Amphiregulin Downregulates E-cadherin Expression by Activating YAP/Egr-1/Slug Signaling in SKOV3 Human Ovarian Cancer Cells.

Amphiregulin (AREG) stimulates human epithelial ovarian cancer (EOC) cell invasion by downregulating E-cadherin expression. YAP is a transcriptional cofactor that has been shown to regulate tumorigenesis. This study aimed to examine whether AREG activates YAP in EOC cells and explore the roles of YAP in AREG-induced downregulation of E-cadherin and cell invasion. Analysis of the Cancer Genome Atlas (TCGA) showed that upregulation of AREG and EGFR were associated with poor survival in human EOC. Treatment of SKOV3 human EOC cells with AREG induced the activation of YAP. In addition, AREG downregulated E-cadherin, upregulated Egr-1 and Slug, and stimulated cell invasion. Using gain- and loss-of-function approaches, we showed that YAP was required for the AREG-upregulated Egr-1 and Slug expression. Furthermore, YAP was also involved in AREG-induced downregulation of E-cadherin and cell invasion. This study provides evidence that AREG stimulates human EOC cell invasion by downregulating E-cadherin expression through the YAP/Egr-1/Slug signaling.

Impact of early myocardial injury on patients with severe pneumonia.

Pneumonia often causes myocardial damage. This study sought to understand how early myocardial injury affects severe pneumonia patients' prognoses. This multi-center prospective cohort study from March 2020 to October 2023 comprised severe pneumonia patients. Binary logistic regression analysis examined how myocardial damage affects cardiac complications and acute renal injury (AKI). We used Spearman correlation analysis to examine the relationship between troponin I levels and the vasoactive inotropic score (VIS) in shock patients with myocardial injury. We used the Kaplan-Meier survival curve to evaluate the impact of myocardial injury on 30-day and 1-year survival rates. Mediation investigations examined how AKI and cardiac complications mediate myocardial injury and death. This study included 363 severe pneumonia patients, of whom 204 (56.2%) developed myocardial damage, 132 (36.4%) had cardiac problems, and 146 (40.2%) had AKI. Myocardial damage independently elevated the incidence of cardiac complications (OR = 2.548, 95% CI = 1.404-4.303, P = 0.002) and AKI (OR = 1.946, 95% CI = 1.177-3.219, P = 0.009). There was a positive link between troponin I and VIS in myocardial injury and shock patients (r = 0.43, P < 0.001). COX regression found myocardial injury to be a death risk (HR = 1.472, 95% CI = 1.043-2.077, P = 0.028). Adjusted Kaplan-Meier survival analysis showed significantly decreased short-term and long-term survival rates with myocardial injury (log-rank test P < 0.05). The mediation study showed that cardiac complications and AKI mediated myocardial injury and death by 19.30% and 17.18%, respectively. Early myocardial injury in severe pneumonia patients raises the likelihood of cardiac problems, AKI, and refractory shock, reducing short- and long-term survival.

Safety evaluation of Indocalamus Iatifolius McClure leaves based on acute toxicity, harmful metals, and 9 organochlorine residue determination.

To investigate the safety of Indocalamu Iatifolius McClur leaves sold in the market, a study was conducted using Indocalamu Iatifolius McClur leaves randomly collected from an online store and a large supermarket. Acute toxicity experiments were performed on mice, and their body weight was monitored for 14 days after administration. After the observation period, blood samples were collected for biochemical analysis, and organ pathology was examined. Then, the content of copper (Cu), lead (Pb), cadmium (Cd), mercury (Hg), arsenic (As), and the residues of nine organochlorine pesticides in Indocalamu Iatifolius McClur leaves were measured according to the National Food Safety Standard (GB/T5009-2003) and the pesticide residue determination methods in the 2020 edition of the Chinese Pharmacopoeia. The results showed that the mice in the Indocalamu Iatifolius McClur leaves (online store) group experienced mortality and severe liver and lung damage. The levels of lead, cadmium, mercury, arsenic, and the nine organochlorine pesticides met the relevant standards and regulations. However, the copper content in the Indocalamu Iatifolius McClur leaves (online store) group was nearly 80 times higher than that in the supermarket group. Mice in the Indocalamu Iatifolius McClur leaves (supermarket) group remained healthy without any abnormalities, and the levels of harmful metals and organochlorine pesticides complied with the standards and regulations. The study suggests the need for regulatory policies and safety standards for the sale of Indocalamu Iatifolius McClur leaves.

Positive feedback loop PU.1-IL9 in Th9 promotes rheumatoid arthritis development.

OBJECTIVES: T helper 9 (Th9) cells are recognised for their characteristic expression of the transcription factor PU.1 and production of interleukin-9 (IL-9), which has been implicated in various autoimmune diseases. However, its precise relationship with rheumatoid arthritis (RA) pathogenesis needs to be further clarified. METHODS: The expression levels of PU.1 and IL-9 in patients with RA were determined by ELISA, western blotting (WB) and immunohistochemical staining. PU.1-T cell-conditional knockout (KO) mice, IL-9 KO and IL-9R KO mice were used to establish collagen antibody-induced arthritis (CAIA), respectively. The inhibitor of PU.1 and IL-9 blocking antibody was used in collagen-induced arthritis (CIA). In an in vitro study, the effects of IL-9 were investigated using siRNAs and IL-9 recombinant proteins. Finally, the underlying mechanisms were further investigated by luciferase reporter analysis, WB and Chip-qPCR. RESULTS: The upregulation of IL-9 expression in patients with RA exhibited a positive correlation with clinical markers. Using CAIA and CIA model, we demonstrated that interventions targeting PU.1 and IL-9 substantially mitigated the inflammatory phenotype. Furthermore, in vitro assays provided the proinflammatory role of IL-9, particularly in the hyperactivation of macrophages and fibroblast-like synoviocytes. Mechanistically, we uncovered that PU.1 and IL-9 form a positive feedback loop in RA: (1) PU.1 directly binds to the IL-9 promoter, activating its transcription and (2) Th9-derived IL-9 induces PU.1 via the IL-9R-JAK1/STAT3 pathway. CONCLUSIONS: These results support that the PU.1-IL-9 axis forms a positive loop in Th9 dysregulation of RA. Targeting this signalling axis presents a potential target approach for treating RA.

The 50 most cited articles on soft tissue integration of dental implants: A bibliometric analysis.

STATEMENT OF PROBLEM: Soft tissue integration helps prevent the bacterial invasion of dental implants, but bibliometric studies on the top 50 most cited articles in the field of soft tissue integration are lacking. PURPOSE: The purpose of this bibliometric study was to analyze the 50 most cited articles since 1999 to explore global trends and research hotspots. MATERIAL AND METHODS: A specific search strategy of the Science Citation Index Expanded (Web of Science) was devised, and relevant article-based, journal-based, and author-based parameters were analyzed. Correlation analysis was performed (α=.05). RESULTS: The number of citations ranged from 71 to 586. Clinical Oral Implants Research was the most cited journal (1722 citations). Berglundh, Tord was the author with the most publications (6 publications) and citations (957 citations). Dental implants and titanium were the keywords with the highest frequency. Switzerland was the country with the highest number of publications (12 publications). Correlation was found between the publication year and average annual citations (P<.001). CONCLUSIONS: This study determined the scientific progress in soft tissue integration. The surface design of dental implant materials is essential for the soft tissue integration of dental implants. Soft tissue integration has been a focus of interest in the past few years, but many experiments still need to be done to improve soft tissue compatibility with innovative materials.

Machine learning risk prediction model for bloodstream infections related to totally implantable venous access ports in patients with cancer.

Objective: This study aimed to develop and validate a machine learning-based risk prediction model for catheter-related bloodstream infection (CRBSI) following implantation of totally implantable venous access ports (TIVAPs) in patients. Methods: A retrospective cohort study design was employed, utilizing the R software package mlr3. Various algorithms including logistic regression, naive Bayes, K nearest neighbor, classification tree, and random forest were applied. Addressing class imbalance, benchmarks were used, and model performance was assessed using the area under the curve (AUC). The final model, chosen for its superior performance, was interpreted using variable importance scores. Additionally, a nomogram was developed to calculate individualized risk probabilities, enhancing clinical utility. Results: The study involved 755 patients across both development and validation cohorts, with a TIVAP-CRBSI rate of 14.17%. The random forest model demonstrated the highest discrimination ability, achieving a validated AUC of 0.94, which was consistent in the validation cohort. Conclusions: This study successfully developed a robust predictive model for TIVAP-CRBSI risk post-implantation. Implementation of this model may aid healthcare providers in making informed decisions, thereby potentially improving patient outcomes.

Cordycepin suppresses steroidogenic acute regulatory protein expression by reducing SP1 in human granulosa-lutein cells.

Cordycepin (COR), a pure compound of Cordyceps, is known as an adenosine analog that exerts many beneficial effects on human health. The steroidogenesis mediated by ovarian granulosa cells is pivotal in maintaining normal female reproductive function. The steroidogenic acute regulatory protein (StAR) regulates the rate-limiting step in steroidogenesis. COR has been shown to stimulate StAR expression in mouse Leydig cells, the steroidogenic cells in the testes. However, the effect of COR on StAR expression in ovarian granulosa cells remains undetermined. In the present study, we show that treatment with COR downregulates StAR expression in a steroidogenic human granulosa-like tumor cell line, KGN, and primary culture of human granulosa-lutein (hGL) cells obtained from patients undergoing in vitro fertilization. Using specific adenosine receptor (AR) antagonists, our results reveal that the inhibitory effect of COR on StAR expression is mediated by AR-A1, -A2A, and -A3. In both KGN and primary hGL cells, COR activates ERK1/2 and AKT signaling pathways, but only activation of ERK1/2 is required for the COR-induced downregulation of StAR expression. In addition, our results demonstrate that COR downregulates StAR expression by reducing the expression of the SP1 transcription factor. These results provide a better understanding of the biological function of COR on StAR expression in the ovary, which may lead to the development of alternative therapeutic approaches for female reproductive disorders.

Structural basis for the activity of the type VII CRISPR-Cas system.

The newly identified type VII CRISPR-Cas candidate system uses a CRISPR RNA-guided ribonucleoprotein complex formed by Cas5 and Cas7 proteins to target RNA1. However, the RNA cleavage is executed by a dedicated Cas14 nuclease, which is distinct from the effector nucleases of the other CRISPR-Cas systems. Here we report seven cryo-electron microscopy structures of the Cas14-bound interference complex at different functional states. Cas14, a tetrameric protein in solution, is recruited to the Cas5-Cas7 complex in a target RNA-dependent manner. The N-terminal catalytic domain of Cas14 binds a stretch of the substrate RNA for cleavage, whereas the C-terminal domain is primarily responsible for tethering Cas14 to the Cas5-Cas7 complex. The biochemical cleavage assays corroborate the captured functional conformations, revealing that Cas14 binds to different sites on the Cas5-Cas7 complex to execute individual cleavage events. Notably, a plugged-in arginine of Cas7 sandwiched by a C-shaped clamp of C-terminal domain precisely modulates Cas14 binding. More interestingly, target RNA cleavage is altered by a complementary protospacer flanking sequence at the 5' end, but not at the 3' end. Altogether, our study elucidates critical molecular details underlying the assembly of the interference complex and substrate cleavage in the type VII CRISPR-Cas system, which may help rational engineering of the type VII CRISPR-Cas system for biotechnological applications.

Absorption, Metabolism, and Excretion of [14C]-Labeled Anaprazole: A New Proton Pump Inhibitor, After a Single Oral Administration in Healthy Chinese Male Subjects.

Anaprazole is a proton pump inhibitor. This study aims to elucidate absorption, metabolism, and excretion pathways of anaprazole sodium in the human body. A total of 4 healthy Chinese male subjects were administered a single oral dose of 20 mg/100 µCi of [14C]-anaprazole sodium enteric-coated capsules. The whole blood, plasma, and excreta were analyzed for a total radioactivity (TRA) and metabolite profile. The cumulative radioactivity excretion rate was 93.2%, with 53.3% and 39.9% of the radioactive dose excreted in urine and feces, respectively, and 91.6% of dose recovered within 96 hours after dosing. The parent drug, anaprazole, showed good absorption and was extensively metabolized majorly to thioether M8-1 via nonenzymatic metabolism. Overall, 35 metabolites were identified in plasma, urine, and fecal samples. Anaprazole was the most abundant component in plasma followed by the thioether M8-1, accounting for 28.3% and 16.6%, respectively, of the plasma TRA. Thioether carboxylic acid XZP-3409 (26.3% of urine TRA) and XZP-3409 oxidation and dehydrogenation product M417a (15.1% of fecal TRA) were the major metabolites present in urine and feces, respectively. Anaprazole was undetectable in urine, while fecal samples showed traces (0.07% dose). Blood/plasma ratios of the radioactivity (approximately 0.60) remained consistent over time. Anaprazole showed good absorption and was extensively metabolized majorly to thioether M8-1 via nonenzymatic metabolism, and cytochrome P450 3A4 also contributed to its metabolism in healthy individuals.

Multi-focus image fusion with parameter adaptive dual channel dynamic threshold neural P systems.

Multi-focus image fusion (MFIF) is an important technique that aims to combine the focused regions of multiple source images into a fully clear image. Decision-map methods are widely used in MFIF to maximize the preservation of information from the source images. While many decision-map methods have been proposed, they often struggle with difficulties in determining focus and non-focus boundaries, further affecting the quality of the fused images. Dynamic threshold neural P (DTNP) systems are computational models inspired by biological spiking neurons, featuring dynamic threshold and spiking mechanisms to better distinguish focused and unfocused regions for decision map generation. However, original DTNP systems require manual parameter configuration and have only one stimulus. Therefore, they are not suitable to be used directly for generating high-precision decision maps. To overcome these limitations, we propose a variant called parameter adaptive dual channel DTNP (PADCDTNP) systems. Inspired by the spiking mechanisms of PADCDTNP systems, we further develop a new MFIF method. As a new neural model, PADCDTNP systems adaptively estimate parameters according to multiple external inputs to produce decision maps with robust boundaries, resulting in high-quality fusion results. Comprehensive experiments on the Lytro/MFFW/MFI-WHU dataset show that our method achieves advanced performance and yields comparable results to the fourteen representative MFIF methods. In addition, compared to the standard DTNP systems, PADCDTNP systems improve the fusion performance and fusion efficiency on the three datasets by 5.69% and 86.03%, respectively. The codes for both the proposed method and the comparison methods are released at https://github.com/MorvanLi/MFIF-PADCDTNP.

Long-term effects of air quality on hospital readmission for heart failure in patients with acute myocardial infarction.

BACKGROUND: Cardiovascular disease (CVD) is the leading cause of death worldwide, with air pollution posing significant risks to cardiovascular health. The effect of air quality on heart failure (HF) readmission in acute myocardial infarction (AMI) patients is unclear.The aim of this study was to evaluate the role of a single measure of air pollution exposure collected on the day of first hospitalization. METHODS: We retrospectively analyzed data from 12,857 acute coronary syndrome (ACS) patients (January 2015-March 2023). After multiple screenings, 4023 AMI patients were included. The air pollution data is updated by the automatic monitoring data of the national urban air quality monitoring stations in real time and synchronized to the China Environmental Monitoring Station. Cox proportional hazards regression assessed the impact of air quality indicators on admission and outcomes in 4013 AMI patients. A decision tree model identified the most susceptible groups. RESULTS: After adjusting for confounders, NO2 (HR 1.009, 95% CI 1.004-1.015, P = 0.00066) and PM10 (HR 1.006, 95% CI 1.002-1.011, P = 0.00751) increased the risk of HF readmission in ST-segment elevation myocardial infarction (STEMI) patients. No significant effect was observed in non-STEMI (NSTEMI) patients (P > 0.05). STEMI patients had a 2.8-fold higher risk of HF readmission with NO2 > 13 µg/m3 (HR 2.857, 95% CI 1.439-5.670, P = 0.00269) and a 1.65-fold higher risk with PM10 > 55 µg/m3 (HR 1.654, 95% CI 1.124-2.434, P = 0.01064). CONCLUSION: NO2 and PM10 are linked to increased HF readmission risk in STEMI patients, particularly when NO2 exceeds 13 µg/m3 and PM10 exceeds 55 µg/m3. Younger, less symptomatic male STEMI patients with fewer underlying conditions are more vulnerable to these pollutants.

Response of soil microbial ecological functions and biological characteristics to organic fertilizer combined with biochar in dry direct-seeded paddy fields.

Biochar and organic fertilizer are commonly used to maintain soil health and sustainable agroecosystems, and the alternate wet-dry management of soil moisture in dry direct-seeded paddy fields can complicate the effects of biochar and organic fertilizer on soil microhabitats. Therefore, this study used chicken manure organic fertilizer to replace some of the inorganic fertilizer and applied biochar to explore the ability of biochar and organic fertilizer to regulate the functions of the soil microhabitat in dry direct-seeded paddy fields. The coupling effect of organic fertilizer and biochar increased the diversity and richness of soil bacteria but had no significant effect on soil fungi. Biochar and organic fertilizer affected the distribution and composition of soil bacteria and fungi, and the total number of soil bacteria and fungi increased by 1365 and -71 (5 t/hm2 biochar and no organic fertilizer), 660 and 79 (10 t/hm2 biochar and no organic fertilizer), 3121 and 7 (no biochar and 20 % organic fertilizer substitution), 1873 and -72 (5 t/hm2 biochar and 20 % organic fertilizer substitution), and -544 and -65 (10 t/hm2 biochar and 20 % organic fertilizer substitution), respectively, compared with that of the control treatment. Compared with the application of biochar alone, the coupling effect of biochar and organic fertilizer increased the average degree (0.95 and 0.16), links (190 and 32), and ratio of fungal positive links (1.651 %), and decreased the modularity (0.034 and 0.052) and ratio of bacterial positive links (6.482 %) of bacterial and fungal networks. In addition, the coupling effect resulted in a more complex association between soil microbial diversity and richness and microbial ecological functions. Random forest predictions indicated that, organic fertilizer as a random factor, changes in the abundance of bacterial Bacteroidetes and Nitrospirae and fungal Monoblepharomycota were the main factors driving the differences in soil microbial ecological functions.

LncRNA CARMN m6A demethylation by ALKBH5 inhibits mutant p53-driven tumour progression through miR-5683/FGF2.

N-methyladenosine (m6A) represents a prevalent RNA modification observed in colorectal cancer. Despite its abundance, the biological implications of m6A methylation on the lncRNA CARMN remain elusive in colorectal cancer, especially for mutant p53 gain-of-function. Here, we elucidate that CARMN exhibits diminished expression levels in colorectal cancer patients with mutant p53, attributed to its rich m6A methylation, which promotes cancer proliferation, invasion and metastasis in vitro and in vivo. Further investigation illustrates that ALKBH5 acts as a direct demethylase of CARMN, targeting 477 methylation sites, thereby preserving CARMN expression. However, the interaction of mutant p53 with the ALKBH5 promoter impedes its transcription, enhancing m6A methylation levels on CARMN. Subsequently, YTHDF2/YTHDF3 recognise and degrade m6A-modified CARMN. Concurrently, overexpressing CARMN significantly suppressed colorectal cancer progression in vitro and in vivo. Additionally, miR-5683 was identified as a direct downstream target of lncRNA CARMN, exerting an antitumour effect by cooperatively downregulating FGF2 expression. Our findings revealed the regulator and functional mechanism of CARMN in colorectal cancer with mutant p53, potentially offering insights into demethylation-based strategies for cancer diagnosis and therapy. The m6A methylation of CARMN that is prime for mutant p53 gain-of-function-induced malignant progression of colorectal cancer, identifying a promising approach for cancer therapy.

CTCF mutation at R567 causes developmental disorders via 3D genome rearrangement and abnormal neurodevelopment.

The three-dimensional genome structure organized by CTCF is required for development. Clinically identified mutations in CTCF have been linked to adverse developmental outcomes. Nevertheless, the underlying mechanism remains elusive. In this investigation, we explore the regulatory roles of a clinically relevant R567W point mutation, located within the 11th zinc finger of CTCF, by introducing this mutation into both murine models and human embryonic stem cell-derived cortical organoid models. Mice with homozygous CTCFR567W mutation exhibit growth impediments, resulting in postnatal mortality, and deviations in brain, heart, and lung development at the pathological and single-cell transcriptome levels. This mutation induces premature stem-like cell exhaustion, accelerates the maturation of GABAergic neurons, and disrupts neurodevelopmental and synaptic pathways. Additionally, it specifically hinders CTCF binding to peripheral motifs upstream to the core consensus site, causing alterations in local chromatin structure and gene expression, particularly at the clustered protocadherin locus. Comparative analysis using human cortical organoids mirrors the consequences induced by this mutation. In summary, this study elucidates the influence of the CTCFR567W mutation on human neurodevelopmental disorders, paving the way for potential therapeutic interventions.

Overall, sex-and race/ethnicity-specific prevalence of thyroid dysfunction in US adolescents aged 12-18 years.

Background: Thyroid dysfunction significantly affects the health and development of adolescents. However, comprehensive studies on its prevalence and characteristics in US adolescents are lacking. Methods: We investigated the prevalence of thyroid dysfunction in US adolescents aged 12-18 years using data from the National Health and Nutrition Examination Survey (NHANES) 2001-2002 and 2007-2012 cycles. Thyroid dysfunction was assessed using serum thyroid-stimulating hormone (TSH) and free thyroxine (fT4) measurements. We analyzed the prevalence across demographic subgroups and identified associated risk factors. Results: The study included 2,182 participants, representing an estimated 12.97 million adolescents. The group had a weighted mean age of 15.1 ± 0.06 years, with males constituting 51.4%. Subclinical hyperthyroidism emerged as the most prevalent thyroid dysfunction, affecting 4.4% of the population. From 2001-2002 to 2011-2012, subclinical hyperthyroidism remained consistent at 4.99% vs. 5.13% in the overall cohort. Subclinical and overt hypothyroidism was found in 0.41 and 1.03% of adolescents respectively, and overt hyperthyroidism was rare (0.04%). The prevalence of thyroid peroxidase antibody (TPOAb) and thyroglobulin antibody (TgAb) positivity in the overall population were 5.8 and 9.8%, respectively. Positivity for TgAb was risk factors for hypothyroidism, while older age, female and Black Americans were risk factors for hyperthyroidism. Female adolescents and adolescents with an older age were more likely to be positive for TPOAb and TgAb, while Black and Mexican Americans had a lower risk of TPOAb and TgAb positivity. Conclusion: Subclinical hyperthyroidism was the most common form of thyroid dysfunction, and its prevalence remained stable from 2001-2002 to 2011-2012. Notable disparities in the prevalence of hyperthyroidism and antibody positivity were observed among different age, sex and racial/ethnic groups.

Sono-promoted piezocatalysis and low-dose drug penetration for personalized therapy via tumor organoids.

Chemotherapy is a widely used cancer treatment, however, it can have notable side effects owing to the high-doses of drugs administered. Sonodynamic therapy (SDT) induced by sonosensitizers has emerged as a promising approach to treat cancer, however, there is limited research evaluating its therapeutic effects on human tumors. In this study, we introduced a dual therapy that combines low-dose chemotherapeutic drugs with enhanced sonodynamic therapy, utilizing barium titanate (BaTiO3, BTO) nanoparticles (NPs) as sonosensitizers to treat tumor organoids. We demonstrated that ultrasound could improve the cellular uptake of chemotherapy drugs, while the chemotherapeutic effect of the drugs made it easier for BTO NPs to enter tumor cells, and the dual therapy synergistically inhibited tumor cell viability. Moreover, different patient-derived tumor organoids exhibited different sensitivities to this therapy, highlighting the potential to evaluate individual responses to combination therapies prior to clinical intervention. Furthermore, this dual therapy exhibited therapeutic effects equivalent to those of high-dose chemotherapy drugs on drug-resistant tumor organoids and showed the potential to enhance the efficacy of killing drug-resistant tumors. In addition, the biosafety of the BTO NPs was successfully verified in live mice via oral administration. This evidence confirms the reliable and safe nature of the dual therapy approach, making it a feasible option for precise and personalized therapy in clinical applications.

SIRT6 suppresses colon cancer growth by inducing apoptosis and autophagy through transcriptionally down-regulating Survivin.

SIRT6, an evolutionarily conserved histone deacetylase, has been identified as a novel direct downstream target of Akt/FoxO3a and a tumor suppressor in colon cancer in our previous research. Nevertheless, the precise mechanisms through which SIRT6 hinders tumor development remain unclear. To ascertain whether SIRT6 directly impacts Survivin transcription, a ChIP assay was conducted using an anti-SIRT6 antibody to isolate DNA. YM155 was synthesized to explore Survivin's role in mitochondrial apoptosis, autophagy and tumor progression. Our investigation into the regulation of Survivin involved real-time fluorescence imaging in living cells, real-time PCR, immunohistochemistry, flow cytometry, and xenograft mouse assays. In this current study, we delved into the role of SIRT6 in colon cancer and established that activated SIRT6 triggers mitochondrial apoptosis by reducing Survivin expression. Subsequent examinations revealed that SIRT6 directly binds to the Survivin promoter, impeding its transcription. Notably, direct inhibition of Survivin significantly impeded colon cancer proliferation by inducing mitochondrial apoptosis and autophagy both in vitro and in vivo. More interestingly, Survivin inhibition reactivated the Akt/FoxO3a pathway and elevated SIRT6 levels, establishing a positive feedback loop. Our results identify Survivin as a novel downstream transcriptional target of SIRT6 that fosters tumor growth and holds promise as a prospective target for colon cancer therapy.

Highly efficient degradation of tetracycline in groundwater by nanoscale zero-valent iron-copper bimetallic biochar: active [H] attack and direct electron transfer mechanism.

Development of carbon materials with high activity was important for rapid degradation of emerging pollutants. In this paper, a novel nanoscale zero-valent iron-copper bimetallic biochar (nZVIC-BC) was synthesized by carbothermal reduction of waste pine wood and copper-iron layered double hydroxides (LDHs). Characterization and analysis of its structural, elemental, crystalline, and compositional aspects using XRD, FT-IR, SEM, and TEM confirmed the successful preparation of nZVIC-BC and the high dispersion of Fe-Cu nanoparticles in an ordered carbon matrix. The experimental results showed that the catalytic activity of nZVIC-BC (Kobs of 0.0219 min-1) in the degradation of tetracycline (TC) in anoxic water environment was much higher than that of Fe-BC and Cu-BC; the effective degradation rate reached 85%. It was worth noting that the negative effects of Ca2+, Mg2+, and H2PO4- on TC degradation at ionic strengths greater than 15 mg/L were due to competition for active sites. Good stability and reusability were demonstrated in five consecutive cycle tests for low leaching of iron and copper. Combined with free radical quenching experiments and XPS analyses, the degradation of TC under air conditions was only 62%, with hydroxyl radicals (·OH) playing a dominant role. The synergistic interaction between Fe2+/Fe3+ and Cu0/Cu+/Cu2+ under nitrogen atmosphere enhances the redox cycling process; π-π adsorption, electron transfer processes, and active [H] were crucial for the degradation of TC; and possible degradation pathways of TC were deduced by LC-MS, which identified seven major aromatic degradation by-products. This study will provide new ideas and materials for the treatment of TC.

DNAJC1 facilitates glioblastoma progression by promoting extracellular matrix reorganization and macrophage infiltration.

BACKGROUND: Glioblastoma (GBM) is a high-grade and heterogeneous subtype of glioma that presents a substantial challenge to human health, characterized by a poor prognosis and low survival rates. Despite its known involvement in regulating leukemia and melanoma, the function and mechanism of DNAJC1 in GBM remain poorly understood. METHODS: Utilizing data from the TCGA, CGGA, and GEO databases, we investigated the expression pattern of DNAJC1 and its correlation with clinical characteristics in GBM specimens. Loss-of-function experiments were conducted to explore the impact of DNAJC1 on GBM cell lines, with co-culture experiments assessing macrophage infiltration and functional marker expression. RESULTS: Our analysis demonstrated frequent overexpression of DNAJC1 in GBM, significantly associated with various clinical characteristics including WHO grade, IDH status, chromosome 1p/19q codeletion, and histological type. Moreover, Kaplan‒Meier and ROC analyses revealed DNAJC1 as a negative prognostic predictor and a promising diagnostic biomarker for GBM patients. Functional studies indicated that silencing DNAJC1 impeded cell proliferation and migration, induced cell cycle arrest, and enhanced apoptosis. Mechanistically, DNAJC1 was implicated in stimulating extracellular matrix reorganization, triggering the epithelial-mesenchymal transition (EMT) process, and initiating immunosuppressive macrophage infiltration. CONCLUSIONS: Our findings underscore the pivotal role of DNAJC1 in GBM pathogenesis, suggesting its potential as a diagnostic and therapeutic target for this challenging disease.

Preparation of porous lignocellulose biochar adsorbent by cold isostatic pressing pretreatment and study on Hg (II) adsorption properties of C and N dual activity sites.

Utilizing corn straw (CS) mainly composed of lignocellulose to prepare physically modified biochar (PCSB) via cold isostatic pressing (CIP) in order to increase the biochar' s Hg (II) adsorption capacity. The results of the characterization indicated that CIP pretreatment renders PCSB-400' s structure more porous and higher N content of 16.65 %, leading to more N-containing functional groups partaking in the adsorption process. PCSB-400 adsorbed Hg (II) primarily via C/N synergistic complexation and electrostatic attraction between pores, in addition to the presence of redox reactions of surface functional groups on PCSB-400. The adsorption experiment reveals that PCSB-400 has a high selectivity for the adsorption of Hg (II). The adsorption process of Hg (II) by PCSB-400 more closely resembles the Langmuir model and pseudo-first-order adsorption kinetics equation. The adsorption quantity at saturation is 282.52 mg/g at 25 °C. This paper provided an effective idea to selectively remove Hg (II) in wastewater.