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Abstract Mycoplasma gallisepticum (MG) can induce persistent inflammatory damage to the tracheal mucosa of poultry and cause chronic respiratory diseases in chickens. To further investigate the mechanism of MG-induced injury to the tracheal mucosa, we used chick embryo tracheal organ culture (TOC) as a model to study the invasion and reproduction of MG, the effect of MG on tracheal morphology, and the potential factors that promote MG tissue invasion. The results showed that MG infection significantly damaged the tracheal epithelial structure and weakened tracheal epithelial barrier function; MG also increased the occurrence of bacterial displacement, with a significant (p

Fostering sustainable development through green supply chains is of paramount significance. Government subsidies emerge as a successful strategy for motivating businesses to actively participate in such eco-friendly practices. This study employs prospect theory and an evolutionary game model to analyze the transition toward carbon peaking and neutrality while promoting the expansion of highly sustainable businesses. By exploring the decision-making processes of businesses and governments regarding sustainability, we develop an evolutionary game-based decision model to assess the impact of government subsidies on businesses engaged in green supply chains. Through numerical simulation obtained via MATLAB, we examine various factors influencing the evolution of the game system between green supply chain businesses and the government. Additionally, we investigate how government incentives impact the decision-making behavior of green supply chain businesses. Our findings indicate that governmental fines can effectively encourage the adoption of green supply chains. Furthermore, moderate government subsidies incentivize enterprises to opt for sustainable supply chains, benefiting both the government and businesses. However, providing hefty government subsidies not only fails to encourage the adoption of green supply chains but also incurs costs for the government, without yielding any positive change in the businesses’ approach. By incorporating evolutionary game theory and prospect theory, this study contributes to the body of knowledge on government-supported green supply chains, offering incentive programs tailored to the real-world conditions faced by businesses while demonstrating practical application values.

ABSTRACTMetabolic reprogramming is an important feature in tumor progression. Long noncoding RNA’s (lncRNA) small nucleolar RNA host gene 6 (SNHG6) acts as a proto-oncogene in hepatocellular carcinoma (HCC) but its role in glycolysis is mostly unknown. The role of SNHG6 and Block of proliferation 1 (BOP1) on glycolysis is assessed by glucose uptake, lactate production, oxygen consumptive rate (OCR) and extracellular acidification rate (ECAR) and glycolytic enzyme levels. The regulatory effect of SNHG6 on BOP1 protein was confirmed by Western blotting, MS2 pull-down, RNA pull-down, and RIP assay. SNHG6 and BOP1 levels were increased in HCC tissues and cells. SNHG6 and BOP1 were prognostic factors in HCC patients and significantly correlated to TP53 mutant and tumor grade. SNHG6 promoted proliferation, inhibited apoptosis, enhanced glucose uptake and lactate production, decreased OCR, and increased ECAR in HCC cell lines. SNHG6 could bind the BOP1 protein and enhance its stability. BOP1 overexpression rescued the change of proliferation, apoptosis, and glycolysis in HCCLM3 and SMMC-7721 cells. Our data indicate that SNHG6 accelerates proliferation and glycolysis and inhibits the apoptosis of HCC cell lines by binding the BOP1 protein and enhancing its stability. Both SNHG6 and BOP1 are promising prognostic and therapeutic markers in HCC.

The construction industry has made an indispensable contribution to China’s environmental and economic development. With the advent of the volatile, uncertain, complex, and ambiguous (VUCA) era, cross-organizational collaboration has enabled megaproject participants to engage significantly in problem-solving and technological innovation. The impact of innovation organization network on the synergy of cross-organizational technological innovation (COTI synergy) in megaprojects is imperative for theoretical researchers and engineering practitioners. Therefore, this study aims to develop a hypothetical model of innovation organization network and COTI synergy, focusing on the mediating role of interorganizational relationships and the moderating effect of the technological innovation environment. The results of 211 questionnaires from the Chinese construction industry show that innovation organization network improves COTI synergy. Trust and communication play a vital mediating role between innovation organization network and COTI synergy. Moreover, innovative culture has a significant positive moderating effect on innovation organization network and interorganizational relationships. From the perspective of organization network, this study provides new insights into the development of technological innovation management research on megaprojects, theoretical references, and practical suggestions for project teams in developing countries to improve collaborative technological innovation efficiency.

Oil-based drilling fluid is currently widely utilized when drilling shale, in which the oleophilic nano-plugging agent is the major component for wellbore strengthening. However, there have been few effective and straightforward evaluation methods for the nano-plugging agent. In this study, an artificial filter cake was created to simulate the microfissure of shale formation, and the performance of the nano-plugging agent was assessed using the fluid-loss reduction rate as the index. The filter cake was made from compound crystal weights and a high molecular weight polymer, and a nano-plugging agent matching the formation pore structures was selected. The performance of three plugging agents with varying particle sizes (ultrafine CaCO3, emulsified modified rubber MORLF, ULIA nano-plugging agent) was compared. Moreover, the validity of the evaluation process was confirmed, and the underlying plugging mechanism was investigated. The proposed technique can produce an artificial filter cake with a constant thickness of 3 × 10−3 m and a permeability in the range of 10−18 to 10−19 m2, and the assessment approach is consistent, precise and easy to use. This work may provide a guideline for evaluating oleophilic nano-plugging agents in the laboratory and field applications.

Without the active participation of enterprises and front-line workers, it is difficult for the government to perform effective supervision to ensure behavioral safety among front-line workers. To overcome inadequate government supervision and information attenuation caused by vertical management mode and limited resources, and to change passive supervision into active control with the proactive participation of enterprises and workers, this paper combines the entity responsibility mechanism and the third-party participation mechanism based on government supervision to analyze the decision-making process of government and enterprises on safety behavior supervision. An evolutionary game model was established to describe the decision-making interactions between the government and construction enterprises under the two mechanisms, and a simulation was performed to illustrate the factors influencing the implementation of the mechanisms. The results show that both mechanisms have a positive effect on government supervision, and the third-party participation mechanism was found to be working better. The implementation of the two mechanisms is influenced by punishment, subsidy, and cost, and it has different sensitivities to the three influencing factors. This study provides a theoretical framework for enhancing the government supervision mechanism, and the decision-making between the government and construction enterprises enhances the management form and guides their actual supervision practices.

Abstract Background A growing number of patients continue to receive total knee replacement (TKR) surgery. Nevertheless, such surgeries result in moderate to severe postoperative pain and difficulty in managing it. Musical interventions are regarded as a type of multimodal analgesia, achieving beneficial results in other clinical treatments. This study aims to evaluate the effect of musical interventions in improving short-term pain outcomes following TKR in order to determine a more reasonable and standard way of delivering musical intervention. Methods A systematic search was conducted to identify available and relevant randomized controlled trials (RCTs) regarding musical interventions compared against non-musical interventions in patients treated with TKR in Embase, MEDLINE, Cochrane Library, Web of Science, CNKI, and Wanfang Med Online up to 8 January 2020. The authors independently assessed study eligibility and risk of bias and collected the outcomes of interest to analyze. The statistical analysis was conducted using the Review Manager (RevMan) version 5.30 software. Results Eight RCTs comprised of 555 patients satisfied the inclusion criteria and were enrolled in the present study. The results showed no significant difference between the music and control groups in pain of the visual analog scale (VAS), during postoperative recovery room, back to the ward after surgery; anxiety degree of VAS; heart rate; respiratory rate; oxygen saturation; blood pressure, systolic blood pressure, and diastolic blood pressure. Nevertheless, significant differences were observed between the two groups in average increase in continuous passive motion (CPM) angles and LF/HF ratio (one kind index of heart rate variability). Conclusions Musical interventions fail to demonstrate an obvious effect in improving short-term pain outcomes following TKR. A reasonable standardization of musical interventions, including musical type, outcome measures used, outcomes measured, duration, timing and headphones or players, may improve pain outcomes with certain advantages and should be further explored after TKR.

Early cancer detection is the key to a positive clinical outcome. While a number of early diagnostics methods exist in clinics today, they tend to be invasive and limited to a few cancer types. Thus, a clear need exists for non-invasive diagnostics methods that can be used to detect the presence of cancer of any type. Liquid biopsy based on analysis of molecular components of peripheral blood has shown significant promise in such pan-cancer diagnostics; however, existing methods based on this approach require improvements, especially in sensitivity of early-stage cancer detection. The improvement would likely require diagnostics assays based on multiple different types of biomarkers and, thus, calls for identification of novel types of cancer-related biomarkers that can be used in liquid biopsy. Whole-blood transcriptome, especially its non-coding component, represents an obvious yet under-explored biomarker for pan-cancer detection. In this study, we show that whole transcriptome analysis using RNA-seq could indeed serve as a viable biomarker for pan-cancer detection. Furthermore, a class of long non-coding (lnc) RNAs, very long intergenic non-coding (vlinc) RNAs, demonstrated superior performance compared with protein-coding mRNAs. Finally, we show that age and presence of non-blood cancers change transcriptome in similar, yet not identical, directions and explore implications of this observation for pan-cancer diagnostics.

3D printing (3DP) is regarded as an innovation that contributes to automation in civil engineering and offers benefits in design, greenness, and efficiency. It is necessary to objectively analyze the current status and challenges associated with 3DP and identify future research directions to properly understand its construction applications. Previous research has focused more on the technical dimension of 3DP; however, the nontechnical dimension of the technology may hinder its implementation and thus must be paid particular attention to. This study presents a systematic review of the existing literature from both technical and nontechnical dimensions by combining quantitative and qualitative studies. The quantitative study was conducted using scientometric methods. The qualitative study analyzed information, including the technical research status and nontechnical challenges and trends. Two aspects of technical research status are presented, including materials and processes. In addition, nontechnical challenges and trends from the economic, environmental, social, and legislative aspects are proposed. This study provides a comprehensive agenda to advance 3DP in construction and proposes research interests, challenges, and future topics. It is intended to help construction practitioners systematically master existing processes and materials and assess the application degree and necessity of 3DP.

Background: The current study aimed to determine the impact of SARS-CoV-2 infection on male fertility. Methods: This is a single-center, hospital-based observational study that included autopsied testicular and epididymal specimens of deceased COVID-19 male patients (n=6) and recruited recovering COVID-19 inpatients (n=23) with an equal number of age-matched controls, respectively. We performed histopathological examinations on testicular and epididymal specimens, and also performed TUNEL assay and immunohistochemistry. Whereas, we investigated the semen specimen for sperm parameters and immune factors. Findings: Autopsied testicular and epididymal specimens of COVID-19 showed the presence of interstitial edema, congestion, red blood cell exudation in testes, and epididymides. Thinning of seminiferous tubules was observed. The number of apoptotic cells within seminiferous tubules was significantly higher in COVID-19 compared to control cases. It also showed an increased concentration of CD3+ and CD68+ in the interstitial cells of testicular tissue and the presence of IgG within seminiferous tubules. Semen from COVID-19 inpatients showed that 39.1% (n=9) of them have oligozoospermia, and 60.9% (n=14) showed a significant increase in leucocytes in semen. Decreased sperm concentration, and increased seminal levels of IL-6, TNF-α, and MCP-1 compared to control males were observed. Interpretation: Impairment of spermatogenesis was observed in COVID-19 patients, which could be partially explained as a result of an elevated immune response in testis. Additionally, autoimmune orchitis occurred in some COVID-19 patients. Further research on the reversibility of impairment and developing treatment are warranted. Funding: This study was supported by Ministry of Science and Technology of China Plan, Hubei Science and Technology Plan, National Key Research and Development Program of China, HUST COVID-19 Rapid Response Call, China and National Natural Science Foundation of China; these funding bodies are public institutions, and they had no role in study conception, design, interpretation of results, and manuscript preparation.

Background: Cervical cancer ranks fourth in incidence and mortality among women. Ubiquitin-specific protein 53 binds to damage-specific DNA binding protein 2 and affects the biological properties of colon cancer. Damage-specific DNA binding protein is involved in nucleotide excision repair, which can repair DNA damage. However, the mechanism by which ubiquitin-specific protein 53 regulates the radiosensitivity of cervical cancer through damage-specific DNA binding protein remains unclear. Methods: Tissue samples from 40 patients with cervical squamous cell carcinoma who received radiotherapy were examined by immunohistochemistry to detect the expression of ubiquitin-specific protein 53, and clinical data were collected for statistical analysis. The cell cycle was detected by flow cytometry in Siha cells transfected with Si-USP53 and exposed to 8 Gy irradiation. Cell viability was determined by the CCK8 method in cells transfected with Si-USP53 and exposed to 0, 2, 4, 6, 8, or 10 Gy. The expression of damage-specific DNA binding protein, cyclin-dependent kinase 1, and cell cycle checkpoint kinase 2 was detected in cells transfected with Si-USP53. Results: The expression of ubiquitin-specific protein 53 in the tissues of patients with cervical squamous cell carcinoma was correlated with the sensitivity to radiotherapy. Knockdown of ubiquitin-specific protein 53 in Siha cells downregulated damage-specific DNA binding protein and caused G2/M cell cycle arrest and decreased the survival rate of cells in response to radiation. Conclusion: Ubiquitin-specific protein 53–induced cell cycle arrest and affected the radiotherapy sensitivity of tumors through damage-specific DNA binding protein.

Particle mixing process is critical for the design and quality control of concrete and composite production. This paper develops an algorithm to simulate the high-shear mixing process of a granular flow containing a high proportion of solid particles mixed in a liquid. DEM is employed to simulate solid particle interactions; whereas SPH is implemented to simulate the liquid particles. The two-way coupling force between SPH and DEM particles is used to evaluate the solid-liquid interaction of a multi-phase flow. Using Darcy’s Law, this paper evaluates the coupling force as a function of local mixture porosity. After the model is verified by two benchmark case studies, i.e., a solid particle moving in a liquid and fluid flowing through a porous medium, this method is applied to a high shear mixing problem of two types of solid particles mixed in a viscous liquid by a four-bladed mixer. A homogeneity metric is introduced to characterize the mixing quality of the particulate mixture. The virtual experiments with the present algorithm show that adding more liquid or increasing liquid viscosity slows down the mixing process for a high solid load mix. Although the solid particles can be mixed well eventually, the liquid distribution is not homogeneous, especially when the viscosity of liquid is low. The present SPH-DEM model is versatile and suitable for virtual experiments of particle mixing process with different blades, solid particle densities and sizes, and liquid binders, and thus can expedite the design and development of concrete materials and particulate composites.

In user-pay public private partnership (PPP) projects, private sectors collect user fees to cover cost and reap revenue. For projects that cannot be self-financed, public sectors usually invest public funds to make them financially feasible. The concession agreement allocates revenues and risks, and lies in the center of balancing public and private interests. However, stakeholders may have contrary opinions regarding the optimization of concession agreement. While private sectors are concerned about earning money, public sectors pay more attention to the efficient use of public funds. To address this challenge, this paper firstly identifies several key concessionary items, including concession period, concession price, capital structure and government subsidy. Then, a multi-objective optimization model is presented using discounted cash flow method, in which key concessionary items act as decision variables and public and private interests are represented by two sub-objectives. Subsequently, the model is solved using non-dominated sorting genetic algorithm-II (NSGA-II). Furthermore, a numerical case based on Beijing No. 4 Metro Line is provided to demonstrate the application of the model. Results show that the proposed model can produce a series of viable combinations of concessionary items that balance public and private interests, which provides practical references for relative decision making activities.

BIM (building information modeling) can be the basis for carrying out various performance analyses. Sustainable infrastructure rating systems are suitable tools for assessing an infrastructure’s environmental performance. It is necessary to integrate them in the design process. The research adopted a thorough literature review to follow the development trends, interviews with professionals from the academia and industry, and a critical analysis of technical requirements for integrating BIM tools and infrastructure sustainability rating systems in the design process. This study propagates a conceptual framework for integrating sustainability rating systems by introducing BIM with a sustainability metric plug-in. The adoption of the proposed solution allows for what-if scenarios to better support the incorporation of sustainability into design decisions and the assessment of sustainability at the design phase of the infrastructure project. The framework is used to refine designs and ensure that sustainable goals are met and to demonstrate compliance with regulatory requirements. This paper concludes that greater emphasis should be placed on supporting technical requirements to facilitate the integration of BIM and sustainability rating systems. It defines the possibility of BIM adoption to influence the sustainable project performance in the infrastructure. This framework could streamline the sustainable design process and lead to more integrated infrastructure delivery.

Conflicting results were reported on the association between the TNF-α -308G/A polymorphism and idiopathic recurrent miscarriage (IRM). Though three meta-analyses have been conducted on this topic, the conclusions were contradictory, and the results may be unreliable as certain crucial conditions were neglected.A complete search was conducted in PubMed, Cochrane Library, and Embase, other sources like Google Scholar, ClinicalTrial.gov and reference lists of relevant articles were also retrieved. All candidate articles were accessed and screened using specific inclusion and exclusion criteria. Statistical analyses were performed on data extracted from eligible studies using the STATA 12.0 software and the TSA 0.9 beta software.Eventually, 12 case-control studies from 11 publications (with 1,807 cases and 2,012 controls) were included in this meta-analysis, and no evidence of any significant association was found in the overall analyses between the TNF-α -308G/A polymorphism and IRM risk. However, significant association was shown in Asian population (four studies from three publications) in the dominant model (AA + GA vs. GG), the allelic model (A vs. G), and the heterozygote model (GA vs. GG).TNF-α -308G/A polymorphism is not associated with IRM risk. Though significant association was found in Asian population, the result needs further confirmation from more studies.

Cholangiocarcinoma, also known as bile duct cancer, is the second most common primary hepatic carcinoma with a median survival of less than 2 years. The molecular mechanisms underlying the development of this disease are not clear. To survey activated tyrosine kinases signaling in cholangiocarcinoma, we employed immunoaffinity profiling coupled to mass spectrometry and identified DDR1, EPHA2, EGFR, and ROS tyrosine kinases, along with over 1,000 tyrosine phosphorylation sites from about 750 different proteins in primary cholangiocarcinoma patients. Furthermore, we confirmed the presence of ROS kinase fusions in 8.7% (2 out of 23) of cholangiocarcinoma patients. Expression of the ROS fusions in 3T3 cells confers transforming ability both in vitro and in vivo, and is responsive to its kinase inhibitor. Our data demonstrate that ROS kinase is a promising candidate for a therapeutic target and for a diagnostic molecular marker in cholangiocarcinoma. The identification of ROS tyrosine kinase fusions in cholangiocarcinoma, along with the presence of other ROS kinase fusions in lung cancer and glioblastoma, suggests that a more broadly based screen for activated ROS kinase in cancer is warranted.