Ultrasound-mediated nanobubbles loaded with STAT6 siRNA inhibit TGF-ß1-EMT axis in LUSC cells via overcoming the polarization of M2-TAMs.

M2-like tumor-associated macrophages (M2-TAMs) are closely correlated with metastasis and poor clinical outcomes in lung squamous cell carcinoma (LUSC). Previous studies have demonstrated that STAT6 is an important signaling molecule involved in the polarization of M2-TAMs, EMT is the main way for TAMs to promote tumor progression. However, little attention has been paid to the effect of STAT6 inhibition on LUSC, and it is difficult to achieve an ideal gene silencing effect in immune cells using traditional gene transfection methods. Here, we investigated the optimal concentration of 12-myristic 13-acetate (PMA), lipopolysaccharide (LPS) for the induction of THP-1 into M1-TAMs and M2-TAMs. The expression of pSTAT6 and STAT6 was confirmed in three types of macrophages, and it was demonstrated that pSTAT6 can be used as a specific target of M2-TAMs derived from THP-1. Ultrasound-mediated nanobubble destruction (UMND) is a non-invasive and safe gene delivery technology. We also synthesized PLGA-PEI nanobubbles (NBs) to load and deliver STAT6 small interfering RNA (siRNA) into M2-TAMs via UMND. The results show that the NBs could effectively load with siRNA and had good biocompatibility. We found that UMND enhanced the transfection efficiency of siRNA, as well as the silencing effect of pSTAT6 and the inhibition of M2-TAMs. Simultaneously, when STAT6 siRNA entered M2-TAMs by UMND, proliferation, migration, invasion and EMT in LUSC cells could be inhibited via the transforming growth factor-ß1 (TGF-ß1) pathway. Therefore, our results confirm that UMND is an ideal siRNA delivery strategy, revealing its potential to inhibit M2-TAMs polarization and ultimately treat LUSC.

Cr dopant mediates hydroxyl spillover on RuO2 for high-efficiency proton exchange membrane electrolysis.

Simultaneously improving the activity and stability of catalysts for anodic oxygen evolution reaction (OER) in proton exchange membrane water electrolysis (PEMWE) remains a notable challenge. Here, we report a chromium-doped ruthenium dioxide with oxygen vacancies, termed Cr0.2Ru0.8O2-x, that drives OER with an overpotential of 170 mV at 10 mA cm-2 and operates stably over 2000 h in acidic media. Experimental and theoretical studies show that the synergy of Cr dopant and oxygen vacancy induces an unconventional dopant-mediated hydroxyl spillover mechanism. Such dynamic hydroxyl spillover from Cr dopant to Ru active site changes the rate-determining step from OOH* formation to O2 formation and thus greatly improves the OER performance. Moreover, the Cr dopant and oxygen vacancy also play a crucial role in stabilizing surface Ru and lattice oxygen in the Ru-O-Cr structural motif. When assembled into the anode of a practical PEMWE device, Cr0.2Ru0.8O2-x enables long-term durability of over 200 h at an ampere-level current density and 60 degrees centigrade.

MARCH8 Mediates K27-Linked Polyubiquitination of IL-7 Receptor α to Negatively Regulate IL-7-Triggered T Cell Homeostasis.

IL-7 is a cytokine produced by stromal cells, which binds to IL-7Rα and plays an important role for homeostasis of T lymphocytes. Excessive activities of IL-7-triggered signaling pathways causes autoimmune diseases. How IL-7-triggered signaling and immune effects are regulated is not fully understood. In this study, we show that the membrane-associated RING-CH (MARCH) E3 ligase family member MARCH8 mediates K27-linked polyubiquitination of IL-7Rα, leading to its lysosomal degradation. Site-directed mutagenesis suggests that MARCH8 meditates polyubiquitination of IL-7Rα at K265/K266, and mutation of these residues renders IL-7Rα resistance to MARCH8-mediated polyubiquitination and degradation. MARCH8 deficiency increases IL-7-triggered activation of the downstream transcription factor STAT5 and transcriptional induction of the effector genes in human T lymphoma cells. MARCH8 deficiency also promotes IL-7-triggered T cell proliferation and splenic memory CD8+ T cell differentiation in mice. Our findings suggest that MARCH8 negatively regulates IL-7-triggered signaling by mediating K27-linked polyubiquitination and lysosomal degradation of IL-7Rα, which reveals a negative regulatory mechanism of IL-7-triggered T cell homeostasis.

Integrating multisource data and machine learning for supraglacial lake detection: Implications for environmental management and sustainable development goals in high mountainous regions.

The accurate detection and monitoring of supraglacial lakes in high mountainous regions are crucial for understanding their dynamic nature and implications for environmental management and sustainable development goals. In this study, we propose a novel approach that integrates multisource data and machine learning techniques for supra-glacial lake detection in the Passu Batura glacier of the Hunza Basin, Pakistan. We extract pertinent features or parameters by leveraging multisource datasets such as radar backscatter intensity VH and VV parameters from Sentinel-1 Ground Range Detected (GRD) data, near-infrared (NIR), NDWI_green, NDWI_blue parameters from Sentinel-2 Multi-spectral Instrument (MSI) data, and surface slope, aspect, and elevation parameters from topographic data. The entire dataset is partitioned into training and testing sets, with machine learning models including the artificial neural network (ANN), the support vector machine (SVM), logistic regression (LR), random forest (RF), and K-nearest neighbour (KNN) trained on the training data (70%). Accuracy assessment employs testing data and involves the evaluation of metrics such as ROC curves and confusion matrices. The best-performing model, ANN, is validated against manually digitized lake polygons derived from Sentinel-2 and Google Earth Pro imagery. Furthermore, the digitized lake polygons are used to analyze glacial lake dynamics from 2016 to 2022. Key findings of this research presented that the NDWI_green, Sigma0_VH, and elevation are the most significant predictors in detecting supra-glacial lakes. Among the various trained and evaluated models, the Artificial Neural Network (ANN) achieved the highest performance (accuracy: 95%, AUC: 0.99) and accurately mapped supra-glacial lakes regardless of their small size. The findings have significant implications for understanding glacial lake behavior in the context of climate change and informing future research and monitoring efforts.

PLK2-mediated phosphorylation of SQSTM1 S349 promotes aggregation of polyubiquitinated proteins upon proteasomal dysfunction.

Dysregulation in protein homeostasis results in accumulation of protein aggregates, which are sequestered into dedicated insoluble compartments so-called inclusion bodies or aggresomes, where they are scavenged through different mechanisms to reduce proteotoxicity. The protein aggregates can be selectively scavenged by macroautophagy/autophagy called aggrephagy, which is mediated by the autophagic receptor SQSTM1. In this study, we have identified PLK2 as an important regulator of SQSTM1-mediated aggregation of polyubiquitinated proteins. PLK2 is upregulated following proteasome inhibition, and then associates with and phosphorylates SQSTM1 at S349. The phosphorylation of SQSTM1 S349 strengthens its binding to KEAP1, which is required for formation of large SQSTM1 aggregates/bodies upon proteasome inhibition. Our findings suggest that PLK2-mediated phosphorylation of SQSTM1 S349 represents a critical regulatory mechanism in SQSTM1-mediated aggregation of polyubiquitinated proteins.

A Flexible Multifunctional Cyanoethyl-Modified Bacterial Cellulose Nanofiber Framework for High-Energy and High-Power Density Aqueous Li-Ion Batteries.

Aqueous rechargeable lithium-ion batteries (ARLIBs) are extensively researched due to their inherent safety, typical affordability, and potential high energy density. However, fabricating ARLIBs with both high energy density and power performance remains challenging. Herein, based on cyanoethyl-modified bacterial cellulose nanofibers (CBCNs), a multifunctional fast ion transport framework is developed to construct the flexible free-standing ARLIBs with high areal loading and excellent rate performance. Benefiting from the unique merits of CBCNs, such as ultra-high aspect ratio, excellent toughness, superior adhesion, good lithiophilicity and ideal stability, the flexible free-standing and highly robust electrodes are fabricated and exhibit a long-term stable cycling of 1200 cycles with a high specific capacity of 117 mAh∙g-1 at 15 C. Remarkably, the corresponding full cell with the free-standing high mass loading (45.5 mg∙cm-2) electrodes under the condition of ultra-low addition of battery binder demonstrates a cycle lifespan of over 1000 cycles with a specific capacity of 120 mAh∙g-1 and a capacity decay as low as 0.03% per cycle, which is far superior to those of almost all previous reports. This work provides a strategy for constructing ARLIBs with high energy density and power performance by introducing a unique fast ion transport nanofiber framework.

Effects of Zishen Yutai pills combined with metformin on women with polycystic ovary syndrome undergoing in vitro fertilization.

In this study, we analyzed the clinical efficacy of Zishen Yutai pills (ZSYTP) combined with metformin hydrochloride on infertile women diagnosed with polycystic ovary syndrome (PCOS) undergoing in vitro fertilization and embryo transfer (IVF-ET). Patients were assigned into 3 groups: the ZSYTP group (n = 50), the metformin group (n = 50), and the combination group (ZSYTP combined with metformin hydrochloride, n = 50), based on their respective and the indicated treatments before undergoing IVF-ET. Then, their glucose metabolism indices, sex hormone indices, traditional Chinese medicine (TCM) syndrome scores, and outcomes of IVF-ET were compared. Baseline characteristics were not significantly different between the 2 groups. After treatment, various parameters such as body mass index (BMI), fasting plasma glucose (FPG), fasting insulin (FIN), homeostatic model assessment of insulin resistance (HOMA-IR), luteinizing hormone (LH), estradiol (E2), follicle-stimulating hormone (FSH), testosterone (T) levels, and TCM syndrome scores were found to be reduced compared to pretreatment levels in both groups. Moreover, the improvement observed in the treatment group exceeded that of the control group. Specifically, the observation group displayed significantly lower gonadotropin (Gn) dosage and duration, as well as a reduced abortion rate compared to the control group. Furthermore, the observation group had higher numbers of obtained eggs, high-quality embryos, eggs obtained through IVF-ET, average transferred embryos, clinical pregnancy rate, and embryo implantation rate compared to the control group. Pretreatment with ZSYTP combined with metformin before IVF-ET in PCOS patients improves the outcome of IVF-ET.

Lecithin-cholesterol acyltransferase is a potential tumor suppressor and predictive marker for hepatocellular carcinoma metastasis.

BACKGROUND: Hepatocellular carcinoma (HCC) is a major cause of cancer mortality worldwide, and metastasis is the main cause of early recurrence and poor prognosis. However, the mechanism of metastasis remains poorly understood. AIM: To determine the possible mechanism affecting HCC metastasis and provide a possible theoretical basis for HCC treatment. METHODS: The candidate molecule lecithin-cholesterol acyltransferase (LCAT) was screened by gene microarray and bioinformatics analysis. The expression levels of LCAT in clinical cohort samples was detected by quantitative real-time polymerase chain reaction and western blotting. The proliferation, migration, invasion and tumor-forming ability were measured by Cell Counting Kit-8, Transwell cell migration, invasion, and clonal formation assays, respectively. Tumor formation was detected in nude mice after LCAT gene knockdown or overexpression. The immunohistochemistry for Ki67, E-cadherin, N-cadherin, matrix metalloproteinase 9 and vascular endothelial growth factor were performed in liver tissues to assess the effect of LCAT on HCC. Gene set enrichment analysis (GSEA) on various gene signatures were analyzed with GSEA version 3.0. Three machine-learning algorithms (random forest, support vector machine, and logistic regression) were applied to predict HCC metastasis in The Cancer Genome Atlas and GEO databases. RESULTS: LCAT was identified as a novel gene relating to HCC metastasis by using gene microarray in HCC tissues. LCAT was significantly downregulated in HCC tissues, which is correlated with recurrence, metastasis and poor outcome of HCC patients. Functional analysis indicated that LCAT inhibited HCC cell proliferation, migration and invasion both in vitro and in vivo. Clinicopathological data showed that LCAT was negatively associated with HCC size and metastasis (HCC size ≤ 3 cm vs 3-9 cm, P < 0.001; 3-9 cm vs > 9 cm, P < 0.01; metastatic-free HCC vs extrahepatic metastatic HCC, P < 0.05). LCAT suppressed the growth, migration and invasion of HCC cell lines via PI3K/AKT/mTOR signaling. Our results indicated that the logistic regression model based on LCAT, TNM stage and the serum level of α-fetoprotein in HCC patients could effectively predict high metastatic risk HCC patients. CONCLUSION: LCAT is downregulated at translational and protein levels in HCC and might inhibit tumor metastasis via attenuating PI3K/AKT/mTOR signaling. LCAT is a prognostic marker and potential therapeutic target for HCC.

Improving the removal rate of bisphenol A and Cu2+ from water using P/N coexisting ß-cyclodextrin-based adsorbents by enhancing adsorbents-pollutants interactions.

Bisphenol A (BPA), a prominent endocrine-disrupting compound, has garnered considerable attention due to its urgent need for rapid removal from water. Herein, we first used a novel reactive phosphine oxide containing tertiary amines as crosslinker to prepare water-insoluble crosslinked ß-cyclodextrin (ß-CD) adsorbent via radical-mediated thiol-ene polymerization. Owing to the synergistic hydrogen-bond (H-bond) interactions of functional groups (tertiary amine and PO groups) toward BPA, the resulted adsorbents showed fast adsorption kinetics to BPA with an adsorption equilibrium time of 5 min. After six adsorption-desorption cycles, the removal efficiency of BPA was 92.5 %, indicating its excellent reusability. Due to the presence of the CS bonds, the ß-CD -derived bio-adsorbents offered binding sites for Cu2+ ions, resulting in a maximum adsorption capacity of 113.89 mg g-1.

Human/mouse CD137 agonist, JNU-0921, effectively shrinks tumors through enhancing the cytotoxicity of CD8+ T cells in cis and in trans.

Agonistic antibodies against CD137 have been demonstrated to completely regress established tumors through activating T cell immunity. Unfortunately, current CD137 antibodies failed to benefit patients with cancer. Moreover, their antitumor mechanisms in vivo remain to be determined. Here, we report the development of a small molecular CD137 agonist, JNU-0921. JNU-0921 effectively activates both human and mouse CD137 through direct binding their extracellular domains to induce oligomerization and signaling and effectively shrinks tumors in vivo. Mechanistically, JNU-0921 enhances effector and memory function of cytotoxic CD8+ T cells (CTLs) and alleviates their exhaustion. JNU-0921 also skews polarization of helper T cells toward T helper 1 type and enhances their activity to boost CTL function. Meanwhile, JNU-0921 attenuates the inhibitory function of regulatory T cells on CTLs. Our current work shows that JNU-0921 shrinks tumors by enhancing the cytotoxicity of CTLs in cis and in trans and sheds light on strategy for developing CD137 small molecular agonists.

Secondhand smoke exposure and asthma status among adolescents: Findings from the 2019-2020 California Student Tobacco Survey.

Background and objectives: Secondhand tobacco smoke is associated with worsening asthma symptoms among children. However, the relationship between secondhand marijuana smoke and asthma symptoms among youth has not been examined. This study compares the prevalence of secondhand tobacco and marijuana smoke exposure, overall and by asthma status, among middle and high school students. Methods: The study assessed participants of the 2019-2020 California Student Tobacco Survey: a large, cross-sectional random sample of 8th, 10th, and 12th graders (N = 158,937). Descriptive analyses examined exposure to combustible tobacco and marijuana secondhand smoke by students' asthma status and sociodemographic characteristics. Results: More students with asthma were exposed to combustible tobacco secondhand smoke (13.4 %) and marijuana secondhand smoke (12.0 %) than students without asthma (10.9 % and 9.3 %, respectively). The prevalence of secondhand marijuana smoke exposure was higher among 12th grade students (12.2 %) while the prevalence of secondhand tobacco smoke exposure was higher among 8th grade students (13.4 %) and those who lived in rural locations (15.4 %). Conclusions: California students are exposed to marijuana secondhand smoke at similar proportions to combustible tobacco secondhand smoke and more students with asthma are exposed to marijuana secondhand smoke. These results expand the public health issue of secondhand smoke exposure among children with asthma by highlighting the need to examine marijuana secondhand smoke. Given the rapid shift in marijuana laws across the US, exposure to secondhand marijuana smoke is likely to increase. Therefore, vulnerable populations, such as children with asthma, should be prioritized for interventions that aim to alleviate secondhand marijuana exposure.

New species and new records of Laccaria (Agaricales, Basidiomycota) from Northern Thailand.

Two new species Laccariapseudoalba and L.subroseoalbescens are described and illustrated, based on morphological characteristics and molecular phylogenetic analysis. Two new records, Laccariaumbilicata and L.yunnanensis from Thailand, are also reported. Laccariasubroseoalbescens is characterized by small basidiomata, stipe equal with an enlarged base, and nearly subclavate, pale pink to light orange. Laccariapseudoalba is characterized by pale orange to orange white pileus, has umbo when young on the pileus, and fistulose stipe of the pale to pastel red color. Phylogenetic analysis based on sequence data from rDNA internal transcribed spacer ITS1-5.8S-ITS2 rDNA (ITS), nuc 28S rDNA (28S), RNA polymerase II subunit 2 (rpb2), and translation elongation factor 1-α (tef1-α) are provided as further evidence. Molecular analysis confirms the phylogenetic positions of the two new species and two new records. The differences in characteristics of these two new species and closely related species are discussed herein.

Bio-inspired Mechanically Responsive Smart Windows for Visible and Near-Infrared Multiwavelength Spectral Modulation.

Mechanochromic light control technology that can dynamically regulate solar irradiation is recognized as one of the leading candidates for energy-saving windows. However, the lack of spectrally selective modulation ability still hinders its application for different scenarios or individual needs. Here, inspired by the generation of structure color and color change of living organisms, a simple layer-by-layer assembly approach toward large-area fabricating mechanically responsive film for visible and near-infrared multiwavelength spectral modulation smart windows is reported here. The assembled SiO2 nanoparticles and W18O49 nanowires enable the film with an optical modulation rate of up to 42.4% at the wavelength of 550 nm and 18.4% for the near-infrared region, separately, and the typical composite film under 50% stretching shows ≈41.6% modulation rate at the wavelength of 550 nm with NIR modulation rate less than 2.7%. More importantly, the introduction of the multilayer assembly structure not only optimizes the film's optical modulation but also enables the film with high stability during 100 000 stretching cycles. A cooling effect of 21.3 and 6.9 °C for the blackbody and air inside a model house in the real environmental application is achieved. This approach provides theoretical and technical support for the new mechanochromic energy-saving windows.

Polytypic metal chalcogenide nanocrystals.

By engineering chemically identical but structurally distinct materials into intricate and sophisticated polytypic nanostructures, which often surpass their pure phase objects and even produce novel physical and chemical properties, exciting applications in the fields of photovoltaics, electronics and photocatalysis can be achieved. In recent decades, various methods have been developed for synthesizing a library of polytypic nanocrystals encompassing IV, III-V and II-VI polytypic semiconductors. The exceptional performances of polytypic metal chalcogenide nanocrystals have been observed, making them highly promising candidates for applications in photonics and electronics. However, achieving high-precision control over the morphology, composition, crystal structure, size, homojunctions, and periodicity of polytypic metal chalcogenide nanostructures remains a significant synthetic challenge. This review article offers a comprehensive overview of recent progress in the synthesis and control of polytypic metal chalcogenide nanocrystals using colloidal synthetic strategies. Starting from a concise introduction on the crystal structures of metal chalcogenides, the subsequent discussion delves into the colloidal synthesis of polytypic metal chalcogenide nanocrystals, followed by an in-depth exploration of the key factors governing polytypic structure construction. Subsequently, we provide comprehensive insights into the physical properties of polytypic metal chalcogenide nanocrystals, which exhibit strong correlations with their applications. Thereafter, we emphasize the significance of polytypic nanostructures in various applications, such as photovoltaics, photocatalysis, transistors, thermoelectrics, stress sensors, and the electrocatalytic hydrogen evolution. Finally, we present a summary of the recent advancements in this research field and provide insightful perspectives on the forthcoming challenges, opportunities, and future research directions.

Three new Melanogaster species (Boletales, Paxillaceae) from southwestern China based on morphological and molecular evidence.

Three newly discovered Melanogaster species, namely M.cyaneus, M.diqingensis, and M.truncatisporus, are introduced and illustrated based on both morphological and molecular data from Sichuan and Yunnan provinces in China. A multigene phylogenetic analysis (nrITS, nrLSU, and rpb2) was performed mainly to verify the placement of the new species in Melanogaster. A second, nrITS-only phylogenetic analysis comprising more Melanogaster species for which only ITS sequences were available, was used to infer the relationship between the new species and as many known Melanogaster species as possible. Specimens of M.cyaneus, M.diqingensis, and M.truncatisporus formed three independent clades in a phylogenetic tree inferred from the ITS data set. The robust support from ITS for these clades and genetic similarity with other species being lower than 93.2% suggest that these three species are indeed distinct from the other Melanogaster species in the phylogeny. Morphologically, M.cyaneus is characterized by its blue or bluish gleba, light brown to yellowish brown peridium, and subglobose to globose basidiospores, 6.2-15 × 4.6-9.0 µm. Melanogasterdiqingensis is distinguished from other Melanogaster species by its pale yellow to brown-yellow peridium and obovate to subglobose basidiospores, 3.0-5.1 × 2.0-4.0 µm. Melanogastertruncatisporus is diagnosed by its subglobose to globose or irregularly elongate-pyriform basidiomata, pale yellow to deeply orange-yellow peridium, and subglobose to globose or pyriform, truncate basidiospores. Additionally, infrageneric classification based on the number of peridium layers, the average thickness of the peridium, and the average length and width of basidiospores was tested with M.cyaneus, M.diqingensis, and M.truncatisporus. Orthogonal partial least squares discriminant (OPLS-DA) analysis placed the three new species within the Melanogaster, Rivulares, and Variegati sections, respectively. However, the morphologically circumscribed sections were not monophyletic in the phylogenetic tree. Therefore, the current infrageneric classification should be abandoned.

Biomineralization-Tuned Nanounits Reprogram the Signal Transducer and Activator of Transcription 3 Signaling for Ferroptosis-Immunotherapy in Cancer Stem Cells.

Cancer stem cells (CSCs) are promising targets for improving anticancer treatment outcomes while eliminating recurrence, but their treatment remains a major challenge. Here, we report a nanointegrative strategy to realize CSC-targeted ferroptosis-immunotherapy through spatiotemporally controlled reprogramming of STAT3-regulated signaling circuits. Specifically, STAT3 inhibitor niclosamide (Ni) and an experimental ferroptosis drug (1S, 3R)-RSL3 (RSL3) are integrated into hyaluronic acid-modified amorphous calcium phosphate (ACP) nanounits through biomineralization (CaP-PEG-HA@Ni/RSL3), which could be recognized by CD44-overexpressing CSCs and released in a synchronized manner. Ni inhibits the CSC-intrinsic STAT3-PD-L1 axis to stimulate adaptive immunity and enhance interferon gamma (IFNγ) secretion by CD8+ T cells to downregulate SLC7A11 and SLC3A2 for blocking glutathione biosynthesis. Meanwhile, Ni-dependent STAT3 inhibition also upregulates ACSL4 through downstream signaling and IFNγ feedback. These effects cooperate with RSL3-mediated GPX4 deactivation to induce pronounced ferroptosis. Furthermore, CaP-PEG-HA@Ni/RSL3 also impairs the immunosuppressive M2-like tumor-associated macrophages, while Ca2+ ions released from degraded ACP could chelate with lipid peroxides in ferroptotic CSCs to avoid CD8+ T-cell inhibition, thus boosting the effector function of activated CD8+ T cells. This study offers a cooperative ferroptosis-immunotherapeutic approach for the treatment of refractory cancer.

Glyco-signatures in patients with advanced lung cancer during anti-PD-1/PD-L1 immunotherapy.

Immune checkpoint inhibitors (ICIs) targeting programmed cell death 1/programmed cell death ligand-1 (PD-1/PD-L1) have significantly prolonged the survival of advanced/metastatic patients with lung cancer. However, only a small proportion of patients can benefit from ICIs, and clinical management of the treatment process remains challenging. Glycosylation has added a new dimension to advance our understanding of tumor immunity and immunotherapy. To systematically characterize anti-PD-1/PD-L1 immunotherapy-related changes in serum glycoproteins, a series of serum samples from 12 patients with metastatic lung squamous cell carcinoma (SCC) and lung adenocarcinoma (ADC), collected before and during ICIs treatment, are firstly analyzed with mass-spectrometry-based label-free quantification method. Second, a stratification analysis is performed among anti-PD-1/PD-L1 responders and non-responders, with serum levels of glycopeptides correlated with treatment response. In addition, in an independent validation cohort, a large-scale site-specific profiling strategy based on chemical labeling is employed to confirm the unusual characteristics of IgG N-glycosylation associated with anti-PD-1/PD-L1 treatment. Unbiased label-free quantitative glycoproteomics reveals serum levels' alterations related to anti-PD-1/PD-L1 treatment in 27 out of 337 quantified glycopeptides. The intact glycopeptide EEQFN 177STYR (H3N4) corresponding to IgG4 is significantly increased during anti-PD-1/PD-L1 treatment (FC=2.65, P=0.0083) and has the highest increase in anti-PD-1/PD-L1 responders (FC=5.84, P=0.0190). Quantitative glycoproteomics based on protein purification and chemical labeling confirms this observation. Furthermore, obvious associations between the two intact glycopeptides (EEQFN 177STYR (H3N4) of IgG4, EEQYN 227STFR (H3N4F1) of IgG3) and response to treatment are observed, which may play a guiding role in cancer immunotherapy. Our findings could benefit future clinical disease management.

Pyroptosis-Related Genes as Diagnostic Markers in Chronic Obstructive Pulmonary Disease and Its Correlation with Immune Infiltration.

Background: Chronic obstructive pulmonary disease (COPD) stands as a predominant cause of global morbidity and mortality. This study aims to elucidate the relationship between pyroptosis-related genes (PRGs) and COPD diagnosis in the context of immune infiltration, ultimately proposing a PRG-based diagnostic model for predicting COPD outcomes. Methods: Clinical data and PRGs of COPD patients were sourced from the GEO database. The "ConsensusClusterPlus" package was employed to generate molecular subtypes derived from PRGs that were identified through differential expression analysis and LASSO Cox analysis. A diagnostic signature including eight genes (CASP4, CASP5, ELANE, GPX4, NLRP1, GSDME, NOD1and IL18) was also constructed. Immune cell infiltration calculated by the ESTIMATE score, Stroma scores and Immune scores were also compared on the basis of pyroptosis-related molecular subtypes and the risk signature. We finally used qRT - PCR to detect the expression levels of eight genes in COPD patient and normal. Results: The diagnostic model, anchored on eight PRGs, underwent validation with an independent experimental cohort. The area under the receiver operating characteristic (ROC) curves (AUC) for the diagnostic model showcased values of 0.809, 0.765, and 0.956 for the GSE76925, GSE8545, and GSE5058 datasets, respectively. Distinct expression patterns and clinical attributes of PRGs were observed between the comparative groups, with functional analysis underscoring a disparity in immune-related functions between them. Conclusion: In this study, we developed a potential as diagnostic biomarkers for COPD and have a significant role in modulating the immune response. Such insights pave the way for novel diagnostic and therapeutic strategies for COPD.

Diagnostic, prognostic, and immunological roles of CDSN in ovarian cancer.

Globally, ovarian cancer (OC) ranks as a principal cause of cancer-related mortality in females. Immunotherapy has revolutionized the treatment of OC, but the efficacy of immunotherapy is often limited by different immune microenvironments. The objective of this research was to pinpoint and validate candidate genes with potential value as diagnostic and prognostic biomarkers and therapeutic targets in OC. Data on genes associated with gene mutation, prognostic survival, and immune infiltration in OC were procured from the Cancer Genome Atlas (TCGA). Gene differential analysis, mutation site analysis, prognosis and survival analysis, and functional and signaling pathway enrichment analysis were conducted to identify and evaluate key genes. The genes were further investigated using immune infiltration analysis, receiver operating characteristic curves, and immunohistochemistry. The impact of CDSN on OC cell proliferation was investigated utilizing CCK-8, colony formation, and apoptosis detection assays. We identified a set of genes (CDSN, WARS, and CD38) that were highly expressed in OC and significantly associated with mutations and prognosis. Immune infiltration analysis and immunohistochemistry results indicated a correlation with immune infiltration in the tumor microenvironment, particularly in antigen-presenting cells. Receiver operating characteristic curve analysis demonstrated the diagnostic potential of these three genes in OC, with all three genes showing the area under the curve (AUC) above 0.8. In vitro studies suggested that knocked down CDSN expression resulted in a marked lower in the proliferative capacity of OC cells. The candidate gene CDSN identified through bioinformatics analysis and in vitro experiments is associated with mutation and immune infiltration, showing promise as a diagnostic and prognostic biomarker, as well as a therapeutic objective in OC.