The brain-heart axis: Integrative analysis of the shared genetic etiology between neuropsychiatric disorders and cardiovascular disease.

BACKGROUND: Multiple observational studies have reported substantial comorbidity between neuropsychiatric disorders and cardiovascular disease (CVD), but the underlying mechanisms remain largely unknown. METHODS: Using GWAS summary datasets of 8 neuropsychiatric disorders and 6 cardiovascular diseases, an integrative analysis incorporating linkage-disequilibrium-score-regression (LDSC), Mendelian randomization (MR), functional mapping and annotation (FUMA), and functional enrichment analysis, was conducted to investigate shared genetic etiology of the brain-heart axis from the whole genome level, single-nucleotide polymorphism (SNP) level, gene level, and biological pathway level. RESULTS: In LDSC analysis, 18 pairwise traits between neuropsychiatric disorders and CVD were identified with significant genetic overlaps, revealing extensive genome-wide genetic correlations. In bidirectional MR analysis, 19 pairwise traits were identified with significant causal relationships. Genetic liabilities to neuropsychiatric disorders, particularly attention-deficit hyperactivity disorder and major depressive disorder, conferred extensive significant causal effects on the risk of CVD, while hypertension seemed to be a risk factor for multiple neuropsychiatric disorders, with no significant heterogeneity or pleiotropy. In FUMA analysis, 13 shared independent significant SNPs and 887 overlapping protein-coding genes were detected between neuropsychiatric disorders and CVD. With GO and KEEG functional enrichment analysis, biological pathways of the brain-heart axis were highly concentrated in neurotransmitter synaptic transmission, lipid metabolism, aldosterone synthesis and secretion, glutathione metabolism, and MAPK signaling pathway. CONCLUSION: Extensive genetic correlations and genetic overlaps between neuropsychiatric disorders and CVD were identified in this study, which might provide some new insights into the brain-heart axis and the therapeutic targets in clinical practice.

Experimental Study on the Characterization of Aging Resistance Properties of Optical Cables in the Hydrogen-Containing Downhole Environment.

The utilization of downhole optical cables has significantly enhanced the efficiency and reliability of oilfield production operations; however, the challenging high-temperature and high-pressure conditions prevalent in oil-gas fields markedly reduce the service lifespan of these optical cables. This limitation severely impedes their application and further development in subterranean environments. In this study, a qualitative analysis was conducted on the structural materials utilized in two types of optical cables to identify these materials and assess the high-temperature tolerance and aging resistance properties of the optical fibers incorporated within. It was discovered that hydrogen infiltration into the subterranean optical cables predominantly accounts for their operational failure. To address this issue, an optical loss testing platform was established, facilitating the execution of a high-temperature and high-pressure hydrogen permeation aging experiment on the optical fibers, allowing for the evaluation of the hydrogen resistance capabilities of the two types of optical fibers. The findings from this study provide a theoretical foundation and methodological guidance for the optimization of optical fibers, aiming to enhance their durability and functional performance in adverse environmental conditions encountered in oil-gas field applications.

1,3-Disubstituted-1,2,4-triazin-6-ones with potent activity against androgen receptor-dependent prostate cancer cells.

Synthesis and biological evaluation of a small, focused library of 1,3-disubstituted-1,2,4-triazin-6-ones for in vitro inhibitory activity against androgen-receptor-dependent (22Rv1) and androgen-receptor independent (PC3) castration-resistant prostate cancer (CRPC) cells led to highly active compounds with in vitro IC50 values against 22Rv1 cells of <200 nM, and with apparent selectivity for this cell type over PC3 cells. From metabolic/PK evaluations of these compounds, a 3-benzyl-1-(2,4-dichlorobenzyl) derivative had superior properties and showed considerably stronger activity, by nearly an order of magnitude, against AR-dependent LNCaP and C4-2B cells compared to AR-independent DU145 cells. This lead compound decreased AR expression in a dose and time dependent manner and displayed promising therapeutic effects in a 22Rv1 CRPC xenograft mouse model. Computational target prediction and subsequent docking studies suggested three potential known prostate cancer targets: p38a MAPK, TGF-ß1, and HGFR/c-Met, with the latter case of c-Met appearing stronger, owing to close structural similarity of the lead compound to known pyridazin-3-one derivatives with potent c-Met inhibitory activity. RNA-seq analysis showed dramatic reduction of AR signalling pathway and/or target genes by the lead compound, subsequently confirmed by quantitative PCR analysis. The lead compound was highly inhibitory against HGF, the c-Met ligand, which fitted well with the computational target prediction and docking studies. These results suggest that this compound could be a promising starting point for the development of an effective therapy for the treatment of CRPC.

G-quadruplexes promote the motility in MAZ phase-separated condensates to activate CCND1 expression and contribute to hepatocarcinogenesis.

G-quadruplexes (G4s) can recruit transcription factors to activate gene expression, but detailed mechanisms remain enigmatic. Here, we demonstrate that G4s in the CCND1 promoter propel the motility in MAZ phase-separated condensates and subsequently activate CCND1 transcription. Zinc finger (ZF) 2 of MAZ is a responsible for G4 binding, while ZF3-5, but not a highly disordered region, is critical for MAZ condensation. MAZ nuclear puncta overlaps with signals of G4s and various coactivators including BRD4, MED1, CDK9 and active RNA polymerase II, as well as gene activation histone markers. MAZ mutants lacking either G4 binding or phase separation ability did not form nuclear puncta, and showed deficiencies in promoting hepatocellular carcinoma cell proliferation and xenograft tumor formation. Overall, we unveiled that G4s recruit MAZ to the CCND1 promoter and facilitate the motility in MAZ condensates that compartmentalize coactivators to activate CCND1 expression and subsequently exacerbate hepatocarcinogenesis.

Exosomes derived from cancer-associated fibroblasts promote tumorigenesis, metastasis and chemoresistance of colorectal cancer by upregulating circ_0067557 to target Lin28.

BACKGROUND: Cancer associated fibroblasts (CAFs) can remodel tumor microenvironment by secreting exosomes. This study aimed to investigate the role of exosomes derived from cancer-associated fibroblasts in colorectal cancer (CRC) progression. METHODS: Circular RNA (circRNA) array was used to identify differentially expressed circRNAs in exosomes from normal fibroblasts (NFs) and CAFs, and confirmed one differentially expressed circRNA circ_0067557 by real-time PCR. The effect of circ_0067557 on proliferation, metastasis, chemoresistance and apoptosis was verified by wound heal, tranwell, CCK8, sphere-forming and flow cytometry assay. RESULTS: Circ_0067557 expression in exosomes from CAFs was higher than those from NFs. CAF-derived exosomes promoted the proliferation, migration, invasion and chemoresistance of CRC cells while suppressed apoptosis. Silencing of circ_0067557 inhibited malignant phenotypes of CRC cells by targeting Lin28A and Lin28B. Moreover, CAF-derived exosomes enhanced the growth of CRC xenograft tumors. CONCLUSION: Circ_0067557/Lin28A and Lin28B signal axis may be a potential therapy target for CRC.

The clinical association between coagulation indexes, platelet-related parameters, and bone metastasis of newly diagnosed prostate cancer.

BACKGROUND: At present, much evidence shows that many cancers have a high risk of thrombosis. Several studies have shown the prognostic value of platelet-related parameters and coagulation indexes in prostate cancer (PCa). However, the association between platelet-related parameters, coagulation indexes and bone metastasis of Pca is unclear. METHODS: A total of 234 pathologically diagnosed patients with Pca were consecutively collected and stratified into the bone metastasis group and non-bone metastasis group according to the results of the bone scan. ROC curve analysis was used to explore the auxiliary predictive value of single and combined parameters for bone metastasis in Pca patients. Univariate and multivariate Logistic regression analyses were used to determine the relationship between platelet-related parameters, coagulation indexes, and bone metastasis of Pca. RESULTS: Platelet count (PLT), fibrinogen (Fib), prostate-specific antigen (PSA), and D-dimer (DD) levels of the bone metastasis group were significantly higher than the non-bone metastasis group (P = 0.010, P < 0.001, P < 0.001, and P < 0.001, respectively). This study confirmed that PLT, PSA, DD and Fib have auxiliary predictive value for prostate cancer bone metastasis. After the combination of PLT, PSA, DD and Fib, the area under the curve, sensitivity and specificity increased significantly. The univariate logistic analysis demonstrated that PLT (OR: 1.008, P = 0.011), DD (OR: 2.690, P < 0.001), PSA (OR: 1.073, P < 0.001), Gleason score (OR: 7.060, P < 0.001), and Fib (OR: 2.082, P < 0.001) were significantly positively correlated with bone metastasis of Pca. Multivariate analysis showed that PSA (OR: 1.075, P < 0.001), DD (OR: 2.152, P < 0.001), Gleason score (OR: 2.904, P < 0.001), and Fib (OR: 1.706, P < 0.001) were independent risk factors for bone metastasis of Pca after adjusting for Age, BMI and other confounding factors. CONCLUSIONS: Higher platelet, D-dimer, prostate-specific antigen, Gleason score, and fibrinogen levels may predict a worse prognosis in patients with Pca. PLT, DD, and Fib, as readily available and relatively inexpensive indicators, help predict bone metastasis of Pca. It is suggested that PLT, DD and Fib may be helpful in the risk stratification of Pca.

Unraveling temporal and spatial biomarkers of epithelial-mesenchymal transition in colorectal cancer: insights into the crucial role of immunosuppressive cells.

The occurrence and progression of tumors can be established through a complex interplay among tumor cells undergoing epithelial-mesenchymal transition (EMT), invasive factors and immune cells. In this study, we employed single-cell RNA sequencing (scRNA-seq) and spatially resolved transcriptomics (ST) to evaluate the pseudotime trajectory and spatial interactive relationship between EMT-invasive malignant tumors and immune cells in primary colorectal cancer (CRC) tissues at different stages (stage I/II and stage III with tumor deposit). Our research characterized the spatiotemporal relationship among different invasive tumor programs by constructing pseudotime endpoint-EMT-invasion tumor programs (EMTPs) located at the edge of ST, utilizing evolution trajectory analysis integrated with EMT-invasion genes. Strikingly, the invasive and expansive process of tumors undergoes remarkable spatial reprogramming of regulatory and immunosuppressive cells, such as myeloid-derived suppressor cells (MDSCs), tumor-associated macrophages (TAMs), regulatory T cells (Treg), and exhausted T cells (Tex). These EMTP-adjacent cell are linked to EMT-related invasion genes, especially the C-X-C motif ligand 1 (CXCL1) and CXCL8 genes that are important for CRC prognosis. Interestingly, the EMTPs in stage I mainly produce an inflammatory margin invasive niche, while the EMTPs in stage III tissues likely produce a hypoxic pre-invasive niche. Our data demonstrate the crucial role of regulatory and immunosuppressive cells in tumor formation and progression of CRC. This study provides a framework to delineate the spatiotemporal invasive niche in CRC samples.

Prognostic Factors of Severe Pneumonia in Adult Patients: A Systematic Review.

Objectives: This systematic review aimed to identify independent prognostic factors of severe pneumonia. Methods: A systematic search was undertaken in Pubmed, Embase, and Web of Science from inception to March 2023 to find cohort studies investigating the association between prognostic factors and adverse outcomes of severe pneumonia in adult patients. The study selection process involved screening the title and abstract of articles to identify relevant studies on severe pneumonia in adult patients. Inclusion criteria included studies with a prospective or retrospective longitudinal design, investigating prognostic factors, and performing multivariate analysis. Exclusion criteria included non-English or non-Chinese studies, studies focusing on severe pneumonia in children, studies conducting only univariate analysis, and conference abstracts, reviews, and case reports. The risk of bias was assessed by the Quality In Prognosis Studies (QUIPS) tool. Results: A total of 27 published studies, including both prospective and retrospective cohort studies, were included. These studies reported on 53 different prognostic factors and covered four unique outcomes. The quality assessment indicated that 59.3% of the studies had a low risk of bias. Age, functional dependence, heart rate, and oxygen saturation/respiratory rate index were found to be associated with mortality. Additionally, various laboratory indexes, such as serum cholinesterase, albumin, and blood urea nitrogen to creatinine ratio, demonstrated either protective or risk factors for prognosis. Injury and comorbidities, including acute renal failure, chronic lung disease, and Glasgow Coma Scale, were identified as risk factors for mortality. Scoring tools like Acute Physiological and Chronic Health Evaluation (APACHE) II score, CURB-65 score, and Pneumonia Severity Index (PSI) score showed associations with mortality. Lastly, certain treatment protocols, such as vasoactive agent use, vasopressor use, and mechanical ventilation, were found to increase the risk of mortality, while invasive mechanical ventilation and the use of remdesivir and steroids had a positive impact on prognosis. These findings provide valuable insights for clinicians in predicting and managing severe pneumonia outcomes. Conclusion: This most comprehensive review identified 53 unique prognostic factors of severe pneumonia, which provided a reference for subsequent researchers to construct models to predict clinical outcomes in patients with severe pneumonia for clinical use. By identifying prognostic factors through multivariate analysis, healthcare providers can better assess the severity and prognosis of individual patients. This knowledge can aid in treatment planning, resource allocation, and determining the appropriate level of care for patients with severe pneumonia. Additionally, understanding the prognostic factors can help identify high-risk patients who may require more intensive monitoring or interventions. Overall, this study provides valuable insights that can inform clinical practice and improve patient outcomes in the management of severe pneumonia.

Delegated Proof of Stake Consensus Mechanism Based on Community Discovery and Credit Incentive.

Consensus algorithms are the core technology of a blockchain and directly affect the implementation and application of blockchain systems. Delegated proof of stake (DPoS) significantly reduces the time required for transaction verification by selecting representative nodes to generate blocks, and it has become a mainstream consensus algorithm. However, existing DPoS algorithms have issues such as "one ballot, one vote", a low degree of decentralization, and nodes performing malicious actions. To address these problems, an improved DPoS algorithm based on community discovery is designed, called CD-DPoS. First, we introduce the PageRank algorithm to improve the voting mechanism, achieving "one ballot, multiple votes", and we obtain the reputation value of each node. Second, we propose a node voting enthusiasm measurement method based on the GN algorithm. Finally, we design a comprehensive election mechanism combining node reputation values and voting enthusiasm to select secure and reliable accounting nodes. A node credit incentive mechanism is also designed to effectively motivate normal nodes and drive out malicious nodes. The experimental simulation results show that our proposed algorithm has better decentralization, malicious node eviction capabilities and higher throughput than similar methods.

Tat-P combined with GAPR1 releases Beclin1 to promote autophagy and improve Bronchopulmonary dysplasia model.

Long-term exposure to hyperoxia can leading to the bronchopulmonary dysplasia (BPD). The progression of BPD is primarily driven by the apoptosis of alveolar epithelial cells, and the regulation of autophagy has an impact on apoptosis. This study aims to investigate the therapeutic potential and underlying mechanism of an autophagy-promoting peptide (Tat-P) in ameliorating BPD. In vitro experiments demonstrated that Tat-P promoted autophagy and partially prevented apoptosis caused by exposure to hyperoxia. Further investigation into the mechanism revealed that Tat-P competitively binds to GAPR1, displacing the Beclin1 protein and thereby inhibiting the apoptosis. In vivo experiments conducted on Sprague-Dawley pups exposed to high oxygen levels demonstrated that Tat-P promoted autophagy and reduced apoptosis in lung tissues and ameliorated BPD-related phenotypes. Our findings elucidate the underlying mechanisms and effects of Tat-P in enhancing autophagy and preventing apoptosis. This study presents an approach for the prevention and treatment of BPD.

Neutrophil extracellular traps-related signature predicts the prognosis and immune infiltration in gastric cancer.

Introduction: Gastric cancer (GC) is the fifth most prevalent cancer globally, with the third highest case fatality rate. Neutrophil extracellular traps (NETs) are a reticulated structure of DNA, histones, and antimicrobial peptides produced by active neutrophils that trap pathogens. Even though NETs are associated with poorer recurrence-free survival (RFS) and overall survival (OS), the specifics of this interaction between NETs and cancer cells are yet unknown. Methods: The keywords "neutrophil extracellular traps and gastric cancer" were used in the GEO database for retrieval, and the GSE188741 dataset was selected to obtain the NETs-related gene. 27 NETs-related genes were screened by univariate Cox regression analysis (p < 0.05). 27 NETs-related genes were employed to identify and categorize NETs-subgroups of GC patients under the Consensus clustering analysis. 808 GC patients in TCGA-STAD combined with GES84437 were randomly divided into a training group (n = 403) and a test group (n = 403) at a ratio of 1:1 to validate the NETs-related signature. Results: Based on Multivariate Cox regression and LASSO regression analysis to develop a NETs-related prognosis model. We developed a very specific nomogram to improve the NETs-clinical score's usefulness. Similarly, we also performed a great result in pan-cancer study with NETs-score. Low NETs scores were linked to higher MSI-H (microsatellite instability-high), mutation load, and immune activity. The cancer stem cell (CSC) index and chemotherapeutic treatment sensitivity were also connected to the NET score. Our comprehensive analysis of NETs in GC suggests that NETs have a role in the tumor microenvironment, clinicopathological features, and prognosis. Discussion: The NETs-score risk model provides a basis for better prognosis and therapy outcomes in GC patients.

Natural killer cells contribute to 'hot' tumor regression in the allergic inflammatory environment.

Systemic immune status influences the elimination of tumor cells. However, it remains unclear how chronic inflammation in allergic diseases affects the tumor microenvironment and tumorigenesis. To investigate tumor progression in a state of heightened allergic inflammation, we established a mouse model of allergic inflammation. We used house dust mite extract to induce a hyper-reactive systemic immune response. Additionally, we subcutaneously inoculated two types of cancer cells (CT26 and 4T1 tumors). We conducted immune profiling of the ex-vivo tumor mass using multicolor flow cytometry staining and performed dynamic analysis of peripheral cytokines to explore the significant relationship between the development of allergic inflammation and tumorigenesis. We found that mice in a state of allergic inflammation were more susceptible to developing tumors. Interestingly, the growth of T cell-inflamed was inhibited in the allergic state, while growth of non-T cell-inflamed was promoted. Further research revealed that natural killer (NK) cells with enhanced tumor-killing or immune-regulating abilities were more active in " hot " tumors. Inhibiting NK cell activity can partially alleviate the impact of allergic inflammation on tumor growth. In summary, our results suggest that NK cells play significant role in suppressing tumor growth in an allergic inflammation mouse model. This phenomenon seems to be closely linked to both the inherent characteristics of the tumor and its interaction with the immune system. The innate immune system can be mobilized to synergize with the adaptive immune system to inhibit tumor growth, which opens a new way for a tumor immunotherapy.

Effects of genetic polymorphisms of LINC-PINT gene on liver cancer susceptibility in the Chinese Han population.

Objective: Liver cancer (LC) is the most common cause of cancer mortality. This study aimed to explore the impact of LINC-PINT polymorphisms on LC. Materials & methods: The authors recruited 591 LC patients and 592 healthy controls. The association between LINC-PINT polymorphisms and susceptibility to LC was determined by logistic regression analysis. Results: The authors found that rs157916 and rs16873842 reduced susceptibility to LC. rs157916 decreased LC risk in patients aged <55 years, nondrinkers and those with BMI <24. rs16873842 had a protective role against LC in patients aged ≥55 years, women, nonsmokers and those with BMI ≥24. rs7801029 decreased LC risk in patients with BMI <24. rs28662387 increased LC risk in women. Conclusion: LINC-PINT polymorphisms exert a protective effect against LC.

Tribological Properties of Solid Lubricant WS2 in Dimples on the Cylinder of Diesel Engine at High Temperature.

Solid lubricant WS2 was encapsulated in the dimples on the cylinder surface by the hot-pressing method. The tribological and releasing performance of the as-prepared sample were investigated under high temperature conditions. The results indicate that, compared with the original cylinder, WS2 in the dimples exhibited better tribological properties at high temperature than at room temperature. The average friction coefficients of the as-prepared samples were about 0.13 and 0.15 at high temperature and room temperature, respectively, which were 27.8% and 16.7% lower than that of the original cylinder, respectively. Moreover, compared with the original cylinder, the anti-adhesion time of the as-prepared sample increased 2.3-fold. Additionally, the reduced viscosity of the lubricating oil caused by high temperature accelerated the erosion effect and release rate of the solid lubricant in the dimples. Thus, the polar additives in the lubricating oil and the chemical reactions between the cylinder substrates and solid lubricants that WS2 released from the dimples are the main factors in friction reduction. This study provides some guidance for anti-friction design of cylinders under high temperature conditions.

Contribution of PNPLA3 gene polymorphisms to hepatocellular carcinoma susceptibility in the Chinese Han population.

OBJECTIVES: The purpose of this study was to investigate the association of PNPLA3 single nucleotide polymorphisms (SNPs) (rs738409 C > G, rs3747207 G > A, rs4823173 G > A, and rs2896019 T > G) with hepatocellular carcinoma (HCC) susceptibility. METHODS: This case-control study included 484 HCC patients and 487 controls. Logistic regression analysis was performed to study the associations of PNPLA3 gene polymorphisms with HCC susceptibility, and odds ratios with their corresponding 95% confidence intervals were calculated to evaluate these correlations. RESULTS: In the overall analysis, we found that the G allele (OR = 1.25, 95% CI = 1.04-1.50, p = 0.018, false discovery rate (FDR)-p = 0.035) and GG genotype (OR = 1.59, 95% CI = 1.06-2.39, p = 0.024, FDR-p = 0.048) of rs2896019 were significantly associated with increased HCC susceptibility. In stratified analysis, we found that all four SNPs were related to increased HCC susceptibility in subjects aged > 55 years. In haplotype analysis, the GAAG haplotype was significantly associated with increased HCC susceptibility (OR = 1.25, 95% CI = 1.03-1.53, p = 0.023, FDR-p = 0.046). Besides, we noticed that rs738409 was significantly correlated with alpha-fetoprotein (AFP) (p = 0.007), and HCC patients with the GG genotype had a higher level of AFP. CONCLUSIONS: Our study suggested that PNPLA3-rs2896019 was significantly associated with an increased susceptibility to HCC.

Clinical progression, pathological characteristics, and radiological findings in children with diffuse leptomeningeal glioneuronal tumors: A systematic review.

Background: Diffuse leptomeningeal glioneuronal tumors are rare leptomeningeal neoplasms composed of oligodendrocyte-like cells characterized by neuronal differentiation and a lack of isocitrate dehydrogenase gene mutation. Purpose: We aimed to analyze the clinical progression, pathological characteristics, and radiological findings of diffuse leptomeningeal glioneuronal tumors in children, as well as the relevance of clinico-radiological data. Data Sources: We searched MEDLINE, PubMed, and Web of Science to identify case reports, original articles, and review articles discussing diffuse leptomeningeal glioneuronal tumors published between 2000 and 2021. Study Selection: The analysis included 145 pediatric patients from 43 previous studies. Data Analysis: Data regarding patient pathology, MRI manifestations, clinical symptoms, and progression were collected. The relationship between imaging classification and pathological findings was using chi-square tests. Overall survival was analyzed using Kaplan-Meier curves. Data Synthesis: Parenchymal tumors were mainly located in the intramedullary areas of the cervical and thoracic spine, and patients which such tumors were prone to 1p-deletion (χ2 = 4.77, p=0.03) and KIAA1549-BRAF fusion (χ2 = 12.17, p<0.001). The median survival time was 173 months, and the survival curve fell significantly before 72 months. Parenchymal tumor location was associated with overall survival (p=0.03), patients with KIAA 1549-BRAF (+) and treated with chemotherapy exhibited a better clinical course (p<0.001). Limitations: The analysis included case reports rather than consecutively treated patients due to the rarity of diffuse leptomeningeal glioneuronal tumors, which may have introduced a bias. Conclusions: Early integration of clinical, pathological, and radiological findings is necessary for appropriate management of this tumor, as this may enable early treatment and improve prognosis.

Design of a Variable Stiffness Gecko-Inspired Foot and Adhesion Performance Test on Flexible Surface.

Adhesion robots have broad application prospects in the field of spacecraft inspection, repair, and maintenance, but the stable adhesion and climbing on the flexible surface covering the spacecraft has not been achieved. The flexible surface is easily deformed when subjected to external force, which makes it difficult to ensure a sufficient contact area and then detach from it. To achieve stable attachment and easy detachment on the flexible surface under microgravity, an adhesion model is established based on the applied adhesive material, and the relationship between peeling force and the rigidity of the base material, peeling angle, and working surface stiffness is obtained. Combined with the characteristics of variable stiffness structure, the adhesion and detachment force of the foot is asymmetric. Inspired by the adhesion-detachment mechanism of the foot of the gecko, an active adhesion-detachment control compliant mechanism is designed to achieve the stable attachment and safe detachment of the foot on the flexible surface and to adapt to surfaces with different rigidity. The experimental results indicate that a maximum normal adhesion force of 7.66 N can be generated when fully extended, and the safe detachment is achieved without external force on a flexible surface. Finally, an air floating platform is used to build a microgravity environment, and the crawling experiment of a gecko-inspired robot on a flexible surface under microgravity is completed. The experimental results show that the gecko-inspired foot with variable stiffness can satisfy the requirements of stable crawling on flexible surfaces.

Model development to predict central lymph node metastasis in cN0 papillary thyroid microcarcinoma by machine learning.

Background: Whether prophylactic central lymph node dissection is necessary for cN0 papillary thyroid microcarcinoma (PTMC) patients remains highly debatable. Surgeons desperately need a way to help with surgical decision-making. While traditional predictive models can better explain changes in variables, machine learning (ML) models may have better predictive performance. This study aims to develop models for predicting the risk of central lymph node metastasis (CLNM) by utilizing ML algorithms. Methods: The clinical records of 1,121 patients with cN0 PTMC who underwent initial thyroid resection at our hospital between January 2014 and December 2018 were retrospectively retrieved. Univariate and multivariate analyses were performed to examine risk factors associated with CLNM. Six ML algorithms for predicting CLNM were established and internally validated. Indices including the area under the receiver operating characteristic (AUROC), sensitivity, specificity, accuracy, positive predictive value (PPV), and negative predictive value (NPV) were calculated to test the performance of the model. Results: The results showed 33.5% (376 out of 1,121) of patients had CLNM. In multivariate logistic regression (LR) analyses, gender, age, tumor size, multifocal lesions, and extrathyroidal extension (ETE) were all independent predictors of CLNM. The AUROC predictive values of the six ML algorithms were between 0.664 and 0.794, with the random forest (RF) model performing the best with an AUROC of 0.794. Therefore, we used the RF model and uploaded the results to a web-based risk calculator to predict an individual's probability of CLNM (https://xijing-thyroid.shinyapps.io/ptmc_clnm). Conclusions: Developing predictive models of CLNM in cN0 PTMC patients using the ML algorithm is a feasible method. Our online risk calculator based on the RF model may be a useful tool for surgical decisions.

Dermatophagoides pteronyssinus allergen Der p 22: Cloning, expression, IgE-binding in asthmatic children, and immunogenicity.

BACKGROUND: Dust mite extract contains multiple components that, while useful in clinical allergy diagnosis and treatment, can cause serious side effects. Defining components of dust mite extract is important their contributions to allergic disease. This study aimed to characterize a novel dust mite allergen, Der p 22. METHODS: We amplified the cDNA encoding Der p 22 from total RNA of the mite Dermatophagoides pteronyssinus, and inserted it into an expression construct for transformation to competent cells. Purified recombinant (r) Der p 22 was tested for IgE-binding reactivity in sera obtained from children with allergic asthma by the Affiliated Wuxi Children's Hospital of Nanjing Medical University (Jiangsu, China). rDer p 22 also was used to challenge BALB/c mice to assess effects on T helper cells and cytokine levels and applied to cultured lung epithelial cells to evaluate apoptosis and cytokine secretion. RESULTS: rDer p 22 bound to IgE in 93.75% of sera from pediatric allergic asthma patients. Mice challenged with rDer p 22 had altered Th1/Th2 ratios in spleen and lymph, and lower levels of cytokines IFN-γ but higher levels of IL-4 and IL-10 in alveolar lavage fluid compared with controls (p < .05). Cultured lung epithelial cells had greater apoptosis rates and exhibited higher levels of IL-6, IL-8, and GM-CSF when treated with rDer p 22 compared with control treatment (p < .05). CONCLUSIONS: Recombinant Der p 22 exhibited high IgE-binding rates in allergic children, indicating the activity of the recombinant protein and suggesting this novel allergen may be appropriate for inclusion in an allergy diagnostic workup. This finding is supported by in vitro and mouse in vivo studies showing rDer p 22 induced strong allergenic reactivity and apoptosis.