Integrated machine learning survival framework develops a prognostic model based on inter-crosstalk definition of mitochondrial function and cell death patterns in a large multicenter cohort for lower-grade glioma.

BACKGROUND: Lower-grade glioma (LGG) is a highly heterogeneous disease that presents challenges in accurately predicting patient prognosis. Mitochondria play a central role in the energy metabolism of eukaryotic cells and can influence cell death mechanisms, which are critical in tumorigenesis and progression. However, the prognostic significance of the interplay between mitochondrial function and cell death in LGG requires further investigation. METHODS: We employed a robust computational framework to investigate the relationship between mitochondrial function and 18 cell death patterns in a cohort of 1467 LGG patients from six multicenter cohorts worldwide. A total of 10 commonly used machine learning algorithms were collected and subsequently combined into 101 unique combinations. Ultimately, we devised the mitochondria-associated programmed cell death index (mtPCDI) using machine learning models that exhibited optimal performance. RESULTS: The mtPCDI, generated by combining 18 highly influential genes, demonstrated strong predictive performance for prognosis in LGG patients. Biologically, mtPCDI exhibited a significant correlation with immune and metabolic signatures. The high mtPCDI group exhibited enriched metabolic pathways and a heightened immune activity profile. Of particular importance, our mtPCDI maintains its status as the most potent prognostic indicator even following adjustment for potential confounding factors, surpassing established clinical models in predictive strength. CONCLUSION: Our utilization of a robust machine learning framework highlights the significant potential of mtPCDI in providing personalized risk assessment and tailored recommendations for metabolic and immunotherapy interventions for individuals diagnosed with LGG. Of particular significance, the signature features highly influential genes that present further prospects for future investigations into the role of PCD within mitochondrial function.

Study on the relationship between genetic polymorphism of reductive folic acid carrier and the risk of neural tube defects.

BACKGROUND: To investigate the association of folate metabolism gene polymorphism with neural tube defects (NTDs) in Chinese population. METHODS: The subjects were divided into two groups, 495 children with NTDs (NTD group) and 255 healthy children (control group). RESULTS: The levels of folic acid, s-adenosine methionine (SAM), and Sam/s-adenosine homocysteine (SAH) in NTD group were lower than those in control group. There were significant differences in hey, SAH, and Sam levels between two groups, but there was no significant difference in folic acid content. High fever in early pregnancy, taking antiepileptic drugs, father's exposure to organic solvents, folic acid deficiency, and mother's diabetes were the important risk factors in NTDs. MTHFR 677C > T gene was a risk factor for NTD in children, while 1298A > C gene was a protective factor. CONCLUSION: Folic acid metabolism markers were different in NTD children and their mothers, and the overall trend showed that folate, SAM, and SAM/SAH levels were decreased, while Hcy and SAH levels were increased; MTHFR 677C > T gene of SNPs was a risk factor for the occurrence of NTDs, and MTHFR 1298A > C gene was a protective factor, and the environmental risk factor had a synergistic effect on occurrence of NTDs.

Effect of enhanced UV-B radiation on growth and photosynthetic physiology of Iris tectorum maxim.

Iris tectorum Maxim. is an important plant that plays a very crucial role in the ecological welfare of wetlands. In this study, the effects of different intensities of UV-B radiation on the growth, photosynthetic pigment content, chlorophyll fluorescence characteristics, chloroplast ultrastructure, and gas exchange parameters of Iris tectorum Maxim. were studied. The results showed that enhanced UV-B radiation had a significant influence on the above-mentioned parameters of iris. Compared with the control, enhanced UV-B radiation caused certain damage to the leaf appearance. With the increasing intensity of radiation, the apparent damage degree became more serious. Enhanced UV-B radiation significantly decreased leaf chlorophyll contents, and the effect accumulated with the exposure time. Enhanced UV-B radiation increased Fo, significantly increased the non-photochemical quenching coefficient NPQ, reduced PSII and Qp, and significantly decreased the Fm, Fv/Fm, and Fv/Fo in leaves. The effect of UV-B radiation on PSII destruction of Iris tectorum Maxim. increased as the radiation intensity increased and the exposure time prolonged. The chloroplast structure was damaged under the enhanced UV-B radiation. More specifically, thylakoid lamellae were distorted, swelling and even blurred, and a large number of starch granules appeared. The effect of the high intensity of radiation on chloroplast ultrastructure was greater than that of lower intensity. Enhanced UV-B radiation reduced significantly the net photosynthetic rate, stomatal conductance, and transpiration rate, and the degree of degradation increased with the increasing irradiation intensity. However, the intercellular CO2 content increased, which suggests that the main reason for the decrease of photosynthetic rate was the non-stomatal factors.

The association between serum adiponectin and 3-month outcome after ischemic stroke.

BACKGROUND: Although adiponectin is a major adipocytokine that affects the pathogenesis of various cardiovascular diseases, its clinical significance in stroke remains controversial. The purpose of this study was to assess the impact of serum adiponectin levels on functional prognosis in patients with ischemic stroke. METHODS: This was a prospective, observational cohort study. Consecutive first-ever ischemic stroke patients without any pre-morbid handicap admitted to our hospital were identified from December 2017 to December 2018. Serum concentration of adiponectin was routinely measured within the first 24 h after admission by a commercially available sandwich ELISA. Associations between adiponectin and either clinical severity at admission, poor outcomes or mortality at 3-month after admission were analyzed using logistic regression to obtain odds ratios (OR) and 95% confidence intervals (CI). RESULTS: The serum level of adiponectin was obtained in 227 patients with a median value of 7.0 µg/ml, which was significantly higher (P < 0.001) than in those heathy control. Adiponectin levels were associated with moderate-to-high stroke, and risk increased by 12% (OR = 1.12; 95% CI 1.03-1.25; P = 0.002). Patients with a poor outcome and nonsurvivors had significantly increased adiponectin levels on admission (P < 0.001, all). In multivariate logistic regression analysis, adiponectin was an independent predictor of functional outcome and mortality, and risk increased by 24% (OR = 1.24, 95% CI 1.13-1.37; P < 0.001) and 31% (1.31 [1.18-1.46], P < 0.001), respectively. Kaplan-Meier analysis suggested that the patients with high serum adiponectin levels had a higher risk of death than those patients with low levels (log-rank test P < 0.001). CONCLUSIONS: Our results show that high adiponectin is associated with stroke severity and support the hypothesis that adiponectin can be serve as a biomarker of poor outcome after stroke, independent of baseline variables. Trial registration ChiCTR-OPC-17013501. Retrospectively Registered 21 September 2017.

Variants in MTHFR gene and neural tube defects susceptibility in China.

Neural tube defect (NTD) is a severe congenital birth abnormalities involving incomplete neural tube closure. 5, 10-methylenetetrahydrofolate reductase (MTHFR) gene plays key role in folate cycle and methylation cycle, which could affect the DNA synthesis, repair and methylation. In this study, we aim to investigate the correlation between MTHFR polymorphisms and NTD-affected pregnancy. There were 444 participants involved in our study. Tag-SNPs were identified in HapMap Databases. Blood samples were collected from all subjects to further extract the genomic DNAs by TaqMan Blood DNA kits. We also carried out a meta-analysis based on previous published studies to further examine the association between MTHFR polymorphisms and NTD. In case-control study analysis, two SNPs were identified to be associated with NTD risk. The 677 C > T genetic variant was correlated with increased risk of NTD-affected pregnancy. However, the 1298 A > C polymorphism was shown to lower the risk of NTD-affected pregnancy. The protective role of 1298 A > C polymorphisms was further supported by the result of meta-analysis. Our study revealed that the SNPs of 677C > T and 1298A > C in MTHFR were associated with NTD-affected pregnancy, in which 677C > T was a risk factor and in contrast 1298A > C was protective factor against NTD. Our results of meta-analysis also revealed the 1298A > C MTHFR polymorphism play protective role in NTD.

Impaired Kidney Function Portended a Bleak Prognosis for Surgically Treated Hypertensive Intracerebral Hemorrhage Patients.

Purpose: Spontaneous intracerebral hemorrhage (ICH) cases caused by hypertension often have poor prognoses. The use of dehydrant agents, such as mannitol, is common to reduce intracranial pressure and alleviate cerebral edema, but they may also pose a risk of worsening kidney function. This study aimed to investigate the impact of impaired kidney function on the outcomes of surgically treated hypertensive ICH patients. Methods: We conducted a retrospective analysis of a consecutive cohort of patients who underwent surgical intervention due to hypertension-related ICH at our institute between December 1, 2017, and January 31, 2022. Demographic, clinical, radiological, and prognostic data were collected. Patients were categorized into two groups based on 90-day mortality: group A [overall survival (OS) ≤3 months] and group B (OS >3 months). Survival analysis was performed to identify factors associated with poor outcomes. Results: Among the 232 eligible patients, group A exhibited significantly impaired kidney function, as indicated by mean estimated glomerular filtration rate (eGFR) at admission, postoperative, 3-day postoperative, and 7-day postoperative time points (91.9, 82.5, 73.5, 75.2 ml/min/1.73 m²). In contrast, group B did not show significant changes in kidney function (mean eGFR for the corresponding time points: 108.1, 106.5, 111.5, 109.6 ml/min/1.73 m²). The 3-day postoperative eGFR showed the strongest predictive ability for assessing prognosis [areas under the curve (AUC): 0.617, 0.675, 0.737, 0.730]. Univariate and multivariate analyses identified low Glasgow Coma Scale (GCS) score (3-8), ventricle intrusion of hematomas, cardiac failure, larger hematoma volume, infection, and lower 3-day postoperative eGFR as adverse factors for survival. Conclusions: Preserving kidney function is crucial for achieving favorable outcomes in hypertensive ICH cases. Impaired 3-day postoperative eGFR emerged as an independent risk factor for overall survival. Patients with cardiac failure, infection, and larger hematoma volume should receive careful management to improve outcomes.

Progress in Prevention and Treatment of Acute Bone Loss in Orthopedics.

Orthopedic patients need to perform limb immobilization for several days to several weeks due to fracture or other special circumstances. When the function of a certain part or the whole body is restricted, the activity of osteoclasts will be enhanced and its life activity will surpass that of osteoblasts, so local or even whole body bone loss will occur. Acute bone loss usually occurs within a few weeks after the immobilization of limbs. At this stage, the patient's bone mass will decrease sharply, and the patient is prone to osteoporotic refracture. After that, the bone mass will gradually recover, but the speed of bone formation and bone absorption is difficult to reach a balanced state, and the bone mass of patients will continue to decline after it has recovered to a certain degree. After acute progressive bone loss, a large number of bones were lost and the strength of bones decreased. It is often difficult to recover to the level before fracture for a long time, which undoubtedly increases the risk of osteoporosis and related refractures. According to this common phenomenon of bone loss, clinical treatment varies greatly. After a series of research and practice, clinicians summed up some rules and put forward some feasible suggestions, thus strengthening clinicians' understanding of the treatment of acute bone loss, effectively improving the treatment effect of acute bone loss, having far-reaching significance for preventing and treating osteoporosis, reducing the risk of fracture, and improving the long-term prognosis of patients.

A preliminary study on the mechanism of VASH2 in childhood medulloblastoma.

To study the differences in VASH2 expression in pediatric medulloblastoma (MB) tumor tissues of different molecular subtypes, to analyze the correlation between VASH2 and the molecular subtypes of medulloblastoma, clinicopathological data, and prognosis, and to explore the specific mechanism of VASH2's role in SHH medulloblastoma cell lines DAOY. We analyzed 47 pediatric medulloblastoma cases admitted to the Department of Pediatric Neurosurgery of the First Affiliated Hospital of Xinjiang Medical University from January 2011 to December 2019, and the expression levels of YAP1 and GAB1 in these tumor tissues were detected by immunohistochemistry (IHC) and molecularly typed (WNT-type, SHH-type, and non-WNT/SHH-type). The correlation between VASH2 and molecular typing of medulloblastoma was analyzed. We also analyzed the medulloblastoma dataset in the GEO database (GSE30074 and GSE202043) to explore the correlation between VASH2 and the prognosis of medulloblastoma patients, as well as performed a comprehensive GO enrichment analysis specifically for the VASH2 gene to reveal the underlying biological pathways of its complex molecular profile. We used vasopressin 2 (VASH2) as a research target and overexpressed and knocked down VASH2 in SHH medulloblastoma cell lines DAOY by lentiviral vectors in vitro, respectively, to investigate its role in SHH medulloblastoma cell lines DAOY cell proliferation, apoptosis, migration, invasion and biological roles in the cell cycle. (1) Among 47 pediatric medulloblastoma cases, 8 were WNT type, 29 were SHH type, and 10 were non-WNT/SHH type. the positive rate of VASH2 was highest in the SHH type with a 68.97% positive rate, followed by non-WNT/SHH and lowest in the WNT type. The results of the multifactorial analysis showed that positive expression of VASH2 was associated with medulloblastoma molecular subtype (SHH type), site of tumor development (four ventricles), and gender (male), P < 0.05. (2) The results of cellular experiments showed that overexpression of VASH2 increased the invasion and migration ability of medulloblast Daoy, while knockdown of VASH2 inhibited the invasion and Overexpression of VASH2 upregulated the expression of Smad2 + 3, Smad4, Mmp2 and the apoptotic indicators Bcl-2 and Caspase3, while knockdown of VASH2 suppressed the expression of Smad2 + 3 and Mmp2, and silenced the expression of Smad4 and the apoptotic indicators Bcl2, Caspase3 expression. Flow cytometric cycle analysis showed that VASH2 overexpression increased the S phase in the Daoy cell cycle, while VASH2 knockdown decreased the S phase in the SHH medulloblastoma cell lines DAOY cell cycle. Bioinformatics analysis showed that there was no statistically significant difference between the expression of VASH2 genes in the GSE30074 and GSE202043 datasets and the prognosis of the patients, but the results of this dataset analysis suggested that we need to continue to expand the sample size of the study in the future. The results of the GO enrichment analysis showed that the angiogenic pathway was the most significantly enriched, and the PPI interactions network of VASH2 was obtained from the STRING database. Using the STRING database, we obtained the PPI interaction network of VASH2, and the KEGG enrichment analysis of VASH2-related genes showed that VASH2-related genes were related to the apoptosis pathway, and therefore it was inferred that VASH2 also affects the development of tumors through apoptosis. We found for the first time that the positive expression rate of VASH2 was closely associated with SHH-type pediatric medulloblastoma and that VASH2 was involved in the invasion, migration, cell cycle, and apoptotic capacity of SHH medulloblastoma cell lines DAOY by affecting downstream indicators of the TGF-ß pathway. This suggests that it is involved in the progression of pediatric medulloblastoma, and VASH2 is expected to be a diagnostic and therapeutic target for SHH-type pediatric medulloblastoma.

MV-CVIB: a microbiome-based multi-view convolutional variational information bottleneck for predicting metastatic colorectal cancer.

Introduction: Imbalances in gut microbes have been implied in many human diseases, including colorectal cancer (CRC), inflammatory bowel disease, type 2 diabetes, obesity, autism, and Alzheimer's disease. Compared with other human diseases, CRC is a gastrointestinal malignancy with high mortality and a high probability of metastasis. However, current studies mainly focus on the prediction of colorectal cancer while neglecting the more serious malignancy of metastatic colorectal cancer (mCRC). In addition, high dimensionality and small samples lead to the complexity of gut microbial data, which increases the difficulty of traditional machine learning models. Methods: To address these challenges, we collected and processed 16S rRNA data and calculated abundance data from patients with non-metastatic colorectal cancer (non-mCRC) and mCRC. Different from the traditional health-disease classification strategy, we adopted a novel disease-disease classification strategy and proposed a microbiome-based multi-view convolutional variational information bottleneck (MV-CVIB). Results: The experimental results show that MV-CVIB can effectively predict mCRC. This model can achieve AUC values above 0.9 compared to other state-of-the-art models. Not only that, MV-CVIB also achieved satisfactory predictive performance on multiple published CRC gut microbiome datasets. Discussion: Finally, multiple gut microbiota analyses were used to elucidate communities and differences between mCRC and non-mCRC, and the metastatic properties of CRC were assessed by patient age and microbiota expression.

DeepTPpred: A Deep Learning Approach With Matrix Factorization for Predicting Therapeutic Peptides by Integrating Length Information.

The abuse of traditional antibiotics has led to increased resistance of bacteria and viruses. Efficient therapeutic peptide prediction is critical for peptide drug discovery. However, most of the existing methods only make effective predictions for one class of therapeutic peptides. It is worth noting that currently no predictive method considers sequence length information as a distinct feature of therapeutic peptides. In this article, a novel deep learning approach with matrix factorization for predicting therapeutic peptides (DeepTPpred) by integrating length information are proposed. The matrix factorization layer can learn the potential features of the encoded sequence through the mechanism of first compression and then restoration. And the length features of the sequence of therapeutic peptides are embedded with encoded amino acid sequences. To automatically learn therapeutic peptide predictions, these latent features are input into the neural networks with self-attention mechanism. On eight therapeutic peptide datasets, DeepTPpred achieved excellent prediction results. Based on these datasets, we first integrated eight datasets to obtain a full therapeutic peptide integration dataset. Then, we obtained two functional integration datasets based on the functional similarity of the peptides. Finally, we also conduct experiments on the latest versions of the ACP and CPP datasets. Overall, the experimental results show that our work is effective for the identification of therapeutic peptides.

Repair of Cranial Defects in Rabbits with 3D-Printed Hydroxyapatite/Polylactic Acid Composites.

Objective: The safety and efficacy of three-dimensional- (3D-) printed hydroxyapatite/polylactic acid (HA-PLA) composites in repairing cranial defects were evaluated in a rabbit experimental model. Methods: Twelve New Zealand rabbits were selected as experimental subjects. Two holes (A and B), each with a diameter of approximately 1 cm, were made in the cranium of each rabbit. Hole A served as the experimental manipulation, and hole B served as the control manipulation. A 3D-printed HA-PLA composite was used for placement onto hole A, whereas autologous bone powder was used for placement onto hole B. Samples from the experimental holes and the control holes were collected at 30 and 90 days after surgery. The obtained materials were examined in terms of their morphologies and histopathologies and were also subjected to simultaneous hardness tests. Results: Both the 3D-printed HA-PLA composite and autologous bone powder were able to repair and fill the cranial defects at 30 days and 90 days after surgery. At 30 days after surgery, the microhardness of the area repaired by the HA-PLA composite was lower than that of the area repaired by autogenous bone powder (p < 0.01), but neither of these treatments reached the hardness of normal bone at this time (p < 0.01). At 90 days after surgery, there was no statistically significant difference in the microhardness of the repaired area from the 3D-printed HA-PLA composite compared with that of the repaired area from autologous bone powder (p > 0.05), and there was no statistically significant difference in the hardness of the two repaired areas compared with that of the normal bone (p > 0.05). Hematoxylin-eosin staining showed that bone cells in the HA-PLA material in the experimental group grew and were arranged in an orderly manner. Bone trabeculae and marrow cavities were formed on the pore surface and inside of the HA-PLA scaffold, and the arrangement of bone trabeculae was regular. Conclusion: 3D-printed HA-PLA composites can induce bone regeneration, are biocompatible, have the same strength as autologous bone powder, are able to degrade, and are ultimately safe and effective for repairing cranial defects in rabbits. However, further research is needed to determine the feasibility of 3D-printed HA-PLA composites in human cranioplasty.

Tumor microenvironment and exosomes in brain metastasis: Molecular mechanisms and clinical application.

Metastasis is one of the important biological features of malignant tumors and one of the main factors responsible for poor prognosis. Although the widespread application of newer clinical technologies and their continuous development have significantly improved survival in patients with brain metastases, there is no uniform standard of care. More effective therapeutic measures are therefore needed to improve prognosis. Understanding the mechanisms of tumor cell colonization, growth, and invasion in the central nervous system is of particular importance for the prevention and treatment of brain metastases. This process can be plausibly explained by the "seed and soil" hypothesis, which essentially states that tumor cells can interact with various components of the central nervous system microenvironment to produce adaptive changes; it is this interaction that determines the development of brain metastases. As a novel form of intercellular communication, exosomes play a key role in the brain metastasis microenvironment and carry various bioactive molecules that regulate receptor cell activity. In this paper, we review the roles and prospects of brain metastatic tumor cells, the brain metastatic tumor microenvironment, and exosomes in the development and clinical management of brain metastases.

The RPL4P4 Pseudogene Is a Prognostic Biomarker and Is Associated with Immune Infiltration in Glioma.

Objective: Research over the past decade has suggested important roles for pseudogenes in gliomas. Our previous study found that the RPL4P4 pseudogene is highly expressed in gliomas. However, its biological function in gliomas remains unclear. Methods: In this study, we analyzed clinical data on patients with glioma obtained from The Cancer Genome Atlas (TCGA), the Chinese Glioma Genome Atlas (CGGA), the Genotype-Tissue Expression (GTEx), and the GEPIA2 databases. We used the R language for the main analysis. Correlations among RPL4P4 expression, pathological characteristics, clinical outcome, and biological function were evaluated. In addition, the correlations of RPL4P4 expression with immune cell infiltration and glioma progression were analyzed. Finally, wound healing, Transwell, and CCK-8 assays were performed to analyze the function of RPL4P4 in glioma cells. Result: We found that RPL4P4 is highly expressed in glioma tissues and is associated with poor prognosis, IDH1 wild type, codeletion of 1p19q, and age. Multivariate analysis and the nomogram model showed that high RPL4P4 expression was an independent risk factor for glioma prognosis and had better prognostic prediction power. Moreover, high RPL4P4 expression correlated with immune cell infiltration, which showed a significant positive association with M2-type macrophages. Finally, RPL4P4 knockdown in glioma cell lines caused decreased glioma cell proliferation, invasion, and migration capacity. Conclusion: Our data suggest that RPL4P4 can function as an independent prognostic predictor of glioma. It also shows that RPL4P4 expression correlates with immune cell infiltration and that targeting RPL4P4 may be a new strategy for the treatment of glioma patients.

Identification of VASH1 as a Potential Prognostic Biomarker of Lower-Grade Glioma by Quantitative Proteomics and Experimental Verification.

Background: VASH1 is a novel angiogenic regulatory factor, that participates in the process of carcinogenesis and the development of diverse tumors. Our study aimed to investigate the expression and prognostic value of the VASH1 in Lower-Grade Glioma (LGG), to explore its functional network in LGG and its effects on biological behaviors. Methods: LGG transcriptome data, somatic mutation profiles and clinical features analyzed in the present study were obtained from the TCGA, GTEx, CCLE, CGGA, UALCAN, and GEPIA2 databases, as well as clinical data and tissue sections of 83 LGG patients in our hospital. The expression characteristics of VASH1 in LGG were investigated by univariate, multivariate, immunohistochemistry, qRT-PCR, and western-blot. Subsequently, we analyzed the prognostic significance of VASH1 in LGG patients by survival analysis, subject operation characteristic curve, correlation analysis, external validation, independent prognostic significance analysis, and clinical stratification, and confirmed its biological effect on glioma cell lines in vitro. Finally, we performed GO, KEGG, and GSEA to clarify biological functions and related pathways. CIBERSORT and ESTIMATE algorithms were used to calculate the proportion of immune cells and immune microenvironment fraction in LGG. Result: We found that VASH1 is highly expressed in LGG tissues and is associated with poor prognosis, WHO grade, IDH1 wild-type, and progressive disease (P < 0.05). Multivariate and the Nomogram model showed that high VASH1 expression was an independent risk factor for glioma prognosis and had better prognostic prediction efficacy in different LGG Patient cohorts (HR = 4.753 and P=0.002). In vitro experiments showed that knockdown of VASH1 expression in glioma cell lines caused increased glioma cell proliferation, invasion, and migration capacity. The mechanism may be related to VASH1 promoting microtubule formation and remodeling of immune microenvironment. Conclusion: Our study firstly found that high VASH1 expression was associated with poor prognosis. In addition, We identified the possible mechanism by which VASH1 functioned in LGG. VASH1 inhibits the invasion and migration of tumor cells by affecting microtubule formation and immune infiltration in the tumor microenvironment. May be an important endogenous anti-tumor factor for LGG and provide a potential biomarker for individualized treatment of LGG.

RMSCNN: A Random Multi-Scale Convolutional Neural Network for Marine Microbial Bacteriocins Identification.

The abuse of traditional antibiotics has led to an increase in the resistance of bacteria and viruses. Similar to the function of antibacterial peptides, bacteriocins are more common as a kind of peptides produced by bacteria that have bactericidal or bacterial effects. More importantly, the marine environment is one of the most abundant resources for extracting marine microbial bacteriocins (MMBs). Identifying bacteriocins from marine microorganisms is a common goal for the development of new drugs. Effective use of MMBs will greatly alleviate the current antibiotic abuse problem. In this work, deep learning is used to identify meaningful MMBs. We propose a random multi-scale convolutional neural network method. In the scale setting, we set a random model to update the scale value randomly. The scale selection method can reduce the contingency caused by artificial setting under certain conditions, thereby making the method more extensive. The results show that the classification performance of the proposed method is better than the state-of-the-art classification methods. In addition, some potential MMBs are predicted, and some different sequence analyses are performed on these candidates. It is worth mentioning that after sequence analysis, the HNH endonucleases of different marine bacteria are considered as potential bacteriocins.

The Role of Exosomal miRNAs in Glioma: Biological Function and Clinical Application.

Gliomas are complex and heterogeneous central nervous system tumors with poor prognosis. Despite the increasing development of aggressive combination therapies, the prognosis of glioma is generally unsatisfactory. Exosomal microRNA (miRNA) has been successfully used in other diseases as a reliable biomarker and even therapeutic target. Recent studies show that exosomal miRNA plays an important role in glioma occurrence, development, invasion, metastasis, and treatment resistance. However, the association of exosomal miRNA between glioma has not been systemically characterized. This will provide a theoretical basis for us to further explore the relationship between exosomal miRNAs and glioma and also has a positive clinical significance in the innovative diagnosis and treatment of glioma.

MALT-1 inhibition attenuates the inflammatory response of ankylosing spondylitis by targeting NF-κB activation.

BACKGROUND: The present study aimed to investigate the effects of mucosa-associated lymphoid tissue lymphoma translocation protein (MALT)-1 on ankylosing spondylitis and its underlying mechanisms. METHODS: Proteoglycan induced ankylosing spondylitis (PGIA) mouse model was established and the expression patterns of MALT-1 were determined in joint tissue. Next, the mice were intraarticularly administrated with MALT-1 in the PGIA mouse model. Meanwhile, shRNA was intraarticularly administrated to PGIA mice. The incidence of arthritis and clinical score was evaluated. Besides, the levels of inflammatory cytokines and matrix metalloproteinases (MMPs) were measured. Protein expressions of full-length CYLD (FL-CYLD), C-terminal cleavage fragment (CYLD-CL), and nuclear factor (NF)-κB were determined. RESULTS: The mRNA and protein levels of MALT1 were increased in the PGIA mouse model. The treatment of MALT-1 accelerated arthritis incidence and joint damage, whereas shMALT-1 suppressed arthritis symptoms in the PGIA mouse model. In addition, treatment of shMALT-1 suppressed the levels of inflammatory cytokines (tumor necrosis factor (TNF)-α, interleukin (IL)-6, and IL-1ß), MMP-3, and MMP-9. Furthermore, the treatment of shMALT-1 suppressed the levels of CYLD and NF-κB in the joint tissues in the PGIA mouse model. CONCLUSION: The inhibition of MALT-1 suppressed the inflammatory response in ankylosing spondylitis in part by the regulation of CYLD and NF-κB.

[Influence of acupuncture combined with rehabilitation therapy on limb motor function and serum cAMP and cGMP in patients with hemiplegia of cerebral ischemic stroke].

OBJECTIVE: To evaluate the therapeutic effect of the combined treatment with balance acupuncture therapy and exercise re-learning rehabilitation therapy and the impact on serum cAMP and cGMP in the patients with hemiplegia of cerebral ischemic stroke. METHODS: A total of 90 patients of hemiplegia of cerebral ischemic stroke were randomized into an observation group and a control group, 45 cases in each one. All of the patients in the two groups received health education, diet guidance, routine symptomatic treatment as well as exercise re-learning rehabilitation therapy. Additionally, in the observation group, balance acupuncture therapy was applied, in which, the acupoints on the yang aspect of the human body, on the governor vessel and bladder meridian were adopted in the morning and those on the yin aspect of the human body, on the conception vessel and kidney meridian were stimulated in the afternoon. In the control group, the regular acupuncture was given. In the two groups, both acupuncture and rehabilitation therapies were given 5 days a week, 2 week-treatment as one course and totally 2 courses were required. Separately, before and after treatment, the score of Fugl-Meyer assessment (FMA) and the score of Chinese stroke scale (CSS) were recorded, the levels of cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP) detected in serum and the clinical therapeutic effect were evaluated in the two groups. RESULTS: After treatment, FMA score was increased in the patients of either of the groups as compared with that before treatment (P<0.01) and CSS score decreased as compared with that before treatment (P<0.01). After treatment, FMA score in the observation group was higher than that in the control group (P<0.01) and CSS score was lower than the control group (P<0.01). After treatment, the level of serum cAMP of the patients in either of the groups was increased as compared with that before treatment (P<0.01) and that of cGMP decreased as compared with that before treatment (P<0.01). After treatment, the level of cAMP in the observation group was higher than that in the control group (P<0.01) and that of cGMP was lower than the control group (P<0.01). The total effective rate was 93.3% (42/45) in the observation group, better than 73.3% (33/45) in the control group (P<0.01). CONCLUSION: The balance acupuncture therapy combined with exercise re-learning rehabilitation effectively improves the motor function of the affected limb, relieves injury and regulate the levels of serum cAMP and cGMP in the patients with hemiplegia of ischemic stroke.

Liquid biopsy in central nervous system tumors: the potential roles of circulating miRNA and exosomes.

The Central nervous system (CNS) tumor still remains the most lethal cancer, and It is hard to diagnose at an earlier stage on most occasions. It is found that recurrent disease is finally observed in patients who occurred chemo-resistance after completely primary treatment. It is a challenge that monitoring treatment efficacy and tumor recurrence of CNS tumors are full of risks and difficulties by brain biopsies. However, the brain biopsies are considered as an invasive technique with low specificity and low sensitivity. In contrast, the liquid biopsy is based on blood and cerebrospinal fluid (CSF) test, which is going to acceptable among the patients through it's minimally invasive and serial bodily fluids. The advantages of liquid biopsy are to follow the development of tumors, provide new insights in real time, and accurate medical care. The major analytical constituents of liquid biopsy contain the Circulating tumor cells (CTCs), circulating tumor DNA (ctDNA), circulating cell-free microRNAs (cfmiRNAs), and circulating exosomes. Liquid biopsy has been widely utilized in CNS tumors in recent years, and the CTCs and ctDNA have become the hot topics for researching. In this review, we are going to explain the clinical potential of liquid biopsy biomarkers in CNS tumor by testing circulating miRNAs and exosomes to evaluate diagnose, prognosis, and response to treatment.

Toll-like receptor 2/4 inhibitors can reduce preterm birth in mice.

OBJECTIVES: Preterm birth (PTB) occurs in 5% to 18% of newborns. However, the underlying inflammatory mechanisms have not been elucidated. METHODS: We established a mouse model of infection-associated PTB. Physical signs in pregnant mice with or without lipopolysaccharide (LPS) treatment were observed, and the frequencies of Toll-like receptor (TLR)2- and TLR4-positive CD11b+ cells were analyzed. Cytokine levels in plasma and pathological changes were assessed following LPS treatment. A rescue experiment was used to probe potential immunologic mechanisms underlying PTB. RESULTS: Lymphocyte infiltration could be observed in the placentas of mice following intrauterine injection with LPS. The percentage of inflammatory cells decreased 12 hours after treatment. Moreover, TLR2 and TLR4 expression in peripheral blood cells was significantly increased 4 hours after intraperitoneal injection of LPS. Peak TLR2 and TLR4 expression in peripheral blood cells occurred 8 hours post-treatment. TLR4 and TLR-2/4 inhibitors reduced levels of interleukin-10, interferon-γ, and tumor necrosis factor-α in peripheral blood and delayed PTB. CONCLUSIONS: TLR2 and TLR4 inhibition could play important roles in PTB.