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Abstract Background Systemic sclerosis (SSc) is a multisystem rheumatic disease. Orofacial manifestations are commonly in SSc but maybe usually ignored and overshadowed by other systemic complications. Multiple comparative studies have been conducted to investigate the possible links between SSc and oral manifestations. The present study aimed to investigate the oral health status in patients with SSc. Methods Pubmed, Embase, Web of Science, and Scopus were searched up to July 2020. Following outcomes were evaluated: Probing depth (PD), Attachment loss (AL), Bleeding on probing (BOP), Number or percentage of Sites with PD ≥ 4 mm, Prevalence of periodontitis, Number of teeth, Decayed Teeth, Missing teeth, Filled teeth, DMFT index, and the interincisal distance. Newcastle-Ottawa Scale (NOS) were applied for quality assessment. The statistical analysis was processed using the software STATA. Results 11 eligible studies were included. The maximum interincisor distance was significantly restricted in SSc patients (SMD − 1.061; 95 %CI [− 1.546, − 0.576]; Z = 4.29, P = 0.000).The prevalence of Periodontitis (OR 7.007; 95 %CI [3.529, 13.915]; Z = 5.56, P = 0.000), PD (SMD 3.101; 95 %CI [1.374, 4.829]; Z = 3.52, P = 0.000), AL(SMD 2.584; 95 %CI [0.321, 4.846]; Z = 2.24, P = 0.025), sites with PD ≥ 4mm (SMD 2.071 ; 95 %CI [0.267, 3.875]; Z = 2.25, P = 0.024) and the number of decayed teeth (SMD, 0.186; 95 %CI [0.007, 0.365]; Z = 2.04, P = 0.041) were increased significantly in SSc population in comparison with the controls. Conclusions SSc patients have limited mouth opening, higher periodontitis prevalence, and worse periodontal status, as well as an increased number of decayed teeth. Routinely oral hygiene instruction and initial periodontal treatment is recommended for SSc patients.

ObjectiveThis study aimed to investigate the correlation between best corrected visual acuity (BCVA) and retinal microstructural parameters detected by optical coherence tomography (OCT) in diabetic retinopathy macular edema (DRME).MethodsThirty-nine patients (64 eyes) with DRME were enrolled in this study. These patients underwent OCT to measure the fracture distance of the external limiting membrane (ELM), junction between the inner and outer segments (IS/OS), central foveal thickness (CFT), and edema layer. The correlation between the above parameters and BCVA was discussed.ResultsCFT and the fracture distances of the ELM and IS/OS layers were negatively correlated with BCVA (p 0.05).ConclusionIn eyes with DRME, thin CFT, intact ELM and IS/OS layers, and edema in inner retina is closely correlated with good BCVA.

This paper presents the fabrication of novel flexible sensors from metalized polymer films and their subsequent utilization for environmental applications. Polyethylene terephthalate films coated with thin-film of aluminum was used as a singular material to form the sensor patches. Optimization was done on the laser parameters to form laser-inscribed interdigitated electrodes on the aluminum side of the polymer films. The sensors were then used to detect the presence of sulfate ions in the water samples. Electrochemical impedance spectroscopy was used to detect the resistive and reactive changes with respect to the corresponding changes in the concentration of the tested solutions. Experiments were conducted using five different concentrations ranging between 0.1 ppm and 1000 ppm. The sensitivity, limit of detection and response time of the salts were 0.874 Ω/ppm, 0.1 ppm and one second, respectively. The repeatability of the sensors was also tested to validate their responses for the target analyte. An optimal frequency was chosen to form an IoT-based system that consisted of an impedance analyzer AD 5933, Wi-Fi embedded Arduino and 2:1 multiplexer ADG849. The interfacing of the microcontroller-sensed data was also done with the cloud server to showcase the potentiality of the developed systems as portable devices for real-time applications.

Face recognition technology is a biometric technology, which is based on the identification of facial features of a person. People collect the face images, and the recognition equipment automatically processes the images. The paper introduces the related researches of face recognition from different perspectives. The paper describes the development stages and the related technologies of face recognition. We introduce the research of face recognition for real conditions, and we introduce the general evaluation standards and the general databases of face recognition. We give a forward-looking view of face recognition. Face recognition has become the future development direction and has many potential application prospects.

Hand gesture recognition has attracted extensive research interest, as an essential approach for human−machine interaction. The development of flexible strain sensors offers the possibility of directly measuring the finger motion behaviors for accurate and cost‐effective hand gesture recognition, by placing the sensors on the fingers or integrating them on data gloves. Herein, the operation mechanisms of various flexible strain sensor designs are introduced first. Progresses on related materials and device structures to achieve the demanded figure of merits for flexible strain sensors are then reviewed. In addition to continuous performance optimization of the flexible strain sensor devices, the development of system‐level algorithms is shown to be important for not only recognition functions but also for suppression of nonidealities of the sensor devices, which are difficult to be addressed at device and material level.

Coordination compounds have undergone booming development in the past 20 years for their applications as multifunctional materials in the field of catalysis and biomedicine. To create compounds with both catalytic and bioactive properties, we selected Cu(II) ion and benzimidazole (Hbim) ligand as the building blocks to fabricate a new cluster-based Cu(II) compound [Cu4OCl6(Hbim)4]n·n(H2O)·2n(EtOH) (1). The exploration of single crystal X-ray diffraction exhibits that complex 1 is a 0D isolated structure on the basis of tetrahedral {Cu4O} clusters. Moreover, such supramolecular framework not only shows excellent photocatalytic effect for the MB photodegradation under the irradiation of ultraviolet light but also has the application values against orbital wall fracture. This work gives new insights on the creation of coordination polymers which might be potentially used as photocatalytic and bioactive reagents.

This study aimed to investigate the impact of fermentation time on antioxidative activities and phenolic composition and sensory quality of kombucha fermented from different teas (green, black, and oolong) and fruits (grape, dragon, and guava). Results: the highest antioxidative activity was observed in kombucha from green tea and grapefruit fermented for 6-7 days at 25–30°C and 48 h at 37°C, respectively. Further analysis revealed that the antioxidative activity of grape kombucha was significantly improved due to an increase in polyphenols’ concentration as compared to original green tea kombucha. Furthermore, the sensory evaluation of grape kombucha suggested that grape-flavoured kombucha is more acceptable by the young-aged group. In conclusion, this study provides a potential and promising method for the first time to produce fruit-flavoured kombucha with increased bioactive compounds in very short fermentation time (48 h) which could fulfil the nutritional requirement for human health.

The COVID-19 pandemic severely hit small and micro-businesses. In the face of the impact of the pandemic, how to help entrepreneurs, especially small- and micro-businesses that are more sensitive to the impact of the pandemic, make decisions to reduce losses has become an issue worth paying attention to. From the perspective of personality approach, this article studied openness, which is the strongest predictor of entrepreneurial performance among the big five personality traits, and explored the impact of entrepreneurs’ openness on entrepreneurial performance during the COVID-19 pandemic, as well as the inconsistent mediating role of strategic decision comprehensiveness on entrepreneurial performance. An online questionnaire survey was conducted among 238 entrepreneurs of small- and micro-businesses when China was recovering from the pandemic and starting to resume work and production (February 18 – February 26, 2020). Entrepreneurial performance during the COVID-19 pandemic was measured by comparing the business conditions before and after the pandemic. The results showed that entrepreneurs’ openness positively impacted strategic decision comprehensiveness and entrepreneurial performance during the COVID-19 pandemic. Among the two competing hypotheses proposed by summarizing previous research, the results supported that strategic decision comprehensiveness negatively affected entrepreneurial performance. It indicated that entrepreneurs who tend to collect and analyze information extensively and then make decisions during the pandemic could not seize opportunities and improve their entrepreneurial performance. The results further supported that strategic decision comprehensiveness was an inconsistent mediator between openness and entrepreneurial performance, showing that entrepreneurs with low openness can also reduce the loss of entrepreneurial performance during the pandemic by making incomplete but rapid strategic decisions. This study found that the openness of entrepreneurs had a positive impact on strategic decision comprehensiveness for the first time and provided more empirical evidence for the negative effect of strategic decision comprehensiveness on entrepreneurial performance in the context of information uncertainty and unanalyzable situations. The inconsistent mediating effect of strategic decision comprehensiveness revealed in this study also has practical significance for helping entrepreneurs make correct decisions to reduce the losses caused by the pandemic.

(1) Background: Ferroptosis is a newly coined form of programmed cell death marked by lethal accumulation of lipid peroxidation and ferrous iron overload. A few studies on the specific mechanism of ferroptosis in the genesis and development of psoriasis are available. (2) Methods: Levels of lipid reactive oxygen species (ROS) and ferrous iron were measured by flow cytometry. Ultrastructure analysis was performed by transmission electron microscopy. Imiquimod-induced psoriasis-like mice were treated with a ferroptosis inducer. The expressions of mRNA of genes were measured by qRT-PCR. HaCaT cells were used to explore the function of Cyb561d2. (3) Results: In this work, we observed that levels of lipid ROS and ferrous iron in the epidermis of psoriasis vulgaris (PV) patients were increased. The existence of ferroptosis activation in the epidermis of individuals with PV was confirmed by transmission electron microscope both in patients with PV and psoriasis-like mice models. Intradermal injection of the ferroptosis inducer RSL3 in psoriasis-like mice significantly promoted and aggravated the development of psoriasis-like dermatitis, and the level of serum transferrin was also increased in PV samples. Moreover, abnormal expression of some genes related to iron metabolism was also proved in the epidermis of PV cases, among which Cyb561d2 was shown to promote ferrous iron overload and lipid peroxidation accumulation in HaCaT cells. (4) Conclusions: In summary, our study suggested that ferroptosis activation owing to iron overload may be a novel mechanism underlying the formation of skin lesions in individuals with PV.

In this study, poly (ε-caprolactone) (PCL)/zein/Ag nanoparticle (AgNP) fibrous membranes were prepared by ultrasonication-assisted electrospinning. The effects of the AgNP content and ultrasonication time on the membrane morphology, chemical structure, biodegradability, mechanical properties, antibacterial/antiviral activity, and air filtration performance were studied. The best-performing membrane (AgNP content = 1% (w/v), sonication time = 30 min) exhibited a bead-on-string morphology, an air permeability of 93.6 ± 1.5 mm s−1, and the Escherichia coli and Staphylococcus aureus removal efficiencies of 98.1 ± 1.2% and 97.4 ± 2.5%, respectively. In an experiment with E. coli phage, the above-mentioned membrane exhibited a 97.1 ± 2.1% virus removal efficiency after 60 min. The high performance of this bead-on-string membrane for air filtration was ascribed to the low packing density due to the presence of open interconnected beaded airflow channels and small beads.

In this study, a coaxial electrospray process was used to produce nanoparticles, in which thymol was encapsulated in a core–shell of zein and shellac. We then investigated fluid velocity and solution concentrations on the electrospray. Scanning electron microscopy revealed that the thymol/zein/shellac particles prepared at a flow rate ratio of 0.6:0.3 mL/h were rounder with smaller diameters. The highest encapsulation efficiency of thymol was 81.34%, the average particle size was 606.53 nm, and the retention rate of thymol was 68.74% after 30 days. Moreover, we investigated the thermal stability, antimicrobial activity, and simulated gastrointestinal release curves of the nanoparticles. Finally, the nanoparticles were used as a coating for fresh-cut cantaloupe. Compared with the blank nanoparticle control group, the coating significantly extended the shelf life of cantaloupe to 16 days. Our results indicate that these nanoparticles have great potential for application in food preservation.

Numerous neuroimaging studies have investigated the neural mechanisms of two mutually independent yet closely related cognitive processes aiding humans to navigate complex societies: social hierarchy-related learning (SH-RL) and social hierarchy-related interaction (SH-RI). To integrate these heterogeneous results into a more fine-grained and reliable characterization of the neural basis of social hierarchy, we combined coordinate-based meta-analyses with connectivity and functional decoding analyses to understand the underlying neuropsychological mechanism of SH-RL and SH-RI. We identified the anterior insula and temporoparietal junction (dominance detection), medial prefrontal cortex (information updating and computation), and intraparietal sulcus region, amygdala, and hippocampus (social hierarchy representation) as consistent activated brain regions for SH-RL, but the striatum, amygdala, and hippocampus associated with reward processing for SH-RI. Our results provide an overview of the neural architecture of the neuropsychological processes underlying how we understand, and interact within, social hierarchy.

Polyvinyl alcohol (PVA)/titanium dioxide nanoparticles (TiO2 NPs)/3,3′,4,4′-Benzophenone tetracarboxylic acid (BPTA) antibacterial films were prepared by solvent casting and chemical grafting using PVA as the base material and TiO2 NPs and BPTA as antibacterial materials. Scanning electron microscopy results showed that the distribution of TiO2 NPs inside the polymer matrix was substantially uniform. X-ray diffraction (XRD) and FTIR-ATR spectroscopy were used to demonstrate the successful embedding of NPs and the formation of ester bonds in the grafting process, respectively. In the antibacterial experiment, the PVA/1%TiO2 NPs/BPTA film exhibited higher antibacterial activity than other films. Compared with the control group, the surviving population of S. aureus and E. coli decreased by 99.62 ± 0.38% and 98.27 ± 1.47%, respectively. The mechanism of reactive oxygen species (ROS) production was discussed, and the amount of ROS produced by the composite films under light and dark conditions was quantitatively measured. A cycling experiment after quenching ROS showed that the PVA/1%TiO2 NPs/BPTA composite film retained 81.01% and 66.12% of the original charging capacity of the OH• radical and H2O2 after seven cycles. In terms of biodegradability, the degradation performance of the PVA/TiO2 NPs/BPTA composite film was stronger than that of the pure PVA film. Thus, the PVA/TiO2 NPs/BPTA film is considered a promising antibacterial material with superior characteristics of structural stability, reusability, and functionality under both light and dark conditions.

The objective of this study was to examine longitudinal trends in the prevalence of dogs that are successfully immunized against rabies virus (as measured by sufficient serum antibodies) in Changsha, an urban center of China. The secondary objective was to investigate the factors affecting the seroprevalence of rabies virus antibodies in dogs. In this study, 4515 canine serum samples were collected from 57 pet hospitals (immunization points) during the period of 2015–2021 in five major urban areas of Kaifu, Furong, Tianxin, Yuhua, and Yuelu in Changsha, China. The enzyme-linked immunosorbent assay (ELISA) method was used to analyze the level and trend of rabies virus antibodies in serum and further evaluate the potential factors affecting the immunization effect from five factors: sex, age, time interval after most recent vaccination and sample collection, number of vaccinations, and vaccine manufacturer. The results showed that the seroconversion from the urban dog in Changsha steadily increased from 46.13% to 73.38% during 2015–2017. The seropositivity prevalence remained above the international standard (70%) from 2018 to 2020 and up to 90.99% in 2021. Further analysis showed that the seroconversion of rabies virus among dogs was significantly affected by the age, the number of vaccinations, time interval after the most recent vaccination and sample collection, and vaccine manufacturer, while sex had less influence. The overall rabies vaccination situation in urban areas of Changsha generally meets international standards, with only a few areas showing low levels of antibodies in dogs after vaccination and risk of infectiousness. Therefore, it is recommended that the first vaccination should be given when the dog is about three months old and regularly repeated every year after that. At the same time, antibody concentrations in dogs, especially in newborn puppies and older dogs, need to be tested promptly after vaccination at the required time to ensure that they are at a high level of immune protection, which can strengthen the supervision of rabies.

Whether to trust or distrust another individual is a complex interpersonal challenge, especially when such individuals behave inconsistently. It is still unclear as to how individuals learn and adapt to fluctuations in the trustworthiness of others and how this process changes from adolescence to adulthood. To address these issues, we implemented repeated rounds of a trust game within the context of a complicated and changeable interpersonal environment. Specifically, adolescents and adults played the role of trustors who had to decide whether to invest money in two anonymous partners carrying the risk of no reciprocation. Unbeknownst to participants, these two partners had different trustworthiness profiles: one partner initially yielded a higher initial return rate (70%) while the other initially yielded a lower initial return rate (30%). Crucially, over repeated rounds, these two partners gradually changed their responses to the point where, finally, return rates were both neutral (50%). Results indicated that all participants showed less updating in the negative direction in response to good-to-neutral partners while more updating in the positive direction in response to the bad-to-neutral partner. Compared to adults, this behavioral disparity in responses to good-to-neutral and bad-to-neutral partners was less pronounced in adolescents. Based on the computational modeling approach, the potential mechanisms underlying their behavioral patterns were revealed: the higher learning rate promoted flexible adaptions in participants to untrustworthy trustees as they changed to neutral. The less pronounced distinction between good-to-neutral and bad-to-neutral partners in adolescents was related to their lower learning rate. Overall, our study extends the understanding of trust behavior to a fluctuating social context and highlights the role of social learning in social emotion and interaction.

Solid-state lithium sulfur batteries are becoming a breakthrough technology for energy storage systems due to their low cost of sulfur, high energy density and high level of safety. However, its commercial application has been limited by the poor ionic conductivity and sulfur shuttle effect. In this paper, a nitrogen-doped porous carbon fiber (NPCNF) active material was prepared by template method as a sulfur-host of the positive sulfur electrode. The morphology was nano fiber-like and enabled high sulfur content (62.9 wt%). A solid electrolyte membrane (PVDF/LiClO4/LATP) containing polyvinylidene fluoride (PVDF) and lithium aluminum titanium phosphate (Li1.3Al0.3Ti1.7(PO4)3) was prepared by pouring and the thermosetting method. The ionic conductivity of PVDF/LiClO4/LATP was 8.07 × 10−5 S cm−1 at 25 °C. The assembled battery showed good electrochemical performance. At 25 °C and 0.5 C, the first discharge specific capacity was 620.52 mAh g−1. After 500 cycles, the capacity decay rate of each cycle was only 0.139%. The synergistic effect between the composite solid electrolyte and the nitrogen-doped porous carbon fiber composite sulfur anode studied in this paper may reveal new approaches for improving the cycling performance of a solid-state lithium-sulfur battery.

This study aimed to investigate the influence of serum folate, vitamin B12 (VitB12) levels, and inflammation-based scores on the motor performance status in Parkinson's disease (PD). We retrospectively collected data from 148 consecutive patients with idiopathic PD first admitted to our hospital. We measured whole blood count, albumin, lactate dehydrogenase, C-reactive protein, folate, and VitB12 levels and calculated the inflammation-based scores. The following scales were applied to assess the motor performance status: activity of daily living scale (ADL, the Barthel Index), the Unified Parkinson's Disease Rating Scale Part III (UPDRS-III), and Hoehn–Yahr (H–Y) classification. The geometric mean of folate and VitB12 levels were 11.87 (ng/ml) and 330.52 (pmol/L), respectively. Folate deficiency (serum level < 4.0 ng/ml) and VitB12 deficiency (serum level < 133 pg/ml) were present in 0.7 and 5.4% of the patients, respectively. The mean prognostic nutritional index (PNI) and systemic immune-inflammation index (SII) were 47.78 ± 4.42 and 470.81 ± 254.05, respectively. The multivariate analyses showed that serum VitB12 level (P = 0.002) and SII (P = 0.005) were significant factors for ADL score; serum folate (P = 0.027) and VitB12 (P = 0.037) levels for UPDRS-III score; and serum folate (P = 0.066) and VitB12 (P = 0.017) levels for H–Y classification. The elevated folate level did correlate with greater decline in UPDRS-III score (P = 0.023) and H–Y classification (P = 0.003), whereas there was an obvious increase in ADL score (P = 0.048). SII was negatively associated (P < 0.001) with the ADL score. The three-dimensional drawing, combined with the effect of folate and VitB12 levels, showed that the lowest level of folate was associated with the lowest ADL score and the highest UPDRS-III score and H–Y classification. This study indicates that serum folate, VitB12 levels, and SII are significant factors influencing the motor performance status in patients with PD. SII is negatively associated with ADL. Elevated serum folate level correlates with mild motor impairment in patients with PD.

This study investigated Chinese university students’ technology-assisted self-regulated learning (SRL) strategies and whether the technology-based SRL strategies mediated the associations between English language self-efficacy, English enjoyment, and learning outcomes. Data were collected from 525 undergraduate students in mainland China through three self-report questionnaires and the performance on an English language proficiency test. While students reported an overall moderate level of SRL strategies, they reported a high level of technology-based vocabulary learning strategies. A statistically significant positive relationship was noted between the use of technology-based SRL strategies and students’ English learning outcomes. English language self-efficacy and English language enjoyment were both related to technology-based SRL strategies. Furthermore, SRL strategies fully mediated the relationship between English enjoyment and English learning outcomes, but the association between English enjoyment and SRL strategies was only partially mediated by English language self-efficacy. Pedagogically, findings of this study suggest that training and instruction aimed at promotion of modern educational technology among students need to give attention to developing their strategic awareness of motivation regulation in optimizing effectiveness of their technology use in learning the target language.

Nocardia usually manifests as opportunistic infections in immunocompromised hosts. Here, we report a rare case of an immunocompetent patient with lymphocutaneous nocardiosis. The patient was a 34-year-old man presenting with fever, multiple scattered pustules on both upper limbs and several subcutaneous nodules on the left elbow and forearm. Skin biopsy of the subcutaneous nodule revealed suppurative inflammation of the lymph nodes. Pus cultures were finally identified as Nocardia brasiliensis . The patient fully recovered without relapse after receiving optimized antimicrobial therapy consisting of linezolid combined with sulfonamides. Nocardiosis is a rare opportunistic disease which may be fatal and usually affects immunocompromised hosts, resulting in suppurative and granulomatous inflammation. Nocardia has a long culture cycle, is difficult to diagnose, and is more likely to be neglected in healthy young people. The present case suggests that physicians should be aware that nocardiosis is a differential diagnosis to consider in patients with suppurative infection, especially when anti-infective treatment is ineffective.

Dimethoate (DT) is an environmental pollutant widely used in agricultural fields and home gardens. Studies have shown that exposure to DT causes reproductive defects in both male and female animals. However, the effects of DT exposure on oocyte maturation and the approach to counteract it are not yet known. Here, we investigated the toxicity of DT on porcine oocyte maturation and the protective effects of melatonin (MT) on DT-exposed oocytes. DT exposure with 1.5 mM partially inhibited cumulus cell expansion and significantly reduced the rate of first polar body extrusion (pb1) during oocyte maturation. Parthenogenetically activated embryos derived from DT-exposed oocytes could not develop to the 2-cell and blastocyst stage. Furthermore, DT exposure led to a significant increase in the rates of misaligned chromosomes, disorganized spindles, and abnormal actin assembly. DT exposure severely disrupted the distribution patterns of mitochondria in oocytes but did not change the subcellular localizations of cortical granules. Importantly, MT supplementation rescued the meiotic and developmental defects of DT-exposed oocytes through repressing the generation of excessive reactive oxygen species (ROS) and autophagy, and DNA damage accumulation. These results demonstrate that melatonin protects against meiotic defects induced by DT during porcine oocyte maturation.

Using 318 household data concerning children during middle childhood (8–13), we examined the association among each parent’s marital satisfaction, the child’s perceived family functioning, and the child’s anxiety and depression. Second, we investigated whether the other parent could buffer or facilitate this chain effect by co-viewing programs via various devices with their child so as to improve the child’s perceived family functioning. Results verified the mediation effect that maternal marital satisfaction was positively associated with the child’s perceived family functioning, which, in turn, decreased the child’s depression. In addition, the results indicated that increased paternal co-viewing enhanced the positive association between maternal marital satisfaction and the child’s perceived family functioning and then decreased the child’s depression. The theoretical and practical implications are discussed within the framework of family systems theory, parental media interventions, and the different roles of the father and mother in family functionality.

The Chevrel phase (CP) (Mo _6 S _8 ), which is used as an electrode material in Mg rechargeable batteries, has a capacity limit owing to ion insertion and trapping. To address this problem, we modify the wire structure of the CP. Mo _6 S _3 I _6 nanowires, in which iodiene is substituted for Mo _6 S _9 nanowires as infinite CP structures, can be synthesized in various ways. When synthesizing stoichiometrically, an unwanted secondary phase may appear. We solved these problems by reducing the synthesis time. Electrochemical analysis was performed using these nanowires as an active material in Mg batteries.

High-risk Human papillomaviruses (HPVs) types are associated with more than 90% of premalignant and malignant squamous lesions of the uterine cervix. The E6 oncoprotein of high-risk HPVs is a key determinant in cell transformation because it induces the degradation of the host pro-apoptotic tumor suppressor p53. E6 recruits the intracellular ubiquitin ligase E6AP and subsequently induces proteasome-dependent p53 degradation. Neither E6 nor E6AP alone interact with p53; however, the precise mechanism of the functional regulation of the E6/E6AP/p53 complex is unclear. Here, we showed that the high-risk HPV E6 proteins are ubiquitinated during E6/E6AP/p53 complex assembly and degraded by the proteasome system. Increasing p53 expression enhanced E6/E6AP/p53 assembly and facilitated E6 ubiquitination and degradation. The dominant negative mutant of p53 R175H, which does not efficiently bind E6, decreased E6 ubiquitination and increased stability. Furthermore, we showed that the ubiquitin ligase E6AP is essential for E6 ubiquitination, and downregulation of E6AP expression increased E6 stability. We also showed that p53 R175H inhibited E6-mediated p53 degradation. Consistently, the host deubiquitinating enzyme USP15 removed ubiquitin chains from E6 proteins and inhibited E6-mediated p53 degradation. Crucially, ectopic expression of either p53 R175H or USP15 promoted p53-triggered apoptosis in human cervical cancer cells. Considering the importance of ubiquitinated E6 on p53 degradation, the disruption of E6 ubiquitination represents an attractive pharmacological intervention against HPV-positive human cervical cancer.ImportanceVirtually 100% of cervical cancers are linked to HPV infection. Commercial HPV vaccines are estimated to prevent up to 90% of HPV-associated cancers, while they do not eliminate persistent HPV infections and have no effect on the progression to malignancy. Hence, the development of novel therapeutic interventions against HPV is urgently required. The HPV oncoprotein E6 binds to the intracellular E3 ubiquitin ligase E6AP and p53 resulting in the degradation of p53. In this study, we demonstrate that HPV E6 is ubiquitinated by E6AP in presence of p53. Crucially, ubiquitination of E6 is important for p53 degradation and blockage of E6 ubiquitination negatively interferes with E6-mediated p53 degradation and enhances the apoptotic effects of p53 and the cytotoxicity of DNA damage in HPV-positive cervical cancer cells. Importantly, our data suggest that the HPV oncogene E6 might be an optimal pharmacologic.

Background Quantitative real-time polymerase chain reaction (RT-qPCR) is a sensitive method for quantifying mRNA abundance. With relative expression analysis, however, reliable data output is dependent on stably expressed reference genes across the samples being studied. In anorectal malformations (ARMs), there is limited data on the selection of appropriate reference genes. Purpose This study was aimed to investigate the optimal reference genes for PCR in ARM rat models. Methods We selected 15 commonly used reference genes (Rps18, Actb, B2m, Gapdh, Ppia, Hprt1, Pgk1, Ywhaz, Tbp, Ubc, Rps16, Rpl13a, Rplp1, Sdha, and Hmbs) as candidate reference genes and detected their mRNA expression in ARM samples by RT-qPCR. The expression stability and variability of these transcripts were subsequently evaluated using four methods (geNorm, NormFinder, comparative ΔCt, and BestKeeper). Results The abundance of the candidate reference genes was qualified by RT-qPCR and the cycle threshold (Ct) values ranged between 14.07 (Rplp1) and 21.89 (Sdha). In the overall candidate genes, different variations existed across the different algorithms. A comprehensive analysis revealed that Rpl13a ranked first among the relatively stable genes, followed by Ywhaz, Rps18, Sdha, and Hmbs. Conclusions The most stable reference genes for RT-qPCR were Rpl13a, Ywhaz, and Rps18 in ETU-induced ARMs in rat fetus. This study provided a foundation for reference gene selection for future gene expression analyses.

This article presents the development and validation of the Pre-Service EFL Teachers' Motivational Beliefs about Instructional Use of Technology scale (PTMB-EFL) using a randomly split sample. Confirmatory factor analysis supported a 23-item six-factor structure of the PTMB-EFL generated from exploratory factor analysis. Significant correlations between the PTMB-EFL factors and teachers' perceived actual classroom technology use practices supported the concurrent validity of the PTMB-EFL. A second-order confirmatory factor analysis further provided empirical evidence to consider motivational beliefs about instructional use of technology as a unitary construct with six correlated but distinct motivational belief factors. In addition, unlike previous technology acceptance studies, this study revealed that among the six types of motivational beliefs, growth mindset was the strongest predictor of perceived actual classroom technology use practices. The PTMB-EFL can be used as an evaluation tool to appraise pre-service EFL or ESL teacher technology-based English teaching experience during their practicum, and as a research tool to investigate more associations between instructional use of technology and other contextual and teacher factors.

The tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) has shown strong and explicit cancer cell-selectivity, which results in little toxicity toward normal tissues, and has been recognized as a potential, relatively safe anticancer agent. However, several cancers are resistant to the apoptosis induced by TRAIL. A recent study found that shikonin b (alkannin, 5,8-dihydroxy-2-[(1S)-1-hydroxy-4-methylpent-3-en-1-yl]naphthalene-1,4-dione) might induce apoptosis in TRAIL-resistant cholangiocarcinoma cells through reactive oxygen species (ROS)-mediated caspases activation. However, the strong cytotoxic activity has limited its potential as an anticancer drug. Thus, the current study intends to discover novel shikonin derivatives which can sensitize the liver cancer cell to TRAIL-induced apoptosis while exhibiting little toxicity toward the normal hepatic cell. The trypan blue exclusion assay, western blot assay, 4′,6-diamidino-2-phenylindole (DAPI) staining and the terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay as well as the ‘comet’ assay, were used to study the underlying mechanisms of cell death and to search for any mechanisms of an enhancement of TRAIL-mediated apoptosis in the presence of ASH. Herein, we demonstrated that non-cytotoxic doses of acetylshikonin (ASH), one of the shikonin derivatives, in combination with TRAIL, could promote apoptosis in HepG2 cells. Further studies showed that application of ASH in a non-cytotoxic dose (2.5 μM) could increase intracellular ROS production and induce DNA damage, which might trigger a cell intrinsic apoptosis pathway in the TRAIL-resistant HepG2 cell. Combination treatment with a non-cytotoxic dose of ASH and TRAIL activated caspase and increased the cleavage of PARP-1 in the HepG2 cell. However, when intracellular ROS production was suppressed by N-acetyl-l-cysteine (NAC), the synergistic effects of ASH and TRAIL on hepatocellular carcinoma (HCC) cell apoptosis was abolished. Furthermore, NAC could alleviate p53 and the p53 upregulated modulator of apoptosis (PUMA) expression induced by TRAIL and ASH. Small (or short) interfering RNA (siRNA) targeting PUMA or p53 significantly reversed ASH-mediated sensitization to TRAIL-induced apoptosis. In addition, Bax gene deficiency also abolished ASH-induced TRAIL sensitization. An orthotopical HCC implantation mice model further confirmed that co-treated ASH overcomes TRAIL resistance in HCC cells without exhibiting potent toxicity in vivo. In conclusion, the above data suggested that ROS could induce DNA damage and activating p53/PUMA/Bax signaling, and thus, this resulted in the permeabilization of mitochondrial outer membrane and activating caspases as well as sensitizing the HCC cell to apoptosis induced by TRAIL and ASH treatment.

This study was aimed to investigate the anti-tumor, anti-metastasis and immunomodulatory effects of Yifei Tongluo (YFTL), a Chinese herbal formula, in Lewis lung carcinoma mice and to explore the underlying mechanisms. LLC cells were inoculated subcutaneously in C57BL/6 mice to establish the Lewis lung carcinoma model. We observed that YFTL effectively inhibited tumor growth and prolonged the overall survival of tumor-bearing mice. Additionally, YFTL treatment resulted in a significantly decreased number of surface lung metastatic lesions compared with the model control group. Meanwhile, TUNEL staining confirmed that the tumors from YFTL-treated mice exhibited a markedly higher apoptotic index. The results suggest that Akt and mitogen-activated protein kinase (MAPKs) pathways may be involved in YFTL-induced apoptosis. The results show that YFTL also inhibited the vascular endothelial growth factor (VEGF), matrix metalloproteinases (MMP)-2, MMP-9, N-cadherin, and Vimentin expression, but increased E-cadherin expression. Mechanistic studies indicated that YFTL could suppress the angiogenesis and the epithelial-mesenchymal transition (EMT) of the tumor through Akt/ERK1/2 and TGFβ1/Smad2 pathways. In addition, YFTL also showed immunomodulatory activities in improving the immunosuppressive state of tumor-bearing mice. Therefore, our findings could support the development of YFTL as a potential antineoplastic agent and a potentially useful anti-metastatic agent for lung carcinoma therapy.

In this study, the aim was to investigate the effect of bergenin on immune function and antioxidation in cyclophosphamide (Cy)-induced immunosuppressed mice. Firstly, we estimated its effect on immune organs. Histological analysis and indexes of immune organs showed that cyclophosphamide exhibited spleen and thymus injury compared with the normal control, which was alleviated by bergenin. Secondly, bergenin also enhanced the humoral immune function through increasing the level of IgM and IgG in serum. Thirdly, bergenin also enhanced the cellular immune function. The results indicate that bergenin increased peritoneal macrophage functions, the proliferation of T and B lymphocytes, NK and CTL cell activities, and T (CD4+ and CD8+) lymphocyte subsets. Besides, bergenin also had the ability to modulate the Th1/Th2 balance. Moreover, bergenin prevented the Cy-induced decrease in numbers of peripheral RBC, WBC and platelets, providing supportive evidence for their anti-leukopenia activities. Finally, bergenin also reversed the Cy-induced decrease in the total antioxidant capacity including activities of superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GSH-Px). In conclusion, bergenin protected against Cy-induced adverse reactions by enhancing humoral and cellular immune functions and augmenting antioxidative activity and could be considered as a potential immunomodulatory agent.

In this paper, the gas relative permeability considering slippage effect has been experimentally examined under various experimental conditions (i.e., ambient, high confining pressure, and high temperature). Experimentally, Klinkenberg permeabilities of 12 core samples have been measured by using steady-state flow experiment. It has been found that the Klinkenberg permeability is independent of the experimental temperature and dramatically decreases as confining pressure is increasing. Furthermore, linear correlations have been newly developed between the Klinkenberg permeability and the gas-measured permeability under various conditions. Subsequently, the developed correlations are correspondingly applied to calibrate the gas relative permeability. It has been found that the gas relative permeability can be overestimated without consideration of the slippage effect, i.e., Klinkenberg effect. In addition, the newly developed correlations have been applied to analyze the sensitivity of gas–water relative permeability to gas-measured permeability, confining pressure, and temperature. It is demonstrated that mobile water greatly alleviates the gas relative permeability in comparison to irreducible water. Although an increased confining pressure simultaneously reduces the effective water phase and gas phase permeability, the gas relative permeability increases and the water relative permeability decreases as the confining pressure increases. It is attributed to the fact that the effective water phase permeability is more sensitive to the confining pressure. Given an elevated experimental temperature, the gas relative permeability is reduced while the water relative permeability is enhanced, implying the significance of temperature effect on gas–water relative permeability measurements.

This study was aimed to investigate the chemical composition, antioxidant activities and hepatoprotective effect of flavonoids from Ziziphus jujuba cv. Jinsixiaozao (ZJF). The composition of ZJF was analyzed by high performance liquid chromatography (HPLC) and Liquid chromatography–mass spectrometry (LC–MS), and antioxidant properties were investigated by biological assays in vitro. The hepatoprotective activity of ZJF was evaluated in acetaminophen (APAP)-treated BALB/c mice. Results indicate that ZJF displayed significant antioxidant capacity. Pretreatment with ZJF significantly decreased APAP-elevated serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP) and total bilirubin (TB). Activities of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) were enhanced with ZJF administration, while malondialdehyde (MDA) level and glutathione (GSH) depletion were reduced. Meanwhile, ZJF reversed the suppression of nuclear factor erythroid 2-related factor 2 (Nrf2) nuclear translocation, and up-regulated the protein expression of NAD(P)H: quinone oxidoreductase 1(NQO1) in liver damage mice. Furthermore, ZJF attenuated APAP-induced inflammatory mediator production, such as nitric oxide (NO), tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6) and interleukin-1β (IL-1β). Expression of p65 showed that ZJF dampened nuclear factor-κB (NF-κB) activation. The results strongly indicate that the hepatoprotective role of ZJF in APAP-induced hepatotoxicity might result from its induction of antioxidant defense via activation of Nrf2 and reduction of inflammation via inhibition of NF-κB.

Nuclear factor E2-related factor 2 (Nrf2) appears to be an attractive therapeutic target for the treatment of cardiac disease. We investigated whether a synthetic triterpenoid derivative of dihydro-CDDO-trifluoroethylamide (dh404), a novel Nrf2 activator, protects against pathological cardiac responses to hemodynamic stress in mice.Cardiac maladaptive remodeling and dysfunction were established by transverse aortic constriction (TAC) in mice. Hypertrophic growth of rat neonatal cardiomyocytes was induced by angiotensin II (Ang II). Cell death of rat neonatal cardiomyocytes was induced with hydrogen peroxide (H₂O₂). Cellular proliferation of rat neonatal cardiac fibroblasts was induced by Ang II, norepinephrine (NE) and phenylephrine (PE). Protein expression was assessed by immunochemical staining and Western blots. Gene expression was determined by real time reverse transcription-polymerase chain reaction (Q-PCR).TAC suppressed myocardial Nrf2 expression, increased myocardial 4-hydroxy-2-nonenal and 8-hydroxydeoxyguanosine levels, and induced cardiac hypertrophy, fibrosis and apoptosis, and overt heart failure and death in mice. Administration of dh404 inhibited the pathological cardiac remodeling and dysfunction, and reduced the mortality. Moreover, dhd404 elevated myocardial levels of Nrf2 and Nrf2 nuclear translocation with a dramatic suppression of the oxidative stress in the heart. Dh404 inhibited hypertrophic growth and death in primary culture of rat neonatal cardiomyocytes and suppressed proliferation in primary culture of rat neonatal cardiac fibroblasts. However, these effects of dh404 were blunted by knocking down of Nrf2.These findings demonstrate that dh404 prevents pathological cardiac remodeling and dysfunction by activating Nrf2, indicating a therapeutic potential of dh404 for cardiac disease.