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Background. As inclusive education and social participatory parity continue to develop, more and more professional-trained people with disabilities are seeking opportunities for integration into the workplace. However, they face various of challenges in the current work environment. From the perspective of the cultural model of disability, employees with disabilities vary from their able-bodied colleagues in terms of cognition or behavioral patterns. As a result, newer concept such as the disability cultural competence has emerged. In order to adapt and function well in diverse and inclusive work teams, the cultural intelligence of employees with disabilities has become vital yet to be deeply explored in Russia. Purpose. This paper attempts to reveal the cultural intelligence level of Russian employees with disabilities and to compare cultural intelligence between employees with disabilities from Russia and China. Materials and methods. Cultural intelligence has been measured through the Russia and Chinese adaptation Cultural Intelligence Scale among 25 Russian and 23 Chinese employees with disabilities. Then, SPSS 26.0 was used to carry out the descriptive analysis, normality test and mean comparison analysis. Results. Both Russian and Chinese employees' cultural intelligence are at average level. And Russian employees with disabilities have higher cultural intelligence level than the Chinese ones. Besides, this study underlined that there is no significant difference in cultural intelligence by ethnic, gender or type of disability while there is significant difference in cultural intelligence depending on the participants' age.

Introduction: The tumor-associated microbiota plays a vital role in cancer development. Accumulating evidence shows that Fusobacterium nucleatum (Fn) participates in the progression of multiple tumor types. However, the underlying mechanisms remain unclear. Objectives: This study examined the expression of methyltransferase-like protein 3 (METTL3) during Fn infection and elucidated the function and pathway of Fn-induced m6A methylation in esophageal squamous cell carcinoma (ESCC). Methods: The abundance of Fn in patient tissues was determined by qPCR. Western blot, qRT-PCR, and immunohistochemistry were performed to measure METTL3 expression in cells and tissues. METTL3 function was evaluated in vitro by colony formation and cell migration assays. MeRIP-qPCR was performed to determine the relationship between METTL3 and c-Myc. In addition, the half-lives of genes that are downstream of METTL3 were determined with RNA stability assays. Results: Fn was enriched in hepatocellular carcinoma (HCC), breast cancer (BRCA), ESCC, and colorectal cancer (CRC) tumor tissues. METTL3 expression was positively associated with Fn abundance in ESCC tissues. Fn could survive and proliferation as well as increase METTL3 expression in ESCC, HCC, CRC, and BRCA cells. Moreover, METTL3 overexpression promoted ESCC cells proliferation, migration in vivo and in vitro. Mechanistically, Intracellular Fn infection increases METTL3 transcription. METTL3 promoted c-Myc mRNA methylation in the 3′-untranslated Region (3′-UTR) and enhanced its mRNA stability in a YTH N6-Methyladenosine RNA binding protein 1(YTHDF1)-dependent manner, which contributes to Fn induced ESCC proliferation and metastasis. Conclusions: This study indicates that intracellular Fn infection promotes ESCC development and metastasis, and eradicating Fn infection may be a promising strategy for treating ESCC.

The Yihe River Basin is a key area for water conservation and soil erosion control in northern China. The excessive development of land resources is a major factor causing soil erosion and ecological degradation. However, the impacts of land use change on soil erosion in the basin are not yet clearly. Understanding the complex relationship between land use and soil erosion is an important way to promote the development of land resources utilization and ecological construction from cognition to decision-making. This study simulated the temporal-spatial changes of soil erosion in the basin from 1956 to 2020 using Integrated Valuation of Ecosystem Services and Tradeoffs (InVEST) model, and evaluated the changes of soil erosion under different land use scenarios from 2020 to 2050 using Future Land Use Simulation (FLUS) model. From 1956 to 2020, the overall soil erosion intensity showed a slight decreasing trend, and the average annual soil erosion modulus was 38.21 t/ha/year. Soil erosion intensity was higher in the central and northern mountainous areas, while it was lower in the flat alluvial plains in the south. Arable land (4.07 t/ha/year) was the largest contributor to the amount of soil erosion, and land use changes caused the soil erosion intensity to fluctuate and decrease after 1995. From 2020 to 2050, soil erosion varied widely under different land use scenarios, and the land use pattern targeting ecological priority development would effectively mitigate soil erosion. Therefore, optimizing land use patterns and structures are critical initiatives to prevent soil erosion.

ABSTRACTRegulatory T (Treg) cells are critical in shaping an immunosuppressive microenvironment to favor tumor progression and resistance to therapies. However, the heterogeneity and function of Treg cells in esophageal squamous cell carcinoma (ESCC) remain underexplored. We identified CD177 as a tumor-infiltrating Treg cell marker in ESCC. Interestingly, expression levels of CD177 and PD-1 were mutually exclusive in tumor Treg cells. CD177+ Treg cells expressed high levels of IL35, in association with CD8+ T cell exhaustion, whereas PD-1+ Treg cells expressed high levels of IL10. Pan-cancer analysis revealed that CD177+ Treg cells display increased clonal expansion compared to PD-1+ and double-negative (DN) Treg cells, and CD177+ and PD-1+ Treg cells develop from the same DN Treg cell origin. Importantly, we found CD177+ Treg cell infiltration to be associated with poor overall survival and poor response to anti-PD-1 immunotherapy plus chemotherapy in ESCC patients. Finally, we found that lymphatic endothelial cells are associated with CD177+ Treg cell accumulation in ESCC tumors, which are also decreased after anti-PD-1 immunotherapy plus chemotherapy. Our work identifies CD177+ Treg cell as a tumor-specific Treg cell subset and highlights their potential value as a prognostic marker of survival and response to immunotherapy and a therapeutic target in ESCC.

Summary: The phenotype-first approach (PFA) and data-driven approach (DDA) have both greatly facilitated anthropological studies and the mapping of trait-associated genes. However, the pros and cons of the two approaches are poorly understood. Here, we systematically evaluated the two approaches and analyzed 14,838 facial traits in 2,379 Han Chinese individuals. Interestingly, the PFA explained more facial variation than the DDA in the top 100 and 1,000 except in the top 10 phenotypes. Accordingly, the ratio of heterogeneous traits extracted from the PFA was much greater, while more homogenous traits were found using the DDA for different sex, age, and BMI groups. Notably, our results demonstrated that the sex factor accounted for 30% of phenotypic variation in all traits extracted. Furthermore, we linked DDA phenotypes to PFA phenotypes with explicit biological explanations. These findings provide new insights into the analysis of multidimensional phenotypes and expand the understanding of phenotyping approaches.

Abstract With the increasing complexity of the shortwave communication environment, the efficiency and accuracy of the manual detection of Morse code no longer meet actual needs. Therefore, this paper proposes a Morse code detection algorithm called YFDM. For the time–frequency image of the received signal, a combination module of deformable convolution and C3 is used to enhance the backbone network’s attention to the abstract semantics and location information of Morse code. GSConv and VOV-GSCSP modules are used to build a lightweight neck network. Finally, the confidence propagation cluster (CP-Cluster) algorithm is used to filter the detection frame. In an ablation experiment, the parameters and giga floating-point operations per second (GFLOPs) of YFDM were 5.961 M and 9.74 G, respectively, 15.11% and 38.9% less than those of YOLOv5. Moreover, when WIoUv1 was used as the loss function of the bounding box, the AP0.5:0.95 and frames per second (FPS) values of the algorithm reached the highest values, 0.68 and 72.4. The experimental results indicate that the algorithm can effectively reduce the weight of the model while ensuring the detection accuracy and inference speed.

In ventilation systems of metal mines, the real-time measurement of the airflow field and a reduction in pollutants are necessary for clean environmental management and human health. However, the limited quantitative data and expensive detection technology hinder the accurate assessment of mine ventilation effectiveness and safety status. Therefore, we propose a new method for constructing a mine intelligent ventilation system with a global scheme, which can realize the intelligent prediction of unknown points in the mine ventilation system by measuring the airflow parameters of multiple known points. Firstly, the nodal wind pressure method combined with the Hardy–Cross iterative algorithm is used to solve the mine ventilation network, and the airflow parameters under normal operation and extreme working conditions are simulated, based on which an intelligent ventilation training database is established. Secondly, we compared the airflow parameter prediction ability of three different machine learning models with different neural network models based on the collected small-sample airflow field dataset of a mine roadway. Finally, the depth learning method is optimized to build the intelligent algorithm model of the mine ventilation system, and a large number of three-dimensional simulation data and field measurement data of the mine ventilation system are used to train the model repeatedly to realize the intelligent perception of air flow parameters of a metal mine ventilation network and the construction of an intelligent ventilation system. The results show that the maximum error of a single airflow measurement point is 1.24%, the maximum overall error is 3.25%, and the overall average error is 0.51%. The intelligent algorithm has a good model training effect and high precision and can meet the requirements of the research and application of this project. Through case analysis, this method can predict the airflow parameters of any position underground and realize the real-time control of mine safety.

Desert areas contain abundant desert sand (DS) resources, and high-volume recycling of DS resources as components of cement-based materials can achieve high-value applications. In this paper, DS was processed into desert sand powder (DSP) and replaced with cement in high volumes (20 wt.%–60 wt.%) to produce cement pastes. The mechanical properties, heat evolution, nanomechanical characteristics, microstructure, and economic and environmental impact of cement pastes were studied. The results show that adding 20 wt.% DSP increases the compressive strength of pastes and accelerates cement hydration, compared with the control group (0 wt.% DSP). Meanwhile, incorporating an appropriate amount of DSP (20 wt.%) effectively reduces porosity, increases the proportion of harmless and less harmful pores, and reduces the proportion of more harmful pores. From the perspective of nanoscopic properties, the addition of 20 wt.% DSP increases the C-S-H volume fraction, especially enhancing the transformation of low-density C-S-H to high-density C-S-H. Notably, the sample incorporating 60 wt.% DSP exhibits the lowest values for CI coefficients (13.02 kg/MPa·m3) and Cp coefficients (2.29 USD/MPa·m3), thereby validating the application of high-volume DSP feasibility in cement-based materials.

This paper introduced a new nonexplosive roadway excavation method, combining the reserved free space technology and the static expansion mechanical fracturing technology, where the former is implemented by the gasbag, while the piston splitter is for the latter. The numerical model of roadway excavation was set up via PFC3D to investigate the mechanical fracturing performance, including the single-hole fracturing and the hole network fracturing. The results show that the reasonable hole margin is about 1.0–1.5 m, and the optimal column spacing of the hole network pattern is 1.0 m, after comprehensively analyzing the fracturing performance and the splitting force evolution. Moreover, the mechanical fracturing excavation method was applied to construct a parking chamber in the Kalatongke Mine, to preliminarily verify the feasibility of the static expansion mechanical fracturing technology. The in situ investigation results indicate that the excavation footage is about 0.8 m with the piston splitter when adopting a hole margin of 1.0–1.5 m. To sum up, the preliminary field application and the numerical simulation result both support the feasibility of mechanical fracturing, and the reasonable fracturing hole margin is about 1.0 m.

Abstract This is the protocol for a Campbell systematic review. The objectives are as follows. We will solve the following questions: (1) What are the characteristics of skills training services for individuals experiencing or at risk of homelessness? (2) How effectively do the different skills training programs improve employment status, work and life skills, or housing stability? (3) What factors are associated with the variation in the effectiveness of skills training services?

Background: Recent studies have shown that bile acids are essential in irritable bowel syndrome (IBS) pathology, and cholecystectomy has direct effects on bile acid metabolism. However, whether cholecystectomy increases the risk of IBS remains unclear. We aimed to investigate the association between cholecystectomy and IBS risk in the UK Biobank (UKB).Methods: This study is a prospective analysis of 413,472 participants who were free of IBS, inflammatory bowel disease, cancer, or common benign digestive tract diseases. We identified incidents of IBS through self-reporting or links to primary healthcare and hospitalization data. We evaluated hazard ratios (HRs) adjusted for sociodemographic characteristics, health behaviours, comorbidities, and medications.Results: During a median follow-up period of 12.7 years, we observed 15,503 new cases of IBS. Participants with a history of cholecystectomy had a 46% higher risk of IBS than those without (HR = 1.46, 95% CI: 1.32–1.60), and further subtype analysis showed that the risk of IBS with diarrhoea was significantly higher than the risk of IBS without diarrhoea (HR = 1.71, 95% CI: 1.30–2.25 vs. HR = 1.42, 95% CI: 1.28–1.58). The overall covariate-adjusted HRs for IBS were similar between the group with both cholecystectomy and gallstones (HR = 1.45, 95% CI: 1.32–1.58) and the group with cholecystectomy without gallstones (HR = 1.50, 95% CI: 1.36–1.67) when the group without both cholecystectomy and gallstones was used as a reference. The overall covariate-adjusted HR was not significantly different in the group without cholecystectomy with gallstones (HR = 1.18, 95% CI: 0.95–1.47). The positive association of cholecystectomy with IBS risk did not change when stratifying the data based on age, sex, BMI, smoking, alcohol consumption, healthy diet, quality sleep, physical activity, type 2 diabetes, hypertension, hyperlipidaemia, mental illness, NSAID intake, or acid inhibitor intake. Sensitivity analyses, including propensity score matching analysis and lagging the exposure for two or four years, indicated that the effects were robust.Conclusion: Cholecystectomy was associated with a higher risk of IBS, especially IBS with diarrhoea. Additional prospective randomized controlled and experimental studies are warranted to further validate the association and to explore the relevant biological mechanisms.

Abstract Background Natural products can serve as one of the alternatives, exhibiting high potential for the treatment and prevention of COVID-19, caused by SARS-CoV-2. Herein, we report a screening platform to test the antiviral efficacy of a natural product library against SARS-CoV-2 and verify their activity using lung organoids. Methods Since SARS-CoV-2 is classified as a risk group 3 pathogen, the drug screening assay must be performed in a biosafety level 3 (BSL-3) laboratory. To circumvent this limitation, pseudotyped viruses (PVs) have been developed as replacements for the live SARS-CoV-2. We developed PVs containing spikes from Delta and Omicron variants of SARS-CoV-2 and improved the infection in an angiotensin-converting enzyme 2 (ACE2)-dependent manner. Human induced pluripotent stem cells (hiPSCs) derived lung organoids were generated to test the SARS-CoV-2 therapeutic efficacy of natural products. Results Flavonoids from our natural product library had strong antiviral activity against the Delta- or Omicron-spike-containing PVs without affecting cell viability. We aimed to develop strategies to discover the dual function of either inhibiting infection at the beginning of the infection cycle or reducing spike stability following SARS-CoV-2 infection. When lung cells are already infected with the virus, the active flavonoids induced the degradation of the spike protein and exerted anti-inflammatory effects. Further experiments confirmed that the active flavonoids had strong antiviral activity in lung organoid models. Conclusion This screening platform will open new paths by providing a promising standard system for discovering novel drug leads against SARS-CoV-2 and help develop promising candidates for clinical investigation as potential therapeutics for COVID-19. Graphical Abstract

Sulfide ore dust is at risk of explosion. To analyze the concentration distribution of sulfide ore dust in the ore loading, transporting, and unloading operations, the migration and dispersion processes of sulfide ore dust were simulated by using FLUENT software and taking the dust generation rate, roadway air velocity, and dust source position as variables. The concentration of sulfide ore dust was analyzed from the four-dimensional perspective of time and space. The results show that the maximum concentration of sulfide ore dust is determined by the dust generation rate. The roadway air velocity exhibits dual effects on the migration and deposition of sulfide ore dust. The ore loading position significantly impacts the distribution of sulfide ore dust, manifesting in varying degrees of superposition effects. Based on the results, this paper proposes a comprehensive dust reduction measure in the form of water curtain and dynamic ventilation, effectively minimizing the concentration of sulfide mine dust within the roadway.

A high temperature is the key factor limiting the safe development of deep mine tunnels. By confronting the phenomenon of serious heat exchange between airflow and the surrounding rocks in the tunnel excavation area, a conceptual model of coupled cooling of auxiliary ventilation and partial thermal insulation is proposed. The performance of a coupled cooling system was investigated and optimized by using the scale model test with a 1:10 geometric scale and the orthogonal test. The results suggest that the average temperatures of the work zone and its central point decrease by 1.5 °C and 3.3 °C, respectively, while partial insulation layers are used. According to the sensitivity analysis for a single factor, as the ventilation duct outlet (VDO) moves away from the working face (WF), the temperature gradually increases, leading to a local high temperature area. When the ventilation duct height is arranged in the middle of the insulation layer, the cooling effect is optimal and the highest average temperature difference is 4.4 °C. The thermal equilibrium temperature can be further decreased by lengthening and thickening the insulation layer. In addition, the range analysis shows that the ventilation velocity has a greater impact on the thermal environment of the tunnel working area than the ventilation duct location and insulation layer length. The coupled cooling method can save on cooling capacity and effectively alleviate the high-temperature problems of the tunnel excavation area.

The escalating pandemic brought about by the novel SARS-CoV-2 virus is threatening global health, and thus, it is necessary to develop effective antiviral drugs. Usenamine A is a dibenzo-furan derivative separated from lichen Usnea diffracta showing broad-spectrum activity against different viruses. We evaluate that usenamine A has antiviral effects against novel SARS-CoV-2 Delta variant pseudotyped viruses (PVs) in A549 cells. In addition, usenamine A significantly suppresses SARS-CoV-2 PV-induced mitochondrial depolarization, elevated reactive oxygen species (ROS) levels, apoptosis, and inflammation. Usenamine A also causes the SARS-CoV-2 spike protein to become less stable. Thus, usenamine A shows potential as an antiviral drug that can provide protection against COVID-19.

DNS root servers are located at the top of the domain name system and are the cornerstone of the Internet. Currently, root servers deploy numerous root instances using anycast technology. Introducing root instances can improve the parsing performance of root servers and the user access experience. However, we found that some root instances do not show optimal performance, and users cannot access the closest root instance when accessing the root instance or even cross-border access. This paper deploys three types of operator detection points in 31 provincial-level administrative regions in mainland China. Each detection point requests the NS record of the top-level domain name from the root instance server introduced in China to obtain the access data of the root instance server hit by domestic users. At the same time, we propose two methods to determine whether users have achieved the optimal choice of root instance, including the method based on the shortest AS path and the method based on geographical distance. In these two methods, we analyze the optimal selection of root instances for each root server. Finally, we analyze the cross-border access of users and find that China Telecom users are more likely to access the root instance across borders.

Abstract Background Bipolar clavicle injury is a rare injury involving any combination of dislocation and/or fracture at both ends of the clavicle. Most reports of bipolar clavicle injury have been based on a single case, and treatment of this injury remains controversial. The present study was performed to evaluate the efficacy of surgical management with internal plating for bipolar clavicle injuries. Methods We performed internal plating to treat seven consecutive bipolar clavicle injuries with different injury patterns from May 2013 to June 2021. A clavicle hook plate was used for five sternoclavicular joint injuries (including a revision surgery) and three acromioclavicular joint dislocations, a T plate was used for one sternoclavicular joint injury, and an anatomic plate was used for one distal clavicle fracture. At follow-up, radiographs were assessed for bone alignment, joint congruity, fracture union or malunion, and implant failure or migration. Clinical evaluation included determination of the Disability of the Arm, Shoulder, and Hand (DASH) score; Constant–Murley score; visual analog scale (VAS) score; and complications. Results The patients were regularly followed up after the operation, and functional parameters were assessed over time. At a mean follow-up of 28.1 ± 22.0 months, each fracture had solid bone union, and each dislocation showed no sign of recurrent instability. The mean shoulder forward flexion was 159.3° ± 7.9°, and the mean DASH score was 8.8 ± 5.1. The mean Constant–Murley score was 88.9 ± 7.9, with six cases assessed as excellent and one case assessed as good. The mean VAS score was 1.0 ± 1.5, and the mean patient satisfaction score was 9.3 ± 0.8. No complications occurred, and each patient was able to resume their preinjury daily activity and was highly satisfied with their treatment. Conclusions In the present study, internal plating for bipolar clavicle injury allowed early mobilization and resulted in good joint function. We recommend fixation of the more severely affected side first because the other side may be passively reduced and acquire stability once the more severely affected side has been fixed. Internal fixation of the other end may therefore be unnecessary unless residual instability exists.

Abstract Immune checkpoint inhibitor (ICI)‐based therapies have shown promising advances for the first‐line treatment of advanced or metastatic esophageal cancer (EC). However, few studies concerning the identification of patients who achieve durable response from ICIs have been previously reported. In the present study, pre‐ and on‐treatment plasma circulating tumor DNA (ctDNA) were analyzed in 10 patients with advanced esophageal squamous cell cancer (ESCC) receiving first‐line chemoimmunotherapy. Patients with decreased molecular tumor burden index (mTBI) >7% experienced longer progression‐free survival (PFS) and durable clinical benefit (DCB, PFS ≥ 6 months). In addition, five patients showed stable disease at first scan, all three patients with decreased mTBI > 7% achieved DCB, while two cases with decreased mTBI ≤ 7% experienced non‐DCB. Our results demonstrate that ctDNA monitor might help identify which ESCC patients respond to chemoimmunotherapy.

IntroductionThe combination of FOLFOX and bevacizumab (FOLFOX-Bev) is a promising treatment for advanced colorectal cancer (CRC). However, the response of the tumor microenvironment to FOLFOX-Bev is still largely unexplored.MethodsWe conducted single-cell transcriptomic analysis of CRC samples derived from a patient before and after treatment to gain insights into the cellular changes associated with FOLFOX-Bev treatment.ResultsWe found that cancer cells with high proliferative, metastatic, and pro-angiogenic properties respond better to FOLFOX-Bev treatment. Moreover, FOLFOX-Bev enhances CD8+ T cell cytotoxicity, thereby boosting the anti-tumor immune response. Conversely, FOLFOX-Bev impairs the functionality of tumor-associated macrophages, plasma cells, and cancer-associated fibroblasts, leading to a decrease in VEGFB-mediated angiogenesis. Furthermore, FOLFOX-Bev treatment reset intercellular communication, which could potentially affect the function of non-cancer cells.DiscussionOur findings provide valuable insights into the molecular mechanisms underlying the response of advanced CRC to FOLFOX-Bev treatment and highlight potential targets for improving the efficacy of this treatment strategy.

The establishment of an isolation layer in submarine mining has been a persistent challenge. In the context of this research, we conducted a similarity simulation test to preliminarily assess the interaction between the thickness and extent of the isolation layer. Subsequently, we introduce an innovative approach that integrates fractal theory and the Bonded Block Model (BBM) to simulate undersea isolation layer mining. The validation of this method relies on on-site borehole scanning and displacement monitoring, which depict the intricate fractal evolution of fractures and predict the optimal thickness of the isolation layer. Our findings affirm the robustness and validity of this method. Evaluation of the fractal dimensions of fractures reveals that a critical threshold of 1.7 is essential to prevent structural failure of the isolation layer, while a limit of 1.5 is necessary to avoid significant water ingress. Remarkably, the correlation dimension of the settlement time series closely aligns with the fractal dimension of the fractures, underscoring the feasibility of ensuring the safety of isolation layer mining through real-time settlement monitoring.

The aim is to explore the predictive value of salivary bacteria for the presence of esophageal squamous cell carcinoma (ESCC). Saliva samples were obtained from 178 patients with ESCC and 101 healthy controls, and allocated to screening and verification cohorts, respectively. In the screening phase, after saliva DNA was extracted, 16S rRNA V4 regions of salivary bacteria were amplified by polymerase chain reaction (PCR) with high-throughput sequencing. Highly expressed target bacteria were screened by Operational Taxonomic Units clustering, species annotation and microbial diversity assessment. In the verification phase, the expression levels of target bacteria identified in the screening phase were verified by absolute quantitative PCR (Q-PCR). Receiver operating characteristic (ROC) curves were plotted to investigate the predictive value of target salivary bacteria. LEfSe analysis revealed higher proportions of Fusobacterium, Streptococcus and Porphyromonas, and Q-PCR assay showed significantly higher numbers of Streptococcus salivarius, Fusobacterium nucleatum and Porphyromonas gingivalis in patients with ESCC, when compared with healthy controls (all P

Understanding the characteristics and evolution of crack propagation in rock masses is crucial for evaluating their stability. By applying clustering theory to analyze recorded microseismic events, we differentiate the development positions of individual cracks amidst multiple crack formations. Three distinct crack cluster distribution patterns are identified, allowing for the evaluation of regional stability through microseismic event density and ellipsoidal model parameters. The process of crack propagation involves independent development at nucleation positions, mutual influence between adjacent locations, and subsequent crack growth and propagation. Additionally, we examine crack evolution prior to roof collapse and establish a connectivity model between surface and goaf roof cracks. When microseismic events are identified as developing along a plane, it indicates a higher risk of damage in that area. Through the analysis of crack propagation location and angle, our study provides a theoretical foundation for predicting crack direction. Notably, our model’s findings align with onsite observations, demonstrating its practical effectiveness. The results of this research offer valuable insights for collapse prediction and early warning systems for mine roofs, contributing to advancements in mining safety and operations.

Thermal environment prediction has become increasingly significant in recent years with its promise of wide application in underground structures. The current work presents a numerical method for the feasible and effective analysis of the airflow and surrounding rock temperatures in ultralong mine ventilation roadways to understand their dynamic heat transfer. To reduce the modeling effort and computation time with satisfactory accuracy, the ventilation roadway is approximated as a one-dimensional (1D) line element. Still, the surrounding rock of the roadway remains three-dimensional (3D). An equivalent heat transfer coefficient calculates the dynamic heat transfer in the radial direction of the roadway. A case analysis of the Sanhejian coal mine ventilation roadways in China is performed, and a comparison between the simulated results and field measurements indicates that the predicted airflow temperature shows good agreement. The change in the underground thermal environment concerning ventilation time is systematically investigated in detail. The surrounding rock of the roadway adjusts the underground thermal environment through heat absorption or heat release, and the temperature distribution of the surrounding rock presents a ''V'' shape in winter and a ''W'' shape in summer. The self-compression of air contributes to a remarkable heat source for the increase in airflow temperature in the air intake shaft. A roadway with a low initial temperature of the surrounding rock after long-term ventilation can effectively cool the high-temperature airflow underground in early summer. The reduction in ventilation volume will increase the cooling degree of airflow by the surrounding rock in long-term ventilation roadways in summer. Still, the airflow will be heated more significantly in short-term ventilation roadways. In addition, the increase in the average annual ambient temperature will result in a linear rise in underground airflow temperature.

People with disabilities have been increasingly regarded as the most powerful and overlooked workforce in the labor market, although frequently confronted with ineffectiveness in cooperation with colleagues without disabilities. The traditional paradigm of inclusion considers blind people as dependents needing help. Inclusive society is highly aimed at effective interactions between the workforce with and without disabilities. The present article regards people with disabilities as those having diverse potentials which stem from different cultural backgrounds, and behaving differently during intercultural interactions with individuals without disabilities. This article proposes a new disability inclusion paradigm involving successful blind professionals in mentoring activities, to share their experience with top managers and experts in Russian organizations. Through focus groups and in-depth interviews, this article finds specific differences in explicit and implicit interactive behaviors between individuals with and without blindness. Furthermore, the present article highlights the positive effect of a disability inclusion paradigm on cultural intelligence development of organizational managers and experts.

Groundwater is a very important natural resource for humanity, however, the degradation of groundwater quality caused by anthropogenic activities may pose a serious hazard to human health and ecosystem. In this study, 143 groundwater samples were analyzed to investigate the spatiotemporal variations of hydrochemistry, groundwater quality and potential human health risk of groundwater in Jinghe River Basin, Chinese Loess Plateau. Based on the mean concentrations value (MCV) and over-standard rate (OSR), the groundwater in Jinghe River Basin were divided into three groups: Group Ⅰ (high MCV: greater than standard values and high OSR: ≥ 10 %) contains TDS (total dissolved solids), TH (total harness), SO42-, F- and Fe; Group Ⅱ (low MCV and high OSR) contains pH, Cl-, NO3-, Cr6+ and As, Group Ⅲ (low MCV and low OSR) contains NO2-, NH4+, Zn, Mn, Pb, I- and Cd. The results of set pair assessment indicated that the unsuitable and doubtful class of comprehensive groundwater quality are mainly distributed in the northern part of study area, accounting for 29 % and 13.6 % of the area in 2004 and 2015, respectively. Human health risk assessment based on the triangular fuzzy number suggested that the variation of risk levels in different age groups is Children > Adult Men > Adult Women. Average carcinogenic risks of As in groundwater for the three groups exceed the acceptable level, and non-carcinogenic risk of NO3- for Children is higher than the acceptable threshold. The findings of this study provide valuable insight into the spatiotemporal characteristics of groundwater quality and potential health risks of polluted groundwater by anthropogenic activities.

Abstract Metformin, the first-line drug for type II diabetes, has recently been considered an anticancer agent. However, the molecular target and underlying mechanism of metformin’s anti-cancer effects remain largely unclear. Herein, we report that metformin treatment increases the sensitivity of hepatocarcinoma cells to methotrexate (MTX) by suppressing the expression of the one-carbon metabolism enzyme DHFR. We show that the combination of metformin and MTX blocks nucleotide metabolism and thus effectively inhibits cell cycle progression and tumorigenesis. Mechanistically, metformin not only transcriptionally represses DHFR via E2F4 but also promotes lysosomal degradation of the DHFR protein. Notably, metformin dramatically increases the response of patient-derived hepatocarcinoma organoids to MTX without obvious toxicity to organoids derived from normal liver tissue. Taken together, our findings identify an important role for DHFR in the suppressive effects of metformin on therapeutic resistance, thus revealing a therapeutically targetable potential vulnerability in hepatocarcinoma.

BackgroundImbalance of oral salivary microbiota has been linked to the pathogenesis of a variety of systemic diseases, and oral bacterial species have been shown to be useful biomarkers for systemic diseases.This study aimed to characterize the alterations of oral microbiota in patients with esophageal squamous cell carcinoma (ESCC) and to evaluate the diagnostic performance of oral microbial biomarkers for ESCC.MethodsThe relative abundance of flora in saliva samples was analyzed by 16S rDNA sequencing, and differences in the species present in samples from ESCC patients and healthy controls (HCs) were identified by analyzing species diversity and performing LEfSe analysis. Receiver operating characteristic (ROC) curve analysis was applied to evaluate the diagnostic performance of the characteristic bacteria individually and in combination.ResultsDifferences in bacterial diversity indexes were observed for the saliva of ESCC patients versus HCs (P0.05). LEfSe analysis showed that Leptotrichia, Porphyromonas (Pg), Streptococcus, Rothia, Lactobacillus and Peptostreptococcus were more abundant in ESCC patient saliva than in HC saliva, whereas Haemophilus, Alloprevotella (All), Prevotella_7, Prevotella (Pre), Prevotella_6, Pasteurellaceae and Pasteurellales were significantly less abundant in ESCC patient saliva (P

Water management is a crucial aspect in the efficient functioning of proton exchange membrane fuel cells (PEMFCs). The presence of a two-phase flow, consisting of water and reactive gas, in the channel of the PEMFC is of utmost importance for effective water management. This study focuses on investigating the removal of liquid water in 3D wave channels and 2D straight channels using the volume of fluid method. The study analyzes the dynamic behavior of droplets emerging from the gas diffusion layer (GDL) into the channel under the influence of gas flow. The study also explores the effects of droplet growth, deformation, detachment, force, and pore size on critical water behavior and water content in the channel. The results indicate that the 3D wave channel is more effective in removing liquid water compared to the 2D straight channel. It is observed that increasing the velocity facilitates the discharge of liquid water. However, excessively high velocities lead to parasitic power losses. Furthermore, while larger pore sizes in the GDL are not advantageous for PEMFC performance, a moderate increase in pore size aids in the discharge of liquid water. The knowledge gained through this study deepens the understanding of droplet dynamics in PEMFC gas channels and assists in optimizing the design and operational conditions of these channels.

PurposeThe present study sets out to evaluate the feasibility, safety, and effectiveness of conversion surgery following induction immunochemotherapy for patients with initially unresectable locally advanced esophageal squamous cell carcinoma (ESCC) in a real-world scenario.Materials and MethodsIn this multi-center, real-world study (NCT04822103), patients who had unresectable ESCC disease were enrolled across eight medical centers in China. All patients received programmed death receptor-1 (PD-1) inhibitor plus chemotherapy every 3 weeks for at least two cycles. Patients with significant relief of cancer-related clinical symptoms and radiological responsive disease were deemed surgical candidates. Feasibility and safety profile of immunochemotherapy plus conversion surgery, radiological and pathological tumor responses, as well as short-term survival outcomes were evaluated. Moreover, data of an independent ESCC cohort receiving induction chemotherapy (iC) were compared.ResultsOne hundred and fifty-five patients were enrolled in the final analysis. Esophagectomy was offered to 116 patients, yielding a conversion rate of 74.8%. R0 resection rate was 94%. Among the 155 patients, 107 (69.0%) patients experienced at least one treatment-related adverse event (TRAE) and 45 (29.0%) patients reported grade 3 and above TRAEs. Significant differences in responsive disease rate were observed between iC cohort and induction immunochemotherapy (iIC) cohort [objective response rate: iIC: 63.2% vs. iC: 47.7%, p = 0.004; pathological complete response: iIC: 22.4% vs. iC: 6.7%, p = 0.001). Higher anastomosis fistula rate was observed in the iC group (19.2%) compared with the iIC group (4%). Furthermore, Significantly higher event-free survival was observed in those who underwent conversion surgery.ConclusionOur results supported that conversion surgery following immunochemotherapy is feasible and safe for patients with initially unresectable locally advanced ESCC. Both radiological and pathological response rates were significantly higher in the iIC cohort compared with those in the traditional iC cohort.

Reduction in river discharge and sediment load has left deltaic lobes in the world’s many river deltas starving, but knowledge of how the subaqueous topography of these abandoned subdeltas responds to environmental changes is limited. In this study, we aimed to determine the long-term dynamics of the subaqueous seabed of abandoned delta lobes to advance current knowledge. As a case study, we selected an abandoned subdelta on the Yellow River Delta of the Bohai Sea, China, for which three-decade long (1984–2017) bathymetric data and long-term river discharge and sediment load records are available. We analyzed the seafloor surface change and quantified the void space from the sea water surface to the seafloor. In addition, we surveyed the seafloor surface with an M80 unmanned surface vehicle carrying a multibeam echo sounder system (MBES) in 2019 to obtain high-resolution microtopography information. We found that a net volume of 5.3 × 108 m3 of sediment was eroded from the study seabed within an area of 3.6 × 108 m2 during 1984–2017. This volumetric quantity is equivalent to 6.89 billion metric tons of sediment, assuming a bulk density of 1.3 t/m3 for the seabed sediment. The seabed erosion from 0 to −5 m, from −5 to −10 m, and below −10 m has showed a similar increasing trend over the past 33 years. These findings suggest that seabed erosion in this abandoned subdelta will very likely continue, and that other abandoned delta lobes in the world may have been experiencing similar seabed erosion due to the interruption of the sediment supply and sea level rise. It is not clear if the seabed erosion of abandoned delta lobes would have any effect on the stability of the coastal shoreline and continental shelf.

Clouds are a significant factor in regional climates and play a crucial role in regulating the Earth’s water cycle through the interaction of sunlight and wind. Meteorological agencies around the world must regularly observe and record cloud data. Unfortunately, the current methods for collecting cloud data mainly rely on manual observation. This paper presents a novel approach to identifying ground-based cloud images to aid in the collection of cloud data. However, there is currently no publicly available dataset that is suitable for this research. To solve this, we built a dataset of surface-shot images of clouds called the SSC, which was overseen by the Macao Meteorological Society. Compared to previous datasets, the SSC dataset offers a more balanced distribution of data samples across various cloud genera and provides a more precise classification of cloud genera. This paper presents a method for identifying cloud genera based on cloud texture, using convolutional neural networks. To extract cloud texture effectively, we apply Gamma Correction to the images. The experiments were conducted on the SSC dataset. The results show that the proposed model performs well in identifying 10 cloud genera, achieving an accuracy rate of 80% for the top three possibilities.

Аim of this study wаs to cаlculаte economic vаlue of destructed lаnd in Mongoliа in order to fаcilitаte restorаtion of mining аreа. Totаl economic vаlue is а universаl frаmework for estimаting аnd evаluаting economicаl dаmаge cаuse to environment due to mining аctivities аnd other technogenic production аctivities. Compensаtion for environmentаl аnd finаnciаl dаmаge cаn be determined bаsed on the following three cаtegories: initia restoration, restoration by compensation and evaluation of ecological damage. Main object of this study is direct economic vаlue of destructed environment due to Tumurtei iron ore mine аctivity. Аll estimаtions in this pаper аre mаde аccording to Mongoliаn legislаtion аnd lаws. During thаt project а totаl of 511.9 hectаres of аreа аre exposed to environment destruction. Estimаtion of ecologicаl dаmаge аre consisting of following pаrts: dаmаge to soil, dаmаge to surfаce аnd groundwаter resources, dаmаge to forest resources, dаmаge to vegetаtion аnd dаmаge to аnimаl fаunа. The аssessment of ecologicаl аnd finаnciаl dаmаge to the environment is performer in following stаges: 1. determine the аmount of potentiаl dаmаge to the environment; 2. cаlculаte аnd determine the аmount of dаmаge reduced аs а result of meаsures to reduce or eliminаte dаmаge to the environment during production аctivities; 3. estimаte the аmount of аctuаl dаmаge resulting from the operаtion. Results of this study concerning interests of mining entities аnd public entities, who аre in chаrge of regulаting such аctivities.

Abstract The model and algorithm of intensity-modulated radiotherapy (IMRT) are updated increasingly quickly, but the hardware upgrade of primary hospitals often lags behind. The new generation of intelligent precise radiotherapy platforms provides users with intelligent medical consortium services using big data, artificial intelligence and industrial Internet of Things technology. This technology can ensure that under the real-time guidance of a professional medical consortium, primary hospitals can realize rapid large-scale reverse planning design and can more accurately consider many factors of postprocessing. Although large-scale healthcare systems, such as volumetric-modulated arc therapy and other accurate radiotherapy technologies, have developed rapidly, the development of step-and-shoot-mode IMRT technology is still very important for developing countries. For software, in addition to the conformity of the dose distribution, the modulation speed, convenience and stability of the later dose delivery should also be considered in inverse planning. Therefore, this paper analyzes the main problems in conventional IMRT inverse planning, including the smoothing of the fluence map, the selection of the gantry angle and the dose leakage of tongue–groove effects. To address these issues, a novel Intelligent IoT-based large-scale inverse planning strategy with the key factors of the postmodulation is developed, and a detailed flow chart is also provided. The scheme consists of two steps. The first step is to obtain a relatively optimal combination of gantry angles by considering the dose distribution requirements and constraints and the modulation requirements and constraints. The second step is to optimize the intensity map, to smooth the map based on prior knowledge according to the determined angles, and to obtain the final modulation scheme according to the relevant objectives and constraints of the map decomposition (leaf sequencing). In an experiment, we calculate and validate the clinical head and neck case. Because of the special gantry angle selection, the angle combination is optimized from the initial equivalent distribution to adapt to the target area and protect the nontarget area. The value of the objective function varies greatly after the optimization, especially in the target area, and the target value decreases by approximately 10%. On this basis, we smooth the fluence map by a partial differential equation with prior knowledge and a minimization of the total number of monitor units. It is also shown from the objective function value that the target value is essentially unchanged for the target area, while for the nontarget area, the value decreases by 16%, which is very impressive.

To explore different operators' eye movement characteristics, which can reflect their degree of attention and hazard identification ability in university laboratories, experiments were carried out with 60 junior students. The laboratories were divided into five areas by function and hazard type. The subjects were divided into two groups based on their safety experience. Using typical university laboratory images as stimulus materials, a Tobii X2 eye tracker was used to measure and record the eye movement parameters of the subjects in five laboratory areas. The results showed that the subjects exhibited greater interest in the equipment area (attracting the focus of 100.00% of the subjects) and less interest in the wireway area (attracting the focus of 46.67% of the subjects); no significant difference was observed between subjects who were or were not specialized in safety. Most subjects could identify the hazard sources in the five areas but paid little attention to electrical sockets. Thus, countermeasures including reasonably matching the color and layout in laboratories and popularizing laboratory safety education are proposed, which will provide a basis for strengthening safety management in university laboratories.

As the underground engineering proceeds to a greater depth, the thermal stresses resulted from high-temperature surrounding rock become a major challenge for the deep construction and safe operation. Understanding of the characteristics of heat and moisture transfer in a roadway is critically required to assist in predicting and improving the thermal environment in the underground. The present work developed a fully coupled model capable of simulating the non-isothermal flow inside the roadway and heat transfer in surrounding rock together with moisture transfer driven by water evaporation. And the proposed model has been validated with the field test data and reasonable agreement was achieved. Comparing the models with or without water evaporation, it is discovered that ignoring latent heat will cause a serious deviation in air temperature prediction. Examining the critical factors on the effect of heat and mass transfer in the roadway is found that dehumidifying the initial airflow or increasing ventilation speed can effectively promote the latent heat release and reduce the temperature of airflow and surrounding rock. And this effect is greater significant for the higher temperature roadway. The present study can provide a robust theoretical basis and foundation for heat hazard control in underground engineering.

Sleep–wake rhythm disturbances have a negative impact on attention. However, how it affects attention and whether the restoration of regular rhythms can restore attention are unclear. This study aims to explore the effects of sleep–wake rhythm disturbances on three subfunctions of attention (alertness, orientation, and executive control) and the restoration of regular rhythms on these functions. Twenty-one participants in the experimental group (who experienced sleep–wake rhythm disturbances for at least one month; aged 18–26) were required to sleep regularly following a sleep schedule, whereas 20 participants in the control group (who maintained regular sleep for at least three months; aged 19–22) received no manipulation of their sleep. All participants were assessed using the attention network test three times in six days. All of them wore spectrum activity monitors and kept sleep diaries every day. The results showed that the effects of alertness and executive control in the experimental group were significantly lower than those in the control group. After five days of regular sleep, the difference in the alertness effect between the two groups significantly decreased. These results suggested that under natural conditions, sleep–wake rhythm disturbances could negatively influence alertness and executive control, and a short period of restoring a regular rhythm has a recovery effect on alertness.

Heat hazard is major challenge for the safe and efficient exploitation of deep resources. Understanding the heat transfer behaviors in roadway is the premise of temperature prediction and ventilation design. A fully coupled model incorporated with a moving mesh method was developed, which considers the convective heat transfer between surrounding rock and airflow, unsteady-state heat transfer in rock, and non-isothermal flow in roadway. The characteristics of thermal performance and its evolution law in an excavating roadway were obtained. The numerical model was validated against previous experimental data with a deviation of less than 3%. Analysis of the airflow and temperature field revealed the characteristic of convection heat transfer in the wall and local heat accumulation in roadway. The air temperature in roadway is associated with the airflow characteristics, and a local high temperature zone is presented in the vortex zone. By comparing the heat flux of the surrounding rock and excavation condition, it is found that the heat released from the working face poses a crucial effect on the airflow temperature in roadway. The present study provided a robust theoretical basis for improving cooling efficiency and thermal comfort in roadway construction.

Low-angle lee-side slopes of dunes are commonly developed on the world’s riverbeds, and dune migration associated with sediment transport exert a major influence on riverine processes. However, the catenary-bead dune has been identified in the Yangtze River (YR) Estuary, featuring a higher lee-side angle. To date, the morphological variation and formation reasons of catenary-bead dunes in the YR Estuary remain uncharacterized. In this study, we used a multibeam echo system (MBES) to investigate the bedforms of the YR estuary during 2014–2015, as well as to discuss the seasonal variation of catenary-bead dunes. The results indicate that the catenary-bead dunes of the YR Estuary are characterized by growth during the flood season and extinction during the dry season. The lee-side angle is typically ~16.7°, which is larger than that of other dune types (3.7–8°) in the estuary; moreover, the catenary-bead dunes are higher than other dune types of the same length in the YR Estuary. The relationship between the dune height (H) and length (L) was found to be H = 0.1667L0.603 (R2 = 0.38), while the other dune types yielded the relationship of H = 0.0845L0.758 (R2 = 0.52). Strong runoff superimposing the ebb tide led to the development of catenary-bead dunes. Furthermore, the higher coarse sediment content (69.9–72%) and lower clay content (6.3–6.7%) of the riverbed sediment are favorable for their formation, while the higher curved crest-lines are favorable for the formation of the associated elliptical pits.

Water resources are crucial for maintaining daily life and a healthy ecological environment. In order to gain a harmonious development among water resources and economic development in Lake Watershed, it is urgent to quantify the lake inflow. However, the calculation of inflow simulations is severely limited by the lack of information regarding river runoff. This paper attempts calculated inflow in an ungauged stream through use of the coupling water balance method and the Xin’anjiang model, applying it to calculate the inflow in the Chaohu Lake Basin, China. Results show that the coupled model has been proved to be robust in determining inflow in an ungauged stream. The error of daily inflow calculated by the water balance method is between 1.4 and −19.5%, which is within the standard error range (±20%). The calibration and verification results of the coupled model suggest that the simulation results are best in the high inflow year (2016), followed by the normal inflow year (2007) and the low inflow year (1978). The Nash-Sutcliffe efficiencies for high inflow year, normal inflow year, and low inflow year are 0.82, 0.72, and 0.63, respectively, all of which have reached a satisfactory level. Further, the annual lake inflow simulation in the normal inflow year is 19.4 × 108 m3, while the annual average land surface runoff of the study area is 18.9 × 108 m3, and the relative error is −2.6% by the two ways. These results of the coupled model offer a new way to calculate the inflow in lake/reservoir basins.

BackgroundLymph node metastasis is a primary contributor to tumor progression in esophageal squamous cell carcinoma (ESCC), and the optimal extent of lymphadenectomy during esophagectomy remains controversial. This study aimed to investigate the appropriate number of lymph nodes to be dissected in pT1-2Nany stage ESCC to achieve the best prognosis and avoid missing positive lymph nodes (PLNs).MethodsA total of 497 patients with pT1 to pT2 esophageal cancer from two institutions were retrospectively analyzed and their surgical and pathological records were critically reviewed. Stepwise analyses were conducted by calculating a serial of hazard ratios and odd ratios to determine the optimal range of lymphadenectomy for overall survival (OS).ResultsThe best survival outcome can be obtained when the number of lymph node examined (NLNE) is 10–18 in pT1N0 ESCC, while the NLNE should exceed 24 in pT2N0 diseases. In patients with pT1-2Nany and pT2Nany ESCC, resection of 15–25 and 24–37 lymph nodes, respectively, could provide significant added value for identifying positive nodal metastasis. When the NLNE exceeds this appropriate range, resection of extra lymph node is not helpful to improve the probability of finding PLNs.ConclusionsFor ESCC patients undergoing radical esophagectomy, the optimal extent of lymphadenectomy is 15–25 for pT1Nany disease and 24–37 for pT2Nany disease.

KRAS mutation-induced Ras activation plays an important role in the pathogenesis of pancreatic cancer, but the role of wild-type Ras and Ras GTPase-activating proteins remains unclear. The present study was designed to determine the expression spectra of Ras GTPase-activating proteins genes in pancreatic cancer cells, and the role of DAB2IP, a Ras GTPase-activating proteins gene, in the development and progression of pancreatic cancer. Following the analyses of the expression profiles of 16 Ras GTPase-activating proteins in 6 pancreatic cancer cell lines including Bxpc-3 (with wild-type KRAS), Capan-2, Sw1990, Aspc-1, CFPAC-1, and Panc-1 (with mutant KRAS) and 1 normal human pancreatic ductal epithelial cell line, H6C7, the expression of DAB2IP messenger RNA was further analyzed by quantitative real-time polymerase chain reaction. The role of DAB2IP in pancreatic cancer was further investigated in vitro and in vivo by upregulating DAB2IP in Bxpc-3 cells through transfection of DAB2IP into Bxpc-3 cells with recombinant lentivirus. The DAB2IP expression in pancreatic cancer cells and tissues with wild-type KRAS was significantly lower than that in cells and tissues with mutant KRAS ( P < .05). In Bxpc-3 cells with wild-type KRAS, overexpression of DAB2IP decreased the expression of P-AKT and P-ERK and the Ras activity; increased the expression of P-JNK and caspase 3; inhibited cell proliferation, invasiveness, and migration; and increased the cell sensitivity to cetuximab. Overexpression of DAB2IP inhibited tumor progression in a mouse model. In conclusion, DAB2IP downregulates Ras activity in wild-type pancreatic cancer cells. Overexpression of DAB2IP decreases the Ras activity, inhibits cell proliferation, and increases sensitivity to cetuximab in wild-type pancreatic cancer cells. In conclusion, DAB2IP may serve as a potential molecular therapeutic target for the treatment of pancreatic cancer.

Breast cancer is now the most common type of cancer worldwide, surpassing lung cancer. This issue is further worsened by the lack of effective therapies for the disease. Recent reports indicate that the inhibition of ubiquitin-like modifier-activating enzyme 5 (UBA5) can impede tumor development. However, there have been few reports regarding UBA5-inhibiting compounds. This work studied usenamine A, a natural product from the lichen Usnea longissimi that exhibits UBA5-inhibitory effects. Bioinformatics analysis was performed using public databases, and the anti-proliferative ability of usenamine A in breast cancer cells was examined through MTS and colony formation assays. Flow cytometry and western blot analysis were also conducted to examine and analyze cell cycle arrest and apoptosis. In addition, LC3B-RFP and UBA5 expression plasmids were used for the analysis of usenamine A-induced autophagy. According to the bioinformatics analysis results, UBA5 was upregulated in breast cancer. According to in vitro studies, usenamine A displayed prominent anti-proliferative activity and resulted in G2/M phase arrest in MDA-MB-231 cells. Moreover, usenamine A induced autophagy and endoplasmic reticulum stress in MDA-MB-231 cells. In conclusion, the findings support the potential of usenamine A as an agent that can attenuate the development and progression of breast cancer.

A non-union, especially atrophic non-unions, is a permanent failure of healing following a fracture and can be difficult to treat. Approximately 5-10% of fractures will result in a non-union during the healing process. non-unions can be classified into two types: atrophic non-union which is often due to impaired bone healing with a potential biological mechanism, and hypertrophic non-union which is due to inadequate fixation after fracture. Genetic variations also play an important role in the fracture healing response. Previous studies based on animal models have indicated that NOS2 might be greatly involved in the bone fracture healing process. In this case-control study, 346 nonunion patients were compared to 883 patients with normal fracture healing to investigate the potential genetic association between NOS2 and the fracture healing process using study subjects of Chinese Han ancestry. Twenty-seven single nucleotide polymorphisms (SNPs) covering NOS2 were genotyped in our study subjects and analyzed. In addition to the single marker-based analysis, we performed a gene-by-environment analysis to examine the potential interactions between genetic polymorphisms and some environmental factors. SNP rs2297514 showed significant association with the fracture healing process after adjusting for age and gender (OR = 1.38, P = 0.0005). Our results indicated that the T allele of rs2297514 significantly increased the risk of a non-union during the fracture healing process by 38% compared to the C allele. Further stratification analyses conducted for this SNP using data from subgroups classified by different sites of fracture indicated that significance could only be observed in the tibial diaphysis subgroup (N = 428, OR = 1.77, P = 0.0007) but not other groups including femur diaphysis, humeral shaft, ulnar shaft, and femur neck. Gene-by-environment interaction analyses of the three environmental factors showed no significant results. In this study, rs2297514 was significantly associated with the non-union status of fracture healing using a large Chinese population-based study sample. Our findings replicated those of a previous preliminary study and offered strong evidence linking NOS2 and fracture healing.