Single-cell analysis is a valuable tool for dissecting cellular heterogeneity in complex systems
. However, a comprehensive single-cell atlas has not been achieved for humans. Here we use single-cell ...mRNA sequencing to determine the cell-type composition of all major human organs and construct a scheme for the human cell landscape (HCL). We have uncovered a single-cell hierarchy for many tissues that have not been well characterized. We established a 'single-cell HCL analysis' pipeline that helps to define human cell identity. Finally, we performed a single-cell comparative analysis of landscapes from human and mouse to identify conserved genetic networks. We found that stem and progenitor cells exhibit strong transcriptomic stochasticity, whereas differentiated cells are more distinct. Our results provide a useful resource for the study of human biology.
The DNA-binding One Zinc Finger (Dof) genes are ubiquitous in many plant species and are especial transcription regulators that participate in plant growth, development and various procedures, ...including biotic and abiotic stress reactions. In this study, we identified 41 PtrDof members from Populus trichocarpa genomes and classified them into four groups. The conserved motifs and gene structures of some PtrDof genes belonging to the same subgroup were almost the same. The 41 PtrDof genes were dispersed on 18 of the 19 Populus chromosomes. Many key stress- or phytohormone-related cis-elements were discovered in the PtrDof gene promoter regions. Consequently, we undertook expression profiling of the PtrDof genes in leaves and roots in response to osmotic stress and abscisic acid. A total of seven genes (PtrDof14, 16, 25, 27, 28, 37 and 39) in the Populus Dof gene family were consistently upregulated at point in all time in the leaves and roots under osmotic and abscisic acid (ABA) stress. We observed that 12 PtrDof genes could be targeted by 15 miRNAs. Moreover, we mapped the cleavage site in PtrDof30 using the 5'RLM-RACE. The results showed that PtrDofs may have a role in resistance to abiotic stress in Populus trichocarpa.
Epigenetic landscapes can shape physiologic and disease phenotypes. We used integrative, high resolution multi-omics methods to delineate the methylome landscape and characterize the oncogenic ...drivers of esophageal squamous cell carcinoma (ESCC). We found 98% of CpGs are hypomethylated across the ESCC genome. Hypo-methylated regions are enriched in areas with heterochromatin binding markers (H3K9me3, H3K27me3), while hyper-methylated regions are enriched in polycomb repressive complex (EZH2/SUZ12) recognizing regions. Altered methylation in promoters, enhancers, and gene bodies, as well as in polycomb repressive complex occupancy and CTCF binding sites are associated with cancer-specific gene dysregulation. Epigenetic-mediated activation of non-canonical WNT/β-catenin/MMP signaling and a YY1/lncRNA ESCCAL-1/ribosomal protein network are uncovered and validated as potential novel ESCC driver alterations. This study advances our understanding of how epigenetic landscapes shape cancer pathogenesis and provides a resource for biomarker and target discovery.
NLRC3, a member of the NLR family, has been reported as a negative regulator of inflammatory signaling pathways in innate immune cells. However, the direct role of NLRC3 in modulation of CD4+ T-cell ...responses in infectious diseases has not been studied. In the present study, we showed that NLRC3 plays an intrinsic role by suppressing the CD4+ T cell phenotype in lung and spleen, including differentiation, activation, and proliferation. NLRC3 deficiency in CD4+ T cells enhanced the protective immune response against Mycobacterium tuberculosis infection. Finally, we demonstrated that NLRC3 deficiency promoted the activation, proliferation, and cytokine production of CD4+ T cells via negatively regulating the NF-κB and MEK-ERK signaling pathways. This study reveals a critical role of NLRC3 as a direct regulator of the adaptive immune response and its protective effects on immunity during M. tuberculosis infection. Our findings also suggested that NLRC3 serves as a potential target for therapeutic intervention against tuberculosis.
The mechanisms by which vitamins regulate immunity and their effect as an adjuvant treatment for tuberculosis have gradually become very important research topics. Studies have found that vitamin B5 ...(VB5) can promote epithelial cells to express inflammatory cytokines. We aimed to examine the proinflammatory and antibacterial effect of VB5 in macrophages infected with
(MTB) strain H37Rv and the therapeutic potential of VB5
with tuberculosis. We investigated the activation of inflammatory signal molecules (NF-κB, AKT, JNK, ERK, and p38), the expression of two primary inflammatory cytokines (tumor necrosis factor and interleukin-6) and the bacterial burdens in H37Rv-infected macrophages stimulated with VB5 to explore the effect of VB5 on the inflammatory and antibacterial responses of macrophages. We further treated the H37Rv-infected mice with VB5 to explore VB5's promotion of the clearance of H37Rv in the lungs and the effect of VB5 on regulating the percentage of inflammatory cells. Our data showed that VB5 enhanced the phagocytosis and inflammatory response in macrophages infected with H37Rv. Oral administration of VB5 decreased the number of colony-forming units of H37Rv in lungs of mice at 1, 2, and 4 weeks after infection. In addition, VB5 regulated the percentage of macrophages and promoted CD4
T cells to express interferon-γ and interleukin-17; however, it had no effect on the percentage of polymorphonuclear neutrophils, CD4
and CD8
T cells. In conclusion, VB5 significantly inhibits the growth of MTB by regulating innate immunity and adaptive immunity.
Educational informatization has become the only way for mankind to enter the information age, and the application of educational resource library is a key issue in the integration of information ...technology disciplines. Aiming at the shortcomings of existing college physical education management technology, this article is dedicated to developing a new online management platform for physical education. Firstly, the introduction of edge computing technology in the architecture design of college physical education system can fully improve the efficiency of the management system. Secondly, based on data cleaning, the BP neural network algorithm modified by particle swarm is used to conduct in-depth analysis of the data of the university sports teaching management system and obtain corresponding optimization measures. Finally, it is verified in actual tests that the system can quickly perform data search, entry, modification, deletion, and other operations, which can ensure the realization of the school sports department’s networked, scientific, standardized, and digitalized management of physical education resources.
ABSTRACT Introduction The continuous practice of martial arts can lead to significant changes in the functioning of respiratory organs in the long term. This habit can improve the body’s physical ...development, including the immune system. Objective To investigate the influence of martial arts classes on the physical fitness of college students who practice them. Methods 53 college students are evaluated. Influencing factors are martial arts dedication and training time. The experiment assesses cardiopulmonary function (cardiac function capacity, maximal oxygen consumption, blood pressure, heart rate, and other indexes). The secondary exercise stress tolerance test method was used to investigate cardiopulmonary exercise function in college students. Results 90% of the cardiopulmonary function assessment of the martial arts exercise group is excellent. The practitioners’ heart rate and maximum oxygen volume are significantly higher (P<0.05). Systolic and diastolic blood pressure between the groups did not show significant changes (< 120/80mmhg). Martial arts did not change systolic, diastolic blood pressure, or heart rate in the long term. Conclusion Martial arts education has a good influence on students’ physical fitness and significantly impacts students’ strength and vital capacity. Evidence Level II; Therapeutic Studies – Investigating the results.
RESUMEN Introducción La práctica continuada de artes marciales puede provocar a largo plazo cambios significativos en el funcionamiento de los órganos respiratorios. Este hábito puede mejorar el desarrollo físico del cuerpo, incluyendo el sistema inmunológico. Objetivo Investigar la influencia que las clases de artes marciales ejercen sobre la aptitud física de los estudiantes universitarios que las practican. Métodos Se evaluaron 53 estudiantes universitarios. Los factores que influyen son la dedicación a las artes marciales y el tiempo de entrenamiento. El experimento evalúa la función cardiopulmonar (capacidad de la función cardíaca, consumo máximo de oxígeno, presión arterial, frecuencia cardíaca entre otros índices). Se utilizó el método de prueba de tolerancia al esfuerzo secundaria para investigar la función de ejercicio cardiopulmonar en estudiantes universitarios. Resultados El 90% de la evaluación de la función cardiopulmonar del grupo de ejercicios de artes marciales es excelente. La frecuencia cardíaca y el volumen máximo de oxígeno de los practicantes es significativamente mayor (P<0,05). La presión arterial sistólica y diastólica entre los grupos no mostró cambios importantes (< 120/80mmhg). Las artes marciales no modificaron la presión arterial sistólica y diastólica ni la frecuencia cardíaca a largo plazo. Conclusión La educación en artes marciales tiene una buena influencia en la aptitud física de los alumnos, además de un impacto significativo en la fuerza y la capacidad vital de los mismos. Nivel de evidencia II; Estudios terapéuticos - Investigación de resultados.
RESUMO Introdução A prática contínua das artes marciais pode levar a mudanças significativas no funcionamento dos órgãos respiratórios à longo prazo. Este hábito pode melhorar o desenvolvimento físico corporal, incluindo o sistema imunológico. Objetivo Investigar a influência que as aulas de artes marciais provocam na aptidão física dos estudantes universitários que a praticam. Métodos 53 universitários são avaliados. Os fatores de influência são a dedicação às artes marciais e o tempo de treino. O experimento avalia a função cardiopulmonar (capacidade de função cardíaca, consumo máximo de oxigênio, pressão arterial, frequência cardíaca entre outros indexadores). Foi utilizado o método de prova de tolerância ao exercício de esforço secundário para investigar a função do exercício cardiopulmonar nos universitários. Resultados 90% da avaliação da função cardiopulmonar do grupo praticante de exercícios de artes marciais é excelente. A frequência cardíaca e o volume máximo de oxigênio dos praticantes são significativamente maiores (P<0,05). A pressão arterial sistólica e diastólica entre os grupos não apresentaram grandes alterações (< 120/80mmhg). As artes marciais não alteraram a pressão arterial sistólica, diastólica nem o ritmo cardíaco à longo prazo. Conclusão O ensino de artes marciais tem uma boa influência sobre a aptidão física dos estudantes além de um impacto significativo sobre a força e a capacidade vital dos estudantes. Nível de evidência II; Estudos Terapêuticos - Investigação de Resultados.
The genomic basis underlying the selection for environmental adaptation and yield-related traits in maize remains poorly understood. Here we carried out genome-wide profiling of the small RNA (sRNA) ...transcriptome (sRNAome) and transcriptome landscapes of a global maize diversity panel under dry and wet conditions and uncover dozens of environment-specific regulatory hotspots. Transgenic and molecular studies of Drought-Related Environment-specific Super eQTL Hotspot on chromosome 8 (DRESH8) and ZmMYBR38, a target of DRESH8-derived small interfering RNAs, revealed a transposable element-mediated inverted repeats (TE-IR)-derived sRNA- and gene-regulatory network that balances plant drought tolerance with yield-related traits. A genome-wide scan revealed that TE-IRs associate with drought response and yield-related traits that were positively selected and expanded during maize domestication. These results indicate that TE-IR-mediated posttranscriptional regulation is a key molecular mechanism underlying the tradeoff between crop environmental adaptation and yield-related traits, providing potential genomic targets for the breeding of crops with greater stress tolerance but uncompromised yield.
Serum cytokines correlate with tuberculosis (TB) progression and are predictors of TB recurrence in people living with HIV. We investigated whether serum cytokine biosignatures could diagnose TB ...among HIV-positive inpatients.
We recruited HIV-positive inpatients with symptoms of TB and measured serum levels of inflammation biomarkers including IL-2, IL-4, IL-6, IL-10, tumour necrosis factor-alpha (TNF-α) and interferon-gamma (IFN-γ). We then built and tested our TB prediction model.
236 HIV-positive inpatients were enrolled in the first cohort and all the inflammation biomarkers were significantly higher in participants with microbiologically confirmed TB than those without TB. A binary support vector machine (SVM) model was built, incorporating the data of four biomarkers (IL-6, IL-10, TNF-α and IFN-γ). Efficacy of the SVM model was assessed in training (n=189) and validation (n=47) sets with area under the curve (AUC) of 0.92 (95% CI 0.88 to 0.96) and 0.85 (95% CI 0.72 to 0.97), respectively. In an independent test set (n=110), the SVM model yielded an AUC of 0.85 (95% CI 0.76 to 0.94) with 78% (95% CI 68% to 87%) specificity and 85% (95% CI 66% to 96%) sensitivity. Moreover, the SVM model outperformed interferon-gamma release assay (IGRA) among advanced HIV-positive inpatients irrespective of CD4
T-cell counts, which may be an alternative approach for identifying
infection among HIV-positive inpatients with negative IGRA.
The four-cytokine biosignature model successfully identified TB among HIV-positive inpatients. This diagnostic model may be an alternative approach to diagnose TB in advanced HIV-positive inpatients with low CD4
T-cell counts.
, which primarily infects mononuclear phagocytes, remains the leading bacterial cause of enormous morbidity and mortality because of bacterial infections in humans throughout the world. The IL-1 ...family of cytokines is critical for host resistance to
As a newly discovered subgroup of the IL-1 family, although IL-36 cytokines have been proven to play roles in protection against
infection, the antibacterial mechanisms are poorly understood. In this study, we demonstrated that IL-36γ conferred to human monocyte-derived macrophages bacterial resistance through activation of autophagy as well as induction of WNT5A, a reported downstream effector of IL-1 involved in several inflammatory diseases. Further studies showed that WNT5A could enhance autophagy of monocyte-derived macrophages by inducing cyclooxygenase-2 (COX-2) expression and in turn decrease phosphorylation of AKT/mTOR via noncanonical WNT signaling. Consistently, the underlying molecular mechanisms of IL-36γ function are also mediated by the COX-2/AKT/mTOR signaling axis. Altogether, our findings reveal a novel activity for IL-36γ as an inducer of autophagy, which represents a critical inflammatory cytokine that control the outcome of
infection in human macrophages.
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