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Abstract Background This study was performed with attempt to explore the clinical value and risk factors of compression supporting screws for the treatment of femoral neck fractures. Methods This retrospective analysis enrolled 102 patients with femoral neck fractures who admitted to our hospital from June 2020 to June 2022. Based on different screws during the operation, the participants were allocated into hollow screw group (52 cases, conventional fixation of parallel partial-thread hollow screw) and compression screw group (50 cases, compression screw fixation). Result The incidence of complications (including internal fixation failure, nonunion, a vascular necrosis of the femoral head, shortening of the femoral neck by less than 10 mm, and lateral screw withdrawal, of the affected limb) in the compression screw group were significantly lower than those in the hollow screw group (P

Abstract Micro RNAs (miRs) have been implicated in various tumorigenic processes. Osteosarcoma (OS) is a primary bone malignancy seen in adolescents. However, the mechanism of miRs in OS has not been fully demonstrated yet. Here, miR-134-5p was found to inhibit OS progression and was also expressed at significantly lower levels in OS tissues and cells relative to normal controls. miR-134-5p was found to reduce vasculogenic mimicry, proliferation, invasion, and migration of OS cells, with miR-134-5p knockdown having the opposite effects. Mechanistically, miR-134-5p inhibited expression of the ITGB1/MMP2/PI3K/Akt axis, thus reducing the malignant features of OS cells. In summary, miR-134-5p reduced OS tumorigenesis by modulation of the ITGB1/MMP2/PI3K/Akt axis, suggesting the potential for using miR-134-5p as a target for treating OS.

Breast cancer is the most common cause of female morbidity and death worldwide. Compared with other cancers, early detection of breast cancer is more helpful to improve the prognosis of patients. In order to achieve early diagnosis and treatment, clinical treatment requires rapid and accurate diagnosis. Therefore, the development of an automatic detection system for breast cancer suitable for patient imaging is of great significance for assisting clinical treatment. Accurate classification of pathological images plays a key role in computer-aided medical diagnosis and prognosis. However, in the automatic recognition and classification methods of breast cancer pathological images, the scale information, the loss of image information caused by insufficient feature fusion, and the enormous structure of the model may lead to inaccurate or inefficient classification. To minimize the impact, we proposed a lightweight PCSAM-ResCBAM model based on two-stage convolutional neural network. The model included a Parallel Convolution Scale Attention Module network (PCSAM-Net) and a Residual Convolutional Block Attention Module network (ResCBAM-Net). The first-level convolutional network was built through a 4-layer PCSAM module to achieve prediction and classification of patches extracted from images. To optimize the network's ability to represent global features of images, we proposed a tiled feature fusion method to fuse patch features from the same image, and proposed a residual convolutional attention module. Based on the above, the second-level convolutional network was constructed to achieve predictive classification of images. We evaluated the performance of our proposed model on the ICIAR2018 dataset and the BreakHis dataset, respectively. Furthermore, through model ablation studies, we found that scale attention and dilated convolution play an important role in improving model performance. Our proposed model outperforms the existing state-of-the-art models on 200 × and 400 × magnification datasets with a maximum accuracy of 98.74 %.

This paper proposes a novel tensor decomposition method, cooperative parallel factor (Co-PARAFAC), that is devised to achieve higher accuracy with lower computational complexity and memory requirements than the conventional PARAFAC. The rationale relies on dividing a given tensor, even with a large size, into smaller disjoint sub-tensors, which are independently and parallelly decomposed using the conventional PARAFAC. The intermediate results are then properly merged to obtain the decomposition of the original tensor. As case study, we apply Co-PARAFAC to estimate the uplink channels of RIS-assisted wireless communications. Simulation results corroborate the efficiency of the Co-PARAFAC in achieving significantly lower computational complexity and higher channel estimation accuracy than the conventional PARAFAC. Broadly, the proposed algorithm is advantageous in various fields requiring efficient and high accurate tensor decomposition.

Abstract Objective There are many injectable treatments for knee osteoarthritis with different characteristics and effects, the aim is to understand which one can lead to better and safer results. Methods The PRISMA principles were followed when doing the literature search. Web of Science databases, Embase, the Cochrane Library, PubMed, and the Wanfang database were searched to identified randomized controlled trials that assessed the efficacy of corticosteroids (CSC), platelet-rich plasma (PRP), hyaluronic acid (HA), and combination therapy in treating KOA. Risk of bias was assessed using the relevant Cochrane tools (version 1.0). The outcome measure included the visual analog scale (VAS) score, the Western Ontario and McMaster Universities Osteoarthritis (WOMAC) score, and treatment-related adverse events. The network meta-analysis was performed using STATA17 software and a Bayesian stratified random effects model. Results Network meta-analysis using the Bayesian random-effects model revealed 35 studies with 3104 participants. PRP showed the best WOMAC score at a 3-month follow-up, followed by PRP + HA, HA, placebo, and CSC; PRP + HA scored the highest VAS, followed by PRP, CSC, HA, and placebo. PRP, CSC, HA, and placebo had the highest WOMAC scores six months following treatment; PRP + HA showed the best VAS scores. PRP showed the best WOMAC score at 12 months, followed by PRP + HA, HA, placebo, and CSC; The best VAS score was obtained with PRP, followed by PRP + HA, HA, and CSC. No therapy demonstrated a rise in adverse events linked to the treatment in terms of safety. Conclusions The current study found that PRP and PRP + HA were the most successful in improving function and alleviating pain after 3, 6, and 12 months of follow-up. CSC, HA, PRP, and combination therapy did not result in an increase in the incidence of treatment-related side events as compared to placebo.

Background: The clinical significance of immune-related antigen CD58 in gliomas remains uncertain. The aim of this study was to examine the clinical importance and possible core related genes of CD58 in gliomas. Methods: Pan-cancer analysis was to observe the association between CD58 and different tumors, glioma RNA sequencing data and clinical sample analyses were used to observe the relationship between CD58 and glioma, shRNA interference models were to observe the impact of CD58 on glioma cell function, and four glioma datasets and two online analysis platforms were used to explore the core related genes affecting the correlation between CD58 and glioma. Results: High CD58 expression was associated with worse prognosis in various tumors and higher malignancy in glioma. Down regulation of CD58 expression was linked to decreased proliferation, increased apoptosis, and reduced metastasis in glioma cells. The pathways involved in CD58-related effects were enriched for immune cell adhesion and immune factor activation, and the core genes were CASP1, CCL2, IL18, MYD88, PTPRC, and TLR2. The signature of CD58 and its core-related genes showed superior predictive power for glioma prognosis. Conclusion: High CD58 expression is correlated with more malignant glioma types, and also an independent risk factor for mortality in glioma. CD58 and its core-related genes may serve as novel biomarkers for diagnosing and treating glioma.

The newly-developed Ni–28W–6Cr alloy is the structural material for the next-generation molten salt reactor (MSR). Due to the detrimental effects of welding hot cracks on the quality of welded structures, it is essential to study the hot cracking behavior and mechanism to achieve the qualified Ni–28W–6Cr alloy welded joint. This paper analyzes the characteristics of the dynamic cracking behavior of welding hot cracks using a high-speed camera. The microstructure, morphology, and cracking mechanism of hot cracks are studied. The results show that solidification cracks and liquation cracks occur in the welded joint. According to the propagation direction of the hot crack, there are longitudinal cracks and transverse cracks, respectively. The quantity and length of hot cracks increase with the laser power. The laser welded joint's hardness value fluctuates from 200 HV to 260 HV. The width of heat affected zone (HAZ) is approximately 0.5–1 mm, and there is a slight softening zone in the HAZ. Meanwhile, the hardness of the weld metal is the highest in the welded joint. The solidification cracks tend to initiate and crack along the solidification grain boundary, which is mainly related to the thermal stress caused by the welding process and the weak bonding strength of grain boundaries caused by the element segregation and precipitation at the grain boundary. Liquation cracking is mainly affected by welding thermal stress and element segregation at the grain boundary in the HAZ. However, the eutectic carbides play the role of inhibiting the propagation of liquation cracks.

Background: The invasive brownrat (Rattus norvegicus) and the Oriental rats (Rattus tanezumi) are common commensal murid that are important hosts for rodent-borne diseases in southeast Asia. Understanding their population structure and genetic diversity is essential to uncover their invasion biology and distribution dynamics that are essential for controlling rodent-borne diseases.Methods: TA total of 103 R. norvegicus and 85 R. tanezumi were collected from 13 to 9 coastal areas of six provincial monitoring sentinel sites, respectivelyto assess patterns in their microsatellite loci and their mitochondrial coxl gene region.Results: Eleven sampled populations of R. norvegicus were divided into two major clusters by region. The observed heterozygosity values of all regional populations were smaller than expected genetic diversity heterozygosity values and deviated from Hardy-Weinberg equilibrium Nine sample populations of R. tanezumi were divided into three clusters; two that included sample from Hainan and Fujian provinces, and one that included samples from the other provinces and cities. The genetic diversity of R. tanezumi was highest in samples from Jiangsu and Guangdong provinces.Conclusion: The data in this paper confirm the two invasive rodent species from the southeastern coastal region of China may have relied on maritime transport to spread from the southern region of China to the Yangtze River basin. R. tanezumi may then hanve migrated unidirectionally, along the southeastern provinces of China towards the north, while R. norvegicus spread in a complex and multidirectional manner in Hainan, Fujian, Zhejiang and Jiangsu Provinces of the country.

BackgroundMounting evidence has demonstrated the associations between gut microbiota, gut microbiota-derived metabolites, and cerebrovascular diseases (CVDs). The major categories of CVD are ischemic stroke (IS), intracerebral hemorrhage (ICH), and subarachnoid hemorrhage (SAH). However, the causal relationship is still unclear.MethodsA two-sample Mendelian randomization (MR) study was conducted leveraging the summary data from genome-wide association studies. The inverse variance-weighted, maximum likelihood, weighted median, and MR.RAPS methods were performed to detect the causal relationship. Several sensitivity analyses were carried out to evaluate potential horizontal pleiotropy and heterogeneity. Finally, reverse MR analysis was conducted to examine the likelihood of reverse causality, and multivariable MR was performed to adjust the potential confounders.ResultsWe collected 1,505 host single nucleotide polymorphisms (SNPs) linked to 119 gut microbiota traits and 1,873 host SNPs associated with 81 gut metabolite traits as exposure data. Among these, three gut bacteria indicated an elevated risk of IS, two of ICH, and one of SAH. In contrast, five gut bacteria were associated with a reduced risk of IS, one with ICH, and one with SAH. Our study also demonstrated the potential causal associations between 11 gut microbiota-derived metabolites and CVD.ConclusionsThis study provided evidence of the causal relationship between gut microbiota, gut microbiota-derived metabolites, and CVD, thereby offering novel perspectives on gut biomarkers and targeted prevention and treatment for CVD.

Abstract Background Recently, increasing attention has been drawn to the impact of the tumor microenvironment (TME) on the occurrence and progression of malignant tumors. A variety of 3D culture techniques have been used to simulate TME in vitro. The purpose of this study was to reveal the differences in transcriptional and metabolic levels between osteosarcoma (OS) 2D cells, 3D cells, 3D cell-printed tissue, isolated tissue, and transplanted tumor tissue in vivo. Methods We cultured the OS Saos-2 cell line under different culture methods as 2D cells, 3D cells, 3D cell-printed tissue and isolated tissue for 14 days and transplanted tumors in vivo as a control group. Through transcriptomic and metabonomic analyses, we determined the changes in gene expression and metabolites in OS tissues under different culture methods. Results At the transcriptional level, 166 differentially expressed genes were found, including the SMAD family, ID family, BMP family and other related genes, and they were enriched in the TGF-β signaling pathway, complement and coagulation cascades, signaling pathways regulating pluripotency of stem cells, Hippo signaling pathway, ferroptosis, cGMP-PKG signaling pathway and other pathways. At the metabolic level, 362 metabolites were significantly changed and enriched in metabolic pathways such as the Fc Epsilon RI signaling pathway, histidine metabolism, primary bile acid biosynthesis, steroid biosynthesis, protein digestion and absorption, ferroptosis, and arachidonic acid metabolism. After integrating the transcriptome and metabolomics data, it was found that 44 metabolic pathways were changed, and the significantly enriched pathways were ferroptosis and pyrimidine metabolism. Conclusion Different culture methods affect the gene expression and metabolite generation of OS Saos-2 cells. Moreover, the cell and tissue culture method in vitro cannot completely simulate TME in vivo, and the ferroptosis and pyrimidine metabolism pathways mediate the functional changes of OS Saos-2 cells in different microenvironments.

Abstract A stable { $$\stackrel{\mathrm{-}}{1}{\text{10}}$$ 1 - 10 } single component sharp texture was obtained during ambient temperature tube High-Pressure Shearing (t-HPS) of 99.999% purity aluminum. It is shown that the grain size and the grain aspect ratio saturate at ~ 8 μm and ~ 1.6, respectively, at an equivalent strain of ~ 30 and the high-angle grain boundary fraction continues to decrease after this saturation even to equivalent strains exceeding ~ 200. The { $$\stackrel{\mathrm{-}}{1}{\text{10}}$$ 1 - 10 } texture emerges at an equivalent strain of ~ 6 to 9 with the completion of recrystallization and develops gradually as a sole component sharp texture with increasing intensity upon further processing. This component is a stable orientation in t-HPS processing although it was not previously observed experimentally as a shear texture. Thus, t-HPS processing provides a new and effective experimental tool for simple shear testing that is distinctly different from earlier shear strain methods such as torsional processing.

Anti-HER2 resistance causes treatment failure in HER2-positive breast cancers. Here the authors identify FGFR4 as one of the vulnerabilities of anti-HER2 resistant breast cancer and show that FGRR4 inhibition enhances sensitivity to anti-HER2 treatment in these resistant cells by triggering ferroptosis.

Abstract Background The purpose of this retrospective study was to investigate the determinants of postoperative respiratory failure in elderly patients with hip fracture. Methods The subjects of this study were 663 elderly patients who had hip fracture and had been treated with total hip arthroplasty at our hospital from January 2014 to May 2020. According to the occurrence of postoperative respiratory failure, 626 patients with no respiratory failure were retrospectively included in the control group, and 37 cases combined with respiratory failure were enrolled in the PRF group. The clinical and surgical data of the two groups were collected and analyzed to evaluate the determinants of respiratory failure by logistic regression analysis. Results There were no significant differences in the demographics and baseline variables including age, gender, fracture type and location between the groups (P > 0.05). All patients received hip surgery including total hip arthroplasty (THA), hemiarthroplasty (HA) and internal fixation with PFNA (proximal femoral nail anti-rotation). There were no significant differences in operative time and intraoperative blood loss between the groups (P > 0.05). However, close associations were found between pulmonary hypertension (univariate analysis: OR = 3.792, 95% CI = 1.421–10.203; multivariate analysis: OR = 1.132, 95% CI = 1.003–1.251), obstructive pulmonary disease (OR = 1.119, 95% CI = 1.009–1.238; multivariate analysis: OR = 13.298, 95% CI = 4.021–43.298), bronchiectasis and emphysema (OR = 4.949, 95% CI = 1.919–9.873; multivariate analysis: OR = 11.231, 95% CI = 187.87), and history of respiratory failure (OR = 6.098, 95% CI = 2.012–12.198; multivariate analysis: OR = 8.389, 95% CI = 2.391–21.982) with postoperative respiratory failure (P

Abstract Background Silencing of the periostin gene (POSTN) can inhibit the biological process of several different cancers, and this inhibition may be related to down-regulation of PI3K/AKT signaling. However, the effect of POSTN on the progression, proliferation, and invasion of osteosarcoma (OS) remain unclear. Methods We used the Gene Expression Omnibus (GEO) database to screen datasets on in situ OS and lung metastases to identify core genes and potential pathways. We used additional bioinformatics tools to identify protein–protein interactions (PPIs) and gene networks, and selected the top seven genes whose expression had the strongest correlations with other genes. Results The results indicated that POSTN was a major hub gene. Subsequent analysis of gene expression profiles showed that POSTN was highly expressed in 262 cases with sarcoma and expression was closely related to poor prognosis. We also performed enrichment analysis to identify differentially expressed genes and used real-time PCR, western blotting, and immunohistochemistry analyses to measure POSTN expression in cells and tissues. Transfection of a POSTN-shRNA plasmid into cultured OS cells (Saos-2) effectively inhibited the proliferation, invasion, and migration of these cells. Taken together, our results suggest that POSTN may play a role in promoting the proliferation and metastasis of OS by activation of the PI3K/Akt signaling pathway. Conclusions Our results provide a preliminary characterization of the mechanism by which POSTN may regulate the migration and invasion of OS cells and also provide a theoretical basis for identifying biomarkers that have potential use for the diagnosis and treatment of OS.

BackgroundAssessing the correlation between gut microbiota (GM) and bone homeostasis has increasingly attracted research interest. Meanwhile, GM dysbiosis has been found to be associated with abnormal bone metabolism. However, the function of GM in disuse-induced osteoporosis (DIO) remains poorly understood. In our research, we evaluated the characteristics of GM and fecal metabolomics to explore their potential correlations with DIO pathogenesis.MethodsDIO rat models and controls (CON) underwent micro-CT, histological analyses, and three-point bending tests; subsequently, bone microstructures and strength were observed. ELISAs were applied for the measurement of the biochemical markers of bone turnover while GM abundance was observed using 16S rDNA sequencing. Metabolomic analyses were used to analyze alterations fecal metabolites. The potential correlations between GM, metabolites, and bone loss were then assessed.ResultsIn the DIO group, the abundance of GM was significantly altered compared to that in the CON group. Moreover, DIO significantly altered fecal metabolites. More specifically, an abnormally active pathway associated with bile acid metabolism, as well as differential bacterial genera related to bone/tissue volume (BV/TV), were identified. Lithocholic acid, which is the main secondary bile acid produced by intestinal bacteria, was then found to have a relationship with multiple differential bacterial genera. Alterations in the intestinal flora and metabolites in feces, therefore, may be responsible for DIO-induced bone loss.ConclusionsThe results indicated that changes in the abundance of GM abundance and fecal metabolites were correlated with DIO-induced bone loss, which might provide new insights into the DIO pathogenesis. The detailed regulatory role of GM and metabolites in DIO-induced bone loss needs to be explored further.

White clover (Trifolium repens L.) is one of the legume herbages with high feed quality, but it is sensitive to water deficiency. The objectives of this study were to compare morpho-physiological responses to drought stress and post-drought recovery in four-leafed white clover cultivars. Under well-watered conditions, drought stress (3 d, 6 d, 9 d and 12 d), and rehydration, the relative water content (RWC), membrane lipid permeability, osmoregulatory substances, photosynthetic characteristics and stomatal features of Chinese native Longping No.1 (LP, small-leafed) and three introduced cultivars, namely Pudi (PD, small-leafed), Rivendel (RD, medium-leafed) and Koala (KL, large-leafed), were evaluated. Results showed that small-leafed white clover maintained higher RWC and better membrane stability and osmotic regulation with increased drought intensities, compared to the medium-leafed and large-leafed cultivars. Following rewatering, small-leafed white clover recovered more rapidly with all of the parameters than the other cultivars. The increase of drought stress intensity led to the decline of net photosynthetic rate (Pn), transpiration rate (Tr) and stomatal conductance (Cs). However, the decreased range of Pn, Tr and Cs in the small-leafed white clover was significantly smaller than that in the medium-leafed and large-leafed white clovers. Meanwhile, the small-leafed white clover showed a smaller size and higher density of stoma either under normal or drought conditions than the intermediate- and large-leafed cultivars. Taken together, the results indicated that the adaptability of small-leafed white clover to drought stresses and post-drought recovery was better than that of medium-leafed and large-leafed white clovers. The study will provide better insights into the mechanism of drought response and recovery potential in different white clover cultivars.

Abstract Background MicroRNAs (miRNAs) show considerable promise as therapeutic agents to improve tumor treatment, as they have been revealed as crucial modulators in tumor progression. However, our understanding of their roles in gastric carcinoma (GC) metastasis is limited. Here, we aimed to identify novel miRNAs involved in GC metastasis and explored their regulatory mechanisms and therapeutic significance in GC. Methods The microRNA expression profiles of GC tumors at different stages and at different metastasis statuses were compared respectively using the stomach adenocarcinoma (STAD) miRNASeq dataset in TCGA. Using the above method, miR-4521 was picked out for further study. miR-4521 expression in GC tissues was examined by quantitative reverse transcription polymerase chain reaction (qRT-PCR) and in situ hybridization (ISH). Highly and lowly invasive cell sublines were established using a repetitive transwell assay. Gain-of-function and loss-of-function analyses were performed to investigate the functions of miR-4521 and its upstream and downstream regulatory mechanisms in vitro and in vivo. Moreover, we investigated the therapeutic role of miR-4521 in a mouse xenograft model. Results In this study, we found that miR-4521 expression was downregulated in GC tissues compared with adjacent normal tissues and that its downregulation was positively correlated with advanced clinical stage, metastasis status and poor patient prognosis. Functional experiments revealed that miR-4521 inhibited GC cell invasion and metastasis in vitro and in vivo. Further studies showed that hypoxia repressed miR-4521 expression via inducing ETS1 and miR-4521 mitigated hypoxia-mediated metastasis, while miR-4521 inactivated the AKT/GSK3β/Snai1 pathway by targeting IGF2 and FOXM1, thereby inhibiting the epithelial-mesenchymal transition (EMT) process and metastasis. In addition, we demonstrated that therapeutic delivery of synthetic miR-4521 suppressed gastric carcinoma progression in vivo. Conclusions Our results suggest an important role for miR-4521 in regulating GC metastasis and hypoxic response of tumor cells as well as the therapeutic significance of this miRNA in GC.

Abstract The increasing demand for exploring and managing the vast marine resources of the planet has underscored the importance of research on advanced underwater acoustic communication (UAC) technologies. However, owing to the severe characteristics of the oceanic environment, underwater acoustic (UWA) propagation experiences nearly the harshest wireless channels in nature. This article resorts to the perspective of machine learning (ML) to cope with the major challenges of adaptive modulation and coding (AMC) design in UACs. First, we present an ML AMC framework for UACs. Then, we propose an attention-aided k-nearest neighbor (A-kNN) algorithm with simplicity and robustness, based on which an ML AMC approach is designed with immunity to channel modeling uncertainty. Leveraging its online learning ability, such A-kNN-based AMC classifier offers salient capabilities of both sustainable self-enhancement and broad applicability to various operation scenarios. Next, aiming at higher implementation efficiency, we take strategies of complexity reduction and present a dimensionality-reduced and data-clustered A-kNN (DRDC-A-kNN) AMC classifier. Finally, we demonstrate that these proposed ML approaches have superior performance over traditional model-based methods by simulations using actual data collected from three lake experiments.

Abstract Importance Cancer is the main cause of death by disease in children. Children experience the highest incidence of cancer in the first year of life. However, there is no comprehensive registration system for children with tumors in China. Objective To summarize the diagnosis and treatment of infant cancer and analyze the status of standardized diagnosis and management among several treatment centers in Beijing, China, thereby providing evidence to guide further clinical research. Methods From January 1, 2010 to December 31, 2019, patients with newly diagnosed infantile malignant solid tumors were admitted to six large tertiary pediatric solid tumor diagnosis and treatment centers in Beijing. The epidemiology, clinical features, and therapeutic effects of tumors in these patients were analyzed retrospectively. All patients were followed up until March 31, 2020. Results In total, 938 patients were enrolled in this study. There were 530 boys (56.5%) and 408 girls (43.5%); the median age was 6.0 months (range, 0–12.0 months). The three most common tumors were retinoblastoma in 366 patients (39.0%), neuroblastoma in 266 patients (28.4%), hepatoblastoma in 133 patients (14.2%), and central nervous system tumors in 52 patients (5.5%). The estimated 5‐year overall survival rate was 81.3% ± 1.8%, and the 5‐year event‐free survival rate was 71.8% ± 2.9%. The 5‐year overall survival rates of non‐rhabdomyosarcoma soft tissue sarcoma, neuroblastoma, and retinoblastoma were 100%, 88% ± 2.2%, and 86.9% ±2.1%, respectively. The 5‐year event‐free survival rates were 81.1% ± 2.7% for neuroblastoma, 81.6% ± 9.8% for non‐rhabdomyosarcoma soft tissue sarcoma, and 72.7% ± 14.1% for extracranial malignant germ cell tumors. Interpretation The three most common infantile malignant solid tumors were retinoblastoma, neuroblastoma, and hepatoblastoma. Multidisciplinary combined diagnosis and treatment is needed for infantile tumors.

Adenosine (ADO) involvement in lung injury depends on the activation of its receptors. The ADO A2A receptor (ADORA2A) and A2B receptor (ADORA2B) are best described to have both tissue-protective and tissue-destructive processes. However, no approach has been effective in delineating the mechanism(s) involved with ADO shifting from its tissue-protective to tissue-destructive properties in chronic airway injury. Using cigarette smoke (CS) as our model of injury, we chronically exposed Nuli-1 cells to 5% CS extract (CSE) for 3 years establishing a long-term CSE exposure model (LTC). We found significant morphological changes, decreased proliferation, and migration resulting in impaired airway wound closure in LTC. Further investigations showed that long-term CSE exposure upregulates CD73 and ADORA2B expression, increases ADO production, inhibits PKC alpha activity and p-ERK signaling pathway. Knocking down ADORA2B and/or CD73 in LTC activates PKC alpha and increases p-ERK signaling. Knocking down both showed better improvement in wound repair than either alone. In vivo experiments also showed that double knockout CD73 and ADORA2B remarkably improved CS-induced lung injury by activating PKC alpha, reducing the inflammatory cell number in bronchoalveolar lavage fluid and the production of inflammatory mediator IL-6, inhibiting the fibrosis-like lesions and decreasing collagen deposition surrounding bronchioles. Collectively, long-term CSE exposure upregulates CD73 expression and increases ADO production, which promotes low affinity ADORA2B activation and subsequent diminution of PKC alpha activity and ERK signaling pathway, and inhibition of airway wound repair. Moreover, the data suggesting ADORA2B and CD73 as potential therapeutic targets may be more efficacious in improving chronic CS lung diseases and impaired wound repair.

The total organic carbon (TOC) content is a critical parameter for estimating shale oil resources. However, common TOC prediction methods rely on empirical formulas, and their applicability varies widely from region to region. In this study, a novel data-driven Bayesian optimization extreme gradient boosting (XGBoost) model was proposed to predict the TOC content using wireline log data. The lacustrine shale in the Damintun Sag, Bohai Bay Basin, China, was used as a case study. Firstly, correlation analysis was used to analyze the relationship between the well logs and the core-measured TOC data. Based on the degree of correlation, six logging curves reflecting TOC content were selected to construct training dataset for machine learning. Then, the performance of the XGBoost model was tested using K-fold cross-validation, and the hyperparameters of the model were determined using a Bayesian optimization method to improve the search efficiency and reduce the uncertainty caused by the rule of thumb. Next, through the analysis of prediction errors, the coefficient of determination (R2) of the TOC content predicted by the XGBoost model and the core-measured TOC content reached 0.9135. The root mean square error (RMSE), mean absolute error (MAE), and mean absolute percentage error (MAPE) were 0.63, 0.77, and 12.55%, respectively. In addition, five commonly used methods, namely, ΔlogR method, random forest, support vector machine, K-nearest neighbors, and multiple linear regression, were used to predict the TOC content to confirm that the XGBoost model has higher prediction accuracy and better robustness. Finally, the proposed approach was applied to predict the TOC curves of 20 exploration wells in the Damintun Sag. We obtained quantitative contour maps of the TOC content of this block for the first time. The results of this study facilitate the rapid detection of the sweet spots of the lacustrine shale oil.

BackgroundThe recent emergence and rapid global spread of coronavirus disease 2019 (COVID-19) is leading to public health crises worldwide. Alcohol consumption and cigarette smoking (CS) are two known risk factors in many diseases including respiratory infections.MethodsWe performed a multi-center study in the four largest hospitals designated for COVID-19 patients in Wuhan. There are totally 1547 patients diagnosed with COVID-19 enrolled in the study, alcohol consumption and CS history were evaluated among these patients. The epidemiology, laboratory findings and outcomes of patients contracted COVID-19 were further studied.ResultsOur findings indicated that COVID-19 patients with a history of CS tend to have more severe outcomes than non-smoking patients. However, alcohol consumption did not reveal significant effects on neither development of severe illness nor death rates in COVID-19 patients.ConclusionCS is a risk factor for developing severe illness and increasing mortality during the SARS-CoV-2 infection. We believe that our findings will provide a better understanding on the effects of alcohol intake and CS exposure in COVID-19 patients.

Understanding the differences in cool-season turfgrass responses to shade is critical for future turfgrass management and breeding for improved shade tolerance. The purpose of this study was to evaluate the shade-tolerance mechanisms of two cool-season turfgrass species in terms of turf performance, growth, and physiological characteristics. Two turfgrass species, namely, ’SupraNova’ (Poa. supina Schrad.) and ‘Lark’ (Lolium perenne L.), were subjected to 0 (CK, unshaded), 35% (LS), 70% (MS), and 92% (HS) shade, respectively. Compared with ‘Lark’, ‘SupraNova’ showed better turf quality (TQ) and turf color intensity (TCI) under shade. The total length and surface area of the roots of ‘Lark’ gradually decreased as the shade increased, while those of ‘SupraNova’ increased and then decreased with increasing shade. The chlorophyll fluorescence photochemical quenching coefficient (qP), electron transport rate (ETR), and maximum quantum yield of primary photosystem II (PSII) photochemistry (Fv/Fm) decreased significantly under HS; however, these decreases were more significant in ‘Lark’ than in ‘SupraNova’. The leaf reflectance of the two turfgrasses under shade was lower than that under CK, but the leaf reflectance of ‘Lark’ was higher than that of ‘SupraNova’ in the visible light band. The normalized difference vegetation index (NDVI) of the two grasses first decreased and then increased. The NDVI of ‘Lark’ under shade was slightly higher than that under CK. ‘SupraNova’ showed strong tolerance on the basis of malondialdehyde (MDA), hydrogen peroxide (H2O2), superoxide anion (O2·−), and ascorbic acid (AsA) contents and superoxide dismutase (SOD), peroxidase (POD), and catalase (CAT) activity. The MDA, H2O2, O2·−, and AsA contents and SOD, POD, and CAT activity (which represent indicators) changed the most under MS. Taken together, the results indicated that the adaptability of ‘SupraNova’ to shade was better than that of ‘Lark’.

Abstract Objective To evaluate the overall diagnostic value related to magnetic resonance imaging (MRI) in patients with early osteonecrosis of the femoral head. Methods By searching multiple databases and sources, including PubMed, Cochrane, and Embase database, by the index words updated in December 2017, qualified studies were identified and relevant literature sources were also searched. The qualified studies included prospective cohort studies and cross-sectional studies. Heterogeneity of the included studies were reviewed to select proper effect model for pooled weighted sensitivity, specificity, and diagnostic odds ratio (DOR). Summary receiver operating characteristic (SROC) analyses were performed for meniscal tears. Results Forty-three studies related to diagnostic accuracy of MRI to detect early osteonecrosis of the femoral head were involved in the meta-analysis. The global sensitivity and specificity of MRI in early osteonecrosis of the femoral head were 93.0% (95% CI 92.0–94.0%) and 91.0% (95% CI 89.0%–93.0%), respectively. The global positive likelihood ratio and global negative likelihood ratio of MRI in early osteonecrosis of the femoral head were 2.74 (95% CI 1.98–3.79) and 0.18 (95% CI 0.14–0.23), respectively. The global DOR was 27.27 (95% CI 17.02–43.67), and the area under the SROC was 93.38% (95% CI 90.87%–95.89%). Conclusions This review provides a systematic review and meta-analysis to evaluate the diagnostic accuracy of MRI in early osteonecrosis of the femoral head. Moderate to strong evidence indicated that MRI appears to be significantly associated with higher diagnostic accuracy for early osteonecrosis of the femoral head.

Abstract Backgroud The purpose of this study was to elucidate the regulation of programmed death ligand 1 (PDL1), lactate dehydrogenase A (LDHA) and miR-34a in triple negative breast cancer (TNBC) and to explore the function and mechanism of PDL1 and LDHA as competitive endogenous RNAs (ceRNAs) in TNBC via regulation of miR-34a. Methods Western blotting, quantitative RT-PCR (qRT-PCR) and immunohistochemistry (IHC) assays were conducted to explore the expression of PDL1, LDHA and miR-34a in TNBC and correlations between them. MTS cell viability, Transwell migration, glucose consumption and lactate production assays and flow cytometry were performed and mouse xenograft models were constructed to explore the functions and regulation of the PDL1 3’UTR and LDHA 3’UTR and miR-34a in TNBC. Results We found that PDL1 and LDHA were synchronously upregulated in TNBC cell lines and tissues. Co-expression of PDL1 and LDHA was correlated with poor outcome in TNBC. Both PDL1 and LDHA are targets of miR-34a, and the 3’UTRs of PDL1 and LDHA both have binding sites for miR-34a. The functions of PDL1 and LDHA were inhibited by miR-34a. In addition, PDL1 and LDHA acted as ceRNAs to promote the expression and function of each other through regulation of miR-34a in TNBC. Conclusions This study provides a new theoretical basis for a novel TNBC therapeutic strategy. Simultaneously targeting PDL1 and LDHA, which would combine immunotherapy and metabolically targeted treatments, might shed some light on the treatment of breast cancer, especially TNBC.

Abstract Background AHNAK, also known as desmoyokin, is a giant protein with the molecular size of approximately 700 kDa and exerts diverse functions in different types of cancer. Results In the present study, we demonstrated that AHNAK mRNA levels were down-regulated in 7 out of 8 human breast cancer cell lines, especially in triple - negative breast cancer (TNBC) cell lines. Moreover, in patients with TNBC, the expression of AHNAK gene was inversely correlated with the tumor status (P = 0.015), lymph node status (P

Background: Although the diagnosis and treatment of glioblastoma (GBM) is significantly improved with recent progresses, there is still a large heterogeneity in therapeutic effects and overall survival. The aim of this study is to analyze gene expressions of transcription factors (TFs) in GBM so as to discover new tumor markers.Methods: Differentially expressed TFs are identified by data mining using public databases. The GBM transcriptome profile is downloaded from The Cancer Genome Atlas (TCGA). The nonnegative matrix factorization (NMF) method is used to cluster the differentially expressed genes to discover hub genes and signal pathways. The TFs affecting the prognosis of GBM are screened by univariate and multivariate COX regression analysis, and the receiver operating characteristic (ROC) curve is determined. The GBM hazard model and nomogram map are constructed by integrating the clinical data. Finally, the TFs involving potential signaling pathways in GBM are screened by Gene Set Enrichment Analysis (GSEA), Gene Ontology (GO), and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis.Results: There are 68 differentially expressed TFs in GBM, of which 43 genes are upregulated and 25 genes are downregulated. NMF clustering analysis suggested that GBM patients are divided into three groups: Clusters A, B, and C. LHX2, MEOX2, SNAI2, and ZNF22 are identified from the above differential genes by univariate/multivariate regression analysis. The risk score of those four genes are calculated based on the beta coefficient of each gene, and we found that the predictive ability of the risk score gradually increased with the prolonged predicted termination time by time-dependent ROC curve analysis. The nomogram results have showed that the integration of risk score, age, gender, chemotherapy, radiotherapy, and 1p/19q can further improve predictive ability towards the survival of GBM. The pathways in cancer, phosphoinositide 3-kinases (PI3K)–Akt signaling, Hippo signaling, and proteoglycans, are highly enriched in high-risk groups by GSEA. These genes are mainly involved in cell migration, cell adhesion, epithelial–mesenchymal transition (EMT), cell cycle, and other signaling pathways by GO and KEGG analysis.Conclusion: The four-factor combined scoring model of LHX2, MEOX2, SNAI2, and ZNF22 can precisely predict the prognosis of patients with GBM.

Ethanol (EtOH) is the world’s most commonly used drug, and has been widely recognized as a risk factor for developing lung disorders. Chronic EtOH exposure affects all of the organ systems in the body and increases the risk of developing pulmonary diseases such as acute lung injury and pneumonia, while exacerbating the symptoms and resulting in increased mortality in many other lung disorders. EtOH and its metabolites inhibit the immune response of alveolar macrophages (AMs), increase airway leakage, produce damaging reactive oxygen species (ROS), and disrupt the balance of antioxidants/oxidants within the lungs. In this article, we review the role of EtOH exposure in the pathogenesis and progression of pulmonary disease.

Website development without prior knowledge of HTML or programming experience would be a significant challenge. This study aims to share the students' experiences developing a website using Wix, a user-friendly website builder. The website was assigned as a project-based assessment of one of the courses required to complete a Foundation programme. The course was delivered using a project-based learning (PBL) approach in this context. The students worked as a group to write a project proposal, plan activities, develop the website, write reports, and present the outcome. As for the website development process, the study demonstrates the completion of the project using the Waterfall model, a sequential approach to the software development lifecycle (SDLC). In summary, this study aims to explore the use of Wix for web development, the PBL approach for course delivery, and the Waterfall model for completing the website project. The result shows that the students could complete the website development project in a timely manner by using Wix as their web design platform and adopting the Waterfall model as their project management approach. In addition, the students also benefitted from the PBL approach. The outcomes of this study will be of great benefit to educators, particularly in their role in helping students complete their website development projects.