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Abstract Background ZBTB11 is a putative transcription factor with an N-terminal BTB domain and tandem C-terminal zinc finger motifs. Recent studies have suggested a potential role for ZBTB11 in tumorigenesis. However, the biological significance of ZBTB11 in different cancer types remains uncertain. Methods The expression levels, prognostic values, genetic mutations, and DNA promoter methylation of ZBTB11 across tumor types were explored via various online websites and databases, including TIMER2.0, GEPIA2, cBioPortal, UALCAN, GSCA, CancerSEA, and others. Additionally, a competing lncRNA-miRNA network of ZBTB11 was constructed, and its interaction with chemicals and genes was investigated. Results Our findings revealed that ZBTB11 was aberrantly expressed in a multitude of tumor types and exhibited variability across various tumor stages. A survival analysis revealed that ZBTB11 predicted a poor prognosis in BRCA, KIRP, LIHC, PCPG, PRAD, SARC, UCEC, and a good prognosis in CHOL, ESCA, GBM, KIRC, and READ. We also found that the most frequent genetic alterations type of ZBTB11 was mutation, and the DNA methylation level of ZBTB11 decreased in various cancers. Furthermore, ZBTB11 expression correlated with immune cells infiltration and genetic markers of immunodulators in cancers. Moreover, the results of single-cell sequencing demonstrated that ZBTB11 could regulate several tumor biological behaviors, including apoptosis, DNA damage, and angiogenesis. A lncRNA-miRNA network regulating ZBTB11 expression in tumor development and progression was constructed. It is of particular significance that ZBTB11 demonstrated a correlation with the CTRP and GDSC drug sensitivity, and that it served as a mediator between chemicals and cancers. Conclusion These findings demonstrate that ZBTB11 is associated with multiple tumor types and disease prognosis. ZBTB11 may represent a potential key biomarker and therapeutic target in cancers.

Mushroom poisoning, predominantly caused by α-amanitin, is a critical food safety concern in worldwide, with severe cases leading to hepatotoxicity and fatalities. This study delves into the hepatotoxic effects of α-amanitin, focusing on the NLRP3 inflammasome and PPAR-γ's regulatory role in inflammation. In vitro studies with L-02 cells showed that α-amanitin reduces cell viability and triggers NLRP3 inflammasome activation, increasing NF-κB phosphorylation and pro-inflammatory cytokines IL-18 and IL-1β. The NLRP3 inhibitor MCC950 mitigated these effects without impacting NF-κB. Conversely, PPAR-γ knockdown intensified the inflammatory response. In vivo, α-amanitin induced dose-dependent liver injury in mice, evident by elevated serum ALT and AST, and histological liver damage. MCC950 pretreatment offered protection against hepatotoxicity, while PPAR-γ inhibition with GW9662 worsened the condition. The study highlights the interplay between α-amanitin, NLRP3, and PPAR-γ in hepatotoxicity, proposing potential therapeutic targets for mushroom poisoning-induced liver diseases.

C44H34Cl2N6O2Zn, triclinic, P 1‾ $\overline{1}$ (no. 2), a = 10.875(9) Å, b = 11.755(9) Å, c = 16.471(13) Å, α = 105.924(14)°, β = 97.552(13)°, γ = 104.507(13)°, V = 1,914(3) Å3, Z = 2, R gt(F) = 0.0455, wR ref(F 2) = 0.1154, T = 296 K.

Tumor metastasis, the apex of cancer progression, poses a formidable challenge in therapeutic endeavors. Circulating tumor cells (CTCs), resilient entities originating from primary tumors or their metastases, significantly contribute to this process by demonstrating remarkable adaptability. They survive shear stress, resist anoikis, evade immune surveillance, and thwart chemotherapy. This comprehensive review aims to elucidate the intricate landscape of CTC formation, metastatic mechanisms, and the myriad factors influencing their behavior. Integral signaling pathways, such as integrin-related signaling, cellular autophagy, epithelial-mesenchymal transition, and interactions with platelets, are examined in detail. Furthermore, we explore the realm of precision nanomedicine design, with a specific emphasis on the anoikis‒platelet interface. This innovative approach strategically targets CTC survival mechanisms, offering promising avenues for combatting metastatic cancer with unprecedented precision and efficacy. The review underscores the indispensable role of the rational design of platelet-based nanomedicine in the pursuit of restraining CTC-driven metastasis.

Background: The concurrent effects of particulate matter (PM) on both blood pressure (BP) and short-chain fatty acids (SCFAs) are insufficiently explored, with limited research on the potential mediating roles of SCFAs. Methods: In this prospective panel study with 4 follow-ups, we recruited 40 college students in Hefei, China, to assess the impacts of short-term exposure to PM (aerodynamic diameter ≤10 μm (PM10), ≤2.5 μm (PM2.5), and ≤1 μm (PM1)) on BP and SCFAs, along with potential mechanisms. Real-time PM data, urinary SCFAs levels, and BP indicators were systematically collected. Linear mixed-effects models assessed the relationships between PM, SCFAs, and BP. Mediation analyses explored SCFAs’ mediating role in the PM-BP association. Results: PM exposure was positively linked to BP and negatively associated with SCFAs. For a 10 μg/m3 rise in PM10 at lag 0–72 h, there were notable reductions of 0.0019 % (95 %CI: −0.0028, −0.0010) in Acetic acid, 0.0262 % (-0.0369, −0.0155) in Propionic acid, and 0.0702 % (-0.1025, −0.0378) in Butyric acid. Systolic BP, diastolic BP, and mean arterial pressure (MAP) increased by 2.60 mmHg (0.96, 4.25), 2.24 mmHg (1.18, 3.31), and 2.36 mmHg (1.20, 3.53), respectively, per 10-μg/m3 rise in PM1 at lag 0–24 h. Decreased SCFAs levels explained significant portions (24.69–31.80 %) of the elevated MAP due to PM10. Stronger associations were found in females and individuals with abnormal BMI. Conclusions: Our study shows that PM exposure decreases urinary SCFAs levels, which partially mediate the impact of PM on elevated BP. These findings enhance our comprehension of the pathways linking PM exposure to BP changes.

Abstract Background Colorectal signet-ring cell carcinoma (SRCC) is a rare cancer with a bleak prognosis. The relationship between its clinicopathological features and survival remains incompletely elucidated. Tumor deposits (TD) have been utilized to guide the N staging in the 8th edition of American Joint Committee on Cancer (AJCC) staging manual, but their prognostic significance remains to be established in colorectal SRCC. Patients and methods The subjects of this study were patients with stage III/IV colorectal SRCC who underwent surgical treatment. The research comprised two cohorts: a training cohort and a validation cohort. The training cohort consisted of 631 qualified patients from the SEER database, while the validation cohort included 135 eligible patients from four independent hospitals in China. The study assessed the impact of TD on Cancer-Specific Survival (CSS) and Overall Survival (OS) using Kaplan-Meier survival curves and Cox regression models. Additionally, a prognostic nomogram model was constructed for further evaluation. Results In both cohorts, TD-positive patients were typically in the stage IV and exhibited the presence of perineural invasion (PNI) (P

Reading is one of the most basic academic skills. An accurate monitor of one's text comprehension (i.e., metacomprehension) is essential for effective reading as it guides learning and choices of appropriate strategy used to maximize overall understanding. The processes of reading comprehension and metacomprehension are affected by text-related, task-related, and reader- /person-related factors. One of the two purposes of this report is to provide a brief review of consistent research findings on the interrelationships among several person-related variables and the complexity of those associations in reading and metacomprehension. The person variables discussed include personality, motivation, goal orientations, self-regulation, reading strategy use, and academic effort expenditure. A second purpose is to highlight practical educational implications from the prominent research evidence for classroom teaching.

Rhythmic transcripts play pivotal roles in driving the daily oscillations of various biological processes. Genetic or environmental disruptions can lead to alterations in the rhythmicity of transcripts, ultimately impacting downstream circadian outputs, including metabolic processes and even behavior. To statistically compare the differences in transcript rhythms between 2 or more conditions, several algorithms have been developed to analyze circadian transcriptomic data, each with distinct features. In this study, we compared the performance of 7 algorithms that were specifically designed to detect differential rhythmicity (DODR, LimoRhyde, CircaCompare, compareRhythms, diffCircadian, dryR, and RepeatedCircadian). We found that even when applying the same statistical threshold, these algorithms yielded varying numbers of differentially rhythmic transcripts, most likely because each algorithm defines rhythmic and differentially rhythmic transcripts differently. Nevertheless, the output for the differential phase and amplitude were identical between dryR and compareRhyhms, and diffCircadian and CircaCompare, while the output from LimoRhyde2 was highly correlated with that from diffCircadian and CircaCompare. Because each algorithm has unique requirements for input data and reports different information as an output, it is crucial to ensure the compatibility of input data with the chosen algorithm and assess whether the algorithm’s output fits the user’s needs when selecting an algorithm for analysis.

Combination antiretroviral therapy (cART) has dramatically reduced mortality in people with human immunodeficiency virus (HIV), but it does not completely eradicate the virus from the brain. Patients with long-term HIV-1 infection often show neurocognitive impairment, which severely affects the quality of life of those infected. Methamphetamine (METH) users are at a significantly higher risk of contracting HIV-1 through behaviors such as engaging in high-risk sex or sharing needles, which can lead to transmission of the virus. In addition, HIV-1-infected individuals who abuse METH exhibit higher viral loads and more severe cognitive dysfunction, suggesting that METH exacerbates the neurotoxicity associated with HIV-1. Therefore, this review focuses on various mechanisms underlying METH and HIV-1 infection co-induced neurotoxicity and existing interventions targeting the sigma 1 receptor, dopamine transporter protein, and other relevant targets are explored. The findings of this review are envisaged to systematically establish a theoretical framework for METH abuse and HIV-1 infection co-induced neurotoxicity, and to suggest novel clinical treatment targets.

Abstract The Gatchina discharge phenomenon holds significant promise as a laboratory model for simulating ball lightning. However, crucial aspects concerning the plasma components of the resulting afterglow remain unresolved. Notably, the measurement of the electron density, a critical parameter, has not been fully achieved thus far. In this study, microwave diagnostics and video recording were employed during a pulsed Gatchina discharge, along with synchronous measurement of discharge current and voltage. Distinct antennas were positioned at different heights to enable separate diagnosis of the discharge and the ensuing long‐lived afterglow. The findings revealed that during the active phase of the Gatchina discharge, the plasma density was substantial enough to cause reflection of an electromagnetic wave with a frequency of 20 GHz from this highly conductive object. In the afterglow, the signal experienced only a moderate weakening of 10–20 percent, facilitating the determination of the time dependence of average electron density during the afterglow's passage between the two antennas. These measurements verified the unusually slow plasma decay in the afterglow of the Gatchina discharge, suggesting the potential significance of chemi‐ionisation processes involving long‐lived (metastable) particles.

Abstract Background Systemic lupus erythematosus (SLE) is a common autoimmune disease that impacts various organs. Lupus nephritis (LN) significantly contributes to death in children with SLE. Toll-like receptor (TLR) adaptor interacting with SLC15A4 on the lysosome (TASL) acts as an innate immune adaptor for TLR and is implicated in the pathogenesis of SLE. A transcription factor known as signal transducer and activator of transcription 3 (STAT3), which is known to be linked to autoimmune diseases, is also involved in the development of SLE. Methods Bioinformatics and real-time quantitative PCR (qRT-PCR) was used to detect the expression of STAT3 and TASL in peripheral blood of SLE patients and their correlation. Bioinformatics analysis, qRT-PCR, luciferase assay and chromatin immunoprecipitation (ChIP) were used to verify the regulation of transcription factor STAT3 on TASL. The expression levels of STAT3, TASL and apoptosis-related genes in LPS-induced HK2 cells were detected by qRT-PCR and Western blot. TUNEL staining were used to detect the apoptosis of HK2 cells after LPS stimulation. ELISA and qRT-PCR were used to detect the levels of inflammatory cytokines in the cell culture supernatant. TASL knockdown in HK2 cells was used to detect the changes in apoptosis-related genes and inflammatory factors. The expression level of TASL in LPS-stimulated HK2 cells and its effect on cell apoptosis and inflammatory factors were observed by knocking down and overexpressing STAT3, respectively. It was also verified in a rescue experiment. Results The expressions of STAT3 and TASL were higher in SLE than in healthy children, and the expression of STAT3 was positively correlated with TASL. Transcription factor STAT3 can directly and positively regulate the expression of TASL through the promoter region binding site. The expression of STAT3, TASL and inflammatory cytokines was elevated, and the change of apoptosis was up-regulated in LPS-stimulated HK2 cells. Inhibition of STAT3 alleviates LPS-stimulated apoptosis and inflammatory response in HK2 cells through transcriptional regulation of TASL. Conclusions These findings provide new insights into the transcriptional regulation of TASL and provide new evidence of a direct regulatory relationship between signaling nodes in the lupus signaling network. Graphical Abstract