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The determination of illegal drugs and psychoactive substances in wastewater is increasingly being used to monitor the use of both by populations in specific areas. This article describes a method for the simultaneous determination of 78 illegal drugs and psychoactive substances in wastewater using direct-injection ultra-high-performance liquid chromatography–tandem mass spectrometry (UHPLC-MS/MS). This method includes the analysis of stimulants, opioids, antidepressants, antipsychotic drugs, anti-anxiety drugs, and hallucinogens. The method was validated in terms of the selectivity, calibration range, recovery, matrix effects, accuracy, precision, limit of detection (LOD), and limit of quantification (LOQ). The correlation coefficients were higher than 0.99 for all analytes, and the calibration range was from 0.2 to 500 ng/L. The LOD and LOQ of this method were 0.1–1 ng/L and 0.2–5 ng/L, respectively. The intra- and inter-day precisions were <9.3% and 11.4%, respectively, and the recovery ranged from 81.3% to 117.7%. The method was applied to real domestic wastewater collected from wastewater treatment plants, and the results showed that morphine, codeine, and ephedrine were detected in all samples. Some samples also contained other illegal drugs and psychoactive substances (such as etomidate, methamphetamine, ketamine, and tramadol). This indicates that the direct-injection UHPLC-MS/MS method can be used for the rapid determination of illegal drugs and psychoactive substances in wastewater. [ABSTRACT FROM AUTHOR]

In recent years, there has been growing concern over the rising incidence of liver diseases, with increasing exposure to environmental toxins as a significant contributing factor. However, the mechanisms of liver injury induced by environmental pollutants are largely unclear. Here, using tetrabromobisphenol A (TBBPA), a widely used brominated flame retardant, as an example, environmental toxin‐induced liver toxicity in mice is characterized via single‐cell sequencing technology. Heterogeneous gene expression profiles after exposure to TBBPA in major cell types of the liver are demonstrated. In hepatocytes, pathway analysis of differentially expressed genes reveals the enhanced interferon response and diminished metabolic processes. The disrupted endothelial functions in TBBPA‐treated cells are then shown. Moreover, the activation of M2‐polarization in Kupffer cells, as well as activated effector T and B cells are unveiled in TBBPA‐treated cells. Finally, ligand‐receptor pair analysis shows that TBBPA disrupts cell‐cell communication and induces an inflammatory microenvironment. Overall, the results reveal that TBBPA‐induced dysfunction of hepatocytes and endothelial cells may then activate and recruit other immune cells such as Kuffer cells, and T/NK cells into the liver, further increasing inflammatory response and liver injury. Thus, the results provide novel insight into undesiring environmental pollutant‐induced liver injury. [ABSTRACT FROM AUTHOR]

The structural stability of the underwater shield tunnel during operations is affected by temperature variations. The effect of different structure temperatures on the underwater shield tunnel during the operation period was studied. By numerical simulation, the variation in the underwater shield tunnel temperature circle was analyzed. The variation patterns of the top arch, bottom arch, waist arch temperature, maximum principal stress, and settlement of the soil under different temperatures were obtained. The results showed that: (1) The early excavation time of the tunnel was short, and the temperature circle was small. The temperature circle expanded rapidly after 50 days of operating. The diffusion range increased from 1.5 m to 5.35 m: an increase of 256.7%. With the increase in time, the expansion rate of the temperature circle gradually slowed down. (2) The higher the temperature of the soil, the more complex the temperature transfer between the soil and the lining was while generating greater temperature stresses and reducing the safety of the tunnel. (3) When the tunnel was just excavated, the compression settlement of the top arch and the waist arch increased rapidly, reaching 5.43 mm and 0.24 mm, respectively. The bottom arch was squeezed by the soil on both sides, resulting in an uplift and rapid increase, reaching 4.94 mm. The settlement rate increased with the increase in the tunnel structure's temperature. After the excavation, with the decrease in temperature, the strength of the soil and lining increased. The settlement of the top arch, bottom arch, and waist arch increased slowly with time, and the growth rate decreased gradually. [ABSTRACT FROM AUTHOR]

Suction bucket foundation is a typical type for offshore turbines. Scour caused by wave and current can reduce the stability of foundation and then endanger the whole structure. This paper details a series of suction bucket model tests performed in sand under wave cyclic loading. The model tests investigate the effect of scour on stability of bucket foundation by artificially excavated scour hole around the foundation. It is revealed that the behavior of foundation bearing capacity can be divided into two stages: the initial cyclic stage and the final stage (showing either cyclic stability or cyclic failure). When the wave circulation is stable, the sand on the front and back sides of the foundation is suspected to be liquefied. With the increase in scour depth, the stability of foundation is gradually reduced, the behavior of foundation gradually changes from a state of cyclic stability to cyclic failure, and the number of waves that can be withstood is drastically reduced. Finally, the height of the center of rotation of the suction bucket was observed to descend with the increase in scour depth. [ABSTRACT FROM AUTHOR]

Background: Chimeric antigen receptor natural killer (CAR-NK) therapy holds great promise for treating hematologic tumors, but its efficacy in solid tumors is limited owing to the lack of suitable targets and poor infiltration of engineered NK cells. Here, we explore whether immunogenic cell death (ICD) marker ERp57 translocated from endoplasmic reticulum to cell surface after drug treatment could be used as a target for CAR-NK therapy., Methods: To target ERp57, a VHH phage display library was used for screening ERp57-targeted nanobodies (Nbs). A candidate Nb with high binding affinity to both human and mouse ERp57 was used for constructing CAR-NK cells. Various in vitro and in vivo studies were performed to assess the antitumor efficacy of the constructed CAR-NK cells., Results: We demonstrate that the translocation of ERp57 can not only be induced by low-dose oxaliplatin (OXP) treatment but also is spontaneously expressed on the surface of various types of tumor cell lines. Our results show that G6-CAR-NK92 cells can effectively kill various tumor cell lines in vitro on which ERp57 is induced or intrinsically expressed, and also exhibit potent antitumor effects in cancer cell-derived xenograft and patient-derived xenograft mouse models. Additionally, the antitumor activity of G6-CAR-NK92 cells is synergistically enhanced by the low-dose ICD-inducible drug OXP., Conclusion: Collectively, our findings suggest that ERp57 can be leveraged as a new tumor antigen for CAR-NK targeting, and the resultant CAR-NK cells have the potential to be applied as a broad-spectrum immune cell therapy for various cancers by combining with ICD inducer drugs., Competing Interests: Competing interests: No, there are no competing interests., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Surgery and targeted therapy are of equal importance for colorectal cancer (CRC) treatment. However, complete CRC tumor resection remains challenging, and new targeted agents are also needed for efficient CRC treatment. Cadherin 17 (CDH17) is a membrane protein that is highly expressed in CRC and, therefore, is an ideal target for imaging-guided surgery and therapeutics. This study utilizes CDH17 nanobody (E8-Nb) with the near-infrared (NIR) fluorescent dye IRDye800CW to construct a NIR-II fluorescent probe, E8-Nb-IR800CW, and a Pseudomonas exotoxin (PE)-based immunotoxin, E8-Nb-PE38, to evaluate their performance for CRC imaging, imaging-guided precise tumor excision, and antitumor effects. Our results show that E8-Nb-IR800CW efficiently recognizes CDH17 in CRC cells and tumor tissues, produces high-quality NIR-II images for CRC tumors, and enables precise tumor removal guided by NIR-II imaging. Additionally, fluorescent imaging confirms the targeting ability and specificity of the immunotoxin toward CDH17-positive tumors, providing the direct visible evidence for immunotoxin therapy. E8-Nb-PE38 immunotoxin markedly delays the growth of CRC through the induction of apoptosis and immunogenic cell death (ICD) in multiple CRC tumor models. Furthermore, E8-Nb-PE38 combined with 5-FU exerts synergistically antitumor effects and extends survival. This study highlights CDH17 as a promising target for CRC imaging, imaging-guided surgery, and drug delivery. Nanobodies targeting CDH17 hold great potential to construct NIR-II fluorescent probes for surgery navigation, and PE-based toxins fused with CDH17 nanobodies represent a novel therapeutic strategy for CRC treatment. Further investigation is warranted to validate these findings for potential clinical translation., Competing Interests: Competing interests: The authors declare that they have no competing interests., (Copyright © 2024 Youbin Ding et al.)

Purpose: So far, there have been no in-depth analyses of the connection between tinnitus sensation-level loudness and sleep quality. Accordingly, the present study was formulated as a mediation analysis focused on exploring this relationship., Method: Overall, 1,255 adults with consecutive subjective tinnitus who had sought outpatient treatment were enrolled in the present study., Results: Direct effects of tinnitus sensation-level loudness on sleep quality were not statistically significant (95% confidence intervals [CI] include zero), as measured by the point estimate, -0.016. However, the 95% CI for indirect effects did not include zero when assessing the Self-Rating Anxiety Scale (SAS) scores, the Self-Rating Depression Scale (SDS) scores, the visual analogue scale (VAS) scores, and self-reported tinnitus annoyance., Conclusions: These results suggest that tinnitus sensation-level loudness does not directly have an effect on sleep quality. However, it indirectly impacts sleep quality, mediated by SAS scores, SDS scores, the impact of tinnitus on life measured using the VAS, and self-reported tinnitus annoyance. As such, alleviating anxiety and depression in patients with tinnitus may result in reductions in their insomnia even if there is no reduction in tinnitus loudness. Importantly, otolaryngologists and other clinicians treating tinnitus should refer patients with tinnitus suffering from insomnia with comorbid depression or anxiety for appropriate psychological and/or psychiatric treatment.