Identification of molecular subtypes and a prognostic signature based on m6A/m5C/m1A-related genes in lung adenocarcinoma.

Lung cancer, specifically the histological subtype lung adenocarcinoma (LUAD), has the highest global occurrence and fatality rate. Extensive research has indicated that RNA alterations encompassing m6A, m5C, and m1A contribute actively to tumorigenesis, drug resistance, and immunotherapy responses in LUAD. Nevertheless, the absence of a dependable predictive model based on m6A/m5C/m1A-associated genes hinders accurately predicting the prognosis of patients diagnosed with LUAD. In this study, we collected patient data from The Cancer Genome Atlas (TCGA) and identified genes related to m6A/m5C/m1A modifications using the GeneCards database. The "ConsensusClusterPlus" R package was used to produce molecular subtypes by utilizing genes relevant to m6A/m5C/m1A identified through differential expression and univariate Cox analyses. An independent prognostic factor was identified by constructing a prognostic signature comprising six genes (SNHG12, PABPC1, IGF2BP1, FOXM1, CBFA2T3, and CASC8). Poor overall survival and elevated expression of human leukocyte antigens and immune checkpoints were correlated with higher risk scores. We examined the associations between the sets of genes regulated by m6A/m5C/m1A and the risk model, as well as the immune cell infiltration, using algorithms such as ESTIMATE, CIBERSORT, TIMER, ssGSEA, and exclusion (TIDE). Moreover, we compared tumor stemness indices (TSIs) by considering the molecular subtypes related to m6A/m5C/m1A and risk signatures. Analyses were performed based on the risk signature, including stratification, somatic mutation analysis, nomogram construction, chemotherapeutic response prediction, and small-molecule drug prediction. In summary, we developed a prognostic signature consisting of six genes that have the potential for prognostication in patients with LUAD and the design of personalized treatments that could provide new versions of personalized management for these patients.

Hetastarch-stabilized polypyrrole with hyperthermia-enhanced release and catalytic activity for synergistic antitumor therapy.

Fenton catalytic medicine that catalyzes the production of ·OH without external energy input or oxygen as a substrate has reshaped the landscape of conventional cancer therapy in recent decades, yet potential biosafety concerns caused by non-safety-approved components restrict their clinical translation from the bench to the bedside. Herein, to overcome this dilemma, we elaborately utilizate safety-approved hetastarch, which has been extensively employed in the clinic as a plasma substitute, as a stabilizer participating in the copper chloride-initiated polymerization of pyrrole monomer before loading it with DOX. The constructed DOX-loaded hetastarch-doped Cu-based polypyrrole (HES@CuP-D) catalyzes the excess H2O2 in tumor cells to ·OH through a Cu+-mediated Fenton-like reaction, which not only causes oxidative damage to tumor cells but also leads to the structural collapse and DOX release. Additionally, HES@CuP-D together with laser irradiation reinforces tumor killing efficiency by hyperthermia-enhanced catalytic activity and -accelerated drug release. As a result, the developed HES@CuP-D provides a promising strategy for Fenton catalytic therapy with negligible toxicity to the body.

Identification and validation of a m7G-related lncRNA signature for predicting the prognosis and therapy response in hepatocellular carcinoma.

BACKGROUND: N7-methylguanosine (m7G) is one of the most common RNA posttranscriptional modifications; however, its potential role in hepatocellular carcinoma (HCC) remains unknown. We developed a prediction signature based on m7G-related long noncoding RNAs (lncRNAs) to predict HCC prognosis and provide a reference for immunotherapy and chemotherapy. METHODS: RNA-seq data from The Cancer Genome Atlas (TCGA) database and relevant clinical data were used. Univariate and multivariate Cox regression analyses were conducted to identify m7G-related lncRNAs with prognostic value to build a predictive signature. We evaluated the prognostic value and clinical relevance of this signature and explored the correlation between the predictive signature and the chemotherapy treatment response of HCC. Moreover, an in vitro study to validate the function of CASC19 was performed. RESULTS: Six m7G-related lncRNAs were identified to create a signature. This signature was considered an independent risk factor for the prognosis of patients with HCC. TIDE analyses showed that the high-risk group might be more sensitive to immunotherapy. ssGSEA indicated that the predictive signature was strongly related to the immune activities of HCC. HCC in high-risk patients was more sensitive to the common chemotherapy drugs bleomycin, doxorubicin, gemcitabine, and lenalidomide. In vitro knockdown of CASC19 inhibited the proliferation, migration and invasion of HCC cells. CONCLUSION: We established a 6 m7G-related lncRNA signature that may assist in predicting the prognosis and response to chemotherapy and immunotherapy of HCC.

A Linearly Polarized Wavelength-Tunable Q-Switched Fiber Laser with a Narrow Spectral Bandwidth of 112 MHz.

A tunable and narrow-bandwidth Q-switched ytterbium-doped fiber (YDF) laser is investigated in this paper. The non-pumped YDF acts as a saturable absorber and, together with a Sagnac loop mirror, provides a dynamic spectral-filtering grating to achieve a narrow-linewidth Q-switched output. By adjusting an etalon-based tunable fiber filter, a tunable wavelength from 1027 nm to 1033 nm is obtained. When the pump power is 1.75 W, the Q-switched laser pulses with a pulse energy of 10.45 nJ, and a repetition frequency of 11.98 kHz and spectral linewidth of 112 MHz are obtained. This work paves the way for the generation narrow-linewidth Q-switched lasers with tunable wavelengths in conventional ytterbium, erbium, and thulium fiber bands to address critical applications such as coherent detection, biomedicine, and nonlinear frequency conversion.

Integrated Analysis of Single-Cell RNA-Seq and Bulk RNA-Seq Combined with Multiple Machine Learning Identified a Novel Immune Signature in Diabetic Nephropathy.

Background: Increasing evidence suggests that immune modulation contributes to the pathogenesis and progression of diabetic nephropathy (DN). However, the role of immune modulation in DN has not been elucidated. The purpose of this study was to search for potential immune-related therapeutic targets and molecular mechanisms of DN. Methods: Gene expression datasets were obtained from the Gene Expression Omnibus (GEO) database. A total of 1793 immune-related genes were acquired from the Immunology Database and Analysis Portal (ImmPort). Weighted gene co-expression network analysis (WGCNA) was performed for GSE142025, and the red and turquoise co-expression modules were found to be key for DN progression. We utilized four machine learning algorithms, namely, random forest (RF), support vector machine (SVM), adaptive boosting (AdaBoost), and k-nearest neighbor (KNN), to evaluate the diagnostic value of hub genes. Immune infiltration patterns were analyzed using the CIBERSORT algorithm, and the correlation between immune cell type abundance and hub gene expression was also investigated. Results: A total of 77 immune-related genes of advanced DN were selected for subsequent analyzes. Functional enrichment analysis showed that the regulation of cytokine-cytokine receptor interactions and immune cell function play a corresponding role in the progression of DN. The final 10 hub genes were identified through multiple datasets. In addition, the expression levels of the identified hub genes were corroborated through a rat model. The RF model exhibited the highest AUC. CIBERSORT analysis and single-cell sequencing analysis revealed changes in immune infiltration patterns between control subjects and DN patients. Several potential drugs to reverse the altered hub genes were identified through the Drug-Gene Interaction database (DGIdb). Conclusion: This pioneering work provided a novel immunological perspective on the progression of DN, identifying key immune-related genes and potential drug targets, thus stimulating future mechanistic research and therapeutic target identification for DN.

Secondary Raman and Brillouin mode suppression in two- and three-mirror-cavity diamond Raman lasers.

We report an investigation into secondary mode suppression in single longitudinal mode (SLM) 1240 nm diamond Raman lasers. For a three-mirror V-shape standing-wave cavity incorporating an intra-cavity LBO crystal to suppress secondary modes, we achieved stable SLM output with a maximum output power of 11.7 W and a slope efficiency 34.9%. We quantify the level of χ(2) coupling necessary to suppress secondary modes including those generated by stimulated Brillouin scattering (SBS). It is found that SBS-generated modes often coincide with higher-order spatial modes in the beam profile and can be suppressed using an intracavity aperture. Using numerical calculations, it is shown that the probability for such higher-order spatial modes is higher for an apertureless V-cavity than in two-mirror cavities due its contrasting longitudinal mode-structure.

Modeling and characterization of high-power single frequency free-space Brillouin lasers.

Free-space Brillouin lasers (BLs) are capable of generating high-power, narrow-linewidth laser outputs at specific wavelengths. Although there have been impressive experimental demonstrations of these lasers, there is an absence of a corresponding theory that describes the dynamic processes that occur within them. This paper presents a time-independent analytical model that describes the generation of the first-order Stokes field within free-space BLs. This model is based on the cavity resonance enhancement theory and coupled wave equations that govern the processes of stimulated Brillouin scattering (SBS). This model is validated using an experimental diamond BL to numerically simulate the influence of the cavity design parameters on the SBS threshold, pump enhancement characteristics, and power of the generated Stokes field. Specifically, the model is used to determine the SBS cavity coupler reflectance to yield the maximum Stokes field output power and efficiency, which is also a function of the pump power and other cavity design parameters. This analysis shows that the appropriate choice of Brillouin cavity coupler reflectance maximizes the Stokes field output power for a given pump power. Furthermore, the onset of higher-order Stokes fields that are undesirable in the context of single-frequency laser operation were inhibited. This study aids in understanding the relationship between the cavity parameters and resultant laser characteristics for the design and optimization of laser systems.

Construction and validation of a prognostic signature based on necroptosis-related genes in hepatocellular carcinoma.

BACKGROUND: Necroptosis is a necrotic programmed cell death with potent immunogenicity. Due to the dual effects of necroptosis on tumor growth, metastasis and immunosuppression, we evaluated the prognostic value of necroptosis-related genes (NRGs) in hepatocellular carcinoma (HCC). METHODS: We first analyzed RNA sequencing and clinical HCC patient data obtained to develop an NRG prognostic signature based on the TCGA dataset. Differentially expressed NRGs were further evaluated by GO and KEGG pathway analyses. Next, we conducted univariate and multivariate Cox regression analyses to build a prognostic model. We also used the dataset obtained from the International Cancer Genome Consortium (ICGC) database to verify the signature. The Tumor Immune Dysfunction and Exclusion (TIDE) algorithm was used to investigate the immunotherapy response. Furthermore, we investigated the relationship between the prediction signature and chemotherapy treatment response in HCC. RESULTS: We first identified 36 differentially expressed genes out of 159 NRGs in hepatocellular carcinoma. Enrichment analysis showed that they were mainly enriched in the necroptosis pathway. Four NRGs were screened by Cox regression analysis to establish a prognostic model. The survival analysis revealed that the overall survival of patients with high-risk scores was significantly shorter than that of patients with low-risk scores. The nomogram demonstrated satisfactory discrimination and calibration. The calibration curves validated a fine concordance between the nomogram prediction and actual observation. The efficacy of the necroptosis-related signature was also validated by an independent dataset and immunohistochemistry experiments. TIDE analysis revealed that patients in the high-risk group were possibly more susceptible to immunotherapy. Furthermore, high-risk patients were found to be more sensitive to conventional chemotherapeutic medicines such as bleomycin, bortezomib, and imatinib. CONCLUSION: We identified 4 necroptosis-related genes and established a prognostic risk model that could potentially predict prognosis and response to chemotherapy and immunotherapy in HCC patients in the future.

Modelling and characterisation of continuous wave resonantly pumped diamond Raman lasers.

We present experimental results and modeling of continuous wave resonantly pumped Raman lasers. The first Stokes diamond Raman ring laser generated 0.6 W at 960 nm with an efficiency of 18%; the second Stokes laser generated 1.5 W at 1485 nm at 9% efficiency. The analytical model, extended to arbitrary Stokes orders, shows the importance of modelling imperfect mode matching and guides the optimization of input and output coupler reflectivity to predict practical watt-level Raman converters of few-watt pump lasers.

Investigating single-longitudinal-mode operation of a continuous wave second Stokes diamond Raman ring laser.

We report a diamond Raman ring cavity laser resonantly pumped by a tunable Ti:sapphire continuous wave laser. We characterize the laser operation generating first Stokes output and, for the first time, generate second Stokes lasing at a maximum output power of 364 mW with 33.4% slope efficiency at 1101.3 nm. Single longitudinal mode operation is achieved for all first Stokes output powers, but only for lower output powers for second Stokes operation. We discuss possible reasons preventing single longitudinal mode operation.