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In the field of bone research, the importance of the function of skeletal macrophages (sMF) and their crucial role in immune homeostasis and bone regeneration has been extensively studied. The aim of the present systematic review was to summarize the role of sMF in bone fracture healing and to evaluate their potential for immunoregulatory therapy in bone regeneration. A systematic literature search of PubMed and Embase® was performed to retrieve studies on the role of sMF in bone injury repair. The Systematic Review Centre for Laboratory animal Experimentation tool was used to assess the risk of bias of the studies included. A total of four articles were included in the present review. A relatively high risk of bias was identified in the included articles as none of the assessors in these studies were blinded. sMF were defined by the surface markers F4/80+, Mac-2-/low, TRAP-, CD169+, Ly6G- and CD115low. All of the studies provided support for the essential role of sMF in intramembranous ossification or endochondral ossification during fracture healing. F4/80+Mac-2-CD169+ sMF are a promising therapeutic target for immunoregulatory therapy of bone repair due to their essential role in bone formation and homeostasis. Future studies aimed at profiling and modulating sMF to promote bone regeneration are required. [ABSTRACT FROM AUTHOR]

Multi-time-scale variabilities of the Indian Ocean (IO) temperature over 0–700m are revisited from the perspective of vertical structure. Analysis of historical data for 1955–2018 identifies two dominant types of vertical structures that account for respectively 70.5% and 21.2% of the total variance on interannual-to-interdecadal time scales with the linear trend and seasonal cycle removed. The leading type manifests as vertically coherent warming/cooling with the maximal amplitude at; 100m and exhibits evident interdecadal variations. The second type shows a vertical dipole structure between the surface (0–60 m) and subsurface (60–400 m) layers and interannual-to-decadal fluctuations. Ocean model experiments were performed to gain insights into underlying processes. The vertically coherent, basinwide warming/cooling of the IO on an interdecadal time scale is caused by changes of the Indonesian Throughflow (ITF) controlled by Pacific climate and anomalous surface heat fluxes partly originating from external forcing. Enhanced changes in the subtropical southern IO arise from positive air–sea feedback among sea surface temperature, winds, turbulent heat flux, cloud cover, and shortwave radiation. Regarding dipole-type variability, the basinwide surface warming is induced by surface heat flux forcing, and the subsurface cooling occurs only in the eastern IO. The cooling in the southeast IO is generated by the weakened ITF, whereas that in the northeast IO is caused by equatorial easterly winds through upwelling oceanic waves. Both El Niño–Southern Oscillation (ENSO) and IO dipole (IOD) events are favorable for the generation of such vertical dipole anomalies. [ABSTRACT FROM AUTHOR]

Cellular collective motion in confluent epithelial monolayers is involved in many processes such as embryo development, carcinoma invasion, and wound healing. The development of new chemical strategies to achieve largescale control of cells' collective motion is essential for biomedical applications. Here a series of DNA nanostructures with different dimensions were synthesized and their influences on cells' collective migration and packing behaviors in epithelial monolayers were investigated. We found that the framed DNA nanoassemblies effectively reduced the cells' speed by increasing the rigidity of cells, while the lipid-DNA micelles had a more pronounced effect on cells' projection area and shape factor. These DNA nanostructures all significantly enhanced the dependence of cells' speed on their shape factor. Our results indicate that cells' mobility in monolayers can be manipulated by chemical intercellular interactions without any genetic intervention. This may provide a new chemical strategy for tissue engineering and tumor therapy. [ABSTRACT FROM AUTHOR]

In order to enhance wear resistance of cold work molds, WC−10Co4Cr coating was fabricated on Cr12MoV steel by laser cladding. The morphologies, chemical compositions, and phases of obtained coatings were analyzed using a scanning electron microscopy (SEM), energy disperse spectroscopy, and X−ray diffraction, respectively. The effect of laser power on the tribological performance was analyzed using a ball−on−plate friction machine, and the wear mechanism was also discussed. The results show that the WC−10Co4Cr coating is composed of WC and Co6W6C phases, and the average hardness of coating cross−sections fabricated at the laser power of 1200, 1500, and 1800 W was 1296, 1375, and 1262 HV0.5, respectively, in which that fabricated at the laser power of 1500 W is the highest among the three kinds of coatings. The average coefficients of friction of coatings fabricated at the laser power of 1200, 1500, and 1800 W are 0.61, 0.52, and 0.59, respectively; and the corresponding wear rates are 64.38, 35.38, and 123.92 μm3•N−1•mm−1, respectively, showing that the coating fabricated at the laser power of 1500 W has best friction reduction and wear resistance. The wear mechanism of WC−10Co4Cr coating is fatigue wear and abrasive wear, which is contributed to the increase of hard WC mass fraction. [ABSTRACT FROM AUTHOR]

The article reports about how, to maintain brain homeostasis, a unique interface known as the blood-brain barrier (BBB) is formed between the blood circulation and the central nervous system (CNS). Topics include how Mfsd2a is essential for sphingosine-1-phosphate (S1P) export from endothelial cells in the brain; and how Mfsd2a and Spinster homolog 2 (Spns2) form a protein complex to ensure the efficient transport of S1P.

In natural images, it remains challenging to estimate dissimilarities between image elements for scene representation due to gradual variations of illuminations, textures or clutters. To tackle this problem, we utilise a path-based bottleneck analysis method that captures the semantic information between image elements to measure the dissimilarity. By integrating both the spatial continuity and feature consistency into the understanding of the semantic information, we detect the bottlenecks on the proposed double-S path to define the bottleneck distance, which demonstrates a favourable capability of grouping image elements that follow a similar pattern and separating different ones. In the experiments, the method is proved to be robust to noises and invariant to changing illumination and arbitrary scales in natural images. Tests on some challenging datasets validate the advantage of applying the path-based bottleneck distance in image ranking and salient object detection. [ABSTRACT FROM AUTHOR]

In the global context of reducing the use of fossil fuels and turning to the usage of electric vehicles. The location and ease of charging stations have the crucial impact on early adopters and volunteers who will eventually become mainstream consumers. In this transition, national planning needs to take into account the final network planning of charging stations and the development and evolution of charging station systems, and seek to develop policies to facilitate the transition of vehicles to electric vehicles, making the best solution for each country. In this paper, we first determine that the standard measurement of full electrified electric vehicles should reach 90%. By fitting and forecasting the data of Tesla electrification rate in recent years, we draw the conclusion that it is difficult to realize a complete electrification at present. Based on this conclusion, we estimate that the number of electric vehicle charging stations required in the United States is about 29.7 million under the constraints of demand and service by using the multi-objective programming model. Moreover, we have suggested to countries the factors to be taken into account in the development of electric vehicles and the timing of banning the use of fuel vehicles. Finally, we use the asymmetric Nash negotiation model to discuss the impact of the number of vehicles, population density, road network density, GDP, geographical environment and other factors. The results show that the urban, suburban, and rural areas have reached 63.52%, 23.41%, and 13.07%. [ABSTRACT FROM AUTHOR]

Achieving reliable and energy-saving broadcast is the main issue discussed in this study. Firstly, a multi-hop broadcast model is introduced, and the energy consumption and reliability of the network are defined in this study. Then five broadcast-based automatic repeat request (ARQ) protocols (automatic retransmission N times, stop-and-wait end-to-end-ARQ, stop-and-wait hop-by-hop-ARQ, stop-and-wait hop-by-hop oriented implicit ARQ, stop-and-wait hop-by-hop implicit and explicit ARQ) are proposed to realise the reliable transmission. Secondly, based on five protocols, the relationship between the system reliability and the number of retransmissions of the root node is established analytically, and the maximum number of retransmissions is solved under the required system reliability. Thirdly, the energy consumptions of the root node are calculated, and then the analytical expressions of the minimum system energy consumption are obtained separately according to five broadcast-based retransmission mechanisms. Finally, the relationships between the maximum number of retransmissions, energy consumption and reliability, the broadcast probability and feedback probability are discussed in the numerical analysis. Specially, for better energy-saving, the modulation technique should be adopted to choose suitable protocol based on a dynamic hop threshold. [ABSTRACT FROM AUTHOR]

Taiwan's National Health Insurance (NHI) implemented in 1995, covers over 99% of Taiwan population of 23 million with positive health outcome, the lowest administration cost in the world of 2 percentand high satisfactory rate. National LTC Need Study (NLTCNS) conducted in 2009-2011 and 2015-2016, indicated Taiwan's disability rate in general population is 2.89%; in elderly population is 16.50%; the disabled population is estimated to raise from 740,000 in 2014 to 1,200,000 in 2031. After implementation of National Health Insurance in 1995, Taiwan government initiated the first 10 year Long Term Care (LTC1.0) Plan in 2008 ending 2017. During initial planning for LTC 2.0, government recognized a major barrier to implement LTC effectively was due to separate operations and lack of coordination of health and social welfare systems. After three years' planning, the Ministry of Health and Welfare (MHW) was established by combining Bureaus of Health and Social Welfare in 2013. Although NLTCNS indicated high public support for long term care insurance (87%), newly elected administration decide paying through a tax-based financing. Integrated Health and LTC Study (IHLTCS) was funded in 2014-2015 to explore integration strategies and resources needed to support system integration. Researchers and policy makers visited the U.S. conducted model reviews. Presenter will discuss findings from both NLTCNS and IHLTCS to describe Taiwan's disability population, service utilization, issues causing fragmentation and stakeholder opinions. In addition, presenter will discuss findings from data analysis, model reviews, focus groups and official interviews, four (4) targeted areas were recommended for initiation and the nature of support structure for implementation. [ABSTRACT FROM AUTHOR]

Inflammasomes are one kind of important innate immune defense against viral and bacterial infections. Several inflammasome- forming sensors detect molecular patterns of invading pathogens and then trigger inflammasome activation and/or pyroptosis in infected cells, and viruses employ unique strategies to hijack or subvert inflammasome activation. Infection with herpesviruses induces the activation of diverse inflammasomes, including AIM2 and IFI16 inflammasomes; however, how Kaposi's sarcoma- associated herpesvirus (KSHV) counteracts inflammasome activation largely remains unclear. Here, we reveal that the KSHV ORF37- encoded SOX protein suppresses AIM2 inflammasome activation independent of its viral DNA exonuclease activity and host mRNA turnover. SOX interacts with the AIM2 HIN domain through the C- terminal Motif VII region and disrupts AIM2:dsDNA polymerization and ASC recruitment and oligomerization. The Y443A or F444A mutation of SOX abolishes the inhibition of AIM2 inflammasome without disrupting SOX nuclease activity, and a short SOX peptide is capable of inhibiting AIM2 inflammasome activation; consequently, infection with SOX- null, Y443A, or F444A Bac16 recombinant viruses results in robust inflammasome activation, suppressed lytic replication, and increased pyroptosis in human lymphatic endothelial cells in an AIM2- dependent manner. These results reveal that KSHV SOX suppresses AIM2 inflammasome activation to promote KSHV lytic replication and inhibit pyroptosis, representing a unique mechanism for evasion of inflammasome activation during KSHV lytic cycle. [ABSTRACT FROM AUTHOR]

How left-right (LR) asymmetry emerges in a patterning field along the anterior-posterior axis remains an unresolved problem in developmental biology. Left-biased Nodal emanating from the LR organizer propagates from posterior to anterior (PA) and establishes the LR pattern of the whole embryo. However, little is known about the regulatory mechanism of the PA spread of Nodal and its asymmetric activation in the forebrain. Here, we identify bilaterally expressed Follistatin (Fst) as a regulator blocking the propagation of the zebrafish Nodal ortholog Southpaw (Spaw) in the right lateral plate mesoderm (LPM), and restricting Spaw transmission in the left LPM to facilitate the establishment of a robust LR asymmetric Nodal patterning. In addition, Fst inhibits the Activin-Nodal signaling pathway in the forebrain thus preventing Nodal activation prior to the arrival, at a later time, of Spaw emanating from the left LPM. This contributes to the orderly propagation of asymmetric Nodal activation along the PA axis. The LR regulation function of Fst is further confirmed in chick and frog embryos. Overall, our results suggest that a robust LR patterning emerges by counteracting a Fst barrier formed along the PA axis. [ABSTRACT FROM AUTHOR]

Background/Aims: miR-146a has recently been shown to promote cell proliferation, migration, and invasion in many cancers, but the role of miR-146a in clear cell renal cell carcinoma (ccRCC) remains unclear. Methods: Reverse transcription quantitative PCR (RTqPCR) was performed to investigate the mRNA expression of miR-146a and CADM2 in ccRCC tissues. The luciferase reporter assay, Western blotting, and ChIP assay were carried out to explore the promoter and the transcription factor of miR-146a. Moreover, the effect of miR-146a and CADM2 on ccRCC cells was explored using methyl thiazolyl tetrazolium, colony formation, and migration and invasion assays. The luciferase reporter assay, RT-qPCR, western blotting, and immunofluorescence assay were carried out to investigate whether CADM2 is directly regulated by miR-146a. A tumor xenograft model and immunohistochemical staining were used to examine the carcinogenic effect of miR-146a and CADM2 in vivo. Results: miR-146a has been shown to promote cell proliferation, migration, and invasion. Here, we found that miR-146a is highly expressed in ccRCC tissues, whereas CADM2 is down-regulated. Hypoxia can induce the expression of miR-146a by stimulating its promoter. In addition, we demonstrated that miR-146a promoted and CADM2 inhibited proliferation, migration, and invasion of ccRCC cells. The 3' untranslated region (UTR) luciferase reporter assay identified that miR-146a targeted the 3' UTR of CADM2 and negatively regulated its expression. Ectopic expression of CADM2 counteracted the promoting effect of miR-146a on cell proliferation, migration, invasion, and the epithelial-mesenchymal transition process. Conclusion: Together, the finding of down-regulation of CADM2 by miR-146a can provide new insights into ccRCC pathogenesis and might contribute to the development of novel therapeutic strategies. [ABSTRACT FROM AUTHOR]

NiCrAl–WC–Ti 3 SiC 2 composite coatings with the different Ti 3 SiC 2 mass fractions were prepared on H13 steel by laser cladding (LC). The influence of Ti 3 SiC 2 mass fraction on the tribological property of obtained composite coatings at 500 °C was investigated using a high temperature wear machine, and the roles of WC and Ti 3 SiC 2 in the friction process were discussed in detail. The results show that the coefficients of friction (COFs) and wear rates of NiCrAl–WC–Ti 3 SiC 2 composite coatings are increased with the Ti 3 SiC 2 mass fraction, exhibiting the appropriate Ti 3 SiC 2 mass fraction plays a certain role in the friction reduction and wear resistance, which are contributed to the coarsening of grains and the decrease of hardness. In addition, it is also found that the Ti 3 SiC 2 is reacted with the WC to generate SiC, TiC, TiWC 2 and other hard phases, and the amount of WC particles of coatings is decreased by the addition of Ti 3 SiC 2 , which is the main factor for the decline of tribological performance. [Display omitted] • The TiWC 2 , SiC and TiC phases are generated by the reactions between the Ti 3 SiC 2 and the WC. • The grains of NiCrAl-WC-Ti 3 SiC 2 coatings become coarser with Ti 3 SiC 2 mass fraction. • The NiCrAl-40%WC-3%Ti 3 SiC 2 coating has the best tribological property. • The wear mechanism of NiCrAl-WC-Ti 3 SiC 2 coatings is adhesive, abrasive and oxidation wear. [ABSTRACT FROM AUTHOR]

Introduction: In 2015, WHO proposed that the care for older people should be organized based on their intrinsic capacity and functional ability with a comprehensive and integrated approach and published Integrated Care for Older People (ICOPE)pathways and tool kits in 2019. Seven countries were selected for demonstration, with China included. In 2020, with support from WHO and funding from Beijing municipal government, an ICOPE pilot project was implemented in Chaoyang District of Beijing. Objectives: In China, although the concept of integrated care has been advocated over the past decade, the fragmentation between tertiary and primary care, health and social care is still substantial. There is a lack of implementation pathways, tools and qualified workforce to support care integration. The ICOPE pilot initiative is aimed to explore feasibility of integration mechanisms and ICOPE applications in context with China policy and cultural environments. Target population: A total of 33,504 Chaoyang District residents aged 65 and over were targeted received preliminary screening, among which 7,482 residents were identified with declining intrinsic capacity. After further assessment, 2,148 medium and high-risk residents were recruited and randomized into intervention (n=537) and control groups (n=1,611). In addition to health education received by the control group, the intervention group received various ICOPE intervention measures such as rehabilitation, nutrition improvement and cognitive stimulation delivered by integrated care teams both online and offline. The project was implemented from September 2020 to August 2021. Highlights: The project was led by a local management team, with experts from tertiary hospitals, community and home health agencies, who played an essential role in coordinating resources across different settings to form integrated care teams, determining payments, performing assessment, delivering needed care and evaluating outcomes. Guided by ICOPE guidelines, an integrated care plan was generated, explained and implemented by the integrated care team, with payment provided on per capita basis directly from the project. A unique feature is the systematic training of the care providers to enable their better understanding of integration concepts and ICOPE implementation. IT system is fully utilized to support real time decision makings and deliver timely interventions. Data were collected at the beginning of the project and six months after. The report showed ADL, physical, mental and nutritional status were improvements for both control and experimental groups, with significantly more improvement for the intervention group. Compared to service utilization for the second half of 2020, 7.7% of less medical visits and 14.3% lower medical expenses were reported. Conclusions: The study found essential elements for implementation include cross-organizational and cross-disciplinary coordination, system capacity building, standardized practice guidelines, interoperative IT platform, evidence-based data collection and incentivized payment system. In the future, locally-relevant interventions and innovative payment methods need to be further explored, developed and evaluated in promoting value-based integrated care and healthy aging. [ABSTRACT FROM AUTHOR]

The article discusses a study on 3D-printed micrometer-scale wireless magnetic cilia with metachronal programmability, published in the journal"Science Advances" The research team fabricated the cilia by printing silk fibroin hydrogel beams onto hard magnetic FePt Janus microparticles, offering a solution for creating bio-inspired microcilia in microfluidic systems, biomedical engineering, and biocompatible implants.

The mammalian NF-κB p52:p52 homodimer together with its cofactor Bcl3 activates transcription of κB sites with a central G/C base pair (bp), while it is inactive toward κB sites with a central A/T bp. To understand the molecular basis for this unique property of p52, we have determined the crystal structures of recombinant human p52 protein in complex with a P-selectin(PSel)-κB DNA (5'-GGGGTGACCCC-3') (central bp is underlined) and variants changing the central bp to A/T or swapping the flanking bp. The structures reveal a nearly two-fold widened minor groove in the central region of the DNA as compared to all other currently available NF-κB-DNA complex structures, which have a central A/T bp. Microsecond molecular dynamics (MD) simulations of free DNAs and p52 bound complexes reveal that free DNAs exhibit distinct preferred conformations, and p52:p52 homodimer induces the least amount of DNA conformational changes when bound to the more transcriptionally active natural G/C-centric PSel-κB, but adopts closed conformation when bound to the mutant A/T and swap DNAs due to their narrowed minor grooves. Our binding assays further demonstrate that the fast kinetics favored by entropy is correlated with higher transcriptional activity. Overall, our studies have revealed a novel conformation for κB DNA in complex with NF-κB and pinpoint the importance of binding kinetics, dictated by DNA conformational and dynamic states, in controlling transcriptional activation for NF-κB. [ABSTRACT FROM AUTHOR]

Background: Myocardial infarction is associated with the autophagy and apoptosis of cardiomyocytes, and the protein kinase B/mammalian target of rapamycin (AKT/mTOR) pathway plays a crucial role in this mechanism. Methods: Acute myocardial infarction rat models were assessed 0.5, 2, 4, and 6 hours after the induction of the myocardial infarction using hematoxylin and eosin staining, triphenyl tetrazolium chloride staining, myocardial enzyme measurements, and levels of autophagic activity. Additionally, diazoxide, 5-hydroxydecanoate, and LY294002 were intraperitoneally administered to rat models at peak myocardial injury to assess their effects on cardiac injury. The expression levels of autophagy-related and apoptosis-related proteins, as well as p-AKT and p-mTOR, were measured. Electron microscopy was used to assess the ultrastructure and the number of autophagosomes in the cardiac tissue. Results: We demonstrated that the degree of myocardial injury and the level of autophagy were significantly elevated in the experimental cohort compared with the control cohort. In addition, the myocardial infarct size was significantly smaller in diazoxidetreated acute myocardial infarction rats compared with untreated rats. Diazoxide also decreased the levels of myocardial injury markers, autophagy, and apoptosis, while it also induced the levels of AKT and mTOR phosphorylation, decreased the number of autophagosomes, and improved the myocardial ultrastructure of the acute myocardial infarction rats. 5-Hydroxydecanoate treatment resulted in an opposite effect to those observed upon diazoxide treatment. LY294002 was also able to reverse diazoxide treatment effects. Conclusion: Peak levels of myocardial tissue injury and autophagy were observed 2 hours post-acute myocardial infarction induction in rats. Diazoxide treatment inhibited myocardial autophagy and apoptosis while protecting cardiac tissue from ischemic injury, which is likely to have proceeded through activation of the AKT/mTOR pathway. [ABSTRACT FROM AUTHOR]

Summary: We present an open source, platform independent tool, called CisGenome Browser, which can work together with any other data analysis program to serve as a flexible component for genomic data visualization. It can also work by itself as a standalone genome browser. By working as a light-weight web server, CisGenome Browser is a convenient tool for data sharing between labs. It has features that are specifically designed for ultra high-throughput sequencing data visualization. [ABSTRACT FROM PUBLISHER]

Yb3+/Al3+/P5+-co-doped silica glasses with different P/Al ratios were prepared using the sol-gel method combined with high-temperature sintering. The evolution of composition-dependent color centers caused by X-ray irradiation in these glasses was correlated with their structural changes, which are controlled by the P/Al ratio. Nuclear magnetic resonance (NMR) and Raman spectra have been used to characterize the glass network structure, and advanced pulse electron paramagnetic resonance (EPR) has been employed to study the local coordination atomic structures of Yb3+ ions in pristine glasses as a function of the P/Al ratio. Si- (Si-E'), Al- (Al-E', Al-ODC, AlOHC), P- (P1, P2, POHC), and Yb-related (Yb2+) color centers in irradiated glasses have been observed and explained by optical absorption and continuous wave-EPR spectroscopies. The formation mechanisms of these centers, the structural models of glasses, and the relationship between them were proposed. Direct evidence confirms that the formation of Yb2+ ions induced by radiation is highly dependent on the coordination environment of Yb3+ ions in glasses. In addition, the glass network structure significantly affects the generation of oxygen hole color centers (AlOHCs/POHCs) caused by radiation. These results are useful in understanding the microstructural origin and the suppression mechanism of the radiodarkening effect by phosphorus co-doping in Yb3+-doped silica fibers. [ABSTRACT FROM AUTHOR]

Smart reconfiguration of a dynamic networking environment is offered by the central control of Software-Defined Networking (SDN). Centralized SDN-based management architectures are capable of retrieving global topology intelligence and decoupling the forwarding plane from the control plane. Routing protocols developed for conventionalWireless Sensor Networks (WSNs) utilize limited iterative reconfiguration methods to optimize environmental reporting. However, the challenging networking scenarios of WSNs involve a performance overhead due to constant periodic iterative reconfigurations. In this paper, we propose the SDN-based Application-aware Centralized adaptive Flow Iterative Reconfiguring (SACFIR) routing protocol with the centralized SDN iterative solver controller to maintain the load-balancing between flow reconfigurations and flow allocation cost. The proposed SACFIR's routing protocol offers a unique iterative path-selection algorithm, which initially computes suitable clustering based on residual resources at the control layer and then implements application-aware threshold-based multi-hop report transmissions on the forwarding plane. The operation of the SACFIR algorithm is centrally supervised by the SDN controller residing at the Base Station (BS). This paper extends SACFIR to SDN-based Application-aware Main-value Centralized adaptive Flow Iterative Reconfiguring (SAMCFIR) to establish both proactive and reactive reporting. The SAMCFIR transmission phase enables sensor nodes to trigger direct transmissions for main-value reports, while in the case of SACFIR, all reports follow computed routes. Our SDN-enabled proposed models adjust the reconfiguration period according to the traffic burden on sensor nodes, which results in heterogeneity awareness, load-balancing and application-specific reconfigurations of WSNs. Extensive experimental simulation-based results show that SACFIR and SAMCFIR yield the maximum scalability, network lifetime and stability period when compared to existing routing protocols. [ABSTRACT FROM AUTHOR]

Stilbene synthase (STS) is a key enzyme that catalyzes the biosynthesis of resveratrol compounds and plays an important role in disease resistance. The molecular pathways linking STS with pathogen responses and their regulation are not known. We isolated an STS gene, VaSTS19, from a Chinese wild grape, Vitis amurensis Rupr. cv. "Tonghua-3", and transferred this gene to Arabidopsis. We then generated VaSTS19-expressing Arabidopsis lines and evaluated the functions of VaSTS19 in various pathogen stresses, including powdery mildew, B. cinerea and Pseudomonas syringae pv. tomato DC3000 (PstDC3000). VaSTS19 enhanced resistance to powdery mildew and B. cinerea, but increased susceptibility to PstDC3000. Aniline blue staining revealed that VaSTS19 transgenic lines accumulated more callose compared to nontransgenic control plants, and showed smaller stomatal apertures when exposed to pathogen-associated molecular patterns (flagellin fragment (flg22) or lipopolysaccharides (LPS)). Analysis of the expression of several disease-related genes suggested that VaSTS19 expression enhanced defense responses though salicylic acid (SA) and/or jasmonic acid (JA) signaling pathways. These findings provide a deeper insight into the function of STS genes in defense against pathogens, and a better understanding of the regulatory cross talk between SA and JA pathways. [ABSTRACT FROM AUTHOR]

The present study aimed to determine cyclooxygenase 2 (COX-2) and survivin expression levels in glioma tissues, and to investigate their association with clinicopathological factors and patient survival. Immunohistochemistry was performed to evaluate COX-2 and survivin expression levels in paraffin-embedded surgically resected tissues from 70 patients with glioma and 7 individuals with normal brain tissues. The association between COX-2 and survivin expression levels and clinicopathological features was investigated using the χ² test, and the survival time was analyzed using the Kaplan Meier method with log-rank test. COX-2 and survivin were overexpressed in glioma tissues, and higher expression levels were observed in glioma tissues of histological grades III-IV compared with those in grade I-II tumor tissues (P<0.05); however, the expression levels were not associated with gender, age, tumor size or location (P>0.05). There was a significant positive association between the expression levels of COX-2 and survivin in the glioma tissues. Additionally, COX-2 and survivin expression levels were significantly negatively correlated with the rate of survival. In conclusion, COX-2 and survivin expression is positively associated with the pathological grade of a glioma and may contribute to glioma tumorigenesis. Therefore, COX-2 and survivin may be sensitive predictors of a negative clinical prognosis for patients with glioma. [ABSTRACT FROM AUTHOR]

The purpose of this study is to calculate the maintenance interval time (MIT) of steel structure of a large gantry crane in shipyard and provide basis for a maintenance plan. By analyzing a mechanical model of the lifting process, stress spectrum and fatigue damage are calculated. Based on the fatigue reliability theory, rational MIT and maintenance strategy are suggested. Compared with the existing empirical regulation, the solution of this study is safer, cheaper, and more efficient. [ABSTRACT FROM AUTHOR]

Background: Several clinical studies have demonstrated that pediatric obstructive sleep apnea (OSA) is associated with dysbiosis of airway mucosal microbiota. However, how oral and nasal microbial diversity, composition, and structure are altered in pediatric OSA has not been systemically explored. Methods: 30 polysomnography-confirmed OSA patients with adenoid hypertrophy, and 30 controls who did not have adenoid hypertrophy, were enrolled. Swabs from four surface oral tissue sites (tongue base, soft palate, both palatine tonsils, and adenoid) and one nasal swab from both anterior nares were collected. The 16S ribosomal RNA (rRNA) V3–V4 region was sequenced to identify the microbial communities. Results: The beta diversity and microbial profiles were significantly different between pediatric OSA patients and controls at the five upper airway sites. The abundances of Haemophilus, Fusobacterium, and Porphyromonas were higher at adenoid and tonsils sites of pediatric patients with OSA. Functional analysis revealed that the differential pathway between the pediatric OSA patients and controls involved glycerophospholipids and amino acid metabolism. Conclusions: In this study, the oral and nasal microbiome of pediatric OSA patients exhibited certain differences in composition compared with the controls. However, the microbiota data could be useful as a reference for studies on the upper airway microbiome. [ABSTRACT FROM AUTHOR]

Purpose: To investigate the protective effect of vitexin on smoke inhalation-induced acute lung injury (SI-ALI), and the underlying mechanism of action. Methods: The ALI rat model was established by inhalation of smoke in a closed smoke chamber. Survival rate, arterial blood gas analysis, wet-to-dry weight ratio of lung tissues, bronchoalveolar lavage fluid protein concentration, lung tissue histology, and oxidative stress and inflammation level were evaluated. Expressions of protein kinase C β (PKC β), p66Shc, and phosphorylated p66Shc were determined by western blot or quantitative reverse transcription-polymerase chain reaction. Results: Compared with smoke inhalation group, vitexin alleviated the decline in arterial partial pressure of oxygen (p < 0.05), reduced lung tissue exudation and pathological lung tissue damage, inhibited the expression of PKC β/p66Shc signaling pathway proteins, downregulated the level of oxidative stress and inflammation, and ultimately improved the survival rate in SI-ALI rats (p < 0.05). Conclusion: Vitexin attenuates SI-ALI in rats by alleviating oxidative stress via inhibition of PKC β/p66Shc signaling pathway. Thus, this compound is a potential agent for the treatment of SI-ALI. [ABSTRACT FROM AUTHOR]

Background: Matrix metalloproteinase-9 (MMP-9) is a significant protease required for synaptic plasticity, learning, and memory. Yet, the role of MMP-9 in the occurrence and development of cognitive decline after ischemic stroke is not fully understood. In this study, we used clinical data experiments to further investigate whether MMP-9 and genetic polymorphism are associated with poststroke cognitive impairment or dementia (PSCID). Materials and Methods: A total of 148 patients with PSCID confirmed by the Montreal Cognitive Assessment (MoCA) 3 months after onset (PSCID group) were included in the study. The MMP-9 rs3918242 polymorphisms were analyzed using polymerase chain reaction coupled with restriction fragment length polymorphism, and the serum level of MMP-9 was measured using enzyme-linked immunosorbent assay (ELISA). The same manipulations have been done on 169 ischemic stroke patients without cognitive impairment (NCI group) and 150 normal controls (NC group). Results: The expression level of serum MMP-9 in the PSCID group and NCI group was higher compared to the NC group, and the levels in the PSCID group were higher than that in the NCI group (all p < 0.05). Diabetes mellitus, hyperhomocysteinemia, and increased serum MMP-9 levels were the main risk factors of cognitive impairment after ischemic stroke. The serum level of MMP-9 was negatively correlated with the MoCA score, including visual-spatial executive, naming, attention, language, and delayed recall. Genetic polymorphism showed that TC genotype with MMP-9 rs3918242 and CC genotype were associated with a significantly increased risk of PSCID; moreover, the TC genotype significantly increased the risk of cognitive impairment. In the TCCC genotype of MMP-9 rs3918242, diabetes mellitus and hyperhomocysteinemia were associated with the increased risk of PSCID; also, hyperhomocysteinemia could increase the risk of cognitive impairment. Conclusions: MMP-9 level and MMP-9 rs3918242 polymorphism have an important role in the occurrence and development of post-stroke cognitive impairment or dementia (PSCID). [ABSTRACT FROM AUTHOR]

The article presents a study which examined the role of primary somatosensory cortex in touch-induced mechanical and heat analgesia. Topics discussed include effect of reafferent signals from self-generated whisking on facial nociception, the activation of somatosensory barrel cortex (S1B) by noxious stimuli, and analysis of the effect of whisking on activity of individual S1B L2/3 neurons in response to noxious stimuli.

Stems are the important residues of Trapa quadrispinosa Roxb., which are abundant in phenolic compounds. Ultrasonic-assisted enzymatic extraction (UAEE) is confirmed as a novel extraction technology with main advantages of enhancing extraction yield and physiological activities of the extracts from various plants. In this study, UAEE was applied to obtain the highest yield of phenolic content, strongest antioxidant, and antitumor activities and to optimize the extraction conditions using response surface methodology (RSM). The extracts from the stems of T. quadrispinosa were characterized by determination of their antioxidant activities through 2,2-azinobis(3-ethylbenzthiazoline)-6-sulfonic acid (ABTS), 1,1-Diphenyl-2-picrylhydrazxyl (DPPH) radical scavenging, total antioxidant capacity (TAC), ferric reducing antioxidant capacity (FRAC) methods and of their antitumor activity by MTT method. The selected key independent variables were cellulase concentration (X1: 1.5%-2.5%), extraction time (X2: 20-30 min) and extraction temperature (X3: 40-60 °C). The optimal extraction conditions for total phenolic content (TPC) value of the extracts were determined as 1.74% cellulase concentration, 25.5 min ultrasonic extraction time and 49.0 °C ultrasonic temperature. Under these conditions, the highest TPC value of 53.6 ± 2.2 mg Gallic acid equivalent (GAE)/g dry weight (DW) was obtained, which agreed well with the predicted value (52.596 mg GAE/g·DW. Furthermore, the extracts obtained from UAEE presented highest antioxidant activities through ABTS, DPPH, TAC and FRAC methods were of 1.54 ± 0.09 mmol Trolox equivalent (TE)/g·DW; 1.45 ± 0.07 mmol·TE/g·DW; 45.2 ± 2.2 mg·GAE/g·DW; 50.4 ± 2.6 μmol FeSO4 equivalent/g·DW and lowest IC50 values of 160.4 ± 11.6 μg/mL, 126.1 ± 10.8 μg/mL, and 178.3 ± 13.1 μg/mL against Hela, HepG-2 and U251 tumor cells, respectively. The results indicated that the UAEE was an efficient alternative to improve extraction yield and enhance the antioxidant and antitumor activities of the extracts. The phenolic extracts from the stems of T. quadrispinosa had significant antioxidant and antitumor activities, which could be used as a source of potential antioxidant and antitumor agents. [ABSTRACT FROM AUTHOR]

The purpose of the present article was to describe the diagnostic evaluation of, and surgical approaches to, lateral skull base tumors (LSBTs). The study is a retrospective review of 21 patients diagnosed with tumors that involve lateral skull base (8 with malignant diseases and 13 with benign lesions) who were surgically treated during a 8-year period. The transparotid-transmandibular (38%) was the most commonly performed surgical procedure, followed by the transmandibular (24%), the transmaxillary (24%), the transcervical approach (10%) and the combined approach (4%). The surgical procedures were uneventful and there were no postoperative mortalities. Complications were encountered in 12 cases, and morbidity was not remarkable during the perioperative stages. After an average follow-up of 46 months, only 1 of 14 patients with benign diseases had a recurrence following the resection of a pleomorphic adenoma. Of 7 patients with malignant tumors, 5 are alive with no evidence of disease. The majority of the benign lateral skull base tumors can be removed surgically with a low rate of complications and recurrence. However, malignant neoplasms carry a poor prognosis and a low rate of disease-free survival. [ABSTRACT FROM AUTHOR]

Despite the importance of innate immunity in invertebrates, the diversity and function of innate immune cells in invertebrates are largely unknown. Using single-cell RNA-seq, we identified prohemocytes, monocytic hemocytes, and granulocytes as the three major cell-types in the white shrimp hemolymph. Our results identified a novel macrophage-like subset called monocytic hemocytes 2 (MH2) defined by the expression of certain marker genes, including Nlrp3 and Casp1. This subtype of shrimp hemocytes is phagocytic and expresses markers that indicate some conservation with mammalian macrophages. Combined, our work resolves the heterogenicity of hemocytes in a very economically important aquatic species and identifies a novel innate immune cell subset that is likely a critical player in the immune responses of shrimp to threatening infectious diseases affecting this industry. [ABSTRACT FROM AUTHOR]

To evaluate hydraulic head distribution in front of a shield tunnel in a saturated soil layer, theoretical analysis and numerical simulations are carried out in this study. Based on the partial differential equilibrium equation of seepage flow, a three-dimensional (3D) theoretical analytical model of the shield tunnel face and the seepage field in front of it is established using the eigenfunction and the Fourier series expansion methods, and the hydraulic head calculation formula is derived. Combined with engineering cases, the theoretical analysis results and the 3D numerical simulation results are compared and analyzed. The effect of the water pressure of the tunnel face on the hydraulic head distribution is also analyzed. The results of the proposed analytical solution are in agreement with those of the numerical simulation solutions; moreover, the proposed analytical solution requires less time to calculate the seepage hydraulic head than the numerical simulation. The ratio of the initial water table to the diameter (D) of tunnel face has a more significant impact on the hydraulic head distribution at a position 0.5D above the tunnel vault. When the water pressure on the tunnel face is not considered, the values of the hydraulic head are significantly underestimated. [ABSTRACT FROM AUTHOR]

Background: Scythe/BAT3 is a member of the BAG protein family whose role in apoptosis has been extensively studied. However, since the developmental defects observed in Bat3-null mouse embryos cannot be explained solely by defects in apoptosis, we investigated whether BAT3 is also involved in cell-cycle progression. Methods/Principal Findings: Using a stable-inducible Bat3-knockdown cellular system, we demonstrated that reduced BAT3 protein level causes a delay in both G1/S transition and G2/M progression. Concurrent with these changes in cell-cycle progression, we observed a reduction in the turnover and phosphorylation of the CDK inhibitor p21, which is best known as an inhibitor of DNA replication; however, phosphorylated p21 has also been shown to promote G2/M progression. Our findings indicate that in Bat3-knockdown cells, p21 continues to be synthesized during cell-cycle phases that do not normally require p21, resulting in p21 protein accumulation and a subsequent delay in cell-cycle progression. Finally, we showed that BAT3 co-localizes with p21 during the cell cycle and is required for the translocation of p21 from the cytoplasm to the nucleus during the G1/S transition and G2/M progression. Conclusion:: Our study reveals a novel, non-apoptotic role for BAT3 in cell-cycle regulation. By maintaining a low p21 protein level during the G1/S transition, BAT3 counteracts the inhibitory effect of p21 on DNA replication and thus enables the cells to progress from G1 to S phase. Conversely, during G2/M progression, BAT3 facilitates p21 phosphorylation by cyclin A/Cdk2, an event required for G2/M progression. BAT3 modulates these pro- and anti-proliferative roles of p21 at least in part by regulating cyclin A abundance, as well as p21 translocation between the cytoplasm and the nucleus to ensure that it functions in the appropriate intracellular compartment during each phase of the cell cycle. [ABSTRACT FROM AUTHOR]

Bond lengths and force constants of a set of closed-shell sixth-row and superheavy element monohydrides and monofluorides are calculated in this work. Kramers restricted coupled-cluster approaches (KR-CC) with spin-orbit coupling (SOC) included at the self-consistent field (SCF) level as well as CC approaches with SOC included in post-SCF treatment (SOC-CC) are employed in calculations. Recently published relativistic effective core potentials are employed, and highly accurate results for superheavy element molecules are achieved with KR-CCSD(T). SOC effects on bond lengths and force constants of these molecules are investigated. Effects of electron correlation are shown to be affected by SOC to a large extent for some superheavy element molecules. Bond lengths and force constants with SOC-CC agree very well with those of KR-CC for most of the sixth-row element molecules. As for superheavy element molecules, SOC-CCSD is able to afford results that are in good agreement with those of KR-CCSD except for 111F, while the error of SOC-CCSD(T) is more pronounced. Large error would be encountered with SOC-CC approaches for molecules when both SOC and electron correlation effects are sizable. [ABSTRACT FROM AUTHOR]

Objective: 15-Deoxy-Δ12,14-prostaglandin J2 (15d-PGJ2) induces reactive oxygen species (ROS)-mediated apoptosis in many malignant cells, which has not been studied in hepatoma cells. In this study, we investigated whether 15d-PGJ2 induced apoptosis in hepatocellular carcinoma (HCC) associated with ROS. Materials and methods: The LM3, SMMC-7721, and Huh-7 HCC cell lines were treated with 15d-PGJ2 (5–40 μM) for 24, 48, and 72 hours. Cholecystokinin 8 was used to detect the cytotoxicity of 15d-PGJ2. Flow cytometry, Hoechst staining, and Western blotting were used to analyze apoptosis. ROS were combined with the fluorescent probe dihydroethidium and then observed by fluorescence microscopy and flow cytometry. Activation of JNK and expression of Akt were detected by Western blotting. Results: 15d-PGJ2 inhibited HCC cell proliferation and induced apoptosis in a dose- and time-dependent manner. Apoptosis was mainly induced via an intrinsic pathway and was ROS-dependent, and was alleviated by ROS scavengers. ROS induced JNK activation and Akt downregulation in HCC cells. Conclusion: 15d-PGJ2 induced ROS in HCC cell lines, and inhibition of cell growth and apoptosis were partly ROS-dependent. [ABSTRACT FROM AUTHOR]

Plant metallothioneins (MTs) are a family of low molecular weight, cysteine-rich, and metal-binding proteins, which play an important role in the detoxification of heavy metal ions, osmotic stresses, and hormone treatment. Sequence analysis revealed that the open-reading frame (ORF) of ZjMT was 225 bp, which encodes a protein composed of 75 amino acid residues with a calculated molecular mass of 7.376 kDa and a predicated isoelectric point (pI) of 4.83. ZjMT belongs to the type I MT, which consists of two highly conserved cysteine-rich terminal domains linked by a cysteine free region. Our studies showed that ZjMT was primarily localized in the cytoplasm and the nucleus of cells and ZjMT expression was up-regulated by NaCl, CdCl2 and polyethylene glycol (PEG) treatments. Constitutive expression of ZjMT in wild type Arabidopsis plants enhanced their tolerance to NaCl stress during the germination stage. Compared with the wild type, transgenic plants accumulate more Cd2+ in root, but less in leaf, suggesting that ZjMT may have a function in Cd2+ retension in roots and, therefore, decrease the toxicity of Cd2+. [ABSTRACT FROM AUTHOR]

Fiber reinforced plastic (FRP) is a widely used structural form in engineering. FRP ribs can absorb most of the impact energy to protect the structure from damage. The purpose of this study is to obtain the impact resistance of FRP ribs by test and simulation. Taking glass fiber reinforced plastic (GFRP) oil sump as the object, the damage degree of structure under different impact angles, impact velocity, and impactor masses is compared and analyzed by material test, impact test, and simulation. It can be seen from the test results that the design of surface ribs has a great influence on the energy absorption effect of the shell. The constitutive parameters of the shell material are obtained by testing, and the failure mode of the ribs is analyzed by finite element simulation. The impact effects of flying stones with different incident angles, velocities, kinetic energy, and geometric dimensions on the shell are compared and analyzed. The results show that, at the same impact energy, the impact resistance characteristics change regularly under different working conditions. Under a certain incident angle, the damage effect caused by flying stones in a specific mass range is greater. Beyond a certain incident angle, the damage begins to occur, and the larger the incident angle is, the greater the damage effect is. Combined with the actual situation and road standards, the defense of medium quality flying stones is a major concern in the design of oil pan. The results are helpful for designing reasonable ribs to improve the reliability of FRP structures. [ABSTRACT FROM AUTHOR]

Security against systemic financial risks is the main theme for financial stability regulation. As modern financial markets are highly interconnected and complex networks, their network resilience is an important indicator of the ability of the financial system to prevent risks. To provide a comprehensive perspective on the network resilience of financial networks, we review the main advances in the literature on network resilience and financial networks. Further, we review the key elements and applications of financial network resilience processing in financial regulation, including financial network information, network resilience measures, financial regulatory technologies, and regulatory applications. Finally, we discuss ongoing challenges and future research directions from the perspective of resilience-based financial systemic risk regulation. [ABSTRACT FROM AUTHOR]

In contrast to a majority of cancer types, the initiation of hepatocellular carcinoma (HCC) is intimately associated with a chronically diseased liver tissue, with one of the most prevalent etiological factors being hepatitis B virus (HBV). Transformation of the liver in HBV-associated HCC often follows from or accompanies long-term symptoms of chronic hepatitis, inflammation and cirrhosis, and viral load is a strong predictor for both incidence and progression of HCC. Besides aiding in transformation, HBV plays a crucial role in modulating the accumulation and activation of both cellular components of the microenvironment, such as immune cells and fibroblasts, and non-cellular components of the microenvironment, such as cytokines and growth factors, markedly influencing disease progression and prognosis. This review will explore some of these components and mechanisms to demonstrate both underlying themes and the inherent complexity of these interacting systems in the initiation, progression, and metastasis of HBV-positive HCC. [ABSTRACT FROM AUTHOR]

Protein storage vacuoles (PSVs) are unique organelles that accumulate storage proteins in plant seeds. Although morphological evidence points to the existence of multiple PSV-trafficking pathways for storage protein targeting, the molecular mechanisms that regulate these processes remain mostly unknown. Here, we report the functional characterization of the rice (Oryza sativa) glutelin precursor accumulation7 (gpa7) mutant, which over-accumulates 57-kDa glutelin precursors in dry seeds. Cytological and immunocytochemistry studies revealed that the gpa7 mutant exhibits abnormal accumulation of storage prevacuolar compartment-like structures, accompanied by the partial mistargeting of glutelins to the extracellular space. The gpa7 mutant was altered in the CCZ1 locus, which encodes the rice homolog of Arabidopsis (Arabidopsis thaliana) CALCIUM CAFFEINE ZINC SENSITIVITY1a (CCZ1a) and CCZ1b. Biochemical evidence showed that rice CCZ1 interacts with MONENSIN SENSITIVITY1 (MON1) and that these proteins function together as the Rat brain 5 (Rab5) effector and the Rab7 guanine nucleotide exchange factor (GEF). Notably, loss of CCZ1 function promoted the endosomal localization of vacuolar protein sorting-associated protein 9 (VPS9), which is the GEF for Rab5 in plants. Together, our results indicate that the MON1-CCZ1 complex is involved in post-Golgi trafficking of rice storage protein through a Rab5- and Rab7-dependent pathway. [ABSTRACT FROM AUTHOR]

Zanubrutinib is a highly selective, potent, orally available, targeted covalent inhibitor (TCI) of Bruton's tyrosine kinase (BTK). This work investigated the in vitro drug metabolism and transport of zanubrutinib, and its potential for clinical drug–drug interactions (DDIs). Phenotyping studies indicated cytochrome P450 (CYP) 3A are the major CYP isoform responsible for zanubrutinib metabolism, which was confirmed by a clinical DDI study with itraconazole and rifampin. Zanubrutinib showed mild reversible inhibition with half maximal inhibitory concentration (IC50) of 4.03, 5.69, and 7.80 μM for CYP2C8, CYP2C9, and CYP2C19, respectively. Data in human hepatocytes disclosed induction potential for CYP3A4, CYP2B6, and CYP2C enzymes. Transport assays demonstrated that zanubrutinib is not a substrate of human breast cancer resistance protein (BCRP), organic anion transporting polypeptide (OATP)1B1/1B3, organic cation transporter (OCT)2, or organic anion transporter (OAT)1/3 but is a potential substrate of the efflux transporter P-glycoprotein (P-gp). Additionally, zanubrutinib is neither an inhibitor of P-gp at concentrations up to 10.0 μM nor an inhibitor of BCRP, OATP1B1, OATP1B3, OAT1, and OAT3 at concentrations up to 5.0 μM. The in vitro results with CYPs and transporters were correlated with the available clinical DDIs using basic models and mechanistic static models. Zanubrutinib is not likely to be involved in transporter-mediated DDIs. CYP3A inhibitors and inducers may impact systemic exposure of zanubrutinib. Dose adjustments may be warranted depending on the potency of CYP3A modulators. [ABSTRACT FROM AUTHOR]

Background The effects of performing a minimally invasive procedure at different stages after intracerebral hemorrhage on perihematomal MMP-9 expression and blood-brain barrier (BBB) permeability were evaluated. Methods Sixty rabbits were randomly distributed into a model control group (MC group, 30 rabbits) or a minimally invasive group (MI group, 30 rabbits). A model of intracerebral hemorrhage was established in the MC and MI group. In the MI group, the intracerebral hematoma was evacuated by stereotactic minimally invasive procedures over 6 hours (6 rabbits), 12 hours (6 rabbits), 18 hours (6 rabbits) 24 hours or 48 hours (6 rabbits) following successful induction of intracerebral hemorrhage. The same procedure was performed in the MC group at the same time point but without evacuating the hematoma. All the animals were sacrificed within two weeks after the hematoma was surgically evacuated. A neurological deficit score was determined, and the perihematomal MMP-9 level and the BBB permeability were measured. Results The neurological deficit score, perihematomal MMP-9 level and BBB permeability of the MI group decreased significantly compared to the MC group. Performing the MI procedure 6-12 h after intracerebral hemorrhage showed the most favorable outcome. Conclusions Regarding the pathophysiological changes surrounding the hematoma, the optimal time window of performing MI procedures for the intracerebral hematoma evacuation might be within 6-12 h after hemorrhage. [ABSTRACT FROM AUTHOR]

Basal elements in archaeal promoters, except for putative initiator elements encompassing transcription start sites, are well characterized. Here, we employed the Sulfolobus araS promoter as a model to study the function of the initiator element (Inr) in archaea. We have provided evidence for the presence of a third core promoter element, the Sulfolobus Inr, whose action depends on a TATA box and the TFB recognition element (BRE). Substitution mutations in the araS Inr did not alter the location of the transcription start site. Using systematic mutagenesis, the most functional araS Inr was defined as +1 GAGAMK +6 (where M is A/C and K is G/T). Furthermore, WebLogo analysis of a subset of promoters with coding sequences for 5' untranslated regions (UTRs) larger than 4 nudeotides (nt) in Sulfolobus solfataricus P2 identified an Inr consensus that exactly matches the functional araS Inr sequence. Moreover, mutagenesis of 3 randomly selected promoters confirmed the Inr sequences to be important for basal promoter strength in the subgroup. Importantly, the result of the araS Inr being added to the Inr-less promoters indicates that the araS Inr, the core promoter element, is able to enhance the strength of Inr-less promoters. We infer that transcription factor B (TFB) and subunits of RNA polymerase bind the Inr to enhance promoter strength. Taken together, our data suggest that the presence or absence of an Inr on basal promoters is important for global gene regulation in Sulfolobus. [ABSTRACT FROM AUTHOR]

Background: Calcium deficiency is a global public-health problem. Although the initial stage of calcium deficiency can lead to metabolic alterations or potential pathological changes, calcium deficiency is difficult to diagnose accurately. Moreover, the details of the molecular mechanism of calcium deficiency remain somewhat elusive. To accurately assess and provide appropriate nutritional intervention, we carried out a global analysis of metabolic alterations in response to calcium deficiency. Methods: The metabolic alterations associated with calcium deficiency were first investigated in a rat model, using urinary metabonomics based on ultra-performance liquid chromatography coupled with quadrupole time-of-flight tandem mass spectrometry and multivariate statistical analysis. Correlations between dietary calcium intake and the biomarkers identified from the rat model were further analyzed to confirm the potential application of these biomarkers in humans. Results: Urinary metabolic-profiling analysis could preliminarily distinguish between calcium-deficient and nondeficient rats after a 2-week low-calcium diet. We established an integrated metabonomics strategy for identifying reliable biomarkers of calcium deficiency using a time-course analysis of discriminating metabolites in a lowcalcium diet experiment, repeating the low-calcium diet experiment and performing a calcium-supplement experiment. In total, 27 biomarkers were identified, including glycine, oxoglutaric acid, pyrophosphoric acid, sebacic acid, pseudouridine, indoxyl sulfate, taurine, and phenylacetylglycine. The integrated urinary metabonomics analysis, which combined biomarkers with regular trends of change (types A, B, and C), could accurately assess calciumdeficient rats at different stages and clarify the dynamic pathophysiological changes and molecular mechanism of calcium deficiency in detail. Significant correlations between calcium intake and two biomarkers, pseudouridine (Pearson correlation, r = 0.53, P = 0.0001) and citrate (Pearson correlation, r = -0.43, P = 0.001), were further confirmed in 70 women. Conclusions: To our knowledge, this is the first report of reliable biomarkers of calcium deficiency, which were identified using an integrated strategy. The identified biomarkers give new insights into the pathophysiological changes and molecular mechanisms of calcium deficiency. The correlations between calcium intake and two of the biomarkers provide a rationale or potential for further assessment and elucidation of the metabolic responses of calcium deficiency in humans. [ABSTRACT FROM AUTHOR]

Background Inflammatory bowel disease (IBD) involves a breakdown in interactions between the host immune response and the resident commensal microbiota. Recent studies have suggested gut physiology and pathology relevant to human IBD can be rapidly modeled in zebrafish larvae. The aim of this study was to investigate the dysbiosis of intestinal microbiota in zebrafish models with IBD-like enterocolitis using culture-independent techniques. Results IBD-like enterocolitis was induced by exposing larval zebrafish to trinitrobenzenesulfonic acid (TNBS). Pathology was assessed by histology and immunofluorescence. Changes in intestinal microbiota were evaluated by denaturing gradient gel electrophoresis (DGGE) and the predominant bacterial composition was determined with DNA sequencing and BLAST and confirmed by real-time polymerase chain reaction. Larval zebrafish exposed to TNBS displayed intestinal-fold architecture disruption and inflammation reminiscent of human IBD. In this study, we defined a reduced biodiversity of gut bacterial community in TNBS-induced coliitis. The intestinal microbiota dysbiosis in zebrafish larvae with IBD-like colitis was characterized by an increased proportion of Proteobacteria (especially Burkholderia) and a decreased of Firmicutes(Lactobacillus group), which were significantly correlated with enterocolitis severity(Pearson correlation p < 0.01). Conclusions This is the first description of intestinal microbiota dysbiosis in zebrafish IBD-like models, and these changes correlate with TNBS-induced enterocolitis. Prevention or reversal of this dysbiosis may be a viable option for reducing the incidence and severity of human IBD. [ABSTRACT FROM AUTHOR]

Background: Numerous epidemiological studies have evaluated the association between TGFBR1 polymorphisms and the risk of cancer, however, the results remain inconclusive. To derive a more precise estimation of the relation, we conducted a comprehensive meta-analysis of all available case- control studies relating the TGFBR1*6A and IVS7+24G>A polymorphisms of the TGFBR1 gene to the risk of cancer. Methods: Eligible studies were identified by search of electronic databases. Overall and subgroup analyses were performed. Odds ratio (OR) and 95% confidence interval (CI) were applied to assess the associations between TGFBR1*6A and IVS7+24G>A polymorphisms and cancer risk. Results: A total of 35 studies were identified, 32 with 19,767 cases and 18,516 controls for TGFBR1*6A polymorphism and 12 with 4,195 cases and 4,383 controls for IVS7+24G>A polymorphism. For TGFBR1*6A, significantly elevated cancer risk was found in all genetic models (dominant OR = 1.11, 95% CI = 1.04∼1.18; recessive: OR = 1.36, 95% CI = 1.11∼1.66; additive: OR = 1.13, 95% CI = 1.05∼1.20). In subgroup analysis based on cancer type, increased cancer risk was found in ovarian and breast cancer. For IVS7+24G>A, significant correlation with overall cancer risk (dominant: OR = 1.39, 95% CI = 1.15∼1.67; recessive: OR = 2.23, 95% CI = 1.26∼3.92; additive: OR = 1.43, 95% CI = 1.14∼1.80) was found, especially in Asian population. In the subgroup analysis stratified by cancer type, significant association was found in breast and colorectal cancer. Conclusions: Our investigations demonstrate that TGFBR1*6A and IVS7+24G>A polymorphisms of TGFBR1 are associated with the susceptibility of cancer, and further functional research should be performed to explain the inconsistent results in different ethnicities and cancer types. [ABSTRACT FROM AUTHOR]