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Background: Evidences indicate that inflammasome compounds participate in amyotrophic lateral sclerosis (ALS), a fatal progressive motoneuron degenerative disease. Researchers have observed the expressions of nucleotide oligomerization domain (NOD)-like receptor protein 3 (NLRP3) related inflammasome components in specific regions of the central nervous system in different ALS models, but the cellular spatiotemporal evolution of this canonical inflammasome pathway and pyroptosis during ALS progression are unclear.Methods: The spinal cords of hSOD1G93A mice (ALS mice) and age-matched littermates (CON mice) were dissected at pre-symptomatic stage (60 d), early- symptomatic stage (95 d), symptomatic stage (108 d) and late-symptomatic stage (122 d) of the disease. By using Nissl staining, double immunofluorescence labelling, qRT-PCR or western blot, we detected morphology change and the expression, cellular location of GSDMD, NLRP3, caspase-1 and IL-1β in the ventral horn of lumbar spinal cords over the course of disease.Results: Neural morphology changes and GSDMD+/NeuN+ double positive cells were observed in ventral horn from ALS mice even at 60 d of age, even though there were no changes of GSDMD mRNA and protein expressions at this stage compared with CON mice. With disease progression, compared with age-matched CON mice, increased expressions of GSDMD, NLRP3, activated caspase-1 and IL-1β were detected. Double immunofluorescence labeling revealed that NLRP3, caspase-1, IL-1β positive signals mainly localized in ventral horn neurons at pre- and early-symptomatic stages. From symptomatic stage to late-symptomatic stage, robust positive signals were co-expressed in reactive astrocytes and microglia.Conclusions: Early activation of the canonical NLRP3 inflammasome induced pyroptosis in ventral horn neurons, which may participate in motor neuron degeneration and initiate neuroinflammatory processes during ALS progression. [ABSTRACT FROM AUTHOR]

Tin mono‐selenide (SnSe) exhibits the world record of thermoelectric conversion efficiency ZT in the single crystal form, but the performance of polycrystalline SnSe is restricted by low electronic conductivity (σ) and high thermal conductivity (κ), compared to those of the single crystal. Here an effective strategy to achieve high σ and low κ simultaneously is reported on p‐type polycrystalline SnSe with isovalent Te ion substitution. The nonequilibrium Sn(Se1−xTex) solid solution bulks with x up to 0.4 are synthesized by the two‐step process composed of high‐temperature solid‐state reaction and rapid thermal quenching. The Te ion substitution in SnSe realizes high σ due to the 103‐times increase in hole carrier concentration and effectively reduced lattice κ less than one‐third at room temperature. The large‐size Te ion in Sn(Se1−xTex) forms weak SnTe bonds, leading to the high‐density formation of hole‐donating Sn vacancies and the reduced phonon frequency and enhanced phonon scattering. This result—doping of large‐size ions beyond the equilibrium limit—proposes a new idea for carrier doping and controlling thermal properties to enhance the ZT of polycrystalline SnSe. [ABSTRACT FROM AUTHOR]

Aging is often associated with cognitive and neural decline, but how these factors interact is still not fully understood. Recently, functional connectivity, or the degree to which brain regions are concurrently active, has provided insight into age-related differences. However, functional connectivities during task and rest differ and few studies have examined how these relate to a broad range of cognitive functions. The present study investigated the effect of age on cognition, whole-brain functional connectivity during resting-state and task, and their relationships across the adult lifespan. Cognition was broadly assessed using a battery of cognitive assessments and mean network characteristics were calculated across the whole brain. Behaviorally, increased age was associated with worse recall, executive function, and verbal working memory abilities but better language performance. Neurally, increased age was associated with lower overall within- and between-network functional connectivities during both rest and task, and these age-connectivity relationships were stronger during task performance. Connectivity was also related to cognition, and for all participants, these relationships were strongest during rest. Specifically, higher resting-state between-network functional connectivity was associated with poorer cognition for all adults and poorer language ability among older adults. Collectively, these findings demonstrate that while age effects were strongest during the task, resting-state functional connectivity was most closely tied to cognition. Moreover, these results are theoretically consistent with dedifferentiation accounts of cognition and aging and show that less differentiated functional connectivities are associated with cognitive costs for both older and younger adults. • Increased age related to worse recall, working memory, executive function. • Increased age related to lower within- and between-network connectivities. • Higher between-network connectivity at rest related to worse cognition at all ages. • Older adults with higher between-network at rest connectivity had worse language. [ABSTRACT FROM AUTHOR]

Introduction. To compare the actual 10-year survival outcomes of early single hepatocellular carcinoma (HCC) patients between 3 first-line treatments: radiofrequency ablation (RFA), surgical resection (SR), or transplantation (LT). Methods. A total of 1255 early single HCC patients retrieved from the Surveillance Epidemiology and End Results (SEER) database were included. Patients survived ≥10 years, and patients died <10 years were compared. Significant predictors associated with 10-year survival were identified by multivariate logistic regression analysis. The 10-year survival outcomes of 3 treatments were compared using multivariate model risk adjustment and inverse probability of treatment weighted (IPTW) adjustment. Results. Of the 1255 patients, 472 patients underwent SR, 259 patients underwent LT, and 524 patients underwent RFA. 149 patients achieved 10-year survival. Multivariate logistic regression analysis showed that age, race, treatment, and fibrosis score were significant predictors for 10-year survival, and LT had the best advantage of 10-year survival, followed by SR. Comparable 10-year survival outcomes were found between SR and RFA after IPTW. Then, a subgroup analysis was performed based on the tumor size, and the results showed that for ≤50 mm tumor, SR showed no significant advantages over RFA for 10-year survival. Conclusions. Estimates of the observational association of different treatments with 10-year survival are sensitive to the analytic method. LT showed the best outcomes for patients. No significant differences for 10-year survival were found between SR and RFA in the IPTW cohort. Subgroup analysis showed that for >50 mm tumor, SR showed significant advantages over RFA after IPTW. [ABSTRACT FROM AUTHOR]

Ferritin is a potential medicine delivery vehicle and vaccine platform, and its efficient expression is a prerequisite for widespread application. This study introduces a soluble expression strategy for recombinant bovine ferritin heavy chain (rFTH) in a prokaryotic system and an improved protein purification method. The amplified rFTH gene was ligated into the prokaryotic expression vector pET30a. The recombinant vectors with the N-terminal His-tag(N-His) or C-terminal His-tag(C-His) were translated and expressed separately. The results showed that the solubility of rFTH with C-His was significantly higher than that with N-His. The expression of rFTH with C-His was attempted at 37 °C and 16 °C, respectively. The results showed that the proportion of soluble protein expressed at 37 °C was more than 90%, higher than that expressed at 16 °C. Then rFTH with C-His was purified successfully using anion exchange chromatography, modified PEG precipitation, and dialysis. The rFTH protein was characterized using SDS-PAGE, Native-PAGE, Western blot, transmission electron microscopy, and dynamic light scattering. The results demonstrated that the purified rFTH protein self-assembled into ferritin nanoparticles with a regular shape and uniform size. This study sheds new light on the soluble expression of ferritin and provides a foundation for the construction of bovine ferritin nanoparticle production platforms. • Bovine ferritin is an ideal platform for antigen delivery and vaccine development. • Bovine ferritin was efficiently expressed in soluble form in the prokaryotic system. • PEG precipitation combined with dialysis is suitable for purification of ferritin. [ABSTRACT FROM AUTHOR]

Prior work has shown that when a word with an initial voiceless stop has a contrasting initial voiced stop neighbour, Voice Onset Times (VOTs) are longer. Higher phonological neighbourhood density (PND) has also been shown to facilitate word retrieval times (RTs), and be associated with longer VOTs. However, these effects have rarely been investigated with picture naming, which is a more semantically driven task. This study examined the effects of phonological neighbours on RTs and phonetic variation, and how these effects differed in word naming and picture naming paradigms. Results showed that PND was positively correlated with longer VOT in both paradigms. Furthermore, the effect of initial stop neighbours on VOTs was only significant in word naming. These results highlight the influence of phonological neighbours on word production in different paradigms, support interactive models of word production, and suggest that hyper-articulation in speech does not solely depend on communicative context. [ABSTRACT FROM AUTHOR]

Purpose. Sepsis is a severe complication in patients following major hepatobiliary and pancreatic surgery. The purpose of this study was to develop and validate a nomogram based on inflammation biomarkers and clinical characteristics. Methods. Patients who underwent major hepatobiliary and pancreatic surgery between June 2015 and April 2017 were retrospectively collected. Multivariate logistic regression was used to identify the independent risk factors associated with postoperative sepsis. A training cohort of 522 patients in an earlier period was used to develop the prediction models, and a validation cohort of 136 patients thereafter was used to validate the nomograms. Results. Sepsis developed in 55 of 522 patients of the training cohort and 19 of 136 patients in the validation cohort, respectively. In the training cohort, one nomogram based on clinical characteristics was developed. The clinical independent risk factors for postoperative sepsis include perioperative blood transfusion, diabetes, operative time, direct bilirubin, and BMI. Another nomogram was based on both clinical characteristics and inflammation biomarkers. Multivariate regression analyses showed that previous clinical risk factors, PCT, and CRP were independent risk factors for postoperative sepsis. The last nomogram showed a good C -index of 0.844 (95% CI, 0.787-0.900) compared with the previous one of 0.777 (95% CI, 0.713-0.840). Patients with a total score more than 109 in the second model are at high risk. The positive predictive value and negative predictive value of the second nomogram were 27% and 97%, respectively. Conclusion. The nomogram achieved good performances for predicting postoperative sepsis in patients by combining clinical and inflammation risk factors. This model can provide the early risk estimation of sepsis for patients following major hepatobiliary and pancreatic surgery. [ABSTRACT FROM AUTHOR]

Background: Sepsis is a common complication following pancreaticoduodenectomy (PD). The aim of this study was to evaluate the risk factors of sepsis based on serum inflammatory markers and clinical characteristics in patients who underwent PD. Methods: A total of 138 patients were enrolled in this study and all patients underwent curative PD. Logistic regression analysis was performed to identify risk factors for post‐operative sepsis. The patients' basic clinical features and inflammatory biomarkers including cytokines (IL‐1, IL‐2, IL‐6, IL‐8, IL‐10 and tumour necrosis factor‐α), procalcitonin, C‐reactive protein and peripheral neutrophil to lymphocyte ratio were analysed. Results: Of 138 patients, 31 developed sepsis during hospitalization. Univariate logistic regression analysis showed that body mass index, blood transfusion, operative time, American Society of Anesthesiologists score and diabetes were significant predictors of sepsis among all clinical characteristic variables. IL‐2, IL‐6, IL‐10, procalcitonin and C‐reactive protein were significant predictors among all inflammation biomarkers. By including different variables, three different regression models were obtained. The full model including all predictors mentioned above showed a C‐index of 0.831 and blood transfusion showed no statistically significance in this model. The reduced model 1 including blood transfusion showed a C‐index of 0.809. Another reduced model which included pre‐operative and intra‐operative variables showed a C‐index of 0.814 and this model could be used for early sepsis risk estimation. Conclusion: Pre‐operative IL‐6 was an independent risk factor for sepsis following PD. The three different predictive models could help early sepsis estimation for patients underwent PD. [ABSTRACT FROM AUTHOR]

Abstract Older adults typically show decline in a variety of cognitive functions including inhibitory control and language production, with corresponding age-related increases in fMRI activation. However, it remains unclear whether such increases are compensatory or whether they reflect neural decline. One factor that may influence these brain-behavior relationships is difficulty. The current study investigated the effect of difficulty on age-related differences in the behavioral and neural bases of language production and inhibitory control using a phonological Go/No-Go picture naming task. Task demands were manipulated by varying the proportion of naming trials (Go trials) and inhibition trials (No-Go trials) across runs. All participants showed task-difficulty related declines in behavioral performance and increases in fMRI activation. Behaviorally, older adults were more sensitive to task difficulty, and elicited more fMRI activation than younger adults. Older adults were less neurally responsive to additional task demands (i.e., picture naming alone vs. Go/No-Go picture naming), but interestingly showed similar within-task increases as younger adults (e.g., Go Bias vs. No-Go Bias). Moreover, the relationships between fMRI activation and behavioral performance in older adults were multifaceted and the strength of these relations changed as a function of task difficulty. Specifically, activation in pre- and post- central gyri, right supramarginal and angular gyri was negatively correlated with naming reaction times, suggesting that activation in these regions may help mitigate age-related declines in language production. These findings are partially consistent with the CRUNCH model, highlighting the important influence of task difficulty on older adults' behavioral performance and their patterns of fMRI activation during language production. Highlights • All adults were slower and had more fMRI activation as task difficulty increased. • Behaviorally, older adults were more sensitive to task difficulty. • Compensation was found in bilateral motor and right parietal regions. • Reduced fMRI activation-behavior correlations were found with increased difficulty. • The findings partially support the CRUNCH model. [ABSTRACT FROM AUTHOR]

Language production and cognitive control are complex processes that involve distinct yet interacting brain networks. However, the extent to which these processes interact and their neural bases have not been thoroughly examined. Here, we investigated the neural and behavioral bases of language production and cognitive control via a phonological go/no-go picture-naming task. Naming difficulty and cognitive control demands (i.e., conflict monitoring and response inhibition) were manipulated by varying the proportion of naming trials (go trials) and inhibition trials (no-go trials) across task runs. The results demonstrated that as task demands increased, participants’ behavioral performance declined (i.e., longer reaction times on naming trials, more commission errors on inhibition trials) whereas brain activation generally increased. Increased activation was found not only within the language network but also in domain-general control regions. Additionally, right superior and inferior frontal and left supramarginal gyri were sensitive to increased task difficulty during both language production and response inhibition. We also found both positive and negative brain-behavior correlations. Most notably, increased activation in sensorimotor regions, such as precentral and postcentral gyri, was associated with better behavioral performance, in both successful picture naming and successful inhibition. Moreover, comparing the strength of correlations across conditions indicated that the brain-behavior correlations in sensorimotor regions that were associated with improved performance became stronger as task demands increased. Overall, our results suggest that cognitive control demands affect language production, and that successfully coping with increases in task difficulty relies on both language-specific and domain-general cognitive control regions. [ABSTRACT FROM AUTHOR]

• Older adults more behaviorally sensitive to task difficulty in word production. • Older adults had lower within language network connectivity compared to younger adults. • Older adults' language network became less segregated as task difficulty increased. • Findings support the Compensation-Related Utilization of Neural Circuits Hypothesis. Older adults typically report increased difficulty with language production, while its neural bases are less clear. The current study investigated the neural bases of age-related differences in language production at the word level and the modulating effect of task difficulty, focusing on task-based functional connectivity. Using an English phonological Go/No-Go picture naming task, task difficulty was manipulated by varying the proportion of naming trials (Go trials) and inhibition trials (No-Go trials) across runs. Behaviorally, compared to younger adults, older adults performed worse, and showed larger effects of task difficulty. Neurally, older adults had lower within language network connectivity compared to younger adults. Moreover, older adults' language network became less segregated as task difficulty increased. These results are consistent with the Compensation-Related Utilization of Neural Circuits Hypothesis, suggesting that the brain becomes less specified and efficient with increased task difficulty, and that these effects are stronger among older adults (i.e., more dedifferentiated). [ABSTRACT FROM AUTHOR]

Objective: This study aimed to compare hard‐ and soft‐tissue changes after ridge preservation in periodontally compromised molar sockets with and without primary wound closure. Materials and Methods: Forty molars with severe periodontitis requiring extraction were included and allocated to two treatment modalities. After tooth extraction, the sockets were filled with deproteinized bovine bone mineral and covered with a bioabsorbable porcine collagen membrane. Primary wound closure was achieved in the control group, whereas the test group underwent minimally invasive open healing. The dimensions of the bone and soft tissue were recorded at baseline and 6 months. Results: Over 6 months, the control and test groups had similar mean ridge heights at the center of sockets of 8.59 ± 2.47 mm and 8.47 ± 2.51 mm, respectively. The total volume of the control group increased from 1070.17 to 1713.52 mm3 for a mean gain of 643.35 mm3, whereas that of the test group increased from 992.51 to 1514.05 mm3 for a mean gain of 521.54 mm3. Compared with the test group, the control group showed a statistically significant decrease in keratinized tissue width of 1.08 ± 1.63 mm. Conclusions: Bone dimensional changes following ridge preservation with and without primary wound closure were comparable. ARP without primary wound closure preserves more keratinized tissue than that with (Chinese Clinical Trial Registry: ChiCTR‐ONN‐16009433). [ABSTRACT FROM AUTHOR]

Whether using two languages enhances executive functions is a matter of debate. Here, we take a novel perspective to examine the bilingual advantage hypothesis by comparing bi-dialect with mono-dialect speakers’ performance on a non-linguistic task that requires executive control. Two groups of native Chinese speakers, one speaking only the standard Chinese Mandarin and the other also speaking the Southern-Min dialect, which differs from the standard Chinese Mandarin primarily in phonology, performed a classic Flanker task. Behavioural results showed no difference between the two groups, but event-related potentials recorded simultaneously revealed a number of differences, including an earlier P2 effect in the bi-dialect as compared to the mono-dialect group, suggesting that the two groups engage different underlying neural processes. Despite differences in the early ERP component, no between-group differences in the magnitude of the Flanker effects, which is an index of conflict resolution, were observed in the N2 component. Therefore, these findings suggest that speaking two dialects of one language does not enhance executive functions. Implications of the current findings for the bilingual advantage hypothesis are discussed. [ABSTRACT FROM AUTHOR]

As we age, language reflects patterns of both stability and change. On the one hand, vocabulary and semantic abilities are largely stable across the adult lifespan, yet lexical retrieval is often slower and less successful (i.e., slower picture naming times, increased tip of the tongue incidents). Although the behavioral bases of these effects have been well established, less is known about the brain regions that support these age-related differences. We used functional Magnetic Resonance Imaging (fMRI) to examine the neural basis of picture naming. Specifically, we were interested in whether older adults would be equally sensitive to semantic characteristics, specifically the number of semantic near neighbors. Near neighbors, defined here as items with a high degree of semantic feature overlap, were of interest as these are thought to elicit competition among potential candidates and increase naming difficulty. Consistent with prior reports, pictures with more semantic near neighbors were named more slowly and less accurately for all adults. Additionally, this interference for naming times was larger as age increased, starting around 30 years old. In contrast to the age-related behavioral slowing, the neural basis of these effects was stable across adulthood. Across all adults, a number of language-relevant regions including left posterior middle temporal gyrus and left inferior frontal gyrus, pars triangularis were sensitive to the number of near neighbors. Our results suggest that although middle-aged and older adults' picture naming is more slowed by increased semantic competition, the brain regions supporting semantic processes remain stable across the adult lifespan. [ABSTRACT FROM AUTHOR]

When bilinguals switch languages they regulate the more dominant language to enable spoken production in the less dominant language. How do they engage cognitive control to accomplish regulation? We examined this issue by comparing the consequences of training on language switching in two different contexts. Chinese-English bilinguals were immersed in English (L2) while studying abroad (this study) or in Chinese (L1) in their native language environment (Zhang et al., 2015). In each study, participants performed the AX-CPT task while EEG was recorded and were then trained on language switching. While Zhang et al. found that training enhanced proactive control in the L1 context, there were no effects of training under L2 immersion conditions. Critically, L2 immersed bilinguals revealed enhanced proactive control at pre-test and greater L1 inhibition on language switching relative to L1 immersed bilinguals. We hypothesize that L2 immersion creates a natural training context that increases reliance on proactive control to enable regulation of the L1. [ABSTRACT FROM AUTHOR]

Purpose. Adipose-derived mesenchymal stem cells (ADSCs) are increasingly applied in tendon repair. However, the underlying mechanisms of ADSC-derived extracellular vesicles (EVs) in tendon healing are largely unknown. In this study, we investigated the effect of the EVs secreted by ADSCs on the recovery of tendon injuries and its potential mechanism. Materials and Methods. We injected ADSCs into the injured tendon, followed by the evaluation of the tissue morphology, tenocyte proliferation, and oxidative stress. Then, the injured tenocytes were treated with EVs secreted by ADSCs, and oxidative stress and proliferation of tenocytes in vitro were detected. After the overexpression and knockdown of miR-19a and its target protein IGFBP3, the oxidative stress and proliferation of tenocytes in vitro were assessed. Finally, the injured tendon was treated with EVs, and the tissue morphology and proliferation of the injured tendon in vivo were examined. Results. ADSC-derived EVs were found to inhibit oxidative stress and promote proliferation of tenocytes isolated from an injury model of rats. EVs were shown to carry miR-19a which regulated the expression of IGFBP3 through binding to 3 ′ UTR of IGFBP3 mRNA. In addition, IGFBP3 promotes oxidative stress and inhibits proliferation of tenocytes. Finally, we found that ADSC-derived EVs promoted tendon wound healing in vivo. Conclusions. Our data suggest that treatment with ADSC-derived EVs ameliorates tendon injury by inhibiting oxidative stress and promoting proliferation in tenocytes. miR-19a carried by ADSC-derived EVs regulates IGFBP3 expression through binding to its 3 ′ UTR. [ABSTRACT FROM AUTHOR]

Neuroimaging studies often either look at functional activation in response to an explicit task, or functional connectivity (i.e., interregional correlations) during resting-state. Few studies have looked at the intensity of brain activity or its relationship with age, behavior, and language. The current study investigated both intensity (i.e., the Amplitude of Low-Frequency Fluctuations, ALFF) and the functional connectivity of spontaneous brain activity during rest and their relationship with age and language. A life-span sample of individuals (N = 152) completed a battery of neuropsychological tests to assess basic cognitive functions and resting-state functional MRI data to assess spontaneous brain activity. Focusing on an extend language network, the mean ALFF and total degree were calculated for this network. We found that increased age was associated with more intense activity (i.e., higher ALFF) but lower within-network connectivity. Additionally, these increases in activity within the language network during resting-state were related to worse language ability, particularly in younger adults, supporting a dedifferentiation account of cognition. Our results support the utility of using resting-state data as an indicator of cognition and support the role of ALFF as a potential biomarker in characterizing the relationships between resting-state brain activity, age, and cognition. • Increased age was associated with higher ALFF but lower connectivity. • Increased ALFF in the language network related to worse language ability. • These results support a dedifferentiation account of cognition. • Resting-state ALFF can link brain activity, age, and cognition. [ABSTRACT FROM AUTHOR]

Healthy older adults commonly report increased difficulties with language production. This could reflect decline in the language network, or age-related declines in other cognitive abilities that support language production, such as executive function. To examine this possibility, we conducted a whole-brain resting-state functional connectivity (RSFC) analysis in older and younger adults using two seed regions-the left posterior superior temporal gyrus and left inferior frontal gyrus. Whole-brain connectivities were then correlated with Stroop task performance to investigate the relationship between RSFC and executive function. We found that overall, younger adults had stronger RSFC than older adults. Moreover, in older, but not younger, adults stronger RSFC between left IFG and right hemisphere executive function regions correlated with better Stroop performance. This suggests that stronger RSFC among older adults between left IFG and right hemisphere regions may serve a compensatory function. [ABSTRACT FROM AUTHOR]

Research has suggested that using two or more languages on a daily basis helps older adults maintain a heightened functional state and improves neurocomputational efficiency. In this review, we discuss studies that have examined the effect of life-long bilingualism on age-related cognitive and neural decline, with a focus on discrepancies between different sources of evidence. We intend to outline and characterize factors which might explain inconsistencies between studies claiming that bilingualism has neurocognitive benefits and those that failed to find such evidence. We argue that individual variation in language proficiency and exposure, especially language switching frequency and daily frequency of use of the two languages, likely account for a significant chunk of the inconsistencies found in the literature and constrain the effectiveness of bilingualism as a cognitive and brain reserve factor. Finally, we briefly review studies of cognitive intervention and speculate on the potential of developing language training protocols to increase cognitive and neural resilience in older adults. [ABSTRACT FROM AUTHOR]

This study investigated how natural language use influences inhibition in language-unbalanced bilinguals. We experimentally induced natural patterns of language use (as proposed by the Adaptive Control Hypothesis) and assessed their cognitive after-effects in a group of 32 Polish–English bilinguals. Each participant took part in a series of three language games involving real conversation. Each game was followed by two inhibition tasks (stop-signal task and Stroop task). The manipulation of language use in the form of language games did not affect the behavioural measures, but it did affect ERPs. Performance of the inhibition tasks was accompanied by a reduction of P3 and the N450 amplitude differences after games involving the use of L2. The ERP modulations suggest that for bilinguals living in an L1 context the use of L2 enhances neural mechanisms related to inhibition. The study provides the first evidence for a direct influence of natural language use on inhibition. [ABSTRACT FROM AUTHOR]

Alzheimer's disease (AD) is currently the most prevalent neurological disease, and no effective and practical treatments and therapies exist. The nucleotide-binding oligomerization domain-, leucine-rich repeat-, and pyrin domain- containing receptor 3 (NLRP3) inflammasome is vital in the human innate immune response. However, when the NLRP3 inflammasome is overactivated by persistent stimulation, several immune-related diseases, including AD, atherosclerosis, and obesity, result. This review will focus on the composition and activation mechanism of the NLRP3 inflammasome, the relevant mechanisms of involvement in the inflammatory response to AD, and AD treatment targeting NLRP3 inflammasome. This review aims to reveal the pathophysiological mechanism of AD from a new perspective and provide the possibility of more effective and novel strategies for preventing and treating AD. [ABSTRACT FROM AUTHOR]

The use of multiple languages has been found to influence individuals' cognitive abilities. Although some studies have also investigated the effect of multilingualism on non-native language proficiency, fewer studies have focused on how multilingual experience affects native language production. This study investigated the effect of multilingualism on native language production, specifically examining control demands through a semantic Go/No-Go picture naming task. The multilingual experience was quantified using language entropy, which measures the uncertainty and diversity of language use. Control demands were achieved by manipulating the proportion of Go (i.e., naming) trials in different conditions. Results showed that as control demands increased, multilingual individuals exhibited poorer behavioral performance and greater brain activation throughout the brain. Moreover, more diverse language use was associated with higher accuracy in naming and more interconnected brain networks with greater involvement of domain-general neural resources and less domain-specific neural resources. Notably, the varied and balanced use of multiple languages enabled multilingual individuals to respond more efficiently to increased task demands during native language production. [ABSTRACT FROM AUTHOR]

Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease that results in the loss of motor function in the central nervous system (CNS) and ultimately death. The mechanisms underlying ALS pathogenesis have not yet been fully elucidated, and ALS cannot be treated effectively. Most studies have applied animal or single-gene intervention cell lines as ALS disease models, but they cannot accurately reflect the pathological characteristics of ALS. Induced pluripotent stem cells (iPSCs) can be reprogrammed from somatic cells, possessing the ability to self-renew and differentiate into a variety of cells. iPSCs can be obtained from ALS patients with different genotypes and phenotypes, and the genetic background of the donor cells remains unchanged during reprogramming. iPSCs can differentiate into neurons and glial cells related to ALS. Therefore, iPSCs provide an excellent method to evaluate the impact of diseases on ALS patients. Moreover, patient-derived iPSCs are obtained from their own somatic cells, avoiding ethical concerns and posing only a low risk of immune rejection. The iPSC technology creates new hope for ALS treatment. Here, we review recent studies on iPSCs and their applications in disease modeling, drug screening and cell therapy in ALS, with a particular focus on the potential for ALS treatment. [ABSTRACT FROM AUTHOR]

How speaking two languages affects executive functions has been a long‐standing debate and the mechanisms underlying the observed cognitive advantages of bilingualism remain unspecified. Here, using multivariate pattern classification methods, we decoded spatial patterns of neural signals associated with Flanker task performance in mono‐dialectal and bi‐dialectal speakers of Chinese. While univariate approach to even‐related potentials (ERPs) showed no between‐group difference, decoding accuracy of ERPs was reduced in bi‐dialectal as compared to mono‐dialectal speakers in both congruent‐neutral and incongruent‐neutral classifications. There was no effect of bidialectalism, however, on decoding accuracy of alpha‐band oscillations, an electrophysiological index implicated in inhibition. Behavioural data analysed using the Drift Diffusion Model (DDM) showed facilitating effects of bidialectalism on non‐decision times but no effect on drift rates. These findings demonstrate that using two dialects on a daily basis enhances general attentional deployment rather than affecting specific component of executive functions such as inhibitory control. Given that the two dialects of Chinese differed almost exclusively in phonology, the bidialectalism effect was most likely motivated by resolving phonological competition at lexical processing level. [ABSTRACT FROM AUTHOR]

In this paper, three different configurations of composite materials models of TiB 2 /Cu homogeneous structure, single TiB 2 /Cu network structure and hybrid reinforced (TiB 2p +TiB w)/Cu network structure are established based on their actual microstructure. The models take into account the ductile fracture of the matrix, the brittle fracture of the reinforcing phase and the traction separation behavior of the interface. Influence of mesh size and mass scaling factor on the simulation results are discussed. The validity of the simulation results is verified by the agreement of the experimental tensile stress-strain curve. The effects of TiB 2 particle size, volume fraction and hybrid effects of TiB 2p +TiB w on plastic deformation and mechanical properties of composites are assessed from the three aspects: interface damage, load-bearing capacity of reinforcement and matrix damage. Compared with the TiB 2 /Cu homogeneous composites and the single TiB 2 /Cu network composites, the hybrid reinforced (TiB 2p +TiB w)/Cu network composites has better comprehensive mechanical properties, and its tensile strength and elongation are 349 MPa and 10.6 %, respectively. The addition of whiskers can effectively improve the bearing capacity of the hybrid reinforced (TiB 2p +TiB w)/Cu network composites, but reduce the elongation of composites. [Display omitted] • Models of homogeneous composites, single TiB 2 network composites and hybrid TiB 2p +TiB w network composites are established. • The particle size, volume fraction and the hybrid effects of TiB 2p +TiB w on the deformation of composites are studied. • The composites are assessed from the three aspects: interface damage, load-bearing capacity of and matrix damage. [ABSTRACT FROM AUTHOR]

Infrared small target detection is a challenging task due to the small target size and complex background clusters. The matrix factorization-based algorithms can work well in addressing this issue. In this paper, to address the residual over-optimized issue in matrix factorization, a novel Pareto frontier optimization-based algorithm is proposed to obtain the best trade-off between a given noise level and the optimal objective value. To suppress background outliers, a robust Huber penalty and non-negative constraints are introduced in matrix factorization. To solve the nuclear norm regularization faster, a randomized SVD algorithm is adopted. Finally, the proposed algorithm is compared with 11 representative detectors on 6 proposed test sequences, which have more than 1500 frames. The experimental results demonstrate the effectiveness of the proposed algorithm in improving speed and suppressing outliers. The source codes and data are available on https://github.com/wahahamyt/ISTD. [ABSTRACT FROM AUTHOR]

In this study, we aimed to investigate the effect of herpes simplex virus type-1 (HSV-1) infection on the phosphorylation of interferon regulatory factor 3 (IRF3) and the expression of interferon-β (IFN-β), as well as to clarify the functions of toll-like receptor 3 (TLR3) in mouse neural stem cells (NSCs) infected with HSV-1. In HSV-1-infected cultured NSCs, immunofluorescence, reverse transcription - polymerase chain reaction, Western blot, and ELISA were performed to reveal the expression patterns of TLR3, IRF3, and IFN-β. Then, lentivirus-mediated RNA interference (RNAi) was used to block the expression of TLR3, and its effect on host resistance to HSV-1 infection was investigated. Under uninfected conditions, NSCs expressed TLR3 and phosphorylated IRF3, but after infection, the expression level of TLR3 was upregulated and the phosphorylation level of IRF3 in the nucleus was significantly enhanced, while IFN-β was also expressed. After TLR3 expression was blocked by lentivirus-mediated RNAi, IRF3 phosphorylation and IFN-β expression were downregulated. Therefore, HSV-1 upregulated the expression of TLR3 in NSCs and promoted nuclear translocation after IRF3 was phosphorylated to induce IFN-β expression. TLR3 exhibited an anti-HSV-1 infection capacity via innate immune functions. [ABSTRACT FROM AUTHOR]

This study established psycholinguistic norms in Cantonese for a set of 1286 colored pictures sourced from several picture databases, including 750 colored line drawings from MultiPic (Duñabeitia et al., 2018) and 536 photographs selected for McRae et al. (2005) concepts. The pictures underwent rigorous normalization processes. We provided picture characteristics including name and concept agreement, familiarity, visual complexity, and frequency of modal responses. Through correlational analyses, we observed strong interrelationships among these variables. We also compared the current Cantonese norming to other languages and demonstrated similarity and variations among different languages. Additionally, we embraced the multilingual diversity within the current sample, and found that higher Cantonese proficiency but lower non-native language proficiency were associated with better spoken picture naming. Last but not least, we validated the predictive power of normed variables calculated from typed responses to spoken picture naming, and the consistency between typed and spoken responses. The present norming provides a timely and valuable alternative for researchers in the field of psycholinguistics, especially those studying Cantonese production and lexical retrieval. All raw data, analysis scripts, and final norming results are available online as psycholinguistic norms for Cantonese in the following link at the Open Science Framework: https://osf.io/dz9j6/?view_only=a452d8a56c92430b9dedf21ac26b1bc1. [ABSTRACT FROM AUTHOR]

Abstract: Iron-induced oxidative stress is thought to play a crucial role in the pathogenesis of Parkinson''s disease. Our previous studies demonstrated that decreased expression of ferroportin 1 contributes to 6-hydroxydopamine induced intracellular iron accumulation and that decreased ferroportin 1 expression is caused by increased expression of iron regulatory protein 1. Iron regulatory protein 1 is a central regulator of iron homeostasis and is a likely target of extracellular agents to program changes in cellular iron metabolism. Therefore, the mechanism of iron regulatory protein 1 upregulation induced by 6-hydroxydopamine has become a significant focus of research. Iron regulatory protein 1 is regulated by protein kinase C, although this regulation is tissue specific. Therefore, in the present study, we aimed to determine whether alteration of protein kinase C activity modified iron regulatory protein 1 expression in the dopaminergic MES23.5 cell line, Furthermore, we investigated whether 6-hydroxydopamine induced iron regulatory protein 1 upregulation is mediated by protein kinase C, thus achieving regulation of cellular iron levels. The results showed that iron regulatory protein 1 was upregulated by phorbol 12-myristate-13-acetate, the PKC activator in dopaminergic MES23.5 cells, and ferroportin 1 expression and iron efflux were decreased as a result of iron regulatory protein 1 upregulation. The protein kinase C inhibitor bisindolylmaleimide I hydrochloride abolished the effect of phorbol 12-myristate-13-acetate. Protein kinase C-δ and protein kinase C-ζ, but not protein kinase C-ɛ were activated by 6-hydroxydopamine. The protein kinase C-δ inhibitor rottlerin inhibited protein kinase C-δ phosphorylation and abolished iron regulatory protein 1 upregulation induced by 6-hydroxydopamine. The protein kinase C-ζ pseudo-substrate inhibitor inhibited protein kinase C-ζ phosphorylation and abolished iron regulatory protein 1 upregulation induced by 6-hydroxydopamine. These data indicate that iron regulatory protein 1 is regulated by protein kinase C in dopaminergic MES23.5 cells and that protein kinase C activated by 6-hydroxydopamine regulates iron regulatory protein 1 expression, thus achieving regulation of cellular iron levels. [Copyright &y& Elsevier]

Underwater Distance Measurement: Precise Underwater Distance Measurement by Dual Acoustic Frequency Combs (Ann. In article number 1900283, Hanzhong Wu, Jingsheng Zhai, and co-workers describe the successful generation of fully stabilized acoustic frequency combs. Long distances are able to be measured underwater using the dual-comb scheme, and the measurement uncertainty can achieve 50 µm. This work paves the way to future underwater applications using acoustic frequency combs. [Extracted from the article]

Underwater acoustics is of fundamental importance for marine science and technology. However, acoustic waves transmitted by state‐of‐the‐art underwater acoustic systems are not inherently phase locked, which hinders the development of underwater acoustic technology. For example, the precision of underwater distance measurement can only achieve centimeter level. As a versatile tool, optical frequency combs have enabled revolutionary progress in optical metrology and precision measurement. In parallel with optical frequency combs, here, the generation of fully stabilized, underwater acoustic frequency combs is reported, in which equidistant acoustic modes are produced via a hydroacoustic transducer. The precision of each individual acoustic mode is measured to be 10−9 at 1 s and 10−12 at 1000 s averaging times. Underwater distance measurements are carried out in an anechoic pool using a dual‐comb scheme. Comparison with reference values shows consistency within 50 µm (7 × 10−6 in relative). The relatively long‐duration experiments at 7 m distance yield an Allan deviation of 1.8 µm (2.6 × 10−7 in relative) at 1 s and further 480 nm (6.8 × 10−8 in relative) at 40 s averaging times. The approach to acoustic frequency comb generation offers a promising and powerful platform for future underwater distance measurement, positioning, and navigation. [ABSTRACT FROM AUTHOR]

Purpose. As we all know, curative resection remains the only effective treatment for hepatocellular cancer (HCC). However, systemic inflammatory response syndrome always correlates with surgery, which may impose an impact on the clinical outcome of HCC patients who had undergone curative treatment. The present study is aimed at exploring the correlation between perioperative inflammatory mediators and recurrence risk of HCC. Methods. This study retrospectively included 157 histologically confirmed single HCC patients (88 patients developed HCC again) who had received radical hepatectomy between January 2016 and May 2018 at the Department of Hepatobiliary Surgery, the People's Liberation Army General Hospital (PLAGH), China. The cut-off values for predicting recurrence were determined by receiver operating characteristic (ROC) curve analysis with estimation of the Youden index. Recurrence-free survival (RFS) was assessed using the Kaplan-Meier method, and the difference was compared between groups by the log-rank test. Univariate/multivariate analysis was performed to identify independent risk factors of postoperative tumor recurrence. Results. The perioperative serum IL1, IL2, and IL10 levels showed no difference between groups, whereas the serum IL6, IL8, and TNF-α levels showed significant differences between groups. High preoperative serum IL6, IL8, and TNF-α levels were significantly associated with shorter RFS. Multivariate analysis revealed that preoperative serum IL6>8.45 pg/ml, preoperative serum IL8>68 pg/ml, preoperative serum TNF−α>14.9 pg/ml, microvascular invasion (MVI), and maximum tumor size>6 cm were independent predictors of RFS. Conclusions. The present study confirmed that high preoperative serum IL6, IL8, and TNF-α levels were distinctly correlated with the postoperative tumor recurrence risk of HCC patients. [ABSTRACT FROM AUTHOR]

In this paper, we experimentally perform the measurement of the backscattered light intensity from the underwater targets with different size. We develop a simple system, which can easily measure the intensity of the backscattered light, after the laser is scattered at the target underwater. We find that, the signal period is related to the particle size, and the stability of the intensity (standard deviation) varies linearly with changing the particle size. After the calibration, our system can be used to precisely determine the particle size of arbitrary targets. Our method could open a new opportunity for the future underwater detection using femtosecond pulse laser. [ABSTRACT FROM AUTHOR]

Abstract: MicroRNAs (miRNAs) are suspected to be a contributing factor in amyotrophic lateral sclerosis (ALS). Here, we assess the altered expression of miRNAs and the effects of miR‐124 in astrocytic differentiation in neural stem cells of ALS transgenic mice. Differentially expressed miRNA‐positive cells (including miR‐124, miR‐181a, miR‐22, miR‐26b, miR‐34a, miR‐146a, miR‐219, miR‐21, miR‐200a, and miR‐320) were detected by in situ hybridization and qRT‐PCR in the spinal cord and the brainstem. Our results demonstrated that miR‐124 was down‐regulated in the spinal cord and brainstem. In vitro, miR‐124 was down‐regulated in neural stem cells and up‐regulated in differentiated neural stem cells in G93A‐superoxide dismutase 1 (SOD1) mice compared with WT mice by qRT‐PCR. Meanwhile, Sox2 and Sox9 protein levels showed converse change with miR‐124 in vivo and vitro. After over‐expression or knockdown of miR‐124 in motor neuron‐like hybrid (NSC34) cells of mouse, Sox2 and Sox9 proteins were noticeably down‐regulated or up‐regulated, whereas Sox2 and Sox9 mRNAs remained virtually unchanged. Moreover, immunofluorescence results indicated that the number of double‐positive cells of Sox2/glial fibrillary acidic protein (GFAP) and Sox9/glial fibrillary acidic protein (GFAP) was higher in G93A‐SOD1 mice compared with WT mice. We also found that many Sox2‐ and Sox9‐positive cells were nestin positive in G93A‐SOD1 mice, but not in WT mice. Furthermore, differentiated neural stem cells from G93A‐SOD1 mice generated a greater proportion of astrocytes and lower proportion of neurons than those from WT mice. MiR‐124 may play an important role in astrocytic differentiation by targeting Sox2 and Sox9 in ALS transgenic mice. Cover Image for this issue: doi: 10.1111/jnc.14171. [ABSTRACT FROM AUTHOR]

Aging is often associated with declines in language production. For example, compared to younger adults, older adults experience more tip-of-the-tongue (TOT) states, show decreased speed and accuracy in naming objects, and have more pauses and fillers in speech, all of which indicate age-related increases in retrieval difficulty. While prior work has suggested that retrieval difficulty may be phonologically based, it is unclear whether there are age-related differences in the organization of phonological information per se or whether age-related difficulties may arise from accessing that information. Here we used fMRI to investigate the neural and behavioral basis of phonological neighborhood denisty (PND) effects on picture naming across the lifespan (N=91, ages 20-75). Consistent with prior work, behavioral results revealed that higher PND led to faster picture naming times and higher accuracies overall, and that older adults were less accurate in their responses. Consistent with the behavioral analyses, fMRI analyses showed that increasing PND was associated with decreased activation in auditory and motor language regions, including bilateral superior temporal gyri and bilateral precentral gyri. Interestingly, although there were age-related increases in functional activation to picture naming, there were no age-related modulations of neural sensitivity to PND. Overall, these results suggest that having a large cohort of phonological neighbors facilitates language production, and although aging is associated with increases in language production difficulty, sensitivity to phonological features during language production is stable across the lifespan. [ABSTRACT FROM AUTHOR]

In this paper, we demonstrate a three-dimensional imaging system based on the laser frequency comb. We develop a compact, all-fiber mode-locked laser at 1 μm, whose repetition frequency can be tightly synchronized to the external frequency reference. The mode-locked state is achieved via the saturable absorber mirror in a linear cavity, and the laser output power can be amplified from 4 mW to 150 mW after a Yb-doped fiber amplifier. Three-dimensional imaging is realized via the spectral interferometry with the aid of an equal-arm Michelson interferometer. Compared with the reference values, the measurement results show the difference can be below 4 μm. Our system could provide a pathway to the real industry applications in future. [ABSTRACT FROM AUTHOR]