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Abstract Melanoma, recognized as the most aggressive type of skin cancer, has experienced a notable increase in cases, especially within populations with fair skin. This highly aggressive cancer is largely driven by UV radiation exposure, resulting in the uncontrolled growth and malignant transformation of melanocytes. The cGAS-STING pathway, an immune signaling mechanism responsible for detecting double-stranded DNA in the cytoplasm, is essential for mediating the immune response against melanoma. This pathway serves a dual purpose: it enhances antitumor immunity by activating immune cells, but it can also promote tumor growth when chronically activated by creating an immunosuppressive environment. This review comprehensively examines the multifaceted implication of the cGAS-STING pathway in melanoma pathogenesis and treatment. We explore its molecular mechanisms, including epigenetic regulation, interaction with signaling pathways such as AR signaling, and modulation by various cellular effectors like TG2 and activin-A. The therapeutic potential of modulating the cGAS-STING pathway is highlighted, with promising results from STING agonists, combination therapies with immune checkpoint inhibitors, and novel drug delivery systems, including nanoparticles and synthetic drugs. Our findings underscore the importance of the cGAS-STING pathway in melanoma, presenting it as a critical target for enhancing anti-tumor immunity. By leveraging this pathway, future therapeutic strategies can potentially convert ‘cold’ tumors into ‘hot’ tumors, making them more susceptible to immune responses.

Abstract Skin cancer is a common disease resulting from genetic defects, and early detection is critical to improve treatment outcomes. Diagnostic programs that use computer aid especially those that use supervised learning are very useful in early diagnosis of skin cancer. This research therefore presents a new approach that integrates optimization methods with supervised learning to improve skin cancer diagnosis using machine vision approach. The presented method is initiated by data pre-processing that involves the removal of unnecessary data. Then, to segment the images, a combination of K-means clustering and social spider optimization technique is employed. The region of interest is then extracted from the segmented image and from this region a convolutional neural network extracts the significant features. To enhance the classification performance as compared with the standard classifiers, this research introduces a new concept of error correcting output codes coupled with a weighted Hamming distance in the group of gamma classifiers. The ability of the proposed approach in segmentation of skin lesions and classifying them was tested using samples from the ISIC-2017 and ISIC-2016 databases. The introduced method obtained state-of-the-art accuracy on both datasets (ISIC-2016: 97.10%, ISIC-2017: 95.17%). In particularly, the accuracy of the introduced approach for both these databases is at least 1.17% higher than the compared methods. This proves the high performance of the suggested method based on the usage of the convolutional neural networks for feature extraction and gamma classifiers with error correcting output codes for classification in skin cancer detection.

BackgroundItraconazole, a widely used antifungal medication, has shown potential in inhibiting tumor growth and reducing angiogenesis. However, its role in melanoma tumor growth remains insufficiently explored. This study investigates the inductive effect of itraconazole on autophagy-mediated apoptosis in melanoma cells.MethodPotential drug targets were identified using the PMF machine learning algorithm. Apoptosis and cell cycle in melanoma cell lines A375 and A2058 were assessed via flow cytometry. Western blot analysis was performed to examine autophagy and associated signaling proteins, while autophagy flux and autophagosome formation were visualized using fluorescence microscopy. A melanoma cell xenograft mouse model was established to evaluate the inhibitory mechanisms of itraconazole on tumor cell proliferation.ResultUsing the PMF machine learning algorithm, SQSTM1 was identified as the primary target of itraconazole. Itraconazole inhibited melanoma cell proliferation by inducing G1 phase arrest and autophagy-mediated apoptosis in A375 and A2058 cells. Furthermore, itraconazole suppressed Hedgehog signaling and counteracted the activation of the Hedgehog agonist recombinant human Sonic Hedgehog (rhShh). In vivo, itraconazole significantly reduced tumor growth in A375 and A2058 xenograft models.ConclusionItraconazole induces autophagy-mediated apoptosis in melanoma cells by inhibiting Hedgehog signaling, underscoring its potential as a therapeutic option for melanoma treatment.

Background: Medical resources, especially blood products, were in short supply during the COVID-19. Less intensive therapy with hypomethylating agents/venetoclax (VEN) seems an effective treatment option for patients with acute myeloid leukemia (AML). Objectives: To retrospectively analyze the efficacy and safety of VEN combined with azacitidine (AZA) in young adult patients with newly diagnosed (ND) AML. Design: This was a retrospective study. Methods: The clinical data of 25 AML patients treated with the VEN + AZA regimen from January 2021 to December 2023 at our center were collected, compared with a randomized historical study cohort that was administered intensive chemotherapy (IC) from January 2018 to December 2019. Results: No rate of complete remission/complete remission with incomplete count recovery differences observed between the two arms reached statistical significance. Compared to traditional IC, minimal residual disease (MRD)-negative remission was achieved more quickly in patients treated with VEN + AZA regimens (after cycle 1: 8% in the IC group vs 56% in the VEN group, p = 0.0004; after cycle 2: 16% in the IC group vs 72% in the VEN group, p = 0.0001), especially in those AML patients who had a poor prognosis. The dependency of transfusion of red blood cell (RBC) and platelets during induction treatment was significantly lower in the VEN + AZA group (RBC: p = 0.0269; platelet: p = 0.0054). Compared with the standard IC, the incidence rate of non-hematological adverse events in VEN + AZA group was significantly decreased (infection: 100% vs 20%, p = 0.0001; gastrointestinal side effects: 48% vs 12%, p = 0.0055). The total hospitalization cost of the VEN group was significantly less than that of the IC group ( p = 0.0395). Conclusion: In conclusion, our study indicated that VEN + AZA with a higher MRD-negative remission rate and less toxic appeared to be a therapy option for young patients with ND AML. However, further well-designed studies with larger numbers of patients are needed to confirm the benefits of VEN + AZA in this population.

Abstract The emergence of abnormal protein bands (APBs), also known as oligoclonal protein bands, has been documented in patients with multiple myeloma (MM) post hematopoietic stem cell transplantation. However, the incidence rate and clinical significance of APBs remain contentious. Few studies have explored the occurrence and prognostic implications of APBs in patients with MM treated with B‐cell maturation antigen (BCMA)–specific chimeric antigen receptor (CAR)‐T therapy. In this retrospective study, we examined the frequency, isotypes, and duration of APBs, as well as their correlation with MM disease characteristics, treatment response, clinical outcomes, and immune signature in patients with relapsed/refractory MM who had received LCAR‐B38M therapy at the Xi'an site of the phase 1 LEGEND‐2 trial. Among 47 patients assessed, 23 (48.9%) developed APBs following CAR‐T therapy, with IgG being the most common isotype. The median onset and duration of APBs post‐CAR‐T infusion were 3.6 and 5.8 months, respectively. Patients with APBs demonstrated significantly improved response to LCAR‐B38M therapy, along with longer overall and progression‐free survival. Furthermore, those with APBs exhibited enhanced recovery rates of immunoglobulins and higher absolute counts of white blood cells, neutrophils, and lymphocytes post‐CAR‐T treatment compared to those without APBs. However, no significant differences were observed between the two groups in the percentages of various T‐cell subsets and natural killer cells. Overall, the presence of APBs in patients with MM following CAR‐T treatment was associated with deeper remission and a more favorable prognosis, suggesting a robust humoral response and subsequent immune reconstitution.

BackgroundMultiple myeloma (MM) exhibits considerable heterogeneity in treatment responses and survival rates, even when standardized care is administered. Ongoing efforts are focused on developing prognostic models to predict these outcomes more accurately. Recently, neutrophil extracellular traps (NETs) have emerged as a potential factor in MM progression, sparking investigation into their role in prognostication.MethodsIn this study, a multi-gene risk scoring model was constructed using the intersection of NTEs and differentially expressed genes (DEGs), applying the least absolute shrinkage and selection operator (LASSO) Cox regression model. A nomogram was established, and the prognostic model’s effectiveness was determined via Kaplan-Meier survival analysis, receiver operating characteristic (ROC) curve, and decision curve analysis (DCA). The ESTIMATE algorithm and immune-related single-sample gene set enrichment analysis (ssGSEA) were employed to evaluate the level of immune infiltration. The sensitivity of chemotherapy drugs was assessed using the Genomics of Drug Sensitivity in Cancer (GDSC) database. Ultimately, the presence of the detected genes was confirmed through quantitative real-time polymerase chain reaction (qRT-PCR) analysis in MM cell specimens.Results64 NETs-DEGs were yielded, and through univariate Cox regression and LASSO regression analysis, we constructed a risk score composed of six genes: CTSG, HSPE1, LDHA, MPO, PINK1, and VCAM1. MM patients in three independent datasets were classified into high- and low-risk groups according to the risk score. The overall survival (OS) of patients in the high-risk group was significantly reduced compared to the low-risk group. Furthermore, the risk score was an independent predictive factor for OS. In addition, interactions between the risk score, immune score, and immune cell infiltration were investigated. Further analysis indicated that patients in the high-risk group were more sensitive to a variety of chemotherapy and targeted drugs, including bortezomib. Moreover, the six genes provided insights into the progression of plasma cell disorders.ConclusionThis study offers novel insights into the roles of NETs in prognostic prediction, immune status, and drug sensitivity in MM, serving as a valuable supplement and enhancement to existing grading systems.

ABSTRACTObjectives Young adults with acute myeloid leukemia (AML) often fail to achieve permanent complete remission (CR) and frequently relapse, indicating an urgent need to explore effective salvage therapies. Recent advances in AML treatment have been attributed to the combination of the B-cell lymphoma 2 (Bcl-2) inhibitor venetoclax (VEN) with hypomethylating agents (HMAs); however, the use of this combination in young adults with relapsed or refractory (R/R) AML has not been reported.Methods We retrospectively examined 31 young patients with R/R AML treated with VEN plus an HMA. We evaluated the demographic data, cytogenetic characteristics, AML types, response rates, and transplantation-related data for the patients in our cohort.Results The combination of VEN + HMA yielded a CR rate of 48.4%. The most prominent hematologic adverse event was neutropenia, which occurred in all patients, with 90.3% of cases being grade ≥3. Non-hematologic toxicities were relatively mild and infrequent, with an incidence of 45.2%. More than half of the patients with sustained CR had received an allogeneic hematopoietic stem cell transplantation (allo-HSCT), of whom two died of transplant-related complications.Conclusion Our results showed that the combination of VEN + HMA appeared to be a highly effective and well-tolerated salvage therapy option for young patients with R/R AML, enabling more young patients to proceed to potentially curative allo-HSCT. However, additional, well-designed studies with larger numbers of patients are required to confirm the advantages of VEN + HMA in this population.

BackgroundMultiple myeloma (MM) is a highly malignant hematological tumor with a poor overall survival (OS). Due to the high heterogeneity of MM, it is necessary to explore novel markers for the prognosis prediction for MM patients. Ferroptosis is a form of regulated cell death, playing a critical role in tumorigenesis and cancer progression. However, the predictive role of ferroptosis-related genes (FRGs) in MM prognosis remains unknown.MethodsThis study collected 107 FRGs previously reported and utilized the least absolute shrinkage and selection operator (LASSO) cox regression model to construct a multi-genes risk signature model upon FRGs. The ESTIMATE algorithm and immune-related single-sample gene set enrichment analysis (ssGSEA) were carried out to evaluate immune infiltration level. Drug sensitivity was assessed based on the Genomics of Drug Sensitivity in Cancer database (GDSC). Then the synergy effect was determined with Cell counting kit-8 (CCK-8) assay and SynergyFinder software.ResultsA 6-gene prognostic risk signature model was constructed, and MM patients were divided into high and low risk groups. Kaplan-Meier survival curves showed that patients in the high risk group had significantly reduced OS compared with patients in the low risk group. Besides, the risk score was an independent predictor for OS. Receiver operating characteristic (ROC) curve analysis confirmed the predictive capacity of the risk signature. Combination of risk score and ISS stage had better prediction performance. Enrichment analysis revealed immune response, MYC, mTOR, proteasome and oxidative phosphorylation were enriched in high risk MM patients. We found high risk MM patients had lower immune scores and immune infiltration levels. Moreover, further analysis found that MM patients in high risk group were sensitive to bortezomib and lenalidomide. At last, the results of the in vitro experiment showed that ferroptosis inducers (RSL3 and ML162) may synergistically enhance the cytotoxicity of bortezomib and lenalidomide against MM cell line RPMI-8226.ConclusionThis study provides novel insights into roles of ferroptosis in MM prognosis prediction, immune levels and drug sensitivity, which complements and improves current grading systems.

The mechanisms of Bisphenol A (BPA) induced learning and memory impairment have still not been fully elucidated. MicroRNAs (miRNAs) are endogenous non-coding small RNA molecules involved in the process of toxicant-induced neurotoxicity. To investigate the role of miRNAs in BPA-induced learning and memory impairment, we analyzed the impacts of BPA on miRNA expression profile by high-throughput sequencing in mice hippocampus. Results showed that mice treated with BPA displayed impairments of spatial learning and memory and changes in the expression of miRNAs in the hippocampus. Seventeen miRNAs were significantly differentially expressed after BPA exposure, of these, 13 and 4 miRNAs were up- and downregulated, respectively. Bioinformatic analysis of Gene Ontology (GO) and pathway suggests that BPA exposure significantly triggered transcriptional changes of miRNAs associated with learning and memory; the top five affected pathways involved in impairment of learning and memory are: 1) Long-term depression (LTD); 2) Thyroid hormone synthesis; 3) GnRH signaling pathway; 4) Long-term potentiation (LTP); 5) Serotonergic synapse. Eight BPA-responsive differentially expressed miRNAs regulating LTP and LTD were further screened to validate the miRNA sequencing data using Real-Time PCR. The deregulation expression levels of proteins of five target genes (CaMKII, MEK1/2, IP3R, AMPAR1 and PLCβ4) were investigated via western blot, for further verifying the results of gene target analysis. Our results showed that LTP and LTD related miRNAs and their targets could contribute to BPA-induced impairment of learning and memory. This study provides valuable information for novel miRNA biomarkers to detect changes in impairment of learning and memory induced by BPA exposure.

Tremendous applications of carbon-based nanomaterials need the individualization of particles in the liquid phase, preferably in an aqueous solution. Currently, one of the main challenges is how to obtain highly monodispersed and high-quality colloidal solutions and make it usable in electronic devices without performing badly. In this study, carbon nanoparticles (i.e., fullerenes, carbon nanotubes, graphene) were individualized and stabilized well in an aqueous solution by using a novel cutting-edge dispersion technique using sodium hypochlorite (NaClO) and sodium bromide (NaBr) assisted by brief low-power sonication treatment. This new method improves colloidal properties, provides a means by which carboxylate groups are introduced to the surface of the carbon nanoparticles that facilitates the formation of Na-carbon salts when the particles are exposed to the NaClO and NaBr mixed-salt solution. As a metal-salt complex, the Na-carbon is then readily susceptible to dispersion within a polar medium. Vacuum-filtration prepared salted carbon nanotube film, graphene and C60 have high electrical conductivity, and the representative carbon nanotube has a value up to 1.72 × 104 S/m, comparable to that dispersed by other traditional dispersants. Because of its nontoxicity and facile water-based solution features, we expect this dispersion and casting technique would pave its way into more device areas, etc.

BackgroundVitamin E has long been linked to skin health, including all of its possible functions in cosmetic products, to its roles in membrane integrity and even the aging process. However, reports on the relationship between serum vitamin E levels and the risk of chronic inflammatory skin diseases have been inconsistent. We performed a systematic review and meta-analysis to evaluate the association between serum vitamin E levels and chronic inflammatory skin diseases.MethodsWe searched the PubMed, Web of Science and Scopus databases, with no time limit up to 30.06.2021. Studies examining serum vitamin E levels in patients with chronic inflammatory skin diseases were selected.ResultsTwenty articles met the inclusion criteria. Compared with controls, a lower vitamin E level was found in patients with vitiligo (SMD: -0.70, 95% CI: -1.21 to -0.19), psoriasis (SMD: -2.73, 95% CI: -3.57 to -1.18), atopic dermatitis (SMD: -1.08, 95% CI: -1.80 to -0.36) and acne (SMD: -0.67, 95% CI: -1.05 to -0.30).ConclusionsOur meta-analysis showed that serum vitamin E levels were lower in patients suffering from vitiligo, psoriasis, atopic dermatitis and acne. This study highlights the need to evaluate vitamin E status to improve its level in patients with skin diseases.

Abstract Halide perovskite quantum dots (PQDs) are promising materials for diverse applications including displays, light‐emitting diodes, and solar cells due to their intriguing properties such as tunable bandgap, high photoluminescence quantum yield, high absorbance, and narrow emission peaks. Despite the prosperous achievements over the past several years, PQDs face severe challenges in terms of stability under different circumstances. Currently, researchers have overcome part of the stability problem, making PQDs sustainable in water, oxygen, and polar solvents for long‐term use. However, halide PQDs are easily degraded under continuous irradiation, which significantly limits their potential for conventional applications. In this study, an oleic acid/oleylamine (traditional surface ligands)‐free method to fabricate perovskite quantum dot papers (PQDP) is developed by adding cellulose nanocrystals as long‐chain binding ligands that stabilize the PQD structure. As a result, the relative photoluminescence intensity of PQDP remains over ≈90% under continuous ultraviolet (UV, 16 W) irradiation for 2 months, showing negligible photodegradation. This proposed method paves the way for the fabrication of ultrastable PQDs and the future development of related applications.

Abstract Chemical sensors detect a variety of chemicals across numerous fields, such as automobile, aerospace, safety, indoor air quality, environmental control, food, industrial production and medicine. We successfully assemble an alcohol-sensing device comprising a thin-film sensor made of graphene nanosheets (GNs) and bacterial cellulose nanofibers (BCNs). We show that the GN/BCN sensor has a high selectivity to ethanol by distinguishing liquid–phase or vapor–phase ethanol (C2H6O) from water (H2O) intelligently with accurate transformation into electrical signals in devices. The BCN component of the film amplifies the ethanol sensitivity of the film, whereby the GN/BCN sensor has 12400% sensitivity for vapor-phase ethanol compared to the pure GN sensor, which has only 21% sensitivity. Finally, GN/BCN sensors demonstrate fast response/recovery times and a wide range of alcohol detection (10–100%). The superior sensing ability of GN/BCN compared to GNs alone is due to the improved wettability of BCNs and the ionization of liquids. We prove a facile, green, low-cost route for the assembly of ethanol-sensing devices with potential for vast application.

Abstract Perovskite quantum dots (PQDs) are a competitive candidate for next‐generation display technologies as a result of their superior photoluminescence, narrow emission, high quantum yield, and color tunability. However, due to poor thermal resistance and instability under high energy radiation, most PQD‐based white light‐emitting diodes (LEDs) show only modest luminous efficiency of ≈50 lm W−1 and a short lifetime of

Cellulose nanocrystal (CNC) is a nanoscale colloid with superior potential for coatings, liquid crystal displays, and optoelectronics. However, to date, the presence of hydrophilicity still limits its application. Multifunction via graft copolymerization modification of CNC appears to be breaking into a new direction. In this study, we used the residual hydroxyl groups on the CNC to react with 2-bromoisobu-tyryl bromide, and the initiator was therefore anchored on the CNC surface. Through atom transfer radical polymerization (ATRP), CNC was successfully grafted to azobenzene monomer, i.e., 9-[4-[2-[4-(trifluorometh) phenyl] diazenyl] phenoxy] nonayl acrylate (FAZO). After a series of characterization methods, such as FTIR, NMR and XRD, it was found that the surface water contact angle of the CNC-PFAZO prepared by the modification was as high as 134.4◦, and the high hydrophilicity of this material could be maintained for up to one month, even longer. [ABSTRACT FROM AUTHOR]

Aggregation is a major problem for hydrophobic carbon nanomaterials such as carbon nanotubes (CNTs) in water because it reduces the effective particle concentration, prevents particles from entering the medium, and leads to unstable electronic device performances when a colloidal solution is used. Molecular ligands such as surfactants can help the particles to disperse, but they tend to degrade the electrical properties of CNTs. Therefore, self-dispersed particles without the need for surfactant are highly desirable. We report here, for the first time to our knowledge, that CNT particles with negatively charged hydrophobic/water interfaces can easily self-disperse themselves in water via pretreating the nanotubes with a salt solution with a low concentration of sodium hypochlorite (NaClO) and sodium bromide (NaBr). The obtained aqueous CNT suspensions exhibit stable and superior colloidal performances. A series of pH titration experiments confirmed the presence and role of the electrical double layers on the surface of the salted carbon nanotubes and of functional groups and provided an in-depth understanding of the phenomenon. [ABSTRACT FROM AUTHOR]

Background Reconstruction of vulvovaginal defects after tumor excision requires good-quality skin cover because of the cosmetic and functional importance of this region. Although numerous techniques for vulvovaginal reconstruction have been described, an ideal approach has yet to be widely accepted. Methods Seven gluteal-fold flaps advanced in a V-Y fashion were used to cover vulvovaginal defects in five patients who underwent surgical treatment for extramammary Paget's disease or carcinoma of the vulva. Results Each flap survived completely with no complication other than partial dehiscence in one case and temporary postoperative discomfort and pain upon sitting. None of the patients suffered from recurrence of the tumor. Conclusions In our experience, this flap is easily elevated, not bulky, and reliable because it is supplied by the internal pudendal artery and vein perforators without excessive skeletonization of the vascular pedicle, and it has matched local skin quality. In addition, it has minimal donor-site morbidity as the scar is concealed in the gluteal fold. It can cover medium-sized vulvovaginal defects after tumor excision. [ABSTRACT FROM AUTHOR]

The article presents the clinical case of a 22-year-old man diagnosed with a mass in the right lower chest. Reportedly, the mass in the right lower chest had grown gradually and become painful over two years. The patient has undergone ultrasound examination, where a well-circumscribed homogeneous solid mass between the external oblique and external intercostal muscle was found. Furthermore, the clinical findings had revealed schwannoma or a hemangioma.

Previous studies of epidermal-specific gene promoters suggested that a limited set of transcription factors regulate keratinocyte-specific and differentiation-specific gene expression in the epidermis. In the present study, we investigated the functional importance of AP-1- and Sp1-binding elements in the determination of cell type-specific and differentiation-specific gene expression by transient transfection into undifferentiated and differentiated keratinocytes as well as into various non-epidermal cell lines. Synthesized short AP-1- and/or Sp1-binding elements were inserted into a minimal reporter vector, and the artificial promoter containing both AP-1 and Sp1 elements showed high levels of transcriptional activity only when transfected into differentiated keratinocytes. Promoters containing either the AP-1 or the Sp1 motif alone showed little activity in any of the cells examined. We also found that close proximity of the Sp1 and AP-1 sites is essential for transcriptional activity, suggesting that the physical interaction between Sp1 and AP-1 factors is important for functional activity. These results clearly demonstrate that the combination of ubiquitously expressed transcription factors AP-1 and Sp1 confers keratinocyte specificity and differentiation specificity on the gene expression. Our findings also provide a simple model of the mechanisms underlying regulation of cell type-specific and cell differentiation-specific gene expression by ubiquitously expressed transcription factors. [ABSTRACT FROM AUTHOR]

Loricrin is a major component of the epidermal cornified cell envelope, and is expressed only in terminally differentiated keratinocytes. This cell differentiation-specific expression pattern suggests specific suppression of loricrin gene expression in undifferentiated keratinocytes as well as its activation in differentiated keratinocytes. We identified a negative regulatory sequence element in the first intron of the mouse loricrin gene involved in suppression of loricrin gene expression in undifferentiated keratinocytes. A database search indicated that this sequence contained the putative inverted Yin-Yang 1 (YY1)-binding motif. Constructs with point mutations in the putative YY1-binding motif showed increased reporter activity, indicating that YY1 negatively regulates loricrin gene transcription. Co-transfection experiments using a YY1 expression vector revealed that YY1 represses loricrin promoter activity. Western blotting and immunohistochemical analyses indicated that YY1 is more abundant in undifferentiated than in differentiated keratinocytes. These findings suggest that YY1 contributes to specific loricrin gene expression in differentiated keratinocytes by suppression of its transcription in undifferentiated keratinocytes. Furthermore, we demonstrated that forced expression of YY1 in differentiated keratinocytes results in specific downregulation of expression of other early and late differentiation markers. [ABSTRACT FROM AUTHOR]