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Abstract This paper primarily explores the modeling method of n-level complex helical structures with coal mining machine cables as the research object. The paper first elaborately introduces the modeling method of n-level helix curves based on parametric equations and coordinate transformations, and compensates for the n-level helix curves with corrected pitch, which can obtain more accurate n-level helix curves and improve the accuracy of n-level helix curves modeling. Subsequently, based on this high-precision n-level helix curves modeling method, the paper elaborates on the method of solving pitch and twisting radius of multi-layer helical structure. Calculation scripts were written based on the above methods, which can be used to batch calculate the twisting radius and pitch of each layer structure in multi-layer structures when satisfying the conditions of in-layer tangency, inter-layer tangency, and extrusion deformation, and retain the actual results through logical judgment. Then, based on the above two methods, the paper developed a modeling method for braided structures based on piecewise functions containing fifth-order polynomials, which can effectively avoid the problem of insufficiently dense arrangement of braided lines and easy interference in traditional methods. Finally, a set of modeling tools was developed using C# and Python in Grasshopper to implement the modeling algorithm. Taking the MCPT-1.9/3.3 3120 + 170 + 4 * 10 coal mining machine cable as an example. The cable was modeled using both the method proposed in this paper and the traditional method. Comparative data shows that the method proposed in this paper can reduce errors by 3.31E6 times in the second-level and above helical structures. In addition this paper compares the standard line length, measured line length, and the line length established by the proposed model, showing that the relative errors are both less than 0.1941%. This paper provides a new, systematic, high-precision, and full-process cable modeling method, in which all parameters except the process parameters are accurately solved by equations. It lays a theoretical foundation for the high-precision simulation and intelligent sensing cables, which is of great significance for improving the safety, stability, and efficient development of the coal mining industry. The research results of the paper can not only be applied to the modeling of coal mining machine cables but also can be extended to the modeling of other complex multi-layer helical structures.

Abstract Celiac Disease (CD) is a primary malabsorption syndrome resulting from the interplay of genetic, immune, and dietary factors. CD negatively impacts daily activities and may lead to conditions such as osteoporosis, malignancies in the small intestine, ulcerative jejunitis, and enteritis, ultimately causing severe malnutrition. Therefore, an effective and rapid differentiation between healthy individuals and those with celiac disease is crucial for early diagnosis and treatment. This study utilizes Raman spectroscopy combined with deep learning models to achieve a non-invasive, rapid, and accurate diagnostic method for celiac disease and healthy controls. A total of 59 plasma samples, comprising 29 celiac disease cases and 30 healthy controls, were collected for experimental purposes. Convolutional Neural Network (CNN), Multi-Scale Convolutional Neural Network (MCNN), Residual Network (ResNet), and Deep Residual Shrinkage Network (DRSN) classification models were employed. The accuracy rates for these models were found to be 86.67%, 90.76%, 86.67% and 95.00%, respectively. Comparative validation results revealed that the DRSN model exhibited the best performance, with an AUC value and accuracy of 97.60% and 95%, respectively. This confirms the superiority of Raman spectroscopy combined with deep learning in the diagnosis of celiac disease.

Abstract The soil environment plays an important role in urban ecosystems. To study the heavy metal contamination of soil in Beilun District, Ningbo, we collected soil samples from 60 points in urban and peri-urban areas of Beilun District and analyzed the spatiotemporal variation and sources of heavy metal pollution in various land-use types. The results shown that the heavy metal contents in 2015 and 2022 were higher than the background soil values of Ningbo city, and there was an accumulation of heavy metals over these 7 years. The contents of heavy metals in green belts and woodland in 2022 were higher than those in 2015, while there was no significant change in agricultural land. The heavy metal contents in both years were mainly in the order green belts > agricultural land > woodland. The spatiotemporal distribution of heavy metal content showed that heavy metal pollution in Beilun District was concentrated in five industrial areas, and there was a trend toward the disappearance of highly polluted points. But the single-factor pollution index, pollution load index (PLI), and geoaccumulation index (Igeo) indicated that there was no significant heavy metal pollution in Beilun District, and individual elements at specific points showed slight pollution. The source analysis results showed that the main source of Hg is chemical, As is mainly derived from agricultural, Cr, Ni and Cu are mainly derived from natural, the main sources of Zn and Cd are electroplating and machinery activities, and the main source of Pb is traffic. These results specify a reference for future investigation on urban soil heavy metals, and the source apportionment results provide a scientific foundation for subsequent soil heavy metal pollution treatment.

Abstract Cryptosporidiosis is a worldwide zoonotic disease. Oxymatrine, an alkaloid extracted and isolated from the plant bitter ginseng, has been reported to have therapeutic effects on cryptosporidiosis. However, the underlying mechanism of its action remains unclear. In this study, we utilized network pharmacology and experimental validation to investigate the mechanism of oxymatrine in the treatment of cryptosporidiosis. First, the potential targets of drugs and diseases were predicted by TCMSP, Gene Cards, and other databases. Following the intersection of drug-disease targets, the DAVID database was used to implement the enrichment analysis of GO functions and KEGG pathways, and then the network diagram of "intersected target-KEGG" relationship was constructed. Autodock 4.2.6 software was used to carry out the molecular docking of core targets to drug components. Based on the establishment of a mouse model of cryptosporidiosis, the validity of the targets in the TNF/NF-κB signaling pathway was confirmed using Western blot analysis and Quantitative Rea-ltime-PCR. A total of 41 intersectional targets of oxymatrine and Cryptosporidium were generated from the results, and five core targets were screened out by network analysis, including RELA, AKT1, ESR1, TNF, and CASP3. The enrichment analysis showed that oxymatrine could regulate multiple gene targets, mediate TNF, Apoptpsis, IL-17, NF-κB and other signaling pathways. Molecular docking experiments revealed that oxymatrine was tightly bound to core targets with stable conformation. Furthermore, we found through animal experiments that oxymatrine could regulate the mRNA and protein expression of IL-6, NF-κB, and TNF-α in the intestinal tissues of post-infected mice through the TNF/NF-κB signaling pathway. Therefore, it can be concluded that oxymatrine can regulate the inflammatory factors TNF-α, NF-κB, and IL-6 through the TNF/NF-κB signaling pathway for the treatment of cryptosporidiosis. This prediction has also been validated by network pharmacology and animal experiments.

Abstract Background Metastasis renal cell carcinoma (RCC) patients have extremely high mortality rate. A predictive model for RCC micrometastasis based on pathomics could be beneficial for clinicians to make treatment decisions. Methods A total of 895 formalin-fixed and paraffin-embedded whole slide images (WSIs) derived from three cohorts, including Shanghai General Hospital (SGH), Clinical Proteomic Tumor Analysis Consortium (CPTAC) and Cancer Genome Atlas (TCGA) cohorts, and another 588 frozen section WSIs from TCGA dataset were involved in the study. The deep learning-based strategy for predicting lymphatic metastasis was developed based on WSIs through clustering-constrained-attention multiple-instance learning method and verified among the three cohorts. The performance of the model was further verified in frozen-pathological sections. In addition, the model was also tested the prognosis prediction of patients with RCC in multi-source patient cohorts. Results The AUC of the lymphatic metastasis prediction performance was 0.836, 0.865 and 0.812 in TCGA, SGH and CPTAC cohorts, respectively. The performance on frozen section WSIs was with the AUC of 0.801. Patients with high deep learning-based prediction of lymph node metastasis values showed worse prognosis. Conclusions In this study, we developed and verified a deep learning-based strategy for predicting lymphatic metastasis from primary RCC WSIs, which could be applied in frozen-pathological sections and act as a prognostic factor for RCC to distinguished patients with worse survival outcomes.

Abstract The aim of this study was to create and validate a ten-item Domain-specific Grit Scale for College Athletic Students (DGSCAS) to assess the level of grit among college athletic students. College athletic students from a single independent college located in a northern city in China (526 participants at time 1 and 589 participants at time 2) were assessed according to the scale. Various analyses were conducted in this study, including exploratory factor analysis (EFA), confirmatory factor analysis (CFA), and measurement invariance analysis across different sex and birthplaces. The results of the EFA revealed two factors: consistency of interests and perseverance of effort. The CFA results demonstrated acceptable fit indices (x 2 = 160.048, df = 34, x 2 /df = 4.707, CFI = 0.983, TLI = 0.978, SRMR = 0.021, and RMSEA = 0.079). The scale exhibited satisfactory convergent validity and discriminant validity. The significant correlation of these factors with the Grit scale provided strong evidence of criterion-related validity. Measurement invariance analysis indicated that the scale performed consistently across different sex and birthplaces. Three limitations and corresponding recommendations were discussed, including sample heterogeneity, the lack of a unified test result as a criterion for predictive validity, and the cross-sectional design of the study. In conclusion, the DGSCAS is a practical and validated instrument that can be used to assess the level of grit among college athletic students in an educational context.

Abstract Lung diseases globally impose a significant pathological burden and mortality rate, particularly the differential diagnosis between adenocarcinoma, squamous cell carcinoma, and small cell lung carcinoma, which is paramount in determining optimal treatment strategies and improving clinical prognoses. Faced with the challenge of improving diagnostic precision and stability, this study has developed an innovative deep learning-based model. This model employs a Feature Pyramid Network (FPN) and Squeeze-and-Excitation (SE) modules combined with a Residual Network (ResNet18), to enhance the processing capabilities for complex images and conduct multi-scale analysis of each channel's importance in classifying lung cancer. Moreover, the performance of the model is further enhanced by employing knowledge distillation from larger teacher models to more compact student models. Subjected to rigorous five-fold cross-validation, our model outperforms existing models on all performance metrics, exhibiting exceptional diagnostic accuracy. Ablation studies on various model components have verified that each addition effectively improves model performance, achieving an average accuracy of 98.84% and a Matthews Correlation Coefficient (MCC) of 98.83%. Collectively, the results indicate that our model significantly improves the accuracy of disease diagnosis, providing physicians with more precise clinical decision-making support.

Abstract. Background:. The goal of the assisted reproductive treatment is to transfer one euploid blastocyst and to help infertile women giving birth one healthy neonate. Some algorithms have been used to assess the ploidy status of embryos derived from couples with normal chromosome, who subjected to preimplantation genetic testing for aneuploidy (PGT-A) treatment. However, it is currently unknown whether artificial intelligence model can be used to assess the euploidy status of blastocyst derived from populations with chromosomal rearrangement. Methods:. From February 2020 to May 2021, we collected the whole raw time-lapse videos at multiple focal planes from in vitro cultured embryos, the clinical information of couples, and the comprehensive chromosome screening results of those blastocysts that had received PGT treatment. Initially, we developed a novel deep learning model called the Attentive Multi-Focus Selection Network (AMSNet) to analyze time-lapse videos in real time and predict blastocyst formation. Building upon AMSNet, we integrated additional clinically predictive variables and created a second deep learning model, the Attentive Multi-Focus Video and Clinical Information Fusion Network (AMCFNet), to assess the euploidy status of embryos. The efficacy of the AMCFNet was further tested in embryos with parental chromosomal rearrangements. The receiver operating characteristic curve (ROC) was used to evaluate the superiority of the model. Results:. A total of 4112 embryos with complete time-lapse videos were enrolled for the blastocyst formation prediction task, and 1422 qualified blastocysts received PGT-A (n = 589) or PGT for chromosomal structural rearrangement (PGT-SR, n = 833) were enrolled for the euploidy assessment task in this study. The AMSNet model using seven focal raw time-lapse videos has the best real-time accuracy. The real-time accuracy for AMSNet to predict blastocyst formation reached above 70% on the day 2 of embryo culture, and then increased to 80% on the day 4 of embryo culture. Combing with 4 clinical features of couples, the AUC of AMCFNet with 7 focal points increased to 0.729 in blastocysts derived from couples with chromosomal rearrangement. Conclusion:. Integrating seven focal raw time-lapse images of embryos and parental clinical information, AMCFNet model have the capability of assessing euploidy status in blastocysts derived from couples with chromosomal rearrangement.

Abstract Background Diagnosis of colorectal cancer (CRC) during early stages can greatly improve patient outcome. Although technical advances in the field of genomics and proteomics have identified a number of candidate biomarkers for non-invasive screening and diagnosis, developing more sensitive and specific methods with improved cost-effectiveness and patient compliance has tremendous potential to help combat the disease. Methods We enrolled three cohorts of 479 subjects, including 226 CRC cases, 197 healthy controls, and 56 advanced precancerous lesions (APC). In the discovery cohort, we used quantitative mass spectrometry to measure the expression profile of plasma proteins and applied machine-learning to select candidate proteins. We then developed a targeted mass spectrometry assay to measure plasma concentrations of seven proteins and a logistic regression classifier to distinguish CRC from healthy subjects. The classifier was further validated using two independent cohorts. Results The seven-protein panel consisted of leucine rich alpha-2-glycoprotein 1 (LRG1), complement C9 (C9), insulin-like growth factor binding protein 2 (IGFBP2), carnosine dipeptidase 1 (CNDP1), inter-alpha-trypsin inhibitor heavy chain 3 (ITIH3), serpin family A member 1 (SERPINA1), and alpha-1-acid glycoprotein 1 (ORM1). The panel classified CRC and healthy subjects with high accuracy, since the area under curve (AUC) of the training and testing cohort reached 0.954 and 0.958. The AUC of the two independent validation cohorts was 0.905 and 0.909. In one validation cohort, the panel had an overall sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of 89.9%, 81.8%, 89.2%, and 82.9%, respectively. In another blinded validation cohort, the panel classified CRC from healthy subjects with a sensitivity of 81.5%, specificity of 97.9%, and overall accuracy of 92.0%. Finally, the panel was able to detect APC with a sensitivity of 49%. Conclusions This seven-protein classifier is a clear improvement compared to previously published blood-based protein biomarkers for detecting early-stage CRC, and is of translational potential to develop into a clinically useful assay.

Abstract Lumbar disc herniation (LDH) is a clinically common degenerative disease of the spine, and spinal–pelvic sagittal balance and paravertebral muscle degeneration have been a research focus in recent years. To explore the relationship between the degeneration of paravertebral muscle and the changes in the spinal–pelvic sagittal parameters in LDH patients, 105 LDH patients (experimental group) and 63 healthy volunteers (control group) hospitalized in Ordos Central Hospital from January 2020 and January 2023 were included as study subjects. All the patients underwent lumbar magnetic resonance imaging and spinal X-ray using uniform criteria. The correlation between the paravertebral muscle and sagittal–pelvic sagittal parameters of the patients with LDH was obtained from two imaging examinations, and the data were organized and grouped to explore the correlation between these parameters. No significant difference in general data existed between the groups (P > 0.05). In the L4/5 LDH patients group, the ratio of fat infiltration (FIR) in the healthy side [multifidus (MF) and erector spinae (ES)] was negatively correlated with the lumbar lordosis (LL) (r = −0.461, r = −0.486, P

Background Biochar amendments enhance crop productivity and improve agricultural quality. To date, studies on the correlation between different amounts of biochar in pakchoi (Brassica campestris L.) quality and rhizosphere soil microorganisms are limited, especially in weakly alkaline soils. The experiment was set up to explore the effect of different concentrations of biochar on vegetable quality and the correlation between the index of quality and soil bacterial community structure changes. Methods The soil was treated in the following ways via pot culture: the blank control (CK) without biochar added and with biochar at different concentrations of 1% (T1), 3% (T2), 5% (T3), and 7% (T4). Here, we investigatedthe synergistic effect of biochar on the growth and quality of pakchoi, soil enzymatic activities, and soil nutrients. Microbial communities from pakchoi rhizosphere soil were analyzed by Illumina MiSeq. Results The results revealed that adding 3% biochar significantly increased plant height, root length, and dry weight of pakchoi and increased the contents of soluble sugars, soluble proteins, Vitamin C (VC), cellulose, and reduced nitrate content in pakchoi leaves. Meanwhile, soil enzyme activities and available nutrient content in rhizosphere soil increased. This study demonstrated that the the microbial community structure of bacteria in pakchoi rhizosphere soil was changed by applying more than 3% biochar. Among the relatively abundant dominant phyla, Gemmatimonadetes, Anaerolineae, Deltaproteobacteria and Verrucomicrobiae were reduced, and Alphaproteobacteria, Gammaproteobacteria, Bacteroidia, and Acidimicrobiia relative abundance increased. Furthermore, adding 3% biochar reduced the relative abundance of Gemmatimonas and increased the relative abundances of Ilumatobacter, Luteolibacter, Lysobacter, Arthrobacter, and Mesorhizobium. The nitrate content was positively correlated with the abundance of Gemmatimonadetes, and the nitrate content was significantly negatively correlated with the relative abundance of Ilumatobacter. Carbohydrate transport and metabolism in the rhizosphere soil of pakchoi decreased, and lipid transport and metabolism increased after biochar application. Conclusion Overall, our results indicated that applying biochar improved soil physicochemical states and plant nutrient absorption, and affected the abundance of dominant bacterial groups (e.g., Gemmatimonadetes and Ilumatobacter), these were the main factors to increase pakchoi growth and promote quality of pakchoi. Therefore, considering the growth, quality of pakchoi, and soil environment, the effect of using 3% biochar is better.

Abstract Even after debulking surgery combined with chemotherapy or new adjuvant chemotherapy paired with internal surgery, the average year of disease free survival in advanced ovarian cancer was approximately 1.7 years1. The development of a molecular predictor of early recurrence would allow for the identification of ovarian cancer (OC) patients with high risk of relapse. The Ovarian Cancer Disease Free Survival Predictor (ODFSP), a predictive model constructed from a special set of 1580 OC tumors in which gene expression was assessed using both microarray and sequencing platforms, was created by our team. To construct gene expression barcodes that were resistant to biases caused by disparate profiling platforms and batch effects, we employed a meta-analysis methodology that was based on the binary gene pair technique. We demonstrate that ODFSP is a reliable single-sample predictor of early recurrence (1 year or less) using the largest pool of OC transcriptome data sets available to date. The ODFSP model showed significantly high prognostic value for binary recurrence prediction unaffected by clinicopathologic factors, with a meta-estimate of the area under the receiver operating curve of 0.64 (P = 4.6E-05) and a D-index (robust hazard ratio) of 1.67 (P = 9.2E-06), respectively. GO analysis of ODFSP’s 2040 gene pairs (collapsed to 886 distinct genes) revealed the involvement in small molecular catabolic process, sulfur compound metabolic process, organic acid catabolic process, sulfur compound biosynthetic process, glycosaminoglycan metabolic process and aminometabolic process. Kyoto encyclopedia of genes and genomes pathway analysis of ODFSP’s signature genes identified prominent pathways that included cAMP signaling pathway and FoxO signaling pathway. By identifying individuals who might benefit from a more aggressive treatment plan or enrolment in a clinical trial but who will not benefit from standard surgery or chemotherapy, ODFSP could help with treatment decisions.

Objective: This study was to investigate whether annexin A7 (AnnexinA7, ANXA7) and its co-related protein tumor celldeath domain silencer [suppressor of death domains (SODD)] regulates the migratory phenotype of liver cancer cells.Materials and Methods: In this experimental study, expression of ANXA7 in Hca-P cells, PANXA7 downregulatedcells and PANXA7 unrelated sequence cells was detected by real-time quantitative polymerase chainreaction (PCR) at mRNA level and western blotting at protein level. Transwell migration and invasion assayswere performed to determine the migratory phenotype.Results: After inhibition of ANXA7 expression, expression of SODD protein was also significantly decreased (P

Abstract Background The coexistence of two myositis-specific autoantibodies (MSA) is considered extremely rare. We describe three patients with both anti-signal recognition particle (SRP) antibodies and another MSA in serum. Methods We performed a retrospective clinical data collection and follow-up studies of the clinical manifestations and treatment outcome of three patients positive with anti-SRP antibodies and other MSAs. IgG antibodies against MSAs were detected using commercial line immunoblot assay. Results The tests of MSA showed positive result of anti-SRP antibodies and another one MSA including anti-TIF1-γ, anti-Jo1, or anti-EJ antibodies, respectively. The proximal muscle weakness appeared in 2 patients; interstitial lung disease presented in 2 patients. The serum CK level was elevated in 1 patient. The muscle biopsy showed necrotizing myopathy in 1 patient and deposition of membrane attack complex on scattered myofibers in the other one patient. One of the two patients with interstitial lung disease died because of respiratory failure. One patient had completely improved and the other one showed partial remission after immunosuppressive therapy. Conclusions The patients with anti-SRP antibodies co-occurred with the other MSA may have various clinical characteristics. The clinicopathological phenotypes of these patients seem to be mainly caused by one of the MSAs, namely the responsible antibody.

IntroductionNon-steroidal anti-inflammatory drugs (NSAIDs) are currently the most widely used anti-inflammatory medications, but their long-term use can cause damage to the gastrointestinal tract(GIT). One of the risk factors for GIT injury is exposure to a high-altitude hypoxic environment, which can lead to damage to the intestinal mucosal barrier. Taking NSAIDs in a high-altitude hypoxic environment can exacerbate GIT injury and impact gut microbiota. The aim of this study is to investigate the mechanisms by which resveratrol (RSV) intervention alleviates NSAID-induced intestinal injury in a high-altitude hypoxic environment, as well as its role in regulating gut microbiota.MethodsAspirin was administered orally to rats to construct a rat model of intestinal injury induced by NSAIDs. Following the induction of intestinal injury, rats were administered RSV by gavage, and the expression levels of TLR4, NF-κB,IκB as well as Zonula Occludens-1 (ZO-1) and Occludin proteins in the different treatment groups were assessed via Western blot. Furthermore, the expression of the inflammatory factors IL-10, IL-1β, and TNF-α was evaluated using Elisa.16sRNA sequencing was employed to investigate alterations in the gut microbiota.ResultsThe HCk group showed elevated expression of TLR4/NF-κB/IκB pathway proteins, increased expression of pro-inflammatory factors IL-1β and TNF-α, decreased expression of the anti-inflammatory factor IL-10, and expression of intestinal mucosal barrier proteins ZO-1 and Occludin. The administration of NSAIDs drugs in the plateau hypoxic environment exacerbates intestinal inflammation and damage to the intestinal mucosal barrier. After treatment with RSV intervention, the expression of TLR4/NF-κB/IκB signaling pathway proteins would be reduced, thereby lowering the expression of inflammatory factors in the HAsp group. The results of HE staining directly show the damage to the intestines and the repair of intestinal mucosa after RSV intervention. 16sRNA sequencing results show significant differences (PConclusionResveratrol can attenuate intestinal damage caused by the administration of NSAIDs at high altitude in hypoxic environments by modulating the TLR4/NF-κB/IκB signaling pathway and gut microbiota composition.

BackgroundTalent transfer (TT) program is an appropriate approach to address the talent gap evident in specific sports activities, while little is known about the injury characteristics of snowboarding athletes involved in the TT program.ObjectiveTo determine the epidemiology of injuries among snowboarders involved in the TT program.MethodsA total of 244 athletes who were not previously engaged in winter sports were selected for training in snowboarding that lasted for 109 days. The injuries and at-risk exposures (A-Es) data were recorded by physicians. Injury rates (IRs), incidence rate ratios (IRRs), and injury proportion ratios (IPRs) were calculated and compared by sex and age groups.ResultsThe overall and time loss (TL) IR were 32.4/1000 A-Es and 12.2/1000 A-Es respectively. The overall and non-time loss (NTL) IRR were higher for female athletes than for male athletes. Additionally, the overall IRR and TL-IRR for female athletes were higher in those athletes who aged ≤15 years old. Over 93% of TL injuries resulted in participation restriction time of ≤7 days (male athletes, 93.94%; female athletes, 94.10%). Trunk (28.43%), knee joints (21.33%), and hand/wrist (16.53%) were found as the common sites of injury in both female and male athletes. The most frequent type of injury was contusion (male athletes: 53.00%, female athletes: 59.10%) resulted from ground/apparatus contact (male athletes: 75.10%, female athletes: 75.20%).ConclusionThe risk injury among snowboarding athletes involved in the TT program during the first snow season training was found noticeable, especially for younger female athletes. The high incidence of ground/apparatus contact-related injuries suggested the necessity of specifically designed training programs and braces for snowboarding athletes involved in the TT program.

PurposeGiven the unique features of the liver, it is necessary to combine immunotherapy with other therapies to improve its efficacy in patients of advanced cancer with liver metastases (LM). High-intensity focused ultrasound (HIFU) ablation is now widely used in clinical practice and can enhanced immune benefits. The study is intended to prospectively evaluate the safety and clinical feasibility of HIFU ablation in combination with systemic immunotherapy for patients with liver metastases.MethodsThe study enrolled 14 patients with LM who received ultrasound-guided HIFU ablation combined with immune checkpoint inhibitors (ICIs) such as anti-programmed cell death protein 1 (anti-PD-1 agents manufactured in China) at Mianyang Central Hospital. Patients were followed up for adverse events (AEs) during the trial, using the CommonTerminology Criteria for Adverse Events v5.0(CTCAE v5.0) as the standard. Tumour response after treatment was assessed using computerized tomography.ResultsThe 14 patients (age range, 35-84 years) underwent HIFU ablation at 19 metastatic sites and systemic immunotherapy. The mean lesion volume was 179.9 cm3 (maximum: 733.1 cm3). Median follow-up for this trial was 9 months (range: 3-21) months. The study is clinically feasible and acceptable to patients.ConclusionThis prospective study confirmed that HIFU combined with immunotherapy is clinically feasible and safe for treating liver metastases.

Shearer cables, subjected to large deformations and exposed to harsh working conditions during frequent back-and-forth movements, pose difficulties in achieving comprehensive mechanical performance and extended fatigue life. This study addresses parametric modeling challenges related to determining tangency within and between layers, recursively generating spiral curves from the (n-1)-th level to the n-th level, and constructing irregular surfaces for insulation and sheath. Investigating tensile and bending properties, the research explores the impact of varying pitch diameter ratios at different stranding levels, stranding directions, and monofilaments on mechanical performance across scales. The results reveal a nonlinear increase in stress in power and control conductors with growing pitch diameter ratios. The optimal combination is determined as a pitch diameter ratio of 6 for cabling, 5 for the control conductor, and 14 for the power conductor. The predicted fatigue life of the improved cable by Ncode aligns with bending test results, demonstrating functionality up to 15.12e4 cycles. Stress distribution in parallel stranding is lower and more even, tending to scatter. Conversely, counter stranding experiences relatively higher stress, ensuring a more stable structure. While maintaining a constant effective conductor cross-sectional area, finer monofilaments result in higher cross-sectional filling ratios, enhancing tensile and bending performance.

Off-the-shelf immunotherapeutics that suppress tumor growth and provide durable protection against relapse could enhance cancer treatment. We report preclinical studies on a CD33 x CD3 bivalent bispecific diabody, AMV564, that not only suppresses tumor growth, but also facilitates memory responses in a mouse model of acute myelogenous leukemia (AML). Mechanistically, a single 5-day treatment with AMV564 seems to reduce tumor burden by redirection of T cells, providing a time window for allogeneic or other T cells that innately recognize tumor antigens to become activated and proliferate. When the concentration of bispecific becomes negligible, the effector: target ratio has also shifted, and these activated T cells mediate long-term tumor control. To test the efficacy of AMV564 in vivo, we generated a CD33+ MOLM13CG bioluminescent human cell line and optimized conditions needed to control these cells for 62 days in vivo in NSG mice. Of note, not only did MOLM13CG become undetectable by bioluminescence imaging in response to infusion of human T cells plus AMV564, but also NSG mice that had cleared the tumor also resisted rechallenge with MOLM13CG in spite of no additional AMV564 treatment. In these mice, we identified effector and effector memory human CD4+ and CD8+ T cells in the peripheral blood immediately prior to rechallenge that expanded significantly during the subsequent 18 days. In addition to the anti-tumor effects of AMV564 on the clearance of MOLM13CG cells in vivo, similar effects were seen when primary CD33+ human AML cells were engrafted in NSG mice even when the human T cells made up only 2% of the peripheral blood cells and AML cells made up 98%. These studies suggest that AMV564 is a novel and effective bispecific diabody for the targeting of CD33+ AML that may provide long-term survival advantages in the clinic.

BackgroundThere is a correlation between obesity and 25-hydroxyvitamin D (25OHD) that tends to be negative. However, this relationship varies among different races. In this study, Asian adults with and without obesity were compared in terms of their levels of 25OHD.MethodsWe carried out a cross-sectional analysis on 2664 non-Hispanic Asian adults who participated in the National Health and Nutrition Examination Survey (NHANES) conducted between 2011 and 2018. To examine the connection between obese status, body mass index (BMI), waist circumference (WC) and weight, and 25OHD, we ran multivariate linear regression models and multivariate logistic regression models.ResultsAfter adjusting for all confounding factors, obesity status shows a significant positive correlation with vitamin D deficiency (model 3: OR = 2.318, 95% CI:1.317, 4.082). This positive correlation remains significant in males (males: OR = 2.713, 95% CI: -13.398, 5.217). In all three models, a negative association was observed between obesity status and 25OHD (model 1: β = -4.535, 95% CI: -6.987, -2.083; model 2 β = -4.249, 95% CI: -6.549, -2.039; model 3 β = -1.734, 95% CI: -7.285, 3.816). After controlling for covariates, there was a significant negative correlation between WC and 25OHD when stratified by gender and obesity status in both males with and without obesity (males with obesity: β = -1.461, 95% CI: -2.485, -0.436; males without obesity: β = -0.855. 95% CI: -1.499, -0.210). In males with obesity, there was a very strong positive connection between body weight and 25OHD (β = 0.912, 95% CI: 0.227, 1.597). In addition, neither gender's obese individuals showed a significant link between BMI and 25OHD.ConclusionThis study demonstrated a positive correlation between obesity and vitamin D deficiency and a negative correlation between obesity and 25OHD in Asian American adults. Additionally, among male obese individuals, there was a significant negative correlation between WC and 25OHD, an observation that needs to be validated in further prospective studies.

Objective(s): Pathological micro angiogenesis is a key pathogenic factor in pulmonary diseases such as pulmonary hypertension and hepatopulmonary syndrome. More and more pieces of evidence show that excessive proliferation of pulmonary microvascular endothelial cells is the key event of pathological micro angiogenesis. The purpose of this research is to reveal the mechanism of miR26-5p regulating pulmonary microvascular hyperproliferation.Materials and Methods: Hepatopulmonary syndrome rat model was made by common bile duct ligation. HE and IHC staining were used for analysis of the pathology of the rat. CCK8, transwell, and wound healing assay were used to assess miR26-5p or target gene WNT5A functioned toward PMVECs. microRNA specific mimics and inhibitors were used for up/down-regulated miR26-5p expression in PMVECs. Recombinant lentivirus was used for overexpression/knockdown WNT5A expression in PMVECs. And the regulation relationship of miR26-5p and WNT5A was analyzed by dual-luciferase reporter assay.Results: qPCR showed that miR26-5p was significantly down-regulated in the course of HPS disease. Bioinformatics data showed that WNT5A was one of the potential key target genes of miR26-5p. Immunohistochemistry and qPCR analysis showed that WNT5A was largely expressed in pulmonary microvascular endothelial cells, in addition, this molecule was significantly up-regulated with the progression of the disease. Furthermore, dual luciferase reporter assay showed that miR26-5p could bind to WNT5A 3 ‘UTR region to inhibit WNT5A synthesis.Conclusion: The results suggested MiR26-5p negatively regulated PMVECs proliferation and migration by WNT5A expression. Overexpression of miR26-5p may be a potentially beneficial strategy for HPS therapy.

Abstract The abscopal is a hypothesis for treating of non-irradiated tumors after localized radiation therapy. It is associated with the products of tumor-associated gene as autoantibodies (aTAAs) in reaction to the tumor-associated antigens (TAAs), with increasing of anti-MAGEA3 and an relationship between the abscopal effect and immune response. The hapten enhanced local chemotherapy (HELC) was studied to kills tumor and release tumor TAAs, then hapten modify the TAAs to neu-TAAs, to produce tumor autologous antibodies, called induced tumor-associated autoantibodies (iTAAs) that is different from natural TAAs. Since the iTAAs and complement (C) are associated with cancer therapy Immunofluorescence (IF) was applied to evaluate the expression of the iTAAs and C3, C5, C9. Traces resulted in a partial staining of the nucleus in C3’s perinuclear reaction. The iTTAs of Survivin, C-MYC, and IMP1 increased significantly in the tumor cells' intranuclear regions (P = 0.02, P = 0.00, P

Abstract Background Apatinib, a highly selective VEGFR2 inhibitor, significantly improved efficacy versus placebo as a third- and later-line treatment for advanced gastric cancer in phase 2 and 3 trials. This prospective, single-arm, multicenter phase IV AHEAD study was conducted to verify the safety and efficacy of apatinib in patients with advanced or metastatic gastric or gastroesophageal adenocarcinoma after at least two lines of systematic therapy in clinical practice settings. Methods Patients with advanced gastric cancer who had previously failed at least two lines of chemotherapy received oral apatinib until disease progression, death or unacceptable toxicity. The primary endpoint was safety. The secondary endpoints included objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS) and overall survival (OS). Adverse events were summarized by the incidence rate. Median OS and PFS were estimated using the Kaplan–Meier method. ORR, DCR, OS at 3 and 6 months, and PFS at 3 and 6 months were calculated, and their 95% CIs were estimated according to the Clopper-Pearson method. Results Between May 2015 and November 2019, a total of 2004 patients were enrolled, and 1999 patients who received at least one dose of apatinib were assessed for safety. In the safety population, 87.9% of patients experienced treatment-related adverse events (TRAEs), with the most common hypertension (45.2%), proteinuria (26.5%), and white blood cell count decreased (25.3%). Additionally, 51% of patients experienced grade ≥ 3 TRAEs. Fatal TRAEs occurred in 57 (2.9%) patients. No new safety concerns were reported. Among the 2004 patients included in the intention-to-treat population, the ORR was 4.4% (95% CI, 3.6–5.4%), and DCR was 35.8% (95% CI, 33.7–38.0%). The median PFS was 2.7 months (95% CI 2.2–2.8), and the median OS was 5.8 months (95% CI 5.4–6.1). Conclusions The findings in the AHEAD study confirmed the acceptable and manageable safety profile and clinical benefit of apatinib in patients with advanced gastric cancer as a third- or later-line of treatment. Trial registration This study was registered with ClinicalTrials.gov NCT02426034. Registration date was April 24, 2015.

Abstract This study aimed to develop a nomogram for predicting the progression-free survival (PFS) of testicular germ cell tumors (TGCT) patients based on DNA methylation signature and clinicopathological characteristics. The DNA methylation profiles, transcriptome data, and clinical information of TGCT patients were obtained from the Cancer Genome Atlas (TCGA) database. Univariate Cox, lasso Cox, and stepwise multivariate Cox regression were applied to identify a prognostic CpG sites-derived risk signature. Differential expression analysis, functional enrichment analysis, immunoinfiltration analysis, chemotherapy sensitivity analysis, and clinical feature correlation analysis were performed to elucidate the differences among risk groups. A prognostic nomogram integrating CpG sites-derived risk signature and clinicopathological features was further established and evaluated likewise. A risk score model based on 7 CpG sites was developed and found to exhibit significant differences among different survival, staging, radiotherapy, and chemotherapy subgroups. There were 1452 differentially expressed genes between the high- and low-risk groups, with 666 being higher expressed and 786 being lower expressed. Genes highly expressed were significantly enriched in immune-related biological processes and related to T-cell differentiation pathways; meanwhile, down-regulated genes were significantly enriched in extracellular matrix tissue organization-related biological processes and involved in multiple signaling pathways such as PI3K-AKT. As compared with the low-risk group, patients in the high-risk group had decreased lymphocyte infiltration (including T-cell and B-cell) and increased macrophage infiltration (M2 macrophages). They also showed decreased sensitivity to etoposide and bleomycin chemotherapy. Three clusters were obtained by consensus clustering analysis based on the 7 CpG sites and showed distinct prognostic features, and the risk scores in each cluster were significantly different. Multivariate Cox regression analysis found that the risk scores, age, chemotherapy, and staging were independent prognostic factors of PFS of TGCT, and the results were used to formulate a nomogram model that was validated to have a C-index of 0.812. Decision curve analysis showed that the nomogram model was superior to other strategies in the prediction of PFS of TGCT. In this study, we successfully established CpG sites-derived risk signature, which might serve as a useful tool in the prediction of PFS, immunoinfiltration, and chemotherapy sensitivity for TGCT patients.

Abstract Background This study aimed to develop a radiogenomic prognostic prediction model for colorectal cancer (CRC) by investigating the biological and clinical relevance of intratumoural heterogeneity. Methods This retrospective multi-cohort study was conducted in three steps. First, we identified genomic subclones using unsupervised deconvolution analysis. Second, we established radiogenomic signatures to link radiomic features with prognostic subclone compositions in an independent radiogenomic dataset containing matched imaging and gene expression data. Finally, the prognostic value of the identified radiogenomic signatures was validated using two testing datasets containing imaging and survival information collected from separate medical centres. Results This multi-institutional retrospective study included 1601 patients (714 females and 887 males; mean age, 65 years ± 14 [standard deviation]) with CRC from 5 datasets. Molecular heterogeneity was identified using unsupervised deconvolution analysis of gene expression data. The relative prevalence of the two subclones associated with cell cycle and extracellular matrix pathways identified patients with significantly different survival outcomes. A radiogenomic signature-based predictive model significantly stratified patients into high- and low-risk groups with disparate disease-free survival (HR = 1.74, P = 0.003). Radiogenomic signatures were revealed as an independent predictive factor for CRC by multivariable analysis (HR = 1.59, 95% CI:1.03–2.45, P = 0.034). Functional analysis demonstrated that the 11 radiogenomic signatures were predominantly associated with extracellular matrix and immune-related pathways. Conclusions The identified radiogenomic signatures might be a surrogate for genomic signatures and could complement the current prognostic strategies.

Abstract Cellular senescence has been listed as a hallmark of cancer, but its role in colorectal cancer (CRC) remains unclear. We comprehensively evaluated the transcriptome, genome, digital pathology, and clinical data from multiple datasets of CRC patients and proposed a novel senescence subtype for CRC. Multi‐omics data was used to analyze the biological features, tumor microenvironment, and mutation landscape of senescence subtypes, as well as drug sensitivity and immunotherapy response. The senescence score was constructed to better quantify senescence in each patient for clinical use. Unsupervised learning revealed three transcriptome‐based senescence subtypes. Cluster 1, characterized by low senescence and activated proliferative pathways, was sensitive to chemotherapeutic drugs. Cluster 2, characterized by intermediate senescence and high immune infiltration, exhibited significant immunotherapeutic advantages. Cluster 3, characterized by high senescence, high immune, and stroma infiltration, had a worse prognosis and maybe benefit from targeted therapy. We further constructed a senescence scoring system based on seven senescent genes through machine learning. Lower senescence scores were highly predictive of longer disease‐free survival, and patients with low senescence scores may benefit from immunotherapy. We proposed the senescence subtypes of CRC and our findings provide potential treatment interventions for each CRC senescence subtype to promote precision treatment.

Background The position of the femoral insertion has a great influence on the laxity of the knee joint after ACLR, especially for rotational laxity. Purpose To compare the effects of different femoral tunnel positions on knee stability after arthroscopic anterior cruciate ligament reconstruction (ACLR). Methods The clinical outcomes of 165 patients after autograft ACLR were analyzed retrospectively. The patients were separated into three groups according to the position of the femoral tunnel, as follows: low center (LC) group, 53 patients; high center (HC) group, 45 patients; and high anteromedial (HAM) group, 67 patients. The side-to-side differences (SSDs) in anteroposterior knee laxity measured using a KT-2000 arthrometer and the pivot shift test (PST) pre- and postoperatively were compared among the three groups and analyzed. Results After 5 years postoperatively, the SSD in the anteroposterior knee laxity in the three groups was significantly decreased postoperatively compared with preoperatively in knees; meanwhile, the negative PST rate was significantly increased in the three groups. The postoperative SSD in anteroposterior knee laxity was significantly increased in the HC group compared with the LC and HAM groups (1.5 ± 1.3 VS 1.0 ± 1.1 VS 1.0 ± 1.0, P0.05). The negative postoperative PST rate was significantly higher in the HAM group than in the LC and HC groups for patients with a high degree of laxity preoperatively (31.3% VS 3.3% VS 14.4%, P>0.05). Conclusion Patients in HAM group showed better control over anteroposterior laxity, rotational laxity, and subjective knee function compared to other groups post operation. Therefore, the HAM point is the closest to the I.D.E.A.L point concept, and is recommended as the preferred location for the femoral tunnel in ACLR.

To evaluate the clinical efficacy of pelvic floor low-frequency electrical stimulation combined with anus lifting training in the treatment of urinary incontinence after radical prostatectomy in a Chinese cohort. Fifty-five patients with urinary incontinence after radical prostatectomy were randomly divided into treatment group and control group. Patients in control group received only anus lifting training therapy, while treatment group combined with pelvic floor low-frequency electrical stimulation. The urinary control including urinary incontinence questionnaire (ICI-Q-SF), urinary incontinence quality of life (I-QOL), visual analogue scale (VAS), and pelvic floor muscle strength assessment (Glazer) of the two groups of patients before treatment and every week was recorded for statistical analysis. There was a statistically significant difference between treatment group and control group in the urinary control curve. The scores of ICI-Q-SF, I-QOL, VAS, and Glazer in the treatment group after 2 weeks were statistically different from those before treatment, and effects were accumulating with the extension of treatment time. Compared with the control group, the scores of treatment group in the 2 to 10 weeks improved more significantly. Especially, in the sixth week, total effective rate of treatment group was significantly better than that of control group (74.07% [20/27], 35.71% [10/28], p < .05). The difference between two groups gradually narrowed after 10 weeks and no significant difference after 10 weeks of treatment between two groups. Pelvic floor low-frequency electrical stimulation combined with anus lifting training after radical prostatectomy can significantly shorten the recovery time of urinary incontinence in patients after radical prostatectomy.

Background Acute respiratory distress syndrome (ARDS), are respiratory diseases with high morbidity and mortality. Clinical trials investigating the efficacy of corticosteroids in the treatment of ARDS often yield contradictory results. We hereby conducted a systematic review and meta-analysis to investigate the efficacy of corticosteroids in ARDS management.Materials and Methods We conducted a search for randomized clinical trials (RCT) and observational studies that utilized corticosteroids for patients with ARDS in Web of Science, PubMed, and Embase. The primary outcome was mortality. Risk of bias was assessed using Cochrane or NOS scales. Statistical effect size was analyzed using the Mantel-Haenszel method.Results A total of 20 studies, comprising 11 observational studies and 9 RCTs, were eligible for analysis. In RCTs, corticosteroids were associated with a reduction of mortality in ARDS patients (relative risk [RR] = 0.80, 95%CI: 0.71-0.91, p = 0.001). Further subgroup analysis indicated that specific variables, such as low-dose (RR = 0.81; 95%CI: 0.67-0.98; p = 0.034), methylprednisolone (RR = 0.70; 95%CI: 0.49-0.98; p = 0.035), and dexamethasone (RR = 0.82; 95%CI: 0.69-0.98; p = 0.029) were associated with mortality among patients receiving corticosteroids. However, in observational studies, corticosteroids increased the risk of death (RR = 1.16, 95%CI: 1.04-1.29; p = 0.001). Subgroup analysis showed that the use of high-dose corticosteroids was associated with higher patient mortality (RR = 1.20; 95%CI: 1.04-1.38; p = 0.001).Conclusions The efficacy of corticosteroids on the mortality of ARDS differed by the type and dosage of corticosteroids used, as well as the etiologies. Current data do not support routine use of corticosteroids in ARDS since protective effects were observed in RCTs but increased mortality was found in observational studies. More well designed and large clinical trials are needed to specify the favorable subgroups for corticosteroid therapy.

Abstract Unrestricted reproduction and spread of pest had caused great damage to the quality and yield of crops in recent years. Besides the use of traditional chemical pesticides, natural products also make a huge contribution against pests. Chasmanthinine, a diterpenoid alkaloid isolated from Aconitum franchetii var. villosulum, shown extremely antifeedant activity against Spodoptera exigua. Therefore, a series of novel Chasmanthinine derivatives were synthesized and their biological activity was studied in this work. Compound 33 showed the strongest antifeedant activity (EC50 = 0.10 mg/cm2) among all the test compounds. The mechanism research of 33 revealed that its antifeedant effect was related to the inhibition of carboxylesterase (CES), and proved the thiophene acyl group could form a strong binding effect with CES by molecular docking. Moreover, compound 10 exhibited the strongest cytotoxicity (IC50 = 12.87 μM) against Sf9 cell line and moderate contact toxicity. The mechanism research indicated that compound 10 could induce Sf9 cells apoptosis. In summary, the results lay a foundation for the application of diterpene alkaloids in plant protection.

Abstract Background Castration-resistant prostate cancer (CRPC) is a major cause of recurrence and mortality among prostate cancer (PCa) patients. Myeloid-derived suppressor cells (MDSCs) regulate castration resistance in PCa. Previously, it was shown that intercellular communication was efficiently mediated by exosomes (Exos), but the role and the mechanism of MDSC-derived Exos in CRPC progression was unclear. Methods In this study, the circRNA expression profiles in PC3 cells treated with MDSC-Exo and control cells were investigated using a circRNA microarray. Results The data showed that circMID1 (hsa_circ_0007718) expression was elevated in PC3 cells treated with MDSC-Exo. Moreover, high circMID1 expression was found in PCa compared with benign prostatic hyperplasia (BPH) tissues and in CRPC patients compared with hormone sensitive prostate cancer (HSPC) patients. Further studies showed that MDSC-Exo accelerated PCa cell proliferation, migration, and invasion, while circMID1 deficiency inhibited MDSC-Exo-regulated CRPC progression in vitro and in vivo. Mechanistically, MDSC-derived exosomal S100A9 increased circMID1 expression to sponge miR-506-3p, leading to increased MID1 expression and accelerated tumor progression. Conclusion Together, our results showed that a S100A9/circMID1/miR-506-3p/MID1 axis existed in MDSC-Exo-regulated CRPC progression, which provided novel insights into MDSC-Exo regulatory mechanisms in CRPC progression.

Abstract A series of new paclitaxel-benzoxazoles hybrids were designed based on both the molecular docking mode of beta-tubulin with paclitaxel derivatives (7a and 7g), and the activity-structure relationship of C-13 side chain in paclitaxel. Palladium-catalyzed direct Csp2–H arylation of benzoxazoles with different aryl-bromides was used as the key synthetic strategy for the aryl-benzoxazoles moieties in the hybrids. Twenty-six newly synthesized hybrids were screened for their antiproliferative activity against human cancer cell lines such as human breast cancer cells (MDA-MB-231) and liver hepatocellular cells (HepG2) by the MTT assay and results were compared with paclitaxel. Interestingly, most hybrids (7a–7e, 7i, 7k, 7l, 7A, 7B, 7D and 7E) showed significantly active against both cell lines at concentration of 50 µM, which indicated that the hybrid strategy is effective to get structural simplified paclitaxel analogues with high anti-tumor activity.

Chronic pain can cause both hyperalgesia and anxiety symptoms. However, how the two components are encoded in the brain remains unclear. The prelimbic cortex (PrL), a critical brain region for both nociceptive and emotional modulations, serves as an ideal medium for comparing how the two components are encoded. We report that PrL neurons projecting to the basolateral amygdala (PrLBLA) and those projecting to the ventrolateral periaqueductal gray (PrLl/vlPAG) were segregated and displayed elevated and reduced neuronal activity, respectively, during pain chronicity. Consistently, optogenetic suppression of the PrL-BLA circuit reversed anxiety-like behaviors, whereas activation of the PrL-l/vlPAG circuit attenuated hyperalgesia in mice with chronic pain. Moreover, mechanistic studies indicated that elevated TNF-α/TNFR1 signaling in the PrL caused increased insertion of GluA1 receptors into PrLBLA neurons and contributed to anxiety-like behaviors in mice with chronic pain. Together, these results provide insights into the circuit and molecular mechanisms in the PrL for controlling pain-related hyperalgesia and anxiety-like behaviors.

Bitcoin is a decentralized digital cryptocurrency. Its network is a Peer-to-peer(P2P) network consisting of distributed nodes. Some of these nodes are always online and in this article are called Bitcoin backbone nodes. They have a significant impact on the stability and security of the Bitcoin network, so it is meaningful to analyze and discuss them. In this paper, we first continuously collect information about Bitcoin nodes from July 2021 through June 2022 (which is the longest duration of data collection to date). In total, we collect information on 127,613 Bitcoin nodes. At the same time, we conclude that the fluctuation of Bitcoin nodes is directly related to the fluctuation of onion network nodes. Further, we filtered 2694 Bitcoin backbone nodes based on our algorithm. By analyzing the backbone nodes' attributes such as geographic distribution, client version, operator, node function, and abnormal port number, it is demonstrated that these nodes are centralized and play an important role in the Bitcoin network. Based on this, three unsupervised machine learning algorithms are selected to cluster multiple attributes of backbone nodes in a more scientific way. In this paper, the whole process from data collection to cluster analysis is completed and the best results are obtained by comparison. The experiments proved the existence of centralization of Bitcoin backbone nodes and obtained the number of nodes within each cluster. Finally, cluster nodes are de-anonymized based on the optimal results. Through our experiments, we obtain organizational information about the deployers of 103 nodes, linking the Bitcoin backbone nodes to the real world, thus accurately demonstrating the existence of Bitcoin centrality.

With the success of pre-trained language models, the performance of story ending generation has been dramatically improved while remaining challenging due to the lack of commonsense reasoning ability. Most previous works mainly focus on using commonsense knowledge to enhance the implicit correlations between words but ignore the hidden causality of sentences or events. In this paper, we propose Causal commonsense Enhanced joint model for story ending Generation (CEG), which incorporates causal commonsense events knowledge to generate a reasonable story ending. Specifically, we first develop a commonsense events inference model trained on GLUCOSE, which converts static knowledge into a dynamic generation model to discover unseen knowledge. It uses prompts to produce various commonsense events behind the stories as pseudo-labels of the dataset. Then, we propose a joint model for the causal events inference task and the story ending generation task to inject inference knowledge into the generation, which consists of a shared encoder, an inference decoder, and a generation decoder. In the causal events inference task, we use the shared encoder and the inference decoder to reason the causal events behind each sentence of the story context to help the model better understand the story and provide long-distance dependencies for the story ending generation. In story ending generation, we combine the hidden states of the causal events with the story context to generate the story ending by the shared encoder and the generation decoder. We jointly train the model on two tasks so that the generation decoder produces the story endings that better match the clues. Experimental results on the ROCStories dataset show that our model outperforms the previous works, demonstrating the effectiveness of the joint model and the generated causal events.

The development of intelligent and unmanned coal mining has put forward higher requirements on the service life and dynamic reliability of shearer cables. However, it is difficult to comprehensively consider the complexity of hosting conditions of coal mining working face and the dynamic characteristics of cables in different towing systems in the design and development of cables. The cables are periodized by pitch and have the same cross-sectional structure and properties. Based on the homogenization theory and volume average principle, the cable was assumed to be an orthotropic elastomer, and the tensile experimental method and finite element method were combined to calibrate the cable equivalent mechanical parameters. Based on the Absolute Node Coordinate Formulation (ANCF) method, the rigid-flexible coupled virtual prototype co-simulation model of shearer cable towing system was constructed to obtain the kinetic and kinematic parameters of each node of the cable and study the dynamic gradual change characteristics of the cable in different working areas. This research method has an important theoretical significance and engineering application value for the acquisition of dynamic characteristic parameters of shearer cables and the optimal design and dynamic reliability of cables.

Aiming at the problems of low accuracy of coal gangue recognition and difficult recognition of mixed gangue rate, a coal rock recognition method based on modal fusion of RGB and infrared is proposed. A fully mechanized coal gangue transportation test bed is built, RGB images are obtained by camera, and infrared images are obtained by industrial microwave heating system and infrared thermal imager. the image data of the whole coal, whole gangue, and coal gangue with different gangue mixing as training and test samples, identify the released coal gangue and its mixing rate. The AlexNet, VGG-16, ResNet-18 classification networks and their convolutional neural networks with modal feature fusion are constructed. results: The classification accuracy of ResNet networks on RGB and infrared image data is higher than AlexNet and VGG-16 networks. The early convergence network performance of ResNet is verified through the convergence of different models. The recognition rate of the network is 97.92 the confusion matrix statistics, which verifies the feasibility of the application of modal fusion method in the field of coal gangue recognition. The fusion of modal features and early models of ResNet coal gangue, which is the basic premise for realizing intelligent coal caving.

Summary: Background: Autism spectrum disorder (ASD) is a common neurodevelopmental disease, characterized by deficits in social communication, restricted and repetitive behaviours, and impaired fear memory processing. Severe gastrointestinal dysfunction and altered gut microbiome have been reported in ASD patients and animal models. Contactin associated protein-like 4 (CNTNAP4) has been suggested to be a novel risk gene, though its role in ASD remains unelucidated. Methods: Cntnap4−/− mice were generated to explore its role in ASD-related behavioural abnormalities. Electrophysiological recording was employed to examine GABAergic transmission in the basolateral amygdala (BLA) and prefrontal cortex. RNA-sequencing was performed to assess underlying mechanisms. 16S rDNA analysis was performed to explore changes in faecal microbial composition. Male Cntnap4−/− mice were fed with Lactobacillus reuteri (L. reuteri) or faecal microbiota to evaluate the effects of microbiota supplementation on the impaired fear conditioning mediated by Cntnap4 deficiency. Findings: Male Cntnap4−/− mice manifested deficiency in social behaviours and tone-cue fear conditioning. Notably, reduced GABAergic transmission and GABA receptor expression were found in the BLA but not the prefrontal cortex. In addition, gut Lactobacillus were less abundant in male Cntnap4−/− mice, and L. reuteri treatment or faecal microbiota transplantation rescued abnormal tone-cued fear memory and improved local GABAergic transmission in the BLA of male Cntnap4−/− mice. Interpretation: Cntnap4 shapes GABAergic transmission of amygdala and fear conditioning, and microbial intervention represents a promising therapy in ASD intervention. Funding: National Natural Science Foundation of China, Science and Technology Planning Project of Guangzhou, Guangzhou Medical University, and China Postdoctoral Science Foundation.

The aim of this study was to investigate the expression of interferon regulatory factor 4 (IRF4) and the inflammatory response in secondary injury of intracerebral haemorrhage (ICH). Twelve SD rats were randomly divided into a sham group and an ICH group, with 6 rats in each group. A rat model of ICH was established by injecting collagenase type IV into the right striatum of rats. The expression of IRF4 was measured by western blot and immunohistochemistry 48 h after ICH. In addition, 15 mm of hemin-induced PC12 cell injury was used to simulate an in vitro ICH model. IRF4 expression was detected by immunofluorescence (IF). Moreover, the inflammatory cytokines (IL-1b and IL-6) were measured by ELISA. The behavioural score of ICH rats was the lowest at 48 h after operation. The expression of IRF4 was significantly higher in the striatal tissue of ICH rats compared with the sham group (p < 0.05). Meanwhile, IF results showed that hemin induced the upregulation of IRF4 expression in rat pheochromocytoma cells PC12. In addition, IL-1b and IL-6 levels were significantly increased in the serum of ICH rats and in the supernatant of hemin-induced PC12 cells (p < 0.01). The inflammation in ICH is related to the increase of IRF4. It provides a theoretical basis for the clinical treatment of ICH.

Lung development is precisely controlled by underlying gene regulatory networks (GRN). Disruption of genes in the network can interrupt normal development and cause diseases such as bronchopulmonary dysplasia (BPD) – a chronic lung disease in preterm infants with morbid and sometimes lethal consequences characterized by lung immaturity and reduced alveolarization. Here, we generated a transgenic mouse exhibiting a moderate severity BPD phenotype by blocking IGF1 signaling in secondary crest myofibroblasts (SCMF) at the onset of alveologenesis. Using approaches mirroring the construction of the model GRN in sea urchin’s development, we constructed the IGF1 signaling network underlying alveologenesis using this mouse model that phenocopies BPD. The constructed GRN, consisting of 43 genes, provides a bird’s eye view of how the genes downstream of IGF1 are regulatorily connected. The GRN also reveals a mechanistic interpretation of how the effects of IGF1 signaling are transduced within SCMF from its specification genes to its effector genes and then from SCMF to its neighboring alveolar epithelial cells with WNT5A and FGF10 signaling as the bridge. Consistently, blocking WNT5A signaling in mice phenocopies BPD as inferred by the network. A comparative study on human samples suggests that a GRN of similar components and wiring underlies human BPD. Our network view of alveologenesis is transforming our perspective to understand and treat BPD. This new perspective calls for the construction of the full signaling GRN underlying alveologenesis, upon which targeted therapies for this neonatal chronic lung disease can be viably developed.

Abstract Natural orifice specimen extraction surgery (NOSES) is an intra-abdominal procedure that does not require an auxiliary incision to take a surgical sample from the abdominal wall through the natural orifice, but there are few systematic clinical studies on it. The aim of this study was to demonstrate the safety and feasibility of NOSES. We retrospectively analyzed the clinical data and follow-up of 165 patients with low rectal cancer who underwent NOSES or conventional laparoscopic surgery at our center from January 2013 to June 2015. From the perioperative data and postoperative follow-up results of both groups, patients in the NOSES group had less intraoperative bleeding (49.3 ± 55.8 ml vs. 75.1 ± 57.3 ml, p = 0.02), shorter postoperative gastrointestinal recovery (42.3 ± 15.5 h vs. 50.1 ± 17.0 h, p = 0.01), less postoperative analgesic use (35.6% vs. 57.6%, p = 0.02), lower postoperative pain scores, lower rate of postoperative complications (6.8% vs. 25.4%, p = 0.01), better satisfaction of the image and cosmesis of the abdominal wall postoperatively, and higher quality of life. Moreover, there was no significant difference in overall survival (OS) and disease-free survival (DFS) between two groups. Overall, NOSES is a safe and reliable minimally invasive surgical technique for patients with low rectal cancer.

Abstract Based on the antibody typing classification, Helicobacter pylori infection can be divided into type I H. pylori infection and type II H. pylori infection. To observe the effects of different H. pylori infection types on the distribution of histopathological characteristics and the levels of three items of serum gastric function (PG I, PG II, G-17). 1175 cases from October 2018 to February 2020 were collected with ratio 1:2. All patients were performed with 14C-Urea breath test (14C-UBT), H. pylori antibody typing classification, three items of serum gastric function detection, painless gastroscopy, pathological examination, etc. According to H. pylori antibody typing classification, patients were divided into three groups: type I H. pylori infection group, type II H. pylori infection group and control group. Significant difference existed among type I H. pylori infection group, type II H. pylori infection group and control group in inflammation and activity (χ 2 = 165.43, 354.88, P all

Abstract The challenge of decoding information about complex diseases hidden in huge number of single nucleotide polymorphism (SNP) genotypes is undertaken based on five dbGaP studies. Current genome-wide association studies have successfully identified many high-risk SNPs associated with diseases, but precise diagnostic models for complex diseases by these or more other SNP genotypes are still unavailable in the literature. We report that lung cancer, breast cancer and prostate cancer as the first three top cancers worldwide can be predicted precisely via 240–370 SNPs with accuracy up to 99% according to leave-one-out and 10-fold cross-validation. Our findings (1) confirm an early guess of Dr. Mitchell H. Gail that about 300 SNPs are needed to improve risk forecasts for breast cancer, (2) reveal an incredible fact that SNP genotypes may contain almost all information that one wants to know, and (3) show a hopeful possibility that complex diseases can be precisely diagnosed by means of SNP genotypes without using phenotypical features. In short words, information hidden in SNP genotypes can be extracted in efficient ways to make precise diagnoses for complex diseases.

Abstract This prospective study was aimed to evaluate the clinical value of narrow-band imaging (NBI), magnification endoscopy with narrow-band imaging (NBIME) and magnification endoscopy with acetic acid enhancement and narrow-band imaging (AA-NBIME) in the diagnosis of small colorectal polyps. We studied 261 small colorectal polyps from 122 patients with the use of above three techniques. Lesions were resected for histopathological analysis. The endoscopic images were independently reviewed by three experts and three non-experts and the diagnostic accuracy and image definition were compared among the modalities. The “experts-agreed” diagnostic accuracy was 87.7% for NBI versus 91.6% for NBIME versus 94.6% for AA-NBIME. The “non-experts-agreed” diagnostic accuracy was 80.1% for NBI versus 84.3% for NBIME versus 89.3% for AA-NBIME. All experts and non-experts diagnosed the small colorectal polyps statistically more accurately with AA-NBIME than NBI (P

Abstract Meniscal degeneration is a very common condition in elderly individuals, but the underlying mechanisms of its occurrence are not completely clear. This study examines the molecular mechanisms of meniscal degeneration. The anterior cruciate ligament (ACL) and lateral collateral ligament (LCL) of the right rear limbs of seven Wuzhishan mini-pigs were resected (meniscal degeneration group), and the left rear legs were sham-operated (control group). After 6 months, samples were taken for gene chip analysis, including differentially expressed gene (DEG) analysis, gene ontology (GO) analysis, clustering analysis, and pathway analysis. The selected 12 DEGs were validated by real time reverse transcription-polymerase chain reaction (RT-PCR). The two groups showed specific and highly clustered DEGs. A total of 893 DEGs were found, in which 537 are upregulated, and 356 are downregulated. The GO analysis showed that the significantly affected biological processes include nitric oxide metabolic process, male sex differentiation, and mesenchymal morphogenesis, the significantly affected cellular components include the endoplasmic reticulum membrane, and the significantly affected molecular functions include transition metal ion binding and iron ion binding. The pathway analysis showed that the significantly affected pathways include type II diabetes mellitus, inflammatory mediator regulation of TRP channels, and AMPK signaling pathway. The results of RT-PCR indicate that the microarray data accurately reflects the gene expression patterns. These findings indicate that several molecular mechanisms are involved in the development of meniscal degeneration, thus improving our understanding of meniscal degeneration and provide molecular therapeutic targets in the future.

Abstract. Background. Accumulating evidence has revealed that circulating microRNAs (miRNAs) can serve as non-invasive biomarkers for cancer diagnosis. This study aimed to identify differentially expressed miRNAs in serum which might become potential biomarkers for non-invasive diagnosis of papillary thyroid carcinoma (PTC). Methods. The experiment was carried out between 2015 and 2017. In the screening stage, the Exiqon miRNA quantitative real-time polymerase chain reaction (qPCR) panel was applied to select candidate miRNAs. In the following training, testing, and external validation stages, the serum samples of 100 patients and 96 healthy controls (HCs) were analyzed to compare the expression levels of the identified miRNAs. The areas under the receiver operating characteristic curves (AUCs) were calculated to assess the diagnostic value of the identified signature. Results. Three miRNAs (miR-25-3p, miR-296-5p, and miR-92a-3p) in serum were consistently up-regulated in PTC patients compared with HCs. A three-miRNA panel was constructed by logistic regression analysis and showed better diagnostic performance than a single miRNA for PTC detection. The AUCs of the panel were 0.727, 0.771, and 0.862 for the training, testing, and external validation stage, respectively. Meanwhile, the panel showed stable capability in differentiating PTC patients from patients with benign goiters, with an AUC as high as 0.969. For further exploration, the three identified miRNAs were analyzed in tissue samples (23 PTC vs. 23 HCs) and serum-derived exosomes samples (24 PTC vs. 24 HCs), and the altered expression in the tumor also indicated their close relationship with PTC disease. Conclusion. We identify a three-miRNA panel in serum which might serve as a promising biomarker for PTC diagnosis.

Abstract. Background. Developing effective spinal cord repair strategies for spinal cord injury (SCI) is of great importance. Emerging evidence suggests that microRNAs (miRNAs) are closely linked to SCI recovery. This study aimed to investigate the function of miR-34c in the neuronal recovery in rats with SCI. Methods. A rat model with SCI was established. Differentially expressed miRNAs were identified by a microarray analysis. MiR-34c expression in rats was measured by reverse transcription quantitative polymerase chain reaction. Altered expression of miR-34c or C-X-C motif ligand 14 (CXCL14) was introduced in SCI rats to measure their roles in neuronal recovery. Western blot analysis was performed to determine the phosphorylation of Janus kinase 2 (JAK2) and signal transducer and activator of transcription-3 (STAT3). Neuronal apoptosis in rat spinal cord tissues was detected. The concentrations of SCI recovery-related proteins thyrotropin releasing hormone (TRH), prostacyclin (PGI2), and ganglioside (GM) were evaluated by enzyme-linked immunosorbent assay. Data were analyzed using a t-test with a one-way or two-way analysis of variance. Results. Rats with SCI presented decreased grip strength (112.03 ± 10.64 vs. 17.32 ± 1.49 g, P