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.

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.

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.

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.

Relief of sports fatigue after marathon races by pnf stretching / Alívio da fadiga esportiva após corridas de maratona por alongamento pnf / Alivio de la fatiga deportiva tras carreras de maratón mediante estiramientos pnf

ABSTRACT Introduction: Marathon running requires stretching practices to relieve fatigue after exercise. The Proprioceptive Neuromuscular Facilitation (PNF) technique is an advanced stretching technique that allows segmenting of a specific muscle group for simultaneous stretching and strengthening. Objective: This paper explores the effect of PNF stretching exercise on relieving sports fatigue after marathon races. Methods: In this paper, 160 marathon runners were selected for the experiment, and randomly divided into experimental and control groups. The experimental group performed the PNF stretching exercise, while the control group remained with traditional stretching without any new intervention. Fatigue was assessed according to the heart rate, collected before, during, and after the experiment. Results: After nine weeks of PNF stretching training, the heart rate in the experimental group changed from 65.35 to 62.46 in the morning; during training, the group's heart rate changed from 180.79 to 173.04; after recovery, the first group's heart rate changed from 82.88 to 81.88. In the control group, the heart rate of the group also showed changes from 65.29 to 68.86 in the morning; during training, it changed from 180.7 to 175.49; and after recovery, from 86.23 to 88.4. Conclusion: PNF stretching exercise has a positive effect on relieving sports fatigue after marathon races. Level of evidence II; Therapeutic studies - investigation of treatment outcomes.

RESUMO Introdução: A corrida de maratona requer práticas de alongamento para aliviar a fadiga após o exercício. A técnica de Facilitação Neuromuscular Proprioceptiva (PNF) é uma técnica avançada de alongamento que permite segmentar um grupo muscular específico, para alongamento e fortalecimento simultâneos. Objetivo: Este artigo tenta explorar o efeito do exercício de alongamento PNF no alívio da fadiga esportiva após corridas de maratona. Métodos: Neste artigo, 160 corredores de maratona foram selecionados para o experimento, divididos aleatoriamente em grupos experimental e controle. O grupo experimental fez o exercício de alongamento PNF, enquanto o grupo de controle permaneceu com o alongamento tradicional, sem qualquer nova intervenção. A fadiga foi avaliada segundo a frequência cardíaca, coletada antes, durante e após o experimento. Resultados: Após nove semanas de treinamento de alongamento PNF, a frequência cardíaca no grupo experimental alterou-se de 65,35 para 62,46 pela manhã; durante o treinamento, a frequência cardíaca do grupo alterou-se de 180,79 para 173,04; após a recuperação, a frequência cardíaca do primeiro grupo alterou-se de 82,88 para 81,88. No grupo de controle, a frequência cardíaca do grupo também exibiu alterações de 65,29 para 68,86 pela manhã; Durante o treinamento, mudou de 180,7 para 175,49; e após a recuperação, de 86,23 para 88,4. Conclusão: O exercício de alongamento PNF tem um efeito positivo no alívio da fadiga esportiva após corridas de maratona. Nível de evidência II; Estudos terapêuticos - investigação dos resultados do tratamento.

RESUMEN Introducción: Las carreras de maratón requieren prácticas de estiramiento para aliviar la fatiga tras el ejercicio. La técnica de Facilitación Neuromuscular Propioceptiva (PNF) es una técnica avanzada de estiramiento que permite segmentar un grupo muscular específico, para estirar y fortalecer simultáneamente. Objetivo: Este trabajo pretende explorar el efecto del ejercicio de estiramiento PNF en el alivio de la fatiga deportiva tras carreras de maratón. Métodos: En este trabajo, se seleccionaron 160 corredores de maratón para el experimento, divididos aleatoriamente en grupos experimental y de control. El grupo experimental realizó el ejercicio de estiramiento PNF, mientras que el grupo de control permaneció con el estiramiento tradicional, sin ninguna nueva intervención. La fatiga se evaluó en función de la frecuencia cardiaca, recogida antes, durante y después del experimento. Resultados: Tras nueve semanas de entrenamiento de estiramientos PNF, la frecuencia cardiaca del grupo experimental pasó de 65,35 a 62,46 por la mañana; durante el entrenamiento, la frecuencia cardiaca del grupo pasó de 180,79 a 173,04; tras la recuperación, la frecuencia cardiaca del primer grupo pasó de 82,88 a 81,88. En el grupo de control, la frecuencia cardiaca del grupo también mostró cambios de 65,29 a 68,86 por la mañana; durante el entrenamiento, cambió de 180,7 a 175,49; y tras la recuperación, de 86,23 a 88,4. Conclusión: El ejercicio de estiramiento PNF tiene un efecto positivo en el alivio de la fatiga deportiva después de correr un maratón. Nivel de evidencia II; Estudios terapéuticos - investigación de los resultados del tratamiento.

Impacts of lower limb training in badminton / Impactos do treinamento de membros inferiores no badminton / Impactos del entrenamiento de miembros inferiores en el bádminton

ABSTRACT Introduction: Badminton is extremely popular among Chinese people, and the development of its training methods is constant. The study of improvement in the training of the lower limbs is the main focus to increase the physical fitness of its practitioners. Objective: Study the effects of a specific lower-limb training protocol on the physical fitness of badminton players. Methods: Twenty-four volunteers were selected from freshmen and sophomore badminton majors in a physical education college. The sample was randomly divided into control and experimental groups with no statistical differences. The control group continued to use the traditional fitness training method, while the experimental group reinforced their training with a lower limb strength protocol. The experiment lasted 6 weeks, consisting of one hour of training thrice a week. Indicators were collected before and after the experiment for statistical analysis. Results: The Illinois sensitivity index was optimized from 17.049 ± 0.9618 to 15.287 ± 0.8146 in the experimental group, with optimization of the blind step index from 4.607 ± 1.2072 to 10.631 ± 5. 3292.4. The 10m return index was optimized from 10.582 ± 0.6085 to 9.853 ± 0.4809, and the reaction action test index was optimized from 1.965 ± 0.1378 to 1.756 ± 0.1378 after the experiment. Conclusion: Increasing the proportion of lower limb training to traditional fitness training can improve athletes' fitness level and competitive level. Level of evidence II; Therapeutic studies - investigation of treatment outcomes.

RESUMO Introdução: O badminton é bastante popular entre os chineses, e o desenvolvimento dos seus métodos de treinamento é constante. O estudo de aprimoramento no treinamento dos membros inferiores é o principal foco para incrementar a aptidão física de seus praticantes. Objetivo: Estudar os efeitos de um protocolo de treinamento específico dos membros inferiores sobre a aptidão física em jogadores de badminton. Métodos: Foram selecionados 24 voluntários entre calouros e alunos do segundo ano de especialidade de badminton numa faculdade de educação física. A amostra foi aleatoriamente dividida em grupos controle e experimental, sem diferenças estatísticas entre os grupos. O grupo de controle continuou a utilizar o método tradicional de treinamento de aptidão física, enquanto o grupo experimental reforçou o treinamento com um protocolo de força para os membros inferiores. O experimento durou 6 semanas, consistindo em uma hora de treinamento, três vezes na semana. Os indicadores foram coletados antes e depois do experimento para análise estatística. Resultados: O índice de sensibilidade de Illinois foi otimizado de 17,049 ± 0,9618 para 15,287 ± 0,8146 no grupo experimental, com otimização do índice de passo cego de 4,607 ± 1,2072 para 10,631 ± 5. 3292,4. O índice de retorno de 10m foi otimizado de 10,582 ± 0,6085 para 9,853 ± 0,4809, o índice do teste de ação de reação foi otimizado de 1,965 ± 0,1378 para 1,756 ± 0,1378 após o experimento. Conclusão: Incrementar a proporção de treinamento dos membros inferiores ao treinamento de aptidão física tradicional pode melhorar o nível de aptidão física e o nível competitivo dos atletas. Nível de evidência II; Estudos terapêuticos - investigação dos resultados do tratamento.

RESUMEN Introducción: El bádminton es muy popular entre los chinos, y el desarrollo de sus métodos de entrenamiento es constante. El estudio de la mejora en el entrenamiento de los miembros inferiores es el principal objetivo para aumentar la forma física de sus practicantes. Objetivo: Estudiar los efectos de un protocolo de entrenamiento específico de los miembros inferiores sobre la forma física en jugadores de bádminton. Métodos: Se seleccionaron 24 voluntarios entre estudiantes de primer y segundo año de la especialidad de bádminton de una facultad de educación física. La muestra se dividió aleatoriamente en grupos de control y experimental, sin diferencias estadísticas entre los grupos. El grupo de control siguió utilizando el método tradicional de entrenamiento físico, mientras que el grupo experimental reforzó el entrenamiento con un protocolo de fuerza de las extremidades inferiores. El experimento duró 6 semanas y consistió en una hora de entrenamiento, tres veces por semana. Se recogieron indicadores antes y después del experimento para su análisis estadístico. Resultados: El índice de sensibilidad de Illinois se optimizó de 17,049 ± 0,9618 a 15,287 ± 0,8146 en el grupo experimental, con una optimización del índice de paso ciego de 4,607 ± 1,2072 a 10,631 ± 5. 3292,4. El índice de retorno de 10 m se optimizó de 10,582 ± 0,6085 a 9,853 ± 0,4809, el índice de prueba de acción de reacción se optimizó de 1,965 ± 0,1378 a 1,756 ± 0,1378 tras el experimento. Conclusión: Aumentar la proporción de entrenamiento de las extremidades inferiores con respecto al entrenamiento físico tradicional puede mejorar la forma física y el nivel competitivo de los deportistas. Nivel de evidencia II; Estudios terapéuticos - investigación de los resultados del tratamiento.

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.

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.

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.

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.

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.

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.

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.

Plasma miR-26a as a Diagnostic Biomarker Regulates Cytokine Expression in Systemic Juvenile Idiopathic Arthritis.

OBJECTIVE: We sought to identify specific microRNA (miRNA) for systemic juvenile idiopathic arthritis (sJIA) and to determine the involvement of these miRNA in regulating the expression of cytokines. METHODS: Microarray profiling was performed to identify differentially expressed miRNA in sJIA plasma. Levels of candidate miRNA and mRNA were assessed by real-time PCR, and cytokines were measured by ELISA. Dual-luciferase reporter assay was used to validate the direct interaction between miR-26a and interleukin 6 (IL-6). RESULTS: Forty-eight miRNA were differentially expressed in the plasma of patients with sJIA compared with healthy controls (HC). Five miRNA were selected for further validation. The expression level of miR-26a was exclusively elevated in the plasma of patients with sJIA as compared with 4 rheumatic diseases and 2 subtypes of JIA (oligoarticular and polyarticular). The levels of IL-6, IL-1ß, and tumor necrosis factor-α in the plasma of patients with sJIA were increased, and only IL-6 presented a positive correlation with miR-26a (r = 0.539, p < 0.0001). After stimulation with IL-6, miR-26a expression was upregulated in THP-1 cells, while the supernatant level of IL-6 was downregulated by transfection of miR-26a mimics. Consistently, direct target relationship between miR-26a and IL-6 was confirmed. CONCLUSION: This study demonstrates that miR-26a is expressed specifically and highly in sJIA plasma and suggests that miR-26a may regulate the levels of cytokines in sJIA. Our findings highlight miR-26a as a potential biomarker for the diagnosis as well as differential diagnosis of sJIA.

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.

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.

Coxsackievirus B3 induces autophagy in HeLa cells via the AMPK/MEK/ERK and Ras/Raf/MEK/ERK signaling pathways.

In a previous study, the number of autophagosomes increased after coxsackievirus B3 (CVB3) infection. However, the exact mechanism by which CVB3 regulates the number of autophagosomes is unclear. Earlier studies have found that infection with CVB3 activates extracellular signal-regulated kinase (ERK). ERK is essential for CVB3 replication and can increase the number of autophagosomes. In the current study, extracellular signal-regulated kinase 1/2 was activated in HeLa cells after CVB3 infection. The ERK kinase inhibitor, U0126, was then used to inhibit the activity of ERK. Treatment with U0126 led to a significant reduction in the number of autophagosomes indicating that the CVB3-induced autophagosome accumulation may have occurred via the ERK pathway. The relationship between CVB3 infection and ERK pathway activation was also investigated. The results showed that the RasGAP protein could be further cleaved, leading to the activation of the Ras/Raf/MEK (mitogen/extracellular signal-regulated kinase)/ERK pathway and that CVB3 infection could result in an increase in the concentration of calcium in the cytoplasm, resulting in mitochondrial damage, a decrease in the concentration of ATP and activation of the AMPK (AMP-activated protein kinase)/MEK/ERK pathway. In summary, CVB3 might directly or indirectly induce autophagy via AMPK/MEK/ERK and Ras/Raf/MEK/ERK signaling pathways in the host cells, representing a pivotal mechanism for CVB3 pathogenesis.