Hypoxia exposure induces lactylation of Axin1 protein to promote glycolysis of esophageal carcinoma cells.

The hypoxic microenvironment in esophageal carcinoma is an important factor promoting the rapid progression of malignant tumor. This study was to investigate the lactylation of Axin1 on glycolysis in esophageal carcinoma cells under hypoxia exposure. Hypoxia treatment increases pan lysine lactylation (pan-kla) levels of both TE1 and EC109 cells. Meanwhile, ECAR, glucose consumption and lactate production were also upregulated in both TE1 and EC109 cells. The expression of embryonic stem cell transcription factors NANOG and SOX2 were enhanced in the hypoxia-treated cells. Axin1 overexpression partly reverses the induction effects of hypoxia treatment in TE1 and EC109 cells. Moreover, lactylation of Axin1 protein at K147 induced by hypoxia treatment promotes ubiquitination modification of Axin1 protein to promote glycolysis and cell stemness of TE1 and EC109 cells. Mutant Axin1 can inhibit ECAR, glucose uptake, lactate secretion, and cell stemness in TE1 and EC109 cells under normal or hypoxia conditions. Meanwhile, mutant Axin1 further enhanced the effects of 2-DG on inhibiting glycolysis and cell stemness. Overexpression of Axin1 also inhibited tumor growth in vivo, and was related to suppressing glycolysis. In conclusion, hypoxia treatment promoted the glycolysis and cell stemness of esophageal carcinoma cells, and increased the lactylation of Axin1 protein. Overexpression of Axin1 functioned as a glycolysis inhibitor, and suppressed the effects of hypoxia exposure in vitro and inhibited tumor growth in vivo. Mechanically, hypoxia induces the lactylation of Axin1 protein and promotes the ubiquitination of Axin1 to degrade the protein, thereby exercising its anti-glycolytic function.

Characterization of renal damage in Wilson's disease-Detailed analysis of 20 Chinese cases.

OBJECTIVE: Copper metabolism disorder disease is thought to contribute to renal symptoms in Wilson's disease (WD). Nonetheless, there remains limited knowledge regarding the precise characteristics of renal damage in individuals with Wilson's disease, encompassing clinical presentations, biochemical indicators, imaging findings, and renal histopathological alterations. METHODS: In this study, 20 patients diagnosed with Wilson's disease and renal involvement were enrolled in our hospital. These patients met the validated European criteria for Wilson's disease, and those with primary kidney disease or secondary renal damage caused by other underlying conditions were excluded. The baseline data of patients were collected. Various biochemical and hematological parameters were monitored. Biochemical examinations were measured using an automatic biochemistry analyzer, blood routines were tested by flow cytometry analysis, 24-h urine copper was tested by atomic absorption spectrophotometer. Besides, CER was measured by turbidimetric immunoassay with a Hitachi 7020 automatic biochemical analyzer (the intraplate and interplate coefficients of variation were 2.7% and 5.13% respectively). Copper oxidase was tested by colorimetric method using p-phenylenediamine hydrochloride (the intraplate and interplate coefficients of variation were both <10%). Diagnostic criteria for Wilson's disease and kidney damage were established based on the European Association for the Study of the Liver (EASL) and CKD Epidemiology Collaboration guidelines, respectively. Statistical analysis was carried out using t-tests and χ2 tests in SPSS 22.0 software. Significant differences were considered when P<0.05. RESULTS: In those patients with Wilson's disease-related renal damage, edema, gross hematuria, oliguria, and lumbar pain were present in most patients. Microscopic haematuria and proteinuria were also observed in 19 patients. Compared to patients without renal involvement, those with renal complications exhibited a significant increase in white blood cell (WBC) and neutrophil counts (P<0.05). Additionally, patients with renal damage showed a noteworthy rise in both diastolic and systolic blood pressure, along with a significant reduction in hemoglobin levels (P<0.05). Color Doppler ultrasound results revealed diffuse lesions in both kidneys in 12 patients, renal cysts were identified in 5 patients, and 2 patients exhibited abnormal renal blood flow signals. Meanwhile, varying degrees of IgA, IgM, IgG-based immunoglobulins, complement C3 and C1q deposition in the glomerular mesangial area were detected by immunofluorescence. Furthermore, renal puncture biopsy results revealed a spectrum of findings, including minimal change nephrosis in 1 case, IgA nephropathy in 3 cases, atypical membranous proliferative nephropathy in 2 cases, and focal segmental glomerulosclerosis in 1 case. CONCLUSION: This study comprehensively elucidates the distinct attributes of renal damage related to Wilson's disease, while also speculating that renal dysfunction in Wilson's disease could be linked to immune complex deposition. Depending on the underlying pathogenesis, kidney injury associated with Wilson's disease can be classified as primary or secondary. To slow down the progression of renal impairment, it is essential to undergo a renal biopsy pathological examination as early as possible to clarify the type of impairment and take the appropriate treatment.

Osthole exhibits the remedial potential for polycystic ovary syndrome mice through Nrf2-Foxo1-GSH-NF-κB pathway.

Polycystic ovary syndrome (PCOS) is the primary cause of female infertility with a lack of universal therapeutic regimen. Although osthole exhibits numerous pharmacological activities in treating various diseases, its therapeutic effect on PCOS is undiscovered. The present study found that application of osthole improved the symptoms of PCOS mice through preventing ovarian granulosa cells (GCs) production of more estrogen and alleviating the liberation of pro-inflammatory cytokine interleukin (IL)-1ß, IL-6, and tumor necrosis factor alpha. Meanwhile, osthole enhanced ovarian antioxidant capacity and alleviated intracellular reactive oxygen species (ROS) accumulation with a concurrent attenuation for oxidative stress, while intervention of antioxidant enzymic activity and glutathione (GSH) synthesis neutralized the salvation of osthole on GCs secretory disorder and chronic inflammation. Further analysis revealed that osthole restored the expression of nuclear factor erythroid 2-related factor 2 (Nrf2) and forkhead box O 1 (Foxo1) whose repression antagonized the amelioration of osthole on the insufficiency of antioxidant capacity and accumulation of ROS. Moreover, Nrf2 served as an intermedium to mediate the regulation of osthole on Foxo1. Additionally, osthole restricted the phosphorylation of IκBα and nuclear factor kappa B (NF-κB) subunit p65 by DHEA and weakened the transcriptional activity of NF-κB, but this effectiveness was abrogated by the obstruction of Nrf2 and Foxo1, whereas adjunction of GSH renewed the redemptive effect of osthole on NF-κB whose activation caused an invalidation of osthole in rescuing the aberration of GCs secretory function and inflammation response. Collectively, osthole might relieve the symptoms of PCOS mice via Nrf2-Foxo1-GSH-NF-κB pathway.

Serum cytokines and creatinine/cystatin C ratio as prognostic biomarkers in advanced cancer patients treated with anti-PD-1/PD-L1 therapy.

OBJECTIVE: Immune checkpoint inhibitors (ICIs), specifically targeting the programmed cell death protein-1 or its ligand (PD-1/PD-L1), have been extensively used in the treatment of a spectrum of malignancies, although the predictive biomarkers remain to be elucidated. This study aims to investigate the association between baseline circulating levels of cytokines and the creatinine/cystatin C ratio (CCR) with the treatment outcomes of ICIs in patients with advanced cancer. METHODS: The pre-treatment circulating levels of 10 cytokines (PD-L1, CTLA4, CXCL10, LAG3, HGF, CCL2, MIG, GRANB, IL-18, and IL-6) were measured via automated capillary-based immunoassay platform in the serum of 65 advanced cancer patients treated with anti-PD-1/PD-L1-based systemic therapy and 10 healthy volunteers. The levels of cytokines and CCR were quantified and categorized into high and low groups based on the median value. The associations of serum cytokines and CCR with response to treatment, survival, and immune-related adverse events were assessed. RESULTS: Elevated circulating levels of 6 cytokines (PD-L1, CXCL10, HGF, CCL2, MIG, and IL-6) were observed in cancer patients compared with that in healthy volunteers. The correlation coefficients between cytokines, CCR and nutritional risk index were also calculated. In the cancer cohort (N = 65), low circulating HGF (P = 0.023, P = 0.029), low IL-6 (P = 0.002, P < 0.001), and high CCR (P = 0.031, P = 0.008) were associated with significantly improved progression-free survival (PFS) and overall survival (OS). Multi-variable COX analyses adjusted for clinicopathological factors revealed that low HGF, low IL-6, and high CCR were independent favorable prognostic factors for PFS (P = 0.028, P = 0.010, and P = 0.015, respectively) and OS (P = 0.043, P = 0.003, and P = 0.026, respectively). Grade 2 irAEs occurred more frequently in patients with low levels of circulating CCL2 and LAG3. CONCLUSIONS: Pre-treatment circulating levels of serum IL-6, HGF, and CCR may serve as independent predictive and prognostic biomarkers in advanced cancer patients treated with ICIs-based systemic therapy. These findings might help to identify potential patients who would benefit from these therapies.

Meta-analysis of the GALAD model for diagnosing primary hepatocellular carcinoma.

BACKGROUND: Ever since the GALAD (gender-age-Lens culinaris agglutinin-reactive alpha-fetoprotein-alpha-fetoprotein-des-gamma-carboxy prothrombin) logistic regression model was established to diagnose hepatocellular carcinoma (HCC), there has been no high-level evidence that evaluates and summarizes it. OBJECTIVE: This meta-analysis was performed to assess the diagnostic ability of the GALAD model. METHODS: The following databases were systematically searched for original diagnostic studies on HCC: PubMed, Embase, Medline, the Web of Science, Cochrane Library, China National Knowledge Infrastructure Wanfang (China), Wiper and the Chinese BioMedical Literature Database. After screening the search results according to our criteria, the Quality Assessment of Diagnostic Accuracy Studies 2 tool was used to evaluate the methodologic qualities, and statistical software were used to output the statistics. RESULTS: Ultimately, 10 studies were included and analyzed. The results revealed the pooled sensitivity and specificity of the GALAD model to be 0.86 (95% confidence interval [CI]: 0.82, 0.90) and 0.90 (95% CI: 0.87, 0.92), respectively, for all-stage HCC. The area under the curve (AUC) was 0.94. For early-stage HCC, the pooled sensitivity and specificity of the GALAD model were 0.83 (95% CI: 0.78, 0.87) and 0.81 (95% CI: 0.78, 0.83), respectively. The AUC was 0.90. CONCLUSION: This meta-analysis confirmed that the GALAD model has excellent diagnostic performance for early-stage and all-stage HCC and can maintain high sensitivity and specificity in early-stage HCC. Therefore, the GALAD model is qualified for screening early-stage canceration from chronic liver disease.

Early cartilage lesion and 5-year incident joint surgery in knee osteoarthritis patients: a retrospective cohort study.

OBJECTIVE: to investigate the association between cartilage lesion-related features observed in knee osteoarthritis (OA) patients' first MRI examination and incident knee surgery within 5 years. Additionally, to assess the predictive value of these features for the incident knee surgery. METHODS: We identified patients diagnosed with knee OA and treated at our institution between January 2015 and January 2018, and retrieved their baseline clinical data and first MRI examination films from the information system. Next, we proceeded to determine joint space narrowing grade, cartilage lesion size grade, cartilage full-thickness loss grade and cartilage lesion sum score for the medial and lateral compartments, respectively. Generalized linear regression models examined the association of these features with 5-year incident knee surgery. Positive and negative predictive values (PPVs and NPVs) were determined referring to 5-year incident knee surgery. RESULTS: Totally, 878 participants (knees) were found eligible to form the study population. Within the 5 years, surgery was performed on 61 knees. None of the cartilage-related features had been found significantly associated with incident surgery. The results were similar for medial and lateral compartments. The PPVs were low for all the features. CONCLUSIONS: Among symptomatic clinically diagnosed OA knees, cartilage lesions observed in the first MRI examinations were not found to be associated with the occurrence of joint surgery within a 5-year period. All these cartilage-related features appear to have no additional value in predicting 5-year incident joint surgery.

Effects of saponins Rb1 and Re in American ginseng combined intervention on immune system of aging model.

Aging is a major risk factor for the development of many pathological processes, such as reduced immunity, cancer, cardiovascular diseases or neurodegenerative diseases, while age-related chronic diseases are the most common causes of death. This paper studies the effects of American ginseng saponin Rb1 and Re alone and combined intervention on the immune system of aging mouse models, by using 30 mg/kg Rb1, 15 mg/kg Re, and Rb1 + Re (30 mg/kg Rb1 and 15 mg/kg Re (co-intervention) was used to intervene in the aging model, and immune indicators such as thymus index, spleen index, interleukin and interferon were detected to evaluate the impact of Rb1 and Re on immune function. The results show that Rb1 and Re intervention alone can increase the spleen index by 7%-12% and the thymus index by 12%-19% in the aging model. After Rb1 or Re alone intervened, the apoptotic cells in the thymus were slightly reduced, and the proportion of apoptotic cells was reduced. The combination of Rb1 + Re can promote the thymus index and spleen index to increase by 23.40% and 25.5% respectively, which is more advantageous than Rb1 or Re alone. In addition, Rb1 and Re intervention can reduce the level of interferon INF to a level comparable to that of young mice. Rb1 + Re can not only reduce the INF content, but also reduce the TNF content. The above results show that American ginseng saponin Rb1 and Re can delay the decline of the immune system in the aging model, and the combined intervention of the two is significantly better than individual intervention in the recovery of the immune system. This paper can provide theoretical basis and data support for the development of American ginseng nutritional supplements and its application in aging groups products to improve immunity.

DNA Damage-Induced Apoptosis Suppressor Triggers Progression and Stemness of Glioma by Enhancing Lymphoid Enhancer-Binding Factor 1 Expression.

Background: DNA damage-induced apoptosis suppressor (DDIAS) has recently been discovered to induce cancer progression, but its functions and mechanisms in glioma have not been well studied. Methods: DDIAS expression in glioma tissues was analyzed by the Gene Expression Profiling Interactive Analysis server (GEPIA) and the Gene Expression database of Normal and Tumor tissue 2 (GENT2) databases. The role of DDIAS in glioma progression was studied by short hairpin RNA (shRNA) targeting DDIAS. The effects of DDIAS on glioma cell viability, cell proliferation, invasion, migration, and tumor sphere formation were determined by cell counting kit-8 (CCK-8), EdU, Transwell, tumor spheroid formation, extreme limiting dilution analysis assays in vitro and xenograft model construction in vivo. In addition, RNA sequencing and further functional experiments were used to analyze the DDIAS regulatory mechanism in glioma. Results: We found that DDIAS was highly expressed in glioma and that upregulated DDIAS indicated poor prognosis. Functionally, DDIAS knockdown inhibited glioma cell viability, cell proliferation, invasion and migration in vitro and tumor growth in vivo. In addition, lymphoid enhancer-binding factor 1 (LEF1) was identified as the downstream effector of DDIAS by RNA sequencing. DDIAS downregulation inhibited LEF1 mRNA and protein expression. The expression of DDIAS and LEF1 was positively correlated, and LEF1 overexpression rescued the inhibitory phenotype induced by DDIAS downregulation. We further showed that DDIAS downregulation inhibited cyclin A1, vimentin and the stemness-related factor CD133 and decreased the sphere formation capability, but these features were rescued by upregulation of LEF1. Conclusion: Taken together, these findings suggest that DDIAS promotes glioma progression and stemness by inducing LEF1 expression, proving that DDIAS may be a potential target for the treatment of glioma.

Prediction of lymph node metastasis in operable cervical cancer using clinical parameters and deep learning with MRI data: a multicentre study.

OBJECTIVES: To develop and validate a magnetic resonance imaging-based (MRI) deep multiple instance learning (D-MIL) model and combine it with clinical parameters for preoperative prediction of lymph node metastasis (LNM) in operable cervical cancer. METHODS: A total of 392 patients with cervical cancer were retrospectively enrolled. Clinical parameters were analysed by logistical regression to construct a clinical model (M1). A ResNet50 structure is applied to extract features at the instance level without using manual annotations about the tumour region and then construct a D-MIL model (M2). A hybrid model (M3) was constructed by M1 and M2 scores. The diagnostic performance of each model was evaluated by the area under the receiver operating characteristic curve (AUC) and compared using the Delong method. Disease-free survival (DFS) was evaluated by the Kaplan‒Meier method. RESULTS: SCC-Ag, maximum lymph node short diameter (LNmax), and tumour volume were found to be independent predictors of M1 model. For the diagnosis of LNM, the AUC of the training/internal/external cohort of M1 was 0.736/0.690/0.732, the AUC of the training/internal/external cohort of M2 was 0.757/0.714/0.765, and the AUC of the training/internal/external cohort of M3 was 0.838/0.764/0.835. M3 showed better performance than M1 and M2. Through the survival analysis, patients with higher hybrid model scores had a shorter time to reach DFS. CONCLUSION: The proposed hybrid model could be used as a personalised non-invasive tool, which is helpful for predicting LNM in operable cervical cancer. The score of the hybrid model could also reflect the DFS of operable cervical cancer. CRITICAL RELEVANCE STATEMENT: Lymph node metastasis is an important factor affecting the prognosis of cervical cancer. Preoperative prediction of lymph node status is helpful to make treatment decisions, improve prognosis, and prolong survival time. KEY POINTS: • The MRI-based deep-learning model can predict the LNM in operable cervical cancer. • The hybrid model has the highest diagnostic efficiency for the LNM prediction. • The score of the hybrid model can reflect the DFS of operable cervical cancer.

MIHIC: a multiplex IHC histopathological image classification dataset for lung cancer immune microenvironment quantification.

Background: Immunohistochemistry (IHC) is a widely used laboratory technique for cancer diagnosis, which selectively binds specific antibodies to target proteins in tissue samples and then makes the bound proteins visible through chemical staining. Deep learning approaches have the potential to be employed in quantifying tumor immune micro-environment (TIME) in digitized IHC histological slides. However, it lacks of publicly available IHC datasets explicitly collected for the in-depth TIME analysis. Method: In this paper, a notable Multiplex IHC Histopathological Image Classification (MIHIC) dataset is created based on manual annotations by pathologists, which is publicly available for exploring deep learning models to quantify variables associated with the TIME in lung cancer. The MIHIC dataset comprises of totally 309,698 multiplex IHC stained histological image patches, encompassing seven distinct tissue types: Alveoli, Immune cells, Necrosis, Stroma, Tumor, Other and Background. By using the MIHIC dataset, we conduct a series of experiments that utilize both convolutional neural networks (CNNs) and transformer models to benchmark IHC stained histological image classifications. We finally quantify lung cancer immune microenvironment variables by using the top-performing model on tissue microarray (TMA) cores, which are subsequently used to predict patients' survival outcomes. Result: Experiments show that transformer models tend to provide slightly better performances than CNN models in histological image classifications, although both types of models provide the highest accuracy of 0.811 on the testing dataset in MIHIC. The automatically quantified TIME variables, which reflect proportions of immune cells over stroma and tumor over tissue core, show prognostic value for overall survival of lung cancer patients. Conclusion: To the best of our knowledge, MIHIC is the first publicly available lung cancer IHC histopathological dataset that includes images with 12 different IHC stains, meticulously annotated by multiple pathologists across 7 distinct categories. This dataset holds significant potential for researchers to explore novel techniques for quantifying the TIME and advancing our understanding of the interactions between the immune system and tumors.

Effects of Seipin on Mouse Mesenchymal Stem Cell Osteo-Adipogenic Balance.

Seipin deficiency is an important cause of type 2 Berardinelli-Seip congenital dyslipidemia (BSCL2). BSCL2 is a severe lipodystrophy syndrome with lack of adipose tissue, hepatic steatosis, insulin resistance, and normal or higher bone mineral density. Bone marrow mesenchymal stem cells (BMSCs) are believed to maintain bone and fat homeostasis by differentiating into osteoblasts and adipocytes. We aimed to explore the role of seipin in the osteogenic/adipogenic differentiation balance of BMSCs. Seipin loxP/loxP mice are used to explore metabolic disorders caused by seipin gene mutations. Compared with wild-type mice, subcutaneous fat deficiency and ectopic fat accumulation were higher in seipin knockout mice. Microcomputed tomography of the tibia revealed the increased bone content in seipin knockout mice. We generated seipin-deficient BMSCs in vitro and revealed that lipogenic genes are downregulated and osteogenic genes are upregulated in seipin-deficient BMSCs. In addition, peroxisome proliferator-activated receptor gamma (PPARγ) signaling is reduced in seipin-deficient BMSCs, while using the PPARγ activator increased the lipogenic differentiation and decreased osteogenic differentiation of seipin-deficient BMSCs. Our findings indicated that bone and lipid metabolism can be regulated by seipin through modulating the differentiation of mesenchymal stem cells. Thus, a new insight of seipin mutations in lipid metabolism disorders was revealed, providing a prospective strategy for MSC transplantation-based treatment of BSCL2.

Iron Complexes as Potential Carriers of Diffuse Interstellar Bands: The Photodissociation Spectrum of Fe+(H2O) at Optical Wavelengths.

The fullerene ion C60+ is the only carrier of diffuse interstellar bands (DIBs) identified so far. Transition-metal compounds feature electronic transitions in the visible and near-infrared regions, making them potential DIB carriers. Since iron is the most abundant transition metal in the cosmos, we here test this idea with Fe+(H2O). Laboratory spectra were obtained by photodissociation spectroscopy at 80 K. Spectra were modeled with the reflection principle. A high-resolution spectrum of the DIB standard star HD 183143 served as an observational reference. Two broad bands were observed from 4120 to 6800 Å. The 4120-4800 Å band has sharp features emerging from the background, which have the width of DIBs but do not match the band positions of the reference spectrum. Calculations show that the spectrum arises from a d-d transition at the iron center. While no match was found for Fe+(H2O) with known DIBs, the observation of structured bands with line widths typical for DIBs shows that small molecules or molecular ions containing iron are promising candidates for DIB carriers.

The endoplasmic reticulum stress-related genes and molecular typing predicts prognosis and reveals characterization of tumor immune microenvironment in lung squamous cell carcinoma.

BACKGROUND: Endoplasmic reticulum stress (ERS) acts critical roles on cell growth, proliferation, and metastasis in various cancers. However, the relationship between ERs and lung squamous cell carcinoma (LUSC) prognoses still remains unclear. METHODS: The consensus clustering analysis of ERS-related genes and the differential expression analysis between clusters were investigated in LUSC based on TCGA database. Furthermore, ERS-related prognostic risk models were constructed by LASSO regression and Cox regression analyses. Then, the predictive effect of the risk model was evaluated by Kaplan-Meier, Cox regression, and ROC Curve analyses, as well as validated in the GEO cohort. According to the optimal threshold, patients with LUSC were divided into high- and low- risk groups, and somatic mutations, immune cell infiltration, chemotherapy response and immunotherapy effect were systematically analyzed. RESULTS: Two ERS-related clusters were identified in patients with LUSC that had distinct patterns of immune cell infiltration. A 5-genes ERS-related prognostic risk model and nomogram were constructed and validated. Kaplan-Meier curves and Cox regression analysis showed that ERS risk score was an independent prognostic factor (p < 0.001, HR = 1.317, 95% CI = 1.159-1.496). Patients with low-risk scores presented significantly lower TIDE scores and significantly lower IC50 values for common chemotherapy drugs such as cisplatin and gemcitabine. CONCLUSION: ERS-related risk signature has certain prognostic value and may be a potential therapeutic target and prognostic biomarker for LUSC patients.

Methionine redox regulation of actin-interacting proteins primarily governs antioxidative signaling and response to the salvianolic acid B treatment in EA.hy926 cells.

Actin-interacting proteins are important molecules for filament assembly and cytoskeletal signaling within vascular endothelium. Disruption in their interactions causes endothelial pathogenesis through redox imbalance. Actin filament redox regulation remains largely unexplored, in the context of pharmacological treatment. This work focused on the peptidyl methionine (M) redox regulation of actin-interacting proteins, aiming at elucidating its role on governing antioxidative signaling and response. Endothelial EA.hy926 cells were subjected to treatment with salvianolic acid B (Sal B) and tert-butyl-hydroperoxide (tBHP) stimulation. Mass spectrometry was employed to characterize redox status of proteins, including actin, myosin-9, kelch-like erythroid-derived cap-n-collar homology-associated protein 1 (Keap1), plastin-3, prelamin-A/C and vimentin. The protein redox landscape revealed distinct stoichiometric ratios or reaction site transitions mediated by M sulfoxide reductase and reactive oxygen species. In comparison with effects of tBHP stimulation, Sal B treatment prevented oxidation at actin M325, myosin-9 M1489/1565, Keap1 M120, plastin-3 M592, prelamin-A/C M187/371/540 and vimentin M344. For Keap1, reaction site was transitioned within its scaffolding region to the actin ring. These protein M oxidation regulations contributed to the Sal B cytoprotective effects on actin filament. Additionally, regarding the Keap1 homo-dimerization region, Sal B preventive roles against M120 oxidation acted as a primary signal driver to activate nuclear factor erythroid 2-related factor 2 (Nrf2). Transcriptional splicing of non-POU domain-containing octamer-binding protein was validated during the Sal B-mediated overexpression of NAD(P)H dehydrogenase [quinone] 1. This molecular redox regulation of actin-interacting proteins provided valuable insights into the phenolic structures of Sal B analogs, showing potential antioxidative effects on vascular endothelium.

ALDH3A1 upregulation inhibits neutrophils N2 polarization and halts oral cancer growth.

OBJECTIVES: Tumor-associated neutrophils (TANs) are among the most abundant inflammatory cells in tumor microenvironment (TME). Aldehyde dehydrogenase 3A1 (ALDH3A1) is significantly reduced in oral squamous cell carcinoma (OSCC), ALDH3A1 overexpression suppresses tumorigenesis by inhibiting inflammation. This study investigated the relationship and mechanisms underlying the crosstalk between ALDH3A1 and TANs in OSCC. MATERIALS AND METHODS: Immunohistochemistry and immunofluorescence were performed to investigate the abundance of TANs and the expression of ALDH3A1. dHL-60 were induced with tumor-conditioned media and recombinant IL-6/IL-8. The expression of key proteins in PI3K/AKT/NF-κB pathway were detected by RT-PCR and western blot. A xenograft model was utilized to examine the effect of ALDH3A1 on tumorigenicity and polarization of TANs. RESULTS: In patients with OSCC, TANs significantly increased and were associated with a worse prognosis. Additionally, ALDH3A1 negatively correlated with TANs infiltration and especially the N2 phenotype which was the prominent part in OSCC. Furthermore, our study demonstrated that tumor-derived IL-8 drives ALDH3A1-mediated TANs N2 polarization in the TME through PI3K/AKT/NF-κB pathway in vitro and in vivo. CONCLUSION: Our results indicate that TANs can serve as a prognostic biomarker and ALDH3A1 could be a promising therapeutic target for regulating TANs N2 polarization in antitumor therapy.

Comparative transcriptome and metabolome analyses revealed quality difference between beauty tea processed through indoor withering and outdoor solar withering.

BACKGROUND: Withering is the first processing procedure of beauty tea, and there are few reports on the impact of withering methods on the quality of beauty tea and its regulatory mechanisms. RESULTS: Through comparison of fresh tea leaves (FT) with the leaves after indoor natural withering for 18 h (IWT-18) and outdoor solar withering for 6 h (OWT-6), which were collected at the end of the two withering processes, 17 282 and 13 984 differentially expressed genes (DEGs) were respectively screened and 267 and 154 differential metabolites (DMs) were respectively identified. The coexpression network revealed that a large number of DEGs and DMs were enriched in phenylpropanoid, flavonoid, and adenosine triphosphate binding cassette (ABC) transporter pathways, and the number of DMs and DEGs in IWT-18 versus FT exceeded that in OWT-6 versus FT. Both withering methods promoted a significant increase in content of phenylalanine and upregulation of ß-glucoside expression in the phenylpropanoid metabolism pathway. Five theaflavin-type proanthocyanidins in the flavonoid synthesis pathway were more significantly accumulated in FT versus IWT-18 than in FT versus OWT-6. Meanwhile, both withering methods can affect the ABC transporter pathway to promote the accumulation of amino acids and their derivatives, but different withering methods affect different ABC transporter families. Outdoor withering with more severe abiotic stress has a greater impact on the ABCG family, whereas indoor withering has a more significant effect on the ABCC family. Sensory evaluation results showed that the dry tea of IWT-18 was slightly better than that of OWT-6 because of the longer withering time and more thorough substance transformation. CONCLUSION: In conclusion, the formation of honey flavor in beauty tea may be closely related to the DEGs and DMs in these three pathways. Our research provides theoretical data support for further revealing the mechanism of quality formation during the withering process of beauty tea. © 2023 Society of Chemical Industry.

Processable circularly polarized luminescence material enables flexible stereoscopic 3D imaging.

Endowing three-dimensional (3D) displays with flexibility drives innovation in the next-generation wearable and smart electronic technology. Printing circularly polarized luminescence (CPL) materials on stretchable panels gives the chance to build desired flexible stereoscopic displays: CPL provides unusual optical rotation characteristics to achieve the considerable contrast ratio and wide viewing angle. However, the lack of printable, intense circularly polarized optical materials suitable for flexible processing hinders the implementation of flexible 3D devices. Here, we report a controllable and macroscopic production of printable CPL-active photonic paints using a designed confining helical co-assembly strategy, achieving a maximum luminescence dissymmetry factor (glum) value of 1.6. We print customized graphics and meter-long luminous coatings with these paints on a range of substates such as polypropylene, cotton fabric, and polyester fabric. We then demonstrate a flexible textile 3D display panel with two printed sets of pixel arrays based on the orthogonal CPL emission, which lays an efficient framework for future intelligent displays and clothing.

Construction of a Prognostic Model Based on Methylation-Related Genes in Patients with Colon Adenocarcinoma.

Purpose: Colon adenocarcinoma (COAD) is the second leading cause of death in the world, and the new incidence rate ranks third among all cancers. Abnormal DNA methylation is related to the occurrence and development of tumors. In this study, we aimed to identify genes associated with abnormal methylation in COAD. Methods: COAD transcriptome data, methylation data and clinical information were downloaded from the TCGA database and GEO database. The differentially expressed genes (DEGs) and methylated genes (DMGs) were analyzed and identified in COAD. PCA analysis was applied to divide COAD into subtypes, and the survival and immune cell infiltration of each subtype were evaluated. Cox and LASSO analyses were performed to construct COAD risk model. GSEA was used to evaluate the enrichment pathways. The Kaplan-Meier was used to analyze the difference in survival. ROC curve was plotted to evaluate the accuracy of the model, and GSE17536 was used to verify the accuracy of the risk model. The risk model is combined with the clinicopathological characteristics of COAD patients to perform multivariate Cox regression analysis to obtain independent risk factors and draw nomograms. Results: In total, 4564 DEGs and 1093 DMGs were screened, among which 298 were found to be overlapping genes. For 220 of these overlapping genes, the methylation was significantly negatively correlated to expression levels. An optimal signature from 4 methylated biomarkers was identified to construct the prognostic model. Conclusion: Our study identified 4 methylated biomarkers in the COAD. Then, we constructed the risk model to provide a theoretical basis and reference value for the research and treatment of COAD.

CRISPR/Cas9-mediated high-mobility group A2 knockout inhibits cell proliferation and invasion in papillary thyroid carcinoma cells.

PURPOSE: Metastasis and recurrence are the prognostic risk factor in patients with thyroid carcinoma. High-mobility group A2 (HMGA2) protein plays a crucial role in papillary thyroid carcinoma (PTC) metastasis. The aim of this study was to investigate the mechanisms underlying the HMGA2 effect on PTC cell proliferation and invasion. MATERIALS AND METHODS: We used the CRISPR/Cas9 system to perform knockout of the HMGA2 gene in the human PTC cell line TPC-1. The knockout monoclonal cells were screened and verified by PCR analysis and genomic sequencing. Cell proliferation was examined after the knockout of the HMGA2 gene using cell counting kit-8 (CCK-8) assays. Furthermore, cell migration and invasion after the knockout were examined by cell scratch tests. Additionally, the changes in cell cycle and apoptosis after the knockout were detected by flow cytometry. RESULTS: The results of the PCR analysis and the genomic sequencing confirmed that the human PTC TPC-1 â€‹cell line with knockout of HMGA2 gene was successfully established. The knockout of the HMGA2 gene significantly reduced the cell proliferation, growth, and invasion. Meanwhile, the knockout of the HMGA2 gene delayed the conversion of the G2/M phase and promoted cell necrosis. CONCLUSION: The CRISPR/Cas9-mediated HMGA2 knockout in the TPC-1 â€‹cell line inhibited cell proliferation and invasion, which might be due to the blockage of the cell cycle in the G2/M phase and the promotion of cell necrosis.