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Introduction: MicroRNAs (miRNAs) are small endogenous non-coding RNAs that play an important role in wood formation in plants. However, the significance of the link between miRNAs and their target transcripts in wood formation remains unclear in rubber tree (Hevea brasiliensis). Methods: In this study, we induced the formation of reaction wood by artificially bending rubber trees for 300 days and performed small RNA sequencing and transcriptome deep sequencing (RNA-seq) to describe the complement of miRNAs and their targets contributing to this process. Results and discussion: We identified 5, 11, and 2 differentially abundant miRNAs in normal wood (NW) compared to tension wood (TW), in NW relative to opposite wood (OW), and between TW and OW, respectively. We also identified 12 novel miRNAs and 39 potential miRNA-mRNA pairs with different accumulation patterns in NW, TW, and OW. We noticed that many miRNAs targeted transcription factor genes, which were enriched in KEGG pathways associated with phenylpropanoid biosynthesis, phenylalanine metabolism, and pyruvate metabolism. Thus, miRNA-TF-mRNA network involved in wood formation via tension wood model were constructed. We validated the differential accumulation of miRNAs and their targets by RT-qPCR analysis and overexpressed miRNA in Nicotiana benthamiana with its potential target gene. These results will provide a reference for a deep exploration of growth and development in rubber tree.

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Long non-coding RNA AK001796 was initially identified altered in lung cancer. Recent research showed it could participate in the prognosis of hepatocellular carcinoma (HCC). However, the general biological role of AK001796 and its underlying mechanisms in HCC remain unclear. Here we demonstrated that the expression level of AK001796 in HCC tissues and cell lines was up-regulated. Silencing AK001796 suppressed the proliferation ability of HCC cells. Through dual luciferase reporter assays and loss/gain of functions studies, we identified that AK001796 could bind to miR-150, a star microRNA, promoting HCC proliferation. Furthermore, it was reported that growth factor receptor binding protein 2-associated binder 1 (GAB1) is a target gene of miR-150. Owing to AK001796 being a decoy for miR-150 and binding the same putative sites of miR-150 as GAB1, we presented that inhibition of miR-150 in AK001796 silencing cells reversed the reduction in GAB1. Subsequently, our findings demonstrated that silencing AK001796 can impair phospho-ERK1/2 and phospho-AKT. In conclusion, our investigation revealed that AK001796 promoted proliferation by enhancing phospho-ERK1/2 and phospho-AKT through AK001796/miR-150/GAB1 axis in HCC. These results provided further evidence for the critical roles of AK001796 accumulating HCC and suggested that AK001796 might act as an HCC biomarker in clinical treatment.

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BACKGROUND: Data-driven development of medical biomarkers of bone requires a large amount of image data but physical measurements are generally too restricted in size and quality to perform a robust training. PURPOSE: This study aims to provide a reliable in silico method for the generation of realistic bone microstructure with defined microarchitectural properties. Synthetic bone samples may improve training of neural networks and serve for the development of new diagnostic parameters of bone architecture and mineralization. METHODS: One hundred-fifty cadaveric lumbar vertebrae from 48 different male human spines were scanned with a high resolution peripheral quantitative CT. After prepocessing the scans, we extracted 10,795 purely spongeous bone patches, each with a side length of 32 voxels (5 mm) and isotropic voxel size of 164 µm. We trained a volumetric generative adversarial network (GAN) in a progressive manner to create synthetic microstructural bone samples. We then added a style transfer technique to allow the generation of synthetic samples with defined microstructure and gestalt by simultaneously optimizing two entangled loss functions. Reliability testing was performed by comparing real and synthetic bone samples on 10 well-understood microstructural parameters. RESULTS: The method was able to create synthetic bone samples with visual and quantitative properties that effectively matched with the real samples. The GAN contained a well-formed latent space allowing to smoothly morph bone samples by their microstructural parameters, visual appearance or both. Optimum performance has been obtained for bone samples with voxel size 32 × 32 × 32, but also samples of size 64 × 64 × 64 could be synthesized. CONCLUSIONS: Our two-step-approach combines a parameter-agnostic GAN with a parameter-specific style transfer technique. It allows to generate an unlimited anonymous database of microstructural bone samples with sufficient realism to be used for the development of new data-driven methods of bone-biomarkers. Particularly, the style transfer technique can generate datasets of bone samples with specific conditions to simulate certain bone pathologies.

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ABSTRACT Introduction: The isometric weight training method combines the benefits of physical endurance and hypertrophy. This teaching method performs the isometric exercise with the appropriate body weight. Objective: Study the effects of isometric training with weights on soccer players' explosive strength of the lower limbs. Methods: Twenty soccer players were randomly selected and divided equally into experimental and control groups. The real training situation of the athletes was used. The experimental group adopted the isometrics teaching method with weight, while the control group used conventional muscle strength training. The lower limb strength of the two groups of athletes was compared before and after the experiment. Results: The extensor force growth rate in the experimental groups was significantly increased at medium, high and low speeds, while the peak torque did not show significant changes. The soccer players had their muscle strength improved. There was a significant difference between the two groups (P<0.05). Conclusion: Isometric weight training significantly improves mid and fast-extensor muscle strength in young soccer players. Level of evidence II; Therapeutic studies - investigation of treatment outcomes.

RESUMO Introdução: O método de ensino por isometria com peso combina os benefícios de resistência física e hipertrofia. Este método de ensino executa o exercício isométrico com o peso corporal adequado. Objetivo: Estudar os efeitos do treinamento isométrico com pesos sobre a força explosiva dos membros inferiores nos jogadores de futebol. Métodos: Selecionou-se 20 jogadores de futebol por amostragem aleatória, divididos igualmente em grupo experimental e controle. Utilizou-se a situação real de treino dos atletas. O grupo experimental adotou o método de ensino por isometria com peso enquanto o grupo de controle utilizou o treinamento convencional de força muscular. A força dos membros inferiores dos dois grupos de atletas foi comparada antes e após o experimento. Resultado: A taxa de crescimento da força extensora nos grupos experimentais foi significativamente aumentada em velocidades médias, altas e baixas, enquanto o torque de pico não apresentou alterações significativas. Os jogadores de futebol tiveram sua força muscular aprimorada. Houve uma diferença significativa entre os dois grupos (P<0,05). Conclusão: O treinamento isométrico com pesos melhora significativamente a força muscular extensora média e rápida nos jovens jogadores de futebol. Nível de evidência II; Estudos terapêuticos - investigação dos resultados do tratamento.

RESUMEN Introducción: El método de enseñanza por isometría con peso combina los beneficios de la resistencia física y la hipertrofia. Este método de enseñanza realiza el ejercicio isométrico con el peso corporal adecuado. Objetivo: Estudiar los efectos del entrenamiento isométrico con pesas sobre la fuerza explosiva de los miembros inferiores en jugadores de fútbol. Métodos: Se seleccionaron 20 jugadores de fútbol por muestreo aleatorio, divididos por igual en grupo experimental y grupo de control. Se utilizó la situación real de entrenamiento de los atletas. El grupo experimental adoptó el método de enseñanza por isometría con peso, mientras que el grupo de control utilizó el entrenamiento de fuerza muscular convencional. Se comparó la fuerza de las extremidades inferiores de los dos grupos de atletas antes y después del experimento. Resultados: La tasa de crecimiento de la fuerza extensora en los grupos experimentales aumentó significativamente a velocidades medias, altas y bajas, mientras que el par máximo no mostró cambios significativos. Los jugadores de fútbol mejoraron su fuerza muscular. Hubo una diferencia significativa entre los dos grupos (P<0,05). Conclusión: El entrenamiento isométrico con pesas mejora significativamente la fuerza de los músculos extensores medios y rápidos en jóvenes futbolistas. Nivel de evidencia II; Estudios terapéuticos - investigación de los resultados del tratamiento.

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Inflammatory processes play a pivotal role in the development and progression of depression. Since Follistatin-like protein 1 (FSTL1) has been identified as a novel inflammatory protein, a variety of studies suggest that targeting FSTL1 may be useful in the treatment of diseases in which inflammation plays a central role. In the study, we aimed to investigate the causal relationship between FSTL1 signaling and the development of depression. To explore the effect and mechanism of FSTL1 on chronic stress-induced depression, the chronic unpredictable mild stress (CUMS) paradigm was used. Animals subjected to CUMS for 4 weeks exhibited depressive-like symptoms, including decreased sucrose preference and obvious behavioral despair, concomitantly with increased FSTL1 level in the hippocampus. In contrast, mice with FSTL1 knockdown abolished CUMS induced depression-like and anxiety-like behaviors. Moreover, FSTL1 knockdown reversed CUMS induced synaptic plasticity deficits in the PP-DG pathway of the hippocampus and increased the expression of synaptic associated proteins in the hippocampus of CUMS exposed mice. Microglia activation induced by CUMS paradigm could be significantly inhibited by FSTL1 knockdown. Furthermore, Western blot revealed that FSTL1 knockdown considerably decreased the expression of indicated molecules TLR4/MyD88/NF-κB signaling pathway in CUMS exposed mice. In conclusion, our data implies that FSTL1 may modulate the microglial activation through TLR4/MyD88/NF-κB signaling, which affects depression-like behaviors and synaptic function deficits induced by CUMS in mice. These results suggested that the role of FSTL1 in mediating microglia-related mechanisms in depression may shed light on developing new therapeutic strategies to treat this prevalent disease.

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Based on detailed household survey of apple farmers in Shandong and Shaanxi, this article used a binary logistic regression model to examine the impact of asset specificity on farmers' intergenerational succession arrangements of apple orchard. The results showed that the farmers' intergenerational willingness of younger generation to succeed them is generally weak. The specificity of human capital, physical assets, land assets and geographic location significantly impacted on farmers' intergenerational succession of family-operated apple orchard. Especially, the production technology level of apple planting decision-makers, the value of orchard facilities and machinery owned by apple growers, orchard topography, orchard fertility, government support, and the length of village hardened roads have significantly positive impacts on farmers' willingness. The education achievement of apple planting decision-makers, orchard irrigation area, and the number of village apple disasters negatively impacted farmers' willingness. Therefore, technical training should be intensified to effectively increase the human capital of farmers, infrastructure construction should be strengthened to improve apple production conditions, and professional farmers' operations should be supported to develop moderate-scale operations.

Com base em uma pesquisa domiciliar detalhada de produtores de maçã em Shandong e Shaanxi, este artigo usou um modelo de regressão logística binária para examinar o impacto da especificidade dos ativos nos arranjos de sucessão intergeracional dos produtores de pomar de maçã. Os resultados mostram que a disposição intergeracional dos agricultores da geração mais jovem para sucedê-los é geralmente fraca. A especificidade do capital humano, ativos físicos, ativos de terra e localização geográfica impactaram significativamente na sucessão intergeracional dos agricultores de pomar de maçã administrado por famílias. Especialmente, o nível de tecnologia de produção dos tomadores de decisão de plantio de maçã, o valor das instalações de pomar e maquinários de propriedade dos produtores, topografia do pomar, fertilidade do pomar, apoio do governo e a extensão das estradas da aldeia têm impactos significativamente positivos na vontade dos agricultores. As conquistas educacionais dos tomadores de decisão de plantio de maçã, a área de irrigação do pomar e o número de desastres de maçã nas aldeias impactam negativamente a vontade dos agricultores. Portanto, o treinamento técnico deve ser intensificado para aumentar efetivamente o capital humano dos agricultores, a construção da infraestrutura deve ser reforçada para melhorar as condições de produção de maçã e as operações dos agricultores profissionais devem ser apoiadas para desenvolver operações em escala moderada.

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Given the importance of wood in many industrial applications, much research has focused on wood formation, especially lignin biosynthesis. However, the mechanisms governing the regulation of lignin biosynthesis in the rubber tree (Hevea brasiliensis) remain to be elucidated. Here, we gained insight into the mechanisms of rubber tree lignin biosynthesis using reaction wood (wood with abnormal tissue structure induced by gravity or artificial mechanical treatment) as an experimental model. We performed transcriptome analysis of rubber tree mature xylem from tension wood (TW), opposite wood (OW), and normal wood (NW) using RNA sequencing (RNA-seq). A total of 214, 1,280, and 32 differentially expressed genes (DEGs) were identified in TW vs. NW, OW vs. NW, and TW vs. OW, respectively. GO and KEGG enrichment analysis of DEGs from different comparison groups showed that zeatin biosynthesis, plant hormone signal transduction, phenylpropanoid biosynthesis, and plant-pathogen interaction pathways may play important roles in reaction wood formation. Sixteen transcripts involved in phenylpropanoid biosynthesis and 129 transcripts encoding transcription factors (TFs) were used to construct a TF-gene regulatory network for rubber tree lignin biosynthesis. Among them, MYB, C2H2, and NAC TFs could regulate all the DEGs involved in phenylpropanoid biosynthesis. Overall, this study identified candidate genes and TFs likely involved in phenylpropanoid biosynthesis and provides novel insights into the mechanisms regulating rubber tree lignin biosynthesis.

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N6-methyladenosine (m6A) is the most thoroughly studied type of internal RNA modification, as this epigenetic modification is the most abundant in eukaryotic RNAs to date. This modification occurs in various types of RNAs and plays significant roles in dominant RNA-related processes, such as translation, splicing, export and degradation. These processes are catalyzed by three types of prominent enzymes: writers, erasers and readers. Increasing evidence has shown that m6A modification is vital for the regulation of gene expression, carcinogenesis, tumor progression and other abnormal changes, and recent studies have shown that m6A is important in the development of hepatocellular carcinoma (HCC). Herein, we summarize the nature and regulatory mechanisms of m6A modification, including its role in the pathogenesis of HCC and related chronic liver diseases. We also highlight the clinical significance and future strategies involving RNA m6A modifications in HCC.

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PURPOSE: To evaluate the effects of controlled decompression and rapid decompression, explore the potential mechanism, provide the theoretical basis for the clinical application, and explore the new cell death method in intracranial hypertension. METHODS: Acute intracranial hypertension was triggered in rabbits by epidural balloon compression. New Zealand white rabbits were randomly put into the sham group, the controlled decompression group, and the rapid decompression group. Brain water content, etc., was used to evaluate early brain injury. Western blotting and double immunofluorescence staining were used to detect necroptosis and apoptosis. RESULTS: Brain edema, neurological dysfunction, and brain injury appeared after traumatic brain injury (TBI). Compared with rapid decompression, brain water content was significantly decreased, neurological scores were improved by controlled decompression treatment. Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining and Nissl staining showed neuron death decreased in the controlled decompression group. Compared with rapid decompression, it was also found that apoptosis-related protein caspase-3/ tumor necrosis factor (TNF)-a was reduced markedly in the brain cortex and serum, and the expression levels of necroptosis-related protein, receptor-interacting protein 1 (RIP1)/receptor-interacting protein 1 (RIP3) reduced significantly in the controlled decompression group. CONCLUSIONS: Controlled decompression can effectively reduce neuronal damage and cerebral edema after craniocerebral injury and, thus, protect the brain tissue by alleviating necroptosis and apoptosis.

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BACKGROUND: Cross talk of tumor­immune cells at the gene expression level has been an area of intense research. However, it is largely unknown at the alternative splicing level which has been found to play important roles in the tumor­immune microenvironment. RESULTS: Here, we re-exploited one transcriptomic dataset to gain insight into tumor­immune interactions from the point of AS level. Our results showed that the AS profiles of triple-negative breast cancer cells co-cultured with activated T cells were significantly changed but not Estrogen receptor positive cells. We further suggested that the alteration in AS profiles in triple-negative breast cancer cells was largely caused by activated T cells rather than paracrine factors from activated T cells. Biological pathway analyses showed that translation initiation and tRNA aminoacylation pathways were most disturbed with T cell treatment. We also established an approach largely based on the AS factor­AS events associations and identified LSM7, an alternative splicing factor, may be responsible for the major altered events. CONCLUSIONS: Our study reveals the notable differences of response to T cells among breast cancer types which may facilitate the development or improvement of tumor immunotherapy.

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