Isolation, structural characterization and immunomodulatory activity on RAW264.7 cells of a novel exopolysaccharide of Dictyophora rubrovalvata.

Fungal polysaccharides have been explored by many for both structural studies and biological activities, but few studies have been done on the extracellular polysaccharides of Dictyophora rubrovalvata, so a new exopolysaccharide was isolated from Dictyophora rubrovalvata and its structure and its immunological activity were investigated. The crude exopolysaccharide (EPS) was purified by DEAE52 cellulose and Sephadex G-200 to obtain a new acidic polysaccharide (DR-EPS). DR-EPS (2.66 × 103 kDa) was consisted mainly of mannose, glucose, galactose and glucuronic acid with a molar ratio of 1: 0.86: 0.20: 0.01. In addition, DR-EPS increased the phagocytic activity of RAW264.7 cells up to 2.67 times of the blank control group. DR-EPS improved intracellular nucleic acid and glycogen metabolism as observed by AO and PAS staining. DR-EPS(40 µg/mL) promoted NO production up to 30.66 µmol, enhanced acid phosphatase (ACP) and superoxide dismutase (SOD) activities, with activity maxima of 660 U/gprot and 96.27 U/mgprot, respectively, and DR-EPS (160 µg / mL) significantly increased the lysozyme content as 2.73 times of the control group. The good immunological activity of extracellular polysaccharides of Dictyophora rubrovalvata provides directions for the use of fermentation broths.

Tumorigenesis of basal muscle invasive bladder cancer was mediated by PTEN protein degradation resulting from SNHG1 upregulation.

BACKGROUND: Phosphatase and tensin homolog deleted on chromosome ten (PTEN) serves as a powerful tumor suppressor, and has been found to be downregulated in human bladder cancer (BC) tissues. Despite this observation, the mechanisms contributing to PTEN's downregulation have remained elusive. METHODS: We established targeted genes' knockdown or overexpressed cell lines to explore the mechanism how it drove the malignant transformation of urothelial cells or promoted anchorageindependent growth of human basal muscle invasive BC (BMIBC) cells. The mice model was used to validate the conclusion in vivo. The important findings were also extended to human studies. RESULTS: In this study, we discovered that mice exposed to N-butyl-N-(4-hydroxybu-tyl)nitrosamine (BBN), a specific bladder chemical carcinogen, exhibited primary BMIBC accompanied by a pronounced reduction in PTEN protein expression in vivo. Utilizing a lncRNA deep sequencing high-throughput platform, along with gain- and loss-of-function analyses, we identified small nucleolar RNA host gene 1 (SNHG1) as a critical lncRNA that might drive the formation of primary BMIBCs in BBN-treated mice. Cell culture results further demonstrated that BBN exposure significantly induced SNHG1 in normal human bladder urothelial cell UROtsa. Notably, the ectopic expression of SNHG1 alone was sufficient to induce malignant transformation in human urothelial cells, while SNHG1 knockdown effectively inhibited anchorage-independent growth of human BMIBCs. Our detailed investigation revealed that SNHG1 overexpression led to PTEN protein degradation through its direct interaction with HUR. This interaction reduced HUR binding to ubiquitin-specific peptidase 8 (USP8) mRNA, causing degradation of USP8 mRNA and a subsequent decrease in USP8 protein expression. The downregulation of USP8, in turn, increased PTEN polyubiquitination and degradation, culminating in cell malignant transformation and BMIBC anchorageindependent growth. In vivo studies confirmed the downregulation of PTEN and USP8, as well as their positive correlations in both BBN-treated mouse bladder urothelium and tumor tissues of bladder cancer in nude mice. CONCLUSIONS: Our findings, for the first time, demonstrate that overexpressed SNHG1 competes with USP8 for binding to HUR. This competition attenuates USP8 mRNA stability and protein expression, leading to PTEN protein degradation, consequently, this process drives urothelial cell malignant transformation and fosters BMIBC growth and primary BMIBC formation.

Optimizing cancer therapy for individuals based on tumor-immune-drug system interaction.

BACKGROUND AND AIM: Chemotherapy is a crucial component of cancer therapy, albeit with significant side effects. Chemotherapy either damages or inhibits the immune system; therefore, its efficacy varies according to the patient's immune state. Currently, there is no efficient model that incorporates tumor-immune-drug (TID) interactions to guide clinical medication strategies. In this study, we compared five different types of existing TID models with the aim to integrate them into a single, comprehensive model; our goal was to accurately reflect the reality of TID interactions to guide personalized cancer therapy. METHODS: We studied four different drug treatment profiles: direct function, normal distribution function, sine function, and trapezoid function. We developed a platform capable of plotting all combinations of parameter sets and their corresponding treatment efficiency scores. Subsequently, we generated 10,000 random parameter combinations for an individual case and plotted two polygon graphs using a seismic colormap to depict efficacy of treatment. Then, we developed a platform providing treatment suggestions for all stages of tumors and varying levels of self-immunity. We created polygons demonstrating successful treatments according to parameters related to tumor and immune status. RESULTS: The trapezoid drug treatment function achieved the best inhibitory effect on the tumor cell density. The treatment can be optimized with a high score indicating that the drug delivery interval had exceeded a specific value. More efficient parameter combinations existed when the immunity was strong compared to when it was weak, thus indicating that increasing the patient's self-immunity can make treatment much more effective. CONCLUSIONS: In summary, we created a comprehensive model that can provide quantitative recommendations for a gentle, yet efficient, treatment customized according to the individual's tumor and immune system characteristics.

MW-MADDPG: a meta-learning based decision-making method for collaborative UAV swarm.

Unmanned Aerial Vehicles (UAVs) have gained popularity due to their low lifecycle cost and minimal human risk, resulting in their widespread use in recent years. In the UAV swarm cooperative decision domain, multi-agent deep reinforcement learning has significant potential. However, current approaches are challenged by the multivariate mission environment and mission time constraints. In light of this, the present study proposes a meta-learning based multi-agent deep reinforcement learning approach that provides a viable solution to this problem. This paper presents an improved MAML-based multi-agent deep deterministic policy gradient (MADDPG) algorithm that achieves an unbiased initialization network by automatically assigning weights to meta-learning trajectories. In addition, a Reward-TD prioritized experience replay technique is introduced, which takes into account immediate reward and TD-error to improve the resilience and sample utilization of the algorithm. Experiment results show that the proposed approach effectively accomplishes the task in the new scenario, with significantly improved task success rate, average reward, and robustness compared to existing methods.

ATG7 upregulation contributes to malignant transformation of human bronchial epithelial cells by B[a]PDE via DNMT3B protein degradation and miR-494 promoter methylation.

Lung cancer primarily arises from exposure to various environmental factors, particularly airborne pollutants. Among the various lung carcinogens, benzo(a)pyrene and its metabolite B[a]PDE are the strongest ones that actively contribute to lung cancer development. ATG7 is an E1-like activating enzyme and contributes to activating autophagic responses in mammal cells. However, the potential alterations of ATG7 and its role in B[a]PDE-caused lung carcinogenesis remain unknown. Here, we found that B[a]PDE exposure promoted ATG7 expression in mouse lung tissues, while B[a]PDE exposure resulted in ATG7 induction in human normal bronchial epithelial cells. Our studies also demonstrated a significant correlation between high ATG7 expression levels and poor overall survival in lung cancer patients. ATG7 knockdown significantly repressed Beas-2B cell transformation upon B[a]PDE exposure, and such promotive effect of ATG7 on cell transformation mediated the p27 translation inhibition. Further studies revealed that miR-373 inhibition was required to stabilize ATG7 mRNA, therefore increasing ATG7 expression following B[a]PDE exposure, while ATG7 induction led to the autophagic degradation of the DNA methyltransferase 3 Beta (DNMT3B) protein, in turn promoted miR-494 transcription via its promoter region methylation status suppression. We also found that the miR-494 upregulation inhibited p27 protein translation and promoted bronchial epithelial cell transformation via its directly targeting p27 mRNA 3'-UTR region. Current studies, to the best of our knowledge, are for the first time to identify that ATG7 induction and its mediated autophagy is critical for B[a]PDE-induced transformation of human normal epithelial cells.

Trichoderma asperellum as a novel source to prepare chitooligosaccharides by enzymatic hydrolysis and its antimicrobial activity.

Chitooligosaccharides (COS), an important biological functional component, are mainly extracted from marine products, but its raw materials are currently facing challenges such as marine resources pollution and demineralization. This study aimed to explore Trichoderma asperellum as a novel source to prepare COS. The COS were prepared by the enzymatic degradation of chitosan from T. asperellum, and single factor experiment and orthogonal designs were used to optimize the enzymatic conditions for the preparation of COS. The composition of COS was performed by thin-layer chromatography, high-performance liquid chromatography, and matrix-assisted laser desorption ionization time-of-flight mass spectrometry. The results showed that the degree of deacetylation of T. asperellum chitosan was 87.59%, and its enzymatic hydrolysis yield was 89.37 % under optimized extraction conditions. Moreover, the composition of COS in T. asperellum included chitotriose, chitopentaose, and chitohexaose. Compared with shrimp shells, COS prepared from T. asperellum showed stronger antibacterial properties against Escherichia coli, Staphylococcus aureus, Bacillus subtilis, and Salmonella bacilli.

Effects of vibration training on the physical fitness of short-distance swimmers / Efeitos do treinamento de vibração sobre a aptidão física dos nadadores de curta distância / Efectos del entrenamiento con vibración en la aptitud física de los nadadores de corta distancia

ABSTRACT Introduction Vibration training is a widespread exercise. Existing experimental results show that using vibration strength exercises under the same loading conditions can improve the muscular strength of swimmers' lower limbs. Objective This paper especially studies the effect of vibration exercise on the physical quality of swimmers under various conditions. Methods The athletes were randomly divided into two groups: the experimental group and the control group. The experimental group used a vibrometer to exercise the lower limb muscles. The control group engaged only in routine training. After eight weeks of practice, the runners tested in the 100m, 150m, 200m, and 400m. The present article also explores the relationship between swimmers of different ages. Results Compared to the control group, there was a significant difference in maximum hip extensor volume between the experimental and control groups. There was also a significant difference between the two groups (P<0.05). The most significant increase in maximal exercise capacity between the two groups was in the ankle. The change in maximum load between the two groups was also significant (P<0.01). Conclusion The vibration training method can improve the swimmer's knee flexor group. Swimmers can improve their body coordination by performing vibration exercises. Level of evidence II; Therapeutic studies - investigation of treatment outcomes.

RESUMO Introdução O treinamento de vibração é um exercício amplamente difundido. Os resultados experimentais existentes mostram que o uso de exercícios de força vibratória sob as mesmas condições de carga pode melhorar a força muscular dos membros inferiores dos nadadores. Objetivo Este trabalho estuda especialmente o efeito do exercício de vibração sobre a qualidade física dos nadadores sob variadas condições. Métodos Os atletas foram divididos aleatoriamente em dois grupos: grupo experimental e grupo de controle. O grupo experimental utilizou um vibrômetro para exercitar os músculos dos membros inferiores. O grupo de controle ocupou-se apenas com o treinamento rotineiro. Após oito semanas de prática, os corredores testaram nos 100m, 150m, 200m e 400m. O presente artigo também explora a relação entre os nadadores de diferentes idades. Resultados Em comparação com o grupo controle, houve uma diferença significativa no volume máximo do extensor do quadril entre os grupos experimental e controle. Houve também uma diferença significativa entre os dois grupos (P<0,05). O aumento mais significativo na capacidade máxima de exercício entre os dois grupos foi no tornozelo. A alteração de carga máxima entre os dois grupos também foi significativa (P<0,01). Conclusão O método de treino por vibração pode melhorar o grupo de flexores do joelho do nadador. Os nadadores podem melhorar a coordenação corporal ao realizar exercícios vibracionais. Nível de evidência II; Estudos terapêuticos - investigação dos resultados do tratamento.

RESUMEN Introducción El entrenamiento con vibración es un ejercicio muy extendido. Los resultados experimentales existentes muestran que el uso de ejercicios de fuerza por vibración en las mismas condiciones de carga puede mejorar la fuerza muscular de los miembros inferiores de los nadadores. Objetivo Este trabajo estudia especialmente el efecto del ejercicio de vibración sobre la calidad física de los nadadores en condiciones variadas. Métodos Los atletas fueron divididos aleatoriamente en dos grupos: grupo experimental y grupo de control. El grupo experimental utilizó un vibrador para ejercitar los músculos de las extremidades inferiores. El grupo de control sólo se ocupó de la formación rutinaria. Después de ocho semanas de práctica, los corredores hicieron pruebas en los 100, 150, 200 y 400 metros. Este documento también explora la relación entre nadadores de diferentes edades. Resultados En comparación con el grupo de control, hubo una diferencia significativa en el volumen máximo de los extensores de la cadera entre los grupos experimental y de control. También hubo una diferencia significativa entre los dos grupos (P<0,05). El aumento más significativo de la capacidad máxima de ejercicio entre los dos grupos se produjo en el tobillo. El cambio en la carga máxima entre los dos grupos también fue significativo (P<0,01). Conclusión El método de entrenamiento con vibración puede mejorar el grupo de flexores de la rodilla del nadador. Los nadadores pueden mejorar la coordinación corporal realizando ejercicios de vibración. Nivel de evidencia II; Estudios terapéuticos - investigación de los resultados del tratamiento.

Changes in vo2max caused by aerobic exercise in swimmers / Alterações de vo2max ocasionadas pelo exercício aeróbico em nadadores / Cambios en el vo2max causados por el ejercicio aeróbico en nadadores

ABSTRACT Introduction The maximal oxygen consumption rate (VO2max) can directly reflect the body's aerobic metabolism and oxygen delivery system. This is a measure of aerobic capacity used to monitor swimmers' levels and their strength and speed performance. Objective Verify the changes in VO2max when incorporating aerobic exercise training into swimmers' regular training. Methods 12 volunteer swimmers were divided into two categories: strength training group and regular training group. Both groups performed a fitness test on the 200-meter track before starting the training. VO2 maximal was measured and worked out statistically to verify the results of this competition. The effects of aerobic exercise on the strength and competitive status of the athletes were investigated according to an updated literature review. Results There was a significant change in the maximal oxygen uptake of the athletes after the experimental protocol. The athletes in the strength training group increased their VO2 max compared to the regular training group. The results showed a significant difference in the VO2max index before and after strength training (P<0.05). This suggests that strength training has a significant effect on maximal oxygen consumption. Conclusion Strength training interventions significantly affect athletes' maximal oxygen consumption intensity and exercise capacity. The aerobic exercise intervention showed evidence of improving the competitive level of athletes. Level of evidence II; Therapeutic studies -investigation of treatment outcomes.

RESUMO Introdução A taxa máxima de consumo de oxigênio (VO2max) pode refletir diretamente o metabolismo aeróbico corporal e o sistema de fornecimento de oxigênio. Esta é uma medida da capacidade aeróbica empregada para monitorar o nível do nadador, e seu desempenho em força e velocidade. Objetivo Verificar as alterações de VO2max ao incorporar o treinamento com exercícios aeróbicos no treino padrão dos nadadores. Métodos 12 nadadores voluntários foram divididos em duas categorias: grupo de treinamento de força e grupo de treinamento regular. Ambos os grupos realizaram um teste de aptidão física na pista de 200 metros antes de iniciar o treinamento. O VO2 máximo foi mensurado e trabalhado estatisticamente para verificar os resultados desta competição. Os efeitos do exercício aeróbico sobre a força e o status competitivo dos atletas foi investigado segundo uma revisão bibliográfica atualizada. Resultados Houve uma mudança significativa na ingestão máxima de oxigênio dos atletas após o protocolo experimental. Os atletas do grupo de treinamento de força aumentaram seu VO2 máximo quando comparados ao grupo de treinamento regular. Os resultados mostraram uma diferença significativa no índice VO2max antes e depois do treinamento de força (P<0,05). Isto sugere que o treinamento de força tem um efeito significativo no consumo máximo de oxigênio. Conclusão As intervenções de treinamento de força afetam significativamente a intensidade máxima de consumo de oxigênio e a capacidade de exercício dos atletas. A intervenção do exercício aeróbico demonstrou evidencias em melhorar o nível competitivo dos atletas. Nível de evidência II; Estudos terapêuticos - investigação dos resultados do tratamento.

RESUMEN Introducción La tasa máxima de consumo de oxígeno (VO2máx) puede reflejar directamente el metabolismo aeróbico del cuerpo y el sistema de suministro de oxígeno. Se trata de una medida de la capacidad aeróbica que sirve para controlar el nivel del nadador y su rendimiento en fuerza y velocidad. Objetivo Verificar los cambios en el VO2máx al incorporar el entrenamiento de ejercicio aeróbico en el entrenamiento habitual de los nadadores. Métodos 12 nadadores voluntarios fueron divididos en dos categorías: grupo de entrenamiento de fuerza y grupo de entrenamiento regular. Ambos grupos realizaron una prueba de aptitud física en 200 metros de pista antes de comenzar el entrenamiento. Se midió el VO2 máximo y se trabajó estadísticamente para verificar los resultados de esta competición. Se investigaron los efectos del ejercicio aeróbico en la fuerza y el estado competitivo de los atletas según una revisión bibliográfica actualizada. Resultados Hubo un cambio significativo en el consumo máximo de oxígeno de los atletas después del protocolo experimental. Los atletas del grupo de entrenamiento de fuerza aumentaron su VO2 máximo en comparación con el grupo de entrenamiento regular. Los resultados mostraron una diferencia significativa en el índice VO2max antes y después del entrenamiento de fuerza (P<0,05). Esto sugiere que el entrenamiento de fuerza tiene un efecto significativo en el consumo máximo de oxígeno. Conclusión Las intervenciones de entrenamiento de fuerza afectan significativamente a la intensidad del consumo máximo de oxígeno y a la capacidad de ejercicio de los atletas. La intervención de ejercicio aeróbico mostró evidencia de mejorar el nivel competitivo de los atletas. Nivel de evidencia II; Estudios terapéuticos - investigación de los resultados del tratamiento.

NF-κB1 p50 stabilizes HIF-1α protein through suppression of ATG7-dependent autophagy.

The function and underlying mechanisms of p50 in the regulation of protein expression is much less studied because of its lacking of transactivation domain. In this study, we discovered a novel function of p50 in its stabilization of hypoxia-inducible factor 1α (HIF-1α) protein under the condition of cells exposed to arsenic exposure. In p50-deficient (p50-/-) cells, the HIF-1α protein expression was impaired upon arsenic exposure, and such defect could be rescued by reconstitutional expression of p50. Mechanistic study revealed that the inhibition of autophagy-related gene 7 (ATG7)-dependent autophagy was in charge of p50-mediated HIF-1α protein stabilization following arsenic exposure. Moreover, p50 deletion promoted nucleolin (NCL) protein translation to enhance ATG7 mRNA transcription via directly binding transcription factor Sp1 mRNA and increase its stability. We further discovered that p50-mediated miR-494 upregulation gave rise to the inhibition of p50-mediated NCL translation by interacting with its 3'-UTR. These novel findings provide a great insight into the understanding of biomedical significance of p50 protein in arsenite-associated disease development and therapy.

Analysis of Electromagnetic Characteristics of Copper-Steel Composite Quadrupole Rail.

The ablation and wear of the four-rail electromagnetic launcher during the working process will aggravate the damage of the armature and rail, and greatly affect the service life of the launcher. To effectively alleviate rail damage, this paper applies the copper-steel composite rail to the four-rail electromagnetic launcher and proposes a new four-rail electromagnetic launcher. Based on the quadrupole magnetic field theory, the physical model of the new four-rail electromagnetic launcher is established, and the electromagnetic characteristics of the ordinary and new launchers are compared and analyzed using the finite element method. On this basis, the influence of composite layer parameters on the electromagnetic characteristics of copper-steel composite quadrupole rail is explored. The study found that the new four-rail electromagnetic launcher can provide a better launch magnetic field environment for smart loads, and the current distribution of the armature and the rail contact surface is more uniform, which can effectively improve the contact condition between the armature and the rail. The composite layer parameters of copper-based composite rail will have a certain impact on electromagnetic characteristics, and copper-steel composite rail of appropriate proportions can be selected according to different needs. The model proposed in this paper has a certain degree of scientificity and rationality.

Induction of RAC1 protein translation and MKK7/JNK-dependent autophagy through dicer/miR-145/SOX2/miR-365a axis contributes to isorhapontigenin (ISO) inhibition of human bladder cancer invasion.

Although our previous studies have identified that isorhapontigenin (ISO) is able to initiate autophagy in human bladder cancer (BC) cells by activating JNK/C-Jun/SESN2 axis and possesses an inhibitory effect on BC cell growth, association of autophagy directly with inhibition of BC invasion has never been explored. Also, upstream cascade responsible for ISO activating JNK remains unknown. Thus, we explored both important questions in the current study and discovered that ISO treatment initiated RAC1 protein translation, and its downstream kinase MKK7/JNK phosphorylation/activation, and in turn promoted autophagic responses in human BC cells. Inhibition of autophagy abolished ISO inhibition of BC invasion, revealing that autophagy inhibition was crucial for ISO inhibition of BC invasion. Consistently, knockout of RAC1 also attenuated induction of autophagy and inhibition of BC invasion by ISO treatment. Mechanistic studies showed that upregulation of RAC1 translation was due to ISO inhibition of miR-365a transcription, which reduced miR-365a binding to the 3'-UTR of RAC1 mRNA. Further study indicated that inhibition of miR-365a transcription was caused by downregulation of its transcription factor SOX2, while ISO-promoted Dicer protein translation increased miR-145 maturation, and consequently downregulating SOX2 expression. These findings not only provide a novel insight into the understanding association of autophagy induction with BC invasion inhibition by ISO, but also identify an upstream regulatory cascade, Dicer/miR145/SOX2/miR365a/RAC1, leading to MKK7/JNKs activation and autophagy induction.

Critical Role of Lkb1 in the Maintenance of Alveolar Macrophage Self-Renewal and Immune Homeostasis.

Alveolar macrophages (AMs) are pivotal for maintaining lung immune homeostasis. We demonstrated that deletion of liver kinase b1 (Lkb1) in CD11c+ cells led to greatly reduced AM abundance in the lung due to the impaired self-renewal of AMs but not the impeded pre-AM differentiation. Mice with Lkb1-deficient AMs exhibited deteriorated diseases during airway Staphylococcus aureus (S. aureus) infection and allergic inflammation, with excessive accumulation of neutrophils and more severe lung pathology. Drug-mediated AM depletion experiments in wild type mice indicated a cause for AM reduction in aggravated diseases in Lkb1 conditional knockout mice. Transcriptomic sequencing also revealed that Lkb1 inhibited proinflammatory pathways, including IL-17 signaling and neutrophil migration, which might also contribute to the protective function of Lkb1 in AMs. We thus identified Lkb1 as a pivotal regulator that maintains the self-renewal and immune function of AMs.

Metabolite reanalysis revealed potential biomarkers for COVID-19: a potential link with immune response.

Aim: To understand the pathological progress of COVID-19 and to explore the potential biomarkers. Background: The COVID-19 pandemic is ongoing. There is metabolomics research about COVID-19 indicating the rich information of metabolomics is worthy of further data mining. Methods: We applied bioinformatics technology to reanalyze the published metabolomics data of COVID-19. Results: Benzoate, ß-alanine and 4-chlorobenzoic acid were first reported to be used as potential biomarkers to distinguish COVID-19 patients from healthy individuals; taurochenodeoxycholic acid 3-sulfate, glucuronate and N,N,N-trimethyl-alanylproline betaine TMAP are the top classifiers in the receiver operating characteristic curve of COVID-severe and COVID-nonsevere patients. Conclusion: These unique metabolites suggest an underlying immunoregulatory treatment strategy for COVID-19.

Identification of the subtypes of gastric cancer based on DNA methylation and the prediction of prognosis.

BACKGROUND: Gastric cancer (GC) is a digestive system cancer with a high mortality rate globally. Previous experiences and studies have provided clinicians with ample evidence to diagnose and treat patients with reasonable therapeutic options. However, there remains a need for sensitive biomarkers that can provide clues for early diagnosis and prognosis assessment. RESULTS: We found 610 independent prognosis-related 5'-cytosine-phosphate-guanine-3' (CpG) sites (P < 0.05) among 21,121 sites in the training samples. We divided the GC samples into seven clusters based on the selected 610 sites. Cluster 6 had relatively higher methylation levels and high survival rates than the other six clusters. A prognostic risk model was constructed using the significantly altered CpG sites in cluster 6 (P < 0.05). This model could distinguish high-risk GC patients from low-risk groups efficiently with the area under the receiver operating characteristic curve of 0.92. Risk assessment showed that the high-risk patients had poorer prognosis than the low-risk patients. The methylation levels of the selected sites in the established model decreased as the risk scores increased. This model had been validated in testing group and its effectiveness was confirmed. Corresponding genes of the independent prognosis-associated CpGs were identified, they were enriched in several pathways such as pathways in cancer and gastric cancer. Among all of the genes, the transcript level of transforming growth factor ß2 (TGFß2) was changed in different tumor stages, T categories, grades, and patients' survival states, and up-regulated in patients with GC compared with the normal. It was included in the pathways as pathways in cancer, hepatocellular carcinoma or gastric cancer. The methylation site located on the promoter of TGFß2 was cg11976166. CONCLUSIONS: This is the first study to separate GC into different molecular subtypes based on the CpG sites using a large number of samples. We constructed an effective prognosis risk model that can identify high-risk GC patients. The key CpGs sites or their corresponding genes such as TGFß2 identified in this research can provide new clues that will enable gastroenterologists to make diagnosis or personalized prognosis assessments and better understand this disease.

Mechanical analysis of the structure of longwall mining hydraulic support.

Existing studies of the structural strength of longwall mining hydraulic support are mainly focused on the force acting on individual supports instead of the general mechanical characteristics of the support group in a fully mechanized coal seam working face. This study combines theoretical analyses and experiments to investigate the mechanical characteristics of a longwall mining hydraulic support group and the stiffness of key support components under different working conditions. The theory of a beam on an elastic foundation was applied to construct a mechanical model for the hydraulic support group. The location and the size of loads on the top beam were determined. Field tests yielded data on the deflection of the roof and loading on the support group along the working face, where the stiffness of end supports varies. The transverse load distribution of the top beam and the offset loading coefficient at different locations along the working-face direction were obtained. A three-dimensional model was constructed for the support group while assembling virtual hydraulic supports using modern virtual modeling theories and methods. Finite element analysis was used to analyze the strength of the hydraulic support. The weakest areas of key components were found to be pinholes connecting the column cylinder to the base and roof of the mine. These results can be applied to achieve secure and stable operations of hydraulic supports in the working face of a thin coal seam, thereby improving the safety and production efficiency of mining operations.

Increased expression of YTHDF1 and HNRNPA2B1 as potent biomarkers for melanoma: a systematic analysis.

BACKGROUND: The incidence and mortality of melanoma is increasing around the world. To deeply explain the mechanism insight into it, we conducted a systematic analysis to examine the levels of regulatory genes of the common RNA epigenetic modification-N6-methyladenosine (m6A) in patients with melanoma compared by the healthy. METHODS: We analyzed the expression of m6A Eraser, Writer, and Reader genes based on publicly available datasets on Oncomine and validated the results with a gene expression omnibus dataset. Hub genes were identified with Cytohubba and the frequency of copy number alterations was analyzed with the cBioPortal tool. RESULTS: The results revealed the up-regulation of YTHDF1 and HNRNPA2B1 in melanoma. Combining the two genes improved the efficacy in diagnosing melanoma by about 10% compared to each gene alone. Hub genes identified with four analysis methods were compared and the overlapping genes were selected. These genes were enriched in several gene ontology terms. Genes related to p53-signaling consisted of CDK2, CDK1, RRM2, CCNB1, and CHEK1. All five genes were positively correlated with either YTHDF1 or HNRNPA2B1, suggesting that both genes may affect m6A modification by the five genes, further up-regulating their expression and facilitate their roles in inhibiting p53 to suppress tumorigenesis. We also observed major mutations in YTHDF1 and HNRNPA2B1 that led to their amplification in melanoma. Significant differences were observed in the clinical characteristics of patients with altered and unaltered m6A regulatory genes such as tumor stage and treatment response. CONCLUSIONS: We, for the first time, identified a combination of m6A regulatory genes to diagnose melanoma. We also analyzed m6A-related genes more comprehensively based on systematic complete data. We found that YTHDF1 and HNRNPA2B1 were altered in melanoma and might influence the development of the disease through signaling pathways such as p53.

An ultrasensitive polydopamine bi-functionalized SERS immunoassay for exosome-based diagnosis and classification of pancreatic cancer.

Early diagnosis and metastasis monitoring for pancreatic cancer are extremely difficult due to a lack of sensitive liquid biopsy methods and reliable biomarkers. Herein, we developed easy-to-prepare and effective polydopamine-modified immunocapture substrates and an ultrathin polydopamine-encapsulated antibody-reporter-Ag(shell)-Au(core) multilayer (PEARL) Surface-Enhanced Raman Scattering (SERS) nano-tag with a quantitative signal of the Raman reporter at 1072 cm-1, which achieved ultrasensitive and specific detection of pancreatic cancer-derived exosomes with a detection limit of only one exosome in 2 µL of sample solution (approximately 9 × 10-19 mol L-1). Furthermore, by analyzing a 2 µL clinical serum sample, the migration inhibitory factor (MIF) antibody-based SERS immunoassay could not only discriminate pancreatic cancer patients (n = 71) from healthy individuals (n = 32), but also distinguish metastasized tumors from metastasis-free tumors, and Tumor Node Metastasis (TNM) P1-2 stages from the P3 stage (the discriminatory sensitivity was 95.7%). Thus, this novel immunoassay provides a powerful tool for the early diagnosis, classification and metastasis monitoring of pancreatic cancer patients.

Abnormal Expression of Long Noncoding RNAs in Primary Immune Thrombocytopenia: A Microarray Related Study.

BACKGROUND/AIMS: Long noncoding RNAs (lncRNAs) are important regulators of biological processes and they contribute to the pathological developments of various diseases, including autoimmune diseases. To gain the further understanding, we estimate the expression of lncRNAs in primary immune thrombocytopenia (ITP). METHODS: In this study, microarray studies were performed to characterize expression profiles of various lncRNAs and mRNAs in blood samples collected from ITP patients. Quantitative real-time PCR (qRT-PCR) was performed to confirm the results, Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis and gene ontology analysis were used to provide functional annotations, co-expression network construction (CNC) analysis was made to reveal the relations between lncRNAs and their targeted genes. RESULTS: A total of 1177 and 632 lncRNAs were significantly up-regulated or down-regulated, respectively, in "newly diagnosed ITP" patients versus healthy individuals. In addition, 1182 genes and 737 genes were up-regulated or down-regulated, respectively, in "chronic recurrent ITP" patients versus healthy individuals. In a KEGG analysis, "TNF signaling pathway-Homo sapiens (human)" was a key result. In a gene ontology analysis, "Granulocyte macrophage colony-stimulating factor production (GO: 0032604, ontology: Biological process, P = 1.69577E-05)" and "coreceptor activity (GO: 0015026, ontology: molecular function, P = 4.67594E-06)" were the two most critical results. Data from qRT-PCR and receiver operating characteristic curves further demonstrated that ENST00000440492, ENST00000528366, NR_038920, and ENST00000552576 can efficiently distinguish different stages of ITP, especially NR_038920 and ENST00000528366. In a CNC analysis, four lncRNAs were emphasized, and NR_038920 and ENST00000528366 were both associated with proteins with important roles in autoimmune diseases. CONCLUSIONS: These results suggest that lncRNAs act through targeted genes to mediate their functions and to mediate their functions and affect the pathogenesis of ITP.

Clinical Significance of Decreased Interleukin-35 Expression in Patients with Psoriasis.

In psoriasis, a chronic, recurrent, inflammatory skin disease, CD4+T cells and their related cytokines play an important role in its pathogenesis. The role of interleukin (IL)-35, an immunosuppressive cytokine involved in many autoimmune diseases, is unclear in the pathogenesis of psoriasis. This study evaluated IL-35 expression and clinical significance in psoriasis. Protein and mRNA levels of specified markers were measured by enzyme-linked immunosorbent assay (ELISA) and real-time quantitative polymerase chain reaction (qRT-PCR), respectively. Results showed that plasma IL-35 concentrations were lower in patients with psoriasis than in healthy individuals (Z = -6.525, P < .0001). Ebi3 and p35 showed lower mRNA levels in peripheral blood mononuclear cells from patients with psoriasis than in healthy individuals (Z = -5.078, P < .0001, Z = -2.609, P = .009, respectively). The areas under the receiver-operating characteristic (ROC) curves of IL-35, Ebi3, and p35 for patients with psoriasis versus the control were 0.86, 0.78, and 0.64, respectively. Pearson correlation analysis showed that plasma IL-35 expression negatively correlated with interferon-gamma, tumor necrosis factor-alpha, levels of IL-23, -17, and -22, or the Psoriasis Activity and Severity Index and positively correlated with levels of transforming growth factor beta and IL-10 levels in patients with psoriasis. Summarily, IL-35 might mediate psoriasis pathogenesis by influencing the expression of Th1/Th17/Treg -related cytokines and might be a putative target in monitoring or treating psoriasis.

DNase I enzyme-aided fluorescence signal amplification based on graphene oxide-DNA aptamer interactions for colorectal cancer exosome detection.

Exosomes have proved to be an effective cancer biomarker with significant potential, and several cell-specific molecules have been found in colorectal cancer (CRC) exosomes. Nevertheless, it is challenging to use exosomes in clinical lab diagnostics due to their nanoscale and the lack of a convenient and effective detection platform. Here, we developed a DNase I enzyme-aided fluorescence amplification method for CRC exosome detection, based on graphene oxide (GO)-DNA aptamer (CD63 and EpCAM aptamers) interactions. The fluorescence of fluorophore-labeled aptamers quenched by GO, recovered after incubation with samples containing CRC exosomes. The DNase I enzyme digested the single-stranded DNA aptamers on the exosome surface and the exosomes were able to interact with more fluorescent aptamer probes, resulting in an increase of signal amplification. The limit of detection for CRC exosomes is 2.1 × 104 particles/µl. Consequently, a rapid and effective method with high sensitivity was established. The method was verified in 19 clinical blood serum samples to distinguish healthy and CRC patients, showing significant diagnostic power. Moreover, it can be expanded to other kinds of cancer exosomes, in addition to CRC.