A thorough investigation into the adsorption behavior of sophorolipid-modified fly ash towards compound pollution of lead and tetracycline.

Heavy metal ions and antibiotics were simultaneously detected in authentic water systems. This research, for the first time, employed synthesized sophorolipid-modified fly ash(SFA) to eliminate tetracycline(TC) and lead(Pb2+) from wastewater. Various characterization techniques, including SEM-EDS, FTIR, XPS, BET, and Zeta, were employed to investigate the properties of the SFA. The results showed that the sophorolipid modification significantly improved the fly ash's adsorption capacities for the target pollutants. The static adsorption experiments elucidated the adsorption behaviors of SFA towards TC and Pb2+ in single and binary systems, highlighting the effects of different Environmental factors on the adsorption behavior in both types of systems. In single systems, SFA exhibited a maximum adsorption capacity of 128.96 mg/g for Pb2+ and 55.57 mg/g for TC. The adsorption of Pb2+ and TC followed pseudo-second-order kinetics and Freundlich isotherm models. The adsorption reactions are endothermic and occur spontaneously. SFA demonstrates varying adsorption mechanisms for two different types of pollutants. In the case of Pb2+, the primary mechanisms include ion exchange, electrostatic interaction, cation-π interaction, and complexation, while TC primarily engages in hydrogen bonding, π-π interaction, and complexion. The interaction between Pb2+ and TC has been shown to improve adsorption efficiency at low concentrations. Additionally, adsorption-desorption experiments confirm the reliable cycling performance of modified fly ash, highlighting its potential as a cost-effective and efficient adsorbent for antibiotics and heavy metals.

Targeting the CDK7-MDK axis to suppresses irinotecan resistance in colorectal cancer.

AIMS: Colorectal cancer (CRC) remains a major global health issue, with metastatic cases presenting poor prognosis despite advances in chemotherapy and targeted therapy. Irinotecan, a key drug for advanced CRC treatment, faces challenges owing to the development of resistance. This study aimed to understand the mechanisms underlying irinotecan resistance in colorectal cancer. MAIN METHODS: We created a cell line resistant to irinotecan using HT29 cells. These resistant cells were utilized to investigate the role of the CDK7-MDK axis. We employed bulk RNA sequencing, conducted in vivo experiments with mice, and analyzed patient tissues to examine the effects of the CDK7-MDK axis on the cellular response to irinotecan. KEY FINDINGS: Our findings revealed that HT29 cells resistant to irinotecan, a crucial colorectal cancer medication, exhibited significant phenotypic and molecular alterations compared to their parental counterparts, including elevated stem cell characteristics and increased levels of cytokines and drug resistance proteins. Notably, CDK7 expression was substantially higher in these resistant cells, and targeting CDK7 effectively decreased their survival and tumor growth, enhancing irinotecan sensitivity. RNA-seq analysis indicated that suppression of CDK7 in irinotecan-resistant HT29 cells significantly reduced Midkine (MDK) expression. Decreased CDK7 and MDK levels, achieved through siRNA and the CDK7 inhibitor THZ1, enhanced the sensitivity of resistant HT29 cells to irinotecan. SIGNIFICANCE: Our study sheds light on how CDK7 and MDK influence irinotecan resistance in colorectal and highlights the potential of MDK-targeted therapies. We hypothesized that irinotecan sensitivity and overall treatment efficacy would improve by inhibiting MDK. This finding encourages a careful yet proactive investigation of MDK as a therapeutic target to enhance outcomes in colorectal cancer patients.

Material flow analysis of heavy metals in large-scale cattle farms and ecological risk assessment of cattle manure application to fields.

This study bridges the knowledge gap pertaining to the pathways of heavy metal accumulation and migration within the industrial chain of large-scale cattle farms. Two such farms in Shaanxi serve as a basis for our exploration into Zn, Cu, Cr, Pb, As, and Cd dynamics. Employing material flow analysis complemented by predictive models, we evaluate the potential ecological risks of arable soil from heavy metal influx via manure application. Our findings indicate that Zn and Cu predominate the heavy metal export from these operations, composing up to 60.00%-95.67% of their total content. Predictive models based on 2021 data reveal a potential increase in Cd soil concentration by 0.08 mg/kg by 2035, insinuating a reduced safe usage period for cattle manure at less than 50 years. Conversely, projections from 2022 data point towards a gradual Cu rise in soil, reaching risk threshold levels after 126 years. These outcomes inform limitations in cattle manure utilisation strategies, underscoring Cu and Cd content as key barriers. The study underscores the criticality of continuous heavy metal surveillance within farm by products to ensure environmental protection and sustainable agricultural practices.

Evaluating Recurrence Risk in Patients Undergoing Breast-conserving Surgery Using E-cadherin Staining as a Biomarker.

BACKGROUND/AIM: Following the National Comprehensive Cancer Network guidelines, radiotherapy is administered after breast-conserving surgery (BCS) in patients with more than four positive lymph nodes. Four positive lymph nodes are typically considered an indicator to assess disease spread and patient prognosis. However, the subjective counting of positive axillary lymph nodes underscores the need for biomarkers to improve diagnostic precision and reduce the risk of unnecessary treatments. Loss of E-cadherin expression is associated with cancer metastasis, but its potential as a predictive marker for cancer treatment remains uncertain. This study aimed to investigate the validity of E-cadherin as a reference for adjuvant radiotherapy in breast cancer patients with positive lymph nodes post-mastectomy. MATERIALS AND METHODS: Immunohistochemistry was performed on 60 clinical tissue specimens to assess these implications. RESULTS: Although no significant result was found in a single E-cadherin subgroup (low, medium, and high subgroups according to the X-tile algorithm), the proposed multivariate model, including the E-cadherin category, breast cancer subtype, and tumor size, yielded satisfactory recurrence risk estimation results for patients undergoing BCS. Patients with a low E-cadherin category, triple-negative breast cancers, and tumor size over 5 cm could have an increased risk of recurrence. CONCLUSION: Our study proposed a multivariate model that serves as a candidate prognostic factor for recurrence-free survival in patients undergoing BCS and radiotherapy. Utilizing this model for patient stratification in high-risk diseases and as a standard for assessing postoperative intensified therapy can potentially improve patient outcomes.

A Water-Based Biocoating to Increase the Infection Resistance and Osteoconductivity of Titanium Surfaces.

As the population ages, the number of patients undergoing total hip arthroplasty (THA) and total knee arthroplasty (TKA) continues to increase. Infections after primary arthroplasty are rare but have high rates of morbidity and mortality, as well as enormous financial implications for healthcare systems. Numerous methods including the use of superhydrophobic coatings, the incorporation of antibacterial agents, and the application of topographical treatments have been developed to reduce bacterial attachment to medical devices. However, most of these methods require complex manufacturing processes. Thus, the main purpose of this study was to apply biocoatings to titanium (Ti) surfaces to increase their infection resistance and osteoconductivity via simple processes, without organic reagents. We modified titanium surfaces with a combination of aminomalononitrile (AMN) and an antibiotic-loaded mesoporous bioactive glass (MBG) and evaluated both the antibacterial effects of the coating layer and its effect on osteoblast proliferation and differentiation. The properties of the modified surface, such as the hydrophilicity, roughness, and surface morphology, were characterized via contact angle measurements, atomic force microscopy, and scanning electron microscopy. The cell proliferation reagent WST-1 assay and the alkaline phosphatase (ALP) assay were used to determine the degrees of adhesion and differentiation, respectively, of the MG-63 osteoblast-like cells on the surface. Antimicrobial activity was evaluated by examining the survival rate and inhibition zone of Escherichia coli (E. coli). The AMN coating layer reduced the water contact angle (WCA) of the titanium surface from 87° ± 2.5° to 53° ± 2.3° and this change was retained even after immersion in deionized water for five weeks, demonstrating the stability of the AMN coating. Compared with nontreated titanium and polydopamine (PDA) coating layers, the AMN surface coating increased MG-63 cell attachment, spreading, and early ALP expression; reduced E. coli adhesion; and increased the percentage of dead bacteria. In addition, the AMN coating served as an adhesion layer for the subsequent deposition of MBG-containing antibiotic nanoparticles. The synergistic effects of the AMN layer and antibiotics released from the MBG resulted in an obvious E. coli inhibition zone that was not observed in the nontreated titanium group.

Cadmium exposure causes transcriptomic dysregulation in adipose tissue and associated shifts in serum metabolites.

Cadmium (Cd) is a toxic heavy metal found in natural and industrial environments. Exposure to Cd can lead to various metabolic disturbances, notably disrupting glucose and lipid homeostasis. Despite this recognition, the direct impact of Cd exposure on lipid metabolism within adipose tissue, and the mechanisms underlying these effects, have not been fully elucidated. In this study, we found that Cd accumulates in adipose tissues of mice subjected to Cd exposure. Intriguingly, Cd exposure in itself did not induce significant alterations in the adipose tissue under normal conditions. However, when subjected to cold stimulation, several notable changes were observed in the mice exposed to Cd, including a reduction in the drop of body temperature, a decrease in the size of inguinal white adipose tissue (WAT), and an increase in the expression of thermogenic genes UCP1 and PRDM16. These results indicate that Cd exposure might enhance the responsiveness of adipose tissue to external stimuli and increase the energy expenditure of the tissue. RNA-seq analysis further revealed that Cd exposure altered gene expression profiles, particularly affecting peroxisome proliferator-activated receptor (PPAR)-mediated metabolic pathways, promoting metabolic remodeling in adipose tissue and resulting in the depletion of lipids stored in adipose tissue for energy. Non-targeted metabolomic analysis of mouse serum showed that Cd exposure significantly disrupted metabolites and significantly increased serum fatty acid and triglyceride levels. Correspondingly, population-level data confirmed an association between Cd exposure and elevated levels of serum total cholesterol, total triglycerides, and low-density lipoprotein cholesterol. In summary, we provide substantial evidence of the molecular events induced by Cd that are relevant to the regulation of lipid metabolism in adipose tissue. Our findings suggest that the toxic effects of Cd can impact adipocyte functionality, positioning adipose tissue as a critical target for metabolic diseases resulting from Cd exposure.

Enhancing the carbon content of coal gangue for composting through sludge amendment: A feasibility study.

Cocomposting coal gangue and sludge eliminates the challenge of utilizing coal gangue. However, there is limited understanding about the feasibility of cocomposting sludge and coal gangue, as well as the composting indicators, functional microorganisms, and safety risks involved. Therefore, this study evaluated the feasibility of enhancing carbon composting in coal gangue by incorporating sludge along with sawdust as a conditioner. Three laboratory-scale reactors were designed and labeled as T1 (20 % coal gangue, 60 % sludge, and 20 % sawdust), T2 (40 % coal gangue, 40 % sludge, and 20 % sawdust), and T3 (60 % coal gangue, 20 % sludge, and 20 % sawdust). Seed germination and plant growth assessments were conducted to ensure compost stability and assess phytotoxicity to cabbage (Brassica rapa chinensis L.) in terms of growth and biomass. The results indicated that the temperature, pH, EC and ammonia nitrogen of all three reactor conditions met the requirements for product decomposition. Composting was successfully achieved when the sludge proportion was 20 % (T3). However, when the sludge proportion was markedly high (T1), the harmlessness of the compost was reduced. The germination indices of T1, T2, and T3 reached 95 %, 122 %, and 119 % at maturity, respectively. This confirmed that the harmless cycle, which involved promoting condensation and aromatization, enhancing decay, and reducing composting time, was shorter in T2 and T3 than in T1. Coal gangue can also serve as a beneficial habitat for microorganisms, promoting an increase in their population and activity. Potting experiments in sandy soil revealed that the mechanism of action of compost products in soil included not only the enhancement of soil nutrients but also the improvement of soil texture. The results of this study suggest that using coal gangue as a raw material for composting is an efficient and environmentally friendly approach for producing organic fertilizers.

Multiplane differential saturated excitation microscopy using varifocal lenses.

Saturated excitation microscopy, which collects nonlinear fluorescence signals generated by saturation, has been proposed to improve three-dimensional spatial resolution. Differential saturated excitation (dSAX) microscopy can further improve the detection efficiency of a nonlinear fluorescence signal. By comparing signals obtained at different saturation levels, high spatial resolution can be achieved in a simple and efficient manner. High-resolution multiplane microscopy is perquisite for volumetric imaging of thick samples. To the best of our knowledge, no reports of multiplane dSAX have been made. Our aim is to obtain multiplane high-resolution optically sectioned images by adapting differential saturated excitation in confocal laser scanning fluorescence microscopy. To perform multiplane dSAX microscopy, a variable focus lens is employed in a telecentric design to achieve focus tunability with constant magnification and contrast throughout the axial scanning range. Multiplane fluorescence imaging of two different types of pollen grains shows improved resolution and contrast. Our system's imaging performance is evaluated using standard targets, and the results are compared with standard confocal microscopy. Using a simple and efficient method, we demonstrate multiplane high-resolution fluorescence imaging. We anticipate that high-spatial resolution combined with high-speed focus tunability with invariant contrast and magnification will be useful in performing 3D imaging of thick biological samples.

SUV39H1 Expression as a Guideline for Omitting Radiotherapy in Lymph Node-positive Triple-negative Breast Cancer Patients.

BACKGROUND/AIM: The role of postoperative radiotherapy (RT) combined with chemotherapy (CT) for lymph node-positive (LN+) triple-negative breast cancer (TNBC) remains controversial. SUV39H1-mediated epigenetic regulation is associated with cancer cell migration, invasion, metastasis, and treatment resistance. This study aims to identify the role of SUV39H1 in TNBCs. MATERIALS AND METHODS: Overall, 498 TNBCs with SUV39H1 RNA-seq profiles were retrieved from TCGA-BRCA and analyzed; the X-tile algorithm was used to stratify the population into low, intermediate, and high SUV39H1. Furthermore, we performed an in vitro clonogenic cell survival assay using the MDA-MB-231 cell line to assess the effects of SUV39H1 on cellular responses. RESULTS: The results showed that SUV39H1 was significantly higher in TNBC than normal tissue and luminal subtype breast cancer. Notably, SUV39H1 is significantly expressed in the basal-like 1 (BL1) and immunomodulatory (IM) subgroups, compared to other subtypes. Compared to patients with a low or medium expression of SUV39H1, omitting RT only worsens disease-free survival (DFS) in those with high SUV39H1 expression. The experimental results showed SUV39H1 was suppressed by si-SUV39H1, and SUV39H1 knockdown in MDA-MB-231-IV2-1 cells enhanced the cellular toxicity of doxorubicin and paclitaxel. CONCLUSION: Targeting SUV39H1 may provide a potential guiding indication of omitting RT to avoid over-treatment and chemosensitivity for TNBC.

The impact of over-distraction on adjacent segment pathology and cage subsidence in anterior cervical discectomy and fusion.

Over-distraction has been shown to be a risk factor for cage subsidence and postoperative neck pain after anterior cervical discectomy and fusion (ACDF). Biomechanical studies have demonstrated increased adjacent segment intradiscal pressure after ACDF. The purpose of this study is to determine if over-distraction of the index disc has an effect on adjacent segment pathology. A consecutive series of 145 patients who received primary ACDF for cervical degenerative pathologies from January 2010 to December 2017 were retrospectively reviewed. The patients were divided into: (1) Over-distraction group (postoperative-preoperative index disc height ≥ 2 mm), and (2) No-distraction group (postoperative-preoperative index disc height < 2 mm). Outcome measures included radiographic parameters, Japanese Orthopaedic Association (JOA) score, and incidences of cage subsidence, radiological and clinical adjacent segment pathologies (RASP and CASP) were compared between the two groups preoperatively, postoperatively, and at the final follow-up. The two groups were comparable with respect to age, follow-up length, JOA score, incidence of CASP, and radiographic parameters. The Over-distraction group (83 patients; 115 levels) had smaller preoperative index disc height (4.5 vs. 5.2 mm, p < 0.001), but taller postoperative index disc height (7.7 vs. 6.6 mm, p < 0.001) than No-distraction group (62 patients; 90 levels) Furthermore, significantly higher incidences of cage subsidence (47% vs. 31%, p = 0.04) and RASP (any progression: 48% vs. 15%, p < 0.001; progress ≥ 2 grades: 25% vs. 7%, p = 0.001) were observed in the Over-distraction group. The multivariate analysis indicated that over-distraction and multilevel fusion were independent risk factors for RASP. There were no clinical outcome differences between the Over-distraction group and the No-distraction group in ACDF. Over-distraction of the index level of ≥ 2 mm should be avoided because it significantly increases the incidences of RASP and cage subsidence.

Remediation of Pb(II) and Cd(II) in polluted waters with calcium thioglycolate-modified straw biochar.

The pollution of water bodies by heavy metals (HMs) such as Pb(II) and Cd(II) poses a serious environmental risk. Herein, rice straw biochar (RBC) modified with calcium thioglycolate was used to remove Pb(II) and Cd(II) from aqueous solutions. The adsorption performance of the modified biochar was investigated via adsorption kinetics and isotherm model fitting. Furthermore, scanning electron microscopy (SEM), X-ray energy-dispersive spectroscopy (EDS), X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FTIR), and X-ray photoelectron spectroscopy (XPS) were used to elucidate the modification and adsorption mechanisms. The results showed that the modification process loaded sulfur-containing functional groups, calcium carbonate, and calcium oxalate crystals on the biochar surface, considerably enhancing its complexation performance and ion-exchange capacity. The equilibrium adsorption amounts for Pb(II) and Cd(II) reached 124.92 and 65.44 mg g-1 in unary systems, respectively; they reached 121.34 and 39.43 mg g-1 in a binary Pb(II) and Cd(II), respectively. Moreover, the optimal adsorption conditions were as follows: pH = 6, temperature = 25 °C, dosage = 0.8 g L-1, and contact time = 2 h. In the binary Pb(II) and Cd(II) system, the adsorption process obeyed the Langmuir competitive adsorption model, which means that one adsorption site on the modified biochar was effective for only one heavy-metal ion, and the modified biochar was more selective for Pb(II) than for Cd(II). The adsorption mechanism, which was dominated by chemisorption, mainly involved complexation, precipitation, ion exchange, and cation-π interactions. Meanwhile, adsorption and desorption experiments indicated that the modified biochar exhibited satisfactory recycling performance, demonstrating its feasibility as an inexpensive and efficient heavy-metal adsorbent for polluted water.

TCF12 Activates TGFB2 Expression to Promote the Malignant Progression of Melanoma.

As one of the most common malignant tumors, melanoma is a serious threat to human health. More than half of melanoma patients have a BRAF mutation, and 90% of them have a BRAF(V600E) mutation. There is a targeted therapy for patients using a BRAF(V600E) inhibitor. However, no response to treatment is generally inevitable due to the heterogeneity of melanoma. Coupled with its high metastatic character, melanoma ultimately leads to poor overall survival. This study aimed to explore the possible mechanisms of melanoma metastasis and identify a more effective method for the treatment of melanoma. In this paper, we report that TCF12 expression is higher in melanoma, especially in metastatic tumors, through analyzing data from TCGA. Then, cell proliferation, colony formation, and transwell assays show that the upregulated expression of TCF12 can promote proliferation and metastasis of melanoma cells in vitro. The same result is confirmed in the subcutaneous tumor formation assay. Moreover, TGFB2 is identified as a direct downstream target of TCF12 by RNA-seq, qPCR, immunoblotting, ChIP, and a dual luciferase reporting assay. Interestingly, depletion of TCF12 can sensitize melanoma to BRAF inhibition both in vitro and in vivo. Overall, our results demonstrate that TCF12 promotes melanoma progression and can be a potential tumor therapeutic target.

Epigenetic suppression of PGC1α (PPARGC1A) causes collateral sensitivity to HMGCR-inhibitors within BRAF-treatment resistant melanomas.

While targeted treatment against BRAF(V600E) improve survival for melanoma patients, many will see their cancer recur. Here we provide data indicating that epigenetic suppression of PGC1α defines an aggressive subset of chronic BRAF-inhibitor treated melanomas. A metabolism-centered pharmacological screen further identifies statins (HMGCR inhibitors) as a collateral vulnerability within PGC1α-suppressed BRAF-inhibitor resistant melanomas. Lower PGC1α levels mechanistically causes reduced RAB6B and RAB27A expression, whereby their combined re-expression reverses statin vulnerability. BRAF-inhibitor resistant cells with reduced PGC1α have increased integrin-FAK signaling and improved extracellular matrix detached survival cues that helps explain their increased metastatic ability. Statin treatment blocks cell growth by lowering RAB6B and RAB27A prenylation that reduces their membrane association and affects integrin localization and downstream signaling required for growth. These results suggest that chronic adaptation to BRAF-targeted treatments drive novel collateral metabolic vulnerabilities, and that HMGCR inhibitors may offer a strategy to treat melanomas recurring with suppressed PGC1α expression.

Combination of FAK inhibitor and cytokine-induced killer cell therapy: An alternative therapeutic strategy for patients with triple-negative breast cancer.

Triple-negative breast cancer (TNBC) is characterized by the loss of expression of several biomarkers, which limits treatment strategies for the disease. In recent years, immunotherapy has shown promising results in the treatment of various tumors. Emerging evidence demonstrated that TNBC is an immune-activated cancer, suggesting that immunotherapy could be a feasible treatment option for TNBC. Cytokine-induced killer (CIK) cell therapy is considered as a potential treatment for cancer treatment. However, it is still not approved as a standard treatment in the clinical setting. Our previous study demonstrated that focal adhesion kinase (FAK) plays important role in regulating the sensitivity of TNBC cells to CIK cells. In this study, we further verify the role of FAK in regulating the immune response in vivo. Our in vitro study indicated that knockdown of FAK in TNBC cells or treat with the FAK inhibitor followed by co-culture with CIK cells induced more cell death than CIK cells treatment only. RNA-seq analysis indicated that suppression of FAK could affect several immune-related gene expressions in TNBC cells that affects the immune response in the tumor microenvironment of TNBC cells. The combination of FAK inhibitor and CIK cells significantly suppressed tumor growth than the treatment of FAK inhibitor or CIK cells alone in vivo. Our findings provide new insights into the cytotoxic effect of CIK cell therapy in TNBC treatment and indicate that the combination of CIK cell therapy with FAK inhibitors may be an alternative therapeutic strategy for patients with TNBC.

BRAFV600E restructures cellular lactylation to promote anaplastic thyroid cancer proliferation.

Anaplastic thyroid cancer (ATC) is a rare but fatal cancer with BRAF mutation ranging from 30 to 50%. Histone lysine lactylation represents a novel epigenetic mark that translates cellular metabolic signals into transcriptional regulation. It is not clear whether the Warburg effect can promote the proliferation of ATC with BRAFV600E mutation via metabolite-mediated histone lactylation. Our study aimed at illustrating how BRAFV600E restructures the cellular protein lactylation landscape to boost ATC proliferation, and determining whether blockade of protein lactylation can sensitize mutant ATC to BRAFV600E inhibitors. Western blotting was used to evaluate lactylation status. Aerobic glycolysis was intervened by adding cell-permeable ethyl lactate or using metabolic inhibitors. Chromatin immunoprecipitation and RT-qPCR were applied to analyze the expression of growth-related genes. Different chemical inhibitors were used to inhibit BRAFV600E and other enzymes. ATC cell line-derived xenograft model was employed to examine the efficacy of mono and combinatorial therapies. The results showed that aerobic glycolysis in ATC increased global protein lactylation via improving cellular lactate availability. In particular, lactylation on Histone 4 Lysine 12 residue (H4K12La) activated the expression of multiple genes essential for ATC proliferation. Furthermore, oncogenic BRAFV600E boosted glycolytic flux to restructure the cellular lactylation landscape, leading to H4K12La-driven gene transcription and cell cycle deregulation. Accordingly, the blockade of cellular lactylation machinery synergized with BRAFV600E inhibitor to impair ATC progression both in vitro and in vivo. Our results demonstrated an extra beneficial effect of aerobic glycolysis on ATC, revealing a novel metabolism-epigenetics axis suitable for combinatorial therapy with BRAFV600E inhibition.

Saturated fatty acids synergizes cadmium to induce macrophages M1 polarization and hepatic inflammation.

Exposure to the toxic metal cadmium (Cd) is a well-established risk factor for hepatic inflammation, but it remains unclear how metabolic components, such as different fatty acids (FAs), interact with Cd to influence this process. Understanding these interactions is essential for identifying potential preventative and therapeutic targets for this disorder. To address this question, we conducted in vitro and in vivo studies to investigate the combinatorial effect of Cd and saturated FAs on hepatic inflammation. Specifically, we assessed the cytotoxicity of Cd on macrophages and their polarization and inflammatory activation upon co-exposure to Cd and saturated FAs. Our results showed that while saturated FAs had minimal impact on the cytotoxicity of Cd on macrophages, they significantly collaborated with Cd in predisposing macrophages towards a pro-inflammatory M1 polarization, thereby promoting inflammatory activation. This joint effect of Cd and saturated FAs resulted in persistent inflammation and hepatic steatohepatitis in vivo. In summary, our study identified macrophage polarization as a novel mechanism by which co-exposure to Cd and saturated lipids induces hepatic inflammation. Our findings suggest that intervening in macrophage polarization may be a potential approach for mitigating the adverse hepatic effects of Cd.

Chromatin Remodeling Enzyme Cluster Predicts Prognosis and Clinical Benefit of Therapeutic Strategy in Breast Cancer.

The treatment provided for breast cancer depends on the expression of hormone receptors, human epidermal growth factor receptor-2 (HER2), and cancer staging. Surgical intervention, along with chemotherapy or radiation therapy, is the mainstay of treatment. Currently, precision medicine has led to personalized treatment using reliable biomarkers for the heterogeneity of breast cancer. Recent studies have shown that epigenetic modifications contribute to tumorigenesis through alterations in the expression of tumor suppressor genes. Our aim was to investigate the role of epigenetic modifications in genes involved in breast cancer. A total of 486 patients from The Cancer Genome Atlas Pan-cancer BRCA project were enrolled in our study. Hierarchical agglomerative clustering analysis further divided the 31 candidate genes into 2 clusters according to the optimal number. Kaplan-Meier plots showed worse progression-free survival (PFS) in the high-risk group of gene cluster 1 (GC1). In addition, the high-risk group showed worse PFS in GC1 with lymph node invasion, which also presented a trend of better PFS when chemotherapy was combined with radiotherapy than when chemotherapy was administered alone. In conclusion, we developed a novel panel using hierarchical clustering that high-risk groups of GC1 may be promising predictive biomarkers in the clinical treatment of patients with breast cancer.

Deciphering the Functions of Telomerase Reverse Transcriptase in Head and Neck Cancer.

Head and neck cancers (HNCs) are among the ten leading malignancies worldwide. Despite significant progress in all therapeutic modalities, predictive biomarkers, and targeted therapies for HNCs are limited and the survival rate is unsatisfactory. The importance of telomere maintenance via telomerase reactivation in carcinogenesis has been demonstrated in recent decades. Several mechanisms could activate telomerase reverse transcriptase (TERT), the most common of which is promoter alternation. Two major hotspot TERT promoter mutations (C228T and C250T) have been reported in different malignancies such as melanoma, genitourinary cancers, CNS tumors, hepatocellular carcinoma, thyroid cancers, sarcomas, and HNCs. The frequencies of TERT promoter mutations vary widely across tumors and is quite high in HNCs (11.9-64.7%). These mutations have been reported to be more enriched in oral cavity SCCs and HPV-negative tumors. The association between TERT promoter mutations and poor survival has also been demonstrated. Till now, several therapeutic strategies targeting telomerase have been developed although only a few drugs have been used in clinical trials. Here, we briefly review and summarize our current understanding and evidence of TERT promoter mutations in HNC patients.

Development of Deep Learning with RDA U-Net Network for Bladder Cancer Segmentation.

In today's high-order health examination, imaging examination accounts for a large proportion. Computed tomography (CT), which can detect the whole body, uses X-rays to penetrate the human body to obtain images. Its presentation is a high-resolution black-and-white image composed of gray scales. It is expected to assist doctors in making judgments through deep learning based on the image recognition technology of artificial intelligence. It used CT images to identify the bladder and lesions and then segmented them in the images. The images can achieve high accuracy without using a developer. In this study, the U-Net neural network, commonly used in the medical field, was used to extend the encoder position in combination with the ResBlock in ResNet and the Dense Block in DenseNet, so that the training could maintain the training parameters while reducing the overall identification operation time. The decoder could be used in combination with Attention Gates to suppress the irrelevant areas of the image while paying attention to significant features. Combined with the above algorithm, we proposed a Residual-Dense Attention (RDA) U-Net model, which was used to identify organs and lesions from CT images of abdominal scans. The accuracy (ACC) of using this model for the bladder and its lesions was 96% and 93%, respectively. The values of Intersection over Union (IoU) were 0.9505 and 0.8024, respectively. Average Hausdorff distance (AVGDIST) was as low as 0.02 and 0.12, respectively, and the overall training time was reduced by up to 44% compared with other convolution neural networks.

Utilization of KOH-modified fly ash for elimination from aqueous solutions of potentially toxic metal ions.

Long-term accumulation of toxic heavy metals in the environment was a potential hidden danger. High energy consumption, complicated operation and low adsorption capacity were the disadvantages of most current adsorbents. This study used one-step modification of fly ash (FA) by low-temperature melting method with KOH as the activator to generate modified fly ash (KFA) with high adsorption capacity to remove heavy metals from aqueous solutions. Various characterization results revealed a destruction that occurred on the surface structure of adsorbent, 12 times increase in specific surface area, and metal ions were successfully adsorbed onto KFA surface. Furthermore, adsorption proceeded most favorably at pH of 5, the presence of ionic strength and co-existing cations significantly influenced the adsorption effects. The description of adsorption data was more suitable by pseudo-second-order kinetics and Langmuir isotherm models. And in single system at 25 °C, for Pb(II), Cu(II), and Cd (II), the qm were 337.41, 310.09 and 125.00 mg·g-1. However, in ternary system, the qm decreased for all three ions in the order Pb(II) > Cu(II) > Cd(II), which was different from the law in single system, and the Pb(II) adsorption was found to have a significant inhibited effect on adsorption of Cd(II) and Cu(II). The adsorption mechanisms including ion exchange, electrostatic attraction and complexation were revealed. And by exploring the bioaccessibility of absorbed heavy metals in four simulated digestive fluids, it was found that KFA could load heavy metal ions and enable their release in organisms and other aquatic environments, which provided the possibility for subsequent related studies. Therefore, KFA with low energy consumption and high adsorption capacity is equipped a prospective development space on removing heavy metals from wastewater.