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Purpose – This study aims to investigate the acoustic roughness of rails on China’s high-speed railways, with a focus on short-wavelength irregularities (less than 80 cm), which are known to significantly contribute to noise. The goal is to develop a specific acoustic roughness spectrum tailored for China’s high-speed railway system, as no such spectrum currently exists. Design/methodology/approach – A long-term tracking study was conducted on major railway lines in China, monitoring rail roughness throughout the initial operational period and the rails’ service life. Data preprocessing techniques such as peak removal and curvature correction were applied for acoustic adjustments. A spatial-wavelength domain transformation was performed, providing the distribution patterns and statistical characteristics of acoustic roughness on China’s high-speed rails. Based on these analyses, a model for constructing the acoustic roughness spectrum was developed. Findings – The study found that the acoustic roughness of China’s high-speed railway rails follows a χ2 distribution with six degrees of freedom. For wavelengths greater than 8 cm, the acoustic roughness spectrum remains below the ISO specified limits. In the wavelength range of 3.2 cm to 6.3 cm, the roughness is comparable to or within the limits specified by ISO 3095:2005 and ISO 3095:2013. However, for wavelengths shorter than 2.5 cm, the roughness exceeds ISO limits. Originality/value – This research fills the gap in the lack of a specific acoustic roughness spectrum for China’s high-speed railways. By establishing a tailored spectrum based on long-term data analysis, the findings provide valuable insights for noise control and rail maintenance in the context of China’s high-speed rail system.

Abstract This study investigates the low‐frequency oscillations (LFOs) in MMC‐MVDC systems with high photovoltaic (PV) penetration, considering the whole operating conditions of the grid‐connected MMC, including both the inverter and rectifier modes. First, the multi‐port impedance models of converters and networks are developed, upon which a stability criterion is defined. The mechanism of LFOs is then identified using bus participation analysis and parameter sensitivity analysis. In addition, the stable zones of the dominant parameters are identified, taking into account the whole operating conditions of the grid‐connected MMC. Interestingly, a phase‐locked loop may induce LFOs in two low‐frequency ranges. Finally, the experimental results confirm the correctness of the theoretical analysis.

Deeper understanding of the crosstalk between host cells and Mycobacterium tuberculosis (Mtb) provides crucial guidelines for the rational design of novel intervention strategies against tuberculosis (TB). Mycobacteria possess a unique complex cell wall with arabinogalactan (AG) as a critical component. AG has been identified as a virulence factor of Mtb which is recognized by host galectin-9. Here, we demonstrate that galectin-9 directly inhibited mycobacterial growth through AG-binding property of carbohydrate-recognition domain 2. Furthermore, IgG antibodies with AG specificity were detected in the serum of TB patients. Based on the interaction between galectin-9 and AG, we developed a monoclonal antibody (mAb) screening assay and identified AG-specific mAbs which profoundly inhibit Mtb growth. Mechanistically, proteomic profiling and morphological characterizations revealed that AG-specific mAbs regulate AG biosynthesis, thereby inducing cell wall swelling. Thus, direct AG-binding by galectin-9 or antibodies contributes to protection against TB. Our findings pave the way for the rational design of novel immunotherapeutic strategies for TB control.

Abstract Antimicrobial peptides (AMPs), ancient scavengers of bacteria, are very poorly induced in macrophages infected by Mycobacterium tuberculosis (M. tuberculosis), but the underlying mechanism remains unknown. Here, we report that L-alanine interacts with PRSS1 and unfreezes the inhibitory effect of PRSS1 on the activation of NF-κB pathway to induce the expression of AMPs, but mycobacterial alanine dehydrogenase (Ald) Rv2780 hydrolyzes L-alanine and reduces the level of L-alanine in macrophages, thereby suppressing the expression of AMPs to facilitate survival of mycobacteria. Mechanistically, PRSS1 associates with TAK1 and disruptes the formation of TAK1/TAB1 complex to inhibit TAK1-mediated activation of NF-κB pathway, but interaction of L-alanine with PRSS1, disables PRSS1-mediated impairment on TAK1/TAB1 complex formation, thereby triggering the activation of NF-κB pathway to induce expression of AMPs. Moreover, deletion of antimicrobial peptide gene β-defensin 4 (Defb4) impairs the virulence by Rv2780 during infection in mice. Both L-alanine and the Rv2780 inhibitor, GWP-042, exhibits excellent inhibitory activity against M. tuberculosis infection in vivo. Our findings identify a previously unrecognized mechanism that M. tuberculosis uses its own alanine dehydrogenase to suppress host immunity, and provide insights relevant to the development of effective immunomodulators that target M. tuberculosis.

In DC distributed power systems (DPSs), the complex impedance interactions possibly lead to DC bus voltage oscillation or collapse. In previous research, the stability analysis of DPSs is implemented based on mathematical analysis in control theory. The specific mechanisms of the instability of the cascade system have not been intuitively clarified. In this paper, the stability analysis of DPSs based on the traditional Nyquist criterion is simplified to the resonance analysis of the series-connected port impedance (Z = R + jX) of source and load converters. It reveals that the essential reason for impedance instability of a DC cascade system is that the negative damping characteristic (R < 0) of the port the overall impedance amplifies the internal resonance source at reactance zero-crossing frequency. The simplified stability criterion for DC cascade systems can be concluded as: in the negative damping frequency ranges (R < 0), there exists no zero-crossing point of the reactance component (i.e., X = 0). According to the proposed stability criterion, the oscillation modes of cascade systems are classified. A typical one is the internal impedance instability excited by the negative damping, and the other one is that the external disturbance amplified by negativity in a low stability margin. Thus, the impedance reshaping method for stability improvement of the system can be further specified. The validity of the simplified criterion is verified theoretically and experimentally by a positive damping reshaping method.

To explore the function and evolutionary relationships of inducible heat shock protein 70 (Hsp70) in Daphnia magna, cDNAs of four Hsp70 family members (DmaHsp70, DmaHsp70-2, DmaHsp70-12, DmaHsp70-14) were cloned. While all DmaHsp70s possess three function domains, it is noteworthy that only DmaHsp70 ends with a “EEVD” motif. Phylogenetic analysis indicates that the Hsp70-12 lineage is distanced from the rest, and therefore it is an uncharacterized lineage of Hsp70. The differences in isoelectric point and 3-dimensional (3D) conformation of the N-terminal nucleotide binding domain (NBD) of DmaHsp70s further support the theory. DmaHsp70s exhibit varied motif distribution patterns and the logo sequences of motifs have diverse signature characteristics, indicating that different mechanisms are involved in the regulation of ATP binding and hydrolysis for the DmaHsp70s. Protein-protein network together with the predicted subcellular locations of DmaHsp70s suggest that they likely fulfill distinct roles in cells. The transcription of four DmaHsp70s were changed during the recovery stage after thermal stress or oxidative stress. But the expression pattern of them were dissimilar. Collectively, these results collectively elucidated the identification of a previously uncharacterizedHsp70 lineage in animal and extended our understanding of the Hsp70 family.

Abstract Acute coronary syndrome (ACS) is a group of clinical syndromes caused by acute myocardial ischemia, which can cause heart failure, arrhythmia and even sudden death. It is the major cause of disability and death worldwide. Neutrophil extracellular traps (NETs) are reticular structures released by neutrophils activation and have various biological functions. NETs are closely related to the occurrence and development of ACS and also the subsequent damage after myocardial infarction. The mechanisms are complex and interdependent on various pathways, which require further exploration. This article reviewed the role and mechanism of NETs in ACS, thereby providing a valuable reference for the diagnosis and clinical treatment of ACS.

Abstract A 33-year male patient presented with a 6-month history of cough and shortness of breath upon physical activity. Echocardiography demonstrated right ventricular space-occupying lesions. Contrast-enhanced computed tomography of the chest showed multiple emboli in the pulmonary artery and its branches. Right ventricle tumor (myxoma) resection, tricuspid valve replacement, and clearance of the pulmonary artery thrombus were performed under cardiopulmonary bypass. Minimally invasive forceps and balloon urinary catheters were used to clear the thrombus. Clearance was confirmed by direct visualization using a choledochoscope. The patient recovered well and was discharged. The patient was prescribed oral warfarin 3 mg/day, and the international normalized ratio for prothrombin time was maintained between 2.0 and 3.0. Pre-discharge echocardiogram showed no lesion in the right ventricle or pulmonary arteries. The 6-month follow-up echocardiography indicated that the tricuspid valve was functioning well and showed no thrombus in the pulmonary artery.

Human trajectories can be tracked by the internal processing of a camera as an edge device. This work aims to match peoples’ trajectories obtained from cameras to sensor data such as acceleration and angular velocity, obtained from wearable devices. Since human trajectory and sensor data differ in modality, the matching method is not straightforward. Furthermore, complete trajectory information is unavailable; it is difficult to determine which fragments belong to whom. To solve this problem, we newly proposed the SyncScore model to find the similarity between a unit period trajectory and the corresponding sensor data. We also propose a Likelihood Fusion algorithm that systematically updates the similarity data and integrates it over time while keeping other trajectories in mind. We confirmed that the proposed method can match human trajectories and sensor data with an accuracy, a sensitivity, and an F1 of 0.725. Our models achieved decent results on the UEA dataset.

In welding tasks, the repeated positioning precision of robots can generally reach the micron level, but the data of each axis during each operation may vary. There may even be out-of-control situations where the robot does not run according to the set welding trajectory, which may cause the robot and equipment to collide and be damaged. Therefore, a real-time judgment method for the welding robot trajectory is proposed. Firstly, multiple sets of axis data are obtained by running the welding robot, and the phase of the data is aligned by using a proposed algorithm, and then the Kendall correlation coefficient is used to identify and remove weak axis data. Secondly, the mean of multiple sets of axis data with strong correlation is calculated as the standard trajectory, and the trajectory threshold of the robot is set using the μ ± nσ method based on the trajectory deviation judgment sensitivity. Finally, the absolute difference between the real-time axis trajectory and the standard trajectory is used to determine the deviation of the running trajectory. When the deviation reaches the threshold, a forewarning starts. When the deviation exceeds the threshold + σ, the robot is stopped. Take the six-axis welding robot as an example, by collecting the axis data of the robot running multiple times under the same conditions, it is proved that the proposed method can accurately warn the deviation of the running trajectory. The research results have important practical value for the prevention of welding robot accidents in industrial production.

Rural tourism spurs economic growth and jobs but harms the Environment due to energy demands. The study accounts for energy use, globalization, and economic growth to assess and mitigate rural tourism's environmental impact. For data covering 2001Q1 to 2019Q4, GMM approaches are utilized to analyze the environmental implications of rural tourist enterprises. The findings suggest that rural tourism-related catering services increased substantial and positive overall environmental quality, except N2O. However, food and beverage services negatively influence greenhouse gas emissions and only PM2.5 in air pollution. Sightseeing hurts greenhouse gas emissions while having a positive impact on air pollution. Furthermore, traveling has a considerable negative influence on CO emissions in air pollutants. Energy use only has a substantial influence on CO2 and CO, but GDP has a negative impact on N2O emissions. Globalization has a negative impact on CO2 and air pollutants other than PM2.5. Catering services associated with rural tourism positively affect overall environmental quality, excluding N2O emissions. Rural tourism's food and beverage services harm greenhouse gas emissions (including CO2) and air pollution (particularly PM2.5). Traveling has a significant negative impact on CO emissions, but sightseeing has a dual impact, both negative on greenhouse gas emissions and positive influence on air pollution. Furthermore, shopping and leisure have little impact on overall environmental quality in China. The crucial efforts' policy ramifications are addressed as well.

Objective: Neurologic complications seriously affect the survival rate and quality of life in patients with extracorporeal cardiopulmonary resuscitation (ECPR) undergoing cardiac arrest. This study aimed to repurpose selective hypothermic cerebral perfusion (SHCP) as a novel approach to protect the brains of these patients. Methods: Rats were randomly allocated to Sham, ECPR, and SHCP combined ECPR (CP-ECPR) groups. In the ECPR group, circulatory resuscitation was performed at 6 minutes after asphyxial cardiac arrest by extracorporeal membrane oxygenation. The vital signs were monitored for 3 hours, and body and brain temperatures were maintained at the normal level. In the CP-ECPR group, the right carotid artery catheterization serving as cerebral perfusion was connected with the extracorporeal membrane oxygenation device to achieve selective brain cooling (26-28 °C). Serum markers of brain injury and pathomorphologic changes in the hippocampus were evaluated. Three biological replicates further received RNA sequencing in ECPR and CP-ECPR groups. Microglia activation and inflammatory cytokines in brain tissues and serum were detected. Results: SHCP rapidly reduced the brain-targeted temperature and significantly alleviated nerve injury. This was evident from the reduced brain injury serum biomarker levels, lower pathologic scores, and more surviving neurons in the hippocampus in the CP-ECPR group. Furthermore, more differentially expressed genes for inflammatory responses were clustered functionally according to Kyoto Encyclopedia of Genes and Genomes pathway analysis. And SHCP reduced microglia activation and the release of proinflammatory mediators. Conclusions: Our preliminary data indicate that SHCP may serve as a potential therapy to attenuate brain injury via downregulation of neuroinflammation in patients with ECPR.

ABSTRACT Introduction: Ventricular septal rupture is an important high-mortality complication in the scope of myocardial infarctions. The effectiveness of different treatment modalities is still controversial. This meta-analysis compares the efficacy of percutaneous closure vs. surgical repair for the treatment of postinfarction ventricular septal rupture (PI-VSR). Methods: A meta-analysis was performed on relevant studies found through PubMed®, Embase, Web of Science, Cochrane Library, China National Knowledge Infrastructure (or CNKI), Wanfang Data, and VIP databases searching. The primary outcome was a comparison of in-hospital mortality between the two treatments, and the secondary outcome was documentation of one-year mortality, postoperative residual shunts, and postoperative cardiac function. Differences were expressed as odds ratios (ORs) with 95% confidence intervals (CIs) to assess the relationships between predefined surgical variables and clinical outcomes. Results: Qualified studies (742 patients from 12 trials) were found and investigated for this meta-analysis (459 patients in the surgical repair group, 283 patients in the percutaneous closure group). When comparing surgical repair to percutaneous closure, it was found that the former significantly reduced in-hospital mortality (OR: 0.67, 95% CI 0.48-0.96, P=0.03) and postoperative residual shunts (OR: 0.03, 95% CI 0.01-0.10, P

ObjectivesRuptured sinus of Valsalva aneurysm (RSVA) often has an abrupt onset, and can chest pain, acute heart failure, and even sudden death. The effectiveness of different treatment modalities remains controversial. Thus, we completed a meta-analysis to evaluate the efficiency and safety of traditional surgery vs. percutaneous closure (PC) for RSVA.MethodsWe carried out a meta-analysis using PubMed, Embase, Web of Science, Cochrane Library, China National Knowledge Infrastructure (CNKI), WanFang Data, and the China Science and Technology Journal Database. The primary outcome was comparing in-hospital mortality between the two procedures, and the secondary outcome was documenting postoperative residual shunts, postoperative aortic regurgitation, and length of hospital stay in the two groups. Differences were expressed as odds ratios (ORs) with 95% confidence intervals (CIs) to assess the relationships between predefined surgical variables and clinical outcomes. This meta-analysis was conducted using Review Manager software (version 5.3).ResultsThe final qualifying studies included 330 patients from 10 trials (123 in the percutaneous closure group, and 207 in the surgical repair group). When PC was compared to surgical repair, there were no statistically significant differences in in-hospital mortality (overall OR: 0.47, 95%CI 0.05–4.31, P = 0.50). However, percutaneous closure did significantly decrease the average length of hospital stay (OR: −2.13, 95% CI −3.05 to −1.20, P

BackgroundLeft subclavian artery (LSA) revascularization during thoracic endovascular aortic repair (TEVAR) is necessary to reduce postoperative complications in patients with Stanford type B aortic dissection and an insufficient proximal anchoring area. However, the efficacy and safety of different LSA revascularization strategies remain unclear. Here, we compared these strategies to provide a clinical basis for selecting an appropriate LSA revascularization method.MethodsIn this study, we included 105 patients with type B aortic dissection who were treated using TEVAR combined with LSA reconstruction in the Second Hospital of Lanzhou University from March 2013 to 2020. They were divided into four groups according to the method used for LSA reconstruction, namely, carotid subclavian bypass (CSB; n = 41), chimney graft (CG; n = 29), single-branched stent graft (SBSG; n = 21), and physician-made fenestration (PMF; n = 14) groups. Finally, we collected and analyzed the baseline, perioperative, operative, postoperative, and follow-up data of the patients.ResultsThe treatment success rate was 100% in all the groups, and CSB + TEVAR was the most commonly used procedure in emergency settings compared with the other three procedures (P 0.05) The median follow-up time of CSB, CG, SBSG, and PMF groups was significantly different (P

Summary: Enhancing chemosensitivity is one of the largest unmet medical needs in cancer therapy. Cyclic GMP-AMP synthase (cGAS) connects genome instability caused by platinum-based chemotherapeutics to type I interferon (IFN) response. Here, by using a high-throughput small-molecule microarray-based screening of cGAS interacting compounds, we identify brivanib, known as a dual inhibitor of vascular endothelial growth factor receptor and fibroblast growth factor receptor, as a cGAS modulator. Brivanib markedly enhances cGAS-mediated type I IFN response in tumor cells treated with platinum. Mechanistically, brivanib directly targets cGAS and enhances its DNA binding affinity. Importantly, brivanib synergizes with cisplatin in tumor control by boosting CD8+ T cell response in a tumor-intrinsic cGAS-dependent manner, which is further validated by a patient-derived tumor-like cell clusters model. Taken together, our findings identify cGAS as an unprecedented target of brivanib and provide a rationale for the combination of brivanib with platinum-based chemotherapeutics in cancer treatment.

A 10-year-old girl presented with obvious cyanosis, and the saturation of arterial blood oxygen (SpO2) was decreased to 60.5% in the outpatient examination. Computed tomography angiography (CTA) and echocardiography suggested congenitally corrected transposition of the great arteries (ccTGAs), membranous ventricular septal aneurysm (MVSA), atrial septal defect (ASD), severe pulmonary stenosis (PS), and severe tricuspid regurgitation (TR). Due to the complex pathological anatomical structures, the three-dimensional printed model was used for preoperative assessment. After a comprehensive evaluation was completed, the operation was performed by physiological correction under cardiopulmonary bypass, including the resection of MVSA, repair using the bovine pericardial patch for ASD, and linear valvuloplasty of the tricuspid valve. Due to the special anatomical structures of ccTGA, PS was treated by extracardiac pipe technique. After the operation, the patient recovered well, cyanosis disappeared, SpO2 was up to 96%, and the extracardiac pipe was well-functioning without regurgitation or obstruction.

Abstract Pathogenic mycobacteria induce the formation of hypoxic granulomas during latent tuberculosis (TB) infection, in which the immune system contains, but fails to eliminate the mycobacteria. Fatty acid metabolism-related genes are relatively overrepresented in the mycobacterial genome and mycobacteria favor host-derived fatty acids as nutrient sources. However, whether and how mycobacteria modulate host fatty acid metabolism to drive granuloma progression remains unknown. Here, we report that mycobacteria under hypoxia markedly secrete the protein Rv0859/MMAR_4677 (Fatty-acid degradation A, FadA), which is also enriched in tuberculous granulomas. FadA acts as an acetyltransferase that converts host acetyl-CoA to acetoacetyl-CoA. The reduced acetyl-CoA level suppresses H3K9Ac-mediated expression of the host proinflammatory cytokine Il6, thus promoting granuloma progression. Moreover, supplementation of acetate increases the level of acetyl-CoA and inhibits the formation of granulomas. Our findings suggest an unexpected mechanism of a hypoxia-induced mycobacterial protein suppressing host immunity via modulation of host fatty acid metabolism and raise the possibility of a novel therapeutic strategy for TB infection.

Cardiovascular disease morbidity/mortality are increasing due to an aging population and the rising prevalence of diabetes and obesity. Therefore, innovative cardioprotective measures are required to reduce cardiovascular disease morbidity/mortality. The role of necroptosis in myocardial ischemia–reperfusion injury (MI–RI) is beyond doubt, but the molecular mechanisms of necroptosis remain incompletely elucidated. Growing evidence suggests that MI–RI frequently results from the superposition of multiple pathways, with autophagy, ferroptosis, and CypD-mediated mitochondrial damage, and necroptosis all contributing to MI–RI. Receptor-interacting protein kinases (RIPK1 and RIPK3) as well as mixed lineage kinase domain-like pseudokinase (MLKL) activation is accompanied by the activation of other signaling pathways, such as Ca2+/calmodulin-dependent protein kinase II (CaMKII), NF-κB, and JNK-Bnip3. These pathways participate in the pathological process of MI–RI. Recent studies have shown that inhibitors of necroptosis can reduce myocardial inflammation, infarct size, and restore cardiac function. In this review, we will summarize the molecular mechanisms of necroptosis, the links between necroptosis and other pathways, and current breakthroughs in pharmaceutical therapies for necroptosis.

This paper provides a Páde interpolation based method for finding improved bounds for the exponential function with cotangent. In principle, it can recover many results in prevailing methods. A new method for proving the corresponding bounds is also proposed, which can also be applied for proving more other bounding functions. Numerical experiments show that the new bounds are better than those of prevailing methods.

The positional accuracy of multi-leaf collimators (MLC) is important in stereotactic body radiotherapy (SBRT). The aim of this study was to investigate the impact between MLC positional error and dosimetry of volume intensity modulated (VMAT) and general intensity modulated (IMRT) plans for non-small cell lung cancer (NSCLC). Fifteen patients with NSCLC were selected to design the 360 SBRT-VMAT plans and the 360 SBRT-IMRT error plans. The DICOM files for these treatment plans were imported into a proprietary computer program that introduced delivery errors. Random and systematic MLC position (0.1, 0.2, 0.5, 1.0, 1.5, and 2.0 mm) errors were introduced. The systematic errors were shift errors (caused by gravity), opening errors, and closing errors. The CI, GI, d2cm and generalized equivalent uniform dose (gEUD) were calculated for the original plan and all treatment plans, accounting for the errors. Dose sensitivity was calculated using linear regression for MLC position errors. The random MLC errors were relatively insignificant. MLC shift, opening, and closing errors had a significant effect on the dose distribution of the SBRT plan. VMAT was more significant than IMRT. To ensure that the gEUD variation of PTV is controlled within 2%, the shift error, opening error, and closing error of IMRT should be less than 2.4 mm, 1.15 mm, and 0.97 mm, respectively. For VMAT, the shift error, opening error, and closing error should be less than 0.95 mm, 0.32 mm, and 0.38 mm, respectively. The dose sensitivity results obtained in this study can be used as a guide for patient-based quality assurance efforts. The position error of the MLC system had a significant impact on the gEUD of the SBRT technology. The MLC systematic error has a greater dosimetric impact on the VMAT plan than on the IMRT plan for SBRT, which should be carefully monitored.

Background. Myocardial bridging (MB) is a congenital anomaly involving the myocardial tissue encasement of a segment of the coronary artery. The purpose of the present study was to assess safety and efficacy of two surgical methods used for treating MB patients at our institute. Methods. Off-pump MB unroofing was performed in 45 adult patients between January 2016 and December 2021 by traditional surgical unroofing techniques (conventional group, n = 26) and blunt dissection techniques (blunt dissection group, n = 19). We retrospectively reviewed our patients by examining the baseline clinical characteristics, risk factors, medications, and diagnostic data for coronary artery disease. The Seattle Angina Questionnaire (SAQ) was used to assess angina symptoms both preoperatively and 6 months postsurgery. Results. No significant difference in preoperative clinical characteristics was observed between the two groups. The blunt dissection group had shorter unroofed period (14.69 vs. 18.91 mins, P=0.001), less ventilator time (16.26 vs. 24.62 hours, P

The measurement and control of residual stresses are crucial to the structural safety of high-speed trains. The critical refraction longitudinal wave method is extensively employed for the residual stress measurement, and the correction of the influencing factors is the key to the detection accuracy. However, the existing methods mostly give purely mathematical expressions which are only applicable to their studied materials. Hence, this paper proposes the specific influence factor correction method to enhance the applicability and accuracy, and the 5083 aluminum alloy welded component is utilized for testing. Subsequently, the stress coefficient K and the compensation acoustic time under the influence of internal factors are obtained by employing the proposed method, combined with the simulation to determine the focused detection zone, the hole-drilling and X-ray methods are utilized for comparisons, and the results indicate that the test data have a good coincidence. Meanwhile, the detection errors of each zone before and after the correction are analyzed. Moreover, combined with the experimental verification, it is found that the penetration depth of a critical refraction longitudinal wave approaches its one wavelength; the corresponding study is conducted with this characteristic and concludes that in the weld zone, the longitudinal residual stresses are mainly concentrated on the surface of the measured material. Finally, the above results indicate that the proposed method can provide more accurate measurements for engineering applications.

BackgroundBladder urothelial carcinoma (BLCA) is one of the most common urinary system malignancies with a high metastasis rate. Cancer stem cells (CSCs) play an important role in the occurrence and progression of BLCA, however, its roles in bone metastasis and the prognostic stemness biomarkers have not been identified in BLCA.MethodIn order to identify the roles of CSC in the tumorigenesis, bone metastasis and prognosis of BLCA, the RNA sequencing data of patients with BLCA were retrieved from The Cancer Genome Atlas (TCGA) databases. The mRNA expression-based stemness index (mRNAsi) and the differential expressed genes (DEGs) were evaluated and identified. The associations between mRNAsi and the tumorigenesis, bone metastasis, clinical stage and overall survival (OS) were also established. The key prognostic stemness-related genes (PSRGs) were screened by Lasso regression, and based on them, the predict model was constructed. Its accuracy was tested by the area under the curve (AUC) of the receiver operator characteristic (ROC) curve and the risk score. Additionally, in order to explore the key regulatory network, the relationship among differentially expressing TFs, PSRGs, and absolute quantification of 50 hallmarks of cancer were also identified by Pearson correlation analysis. To verify the identified key TFs and PSRGs, their expression levels were identified by our clinical samples via immunohistochemistry (IHC).ResultsA total of 8,647 DEGs were identified between 411 primary BLCAs and 19 normal solid tissue samples. According to the clinical stage, mRNAsi and bone metastasis of BLCA, 2,383 stage-related DEGs, 3,680 stemness-related DEGs and 716 bone metastasis-associated DEGs were uncovered, respectively. Additionally, compared with normal tissue, mRNAsi was significantly upregulated in the primary BLCA and also associated with the prognosis (P = 0.016), bone metastasis (P < 0.001) and AJCC clinical stage (P < 0.001) of BLCA patients. A total of 20 PSRGs were further screened by Lasso regression, and based on them, we constructed the predict model with a relatively high accuracy (AUC: 0.699). Moreover, we found two key TFs (EPO, ARID3A), four key PRSGs (CACNA1E, LINC01356, CGA and SSX3) and five key hallmarks of cancer gene sets (DNA repair, myc targets, E2F targets, mTORC1 signaling and unfolded protein response) in the regulatory network. The tissue microarray of BLCA and BLCA bone metastasis also revealed high expression of the key TFs (EPO, ARID3A) and PRSGs (SSX3) in BLCA.ConclusionOur study identifies mRNAsi as a reliable index in predicting the tumorigenesis, bone metastasis and prognosis of patients with BLCA and provides a well-applied model for predicting the OS for patients with BLCA based on 20 PSRGs. Besides, we also identified the regulatory network between key PSRGs and cancer gene sets in mediating the BLCA bone metastasis.

Residues of the psychoactive drug diazepam (DZP) may pose potential risks to fish in aquatic environments, especially by disrupting their behavioral traits. In this study, female and male zebrafish were subjected to chronic exposure (21 days) to sublethal doses (120 and 12 µg/L) of DZP, aimed to compare the characteristics of their behavioral responses to DZP exposure, and to investigate the possible links between those behavioral responses and variations in their brain γ-aminobutyric acid (GABA) and acetylcholinesterase (AChE) levels. Chronic exposure to DZP significantly decreased the swimming velocity and locomotor activity of both genders, indicating a typical sedative effect. Compared with males, whose locomotor activity was only significantly decreased by exposure to DZP for 21 days, females became hypoactive on day 14 (i.e., more sensitive), and they developed tolerance to the hypoactive effect induced by 120 μg/L DZP by day 21. Exposure to DZP significantly disturbed the behavioral traits related to social interactions in females but not in males. Those results indicate that DZP exhibits sex-dependent effects on the behaviors of fish. Moreover, exposure to DZP for 21 days significantly disturbed almost all of the tested behavioral traits associated with courtship when both genders were put together. Sex-dependent responses in brain GABA and AChE levels due to DZP exposure were also identified. Significant relationships between the brain GABA/AChE levels and some behavioral parameters related to locomotor activity were detected in females, but not in males.

The combined application of nanoparticles and surfactants has attracted tremendous attention in basic research and industry. However, knowledge of their combined toxicity remains scarce. In this study, we exposed zebrafish embryos to cetylpyridinium chloride (CPC, a cationic surfactant, at 0 and 20 μg/L), zeolitic imidazolate framework nanoparticles (ZIF-NPs, at 0, 30, and 60 mg/L), and their mixtures until 120 h post-fertilization (hpf). Within the used concentration range, both single and combined exposures exhibited limited effects on the survival and hatching of zebrafish. However, the combined exposure of ZIF-NPs and CPC caused more severe effects on the heart rate at both 48 and 72 hpf. The combined exposure also induced significant hyperactivity (i.e., increasing the average swimming velocity) and oxidative stress in zebrafish larvae (at 120 hpf), although all single exposure treatments exhibited limited impacts. Furthermore, the level of reactive oxygen species (or malondialdehyde) exhibited a significantly positive correlation with the heart rate (or average swimming velocity) of zebrafish, suggesting that oxidative stress plays a role in mediating the combined toxicity of CPC and ZIF-NPs to zebrafish. Our findings suggest that the interaction of CPC and ZIF-NPs should not be ignored when assessing the potential risks of their mixtures.

Cetylpyridinium chloride (CPC) is a widely used surfactant that has been detected in various water ecosystems. However, knowledge on the toxicity of CPC to fish remains scarce. Here, we examined the survival, development, behavior, and oxidative stress in the early life stages of zebrafish exposed to CPC (0, 4, 40, 400, and 1200 μg/L) until 120 h post-fertilization (hpf). Results showed that CPC induced significant mortality at 400 and 1200 μg/L, with a 120 h-EC50 value of 175.9 μg/L. CPC significantly decreased the heart rate of embryos (48 hpf; 4–400 μg/L) and larvae (72 hpf; 40 and 400 μg/L). At 120 hpf, CPC exhibited a dual effect on the locomotion activity (decreased at 400 μg/L and increased at 4 and 40 μg/L) and elevated the reactive oxygen species, superoxide dismutase, and glutathione levels in zebrafish larvae at 400 µg/L. In addition, a correlation analysis revealed that CPC-induced oxidative stress might play a critical role in mediating the cardiac and behavioral toxicity of CPC to zebrafish larvae. Our findings suggest that CPC may disturb the fish’s development, behavior, and oxidative status at environmentally relevant concentrations, which should not be ignored when assessing its potential risks to aquatic ecosystems.

The degenerative transfer of xanthates to olefins is enabled by the iridium-based photocatalyst [Ir{dF(CF3)ppy}2(dtbbpy)](PF6) under blue LED light irradiation. Detailed mechanistic investigations through kinetics and photophysical studies revealed that the process operates under a radical chain mechanism, which is initiated through triplet-sensitization of xanthates by the long-lived triplet state of the iridium-based photocatalyst.

Genetic risk loci for tuberculosis (TB) have so far been identified in African and Russian populations. Here, the authors perform a three-stage GWAS for TB in Han Chinese populations and find two risk loci near ESRRB and TGM6 and further demonstrate that tgm6 protects mice from Mtb infection.

Urinary tract infections are a common side effect of urethral catheters. Here, the authors report on the development of antibiotic loaded NPs with functional polymer coatings which attach too and are removed by motile bacteria to trigger the release of antibiotic.