BLM exposure. The suppression of macrophage polarization accompanied the downregulated hypoxia-inducible factor-1α (HIF-1α) and its target molecule heme oxygenase-1 (HO-1), suggesting a HIF-1α/HO-1 pathway for modulating macrophage reprogramming. As the downstream event of anti-inflammatory macrophage polarization, the alveolar epithelial to mesenchymal transition that is the major source of myofibroblast, the hallmark of IPF, was significantly suppressed by SMA/CORM2 via a TGF-β/Smad2/3 pathway. Compared to native CORM2 of equivalent dose, SMA/CROM2 exhibited a much better protective effect indicating its superior bioavailability as an enhanced permeability and retention (EPR) effect-based nanomedicine. We thus anticipate the application of SMA/CORM2 as a therapeutic candidate for IPF as well as other inflammatory diseases and disorders. [Display omitted] • SMA/CORM2 exhibits therapeutic potential for BLM induced pulmonary fibrosis. • SMA/CORM2 suppresses anti-inflammatory macrophage reprogramming upon CO production. • Suppression of EMT by TGF-β/Smad2/3 pathway confers to protection against fibrosis. • Shift of macrophage polarization is via suppressing HIF-1α/HO-1 signals by CO. • SMA/CORM2 reveals superior bioavailability than native CORM2 with high safety. [ABSTRACT FROM AUTHOR]

[Display omitted] • Chronic Cd exposure induces EMT and malignant changes of prostate cancer cells. • EMT is triggered via a TGF-β- independent pathway. • ROS-mediated ER stress/ Smad3 pathway play essential role on Cd induced EMT. • NAC could reverse malignant changes of prostate cancer cells evoked by Cd. • Antioxidant or targeting ER stress may be a useful tool to control prostate cancer. In this study, we aimed to elucidate the role of chronic cadmium (Cd) exposure in epithelial-mesenchymal transition (EMT) and thus malignant phenotypic changes of prostate cancer cells. Prostate cancer cells (PC-3 and DU145) were exposed to a non-toxic level (0.5 or 2 μM) of Cd for up to 3 months, which resulted in significantly promoted migration and invasion of the cells. These phenotypic changes were considered to be the consequence of enhanced EMT as evidenced by diminished expression of E-cadherin and increased vimentin expression. Regarding the mechanisms of Cd-induced EMT, we found Smad3 was activated but without upregulation of TGF-β. Alternatively, we found endoplasmic reticulum (ER) stress of prostate cancer cells was significantly evoked, which was parallel with the increased reactive oxygen species (ROS). Removal of ROS by N-acetylcysteine significantly reduced ER stress in prostate cancer cells, followed by the decrease of Smad3 phosphorylation and expression of nuclear Snail, resulting in the inhibition of EMT and malignant phenotypic changes of prostate cancer cells. These findings indicated a new TGF-β independent, ROS-mediated ER stress/Smad signaling pathway in chronic Cd exposure-induced EMT of prostate cancer cells, which could be a novel mechanism involved in cadmium-mediated cancer cells malignant transformation. Accordingly, ROS-induced ERs may become a novel preventive and therapeutic target for cancer. [ABSTRACT FROM AUTHOR]

Background: The rapidly increasing case reports revealed that neuronal intranuclear inclusion disease (NIID) had concomitant other system symptoms besides nervous system symptoms. In this study, we systematically evaluated the symptoms, signs, auxiliary examination, and pathological changes in different systems in NIID patients. Methods: NIID patients were confirmed by examining GGC repeats in the NOTCH2NLC gene. Clinical data of NIID patients including symptoms, signs, and auxiliary examinations were collected for analysis. Ubiquitin and p62 were detected in different tissues from previous surgical samples. Results: Fifty‐one NIID patients from 17 families were included in this study. Except neurological symptoms, clinical manifestations from other systems were very notable and diverse. The proportions of different system symptoms were 88.2% in nervous system, 78.4% in respiratory system, 72.5% in circulatory system, 72.5% in locomotor system, 66.7% in urinary system, 64.7% in digestive system, 61.5% in reproductive system, and 50.0% in endocrine system. In addition, other common symptoms included sexual dysfunction (43.1%), pupil constriction (56.9%), blurred vision (51.0%), and hearing loss (23.5%). Ubiquitin and p62‐positive cells were found in different tissues and systems in 24 NIID patients with previous surgery. Initial symptoms of NIID and median onset age in different systems also revealed system heterogeneity of NIID. Interpretation: For the first time, we systematically demonstrated that NIID is a heterogeneous and systemic neurodegenerative disease by providing clinical and pathological evidence. In addition to the nervous system, the clinical symptomatic and pathological spectrum of NIID has been extended to almost all systems. [ABSTRACT FROM AUTHOR]

BACKGROUND: Studies have shown that the nano-hydroxyapatite coating on the surface of zirconia has not only high strength and toughness, but also good biocompatibility. It is an ideal substitute for hard tissue. However, the coating is easy to fall off from the surface of zirconia, which is a fatal defect. OBJECTIVE: To prepare functionally graded bioceramics with pure zirconia as matrix, gradient layer in the middle and nano-hydroxyapatite on the surface by gradient composite technology and to screen the optimal mechanical properties and sintering temperature. METHODS: Using zirconia and nano hydroxyapatite powder as raw materials, ceramic specimens were prepared by the lamination method in powder metallurgy. According to the thickness of zirconia layer, three groups A (40 mm), B (30 mm) and C (20 mm) were designated. Each group was sub-divided into three subgroups 1 (3 layers), 2 (Slayers) and 3 (7 layers). Thus, there were 162 ceramic specimens in nine subgroups. The ceramic specimens were sintered at different temperatures (1 300, 1 350, 1 400, 1 450, 1500, and 1 550 °C) and then processed into rectangular specimens for mechanical property testing. RESULTS AND CONCLUSION: The zirconia-based nano-hydroxyapatite functionally graded material can be formed by 10 MPa single side vertical pressure. With the increases in the number of gradient layers and sintering temperature, the mechanical properties of the functionally graded bioceremics in each group were enhanced. The functionally graded bioceramics had the optimal mechanical properties when sintering temperature was 1 550 °C. the number of gradient layers was 7. and substrate thickness was 40 mm. The optimal mechanical property of the functionally graded bioceramics produced at above parameter was significantly superior to that produced at other eight sets of parameters (P < 0.05). According to the optimal gradient design, the zirconia-based nano-hydroxyapatite functionally graded ceramic specimens prepared by high temperature sintering technique have stronger mechanical properties. [ABSTRACT FROM AUTHOR]

Recycling endosomes regulate plasma membrane recycling. Recently, recycling endosome–associated proteins have been implicated in the positioning and orientation of the mitotic spindle and cytokinesis. Loss of MYO5B, encoding the recycling endosome–associated myosin Vb, is associated with tumor development and tissue architecture defects in the gastrointestinal tract. Whether loss of MYO5B expression affects mitosis is not known. Here, we demonstrate that loss of MYO5B expression delayed cytokinesis, perturbed mitotic spindle orientation, led to the misorientation of the plane of cell division during the course of mitosis, and resulted in the delamination of epithelial cells. Remarkably, the effects on spindle orientation, but not cytokinesis, were a direct consequence of physical hindrance by giant late endosomes, which were formed in a chloride channel–sensitive manner concomitant with a redistribution of chloride channels from the cell periphery to late endosomes upon loss of MYO5B. Rab7 availability was identified as a limiting factor for the development of giant late endosomes. In accordance, increasing rab7 availability corrected mitotic spindle misorientation and cell delamination in cells lacking MYO5B expression. In conclusion, we identified a novel role for MYO5B in the regulation of late endosome size control and identify the inability to control late endosome size as an unexpected novel mechanism underlying defects in cell division orientation and epithelial architecture. Loss of the recycling endosome-associated motor protein myosin Vb causes the formation of giant late endo-lysosomes; these in turn hinder the orientation of the mitotic spindle and chromosome segregation. Deregulated endosome size thus hampers faithful cell division. [ABSTRACT FROM AUTHOR]

The first discovery of an insect wing from the Taiyuan Formation, near Yangquan City, Shanxi Province, China, is described. The combination of its wing venation characters makes it difficult to assign it to any known major Paleozoic group. The comparison is made among the new material, stem-Orthoptera species, and "fossil Grylloblattodea". Further investigation on fossil insects from this locality is needed. [ABSTRACT FROM AUTHOR]

Acetaminophen (APAP) overdose-induced hepatotoxicity is the most common cause of acute liver failure. Excessive generation of reactive oxygen species (ROS) and inflammatory responses are the major causes of necrosis and/or necroptosis of the liver cells. Currently, the treatment options for APAP-induced liver injury are very limited, N-acetylcysteine (NAC) is the only approved drug to treat APAP overdose patients. It is of great necessity to develop new therapeutic strategies. In a previous study, we focused on the anti-oxidative, anti-inflammatory signal molecule carbon monoxide (CO), and developed a nano-micelle encapsulating CO donor, i.e., SMA/CORM2. Administration of SMA/CORM2 to the mice exposed to APAP significantly ameliorated the liver injury and inflammatory process, in which modulating macrophage reprogramming plays a critical role. Along this line, in this study, we investigated the potential effect of SMA/CORM2 on toll-like receptor 4 (TLR4) and high mobility group protein B1 (HMGB1) signaling pathways that are known to be closely involved in many inflammatory responses and necroptosis. In a mouse APAP-induced liver injury model, similar to the previous study, SMA/CORM2 at 10 mg/kg remarkably improved the condition of the liver after injury as evidenced by histological examination and liver function. During the process of liver injury triggered by APAP, TLR4 expression gradually increased over time, and it was significantly upregulated as early as 4 h after APAP exposure, whereas, an increase of HMGB1 was a late-stage event. Notably, SMA/CORM2 treatment suppressed significantly both TLR4 and HMGB1, consequently inhibiting the progression of inflammation and liver injury. Compared to CORM2 without SMA modification (native CORM2) of 1 mg/kg that is equivalent to 10 mg/kg of SMA/CORM2 (the amount of CORM2 in SMA/CORM2 is 10% [w/w]), SMA/CORM2 exhibited a much better therapeutic effect, indicating its superior therapeutic efficacy to native CORM2. These findings revealed that SMA/CORM2 protects against APAP-induced liver injury via mechanisms involving the suppression of TLR4 and HMGB1 signaling pathways. Taking together the results in this study and previous studies, SMA/CORM2 exhibits great therapeutic potential for APAP overdose-induced liver injury, we thus anticipate the clinical application of SMA/CORM2 for the treatment of APAP overdose, as well as other inflammatory diseases. [Display omitted] [ABSTRACT FROM AUTHOR]

Summary Symbiosis [ 1 ], understood as prolonged interspecific association, is as ancient as the eukaryotic cell [ 2, 3 ]. A variety of such associations have been reported in the continental fossil record, albeit sporadically. As for mites, which as a group have been present since the Devonian (ca. 390 mya) [ 4, 5 ] and are involved in a tremendous variety of modern-day symbioses, reported associations are limited to a few amber-preserved cases [ 6–11 ], with the earliest instance in the Cretaceous (ca. 85 mya) [ 11 ]. As a consequence, the antiquity and origin of associations involving small-sized mites and larger animals are poorly understood. Here we report, recovered from the Carboniferous Xiaheyan locality (ca. 320 mya), an oribatid mite located on the thorax of an extinct relative of grasshoppers, crickets, and katydids [ 12 ]. The mite was investigated using several methods, including phase-contrast tomography. The detailed morphological data allowed the placement of the mite in a new family within Mixonomata, whose fossil record is thus extended by ca. 250 Ma. Specimen and abundance distribution data derived from the fossil insect sample indicate that specimens from the corresponding excavation site were buried rapidly and were sub-autochthonous, indicating a syn vivo association. Moreover, the mite is located in a sequestered position on the insect. The observed interaction best fits the definition for phoresy, in which the benefit is transport and protection for the mite. This discovery demonstrates that this association, a trait shared by representatives of the most speciose mite taxa, arose very early during mite evolution. [ABSTRACT FROM AUTHOR]

Evaluation of bone marrow involvement (BMI) by conventional bone marrow biopsy (BMB) can generate false-negative results if marrow disease is focal. The sensitivity of 18F-2-fluoro-2-deoxy- d-glucose positron emission tomography/computed tomography (FDG-PET/CT) in assessing BMI in extranodal NK/T cell lymphoma (ENKL) has not been determined. We retrospectively collected clinical data from a series of 55 patients with newly diagnosed ENKL, who have received both FDG-PET/CT and BMB prior to treatment. BMB results were used as reference standard. Twelve patients (21.8 %) were considered positive lymphomatous infiltration by FDG-PET/CT (PET-CT/BM+), and five patients (9 %) were identified positive by BMB (BMB/BM+). There was a discordant result in seven patients who were PET-CT/BM+ but BMB/BM−. The sensitivity and specificity of FDG-PET/CT for identifying BMI were 100 and 86 %, respectively. Then, we analyzed the overall survival (OS) and progression-free survival (PFS) of patients who were PET-CT/BM+ and PET-CT/BM−. The median follow-up time was 16 months (range, 3 to 43 months). PET-CT/BM+ patients possessed worse 2-year OS than PET-CT/BM− patients (84.8 vs 67.9 %, P < 0.05). The estimated 2-year PFS for PET-CT/BM− and PET-CT/BM+ patients were 72.7 and 41.9 % ( P < 0.05), respectively. However, it was hard to conclude that patients who were PET-CT/BM+ had similar survivals to advanced-stage patients due to the low number of patients who were PET-CT/BM+. In conclusion, FDG-PET/CT can complementally detect positive BMI patients missed by BMB in ENKL. The utility of FDG-PET/CT for defining bone marrow status has important prognostic value. [ABSTRACT FROM AUTHOR]

Background: Fossil species that can be conclusively identified as stem-relatives of stick- and leaf-insects (Phasmatodea) are extremely rare, especially for the Mesozoic era. This dearth in the paleontological record makes assessments on the origin and age of the group problematic and impedes investigations of evolutionary key aspects, such as wing development, sexual size dimorphism and plant mimicry. Methodology/Principal Findings: A new fossil insect species, Cretophasmomima melanogramma Wang, Béthoux and Ren sp. nov., is described on the basis of one female and two male specimens recovered from the Yixian Formation (Early Cretaceous, ca. 126±4 mya; Inner Mongolia, NE China; known as ‘Jehol biota’). The occurrence of a female abdominal operculum and of a characteristic ‘shoulder pad’ in the forewing allows for the interpretation of a true stem-Phasmatodea. In contrast to the situation in extant forms, sexual size dimorphism is only weakly female-biased in this species. The peculiar wing coloration, viz. dark longitudinal veins, suggests that the leaf-shaped plant organ from the contemporaneous ‘gymnosperm’ Membranifolia admirabilis was used as model for crypsis. Conclusions/Significance: As early as in the Early Cretaceous, some stem-Phasmatodea achieved effective leaf mimicry, although additional refinements characteristic of recent forms, such as curved fore femora, were still lacking. The diversification of small-sized arboreal insectivore birds and mammals might have triggered the acquisition of such primary defenses. [ABSTRACT FROM AUTHOR]

• Long-term soil nutrient deficiency caused chlorophyll decrease and leaf etiolation. • Nutrient deficiency decreased total amino acids, caffeine and many aroma compounds. • Decrease in quality-related metabolites was related to structural gene expression. • Long-term nutrient deficiency reduced the quality of tea color, taste and aroma. The long-term cultivation of tea plants without fertilization can severely decrease yield, but it remains unclear whether this soil nutrient deficiency affects tea quality. In this study, tea plants (Camellia sinensis (L.) Kuntze) cultivated in unfertilized soil for 11 years were analyzed. The soil nutrient deficiency down-regulated protochlorophyllide oxidoreductase-encoding gene expression, which adversely affected chlorophyll biosynthesis, ultimately leading to leaf etiolation. Because of decreased synthesis and increased degradation in response to nutrient deficiency, l -theanine content decreased to 11.4% of the control level, which increased the phenol-ammonia ratio and decreased taste quality. Soil nutrient deficiency also decreased the abundance of many aroma compounds (e.g., green leaf volatile, linalool and its oxides, and methyl salicylate). Thus, nutrient deficiency adversely influences tea color, taste, and aroma. This study provides researchers and tea growers with important information regarding the effects of soil nutrient deficiency on tea quality and the rational fertilization of tea gardens. [ABSTRACT FROM AUTHOR]

Abstract: Robust and real-time foreground segmentation is a crucial topic in many computer vision applications. Background subtraction is a typical approach to segment foreground by comparing each new frame with a learned model of the scene background in image sequences taken from a static camera. In this paper, we propose a flexible method to estimate the background model with the finite Gaussian mixture model. A stochastic approximation procedure is used to recursively estimate the parameters of the Gaussian mixture model, and to simultaneously obtain the asymptotically optimal number of the mixture components. Our method is highly memory and time efficient. Moreover, it can effectively deal with the many scenes, such as the indoor scene, the outdoor scene, and the clutter scene. The experimental results show our method is efficient and effective. [Copyright &y& Elsevier]

Knowledge of the establishment of the upper and middle reaches of the Yellow River is essential for understanding the origin of the Yellow River and the interplay between tectonic deformation and climate change in the region. However, the timing of the integration of the upper and middle reaches of the Yellow River is debated, ranging from the Late Miocene to the Late Pleistocene. Here we present detrital zircon U Pb age spectra and heavy mineral assemblages of sediments of Pliocene through Pleistocene age from the Weihe Basin and Sanmen Basin in the middle reach of the Yellow River. The post 1.8 Ma sediments of the Weihe Basin have similar detrital zircon U Pb age spectra and heavy mineral assemblages to those of the modern Weihe River, and the post ~5 Ma sediments of the Sanmen Basin have similar U Pb age spectra to those of the modern middle Yellow River. Our results reveal that a fluvial system similar to that of the modern upper-middle Yellow River was established by ~5 Ma. We propose that this was most likely the result of tectonic deformation in the middle and upper reaches of the Yellow River. • Zircon and heavy mineral evidence show the upper-middle of YR integrated at 5 Ma. • A fluvial system similar to the modern Weihe drainage existed by 1.8 Ma or 2.6 Ma. • The integration was likely controlled by tectonic deformation in NE Tibetan Plateau. [ABSTRACT FROM AUTHOR]

Background: The pro-oncogenic anterior gradient 2 (AGR2) is involved in tumor growth and drug resistance of breast cancer. Mechanisms that regulate expression of AGR2 still need to be elucidated. Methods: In this study, expression levels of AGR2 and miR-135b-5p were analyzed in different breast cancer cell lines as well as in clinical breast cancer tissues. The in vitro and in vivo functional effect of AGR2 and miR-135b-5p were also investigated. A luciferase reporter assay was applied to confirm the interaction between miR-135b-5p and AGR2 mRNA. Results: We identified AGR2 as a target of miR-135b-5p. Expression of AGR2 was up-regulated in doxorubicin-resistant breast cancer cells. AGR2 mediated doxorubicin-sensitivity of breast cancer cells both in vitro and in vivo. miR-135b-5p negatively regulated AGR2-expression of breast cancer cells increasing doxorubicin-sensitivity. However, miR-135b-5p was down-regulated in doxorubicin-resistant breast cancer cells as well as during treatment with doxorubicin, which might be a probable reason for over-expression of AGR2. Up-regulation of miR-135b-5p increased doxorubicin-sensitivity of breast cancer cells in vivo. In addition, levels of AGR2 negatively correlated with levels of miR-135b-5p in clinical breast cancer tissue samples. Conclusion: Our results highlight the potential of miR-135b-5p as a target for treating AGR2-expressing breast cancer with doxorubicin-resistance. [ABSTRACT FROM AUTHOR]

The discovery and creation of biocatalysts for plant biomass conversion are essential for industrial demand and scientific research of the plant cell wall. α-1,2 and α-1,3-l-arabinofuranosidases are debranching enzymes that catalyzing hydrolytic release of α-l-arabinofuranosyl residues in plant cell wall. Gene database analyses shows that GH62 family only contains specific α-l-arabinofuranosidases that play an important role in the degradation and structure of the plant cell wall. At present, there are only 22 enzymes in this group has been characterized. In this study, we cloned a novel α-1,3-arabinofuranosidase gene (poabf62a) belonging to glycoside hydrolase family 62 from Penicillium oxalicum sp. 68 and expressed it in Pichia pastoris. The molecular mass of recombinant PoAbf62A was estimated to be 32.9 kDa. Using p-nitrophenyl-α-l-arabinofuranoside (pNPαAbf) as substrate, purified PoAbf62A exhibited an optimal pH of 4.5 and temperature of 35 °C. Results of methylation and 13C NMR analyses showed that PoAbf62A was exclusively α-1,3-arabinofuranosidase, specific for cleavage of α-1,3-arabinofuranosyl residues, and with the absence of activity towards α-1,2-arabinofuranose and α-1,5-arabinofuranose. Therefore, PoAbf62A exhibits high activity on sugar beet arabinan and wheat arabinoxylan, because their branched side chain are decorated with α-1,3-arabinofuranose. On the other hand, there is a lack of activity with linear-α-l-1,5-arabinan and xylan that only contained α-l-1,5-arabinofuranose or β-1,4-xylose. The α-1,3-arabinofuranosidase activity identified here provides a new biocatalytic tool to degrade hemicellulose and analyze the structure of plant cell walls. [ABSTRACT FROM AUTHOR]

A plasmonic Ag/TiO2 photocatalytic composite was designed by selecting Ag quantum dots (Ag QDs) to act as a surface plasmon resonance (SPR) photosensitizer for driving the visible-light driven photoelectrocatalytic hydrogen evolution. Vertically oriented hierarchical TiO2 nanotube arrays (H-TiO2-NTAs) with macroporous structure were prepared through a two-step method based on electrochemical anodization. Subsequently, Ag QDs, with tunable size (1.3-21.0 nm), could be uniformly deposited on the H-TiO2 NTAs by current pulsing approach. The unique structure of the as-obtained photoelectrodes greatly improved the photoelectric conversion efficiency. The as-obtained Ag/H-TiO2-NTAs exhibited strong visible-light absorption capability, high photocurrent density, and enhanced photoelectrocatalytic (PEC) activity toward photoelectrocatalytic hydrogen evolution under visible-light irradiation (λ > 420 nm). The enhancement in the photoelectric conversion efficiency and activity was ascribed to the synergistic effects of silver and the unique hierarchical structures of TiO2 nanotube arrays, strong SPR effect, and anti-shielding effect of ultrafine Ag QDs. [ABSTRACT FROM AUTHOR]