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The present study explores the function of FANCA gene, a pivotal member of the Fanconi anaemia (FA) pathway crucial for preserving genomic stability and preventing cancer, particularly in the context of gastric cancer (GC). Using immunohistochemistry, quantitative real-time PCR, and western blot analysis, we evaluate FANCA mRNA and protein expressions in GC cell lines. The relationship between FANCA expression and clinicopathological characteristics is also explored. Various assays, including CCK8, colony formation, wound healing, and Transwell assays, are used to assess functional changes in cells associated with FANCA. Flow cytometry is utilized to evaluate alterations in the cell cycle resulted from FANCA knockdown and overexpression. Our findings show elevated FANCA expression in GC cell lines, with levels correlated with pathologic stage and lymphatic metastasis. FANCA knockdown impedes cell proliferation, migration, and invasion and induces G1/S phase cell cycle arrest. Conversely, FANCA overexpression stimulates cell proliferation, migration, and invasion. In vivo xenograft experiments confirm the promotional role of FANCA in GC tumor progression. Moreover, FANCA overexpression is associated with the activation of cell cycle. Collectively, our results suggest that FANCA drives malignant cell behaviors in GC through the cell cycle pathway, highlighting its potential as a therapeutic target for the treatment of GC.

an era of increased sustainable transport, the European inland navigation industry has received significant attention to attain sustainable transport. Tremendous opportunities to substantially move freight on waterways are present in the UK; however, several challenges have been appropriately addressed, including infrastructural gaps and various institutional support programs. The paper addresses the UK’s current situation of inland navigation and the key challenges affecting the sectors as a viable alternative transport solution. The article explores and summarises the geographic opportunities, commercial feasibility, and the current condition of the UK’S inland navigation sector. From the practical scenario of the UK’s experience, an attempt was made by the authors to find the critical challenges and issues faced by the industry. The emerging themes from the analysis of this paper indicated governance and leadership issues, cooperation, and coordination mechanism between establishments with various functions and responsibilities, merged with infrastructural investment, are strategic elements for expansion in the UK. Conclusively, the authors presented recommendations for improvement and sustainable development.

Binge drinking exerts cardiac toxicity through various mechanisms, including oxidative stress and inflammation. NLRP3 inflammasomes possess both pro- and anti-inflammatory properties, although the role of NLRP3 in ethanol-induced cardiotoxicity remains unknown. This study is designed to examine the role of NLRP3 inflammasome in acute ethanol cardiotoxicity and the underlying mechanisms of action. Nine- to twelve-week-old adult male C57BL/6 mice are administered with ethanol (1.5 g/kg, twice daily, i.p.) for 3 days. A cohort of control and ethanol-challenged mice are treated with the NLRP3 inhibitor MCC950 (10 mg/kg/day, i.p., days 1 and 3). Myocardial geometry and function are monitored using echocardiography and cardiomyocyte edge-detection techniques. Levels of NLRP3 inflammasome, mitophagy and apoptosis are evaluated by western blot analysis and immunofluorescence techniques. Acute ethanol challenge results in abnormally higher cardiac systolic function, in conjunction with deteriorated cardiac diastolic function and cardiomyocyte contractile function. Levels of NLRP3 inflammasome and apoptosis are elevated, and mitophagy flux is blocked (elevated Pink1-Parkin and LC3B along with diminished p62 and Rab7) in mice receiving acute ethanol challenge. Although MCC950 does not elicit a notable effect on myocardial function, apoptosis or inflammasome activation in the absence of ethanol exposure, it effectively rescues acute ethanol cardiotoxicity, as manifested by restored myocardial and cardiomyocyte functional homeostasis, suppressed NLRP3 inflammasome activation and apoptosis, and improved mitophagy flux. Our data further suggest that FBXL2, an E3 ubiquitin ligase associated with mitochondrial homeostasis and mitophagy, is destabilized due to proteasomal degradation of caspase-1 by ethanol-induced hyperactivation of NLRP3-caspase-1 inflammasome signaling, resulting in mitochondrial injury and apoptosis. These findings denote a role for NLRP3 inflammasome in acute ethanol exposure-induced cardiotoxicity in an FBXL2-dependent manner and the therapeutic promise of targeting NLRP3 inflammasome for acute ethanol cardiotoxicity.

Severe acute respiratory syndrome (SARS)-CoV-2 virus causes novel coronavirus disease 2019 (COVID-19), and there is a possible role for oxidative stress in the pathophysiology of neurological diseases associated with COVID-19. Excessive oxidative stress could be responsible for the thrombosis and other neuronal dysfunctions observed in COVID-19. This review discusses the role of oxidative stress associated with SARS-CoV-2 and the mechanisms involved. Furthermore, the various therapeutics implicated in treating COVID-19 and the oxidative stress that contributes to the etiology and pathogenesis of COVID-19-induced neuronal dysfunction are discussed. Further mechanistic and clinical research to combat COVID-19 is warranted to understand the exact mechanisms, and its true clinical effects need to be investigated to minimize neurological complications from COVID-19.

The novel coronavirus, namely, SARS-CoV-2 (COVID-19), broke out two years ago and has caused major global health issues. Adequate treatment options are still lacking for the management of COVID-19 viral infections. Many patients afflicted with COVID-19 may range from asymptomatic to severe symptomatic, triggering poor clinical outcomes, morbidity, and mortality. Cancer is one of the leading causes of death worldwide. It is pertinent to re-examine cancer prevalence during the COVID-19 pandemic to prevent mortality and complications. Understanding the impact of SARS-CoV-2 on cancer is key to appropriate healthcare measures for the treatment and prevention of this vulnerable population. Data was acquired from PubMed using key search terms. Additional databases were utilized, such as the Centers for Disease Prevention and Control, American Cancer Society (ACS), and National Cancer Institute (NCI). Cancer patients are more prone to SARS-CoV-2 infection and exhibit poor health outcomes, possibly due to a chronic immunosuppressive state and anticancer therapies. Male sex, older age, and active cancer disease or previous cancer are risk factors for COVID-19 infection, leading to possible severe complications, including morbidity or mortality. The speculated mechanism for potentially higher mortality or COVID-19 complications is through reduced immune system function and inflammatory processes through cancer disease, anticancer therapy, and active COVID-19 infection. This review includes prostate, breast, ovarian, hematologic, lung, colorectal, esophageal, bladder, pancreatic, cervical, and head and neck cancers. This review should help better maintain the health of cancer patients and direct clinicians for COVID-19 prevention to improve the overall health outcomes.

Neuronal regeneration and functional recovery are severely compromised following traumatic brain injury (TBI). Treatment options, including cell transplantation and drug therapy, have been shown to benefit TBI, although the underlying mechanisms remain elusive. In this study, neural stem cells (NSCs) are transplanted into TBI-challenged mice, together with olfactory ensheathing cells (OECs) or followed by valproic acid (VPA) treatment. Both OEC grafting and VPA treatment facilitate the differentiation of NSCs into neurons (including endogenous and exogenous neurons) and significantly attenuate neurological functional defects in TBI mice. Combination of NSCs with OECs or VPA administration leads to overt improvement in axonal regeneration, synaptogenesis, and synaptic plasticity in the cerebral cortex in TBI-challenged mice, as shown by retrograde corticospinal tract tracing, electron microscopy, growth-associated protein 43 (GAP43), and synaptophysin (SYN) analyses. However, these beneficial effects of VPA are reversed by local delivery of N-methyl-D-aspartate (NMDA) into tissues surrounding the injury epicenter in the cerebral cortex, accompanied by a pronounced drop in axons and synapses in the brain. Our findings reveal that increased axonal regeneration and synaptogenesis evoked by cell grafting and VPA fosters neural repair in a murine model of TBI. Moreover, VPA-induced neuroprotective roles are antagonized by exogenous NMDA administration and its concomitant decrease in the number of neurons of local brain, indicating that increased neurons induced by VPA treatment mediate axonal regeneration and synaptogenesis in mice after TBI operation. Collectively, this study provides new insights into NSC transplantation therapy for TBI.

Obstructive sleep apnea (OSA) is a common respiratory disorder characterized by partial obstruction of upper respiratory tract and repetitive cessation of breathing during sleep. The etiology behind OSA is associated with the occurrence of intermittent hypoxemia, recurrent arousals and intrathoracic pressure swings. These contributing factors may turn on various signaling mechanisms including elevated sympathetic tone, oxidative stress, inflammation, endothelial dysfunction, cardiovascular variability, abnormal coagulation and metabolic defect ( e.g., insulin resistance, leptin resistance and altered hepatic metabolism). Given its close tie with major cardiovascular risk factors, OSA is commonly linked to the pathogenesis of a wide array of cardiovascular diseases (CVDs) including hypertension, heart failure, arrhythmias, coronary artery disease, stroke, cerebrovascular disease and pulmonary hypertension (PH). The current standard treatment for OSA using adequate nasal continuous positive airway pressure (CPAP) confers a significant reduction in cardiovascular morbidity. Nonetheless, despite the availability of effective therapy, patients with CVDs are still deemed highly vulnerable to OSA and related adverse clinical outcomes. A better understanding of the etiology of OSA along with early diagnosis should be essential for this undertreated disorder in the clinical setting.

Abstract Background Understanding how the tumor microenvironment is shaped by various factors is important for the development of new therapeutic strategies. Tumor cells often undergo spontaneous apoptotic cell death in tumor microenvironment, these apoptotic cells are histologically co‐localized with immunosuppressive macrophages. However, the mechanism by which tumor cell apoptosis modulates macrophage polarization is not fully understood. In this study, we aimed to explore the tumor promoting effects of apoptotic tumor cells and the signal pathways involved. Methods Apoptotic cells and macrophages in tumors were detected by immunohistochemical staining. Morphological analysis was performed with Giemsa staining. Lipids generated from apoptotic cells were detected by liquid chromatography‐mass spectrometry. Phosphatidylserine‐containing liposomes were prepared to mimic apoptotic cells. The expression of protein was determined by real‐time PCR, immunohistochemistry enzyme‐linked immunosorbent assay and Western blotting. Mouse malignant ascites and subcutaneous tumor models were designed for in vivo analysis. Transgenic mice with specific genes knocked out and inhibitors specific to certain proteins were used for the mechanistic studies. Results The location and the number of apoptotic cells were correlated with that of macrophages in several types of carcinomas. Phosphatidylserine, a lipid molecule generated in apoptotic cells, induced polarization and accumulation of M2‐like macrophages in vivo and in vitro. Moreover, sustained administration of phosphoserine promoted tumor growth in the malignant ascites and subcutaneous tumor models. Further analyses suggested that phosphoserine induced a M2‐like phenotype in macrophages, which was related to the activation of phosphoserine receptors including T‐cell immunoglobin mucin 4 (TIM4) and the FAK‐SRC‐STAT3 signaling pathway as well as elevated the expression of the histone demethylase Jumonji domain‐containing protein 3 (JMJD3). Administration of specific inhibitors of these pathways could reduce tumor progression. Conclusions This study suggest that apoptotic cell‐generated phosphoserine might be a notable signal for immunosuppressive macrophages in tumors, and the related pathways might be potential therapeutic targets for cancer therapy.

BACKGROUND Heavy metal pollution in soil has been a serious threat to human health and ecological environmental safety. Stabilization remediation has become an important means of remediation of heavy metal contaminated soil due to the high efficiency and low cost. Attapulgite modified by alkali with an improved performance, provides an important basis for its stabilization and remediation of heavy metal contaminated soil. OBJECTIVES To analyze the changes in physical and chemical properties of attapulgite before and after modification, and to study the effects of attapulgite modified by NaOH on the chemical speciation changes and environmental risks of Cd in contaminated soil, and to explore the stabilization effects of attapulgite modified by NaOH on Cd in the soil. METHODS Different proportions of NaOH were used to modify attapulgite. The surface characteristics, crystal structure and functional groups of the materials were analyzed by scanning electron microscopy (SEM), X-ray diffraction (XRD) and Fourier transform infrared (FTIR) spectroscopy. Stabilization experiments were carried out on artificially prepared heavy metal Cd contaminated soil to study the effects of NaOH-modified attapulgite on the changes of chemical speciation of Cd and environmental risks in contaminated soil. RESULTS By adding the modified material with the mass ratio of NaOH to attapulgite of 1:2, the pH value of the soil was significantly increased by 0.85 units. The exchangeable Cd content decreased by 46.28% and the residual Cd content increased by 1.98 times. The risk assessment code (RAC) and potential risk index (PRI) of Cd in soil decreased the most from 36.70% and 207.90 to 20.08% and 86.40, respectively, which effectively reduced the transfer capacity and environmental risk of Cd in soil. According to SEM, XRD and FTIR analyses, after modification, the surface roughness of attapulgite increased, chemical bonds such as Si-O-Si bonds were opened, so active sites for adsorption of heavy metals increased. Attapulgite modified by alkali immobilized Cd mainly through adsorption, and the reaction of silanol and hydroxide with Cd2+ generated precipitate, so as to achieve the effect of stabilizing and repairing Cd contaminated soil. CONCLUSIONS Alkali-modified attapulgite can effectively stabilize Cd in soil, which has a significant application prospect in remediation of heavy metal contaminated soil.

Gap junction protein, alpha 1 (GJA1), which is correlated with recurrences and unfavorable prognoses in hepatocellular carcinomas (HCCs), is one of the specific proteins expressed by activated hepatic stellate cells (HSCs).

Palygorskite was applied in complexation-ultrafiltration treatment of heavy metals in wastewater under different pH and ionic strength. The results indicated that the rejection of heavy metals increased significantly with pH value, and decreased slightly with an increase of ionic strength of Na+ and Cl–. A certain concentration of NaCl significantly reduced the rejection rate of Cu2+. The rejection of Cu2+, Zn2+ and Cd2+ could reach over 86.8%, 93.6% and 93.7% at pH of 7 and 0.1 mol/L NaCl. The rejection of heavy metals was severely affected by low molecular weight competing complexing agents and the effect of sodium tartrate was greater than triethanolamine. In the presence of sodium tartrate, the rejection of Cu2+, Zn2+ and Cd2+ could arrive over 81.4%, 57.6% and 60.5% at pH of 7 in 20 min. Palygorskite was offered a potential complexing agent for the removal of heavy metals in wastewater at the complexation-ultrafiltration process.

The nanoscratch test has been identified as one of the important tools for evaluating the mechanical and tribological properties of materials. This paper reviews the current researches on the nanoscratch test using to characterise the mechanical properties of three typical materials, including thin film, polymer composite and concrete, from the perspectives of the Berkovich indenter, parameter selection, mode selection, and analysis of resulting data. In addition, to provide a deep understanding on the test from different magnitude, a comparison between the microscratch test and nanoscratch test on the evaluation of tribological performance is also provided in this paper. The characterisation by nanoscratch test of two structural samples, in terms of layered film structures (thin film and coating sample) and single layer block structure (polymer composite sample and concrete samples) are also described in this paper, which aims to provides a deep understand on the evaluation the adhesion, tribological and interfacial properties of the typical materials samples by nanoscratch test. Finally, the coefficient of friction and critical load are discussed, which are two important parameters in tribological properties and adhesion properties.

In the past several years, the CRISPR (clustered regularly interspaced short palindromic repeats)/Cas (CRISPR-associated protein) system has been harnessed as an efficient and powerful tool for targeted genome editing in different prokaryotic and eukaryotic species. Here, we review the development and application of CRISPR/Cas system in rice, emphasizing different varieties of CRISPR/Cas systems have been applied, strategies for multiplex editing, methods for precise gene insertion and replacement, and efficient systems for base editing and site-specific transcriptional regulation. In addition, the biosecurity of CRISPR/Cas system is also discussed, including transgene-free methods and off-target effects of CRISPR/Cas system. Thus, the development and application of CRISPR/Cas system will have significant impact on functional genomic research and variety improvement in rice. Keywords: rice, CRISPR, Cas, genome editing, protospacer adjacent motif

A 16-DOF heavy-load RV reducer dynamics model is established by the lumped parameter method. Taking the RV-550E heavy-load reducer as the research object, the natural frequency of the reducer is obtained by solving the dynamics equation, and the influence of the pin-tooth shell stiffness on the natural frequency of the system is analyzed, which provides the basis for the design of the pin-toothed shell. In order to reveal the law of the influence of system parameters on the inherent characteristics of the whole machine, the sensitivity of the natural frequency of the whole machine to the moment of inertia and stiffness of the system is further analyzed. The analysis results show that the low-order natural frequency is more sensitive to the crankshaft arm bearing stiffness, the planet carrier support bearing stiffness and the crankshaft inertia. The research results provide a theoretical basis for the structural optimization design of this type of heavy-load reducer.

The temperature field of FeCrNiCu alloy forming layers of continuous wave(CW) and pulsed laser remanufacture was analyzed using the non-contact infrared thermometer.The general rule of temperature field distribution of molten pool and heat-affected zone of the two modes was obtained. The pulsed laser process superiority in heat input, forming deformation control and reducing the temperature in molten pool and heat-affected zone was vilidated. The results show that during pulsed laser forming the peak temperature in the heat-affected zone is 730.4-810.5℃,the peak temperature in the molten pool is 998.7-1383.4℃,which are all obviously lower than the same process of the CW mode; the temperature-rise rate and cooling rate of pulsed laser are higher, which is helpful to the forming of fine grain structures and good mechanical performance; the forming experiment also further verifies more narrow heat-affected zone in pulsed laser process.

The task of producing a generic model of the modal choice decision making process is a challenging one. Modal choice is strongly influenced by the infrastructure limitations and geographical constraints of the area in which the decision is being made. With this in mind, addressing modal choice on an individual basis for each region may be the optimal solution. This is the approach adopted in this paper. The creation of a modal choice model is a multistage process of which this paper addresses the first stage, the production a framework of the decision making process. Firstly, a number of criteria that are commonly used in modal choice models are identified. Then a number of gaps in the criteria utilized in previous papers are established. Subsequently, the method used to produce a framework of the decision making process within North West England’s Atlantic Gateway is outlined. Through consultation with transport industry experts in North West England, an initial list of sixty eight papers was reduced to thirty six that were considered to be of specific relevance to modern day freight transportation within their region. The criteria used in each of these papers were then, along with further industry input, used to create the foundation on which a modal choice framework specific to the Atlantic Gateway could be built. A greater understanding of what influences modal choice within this region will allow informed decisions to be made by policy makers on how to more efficiently utilize the available modes of freight transport. Having established this, future work can then go on to build upon these findings. This paper recommends that future work is performed to establish the weights of each criteria and sub-criteria within the framework. This should then be followed by establishing industry’s perceptions of the best and worst alternatives for moving freight within the Atlantic Gateway.

In the North West of England the issue of a perceived infrastructure gap is of increasing concern. Investment needs to be made to improve the transport infrastructure of the region if it is to be expected to promote the development of its own regional logistics gateway. Funding tools have been set up to address the challenges arising from the imbalance in infrastructure development that exists between regions in the north of the United Kingdom and those in the south. For regions with well developed economies the outlook is promising as the availability of modern transport infrastructure looks set to improve. However, some sources believe that the development of new transport infrastructure will have a negative impact upon sustainable development. It is expected that this will occur in a range of both direct and indirect ways. As a result, it is critical that planning for the creation of new intermodal transport infrastructure, or the upgrading of that which already exists, takes into account the impact that these developments will have on the sustainable development of the host region. A scenario based development methodology is proposed in this paper. It was developed to provide a way to identify potential scenarios that may arise within a given region as a result of transport infrastructure projects. To create significant scenarios the methodology is dependent on the availability of a sufficient quantity of quality data. For this paper that data was collected through a focus group composed of stakeholders from the region in question. This was further supported by the performance of an impact survey using the same group of stakeholders.

Streptomyces species 1-14 isolated from cassava rhizosphere soil were evaluated for their antibacterial efficacy against Fusarium oxysporum f.sp. cubense race 4 (FOC4). Of the 63 strains tested, thirteen exhibited potent antibacterial properties and were further screened against eight fungal pathogens. The strain that showed maximum inhibition against all of the test pathogens was identified by 16S rDNA sequencing as Streptomyces sp. 1-14, was selected for further studies. Through the propagation of Streptomyces sp. 1-14 in soil under simulated conditions, we found that FOC4 did not significantly influence the multiplication and survival of Streptomyces sp. 1-14, while indigenous microorganisms in the soil did significantly influence Streptomyces sp. 1-14 populations. To achieve maximum metabolite production, the growth of Streptomyces 1-14 was optimized through response surface methodology employing Plackett-Burman design, path of steepest ascent determinations and Box-Behnken design. The final optimized fermentation conditions (g/L) included: glucose, 38.877; CaCl2•2H2O, 0.161; temperature, 29.97°C; and inoculation amount, 8.93%. This optimization resulted in an antibacterial activity of 56.13% against FOC4, which was 12.33% higher than that before optimization (43.80%). The results obtained using response surface methodology to optimize the fermentation medium had a significant effect on the production of bioactive metabolites by Streptomyces sp. 1-14. Moreover, during fermentation and storage, pH, light, storage temperature, etc., must be closely monitored to reduce the formation of fermentation products with reduced antibacterial activity. This method is useful for further investigations of the production of anti-FOC4 substances, and could be used to develop bio-control agents to suppress or control banana fusarium wilt.