First in human intraarterial delivery of tislelizumab for the treatment of pMMR locally advanced rectal cancer: A single-arm, open label, phase II clinical trial.

BACKGROUND: Intravenous immune checkpoint inhibitors (ICIs) have shown efficacy in treating locally advanced rectal cancer (LARC), but concerns about systemic toxicity persist. This study developed a unique approach termed chemo-immuno-embolization with transcatheter rectal arterial intervention (CIETAI), aiming to enhance the anti-tumor response while minimizing systemic toxicity. METHOD: This is a prospective, single-arm, phase II clinical trial conducted in Daping hospital. Patients with previously untreated stage II/III LARC underwent preoperative CIETAI combined with PD-1 inhibitor tislelizumab plus oxaliplatin, followed by standard concomitant chemoradiotherapy (capecitabine and 50.4 Gy radiation). Intravenous tislelizumab was administered for an additional two cycles. RESULTS: Between January 2023 and December 2023, a total of 38 patients were enrolled. As the primary endpoint, 17 (44.74 %) patients achieved pathological complete response (TRG0), with a major pathologic response (MPR) rate of 65.79 %. The anal preservation rate was 84.21 % (32/38), and importantly, 15 of 21 patients with low rectal cancer achieved organ preservation with functional maintenance. Eight patients experienced grade 3-4 adverse events (AEs). All immune-related AEs were grade 1-2, with the most common being endocrine toxicity (5/6, 83.33 %). No grade 5 AEs occurred. CONCLUSION: This study provides preliminary evidence supporting the safety and efficacy of intraarterial tislelizumab delivery in the neoadjuvant setting for LARC. These promising results encourage further exploration in larger cohorts to validate the clinical impact of this novel CIETAI strategy. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT05957016.

APEX1 in intestinal epithelium triggers neutrophil infiltration and intestinal barrier damage in ulcerative colitis.

Ulcerative colitis (UC) can lead to the generation of large amounts of reactive oxygen species and DNA damage. DNA repair caused by base excision repair (BER) enzymes is an important mechanism for maintaining genomic integrity. However, the specific relationship between the function of BER enzymes and UC remains unclear. To address this, we conducted a study on non-cancerous colon tissue from patients with UC, focusing on the role of apurinic/apyrimidinic endonuclease 1 (APEX1) in BER to explore its significance in the progression of UC. Our research found that the expression of APEX1 in epithelium cells was significantly correlated to the severity of inflammatory bowel disease (IBD) and the infiltration and function of neutrophils in human UC and mouse models, particularly in relation to neutrophil extracellular traps (NETs) and the degranulation processes. APEX1 deficiency resulted in decreased production of the chemokines CXCL1 by the NF-κB pathway in epithelium cells, leading to reduced accumulation and activation of neutrophils associated with colitis in colon tissue, as well as decreased levels of IL-1ß. Furthermore, APEX1 deficiency reduced symptoms of colitis by decreasing epithelial cell apoptosis and altering the gut microbiome. Studies related to the redox activity of APEX1 have shown that the combination of the redox inhibitor E3330 with 5-aminosalicylic acid (5-ASA) can effectively alleviate colitis, indicating that APEX1 has promising prospects for clinical treatment of IBD. APEX1 is required for interactions between neutrophil and intestinal epithelial cells. This study provided a mechanism demonstrating that APEX1 protein triggered the risk of UC by promoting neutrophil infiltration and compromising intestinal epithelial barrier function.

Construction and interpretation of machine learning-based prognostic models for survival prediction among intestinal-type and diffuse-type gastric cancer patients.

BACKGROUND: Gastric cancer is one of the most common malignant tumors worldwide, with high incidence and mortality rates, and it has a complex etiology and complex pathological features. Depending on the tumor type, gastric cancer can be classified as intestinal-type and diffuse-type gastric cancer, each with distinct pathogenic mechanisms and clinical presentations. In recent years, machine learning techniques have been widely applied in the medical field, offering new perspectives for the diagnosis, treatment, and prognosis of gastric cancer patients. METHODS: This study recruited 2158 gastric cancer patients and constructed prognostic prediction models for both intestinal-type and diffuse-type gastric cancer. Clinical pathological data were collected from patients, and machine learning algorithms were used for feature selection and model construction. The performance of the models was validated with training and testing datasets. The Shapley additive explanations (SHAP) values were used to interpret the model predictions and identify the main factors that influence patient survival. RESULTS: In the prognostic model for intestinal-type gastric cancer, the gradient boosting decision tree (GBDT) model demonstrated the best performance, with key features including pTNM, CA125, tumor size, CA199, and PALB. Similarly, in the prognostic model for diffuse-type gastric cancer, the GBDT model was utilized, with key features comprising pTNM, Borrmann type IV disease, lymphocyte (LYM), lactate dehydrogenase (LDH), potassium (K), perineural invasion (PNI), tumor size, and whole stomach location. Risk stratification analysis revealed that the prognosis of high-risk patients was significantly worse than that of low-risk patients. CONCLUSION: Machine learning shows great potential in predicting survival outcomes of gastric cancer patients, providing strong support for the development of personalized treatment plans.

Engineering supramolecular peptide nanofibers for in vivo platelet-hitchhiking beyond ligand-receptor recognition.

Ex vivo or in vivo cell-hitchhiking has emerged as a potential means for efficient drug delivery and various disease therapies. However, many challenges remain, such as the complicated engineering process and dependence on ligand-receptor interaction. Here, we present a simple in vivo platelet-hitchhiking strategy based on self-assembling peptides without ligand modification. The engineered peptide nanofibers can hitchhike ultrafast (<5 s) and efficiently on both resting and activated platelets in a receptor-independent and species-independent manner. Mechanistic studies showed that unique secondary structure of nanofibers, which lead to surface exposure of hydrophobic and hydrogen bond-forming groups, might primarily contribute to the selective and efficient platelet-hitchhiking behavior. After intravenous injection, these peptide nanofibers hitchhiked in situ on circulating platelets and achieved almost 20-fold lung accumulation. Our study provides not only a different paradigm of in vivo platelet-hitchhiking beyond ligand-receptor recognition but also a potential strategy for lung-targeted drug delivery and pulmonary disease therapy.

A 47-Year-old Asian female with tracheobronchial space-occupying lesions caused by chronic lymphocytic leukemia.

CASE PRESENTATION: A 47-year-old Asian woman was admitted with worsening chest tightness and dyspnea for 10 days. Computed tomography (CT) showed changes in the trachea and segmental bronchi. Pulmonary function results suggestive of severe obstructive ventilatory dysfunction. Bronchoscopic findings showed the presence of multiple nodular lesions in the patient's trachea and left and right main bronchi. Bronchoscopic biopsy, lymph node biopsy and bone marrow aspiration flow cytometry test results led to a definitive diagnosis of chronic lymphocytic leukemia (CLL), staged as Binet stage B and Rai stage 2.

The role of Gαq in regulating NLRP3 inflammasome activation.

BACKGROUND: G proteins are a class of important signal transducers in mammalians. G proteins can corpoarated with G proteincoupled receptors (GPCRs) and transmit signals from extracellular stimuli into intracellular response, which will regulate a series of biological functions. G-proteins are heterotrimeric proteins composed of Gα, Gß, and Gγ subunits. Based on structural and functional similarity of their α-subunits, G proteins are typically grouped into four classes (Gi, Gs, Gq/11, and G12/13). The Gq/11 subfamily consists of Gq, G11, G14, and G15/16 proteins. Gαq is the α-subunit of Gq protein and encoded by GNAQ. Our previous studies revealed that Gαq play an important role in regulating T cell survival and T cell differentiation. Inflammasomes are multiprotein complexes that play a critical role in modulating innate inflammatory response. NLRP3 inflammasome is currently the most extensively studied inflammasome. METHODS: We found that Gαq suppressed NLRP3 inflammasome activation in macrophage, Gαq also suppressed NLRP3 inflammasome activation in a LPS-induced sepsis mouse model. Gαq can locate to mitochondria and Gαq was required for the maintenance of mitochondrial homeostasis. Gαq regulated NLRP3 inflammasome activation by modulating mitochondrial reactive oxygen species (mtROS). RESULTS: We found that Gαq suppressed NLRP3 inflammasome activation in macrophage, Gαq also suppressed NLRP3 inflammasome activation in a LPS-induced sepsis mouse model. Gαq can locate to mitochondria and Gαq was required for the maintenance of mitochondrial homeostasis. Gαq regulated NLRP3 inflammasome activation by modulating mitochondrial reactive oxygen species (mtROS). CONCLUSION: Our results indicate that Gαq regulates NLRP3 inflammasome activation by modulating mitochondrial ROS production. Our research provides new mechanistic insight into the activation of NLRP3 inflammasome. As it has been proved that NLRP3 inflammasome plays an important role in the pathogenesis many diseases such as Alzheimer's disease, cancer, and inflammatory bowel disease, Gαq might become a novel drug target for these diseases in future.

Risk stratification of thymic epithelial tumors based on peritumor CT radiomics and semantic features.

OBJECTIVES: To develop and validate nomograms combining radiomics and semantic features to identify the invasiveness and histopathological risk stratification of thymic epithelial tumors (TET) using contrast-enhanced CT. METHODS: This retrospective multi-center study included 224 consecutive cases. For each case, 6764 intratumor and peritumor radiomics features and 31 semantic features were collected. Multi-feature selections and decision tree models were performed on radiomics features and semantic features separately to select the most important features for Masaoka-Koga staging and WHO classification. The selected features were then combined to create nomograms for the two systems. The performance of the radiomics model, semantic model, and combined model was evaluated using the area under the receiver operating characteristic curves (AUCs). RESULTS: One hundred eighty-seven cases (56.5 years ± 12.3, 101 men) were included, with 62 cases as the external test set. For Masaoka-Koga staging, the combined model, which incorporated five peritumor radiomics features and four semantic features, showed an AUC of 0.958 (95% CI: 0.912-1.000) in distinguishing between early-stage (stage I/II) and advanced-stage (III/IV) TET in the external test set. For WHO classification, the combined model incorporating five peritumor radiomics features and two semantic features showed an AUC of 0.857 (0.760-0.955) in differentiating low-risk (type A/AB/B1) and high-risk (B2/B3/C) TET. The combined models showed the most effective predictive performance, while the semantic models exhibited comparable performance to the radiomics models in both systems (p > 0.05). CONCLUSION: The nomograms combining peritumor radiomics features and semantic features could help in increasing the accuracy of grading invasiveness and risk stratification of TET. CRITICAL RELEVANCE STATEMENT: Peripheral invasion and histopathological type are major determinants of treatment and prognosis of TET. The integration of peritumoral radiomics features and semantic features into nomograms may enhance the accuracy of grading invasiveness and risk stratification of TET. KEY POINTS: Peritumor region of TET may suggest histopathological and invasive risk. Peritumor radiomic and semantic features allow classification by Masaoka-Koga staging (AUC: 0.958). Peritumor radiomic and semantic features enable the classification of histopathological risk (AUC: 0.857).

RNA editing in response to COVID-19 vaccines: unveiling dynamic epigenetic regulation of host immunity.

Background: COVID-19 vaccines are crucial for reducing the threat and burden of the pandemic on global public health, yet the epigenetic, especially RNA editing in response to the vaccines remains unelucidated. Results: Our current study performed an epitranscriptomic analysis of RNA-Seq data of 260 blood samples from 102 healthy and SARS-CoV-2 naïve individuals receiving different doses of the COVID-19 vaccine and revealed dynamic, transcriptome-wide adenosine to inosine (A-to-I) RNA editing changes in response to COVID-19 vaccines (RNA editing in response to COVID-19 vaccines). 5592 differential RNA editing (DRE) sites in 1820 genes were identified, with most of them showing up-regulated RNA editing and correlated with increased expression of edited genes. These deferentially edited genes were primarily involved in immune- and virus-related gene functions and pathways. Differential ADAR expression probably contributed to RNA editing in response to COVID-19 vaccines. One of the most significant DRE in RNA editing in response to COVID-19 vaccines was in apolipoprotein L6 (APOL6) 3' UTR, which positively correlated with its up-regulated expression. In addition, recoded key antiviral and immune-related proteins such as IFI30 and GBP1 recoded by missense editing was observed as an essential component of RNA editing in response to COVID-19 vaccines. Furthermore, both RNA editing in response to COVID-19 vaccines and its functions dynamically depended on the number of vaccine doses. Conclusion: Our results thus underscored the potential impact of blood RNA editing in response to COVID-19 vaccines on the host's molecular immune system.

Constructing a Large Language Model to Generate Impressions from Findings in Radiology Reports.

Background The specialization and complexity of radiology makes the automatic generation of radiologic impressions (ie, a diagnosis with differential diagnosis and management recommendations) challenging. Purpose To develop a large language model (LLM) that generates impressions based on imaging findings and to evaluate its performance in professional and linguistic dimensions. Materials and Methods Six radiologists recorded imaging examination findings from August 2 to 31, 2023, at Shanghai General Hospital and used the developed LLM before routinely writing report impressions for multiple radiologic modalities (CT, MRI, radiography, mammography) and anatomic sites (cranium and face, neck, chest, upper abdomen, lower abdomen, vessels, bone and joint, spine, breast), making necessary corrections and completing the radiologic impression. A subset was defined to investigate cases where the LLM-generated impressions differed from the final radiologist impressions by excluding identical and highly similar cases. An expert panel scored the LLM-generated impressions on a five-point Likert scale (5 = strongly agree) based on scientific terminology, coherence, specific diagnosis, differential diagnosis, management recommendations, correctness, comprehensiveness, harmlessness, and lack of bias. Results In this retrospective study, an LLM was pretrained using 20 GB of medical and general-purpose text data. The fine-tuning data set comprised 1.5 GB of data, including 800 radiology reports with paired instructions (describing the output task in natural language) and outputs. Test set 2 included data from 3988 patients (median age, 56 years [IQR, 40-68 years]; 2159 male). The median recall, precision, and F1 score of LLM-generated impressions were 0.775 (IQR, 0.56-1), 0.84 (IQR, 0.611-1), and 0.772 (IQR, 0.578-0.957), respectively, using the final impressions as the reference standard. In a subset of 1014 patients (median age, 57 years [IQR, 42-69 years]; 528 male), the overall median expert panel score for LLM-generated impressions was 5 (IQR, 5-5), ranging from 4 (IQR, 3-5) to 5 (IQR, 5-5). Conclusion The developed LLM generated radiologic impressions that were professionally and linguistically appropriate for a full spectrum of radiology examinations. © RSNA, 2024 Supplemental material is available for this article.

The mediating and moderating role of nursing information competence between nurses' creative self-efficacy and innovation behavior in a specialized oncology hospital.

OBJECTIVE: This study aims to examine the impact of nurses' nursing information competence on their creative self-efficacy and innovation behavior, and to investigate its role as a mediating factor between these two elements. METHODS: A survey was conducted from July to September 2023 involving 1,200 nurses from two tertiary-level oncology specialty hospitals in Beijing, selected through convenience sampling. Instruments used included the Creative Self-Efficacy Scale, Nursing Information Competence Assessment Scale, and Nurses' Innovative Behavior Scale. Data analysis was conducted using SPSS 25.0 and R 4.1.2; AMOS26 was used to construct structural equation models and Bootstrap method was used to test the mediating hypotheses. RESULTS: Out of the distributed questionnaires, 1,166 were valid, yielding an effective response rate of 97.16%. Pearson correlation analysis revealed significant correlations between innovation self-efficacy, nursing information competence, and nurses' innovative behaviors (P < 0.001). The Bootstrap method indicated that nursing information competence serves as a mediating factor in the relationship between creative self-efficacy and innovative behaviors, contributing to 24.5% of the observed effect. Additionally, regression analysis suggested that nursing information competence moderates the relationship between creative self-efficacy and innovation behavior. CONCLUSION: The findings suggest that nursing information competence not only mediates but also moderates the relationship between creative self-efficacy and innovative behavior. Enhancing nurses' information competence could therefore foster creative self-efficacy, leading to an increase in innovative behavior and, subsequently, improvements in the quality of oncology nursing care.

[Corrigendum] (­)­Epigallocatechingallate induces apoptosis in B lymphoma cells via caspase­dependent pathway and Bcl­2 family protein modulation.

Subsequently to the publication of the above article, an interested reader drew to the authors' attention that, in Fig. 3 on p. 1510, the western blot images selected to portray the caspase 7 and PARP/cleaved PARP experiments were remarkably similar. After having referred to their original data, the authors realized that the PARP/cleaved PARP blots had been inadvertently duplicated in the figure. The revised version of Fig. 3, showing the correct data for the caspase­7 experiment, is shown below. The authors confirm that the errors made during the assembly of Fig. 3 did not adversely affect the major conclusions presented in this paper, and are grateful to the Editor of International Journal of Oncology for allowing them this opportunity to publish a corrigendum. They also apologize to the readership for any inconvenience caused. [International Journal of Oncology 46: 1507­1515, 2015; DOI: 10.3892/ijo.2015.2869].

Exploring the relationship between the interleukin family and lung adenocarcinoma through Mendelian randomization and RNA sequencing analysis.

BACKGROUND: Lung adenocarcinoma (LUAD) is still one of the most prevalent malignancies. Interleukin factors are closely associated with the initiation and progression of cancer. However, the relationship between interleukin factors and LUAD has not been fully elucidated. This study aimed to use Mendelian randomization (MR) and RNA sequencing (RNA-seq) analyses to identify the interleukin factors associated with the onset and progression of LUAD. METHODS: Exposure-related instrumental variables were selected from interleukin factor summary datasets. The LUAD summary dataset from FINGENE served as the outcome. MR and sensitivity analyses were conducted to screen for interleukin factors associated with LUAD occurrence. Transcriptome analyses revealed the role of interleukin factors in lung tissues. The results were validated through Western blotting and further confirmed with driver gene-negative patients from multiple centers. Potential mechanisms influencing LUAD occurrence and development were explored using bulk RNA-seq and single-cell RNA-seq data. RESULTS: MR analysis indicated that elevated plasma levels of IL6RB, IL27RA, IL22RA1, and IL16 are causally associated with increased LUAD risk, while IL18R1 and IL11RA exhibit the opposite effect. Transcriptome analyses revealed that IL11RA, IL18R1, and IL16 were downregulated in tumor tissues compared with normal lung tissue, but only higher expression of IL11RA correlated with improved prognosis in patients with LUAD from different centers and persisted even in driver-gene negative patients. The IL11RA protein level was lower in various LUAD cell lines than in human bronchial epithelial cells. The genes co-expressed with IL11RA were enriched in the Ras signaling pathway and glycosylation processes. Fibroblasts were the primary IL11RA-expressing cell population, with IL11RA+fibroblasts exhibiting a more immature state. The genes differentially expressed between IL11RA+and IL11RA- fibroblasts were involved in the PI3K-Akt/TNF signaling pathway. CONCLUSION: According to the MR and transcriptome analyses, the downregulation of IL11RA was closely related to the occurrence and development of LUAD.

The Circulating CDC42 Expression in Sepsis: Relation to Disease Susceptibility, Inflammation, Multiple Organ Dysfunctions and Mortality Risk.

OBJECTIVE: Cell division cycle 42 (CDC42) modulates inflammation and multiple organ dysfunction by regulating T-cell differentiation and macrophage polarization. This research intended to explore the association of blood CDC42 expression with septic risk, multi-organ dysfunctions, and mortality. METHODS: 145 sepsis patients and 50 health controls were recruited, then CDC42 expression in peripheral blood mononuclear cell (PBMC) from them was measured by RT-qPCR. RESULTS: CDC42 was decreased in sepsis patients versus health controls (P<0.001); meanwhile, the receiver operating characteristic (ROC) curve showed that CDC42 had a certain value to predict sepsis risk with an area under the curve (AUC) (95% confidence interval (CI): 0.797 (0.725-0.869). Furthermore, CDC42 was negatively correlated with C-reactive protein (P<0.001), tumor necrosis factor-alpha (P<0.001) and interleukin-17A (P<0.001) but less with interleukin-6 (P=0.056). Moreover, CDC42 was negatively related to the SOFA score (P<0.001) and its several subscales (respiratory system, liver, cardiovascular, and renal system) (P<0.05). Furthermore, CDC42 was lower in septic deaths versus survivors (P<0.001); meanwhile, the ROC curve exhibited a certain ability of CDC42 in estimating 28-day mortality with an AUC (95%CI) of 0.766 (0.676-0.855). CONCLUSION: Circulating CDC42 exhibits potency to be a prognostic biomarker reflecting multi-organ dysfunctions and higher mortality risk in sepsis.

Aucklandiae radix targeted PKM2 to alleviate ulcerative colitis: Insights from the photocrosslinking target fishing technique.

BACKGROUND: Inflammatory bowel disease (IBD) is a chronic and relapsing disease marked by chronic tissue inflammation that alters the integrity and function of the gut, seriously impacting patient health and quality of life. Aucklandiae Radix (AR), known as Mu Xiang in Chinese, is a traditional Chinese medicine documented in Chinese Pharmacopoeia with effects of strengthening the intestine and stopping diarrhea. However, the potential of AR in treating intestinal inflammation and its underlying mechanism have yet to be further elucidated. PURPOSE: The objective of this study was to explore the protective effect and the potential mechanism attributable to AR for treating ulcerative colitis (UC). STUDY DESIGN AND METHODS: A murine model of UC was constructed using dextran sulfate sodium (DSS) to examine the therapeutic potential of AR in alleviating inflammation and modulating the immune response. Advanced techniques such as photocrosslinking target fishing technique, click chemistry, Western blot analysis, real-time quantitative PCR, flow cytometry, immunofluorescence, and immunohistochemistry were employed to unveil the therapeutic mechanism of AR for treating IBD. RESULTS: AR decreased disease activity index (DAI) score to alleviate the course of IBD through ameliorating intestinal barrier function in DSS-induced mice. Furthermore, AR suppressed NF-κB and NLRP3 pathways to reduce the release of pro-inflammatory factors interleukin-6 and 1ß (IL-6 and IL-1ß) and tumor necrosis factor α (TNF-α), allowing to alleviate the inflammatory response. Flow cytometry revealed that AR could reduce the accumulation of intestinal macrophages and neutrophils, maintaining intestinal immune balance by regulating the ratio of Treg to Th17 cells. It was worth noting that pyruvate kinase isozyme type M2 (PKM2) served as a potential target of AR using the photocrosslinking target fishing technology, which was further supported by cellular thermal shift assay (CETSA), drug affinity target stability (DARTS), and PKM2 knockdown experiments. CONCLUSION: AR targeted PKM2 to inhibit NF-κB and NLRP3 pathways, thereby modulating the inflammatory response and immunity to alleviate DSS-induced UC. These findings suggested the potential of AR in the treatment of UC and AR as a candidate for developing PKM2 regulators.

Telomeres and telomerase in Sarcoma disease and therapy.

Sarcoma is a rare tumor derived from the mesenchymal tissue and mainly found in children and adolescents. The outcome for patients with sarcoma is relatively poor compared with that for many other solid malignant tumors. Sarcomas have a highly heterogeneous pathogenesis, histopathology and biological behavior. Dysregulated signaling pathways and various gene mutations are frequently observed in sarcomas. The telomere maintenance mechanism (TMM) has recently been considered as a prognostic factor for patients with sarcomas, and alternative lengthening of telomeres (ALT) positivity has been correlated with poor outcomes in patients with several types of sarcomas. Therefore, telomeres and telomerases may be useful targets for treating sarcomas. This review aims to provide an overview of telomere and telomerase biology in sarcomas.

Aged fragmented-polypropylene microplastics induced ageing statues-dependent bioenergetic imbalance and reductive stress: In vivo and liver organoids-based in vitro study.

Ageing is a nature process of microplastics that occurrs daily, and human beings are inevitably exposed to aged microplastics. However, a systematic understanding of ageing status and its toxic effect is currently still lacking. In this study, plastic cup lids-originated polypropylene (PP) microplastics were UV-photoaged until the carbonyl index (CI), a canonical indicator for plastic ageing, achieved 0.08, 0.17, 0.22 and 0.28. The adverse hepatic effect of these aged PPs (aPPs) was evaluated in Balb/c mice (75 ng/mL water, about 200 particles/day) and human-originated liver organoids (LOs, 50 particles/mL, ranged from 5.94 to 13.15 ng/mL) at low-dose equivalent to human exposure level. Low-dose of aged PP could induce hepatic reductive stress both in vitro and in vivo, by elevating the NADH/NAD+ratio in a CI-dependent manner, together with hepatoxicity (indicated by increased AST secretion and cytotoxicity), and disrupted the genes encoding the nutrients transporters and NADH subunits accompanied by the restricted ATP supply, declined mitochondrial membrane potential and mitochondrial complexI/IV activities, without significant increase in MDA levels in the liver. These changes in the liver disrupted systematic metabolism, representing a circulatory panel of increases in the lactate, triglyceride, Fgf21 levels, and decreases in the pyruvate level, linked the reductive stress to the declined body weight gain but elevated hepatic NADH contents following aPPs exposure. Additionally, assessing by the LOs, it was found that digestion drastically accelerated the ageing of aPPs and worsen the energy supply upon mitochondria, representing a "scattergun effect" induced by the formation of micro- and nano-plastics mixture toward NADH/NAD+imbalance.

Interaction of ncRNAs and the PI3K/AKT/mTOR pathway: Implications for osteosarcoma.

Osteosarcoma (OS) is the most common primary malignant bone tumor in children and adolescents, and is characterized by high heterogeneity, high malignancy, easy metastasis, and poor prognosis. Recurrence, metastasis, and multidrug resistance are the main problems that limit the therapeutic effect and prognosis of OS. PI3K/AKT/mTOR signaling pathway is often abnormally activated in OS tissues and cells, which promotes the rapid development, metastasis, and drug sensitivity of OS. Emerging evidence has revealed new insights into tumorigenesis through the interaction between the PI3K/AKT/mTOR pathway and non-coding RNAs (ncRNAs). Therefore, we reviewed the interactions between the PI3K/AKT/mTOR pathway and ncRNAs and their implication in OS. These interactions have the potential to serve as cancer biomarkers and therapeutic targets in clinical applications.

Construction and Biological Evaluation of Different Nanoshell Thickness Ni@SiO2 Nanotubes as Good Protein Separation Carriers for Bovine Hemoglobin.

BACKGROUND: Nickel nanomaterials play an important role in biological applications, but they have high toxicity and poor biocompatibility. To overcome these defects, we coated the surface of Ni nanotubes with different thicknesses of SiO2 to reduce cytotoxicity, improve biocompatibility, and broaden their biological application value. OBJECTIVE: This study aimed to construct Ni nanotubes with different thicknesses of SiO2 nanoshells; investigate the effects of silicon layer thickness, incubation time, and cell line category on the cytotoxicity of the as-synthesized materials, and evaluate the biocompatibility of the materials by biological enzymes. The Ni@SiO2-NH2 was selected for use as an adsorbent for the adsorption and purification of histidine-rich proteins, such as Bovine Hemoglobin (BHb). METHODS: Magnetic Ni nanotubes were prepared by the template-chemical deposition method. A modified version of the Stöber process was used for the SiO2 coating of Ni@SiO2 nanotubes, and adjusted by changing the volume of TEOS for different thicknesses of SiO2 nanoshells. RESULTS: Different cell lines containing tumor cells and normal cells were used in the toxicity experiment, which confirmed the low cytotoxicity and good biocompatibility of Ni@SiO2. To achieve high efficiency of immobilization and purification of histidine- rich proteins, Ni@SiO2-NH2 was obtained by introducing the amino functional group. The Ni@SiO2-NH2 was found to possess lower cytotoxicity and higher adsorption capacity compared to other synthesized materials. Besides, the Ni@SiO2-NH2 also exhibited good selectivity of histidine-rich proteins. CONCLUSION: This work has not only provided ideas for reducing the cytotoxicity and improving the biocompatibility of biological nanomaterials, but also laid a foundation for subsequent biological applications.