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Background: Accurately stratifying patients with pulmonary arterial hypertension (PAH) is very important, and traditional risk scores still have internal heterogeneity. This study aimed to construct a risk stratification model that can accurately identify clinical worsening (CW) events in conventional low‐intermediate risk patients with pulmonary hypertension under targeted drug treatment by using echocardiographic parameters. Methods: This study is a single‐center, prospective study, including 105 PAH patients who underwent regular follow‐up at Guangdong Provincial People's Hospital from October 2021 to April 2023. The primary endpoint was the occurrence of CW, including death, hospitalization due to pulmonary hypertension, escalation of targeted drug therapy, and worsening of PAH. The predictive value of the echocardiography‐based three‐strata risk model was assessed using Kaplan‐Meier curves and COX regression analysis. Results: A total of 98 PAH patients were ultimately included in this study. The median follow‐up duration was 26 months (range 7–28 months). The echocardiography‐based three‐strata model included the ratio of tricuspid annular plane systolic excursion and pulmonary artery systolic pressure (TAPSE/PASP) and inferior vena cava (IVC). The echocardiography‐based three‐strata model had higher diagnostic value (C‐index =.76) compared to the 2022 ESC/ERS three‐strata model and four‐strata model (C‐index =.66 and C‐index =.61, respectively). PAH patients with lower TAPSE/PASP and wider IVC showed a higher CW rate compared to patients with higher TAPSE/PASP and normal IVC (HR = 15.1, 95%CI:4.4‐51.9, p <.001). Conclusion: The echocardiography‐based three‐strata model based on TAPSE/PASP and IVC can effectively improve the stratification of low‐intermediate risk PAH patients under targeted treatment. [ABSTRACT FROM AUTHOR]

The ZnIn 2 S 4 @CdS photocatalyst with tuned catalytic sites promotes selective benzyl alcohol oxidation on the ZnIn 2 S 4 surface and H 2 evolution on the CdS surface. [Display omitted] Photocatalytic selective oxidation of alcohols into aldehydes and H 2 is a green strategy for obtaining both value-added chemicals and clean energy. Herein, a dual-purpose ZnIn 2 S 4 @CdS photocatalyst was designed and constructed for efficient catalyzing benzyl alcohol (BA) into benzaldehyde (BAD) with coupled H 2 evolution. To address the deep-rooted problems of pure CdS, such as high recombination of photogenerated carriers and severe photo-corrosion, while also preserving its superiority in H 2 production, ZnIn 2 S 4 with a suitable band structure and adequate oxidizing capability was chosen to match CdS by constructing a coupled reaction. As designed, the photoexcited holes (electrons) in the CdS (ZnIn 2 S 4) were spatially separated and transferred to the ZnIn 2 S 4 (CdS) by electrostatic pull from the built-in electric field, leading to expected BAD production (12.1 mmol g−1 h−1) at the ZnIn 2 S 4 site and H 2 generation (12.2 mmol g−1 h−1) at the CdS site. This composite photocatalyst also exhibited high photostability due to the reasonable hole transfer from CdS to ZnIn 2 S 4. The experimental results suggest that the photocatalytic transform of BA into BAD on ZnIn 2 S 4 @CdS is via a carbon-centered radical mechanism. This work may extend the design of advanced photocatalysts for more chemicals by replacing H 2 evolution with N 2 fixation or CO 2 reduction in the coupled reactions. [ABSTRACT FROM AUTHOR]

Simple Summary: Our study investigated how pigeons learn and make decisions. We found that pigeons showed a tendency to learn differently from good and bad experiences similar to humans and other animals; a pattern we call learning rate bias. Initially, pigeons are cautious and tend to learn more from the negative outcomes. As they learn and gain experience, they start to become more optimistic, favoring learning from the positive outcomes. We observed these changes through behavioral models and the neural activity in the striatum, a brain region involved in reward and learning. The shift from a cautious to a more confident approach in their decision-making suggests that pigeons use a flexible strategy for learning, which changes as they gather more information about what to expect from their choices. Understanding these patterns can help us learn more about basic learning processes shared across different species. Research in reinforcement learning indicates that animals respond differently to positive and negative reward prediction errors, which can be calculated by assuming learning rate bias. Many studies have shown that humans and other animals have learning rate bias during learning, but it is unclear whether and how the bias changes throughout the entire learning process. Here, we recorded the behavior data and the local field potentials (LFPs) in the striatum of five pigeons performing a probabilistic learning task. Reinforcement learning models with and without learning rate biases were used to dynamically fit the pigeons' choice behavior and estimate the option values. Furthemore, the correlation between the striatal LFPs power and the model-estimated option values was explored. We found that the pigeons' learning rate bias shifted from negative to positive during the learning process, and the striatal Gamma (31 to 80 Hz) power correlated with the option values modulated by dynamic learning rate bias. In conclusion, our results support the hypothesis that pigeons employ a dynamic learning strategy in the learning process from both behavioral and neural aspects, providing valuable insights into reinforcement learning mechanisms of non-human animals. [ABSTRACT FROM AUTHOR]

Simple Summary: Model-based decision-making guides organism behavior by representing the relationships between states. Previous studies have shown that the mammalian hippocampus (Hp) plays a key role in model-based learning. However, the hippocampal neural mechanisms of birds for model-based learning are largely unknown. We trained pigeons to perform a two-step task. Using a combination of neural analysis and computational modeling, we show that the pigeons use model-based inferences to learn multi-step tasks, and multiple LFP frequency bands collaboratively contribute to model-based learning. Specifically, the high-frequency (12–100 Hz) oscillations represent model-based valuations, while the low-frequency (1–12 Hz) neural similarity is influenced by the relationship between temporal context states. These findings expand the understanding of the hippocampus' role in avian model-based learning. Model-based decision-making guides organism behavior by the representation of the relationships between different states. Previous studies have shown that the mammalian hippocampus (Hp) plays a key role in learning the structure of relationships among experiences. However, the hippocampal neural mechanisms of birds for model-based learning have rarely been reported. Here, we trained six pigeons to perform a two-step task and explore whether their Hp contributes to model-based learning. Behavioral performance and hippocampal multi-channel local field potentials (LFPs) were recorded during the task. We estimated the subjective values using a reinforcement learning model dynamically fitted to the pigeon's choice of behavior. The results show that the model-based learner can capture the behavioral choices of pigeons well throughout the learning process. Neural analysis indicated that high-frequency (12–100 Hz) power in Hp represented the temporal context states. Moreover, dynamic correlation and decoding results provided further support for the high-frequency dependence of model-based valuations. In addition, we observed a significant increase in hippocampal neural similarity at the low-frequency band (1–12 Hz) for common temporal context states after learning. Overall, our findings suggest that pigeons use model-based inferences to learn multi-step tasks, and multiple LFP frequency bands collaboratively contribute to model-based learning. Specifically, the high-frequency (12–100 Hz) oscillations represent model-based valuations, while the low-frequency (1–12 Hz) neural similarity is influenced by the relationship between temporal context states. These results contribute to our understanding of the neural mechanisms underlying model-based learning and broaden the scope of hippocampal contributions to avian behavior. [ABSTRACT FROM AUTHOR]

The ZnO/Zn 3 In 2 S 6 /Pt photocatalyst with integrated S-scheme/Schottky heterojunctions exhibited an enhanced H 2 evolution and an efficient bisphenol A removal. [Display omitted] Photocatalytic water splitting has been identified as a promising solution to tackle the current environmental and energy crisis in the world. However, the challenge of this green technology is the inefficient separation and utilization of photogenerated electron-hole pairs in photocatalysts. To overcome this challenge in one system, a ternary ZnO/Zn 3 In 2 S 6 /Pt material was prepared as a photocatalyst using a stepwise hydrothermal process and in-situ photoreduction deposition. The integrated S-scheme/Schottky heterojunction in the constructed ZnO/Zn 3 In 2 S 6 /Pt photocatalyst enabled it to exhibit efficient photoexcited charge separation/transfer. The evolved H 2 reached up to 3.5 mmol g-1h-1. Meanwhile, the ternary composite possessed a high cyclic stability against photo-corrosion under irradiation. Practically, the ZnO/Zn 3 In 2 S 6 /Pt photocatalyst also showed great potential for H 2 evolution while simultaneously degrading organic contaminants like bisphenol A. It is hoped in this work that the incorporation of Schottky junctions and S-scheme heterostructures in the construction of photocatalysts would lead to accelerated electron transfer and high photoinduced electron-hole pair separation, respectively, to synergistically enhance the performance of photocatalysts. [ABSTRACT FROM AUTHOR]

Copper (Cu) homeostasis is attributed to a fine interplay among intake, transport, and clearance of the micronutrient in the governance of physiological processes. Cuproptosis, or Cu-induced cell death, develops as a result of intracellular Cu accumulation, and is dependent on mitochondrial respiration and tricarboxylic acid cycle to evoke protein lipidation, membrane permeabilization, cellular disruption, and cell death. Serum Cu level, which is often prognostic for disease prevalence, is closely associated with cardiometabolic risk factors, such as atherosclerosis, coronary heart disease, ischemic heart disease, heart failure, type 2 diabetes mellitus, and obesity. Preclinical evidence demonstrates that modulation of Cu intake, transport, and clearance can be harnessed for therapeutic purpose in cardiovascular and metabolic diseases. Copper (Cu) homeostasis is gaining increasing attention in human health as both Cu overload and deficiency evokes pathological changes including cardiovascular diseases (CVDs). Cu supplementation, nanocarriers, and chelators have all exhibited therapeutic promise in some human diseases, although how Cu dyshomeostasis and cuproptosis, a novel form of regulated cell death, contribute to CVD pathology remains elusive. Here, we discuss Cu dyshomeostasis and the potential role of cuproptosis in various CVDs. We evaluate underlying cellular mechanisms, aiming to provide some insights regarding the utility of targeting Cu dyshomeostasis and cuproptosis as a novel strategy in the management of CVDs. [ABSTRACT FROM AUTHOR]

Medicinal plants are the main source of natural metabolites with specialised pharmacological activities and have been widely examined by plant researchers. Numerous omics studies of medicinal plants have been performed to identify molecular markers of species and functional genes controlling key biological traits, as well as to understand biosynthetic pathways of bioactive metabolites and the regulatory mechanisms of environmental responses. Omics technologies have been widely applied to medicinal plants, including as taxonomics, transcriptomics, metabolomics, proteomics, genomics, pangenomics, epigenomics and mutagenomics. However, because of the complex biological regulation network, single omics usually fail to explain the specific biological phenomena. In recent years, reports of integrated multi-omics studies of medicinal plants have increased. Until now, there have few assessments of recent developments and upcoming trends in omics studies of medicinal plants. We highlight recent developments in omics research of medicinal plants, summarise the typical bioinformatics resources available for analysing omics datasets, and discuss related future directions and challenges. This information facilitates further studies of medicinal plants, refinement of current approaches and leads to new ideas. [ABSTRACT FROM AUTHOR]

A novel bacterium of the genus Pontibacter, designated GY10130T, was isolated from rhizosphere soil of a mangrove plant Rhizophora stylosa collected from Guangxi province, China. Strain GY10130T was Gram-stain negative, positive for oxidase activities, aerobic, short rod-shaped cells without flagella. Growth was observed at 10–40 °C (optimum, 28 °C), pH 6.0–9.0 (optimum, 7.0) and NaCl concentrations of 0–4% (optimum, 1%). Strain GY10130T is closely related to members of the genus Pontibacter, namely P. beigongshangensis CGMCC 1.17104T (97.8%) and P. amylolyticus CGMCC 1.12749T (95.0%), P. humi SWU8T (94.7%), and less than 94.0% with other currently described type strains of Pontibacter. The strain GY10130T showed an ANI value of 80.6% and dDDH value of 23.2% with P. beigongshangensis CGMCC 1.17104T, followed by P. amylolyticus CGMCC 1.12749T with ANI and dDDH values of 72.9 and 13.8%, respectively. Strain GY10130T contains carotenoid-like pigments, but flexirubin-type pigments were absent. The cellular fatty acids (> 10%) consist of summed feature 4 (17:1 iso I/anteiso B) and iso-C15:0. The predominant menaquinone is MK-7. The polar lipids comprise phosphatidylethanolamine, two unidentified glycolipids, two unidentified aminolipids and six unidentified phospholipids. The genome length of strain GY10130T was 6.2 Mbp with a DNA G + C content of 47.1 mol% and 4727 protein-coding genes. The result of polyphasic taxonomic study show strain GY10130T represents one novel species of Pontibacter, Pontibacter qinzhouensis sp. nov., with the type strain GY10130T (=NBRC 113901T = CGMCC 1.16772T). [ABSTRACT FROM AUTHOR]

Panax japonicus var. major (PJ) is a valuable traditional Chinese medicinal plant that belongs to the Panax genus. Numerous studies have been conducted on the other Panax species, but only a limited number of studies have investigated the transcriptome and metabolome of PJ. Here, we analysed the transcriptome and metabolome from roots, stems, fruits, and leaves of PJ. A total of 507 plant defense-related nucleotide binding site (NBS) genes were identified, this result showed that PJ has the highest number of NBS genes compared with the other Panax species. Which indicated that NBS gene family has expanded in PJ, may be the key reason for stronger disease resistance of PJ. Moreover, 59 candidate genes involved in upstream pathways of saponins biosynthesis, 311 cytochrome P450 genes, and 147 UDP-dependent glycosyltransferase genes were identified, which were highly expressed in roots and leaves. Additionally, we also detected 1161 metabolites and 792 differentially accumulated metabolites, especially in leaves, fruits, and roots. Transcriptome, metabolome and RT-qPCR identified three UGT genes that could regulate triterpene saponin biosynthesis. This research will enhance our knowledge of saponins biosynthesis and disease resistance breeding of PJ. [Display omitted] • This study integrated transcriptomic and metabolomic analyses on four PJ tissues. • This study identified 216,108 unigenes, surpassing previous studies. • DEGs related to plant growth, disease resistance, and secondary metabolites were identified. • PJ has the highest number of NBS genes with higher expression levels, aiding stronger disease resistance. • Triterpenoid saponin biosynthesis upstream pathways occur in leaves, while downstream pathways occur in roots. [ABSTRACT FROM AUTHOR]

Anesthetic-induced brain activity study is crucial in avian cognitive-, consciousness-, and sleep-related research. However, the neurobiological mechanisms underlying the generation of brain rhythms and specific connectivity of birds during anesthesia are poorly understood. Although different kinds of anesthetics can be used to induce an anesthesia state, a comparison study of these drugs focusing on the neural pattern evolution during anesthesia is lacking. Here, we recorded local field potentials (LFPs) using a multi-channel micro-electrode array inserted into the nidopallium caudolateral (NCL) of adult pigeons (Columba livia) anesthetized with chloral hydrate, pelltobarbitalum natricum or urethane. Power spectral density (PSD) and functional connectivity analyses were used to measure the dynamic temporal neural patterns in NCL during anesthesia. Neural decoding analysis was adopted to calculate the probability of the pigeon’s brain state and the kind of injected anesthetic. In the NCL during anesthesia, we found elevated power activity and functional connectivity at low-frequency bands and depressed power activity and connectivity at high-frequency bands. Decoding results based on the spectral and functional connectivity features indicated that the pigeon’s brain states during anesthesia and the injected anesthetics can be effectively decoded. These findings provide an important foundation for future investigations on how different anesthetics induce the generation of specific neural patterns.Graphical Abstract: Anesthetic-induced brain activity study is crucial in avian cognitive-, consciousness-, and sleep-related research. However, the neurobiological mechanisms underlying the generation of brain rhythms and specific connectivity of birds during anesthesia are poorly understood. Although different kinds of anesthetics can be used to induce an anesthesia state, a comparison study of these drugs focusing on the neural pattern evolution during anesthesia is lacking. Here, we recorded local field potentials (LFPs) using a multi-channel micro-electrode array inserted into the nidopallium caudolateral (NCL) of adult pigeons (Columba livia) anesthetized with chloral hydrate, pelltobarbitalum natricum or urethane. Power spectral density (PSD) and functional connectivity analyses were used to measure the dynamic temporal neural patterns in NCL during anesthesia. Neural decoding analysis was adopted to calculate the probability of the pigeon’s brain state and the kind of injected anesthetic. In the NCL during anesthesia, we found elevated power activity and functional connectivity at low-frequency bands and depressed power activity and connectivity at high-frequency bands. Decoding results based on the spectral and functional connectivity features indicated that the pigeon’s brain states during anesthesia and the injected anesthetics can be effectively decoded. These findings provide an important foundation for future investigations on how different anesthetics induce the generation of specific neural patterns. [ABSTRACT FROM AUTHOR]

Background: Panax notoginseng (Burk.) F. H. Chen (PN) belonging to the genus Panax of family Araliaceae is widely used in traditional Chinese medicine to treat various diseases. PN taproot, as the most vital organ for the accumulation of bioactive components, presents a variable morphology (oval or long), even within the same environment. However, no related studies have yet explained the molecular mechanism of phenotypic differences. To investigate the cause of differences in the taproot phenotype, de novo and comparative transcriptomic analysis on PN taproot was performed. Results: A total of 133,730,886 and 114,761,595 paired-end clean reads were obtained based on high-throughput sequencing from oval and long taproot samples, respectively. 121,955 unigenes with contig N50 = 1,774 bp were generated by using the de novo assembly transcriptome, 63,133 annotations were obtained with the BLAST. And then, 42 genes belong to class III peroxidase (PRX) gene family, 8 genes belong to L-Ascorbate peroxidase (APX) gene family, and 55 genes belong to a series of mitogen-activated protein kinase (MAPK) gene family were identified based on integrated annotation results. Differentially expressed genes analysis indicated substantial up-regulation of PnAPX3 and PnPRX45, which are related to reactive oxygen species metabolism, and the PnMPK3 gene, which is related to cell proliferation and plant root development, in long taproots compared with that in oval taproots. Furthermore, the determination results of real-time quantitative PCR, enzyme activity, and H2O2 content verified transcriptomic analysis results. Conclusion: These results collectively demonstrate that reactive oxygen species (ROS) metabolism and the PnMPK3 gene may play vital roles in regulating the taproot phenotype of PN. This study provides further insights into the genetic mechanisms of phenotypic differences in other species of the genus Panax. [ABSTRACT FROM AUTHOR]

As one of the major constitutes of human society, education has been continuously producing a huge amount of data and become an important of sources of big data. Deeply mining and analyzing these big education data are of practical significance for optimizing education resource deployment and improving education quality. However, the big education data are often of diverse types and from multiple parties, which raises a big challenge for accurate and reasonable educational data fusion especially when the educational data are correlated with each other. In view of this challenge, we put forward a novel cloud computing-aided multi-type data fusion approach considering data correlation in education, to accommodate the big volume, diverse types and correlation of educational data. In concrete, the data fusion operation is mainly based on the Mahalanobis distances which can overcome the data diversity in multiple-dimensional data fusion for education. Afterwards, we provide a case study to show the concrete steps of our proposal. At last, a set of experiments are deployed to validate the feasibility of our proposal in this paper. Experimental results prove the effectiveness and efficiency of our approach in dealing with multi-type data fusion with correlation in education. [ABSTRACT FROM AUTHOR]

• Three pigeons performed social cooperation tasks by using neural feedback training. • They can achieve cross-brain neural synchronization after training. • The intra- and inter-brain functional connectivity enhance with the training time. • This phenomenon is related to the promotion of social cooperation among pigeons. Multi-brain network, also known as social cooperative network, is formed by multiple animal or human brains, whose changes of functional connectivity in the intra- and inter-brain during construction are unclear at present. To investigate the intra- and inter-brain functional connectivity of pigeons while performing a social cooperation task, we designed an inter-brain synchronization task to train three pigeons to synchronize their neural activities using cross-brain neurofeedback. Then the neural signals of three pigeons were simultaneously recorded by using a hyperscanning approach, and inter-brain synchronization was calculated using the phase-locked value (PLV) online. Finally, the intra- and inter-brain functional connectivity of three pigeons were analyzed. We found that during long-term neurofeedback training, with the increase of the inter-brain synchronization of three pigeons, the intra- and inter-brain functional connectivity also enhance significantly. Moreover, we also found that the above phenomenon relies on the external visual cue. These results suggest that the promotion of social cooperation is the result of the modulation between the intra- and inter-brain, which may be an underlying neural mechanism of the communication and cooperation among individuals in social networks. [ABSTRACT FROM AUTHOR]

CD74, a non-polymorphic type II transmembrane glycoprotein and MHC class II chaperone, is the cell surface receptor for the inflammatory cytokine macrophage migration inhibitory factor (MIF) and participates in inflammatory signaling regulation. This study examined the potential role of CD74 in binge drinking-induced cardiac contractile dysfunction. WT and CD74 knockout mice were exposed to ethanol (3 g/kg/d, i.p., for 3 days). Echocardiography, cardiomyocyte function, histological staining and autophagy signaling including AMPK, mTOR, and AMPK downstream signals Skp2 and Sirt1 were evaluated. Our results revealed that ethanol challenge overtly compromised echocardiographic, cardiomyocyte contractile, intracellular Ca2+ and ultrastructural properties along with overt apoptosis, inflammation (elevated MIF, IL-1β and IL-6) and mitochondrial O 2 – production (p < 0.01), the effect of which was reconciled by CD74 ablation (p < 0.01 vs. ethanol group) with the exception of MIF expression. Ethanol challenge upregulated autophagy (p < 0.001), promoted AMPK phosphorylation and Sirt1 levels (p < 0.003) while suppressing mTOR phosphorylation and Skp2 levels (p < 0.02). These effects were reversed by CD74 ablation. In vitro studies demonstrated that short-term ethanol challenge compromised cardiomyocyte contractile function and facilitated GFP-Puncta formation, which were mitigated by CD74 knockout (p < 0.0001). Moreover, the CD74 ablation-offered beneficial effects against ethanol-induced cardiomyocyte dysfunction, and GFP-Puncta formation were nullified by the AMPK activator AICAR, the Skp2 inhibitor C1 or the Sirt1 activator SRT1720 (p < 0.0001). Taken together, our data revealed that CD74 ablation counteracts acute ethanol challenge-induced myocardial dysfunction, inflammation and apoptosis possibly through an AMPK-mTOR-Skp2-mediated regulation of autophagy. • We examined the effect of CD74 ablation on ethanol-induced cardiac anomalies. • CD74 ablation protects against ethanol challenge-induced cardiac contractile anomalies and mitochondrial injury. • CD74 inhibition offers benefit against ethanol-induced cardiac anomalies via suppression of AMPK-mediated autophagy. [ABSTRACT FROM AUTHOR]

Steroidal saponins, one of the most diverse groups of plant-derived natural products, elicit biological and pharmacological activities; however, the genes involved in their biosynthesis and the corresponding biosynthetic pathway in monocotyledon plants remain unclear. This study aimed to identify genes involved in the biosynthesis of steroidal saponins by performing a comparative analysis among transcriptomes of Paris polyphylla var. chinensis (PPC), Ypsilandra thibetica (YT), and Polygonatum kingianum (PK). De novo transcriptome assemblies generated 57,537, 140,420, and 151,773 unigenes from PPC, YT, and PK, respectively, of which 56.54, 47.81, and 44.30% were successfully annotated, respectively. Among the transcriptomes for PPC, YT, and PK, we identified 194, 169, and 131; 17, 14, and 26; and, 80, 122, and 113 unigenes corresponding to terpenoid backbone biosynthesis; sesquiterpenoid and triterpenoid biosynthesis; and, steroid biosynthesis pathways, respectively. These genes are putatively involved in the biosynthesis of cholesterol that is the primary precursor of steroidal saponins. Phylogenetic analyses indicated that lanosterol synthase may be exclusive to dicotyledon plant species, and the cytochrome P450 unigenes were closely related to clusters CYP90B1 and CYP734A1, which are UDP-glycosyltransferases unigenes homologous with the UGT73 family. Thus, unigenes of β-glucosidase may be candidate genes for catalysis of later period modifications of the steroidal saponin skeleton. Our data provide evidence to support the hypothesis that monocotyledons biosynthesize steroidal saponins from cholesterol via the cycloartenol pathway. Unlabelled Image [ABSTRACT FROM AUTHOR]

Simple Summary: The hippocampus (Hp) is involved in various aspects of spatial cognition during navigation, reflected in multiple neural oscillations across different frequencies. Given the structure homology between the avian and mammalian Hp, does it exhibit similar cross-frequency interaction mechanisms? Unlike rodents, birds can navigate by walking and flying. So, does the avian Hp share the same information interaction under different locomotor modes? In this study, we employed rock pigeons with exceptional spatial navigation abilities and conducted two goal-directed navigational experiments: a ground maze task with a circuitous paradigm and an outdoor homing flight task. These experiments were designed to explore the interactions between different frequency bands in the avian Hp during walking and flying navigation. The study revealed that phase–amplitude coupling (PAC) existed in the avian Hp during the navigational active phases. Meanwhile, the sub-frequency bands modulated by theta oscillations are different in different modes of locomotion. These findings support evidence for cross-frequency interactions in the avian Hp during spatial navigation and contribute to explaining the role of coupling, at least partially, in the ongoing cognitive demands during the navigation process. Navigation is a complex task in which the hippocampus (Hp), which plays an important role, may be involved in interactions between different frequency bands. However, little is known whether this cross-frequency interaction exists in the Hp of birds during navigation. Therefore, we examined the electrophysiological characteristics of hippocampal cross-frequency interactions of domestic pigeons (Columba livia domestica) during navigation. Two goal-directed navigation tasks with different locomotor modes were designed, and the local field potentials (LFPs) were recorded for analysis. We found that the amplitudes of high-frequency oscillations in Hp were dynamically modulated by the phase of co-occurring theta-band oscillations both during ground-based maze and outdoor flight navigation. The high-frequency amplitude sub-frequency bands modulated by the hippocampal theta phase were different at different tasks, and this process was independent of the navigation path and goal. These results suggest that phase–amplitude coupling (PAC) in the avian Hp may be more associated with the ongoing cognitive demands of navigational processes. Our findings contribute to the understanding of potential mechanisms of hippocampal PAC on multi-frequency informational interactions in avian navigation and provide valuable insights into cross-species evolution. [ABSTRACT FROM AUTHOR]

Objective We aimed to explore the mechanism of action of cervical transverse process tip acupuncture in a rat model of posterior circulation ischemic vertigo (PCIV) based on the G protein-coupled receptor (Mas)/protein kinase A(PKA)/cyclophosphoadenosine effector binding protein (CREB) pathway. Methods According to the random number table method, 32 male SD rats were divided into the sham operation group (n=8), the model group (n=8), the nimodipine group (n=8), and the electroacupuncture group (n=8). In all groups except for the sham operation group, the PCIV model was established by ligating the right common carotid artery (CCA) and the right subclavian artery (SCA). In the sham operation group, only the right CCA and the right SCA were removed and sutured directly without ligation. The nimodipine group was given intragastric administration of nimodipine suspension (12 mg/kg), and the electroacupuncture group selected C2, C4, and C6 transverse process tip for acupuncture, and performed electroacup uncture treatment on both sides of C2 and C6, 20 minutes each time. There was no intervention in the sham operation group and the model group. The intervention was given once a day for 14 days. Cerebral blood flow, the decrease decline rate of cerebral blood flow, and the step-down avoidance time were recorded in each group. Apoptosis of neurons in the vestibular nucleus of the right brainstem was observed by TUNEL staining, and the protein expression levels of Mas, PKA-Ca, CREB, p-CREB, Bcl-2, and Bax in the vestibular nucleus of the right brainstem were determined by Western blotting. Results Before intervention, compared with the sham operation group, cerebral blood flow in the right vestibular nucleus was decreased and decline rate of cerebral blood flow in the right vestibular nucleus was increased in the remaining three groups (P<0.05), which suggested that the model was successfully established. After intervention, compared with the sham operation group, the model group showed lower cerebral blood flow in the right vestibular nucleus, larger decline rate of cerebral blood flow in the right vestibular nucleus, apoptosis rate in the vestibular nucleus of the right brainstem and protein expression level of Bax increased, and reduced protein expression levels of Bcl-2, Mas, PKA-Ca, and p-CREB/CREB (P<0.05). Compared with the model group, the electroacupuncture group and the nimodipine group showed increased cerebral blood flow in the right vestibular nucleus, a smaller decline rate of cerebral blood flow in the right vestibular nucleus, a shorter step-down avoidance time, a decrease in apoptosis rate in the vestibular nucleus of the right brainstem, decreased protein expression level of Bax, and increased protein expression levels of Bcl-2, Mas, PKA-Ca, and p-CREB/CREB (P<0.05). Compared with the nimodipine group, the electroacupuncture group had increased cerebral blood flow in the right vestibular nucleus, a smaller decline rate of cerebral blood flow in the right vestibular nucleus, a shorter step-down avoidance time, a decrease in apoptosis rate in the vestibular nucleus of the right brainstem, decreased protein expression level of Bax, and increased protein expression levels of Bcl-2, Mas, PKA-Ca, and p-CREB/CREB (P<0.05). Conclusion Cervical transverse process tip acupuncture can effectively inhibit apoptosis in the vestibular nucleus in rats with PCIV. Its mechanism may be related to improving cerebral blood flow of the vestibular nucleus and activation of the Mas/PKA/CREB signaling pathway, followed by the modulation of the levels of relevant proteins to inhibit apoptosis in the vestibular nucleus. [ABSTRACT FROM AUTHOR]

Aging is accompanied with unfavorable geometric and functional changes in the heart involving dysregulation of Akt and autophagy. This study examined the impact of Akt2 ablation on life span and cardiac aging as well as the mechanisms involved with a focus on autophagy and mitochondrial integrity. Cardiac geometry, contractile, and intracellular Ca2+ properties were evaluated using echocardiography, IonOptix® edge-detection and fura-2 techniques. Levels of Sirt1, mitochondrial integrity, autophagy, and mitophagy markers were evaluated using Western blot. Our results revealed that Akt2 ablation prolonged life span (by 9.1%) and alleviated aging (24 months)-induced unfavorable changes in myocardial function and intracellular Ca2+ handling ( SERCA2a oxidation) albeit with more pronounced cardiac hypertrophy (58.1%, 47.8%, and 14.5% rises in heart weight, wall thickness, and cardiomyocyte cross-sectional area). Aging downregulated levels of Sirt1, increased phosphorylation of Akt, and the nuclear transcriptional factor Foxo1, as well as facilitated acetylation of Foxo1, the effects of which (except Sirt1 and Foxo1 acetylation) were significantly attenuated or negated by Akt2 ablation. Advanced aging disturbed autophagy, mitophagy, and mitochondrial integrity as evidenced by increased p62, decreased levels of beclin-1, Atg7, LC3B, BNIP3, PTEN-induced putative kinase 1 ( PINK1), Parkin, UCP-2, PGC-1α, and aconitase activity, the effects of which were reversed by Akt2 ablation. Aging-induced cardiomyocyte contractile dysfunction and loss of mitophagy were improved by rapamycin and the Sirt1 activator SRT1720. Activation of Akt using insulin or Parkin deficiency prevented SRT1720-induced beneficial effects against aging. In conclusion, our data indicate that Akt2 ablation protects against cardiac aging through restored Foxo1-related autophagy and mitochondrial integrity. [ABSTRACT FROM AUTHOR]

A reduction-type S-scheme photocatalyst with bifunctional ability shows efficient and stable activity for simultaneous water purification and H 2 production. [Display omitted] • The stepwise fabrication well preserves the microsphere morphology of Zn 3 In 2 S 6. • The in situ growth of In 2 S 3 on Zn 3 In 2 S 6 shows an efficient construction of S-scheme heterojunction. • The photogenerated holes and electrons are simultaneously utilized for pollutant degradation and H 2 production. • The engineered In 2 S 3 /Zn 3 In 2 S 6 photocatalyst displays an enhanced photocatalytic performance. S-scheme In 2 S 3 /Zn 3 In 2 S 6 microspheres were successfully prepared through hydrothermal means for enhanced photocatalytic H 2 evolution with simultaneous photodegradation of bisphenol A. The microspheres were assembled by embedding 2D In 2 S 3 nanosheets into 2D-3D Zn 3 In 2 S 6 hierarchical microspheres to enhance visible light absorption and separation/migration of photo-excited charge carriers. In bisphenol A aqueous solution, the photocatalytic H 2 evolution rate on In 2 S 3 /Zn 3 In 2 S 6 shows 15.7 and 7.9-folds improvements against that of the individual In 2 S 3 and Zn 3 In 2 S 6. Meanwhile, the degradation efficiency of bisphenol A is up to 95.8 %. The S-scheme charge transfer mechanism in In 2 S 3 /Zn 3 In 2 S 6 microspheres maximizes exerting the redox capability of Zn 3 In 2 S 6 for H 2 evolution and In 2 S 3 for bisphenol A degradation. [ABSTRACT FROM AUTHOR]

Doxorubicin as anticancer agent can cause dose-dependent cardiotoxicity and heart failure in the long term. Rutin as a polyphenolic flavonoid has been illustrated to protect hearts from diverse cardiovascular diseases. Its function is known to be related to its antioxidant and antiinflammatory activity which may regulate multiple cellular signal pathways. However, the role of rutin on doxorubicin-induced cardiotoxicity has yet to be discovered. In this study, we explored the protective role of rutin on doxorubicin-induced heart failure and elucidated the potential mechanisms of protective effects of rutin against cardiomyocyte death. We analyzed cardiac tissues at the time point of 8 weeks after doxorubicin treatment. The results by echocardiography, TUNEL staining, Masson's trichrome staining as well as Western blot analysis revealed that doxorubicin induced remarkable cardiac dysfunction and cardiotoxicity in mice hearts and cardiomyocytes, which were alleviated by rutin treatment. Western blot analysis indicated that the underlying mechanisms included inhibition excessive autophagy and apoptosis mediated by Akt activation. Collectively, our findings suggest that suppression of autophagy and apoptosis by administration of rutin could attenuate doxorubicin-induced cardiotoxicity, which enhances our knowledge to explore new drugs and strategies for combating this devastating side effect induced by doxorubicin. This article is part of a Special Issue entitled: Genetic and epigenetic control of heart failure - edited by Jun Ren & Megan Yingmei Zhang. [ABSTRACT FROM AUTHOR]

We calculate the electronic structure and magnetism of monolayer phosphorene doped by nonmagnetic atoms. O, S and Se impurities can induce the magnetic moment. O doping makes it become a spin-gapless semiconductor, but S and Se doping induces a half-metallic characteristic. The p orbital of dopant has a strong hybridization with P around impurities, which induces spin splitting of P and impurities. C induces a metallic character. B acts as n -type dopant and F results in p -type dopant. The magnetism of phosphorene doped by two O atoms strongly depends on the doping sites and distance between two O atoms. [ABSTRACT FROM AUTHOR]

Second hand smoke is an independent risk factor for cardiovascular disease. Adiponectin (APN), an adipose-derived adipokine, has been shown to offer cardioprotective effect through an AMPK-dependent manner. This study was designed to evaluate the impact of adiponectin deficiency on second hand smoke-induced cardiac pathology and underlying mechanisms using a mouse model of side-stream smoke exposure. Adult wild-type (WT) and adiponectin knockout (APNKO) mice were placed in a chamber exposed to cigarette smoke for 1 hour daily for 40 days. Echocardiographic, cardiomyocyte function, and intracellular Ca 2+ handling were evaluated. Autophagy and apoptosis were examined using western blot. 2′,7′-dichlorodihydrofluorescein diacetate (H 2 DCFDA) staining was used to evaluate reactive oxygen species (ROS) generation. Masson trichrome staining was employed to measure interstitial fibrosis. Our data revealed that adiponectin deficiency provoked smoke exposure-induced cardiomyopathy (compromised fractional shortening, disrupted cardiomyocyte function and intracellular Ca 2+ homeostasis, apoptosis and ROS generation). In addition, these detrimental effects of side-stream smoke were accompanied by defective autophagolysosome formation, the effect of which was exacerbated by adiponectin deficiency. Blocking autophagolysosome formation using bafilomycin A1 (BafA1) negated the cardioprotective effect of rapamycin against smoke extract. Induction of autophagy using rapamycin and AMPKα activation using AICAR rescued against smoke extract-induced myopathic anomalies in APNKO mice. Our data suggest that adiponectin serves as an indispensable cardioprotective factor against side-stream smoke exposure-induced myopathic changes possibly through facilitating autophagolysosome formation. [ABSTRACT FROM AUTHOR]

Hypertension is an independent risk factor for heart disease and is responsible for the increased cardiac morbidity and mortality. Oxidative stress plays a key role in hypertensive heart diseases although the precise mechanism remains unclear. This study was designed to examine the effect of cardiac-specific overexpression of metallothionein, a cysteine-rich antioxidant, on myocardial contractile and intracellular Ca 2+ anomalies in N G -nitro- l -arginine methyl ester ( l -NAME)-induced experimental hypertension and the mechanism involved with a focus on autophagy. Our results revealed that l -NAME treatment (14 days) led to hypertension and myocardial anomalies evidenced by interstitial fibrosis, cardiomyocyte hypertrophy, increased LV end systolic and diastolic diameters (LVESD and LVEDD) along with suppressed fractional shortening. l -NAME compromised cardiomyocyte contractile and intracellular Ca 2+ properties manifested as depressed peak shortening, maximal velocity of shortening/relengthening, electrically-stimulated rise in intracellular Ca 2+ , elevated baseline and peak intracellular Ca 2+ . These l -NAME-induced histological and mechanical changes were attenuated or reconciled by metallothionein. Protein levels of autophagy markers LC3B and p62 were decreased and increased, respectively. Autophagy signaling molecules AMPK, TSC2 and ULK1 were inactivated while those of mTOR and p70s6K were activated by l -NAME, the effects of which were ablated by metallothionein. Autophagy induction mimicked whereas autophagy inhibition nullified the beneficial effect of metallothionein against l -NAME. These findings suggested that metallothionein protects against l -NAME-induced myocardial anomalies possibly through restoration of autophagy. [ABSTRACT FROM AUTHOR]

Endoplasmic reticulum (ER) stress, together with the unfolded protein response (UPR), is initially considered an adaptive response aiming at maintenance of ER homeostasis. Nonetheless, ER stress, when in excess, can eventually trigger cell apoptosis and loss of function. UPR is mediated by three major transmembrane proteins, including inositol-requiring enzyme 1 (IRE1), protein kinase RNA-like ER kinase (PERK), and activating transcription factor (ATF) 6. A unique role has been speculated for ER stress in the pathogenesis of diabetes mellitus (DM) and its complications. Recent studies have shown that ER stress is an early event associated with diabetic cardiomyopathy, and may be triggered by hyperglycemia, free fatty acids (FFAs) and inflammation. In this mini-review, we attempted to discuss the activation machinery for ER stress in response to these triggers en route to disrupted ER function and cellular autophagy or apoptosis, ultimately insulin resistance and development of diabetic cardiomyopathy. This article is part of a Special Issue entitled: Autophagy and protein quality control in cardiometabolic diseases. [ABSTRACT FROM AUTHOR]

Cardiovascular disease (CVD) is the leading cause of morbidity and mortality worldwide. Although a cadre of therapeutic strategies have been made available for CVDs in the clinical setting, predominantly through medication and surgery, these do not fully address the clinical needs of patients with CVD. As a new technique for CVD treatment, nanocarriers are employed to modify and package medications to ease the targeting of tissues, cells and molecules within the cardiovascular system. Nanocarriers are made of biomaterials, metals, or a combination of these materials, with sizes similar to bioactive molecules such as proteins and DNA. Cardiovascular nanomedicine (CVN) has only surfaced in recent years and is still in its infancy. Ample studies have displayed promise for the clinical utility of nanomedicine techniques, courtesy of continued perfection in nanocarrier design to optimize drug delivery and treatment outcomes. Here in this review, we will summarize the research advances in the literature on nanoparticles in the management of CVDs, including ischemic and coronary heart disease (e.g., atherosclerosis, angina pectoris and myocardial infarction), myocardial ischemia-reperfusion injury, aortic aneurysm, myocarditis, hypertension, and pulmonary artery hypertension and thrombosis. [ABSTRACT FROM AUTHOR]

Objectives: The objective of this study was to evaluate the safety and efficacy of the surgical versus transcatheter approach to correct perimembranous ventricular septal defects (pmVSDs) in a prospective, randomized, controlled clinical trial. Background: pmVSD is a common congenital heart disease in children. Surgical closure of pmVSD is a well-established therapy but requires open-heart surgery with cardiopulmonary bypass. Although the transcatheter approach is associated with significant incidence of complete atrioventricular block, it may provide a less invasive alternative. Critical comparison of the safety and efficacy of the 2 interventions necessitates a prospective, randomized, controlled trial. Methods: Between January 2009 and July 2010, 229 children with pmVSD were randomly assigned to surgical or transcatheter intervention. Clinical, laboratory, procedural, and follow-up data over a 2-year period were compared. Results: Neither group had mortality or major complications. However, statistical analysis of the 2 groups demonstrated significant differences (p < 0.001) in minor adverse events (32 vs. 7), quantity of blood transfused, duration of the procedure, median hospital stay, median intensive care unit stay, median hospitalization cost, and median blood loss. During a median follow-up of 2 years, the left ventricular end-diastolic dimension of both groups returned to normal and there was no difference in closure rate, adverse events, and complications between groups. Conclusions: Transcatheter device closure and surgical repair are effective interventions with excellent midterm results for treating pmVSD in children. Transcatheter device closure has a lower incidence of myocardial injury, less blood transfused, faster recovery, shorter hospital stay, and lower medical expenses. (Transcatheter Closure Versus Surgery of Perimembranous Ventricular Septal Defects; NCT00890799) [Copyright &y& Elsevier]

Highlights: [•] We examined the effect of metallothionein on ER stress-induced heart dysfunction. [•] Metallothionein rescues against ER stress-induced cardiac dysfunction. [•] The beneficial effect of metallothionein was related to attenuated autophagy. [Copyright &y& Elsevier]

ABSTRACT A new kind of bichromophoric poly(acrylamide) covalently linked with norfloxacin (NF) and proflavine (PF) was synthesized. The photophysical properties of the polymer were investigated. Energy transfer from NF to PF was observed in the film state of the polymer but not effective in aqueous solution. Responses of different metal cations on the fluorescence intensity of the polymer solution were investigated. Only Fe3+ ions exhibited remarkable fluorescence intensity quenching to the polymer. The effect of Fe3+ on the solution and film of the polymer was investigated in detail. The fluorescence intensity of the bichromophoric polymer exhibited a good linear correlation with the concentration of Fe3+. © 2013 Wiley Periodicals, Inc. Adv Polym Technol 2014, 33, 21382; View this article online at . DOI 10.1002/adv.21382 [ABSTRACT FROM AUTHOR]

The ability of the 10-23 DNAzyme to specifically cleave RNA with high efficiency has fuelled expectation that this agent may have useful applications for targeted therapy. Here, we, for the first time, investigated the antitumor and radiosensitizing effects of a DNAzyme (DZ1) targeted to the Epstein-Barr virus (EBV)-LMP1 mRNA of nasopharyngeal carcinoma (NPC) in patients. Preclinical studies indicated that the DNAzyme was safe and well tolerated. A randomized and double-blind clinical study was conducted in 40 NPC patients who received DZ1 or saline intratumorally, in conjunction with radiation therapy. Tumor regression, patient survival, EBV DNA copy number and tumor microvascular permeability were assessed in a 3-month follow-up. The mean tumor regression rate at week 12 was significantly higher in DZ1 treated group than in the saline control group. Molecular imaging analysis showed that DZ1 impacted on tumor microvascular permeability as evidenced by a faster decline of the Ktrans in DZ1-treated patients. The percentage of the samples with undetectable level of EBV DNA copy in the DZ1 group was significantly higher than that in the control group. No adverse events that could be attributed to the DZ1 injection were observed in patients. [ABSTRACT FROM AUTHOR]

DNAzymes (Dzs) are single-stranded DNA catalysts that specifically cleave the mRNA of targeted genes. Compared with other gene-silencing technologies, such as ribozymes, antisense oligonucleotide and small interference RNA (siRNA), DNAzymes have several advantages, including small molecular weight, diversity, low cost and relative stability in serum. With the evolution of molecular technology, the first DNAzyme was generated in vitro in 1994. From then on, DNAzymes have been studied in order to understand their structures, chemistry and biological applications. Particularly, DNAzymes have been widely applied as a new interference strategy in the treatment of many conditions, including cancer, viral diseases, and cardiovascular diseases. This review mainly summarizes the use of DNAzymes in the areas of cancer research and therapy. [ABSTRACT FROM AUTHOR]

Abstract: Nasopharyngeal carcinoma (NPC) is a highly metastatic cancer. The 2-year survival rate of patients with stage III or IV disease is only about 50%. Due to its high radiosensitivity, radiotherapy is the standard treatment for early-stage of NPC. However, the radioresistance observed in some patients can cause distant metastases and local recurrence after radiotherapy. Special emphasis has been given to the discovery of effective radiosensitizers. Oncogenic proteins encoded by EBV genomes may serve as part of targeted radiosensitization, such as NF кB-mediated expression of latent membrane protein-1. We here review the major nucleic acid-based options currently used in cancer therapeutic approaches and the selected candidate genes that can be targeted for NPC radiosensitization. [Copyright &y& Elsevier]

Many human tumor cells are characterized by overexpression or mutation of epidermal growth factor receptor (EGFR). Emerging evidence indicates that EGFR, as well as some of its downstream components, can translocate to the nucleus and play roles in transcriptional regulation, signaling conduction and repair of DNA double strands breaks (DSBs). EGFR in its nuclear manifestation promotes DSB repair by interacting with proteins including DNA-PK, ATM, Rad51 and BRCA1, involved in DSB repair, via the PI3K-Akt and Ras-Raf-MAPK pathways. DNA damage repair in tumor cells is emerging as an attractive target in radiotherapy and chemotherapy. Interruption of EGFR functions, or those of its downstream components, presents a promising strategy for confounding DNA damage repair in tumor cells. [ABSTRACT FROM AUTHOR]

Abstract: ZL11n is a novel furoxan-based nitric oxide (NO)-releasing derivative of farnesylthiosalicylic acid. In this study, we examined the anticancer effects and the potential mechanism of action of ZL11n in vitro and in vivo. It was found that ZL11n exhibited a favorable, selective cytotoxic effect in the HepG2 cell line. The yield of NO in the ZL11n treated HepG2 cells was much higher than in the control group and the normal human liver L-02 cells. Furthermore, the NO concentration was correlated to the degree of cytotoxicity observed. The ZL11n-induced apoptosis was assessed by Annexin V-FITC/propidium iodide flow cytometry assay. ZL11n triggered the mitochondrial/caspase apoptotic pathway by decreasing mitochondrial membrane potential, cytochrome c release from mitochondrial, and reducing the Bcl-2-to-Bax ratio, in addition to activating the caspase cascade. Simultaneously, we found that ZL11n treatment led to an increase in JNK and ERK1/2 phosphorylation. Furthermore, treatment with SP600125 (a JNK inhibitor) and PD98059 (an ERK1/2 inhibitor) prior to ZL11n treatment was found to significantly reverse ZL11n-induced apoptosis. The in vivo findings also revealed that ZL11n significantly reduced tumor volume and weight in the H22 solid tumor mouse model examined. In short, our findings suggest that ZL11n induced apoptosis through the coordination of the mitochondrial apoptotic pathway (activated by NO) and MAPKs signaling pathway (triggered by JNK or ERK). [Copyright &y& Elsevier]

When an electrode (negative/positive) with excellent capacity matches a counter electrode with relatively low capacity or a pair of excellent electrodes cannot match each other, overall performance of the constructed supercapacitors (SCs) will be limited. Here, we report a novel electrode material 1,5-diamino-4,8-dihydroxyanthraquinone (DHAQ) grafted nitrogen-doped graphene aerogel (DHAQ-NGA) prepared by simple hydrothermal method. Since DHAQ molecule contains –C(=O)− and −NH−/−OH groups, the DHAQ-NGA composite can act as both the negative and positive electrode materials for a supercapacitor in ionic liquid electrolyte to improve capacity by faradaic reactions on these two electrodes. In addition, the intramolecular hydrogen bonding of DHAQ can improve the stability of the material. Therefore, DHAQ-NGA displays an enhanced specific capacity of 410 C g−1 for the positive electrode and 454 C g−1 for the negative electrode material. The assembled device can deliver a high energy density of 117 Wh kg−1 at a power density of 822 W kg−1. [Display omitted] [ABSTRACT FROM AUTHOR]

Objective. A new generation of the laser fluorescence device, DIAGNOdent, for caries detection and quantification has been introduced recently. It is the DIAGNOdent pen. The aim of this study was to compare the validity and reliability of both laser-based devices, DIAGNOdent and the DIAGNOdent pen, in quantifying smooth surface caries. Material and Methods. The material comprised a sample of 52 premolar teeth extracted on orthodontic indication. The teeth were visually sound or had various stages of non-cavitated carious lesions on smooth surfaces. All teeth were photographed and measured with both DIAGNOdent and the DIAGNOdent pen by two examiners independently. The teeth were then sectioned into 300-µm slices and analysed under a microscope for verification of lesion depth. Histopathological analyses were performed by two observers to assess lesion depth, which was classified into five categories ranging from sound to dentinal caries. Reliability and validity of the two devices were evaluated in terms of intra-class coefficients and Spearman rank correlation coefficient, respectively. The relation between measurements performed by DIAGNOdent and the DIAGNOdent pen was analyzed using Pearson's correlation coefficient. Results . Both DIAGNOdent and the DIAGNOdent pen had excellent intra-observer agreement and acceptable inter-observer agreement. The correlation with histology for DIAGNOdent and the DIAGNOdent pen ranged between 0.47 and 0.57, although the correlation between DIAGNOdent and the DIAGNOdent pen was high. Conclusions. In this in vitro study, the new laser fluorescence device, the DIAGNOdent pen, showed similar reliability and validity at quantification of smooth surface caries compared to the conventional DIAGNOdent device. Agreement between DIAGNOdent and the DIAGNOdent pen was excellent. [ABSTRACT FROM AUTHOR]

Summary: Objectives: The purpose of this study was (1) to compare the fluoride release profile of an experimental composite to commercial GICs, resin-modified GICs, and composite resins; (2) to assess the fluoride release process. Methods: Commercial materials (n=3) were prepared according to manufacturers'' directions. The experimental composite (n=3) consisted of 78wt% filler and 22wt% resin. The resin consisted of 19wt% BisGMA, 38wt% UDMA, 19wt% TEGDMA, and 24wt% HEMA. Disc specimens were placed into 25ml of deionized water in sealed polyethylene vials and shaked at 1.4Hz at 37°C. Fluoride release was measured using a fluoride-ion specific electrode at different time intervals up to 284 days. Results: The fluoride release rate of the experimental composite demonstrated the highest rate of release within the first day (p=0.05), but decreased significantly by day 7. Release rates of the commercial glass-ionomer cements and resin-modified glass-ionomer cements thereafter were significantly higher than the experimental and commercial composites at p=0.05. Among the materials studied, cumulative fluoride release is adequately described by a two-term equation consisting of an initial fluoride release via a rapid dissolution process followed by a long-term diffusive release. Significance: An increase in the hydrophilicity of the polymer matrix through the introduction of HEMA improved the fluoride release over the short term during which dissolution occurs. Such a release behavior could be beneficial if it results in a fluoride reservoir that could be maintained by a prolonged slower release thereafter. [Copyright &y& Elsevier]

Gallic acid (GA) is a common phenolic acid that is widely used as an antibacterial agent in the food industry. In order to increase its applicability, this study investigated the antibacterial effects and mechanisms of GA on Escherichia coli O157:H7 (E. coli O157:H7) after UV-C light treatment combined with photodynamic therapy. This study evaluated the photodynamic effects of GA after UV-C irradiation (UVC-GA) based on changes in substances and ROS generation. Using E. coli O157:H7 as a model bacterium, the antibacterial effects were evaluated from various aspects, including MIC, MBC, time-kill curve, cell membrane damage, DNA damage, protein damage, motility changes, biofilm formation, and activity. In addition, the antibacterial mechanisms were further investigated by combining RT-qPCR analysis of gene expression. The results of this study demonstrated that GA has the ability to exert photodynamic effects, even after the removal of the UV-C light source, and can effectively reduce the number of viable E. coli O157:H7 cells. Moreover, UVC-GA caused significant damage to the cell membrane, DNA, and proteins, and according to the RT-qPCR results, the antibacterial mechanisms of UVC-GA and GA on E. coli O157:H7 were completely different. Based on the above results, food-sterilizing detergents can be developed and applied to contaminated oyster to provide an effective food cleaning effect. [ABSTRACT FROM AUTHOR]

Background: Studies have shown that oxidative stress and its resistance plays important roles in the process of tumor metastasis, and mitochondrial dysfunction caused by mitochondrial DNA (mtDNA) damage is an important molecular event in oxidative stress. In lung cancer, the normal fibroblasts (NFs) are activated as cancer-associated fibroblasts (CAFs), and act in the realms of the tumor microenvironment (TME) with consequences for tumor growth and metastasis. However, its activation mechanism and whether it participates in tumor metastasis through antioxidative stress remain unclear. Methods: The role and signaling pathways of tumor cell derived extracellular vesicles (EVs) activating NFs and the characteristic of induced CAFs (iCAFs) were measured by the transmission electron microscopy, nanoparticle tracking analysis, immunofluorescence, collagen contraction assay, quantitative PCR, immunoblotting, luciferase reporter assay and mitochondrial membrane potential detection. Mitochondrial genome and single nucleotide polymorphism sequencing were used to investigate the transport of mtDNA from iCAFs to ρ0 cells, which were tumor cells with mitochondrial dysfunction caused by depletion of mtDNA. Further, the effects of iCAFs on mitochondrial function, growth and metastasis of tumor cells were analysed in co-culture models both in vitro and in vivo, using succinate dehydrogenase, glutathione and oxygen consumption rate measurements, CCK-8 assay, transwell assay, xenotransplantation and metastasis experiments as well as in situ hybridization and immunohistochemistry. Results: Our findings revealed that EVs derived from high-metastatic lung cancer cells packaged miR-1290 that directly targets MT1G, leading to activation of AKT signaling in NFs and inducing NFs conversion to CAFs. The iCAFs exhibit higher levels of autophagy and mitophagy and more mtDNA release, and reactive oxygen species (ROS) could further promote this process. After cocultured with the conditioned medium (CM) of iCAFs, the ρ0 cells may restore its mitochondrial function by acquisition of mtDNA from CAFs, and further promotes tumor metastasis. Conclusions: These results elucidate a novel mechanism that CAFs activated by tumor-derived EVs can promote metastasis by transferring mtDNA and restoring mitochondrial function of tumor cells which result in resistance of oxidative stress, and provide a new therapeutic target for lung cancer metastasis. [ABSTRACT FROM AUTHOR]

Grain size is one of the most important parameters for metallographic microstructure analysis, which can partly determine the material performance. The measurement of grain size is based on accurate image segmentation methods, which include traditional image processing methods and emerging machine-learning-based methods. Unfortunately, traditional image processing methods can hardly segment grains correctly from metallographic images with low contrast and blurry boundaries. Moreover, the proposed machine-learning-based methods need a large dataset to train the model and can hardly deal with the segmentation challenge of complex images with fuzzy boundaries and complex structure. In this paper, an improved U-Net model is proposed to automatically accomplish image segmentation of complex metallographic images with only a small training set. The experiments on metallographic images show the significant advantage of the method, especially for the metallographic images with low contrast, a fuzzy boundary and complex structure. Compared with other deep learning methods, the improved U-Net scored higher in ACC, MIoU, Precision, and F1 indexes, among which ACC was 0.97, MIoU was 0.752, Precision was 0.98, and F1 was 0.96. The grain size was calculated based on the segmentation according to the American Society for Testing Material (ASTM) standards, producing a satisfactory result. [ABSTRACT FROM AUTHOR]

Structural models based on Attention can not only record the relationships between features' position, but also can measure the importance of different features based on their weights. By establishing dynamically weighted parameters for choosing relevant and irrelevant features, the key information can be strengthened, and the irrelevant information can be weakened. Therefore, the efficiency of Deep Learning algorithms can be significantly elevated and improved. Although Transformer have been performed very well in many fields including Reinforcement Learning (RL). We tried to integrate Transformers into RL, however there are some challenge in this task. Especially, MARL (known as Multi-Agent Reinforcement Learning), which can be recognized as a set of independent agents trying to adapt and learn through their way to reach the goal. In order to emphasize the relationship between each MDP decision in a certain time period, we applied the hierarchical coding method and validated the effectiveness of this method. This paper proposed a Hierarchical Transformer MADDPG based on recurrent neural network(RNN) which we call it Hierarchical RNNs-Based Transformers MADDPG(HRTMADDPG). It consists of a lower level encoder based on RNNs that encodes multiple step sizes in each time sequence, and it also consists of an upper sequence level encoder based on Transformer for learning the correlations between multiple sequences. Then we can capture the causal relationship between sub-time sequences and make HRTMADDPG more efficient. [ABSTRACT FROM AUTHOR]

It is not clear how the amino acid composition of the X sites in GXSXG domain affects the properties of the lipase. To address this, saturation mutation at these sites of Penicillium expansum lipase (PEL) was carried out. After screening, a mutant L133M with significantly different activity was obtained. The activity of L133M was lower than that of wild-type PEL (WT) when the reaction time was 3–10 min. However, it was 1.61 times that of WT under long-term (48 h) catalysis. WT exhibited interfacial activation when the concentration of p-nitrophenylbutyrate was higher than 3 mM, whereas L133M could only show interfacial activation at higher micelle concentration (p-nitrophenylbutyrate concentration > 5 mM), which seemed to be slower. Further analysis showed that a new hydrophobic interaction was generated between the methionine introduced at position 133 and the lid, which made the interface activation process more difficult. However, the binding energy between the activated mutant and the substrate was smaller, showing stronger activity. This work provides some reliable clues for further understanding the complex role of GXSXG domain in enzyme catalysis. [ABSTRACT FROM AUTHOR]

Due to the highly complex biological formation procedure, tumor is still difficult to be treated efficiently and always associated with proliferation, migration and inflammation during treatment. Herein, a novel strategy of boosted photocatalytic activity induced NAMPT-regulating therapy is used for tumors inhibition based on FK866 loaded bismuth-humic acids heterojunction (Bi-HA/FK866). With the reduction function of HA, Bi (Ⅲ) can be reduced to elemental Bi, which can be excited by NIR laser to form electron-hole pair due to the narrow bandgap. Moreover, the coated HA and Bi could form a heterojunction structure, which could decrease the electron–hole recombination, and further boost the photocatalytic activity, leading to highly efficient ROS generation and GSH depletion. The resulted ROS could induce DNA damage of the tumor cells, thus enhancing the sensitivity to the inhibitor of NAMPT (FK866) to downregulate NAD/ERK/NF-κB signal pathways, and eventually simultaneously prevent cancer progression. Moreover, the decreased NAD could downregulate NADPH and further suppress the innate antioxidant defense system by inhibiting reduction of GSSG. The boosted photocatalytic activity induced NAMPT-regulating therapy offers a promising way to address the important issue of penetration depth limitation induced cancer relapse and migration, providing more possibilities toward successful clinical application. [ABSTRACT FROM AUTHOR]

Background: Paris (Melanthiaceae) is an economically important but taxonomically difficult genus, which is unique in angiosperms because some species have extremely large nuclear genomes. Phylogenetic relationships within Paris have long been controversial. Based on complete plastomes and nuclear ribosomal DNA (nrDNA) sequences, this study aims to reconstruct a robust phylogenetic tree and explore historical biogeography and clade diversification in the genus. Results: All 29 species currently recognized in Paris were sampled. Whole plastomes and nrDNA sequences were generated by the genome skimming approach. Phylogenetic relationships were reconstructed using the maximum likelihood and Bayesian inference methods. Based on the phylogenetic framework and molecular dating, biogeographic scenarios and historical diversification of Paris were explored. Significant conflicts between plastid and nuclear datasets were identified, and the plastome tree is highly congruent with past interpretations of the morphology. Ancestral area reconstruction indicated that Paris may have originated in northeastern Asia and northern China, and has experienced multiple dispersal and vicariance events during its diversification. The rate of clade diversification has sharply accelerated since the Miocene/Pliocene boundary. Conclusions: Our results provide important insights for clarifying some of the long-standing taxonomic debates in Paris. Cytonuclear discordance may have been caused by ancient and recent hybridizations in the genus. The climatic and geological changes since the late Miocene, such as the intensification of Asian monsoon and the rapid uplift of Qinghai-Tibet Plateau, as well as the climatic fluctuations during the Pleistocene, played essential roles in driving range expansion and radiative diversification in Paris. Our findings challenge the theoretical prediction that large genome sizes may limit speciation. [ABSTRACT FROM AUTHOR]

The accurate detection of biogenic amines (BAs) is an important means of ensuring the quality and safety of cephalopod seafood products. In this study, the pre‐column derivatization of high‐performance liquid chromatography (HPLC) was optimized using dansyl chloride (Dns‐Cl) to detect BAs in octopus, cuttlefish, and squid. The reasons for the formation of BAs were investigated by assessing their decarboxylase activity and the rates of decomposition. The findings demonstrated that using Dns‐Cl to optimize pre‐column derivatization enabled the separation of nine different BAs. The detection limits ranged from 0.07 to 0.25 mg/L, and the results exhibited a high level of linearity (R2 ≥ 0.997). The decarboxylase activity and biodegradation rate positively correlated with the formation of BAs at temperatures below 0°C. Notably, the decarboxylase activity of octopus, cuttlefish, and squid exhibited a significant increase with prolonged storage time, and formyltransferase and carbamate kinase may be the key decarboxylase in cephalopod products. These findings serve as a valuable reference for further investigations into the mechanisms behind BAs production and the development of control technologies for BAs in cephalopod products. This study has successfully demonstrated the effectiveness of the Dns‐Cl pre‐column derivatization‐HPLC method in accurately and efficiently detecting BAs in octopus, cuttlefish, and squid. Moreover, it highlights the influence of decarboxylase content and biodegradation rate on the formation of BAs. Importantly, this method can serve as a reference for detecting BAs in various seafood products. [ABSTRACT FROM AUTHOR]

Background: Robust phylogenies for species with giant genomes and closely related taxa can build evolutionary frameworks for investigating the origin and evolution of these genomic gigantisms. Paris japonica (Melanthiaceae) has the largest genome that has been confirmed in eukaryotes to date; however, its phylogenetic position remains unresolved. As a result, the evolutionary history of the genomic gigantisms in P. japonica remains poorly understood. Results: We used next-generation sequencing to generate complete plastomes of P. japonica, P. verticillata, Trillium govanianum, Ypsilandra thibetica and Y. yunnanensis. Together with published plastomes, the infra-familial relationships in Melanthiaceae and infra-generic phylogeny in Paris were investigated, and their divergence times were calculated. The results indicated that the expansion of the ancestral genome of extant Paris and Trillium occurred approximately from 59.16 Mya to 38.21 Mya. The sister relationship between P. japonica and the section Euthyra was recovered, and they diverged around the transition of the Oligocene/Miocene (20 Mya), when the Japan Islands were separated from the continent of Asia. Conclusions: The genome size expansion in the most recent common ancestor for Paris and Trillium was most possibly a gradual process that lasted for approximately 20 million years. The divergence of P. japonica (section Kinugasa) and other taxa with thick rhizome may have been triggered by the isolation of the Japan Islands from the continent of Asia. This long-term separation, since the Oligocene/Miocene boundary, would have played an important role in the formation and evolution of the genomic gigantism in P. japonica. Moreover, our results support the taxonomic treatment of Paris as a genus rather than dividing it into three genera, but do not support the recognition of T. govanianum as the separate genus Trillidium. [ABSTRACT FROM AUTHOR]

Atherosclerosis (AS) is a chronic inflammatory vascular disease. Myocardial ischemia originated from AS is the main cause of cardiovascular diseases, one of the major factors contributing to the global disease burden. AS is typically quiescent until occurrence of plaque rupture and thrombosis, leading to acute coronary syndrome and sudden death. Currently, clinical diagnostic techniques suffer from major pitfalls including lack of accuracy and specificity, which makes it rather difficult for drugs to directly target plaques to achieve therapeutic effect. Therefore, how to accurately diagnose and effectively intervene vulnerable AS plaques to achieve accurate delivery of drugs has become an urgent and evolving clinical problem. With the rapid development of nanomedicine and nanomaterials, nanotechnology has shown unique advantages in monitoring vulnerable plaques and thrombus and improving drug efficacy. Recent studies have shown that application of nanoparticle drug delivery system can booster the safety and effectiveness of drug therapy, and molecular imaging technology and nanomedicine also exhibit high clinical application potentials in disease diagnosis. Therefore, nanotechnology provides another promising avenue for diagnosis and treatment of AS and thrombosis, and has shown excellent performance in the development of targeted drug therapy and biomaterials. In this review, the research progress, challenges and prospects of nanotechnology in AS and thrombosis are discussed, expecting to provide new ideas for the prevention, diagnosis and treatment of AS and thrombosis. [ABSTRACT FROM AUTHOR]

Purpose: Although EGFR inhibitor (EGFRi) is used in cancer therapy to suppress tumor growth and resistance to treatment including radiotherapy, EGFRi resistance frequently developed, which significantly reduced treatment outcomes. Therefore, developing alternative approaches for EGFRi is of great importance. Based on our recent observation that ATM inhibitor (ATMi) efficiently inhibited ionizing radiation (IR)-induced EGFR activation in mouse embryo fibroblasts (MEF), the main purpose of this study is to determine whether ATMi could inhibit IR-induced EGFR activation in human tumor cell lines and explore its potential in EGFRi-alternative therapies. Materials and methods: We compared the effects of ATMi, EGFRi individually or in combination on IR-induced EGFR phosphorylation, cell growth and radio-sensitization in nine human tumor cell lines including lung adenocarcinoma (A549 and H358), glioblastoma (LN229), cervical cancer (HeLa), colorectal carcinoma (SW480 and HCT116) and nasopharygeal carcinoma (5–8 F, 6–10B and HK1) cell lines. In addition, we detected the effects of ATMi, EGFRi alone or both on the efficiency of non-homologous end-joining (NHEJ) and homologous recombination (HR) using I-SceI –GFP based NHEJ or HR reporter cell lines. Results: Compared to EGFRi treatment, ATMi treatment decreased IR-induced EGFR phosphorylation, suppressed growth and increased IR sensitization in tested cell lines at a similar or even more efficient level. Combining ATMi and EGFRi did not significantly increased the effects on these phenotypes as ATMi treatment alone. Also, similar to ATMi, EGFRi mainly reduced the efficiency of HR but not NHEJ although combining ATMi and EGFRi further inhibited the HR efficiency. Conclusions: Our study demonstrates that ATMi can function like EGFRi in human tumor cells to inhibit tumor cell growth and sensitize the tumor cells to IR, suggesting that ATMi treatment as an alternative approach may exert anticancer effects on EGFRi-resistant tumor cells and facilitate radiotherapy. [ABSTRACT FROM AUTHOR]