Potent NKT cell ligands overcome SARS-CoV-2 immune evasion to mitigate viral pathogenesis in mouse models.

One of the major pathogenesis mechanisms of SARS-CoV-2 is its potent suppression of innate immunity, including blocking the production of type I interferons. However, it is unknown whether and how the virus interacts with different innate-like T cells, including NKT, MAIT and γδ T cells. Here we reported that upon SARS-CoV-2 infection, invariant NKT (iNKT) cells rapidly trafficked to infected lung tissues from the periphery. We discovered that the envelope (E) protein of SARS-CoV-2 efficiently down-regulated the cell surface expression of the antigen-presenting molecule, CD1d, to suppress the function of iNKT cells. E protein is a small membrane protein and a viroporin that plays important roles in virion packaging and envelopment during viral morphogenesis. We showed that the transmembrane domain of E protein was responsible for suppressing CD1d expression by specifically reducing the level of mature, post-ER forms of CD1d, suggesting that it suppressed the trafficking of CD1d proteins and led to their degradation. Point mutations demonstrated that the putative ion channel function was required for suppression of CD1d expression and inhibition of the ion channel function using small chemicals rescued the CD1d expression. Importantly, we discovered that among seven human coronaviruses, only E proteins from highly pathogenic coronaviruses including SARS-CoV-2, SARS-CoV and MERS suppressed CD1d expression, whereas the E proteins of human common cold coronaviruses, HCoV-OC43, HCoV-229E, HCoV-NL63 and HCoV-HKU1, did not. These results suggested that E protein-mediated evasion of NKT cell function was likely an important pathogenesis factor, enhancing the virulence of these highly pathogenic coronaviruses. Remarkably, activation of iNKT cells with their glycolipid ligands, both prophylactically and therapeutically, overcame the putative viral immune evasion, significantly mitigated viral pathogenesis and improved host survival in mice. Our results suggested a novel NKT cell-based anti-SARS-CoV-2 therapeutic approach.

Action recognition for sports combined training based on wearable sensor technology and SVM prediction.

In the field of sports, coaches have mainly relied on observing the performance of athletes on the spot to formulate suitable training plans for athletes, which has extremely high requirements for the professionalism of coaches. Based on the above requirements, this paper designs a sports action recognition system for sports enthusiasts based on the SVM algorithm optimization model, and for the purpose of verifying the applicability of the system to different sports fields, experiments are carried out on basketball actions and race walking actions. The system uses wearable sensors to capture the motion data of the user, and then analyzes and identifies the user's actions through the SVM algorithm optimization model. By standardizing the user's sports combination training under the system algorithm, the user can improve their training efficiency and reduce the risk of injury. To establish the human body motion model, this paper divides the human skeleton model into five motion branches. The rotation freedom constraints and joint rotation angle range limits are added to the model to ensure the accuracy of the motion analysis. Combining the forward kinematics of the robot and the homogeneous coordinate transformation, the human body joint rotation motion model and the human bone position and posture model are established. In the end, the user can standardize the sports combination training under the system algorithm. In this paper, through the research of wearable sensor technology and sports combined training action recognition, and apply it to practical life, it aims to promote its development and application.

Beyond Residence: A Mobility-based Approach for Improved Evaluation of Human Exposure to Environmental Hazards.

Standard environmental hazard exposure assessment methods have been primarily based on residential places, neglecting individuals' hazard exposures due to activities outside home neighborhood and underestimating peoples' overall hazard exposures. To address this limitation, this study proposes a novel mobility-based index for the hazard exposure evaluation. Using large-scale human mobility data, we quantify the extent of population dwell time in high environmental hazard places in 239 US counties for three environmental hazards. We explore how human mobility extends the reach of environmental hazards and leads to the emergence of latent exposure for populations living outside high-hazard areas. Notably, neglect of mobility can lead to over 10% underestimation of hazard exposures. The interplay of spatial clustering in high-hazard regions and human movement trends creates "environmental hazard traps." Poor and ethnic minority residents disproportionately face multiple types of environmental hazards. This data-driven evidence supports the severity of these injustices. We also studied latent exposure arising from visits outside residents' home areas, revealing millions of the population having 5 to 10% of daily activities occur in high-exposure zones. Despite living in perceived safe areas, human mobility could expose millions of residents to different hazards. These findings provide crucial insights for targeted policies to mitigate these severe environmental injustices.

The fine-scale associations between socioeconomic status, density, functionality, and spread of COVID-19 within a high-density city.

BACKGROUND: Motivated by the need for precise epidemic control and epidemic-resilient urban design, this study aims to reveal the joint and interactive associations between urban socioeconomic, density, connectivity, and functionality characteristics and the COVID-19 spread within a high-density city. Many studies have been made on the associations between urban characteristics and the COVID-19 spread, but there is a scarcity of such studies in the intra-city scale and as regards complex joint and interactive associations by using advanced machine learning approaches. METHODS: Differential-evolution-based association rule mining was used to investigate the joint and interactive associations between the urban characteristics and the spatiotemporal distribution of COVID-19 confirmed cases, at the neighborhood scale in Hong Kong. The associations were comparatively studied for the distribution of the cases in four waves of COVID-19 transmission: before Jun 2020 (wave 1 and 2), Jul-Oct 2020 (wave 3), and Nov 2020-Feb 2021 (wave 4), and for local and imported confirmed cases. RESULTS: The first two waves of COVID-19 were found mainly characterized by higher-socioeconomic-status (SES) imported cases. The third-wave outbreak concentrated in densely populated and usually lower-SES neighborhoods, showing a high risk of within-neighborhood virus transmissions jointly contributed by high density and unfavorable SES. Starting with a super-spread which considerably involved high-SES population, the fourth-wave outbreak showed a stronger link to cross-neighborhood transmissions driven by urban functionality. Then the outbreak diffused to lower-SES neighborhoods and interactively aggravated the within-neighborhood pandemic transmissions. Association was also found between a higher SES and a slightly longer waiting period (i.e., the period from symptom onset to diagnosis of symptomatic cases), which further indicated the potential contribution of higher-SES population to the pandemic transmission. CONCLUSIONS: The results of this study may provide references to developing precise anti-pandemic measures for specific neighborhoods and virus transmission routes. The study also highlights the essentiality of reliving co-locating overcrowdedness and unfavorable SES for developing epidemic-resilient compact cities, and the higher obligation of higher-SES population to conform anti-pandemic policies.

Social media mining under the COVID-19 context: Progress, challenges, and opportunities.

Social media platforms allow users worldwide to create and share information, forging vast sensing networks that allow information on certain topics to be collected, stored, mined, and analyzed in a rapid manner. During the COVID-19 pandemic, extensive social media mining efforts have been undertaken to tackle COVID-19 challenges from various perspectives. This review summarizes the progress of social media data mining studies in the COVID-19 contexts and categorizes them into six major domains, including early warning and detection, human mobility monitoring, communication and information conveying, public attitudes and emotions, infodemic and misinformation, and hatred and violence. We further document essential features of publicly available COVID-19 related social media data archives that will benefit research communities in conducting replicable and reproducible studies. In addition, we discuss seven challenges in social media analytics associated with their potential impacts on derived COVID-19 findings, followed by our visions for the possible paths forward in regard to social media-based COVID-19 investigations. This review serves as a valuable reference that recaps social media mining efforts in COVID-19 related studies and provides future directions along which the information harnessed from social media can be used to address public health emergencies.

Examining the diffusion of coronavirus disease 2019 cases in a metropolis: a space syntax approach.

BACKGROUND: The urban built environment (BE) has been globally acknowledged as one of the main factors that affects the spread of infectious disease. However, the effect of the street network on coronavirus disease 2019 (COVID-19) incidence has been insufficiently studied. Severe acute respiratory syndrome coronavirus 2, which causes COVID-19, is far more transmissible than previous respiratory viruses, such as severe acute respiratory syndrome coronavirus, which highlights the role of the spatial configuration of street network in COVID-19 spread, as it is where humans have contact with each other, especially in high-density areas. To fill this research gap, this study utilized space syntax theory and investigated the effect of the urban BE on the spatial diffusion of COVID-19 cases in Hong Kong. METHOD: This study collected a comprehensive dataset including a total of 3815 confirmed cases and corresponding locations from January 18 to October 5, 2020. Based on the space syntax theory, six space syntax measures were selected as quantitative indicators for the urban BE. A linear regression model and Geographically Weighted Regression model were then applied to explore the underlying relationships between COVID-19 cases and the urban BE. In addition, we have further improved the performance of GWR model considering the spatial heterogeneity and scale effects by adopting an adaptive bandwidth. RESULT: Our results indicated a strong correlation between the geographical distribution of COVID-19 cases and the urban BE. Areas with higher integration (a measure of the cognitive complexity required for a pedestrians to reach a street) and betweenness centrality values (a measure of spatial network accessibility) tend to have more confirmed cases. Further, the Geographically Weighted Regression model with adaptive bandwidth achieved the best performance in predicting the spread of COVID-19 cases. CONCLUSION: In this study, we revealed a strong positive relationship between the spatial configuration of street network and the spread of COVID-19 cases. The topology, network accessibility, and centrality of an urban area were proven to be effective for use in predicting the spread of COVID-19. The findings of this study also shed light on the underlying mechanism of the spread of COVID-19, which shows significant spatial variation and scale effects. This study contributed to current literature investigating the spread of COVID-19 cases in a local scale from the space syntax perspective, which may be beneficial for epidemic and pandemic prevention.

The protective role of microRNA-21 against coxsackievirus B3 infection through targeting the MAP2K3/P38 MAPK signaling pathway.

BACKGROUND: The P38 mitogen-activated protein kinase (MAPK) pathway plays an essential role in CVB3-induced diseases. We previously demonstrated microRNA-21 has potential inhibitory effect on the MAP2K3 which locates upstream of P38 MAPK and was upregulated in mouse hearts upon CVB3 infection. However, the effect and underlying mechanism of miRNA-21 on CVB3 infection remain unclear. METHODS: We detected continuous changes of cellular miRNA-21 and P38 MAPK proteins expression profiling post CVB3 infection in vitro within 12 h. P38 MAPK signaling was inhibited by the specific inhibitor, small interfering RNA and miRNA-21 mimic in vitro, CVB3 replication, cell apoptosis rate and proliferation were detected. Viral load in the mice heart, cardiomyocyte apoptosis rate and histological of the heart were also detected in the mice model of viral myocarditis pretreated with miRNA-21-lentivirus. RESULTS: We observed significant upregulation of miRNA-21 expression followed by suppression of the MAP2K3/P38 MAPK signaling in CVB3-infected Hela cells. The inactivation of the MAP2K3/P38 MAPK signaling by P38 MAPK specific inhibitor, small interfering RNA against MAP2K3, or miRNA-21 overexpression significantly inhibited viral progeny release from CVB3-infected cells. Mechanistically, when compared with control miRNA, miRNA-21 showed no effect on capsid protein VP1 expression and viral load within host cells, while significantly reversing CVB3-induced caspase-3 activation and cell apoptosis rate, further promoting proliferation of infected cells, which indicates the inhibitory effect of miRNA-21 on CVB3 progeny release. In the in vivo study, when compared with control miRNA, miRNA-21 pretreatment remarkably inactivated the MAP2K3/P38 MAPK signaling in mice and protected them against CVB3 infection as evidenced by significantly alleviated cell apoptosis rate, reduced viral titers, necrosis in the heart as well as by remarkably prolonged survival time. CONCLUSIONS: miRNA-21 were reverse correlated with P38 MAPK activation post CVB3 infection, miRNA-21 overexpression significantly inhibited viral progeny release and decreased myocytes apoptosis rate in vitro and in vivo, suggesting that miRNA-21 may serve as a potential therapeutic agent against CVB3 infection through targeting the MAP2K3/P38 MAPK signaling.

Plasma interleukin-37 is increased and inhibits the production of inflammatory cytokines in peripheral blood mononuclear cells in systemic juvenile idiopathic arthritis patients.

BACKGROUND: Interleukin (IL)-37 has emerged as a novel anti-inflammatory cytokine that play an immunosuppressive role in regulating inflammatory response. This study aimed to measure IL-37 levels in the plasma and peripheral blood mononuclear cells (PBMCs) of patients with systemic juvenile idiopathic arthritis (sJIA), and to establish the correlation between IL-37 levels and disease activity, laboratory parameters and inflammatory cytokines. METHODS: The mRNA levels of IL-37 in PBMCs and plasma IL-37 concentrations in 46 sJIA patients and 30 age- and sex-matched healthy controls were measured by real-time polymerase chain reaction (RT-PCR) and enzyme-linked immunosorbent assay (ELISA), respectively. The correlations between plasma IL-37 levels and disease activity, laboratory parameters and inflammatory cytokines in sJIA were analyzed by Spearman correlation test. PBMCs from the sJIA patients were stimulated with recombinant human IL-37 (rhIL-37) protein, expressions of IL-1ß, IL-6, TNF-α and IL-17 were detected by RT-PCR and ELISA. RESULTS: Plasma levels of IL-37 and relative IL-37 mRNA expression were significantly elevated in sJIA patients, especially in active sJIA patients, when compared with the healthy controls (P < 0.001). Furthermore, patients with active disease showed higher IL-37 mRNAs and plasma protein levels than those with inactive disease as well as healthy controls. Plasma IL-37 levels were correlated with disease activity and inflammatory cytokines (IL-6, TNF-α, IL-17 and GM-CSF) in sJIA patients. The productions of inflammatory cytokines such as IL-6, TNF-α, IL-17 in PBMCs from sJIA patients were obviously decreased after recombinant IL-37 stimulation, whereas the production of IL-1ß was not changed. CONCLUSIONS: Our results demonstrate that levels of IL-37 were higher in sJIA patients, which were correlated with disease activity and sJIA related inflammatory cytokines. In addition, rhIL-37 down-regulates the expressions of inflammatory cytokines form PBMCs in sJIA patients, suggesting that IL-37 may have the potential role as a natural inhibitor for the pathogenesis and therapy of sJIA.

Coxsackievirus B3 engineered to contain microRNA targets for muscle-specific microRNAs displays attenuated cardiotropic virulence in mice.

UNLABELLED: Coxsackievirus B3 (CVB3) is trophic for cardiac tissue and is a major causative agent for viral myocarditis, where local viral replication in the heart may lead to heart failure or even death. Recent studies show that inserting microRNA target sequences into the genomes of certain viruses can eradicate these viruses within local host tissues that specifically express the cognate microRNA. Here, we demonstrated both in vitro and in vivo that incorporating target sequences for miRNA-133 and -206 into the 5' untranslated region of the CVB3 genome ameliorated CVB3 virulence in skeletal muscle and myocardial cells that specifically expressed the cognate cellular microRNAs. Compared to wild-type CVB3, viral replication of the engineered CVB3 was attenuated in human TE671 (rhabdomyosarcoma) and L6 (skeletal muscle) cell lines in vitro that expressed high levels of miRNA-206. In the in vivo murine CVB3-infection model, viral replication of the engineered CVB3 was attenuated specifically in the heart that expressed high levels of both miRNAs, but not in certain tissues, which allowed the host to retain the ability to induce a strong and protective humoral immune response against CVB3. The results of this study suggest that a microRNA-targeting strategy to control CVB3 tissue tropism and pathogenesis may be useful for viral attenuation and vaccine development. IMPORTANCE: Coxsackievirus B3 (CVB3) is a major causative agent for viral myocarditis, and viral replication in the heart may lead to heart failure or even death. Limiting CVB3 replication within the heart may be a promising strategy to decrease CVB3 pathogenicity. miRNAs are ∼21-nucleotide-long, tissue-specific endogenous small RNA molecules that posttranscriptionally regulate gene expression by imperfectly binding to the 3' untranslated region (UTR), the 5' UTR, or the coding region within a gene. In our study, muscle-specific miRNA targets (miRT) were incorporated into the CVB3 genome. Replication of the engineered viruses was restricted in the important heart tissue of infected mice, which reduced cardiac pathology and increased mouse survival. Meanwhile, replication ability was retained in other tissues, thus inducing a strong humoral immune response and providing long-term protection against CVB3 rechallenge. This study suggests that a microRNA-targeting strategy can potentially control CVB3 tissue tropism and pathogenesis and may be useful for viral attenuation and vaccine development.

Antinuclear antibody-positive cohort constitutes homogeneous entity in juvenile idiopathic arthritis.

OBJECTIVE: To identify a homogeneous entity for antinuclear antibody (ANA)-positive patients suffering from juvenile idiopathic arthritis (JIA). METHODS: All of the clinical features were recorded retrospectively. ANA positivity was defined as more than twice positive results at a titer of > 1:100. The correlation between ANA positivity and clinical parameters was assessed by multiple logistic regression analysis. RESULT: Of 120 patients, 49 patients were ANA positive (31 oligoarthritis, 18 rheumatoid factor [RF]-negative polyarthritis) and 71 patients were ANA negative (48 oligoarthritis, 23 RF-negative polyarthritis), and were recruited retrospectively to this study according to the International League of Associations for Rheumatology (ILAR) criteria. In ANA-positive cohort, the characteristics of early-onset age, female predominance, and asymmetric arthritis were observed compared with ANA-negative cohort including oligoarthritis and RF-negative polyarthritis. Correspondingly, we found that ANA-positive cohort had higher cumulative number of joints affected at 9 and 12 months after disease presentation than ANA-negative cohort, had lower frequency of occurrence of image change, and had a different pattern of affected arthritis than ANA-negative cohort, which was more likely to have knee involvement and less likely to have hip and shoulder involvement. ANA positivity correlated strongly with asymmetric arthritis, female predominance and wrist involvement. CONCLUSION: This study demonstrates that ANA-positive cohort divided into different subgroups by present ILAR criteria share the similar features and suggests that ANA positivity might serve as a novel potential value for JIA classification.

Differential plasma microRNAs expression in juvenile idiopathic arthritis.

OBJECTIVES: To identify potential novel biomarkers for juvenile idiopathic arthritis (JIA), we evaluated the correlation between plasma expression levels of specific miRNAs and disease characteristics of JIA. METHODS: Differentially expressed miRNAs in JIA plasma were identified by microarray analysis. Five candidate plasma miRNAs with differential expression were further evaluated by qRT-PCR. The correlation between the expression of candidate plasma miRNAs and clinical parameters of JIA patients was assessed. RESULTS: The expression of miR-16, miR-146a, and miR-223 was higher, and miR-132 was lower, in the plasma of JIA patients as compared with healthy subjects and juvenile ankylosing spondylitis patients (p < 0.05). Plasma miR-16 concentrations were considerably higher for polyarticular JIA patients than oligoarticular JIA patients and correlated with the juvenile arthritis magnetic resonance imaging scores for the hip and plasma interleukin-6 or IL-6 levels. Additionally, miR-146a levels correlated directly with the Juvenile Arthritis Disease Activity Scores in 27 joints, the swollen joint count, the limited joint count, and the juvenile arthritis magnetic resonance imaging scores for the hip, but correlated inversely with plasma tumor necrosis factor-α or TNF-α levels. CONCLUSIONS: This study demonstrates that the expression of plasma miRNAs correlates with JIA disease and suggests that plasma miR-16 and miR-146a have potential novel value for JIA diagnosis.

Inhaled heparin: Past, present, and future.

While heparin has traditionally served as a key anticoagulant in clinical practice for nearly a century, recent years have witnessed a growing interest in its role as a potent antiinflammatory and antiviral agent, as well as an anticancer agent. To address challenges with injection-based delivery, exploring patient-friendly routes such as oral and pulmonary delivery is crucial. This review specifically highlights the multiple therapeutic benefits of inhaled heparin. In summary, this review serves as a valuable source of information, providing deep insights into the diverse therapeutic advantages of inhaled heparin and its potential applications within clinical contexts.

The lncRNA MEG3/miRNA-21/P38MAPK axis inhibits coxsackievirus 3 replication in acute viral myocarditis.

Evidence is emerging on the roles of long noncoding RNAs (lncRNAs) as regulatory factors in a variety of viral infection processes, but the mechanisms underlying their functions in coxsackievirus group B type3 (CVB3)-induced acute viral myocarditis have not been explicitly delineated. We previously demonstrated that CVB3 infection decreases miRNA-21 expression; however, lncRNAs that regulate the miRNA-21-dependent CVB3 disease process have yet to be identified. To evaluate lncRNAs upstream of miRNA-21, differentially expressed lncRNAs in CVB3-infected mouse hearts were identified by microarray analysis and lncRNA/miRNA-21 interactions were predicted bioinformatically. MEG3 was identified as a candidate miRNA-21-interacting lncRNA upregulated in CVB3-infected mouse hearts. MEG3 expression was verified to be upregulated in HeLa cells 48 h post CVB3 infection and to act as a competitive endogenous RNA of miRNA-21. MEG3 knockdown resulted in the upregulation of miRNA-21, which inhibited CVB3 replication by attenuating P38-MAPK signaling in vitro and in vivo. Knockdown of MEG3 expression before CVB3 infection inhibited viral replication in mouse hearts and alleviated cardiac injury, which improved survival. Furthermore, the knockdown of CREB5, which was predicted bioinformatically to function upstream of MEG3, was demonstrated to decrease MEG3 expression and CVB3 viral replication. This study identifies the function of the lncRNA MEG3/miRNA-21/P38 MAPK axis in the process of CVB3 replication, for which CREB5 could serve as an upstream modulator.

MicroRNAs regulate the pathogenesis of CVB3-induced viral myocarditis.

AIMS: To evaluate the role of microRNAs (miRNAs) in the pathogenesis of Coxsackievirus B3 (CVB3)-induced viral myocarditis. METHODS: We detected miRNA expression profiling by microarray utilizing a mouse model on day 4 after CVB3 infection. Then we validated differentially expressed miRNAs using real-time polymerase chain reaction (PCR). We predicted target genes using miRNA target prediction databases and assessed them using mRNA microarray and qualitative reverse transcription PCR measurements. By analyzing the target function of differentially expressed miRNAs, we initially explored the regulating role of miRNAs in viral myocarditis. RESULTS: We found five differentially expressed miRNAs that are involved in regulating several important innate immune and antiviral pathways such as the Toll-like receptor signaling pathway, RIG-I-like receptor signaling pathway, NOD-like receptor signaling pathway, cytokine- cytokine receptor interaction, MAPK signaling pathway, JAK-STAT signaling pathway, and natural killer cell-mediated cytotoxicity. CONCLUSION: miRNAs regulate the pathogenesis of viral myocarditis. This study may provide a new perspective and a deeper understanding of the pathogenesis of viral myocarditis that may help with the development of novel therapies against CVB3 infection.

Short hairpin RNA targeting 2B gene of coxsackievirus B3 exhibits potential antiviral effects both in vitro and in vivo.

BACKGROUND: Coxsackievirus B3 is an important infectious agent of viral myocarditis, pancreatitis and aseptic meningitis, but there are no specific antiviral therapeutic reagents in clinical use. RNA interference-based technology has been developed to prevent the viral infection. METHODS: To evaluate the impact of RNA interference on viral replication, cytopathogenicity and animal survival, short hairpin RNAs targeting the viral 2B region (shRNA-2B) expressed by a recombinant vector (pGCL-2B) or a recombinant lentivirus (Lenti-2B) were tansfected in HeLa cells or transduced in mice infected with CVB3. RESULTS: ShRNA-2B exhibited a significant effect on inhibition of viral production in HeLa cells. Furthermore, shRNA-2B improved mouse survival rate, reduced the viral tissues titers and attenuated tissue damage compared with those of the shRNA-NC treated control group. Lenti-2B displayed more effective role in inhibition of viral replication than pGCL-2B in vivo. CONCLUSIONS: Coxsackievirus B3 2B is an effective target of gene silencing against coxsackievirus B3 infection, suggesting that shRNA-2B is a potential agent for further development into a treatment for enterviral diseases.

Three-Dimensional Reconstruction of National Traditional Sports Cultural Heritage Based on Feature Clustering and Artificial Intelligence.

The development of three-dimensional reconstruction technology with cultural heritage in traditional sports allows an accurate portrayal of this aspect of life. Cultural heritage can be documented, recovered, and shown with the tools and techniques. It is an important aspect of self-determination and the ability of marginalized groups to engage in social and cultural life fully. The most challenging aspects of national cultural sports heritage in reconstruction, including armed conflict and war, improper disposal, pollution, poaching, natural disasters, and destruction of heritage sites, have been determined. This article introduces (SCH-AI) new technology for sports cultural heritage (SCH), which develops an improved artificial intelligence (AI) that helps reduce armed conflict and war and promotes tolerance toward religions and people. Athletics improves by bringing individuals together in a social and economic context. Sports engagement boosts community health and productivity. When a clustering algorithm is used, it analyses the data that were provided identifying organic clusters or patterns in the space of features. Clustering is the process of dividing data into distinct subsets. The scenario depicts a strength and conditioning coach who wishes to establish alternative training in sports regimens for players with varying refinement sprint timing. The research of SCH-AI has many advantages; accessing traditional games is regarded as the ideal platform for promoting peace, harmony, and cultural heritage preservation. Sports are also part of the steps to recognize and preserve the rights of people, and it is the protection of their cultural legacy. Cultural heritage gives users a sense of belonging and harmony within a community and a greater understanding of earlier generations and their history.

Engineered coxsackievirus B3 containing multiple organ-specific miRNA targets showed attenuated viral tropism and protective immunity.

Coxsackievirus B3 (CVB3) can cause viral myocarditis, pancreatitis, and aseptic meningitis. This study aimed to construct an engineered CVB3 harboring three different tissue-specific miRNA targets (CVB3-miR3*T) to decrease the virulence of CVB3 in muscles, pancreas, and brain. CVB3-miR3*T and CVB3-miR-CON (containing three sequences not found in the human genome) were engineered and replicated in HELA cells. A viral plaque assay was used to determine the titers in HELA cells and TE671 cells (high miRNA-206 expression), MIN-6 cells (high miRNA-29a-3p expression), and mouse astrocytes (high miRNA-124-3p expression). We found that engineered CVB3 showed attenuated replication and reduced cytotoxicity, the variability of each type of cell was also increased in the CVB3-miR3*T group. Male BALB/c mice were infected to determine the LD50 and examine heart, pancreas, and brain titers and injury. Viral replication of the engineered viruses was restricted in infected mouse heart, pancreas, and brain, and viral plaques were about 100 fold lower compared with the control group. Mice immunized using CVB3-miR3*T, UV-inactivated CVB3-WT, and CVB3-miR-CON were infected with 100 × LD50 of CVB3-WT to determine neutralization. CVB3-miRT*3-preimmunized mice exhibited complete protection and remained alive after lethal virus infection, while only 5/15 were alive in the UV-inactivated mice, and all 15 mice were dead in the PBS-immunized group. The results demonstrate that miR-206-, miRNA-29a-3p-, and miRNA-124-3p-mediated CVB3 detargeting from the pancreas, heart, and brain might be a highly effective strategy for viral vaccine development.

Invariant natural killer T cells minimally influence gut microbiota composition in mice.

Invariant Natural Killer T (iNKT) cells are unconventional T cells that respond to glycolipid antigens found in microbes in a CD1d-dependent manner. iNKT cells exert innate-like functions and produce copious amounts of cytokines, chemokines and cytotoxic molecules within only minutes of activation. As such, iNKT cells can fuel or dampen inflammation in a context-dependent manner. In addition, iNKT cells provide potent immunity against bacteria, viruses, parasites and fungi. Although microbiota-iNKT cell interactions are not well-characterized, mounting evidence suggests that microbiota colonization early in life impacts iNKT cell homeostasis and functions in disease. In this study, we showed that CD1d-/- and Vα14 Tg mice, which lack and have increased numbers of iNKT cells, respectively, had no significant alterations in gut microbiota composition compared to their littermate controls. Furthermore, specific iNKT cell activation by glycolipid antigens only resulted in a transient and minimal shift in microbiota composition when compared to the natural drift found in our colony. Our findings demonstrate that iNKT cells have little to no influence in regulating commensal bacteria at steady state.Abbreviations: iNKT: invariant Natural Killer T cell; αGC: α-galactosylceramide.

Cost-Sensitive Siamese Network for PCB Defect Classification.

After the production of printed circuit boards (PCB), PCB manufacturers need to remove defected boards by conducting rigorous testing, while manual inspection is time-consuming and laborious. Many PCB factories employ automatic optical inspection (AOI), but this pixel-based comparison method has a high false alarm rate, thus requiring intensive human inspection to determine whether alarms raised from it resemble true or pseudo defects. In this paper, we propose a new cost-sensitive deep learning model: cost-sensitive siamese network (CSS-Net) based on siamese network, transfer learning and threshold moving methods to distinguish between true and pseudo PCB defects as a cost-sensitive classification problem. We use optimization algorithms such as NSGA-II to determine the optimal cost-sensitive threshold. Results show that our model improves true defects prediction accuracy to 97.60%, and it maintains relatively high pseudo defect prediction accuracy, 61.24% in real-production scenario. Furthermore, our model also outperforms its state-of-the-art competitor models in other comprehensive cost-sensitive metrics, with an average of 33.32% shorter training time.