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Spindle component 25 (SPC25) is one of the four proteins that make up the nuclear division cycle 80 (NDC80) complex, the other three components being Ndc80p, Nuf2p, and spindle component 24. Deregulation of the components of this complex can lead to uncontrolled proliferation and reduced apoptosis. However, the prognostic and immunotherapeutic value of SPC25 in pan-cancer remains unclear. Data from the UCSC Xena, TIMER2.0, and TCGA were analyzed to investigate the overall differential expression of SPC25 across multiple cancer types. The survival prognosis, clinical features, and genetic changes of SPC25 were also evaluated. Finally, the relationship between SPC25 and immunotherapy response was further explored through Gene Set Enrichment Analysis, tumor microenvironment, and immune cell infiltration. The transcription and protein expression of SPC25 were significantly increased in most cancer types and had prognostic value for the survival of certain cancer patients such as ACC, CESC, KIRC, KIRP, LIHC, LUAD, MESO, STAD, THYM, and UCEC. In some cancer types, SPC25 expression was also markedly correlated with the TMB, MSI, and clinical characteristics. Gene Set Enrichment Analysis showed that SPC25 was significantly associated with immune-related pathways. In addition, it was also confirmed that the expression level of SPC25 was strongly correlated with immune cell infiltration, immune checkpoint genes, immune regulatory genes, Ferroptosis-related genes, Cuproptosis-related genes, and lactate metabolism-related genes. This study comprehensively explored the potential value of SPC25 as a prognostic and immunotherapeutic marker for pan-cancer, providing new direction and evidence for cancer therapy.

Emerging research supports that triclosan (TCS), an antimicrobial agent found in thousands of consumer products, exacerbates colitis and colitis-associated colorectal tumorigenesis in animal models. While the intestinal toxicities of TCS require the presence of gut microbiota, the molecular mechanisms involved have not been defined. Here we show that intestinal commensal microbes mediate metabolic activation of TCS in the colon and drive its gut toxicology. Using a range of in vitro, ex vivo, and in vivo approaches, we identify specific microbial β-glucuronidase (GUS) enzymes involved and pinpoint molecular motifs required to metabolically activate TCS in the gut. Finally, we show that targeted inhibition of bacterial GUS enzymes abolishes the colitis-promoting effects of TCS, supporting an essential role of specific microbial proteins in TCS toxicity. Together, our results define a mechanism by which intestinal microbes contribute to the metabolic activation and gut toxicity of TCS, and highlight the importance of considering the contributions of the gut microbiota in evaluating the toxic potential of environmental chemicals. Triclosan (TCS), an antimicrobial agent commonly found in consumer products, has been reported to exacerbates colitis in animal models. Here, using in vitro and in vivo approaches, the authors show that gut bacterial enzymes can drive the metabolic activation and gut toxicity of TCS, highlighting an important role of intestinal microbial factors in the complex etiology of colitis.

Common vaccinations may have impacts on dementia risk, but current evidence is inconsistent. We therefore investigated the association between vaccinations and dementia risk by systematic review and meta-analysis approach. We conducted an extensive search of PubMed, Embase, Cochrane Library, and Web of Science to identify studies that compared the risk of dementia in vaccinated versus unvaccinated populations. The adjusted hazard ratio (HR) and corresponding 95% confidence intervals (CIs) were pooled as measures. Of the 9124 records initially retrieved, 17 studies with 1857134 participants were included in our analysis. The overall pooled results showed that vaccinations were associated with a 35% lower dementia risk (HR=0.65, 95% CI: 0.60-0.71, < 0.001; 91.8%, <0.001). All types of vaccination were associated with a trend toward reduced dementia risk, with rabies (HR=0.43), tetanus & diphtheria & pertussis (Tdap) (HR=0.69), herpes zoster (HR=0.69), influenza (HR=0.74), hepatitis A (HR=0.78), typhoid (HR=0.80), and hepatitis B (HR=0.82) vaccinations being significant. Individuals with more full vaccination types and more annual influenza vaccinations were less likely to develop dementia. Gender and age had no effect on this association. Routine adult vaccinations are associated with a significant reduction in dementia risk and may be an effective strategy for dementia prevention. Further research is needed to elucidate the causal effects of this association and the underlying mechanisms.

Background Immune checkpoint inhibitor-related pneumonitis in patients with lung cancer has been well managed. However, pulmonary infections following the use of immune checkpoint inhibitors (ICIs) have not been fully studied. This study aimed to investigate the incidence, pathogen distribution, and risk factors of pulmonary infections in lung cancer patients receiving ICIs therapy. Methods A retrospective analysis was conducted on 107 lung cancer patients treated with PD-1/PD-L1 inhibitors at a single institution. Pulmonary infections were defined as grade ≥2 (CTCAE v5.0) and confirmed microbiologically or clinically. Data on demographics, comorbidities, treatment details, and outcomes were analyzed. Cumulative incidence of grade 2-5 pulmonary infections following ICIs therapy was assessed using Kaplan-Meier methodology. Univariate and multivariate logistic regression identified risk factors. Results Among the 107 patients, 44 (41.1%, 44/107) developed pulmonary infections during a median follow-up of 8 months.Of these, 25 (56.8%, 25/44) cases of pulmonary infection were confirmed by etiological examination, and 19 were diagnosed clinically. The 25 infected patients had a total of 58 infections (primary causative microorganisms), among which the frequencies of bacterial, fungal, viral, and mycobacterial infections were 24 (41.4%, 24/58), 21 (36.2%, 21/58), 9 (15.5%, 9/58), and 4 (6.9%, 4/58), respectively. Notably, in the confirmed cases, 76.0%(19/25) exhibited mixed infections.Among 18 lung cancer patients with concurrent pulmonary tuberculosis(PTB), 11 developed pulmonary infections (61.1%,11/18), and 5 of these experienced progression or new-onset PTB. The incidence of pulmonary infection among those receiving thoracic radiotherapy (TRT) was 58.3% (21/36), and the V20 value in the infection group was significantly higher than in the non-infection group ( p = 0.0395). Independent risk factors for pulmonary infection included age ≥65 years (adjusted OR = 3.705, p =0.007), lmaging-Suggested Interstitial Pulmonary Abnormality (ISIPA) (adjusted OR = 7.459, p = 0.001), TRT (adjusted OR = 5.141, p= 0.002), and a history of tuberculosis (adjusted OR = 4.676, p = 0.015). Conclusions Among lung cancer patients receiving immune checkpoint inhibitors (ICIs), there is a notably high incidence of pulmonary infections. The prevalence of mixed infections suggests the need for multiple coverage of pathogenic microorganisms. Independent risk factors included age ≥65, pre-existing ISIPA, thoracic radiotherapy, and prior PTB. The association between ICI therapy and radiotherapy warrants further investigation. Additional prospective studies are required to confirm these findings and guide optimal clinical management strategies.

Cancer therapy is a double-edged sword, as surgery and chemotherapy can induce an inflammatory/immunosuppressive injury response that promotes dormancy escape and tumor recurrence. We hypothesized that these events could be altered by early blockade of the inflammatory cascade and/or by accelerating the resolution of inflammation. Preoperative, but not postoperative, administration of the nonsteroidal antiinflammatory drug ketorolac and/or resolvins, a family of specialized proresolving autacoid mediators, eliminated micrometastases in multiple tumor-resection models, resulting in long-term survival. Ketorolac unleashed anticancer T cell immunity that was augmented by immune checkpoint blockade, negated by adjuvant chemotherapy, and dependent on inhibition of the COX-1/thromboxane A2 (TXA2) pathway. Preoperative stimulation of inflammation resolution via resolvins (RvD2, RvD3, and RvD4) inhibited metastases and induced T cell responses. Ketorolac and resolvins exhibited synergistic antitumor activity and prevented surgery- or chemotherapy-induced dormancy escape. Thus, simultaneously blocking the ensuing proinflammatory response and activating endogenous resolution programs before surgery may eliminate micrometastases and reduce tumor recurrence.

Chronic obstructive pulmonary disease (COPD) is one of the most widespread diseases. Previous research has found that immune cells and telomeres may affect COPD's pathogenesis, but their combined mechanism in COPD remains unclear. This study aims to investigate the diagnostic value of telomere-associated genes and immune cells in COPD, as well as their synergistic mechanisms, thereby providing novel insights for the clinical management of COPD. Data comprising 19 COPD cases, 24 control samples, and 2086 telomere-related genes (TRGs) were obtained from public databases. The differentially expressed genes (DEGs) between COPD and control were obtained by differential expression analysis. The key module genes related to different immune cells (DICs) were obtained via weighted gene co-expression network analysis (WGCNA). Subsequently, biomarkers were further identified by intersecting all genes, utilizing machine learning algorithm, and verifying the expression level.Furthermore, the nomogram was constructed, and gene set enrichment analysis (GSEA) of biomarkers was adopted. The transcription factors (TFs), microRNAs (miRNAs) and drugs linked to biomarkers were obtained from the databases. The expression of biomarkers in 10 clinical samples was validated via reverse transcription quantitative polymerase chain reaction (RT-qPCR). In this study, ALDH2 and HNMT were identified as biomarkers. The nomogram results demonstrated that the model had an outstanding predictive ability for COPD (area under curve (AUC) = 0.88). Besides, ALDH2 and HNMT were enriched in junction, starch, and sucrose metabolism. In addition, a total of 6 TFs such as ELF3, and 2 miRNAs, such as miR-206, were linked to ALDH2 and HNMT, and clozapine was the drug that had been found to be associated with both ALDH2 and HNMT. Finally, the RT-qPCR results were consistent with bioinformatics analysis. This study identified 2 biomarkers (ALDH2 and HNMT), which might serve as potential targets for COPD. A nomogram model constructed based on biomarkers was employed for the clinical auxiliary diagnosis of COPD. This study provided new scientific evidence for improving the diagnostic process and individualized treatment strategies for COPD.

In recent years, large-capacity, high-head pump–turbine units have been developed for pumped storage power plants to effectively utilise water energy and store large amounts of electricity. Compared with the traditional Francis turbine unit, the radial distance between the trailing edge of the guide vanes and the leading edge of runner blades of high-head pump–turbine unit is smaller, so the rotor–stator interaction and the corresponding pressure fluctuations in the vaneless space of pumped storage units are more intense. The pressure fluctuations with high amplitudes and high frequencies induced by rotor–stator interaction (RSI) become the main hydraulic excitation source for the structures of the unit and may cause violent vibration and fatigue damage to structural components, and seriously affect the safe operation of the units. In this paper, the RSI of a high-head pump–turbine in turbine mode of operation is studied in detail by means of site measurement and full three-dimensional unsteady simulations. The results of RSI-induced pressure fluctuations in turbine mode are analysed experimentally and numerically. The accuracy of the numerical calculations is verified by comparing with the measured results, and the variation law of RSI is deeply analysed. The results show that the pressure fluctuations in the vaneless space are affected by the wake of the guide vane, the rotating excitation of the runner, the low-frequency excitation of the draft tube, and the asymmetric characteristics of the incoming flow of the spiral case, and shows significant differences in spatial position. The findings of the investigation are an important and valuable reference for the design and safe operation of the pumped storage power station. It is recommended to design the runner with inclined inlets to reduce the amplitudes of RSI-induced pressure fluctuations and to avoid operating the pump–turbine units under partial load for long periods of time to reduce the risk of pressure fluctuation induced severe vibration on the structures.

During the load rejection transient process of the prototype pump turbine units, the pressure fluctuations of the entire flow passage change drastically due to the rapid closing of guide vanes. The extremely unsteady pressure distribution in the flow domains including the crown chamber and the band chamber may cause a strong vibration on the stationary structures of the unit and result in large dynamic stress on the head cover, stay ring and bottom ring. In this paper, the numerical fluid dynamic analysis of the entire flow passage of a reversible prototype pump turbine during load rejection was performed. The flow characteristics in the runner passage, crown chamber, band chamber, seal labyrinths and balance tubes are analysed. The corresponding unsteady flow-induced dynamic behaviour of the head cover, stay vanes and bottom ring was investigated in detail. The analysed results show that the total deformation of the inner edge of the head cover closed to the main shaft is larger than that of other stationary structures of the unit during the load rejection. The maximum stress of the stay ring is larger than that of the head cover and the bottom ring and the maximum equivalent stress is located at the fillet of the stay vane trailing edge. The fluid–structure coupling calculation method and the analysed results can provide guidance for the design of stationary components of hydraulic machinery such as pump turbines, Francis turbines and centrifugal pumps with different heads.

Water depth estimation is paramount in various domains, including navigation, environmental monitoring, and resource management. Traditional depth measurement methods, such as bathymetry, can often be expensive and time-consuming, especially in remote or inaccessible areas. This study delves into the application of machine learning techniques, specifically focusing on the Baidu Easy DL model for water depth estimation leveraging satellite imagery. Utilizing Sentinel-2 satellite data over Rushikonda Beach in India and processing it into remote sensing reflectance using ACOLITE software, this research compares the performance of several machine learning algorithms, including the Stumpf model, Log-Linear model, and the Baidu Easy DL model, for accurate depth estimation. The results indicate that the Easy-DL model outperforms traditional methods, particularly excelling in the 0–11 m depth range. This study showcases the substantial potential of machine learning in remote sensing, offering robust water depth estimates, even in complex coastal environments. Furthermore, it underscores the critical role of comprehensive training datasets and ensemble learning techniques in enhancing accuracy. This research opens avenues for the further exploration of machine learning applications in remote sensing and highlights the promising prospects of online model APIs when streamlining remote sensing data processing.

Inflammation is important and has been found to be an underlying cause in many acute and chronic human diseases. Nuciferine, a natural alkaloid containing an aromatic ring, is found in the nelumbo nucifera leaves. It has been shown to have potential anti-inflammatory activities, but the molecular mechanism has remained unclear. In this study, we found that nuciferine (10 μM) significantly inhibited the lipopolysaccharide (LPS)-induced inflammatory cytokine IL-6 and TNF-α production in RAW 264.7 cells. In addition, the luciferase reporter assay results of different subtypes of the peroxisome proliferator-activated receptor (PPAR) showed that nuciferine dose-dependently activated all the PPAR activities. Specific inhibitors of PPARα and PPARγ significantly abolished the production of inflammatory cytokines as well as IκBα degradation. However, PPARδ inhibitor did not show this effect. Our results suggested a potential molecular mechanism of the anti-inflammatory effects of nuciferine in LPS-induced inflammation, at least in part, by activating PPARα and PPARγ in RAW 264.7 cells.