Multiple Substrates Research Articles

Thermophilic lignin-based laccase nanozyme with CuNx center for the detection of epinephrine and degradation of phenolic pollutants.

Natural laccases are a family of multi‑copper oxidases that can oxidize multiple phenol substrates and of great importance to contaminant remediation and biosensing. However, the construction of substitutes for the expensive and perishable laccase used in harsh conditions remains a great challenge. Here, we reported a novel strategy for the fabrication of copper-doped lignin-based laccase nanozymes (Cu-AL) through the coordination of aminated lignin and different copper sources. The Cu-AL prepared from CuSO4, possessed highest Cu content and Cu+ proportion, exhibited the best laccase-like activity to various phenols degradation. Strikingly, the thermophilic Cu-AL exhibited superior catalytic activity at 100 °C (3.23 times than that of 60 °C) and durability (> 50 % activity even after 160 days stored in water). Furthermore, a smartphone-based detection platform was successfully developed to achieve the rapid, convenient, and accurate detection of epinephrine concentration. In summary, this work provides a new sustainable and low-cost way to design robust laccase nanozymes from lignocellulose biomass, especially for expanding the applications of enzymatic reaction with high-temperature operation and/or long-term storage in environmental remediation and biosensing.

The E3 ubiquitin ligase RNF220 maintains hindbrain Hox expression patterns through regulation of WDR5 stability.

The spatial and temporal linear expression of Hox genes establishes a regional Hox code, which is crucial for the antero-posterior (A-P) patterning, segmentation, and neuronal circuit development of the hindbrain. RNF220, an E3 ubiquitin ligase, is widely involved in neural development via targeting of multiple substrates. Here, we found that the expression of Hox genes in the pons was markedly up-regulated at the late developmental stage (post-embryonic day E15.5) in Rnf220-/- and Rnf220+/- mouse embryos. Single-nucleus RNA sequencing (RNA-seq) analysis revealed different Hox de-repression profiles in different groups of neurons, including the pontine nuclei (PN). The Hox pattern was disrupted and the neural circuits were affected in the PN of Rnf220+/- mice. We showed that this phenomenon was mediated by WDR5, a key component of the TrxG complex, which can be polyubiquitinated and degraded by RNF220. Intrauterine injection of WDR5 inhibitor (WDR5-IN-4) and genetic ablation of Wdr5 in Rnf220+/- mice largely recovered the de-repressed Hox expression pattern in the hindbrain. In P19 embryonal carcinoma cells, the retinoic acid-induced Hox expression was further stimulated by Rnf220 knockdown, which can also be rescued by Wdr5 knockdown. In short, our data suggest a new role of RNF220/WDR5 in Hox pattern maintenance and pons development in mice.

The E3 ubiquitin ligase RNF220 maintains hindbrain Hox expression patterns through regulation of WDR5 stability

The spatial and temporal linear expression of Hox genes establishes a regional Hox code, which is crucial for the antero-posterior (A-P) patterning, segmentation, and neuronal circuit development of the hindbrain. RNF220, an E3 ubiquitin ligase, is widely involved in neural development via targeting of multiple substrates. Here, we found that the expression of Hox genes in the pons was markedly up-regulated at the late developmental stage (post-embryonic day E15.5) in Rnf220-/- and Rnf220+/- mouse embryos. Single-nucleus RNA sequencing (RNA-seq) analysis revealed different Hox de-repression profiles in different groups of neurons, including the pontine nuclei (PN). The Hox pattern was disrupted and the neural circuits were affected in the PN of Rnf220+/- mice. We showed that this phenomenon was mediated by WDR5, a key component of the TrxG complex, which can be polyubiquitinated and degraded by RNF220. Intrauterine injection of WDR5 inhibitor (WDR5-IN-4) and genetic ablation of Wdr5 in Rnf220+/- mice largely recovered the de-repressed Hox expression pattern in the hindbrain. In P19 embryonal carcinoma cells, the retinoic acid-induced Hox expression was further stimulated by Rnf220 knockdown, which can also be rescued by Wdr5 knockdown. In short, our data suggest a new role of RNF220/WDR5 in Hox pattern maintenance and pons development in mice.

Advancements in the Engineering Modification of Sucrose Phosphorylase

Sucrose phosphorylase (SPase) is a member of the glycoside hydrolase family 13, catalyzing the reversible phosphorolysis of sucrose to produce α–glucose–1–phosphate and exhibiting transglycosylation activity toward multiple substrates. Its wide substrate specificity enables the synthesis of various glycosides, which are broadly applied in food, cosmetics, and pharmaceuticals. However, the industrial application of SPase is constrained by its poor thermostability and limited transglycosylation activity. Therefore, current research focuses on enhancing the thermostability and transglycosylation activity of SPase through efficient engineering strategies based on its crystal structure and catalytic mechanism. This paper systematically reviews the crystal structure and catalytic mechanism of SPase, outlines the application of protein engineering and immobilization strategies in improving the thermostability of SPase, and analyzes how modifications at key amino acid sites affect the synthesis of typical glycosylation products. It also summarizes the limitations of SPase engineering modification strategies and explores the potential of diversified approaches for SPase modification, highlighting its broad application prospects in industrial production and laying a solid foundation for further advancements in SPase engineering modification and its industrial application.

Diagnosing Autoimmune Bullous Diseases—An Indian Perspective

Abstract Introduction: Autoimmune bullous diseases (AIBDs) are a group of illnesses characterized by autoantibodies targeting adhesion molecules in the skin and mucosa. Accurate diagnosis of the specific subtype of AIBD is crucial for effective management and predicting prognosis, especially in cases with an increased risk of malignancy. However, differentiating between subtypes can be challenging due to overlapping symptoms. Overview of diagnostic tests: Direct immunofluorescence microscopy (DIF) detects in vivo bound antibodies in perilesional tissue biopsies and provides details about the probable site of autoantibody deposition within the skin/mucosae, immunoglobulin type, and pattern of antibody deposition. Indirect immunofluorescence (IIF) microscopy with organ substrate is a minimally invasive serological test that detects circulating autoantibodies. Enzyme-linked immunosorbent assay (ELISA) quantifies serum autoantibodies against specific autoantigens. Quantitative ELISA is useful for diagnosis, monitoring therapy, and assessing disease activity. Commercially available ELISA kits, including the multi-variant ones, can detect antibodies associated with AIBDs. BIOCHIP is a technique based on IIF that offers a sensitive and specific diagnostic alternative to ELISA. It uses microarrays with multiple antigenic substrates to simultaneously screen common AIBDs. The BIOCHIP slides contain different substrates, allowing the identification of multiple types of autoantibodies in a single test. Indian context: While these diagnostic tests offer valuable insights into target antigens, antibody patterns, and disease subtypes, it is important to note that the availability of these tests is limited in most centers across India. This limitation can be attributed to factors such as the relatively higher cost of these investigations, challenges related to the stability of immuno-reactants, and a shortage of trained personnel capable of performing such tests. Conclusion: This review discusses the diagnosis of AIBDs based on resources available in India, as of today. It also provides with practically applicable diagnostic algorithms for pragmatic diagnosis of AIBDs in Indian scenario.

Interval Analysis of Volatile Solid (VS) and Biochemical Oxygen Demand (BOD) in Batch Anaerobic Fermentation of Selected Agrowaste

This study investigated the degradation of volatile solids (VS) and biochemical oxygen demand (BOD) during the anaerobic digestion of selected agro-waste, specifically cassava peels, maize husks, pig slurry, and the composite. The objective was to evaluate the biodegradability of these feedstocks, in line with their potential for biogas production. The Research was conducted at the National Centre for Energy Research and Development (NCERD) laboratory, University of Nigeria Nsukka (UNN). Batch reactors were used to conduct experiments over a period of 45 days. The digesters were operated under controlled conditions, and samples were analyzed at three (3) different points: 24 hours, peak of gas production (day 30), and at the end of the digestion (day 45). The results demonstrated that all the substrates exhibited a reduction in VS and BOD in the course of digestion. However, the most significant reduction in VS and BOD occurred around the peak of gas production. This entails that this period is critical for microbial activity and biogas yield. Corn husks had high initial VS and BOD values of 4.73±0.22 % and 92.80±3.26 mg/L respectively. However, that did not translate to higher biogas production compared with the composite that had initial values of 4.34±0.19 % and 88.00±5.50 mg/L respectively. By the end of the digestion, an average VS reduction of 65% and a BOD reduction of 70% were observed across all substrates, indicating a substantial degradation of organic material. Biogas production was better in the composite (72.580±4.53 %), an indication that higher VS and BOD do not automatically translate to higher gas yield. Thus, factors like multiple substrate interaction affect gas yield and process efficiency.

The NEDD4-binding protein N4BP1 degrades mRNA substrates through the coding sequence independent of nonsense-mediated decay

3'-Untranslated regions (3'UTRs) are recognized for their role in regulating mRNA turnover while the turnover of a specific group of mRNAs mediated by coding sequences (CDS) remains poorly understood. N4BP1 is a critical inflammatory regulator in vivo with a molecular mechanism that is not yet clearly defined. Our study reveals that N4BP1 efficiently degrades its mRNA targets via CDS rather than the 3'-UTR. This CDS-dependent mRNA turnover mechanism appears to be a general feature of N4BP1, as evidenced by testing multiple mRNA substrates, such as Fos-C, Fos-B, Jun-B and CXCL1. Detailed mapping of the motif identified a crucial 33nt (289-322) sequence near the 5'-end of Fos-C-CDS, where the presence of polyC is necessary for N4BP1-mediated degradation. Functional studies involving domain deletion and point mutations showed that both the KH and NYN domains are essential for N4BP1 to restrict mRNA substrates. The function of N4BP1 in mRNA turnover is not dependent on nonsense-mediated decay as it efficiently restricts mRNA substrates even in cells deficient in UPF1, UPF3A, and UPF3B. Additionally, the function of N4BP1 is not reliant on LUC7L3 despite its known association with this protein. Our findings suggest that N4BP1 acts as an endoribonuclease to degrade mRNA substrates primarily through coding sequences containing a C-rich motif.

Redox-Neutral, Iron-Mediated Directed C-H Activation: General Principles and Mechanistic Insights.

Experimental and computational studies have been conducted and established the general principles for enabling redox-neutral C-H activation by iron(II) complexes. The idealized octahedral iron(II) dimethyl complex, (depe)2Fe(CH3)2 (depe = 1,2-bis(diethylphosphino)ethane) promoted the directed, regioselective ortho C(sp2)-H methylation of pivalophenone. The rate of the iron(II)-mediated C(sp2)-H functionalization depended on the lability of L-type phosphine ligands, the spin state of the iron center, and the size of the X-type ligands (halide, hydrocarbyl) in P4FeIIX2 complexes. The C(sp2)-H alkylation reaction proved general among multiple substrates with directing groups including carbonyl, imines and pyridines. Among these, ketones and aldehydes were identified as optimal and were compatible with various steric environments and presence of acidic α-hydrogens. With stronger nitrogen donors, higher barriers for product-forming reductive elimination were observed. The effect of orbital hybridization on the chemoselectivity of C-H activation through a σ-CAM pathway by dn>0 transition metals was also established by studying the stoichiometric reactivity of the differentially substituted (depe)2Fe(Me)R complexes (R = alkyl, aryl), where the Fe-R bond with greater s-character preferentially promoted selective C-H activation. Deuterium labeling and kinetic studies, coupled with computational analysis, supported a pathway involving phosphine dissociation and rate-determining C-H bond activation, leading to the observed products.

Functions and mechanisms of CDPKs in plant responses to abiotic stress

Calcium-dependent protein kinases (CDPKs/CPKs) are members of the Ca2+-sensitive Ser/Thr protein kinase family and play a crucial role in plant growth and development and responses to abiotic stress. CDPKs are capable of rapidly sensing changes in intracellular Ca2+ signals and recognizing and phosphorylating specific substrates, thereby transmitting and amplifying Ca2+ signal cascades downstream. They are involved in plant responses to stress conditions such as drought, saline-alkali stress, and injuries and regulate plant growth and development, gene expression, ion channel activity, and stomatal movement. The autophosphorylation of CDPKs can affect their activities and substrate specificity. CDPKs have the ability to bind to and phosphorylate multiple substrates. In addition to participating in respiratory burst oxidase homolog (RBOH), mitogen-activated protein kinase (MAPK), and plant hormone signaling pathways, CDPKs can also bind to 14-3-3 proteins, which enables the regulation of plant responses to stress and promotes plant growth and development. This paper summarized the research findings on the discovery, structure, classification, and roles of CDPKs in plant responses to stress and proposed the future research directions, aiming to provide the genetic resources and a theoretical basis for improving the stress tolerance of crops.

Flexible multifunctional composite films for adjustable EMI shielding behavior under self-fixed deformation

With the widespread application of electromagnetic technology, the significance of intelligent electronic devices in modern communication is increasingly prominent. Despite this, the public focuses more on the harm caused by electromagnetic pollution. However, traditional EMI shielding materials struggle to meet the diverse and dynamic application requirements. Hence, developing materials capable of adjusting EMI shielding has become imperative to satisfy various scenarios. This paper presents the composite film TAPU-MXene, which is capable of adjustable EMI SE under self-fixed deformation. Introducing tannic acid increases the innermolecular interactions of TAPU. This enhancement leads to remarkable improvements in mechanical performance, achieving a stress level of 36.6 MPa at a strain of 560 %. Furthermore, the catechol groups can establish non-covalent interactions with multiple substrates, endowing the TAPU film with remarkable adhesion and self-healing capabilities. By combining the highly conductive nano-filler MXene with TAPU, the EMI shielding composite film TAPU-MXene is obtained. The EMI SE of TAPU-MXene was up to 56.7 dB when MXene loading was 3 mg cm−2. Most importantly, TAPU-MXene exhibits the ability to adjust the EMI shielding effectiveness from 56.7 dB to 2.75 dB under self-fixing deformation through shape memory mechanism, demonstrating promising applications in the field of adjustable EMI shielding materials.

Species Differences in Ezetimibe Glucuronidation

Background: Peclinical and clinical studies have revealed that ezetimibe, an approved cholesterol-absorption inhibitor, is rapidly and extensively metabolized to a more potent metabolite, ezetimibe glucuronide. Since different species are commonly used in the pharmacokinetic and pharmacodynamic studies of ezetimibe, it is essential to determine the species difference in glucuronidation of ezetimibe in order to accurately evaluate ezetimibe’s pharmacokinetics and pharmacodynamics. The purpose of the study was to compare species differences in ezetimibe glucuronidation rates using intestinal microsomes from humans, rats, mice, monkeys, and dogs. Method: Intestinal microsomes from different species were used to assess the ezetimibe glucuronidation rates. Multiple substrate concentrations at 0.5, 2, 5, 10, 20, 30, 40, and 50 µM were tested and fitted into the Michaelis–Menten model to determine the enzyme kinetic parameters. Results: The results showed that the glucuronidation rates with these tested species were significantly different. Kinetic studies revealed that the maximum metabolic rate (Vmax) was higher in monkeys (3.87 ± 0.22 nmol/mg/min) than that in rat (2.40 ± 0.148 nmol/mg/min) and mouse (2.23 ± 0.10 nmol/mg/min), and then human (1.90 ± 0.08 nmol/mg/min) and dog (1.19 ± 0.06 nmol/mg/min). The CLint was an 8.17-fold difference among these species, following the order of mouse > dog > human > rat = monkey. Conclusions: The study revealed that the rate of ezetimibe glucuronidation in the intestine was different in different species and has an impact on ezetimibe glucuronidation in the intestine. When analyzing the pharmacodynamics, pharmacokinetics, or toxicology of ezetimibe using different models, these species differences must be taken into consideration.

Abiotic Acyl Transfer Cascades Driven by Aminoacyl Phosphate Esters and Self-Assembly.

Biochemical acyl transfer cascades, such as those initiated by the adenylation of carboxylic acids, are central to various biological processes, including protein synthesis and fatty acid metabolism. Designing cascade reactions in aqueous media remains challenging due to the need to control multiple, sequential reactions in a single pot and manage the stability of reactive intermediates. Herein, we developed abiotic cascades using aminoacyl phosphate esters, the synthetic counterparts of biological aminoacyl adenylates, to drive sequential chemical reactions and self-assembly in a single pot. We demonstrated that the structural elements of amino acid side chains (aromatic versus aliphatic) significantly influence the reactivity and half-lives of aminoacyl phosphate esters, ranging from hours to days. This behavior, in turn, affects the number of couplings we can achieve in the network and the self-assembly propensity of activated intermediate structures. The cascades are constructed using bifunctional peptide substrates featuring side chain nucleophiles. Specifically, aromatic amino acids facilitate the formation of transient thioesters, which preorganized into spherical aggregates and further couple into chimeric assemblies composed of esters and thioesters. In contrast, aliphatic amino acids, which lack the ability to form such structures, predominantly undergo hydrolysis, bypassing further transformations after thioester formation. Additionally, in mixtures containing multiple aminoacyl phosphate esters and peptide substrates, we achieved selective product formation by following a distinct pathway that favors subsequent reactions through reactivity changes and self-assembly. By coupling chemical reactions with molecules of varying reactivity time scales, we can drive multiple reaction clocks with distinct lifetimes and self-assembly dynamics, facilitating precise temporal and structural regulation.

The DNA Damage Repair Function of Fission Yeast CK1 Involves Targeting Arp8, a Subunit of the INO80 Chromatin Remodeling Complex.

The CK1 family are conserved serine/threonine kinases with numerous substrates and cellular functions. The fission yeast CK1 orthologues Hhp1 and Hhp2 were first characterized as regulators of DNA repair, but the mechanism(s) by which CK1 activity promotes DNA repair had not been investigated. Here, we found that deleting Hhp1 and Hhp2 or inhibiting CK1 catalytic activities in yeast or in human cells increased double-strand breaks (DSBs). The primary pathways to repair DSBs, homologous recombination and nonhomologous end joining, were both less efficient in cells lacking Hhp1 and Hhp2 activity. To understand how Hhp1 and Hhp2 promote DNA damage repair, we identified new substrates of these enzymes using quantitative phosphoproteomics. We confirmed that Arp8, a component of the INO80 chromatin remodeling complex, is a bona fide substrate of Hhp1 and Hhp2 important for DNA repair. Our data suggest that Hhp1 and Hhp2 facilitate DNA repair by phosphorylating multiple substrates, including Arp8.

7657 Single Cell RNAseq And Omics Revealed Novel Role Of Liver Group 2 Innate Lymphocytes In Regulation Of Hepatic Gluconeogenesis

Abstract Disclosure: M. Fujimoto: None. T. Tanaka: None. Background: The liver is an important organ that maintains homeostasis of glucose metabolism in the body through gluconeogenesis. It is considered that gluconeogenesis in hepatocytes is particularly active around the portal vein. However, since excessive gluconeogenesis aggravates the pathogenesis of diabetes, it is necessary to elucidate the regulatory mechanism of gluconeogenesis. Although several studies revealed that group 2 innate lymphocytes (ILC2) contribute to blood glucose maintenance in adipose and pancreatic tissues, the contribution of liver ILC2s to glucose metabolism is unknown. This study aims to elucidate the contribution of liver ILC2s to glucose metabolism and its molecular mechanism. Methods: We administered IL-33, an endogenous ILC2 activator, to BALB/c and NSG mice, and measured fasting blood glucose levels and blood glucose elevation by gluconeogenic substrate pyruvate, and blood glucose levels in liver ILC2s transplanted NSG mice. Molecular mechanisms were analyzed by single cell-RNAseq (scRNA-seq) of liver ILC2s, lung ILC2s and hepatocytes, GATA3 transcription complex, ATAC-seq, GATA3-ChIP-seq, and Metabolomics of primary hepatocytes. Results: IL-33 strongly induced IL-13 production by liver ILC2s, lowered fasting blood glucose, and suppressed pyruvate-induced glucose elevation; these effects were not observed in NSG mice lacking immune cells including ILC2s. A hypoglycemic effect of IL-33 was observed in liver ILC2-transplanted NSG mice, but not in mice transplanted with IL-13-deficient ILC2s, suggesting the effect is IL-13-dependent. scRNA-seq results showed that liver ILC2s showed higher IL-13 expression than lung ILC2s, and IL-33 treatment suppressed the expression of gluconeogenic enzymes in the G6pc-high hepatocyte population. The interaction between liver ILC2s and G6pc-high hepatocytes via IL-13/IL-13 receptors was also demonstrated; co-culture of ILC2s with primary cultured hepatocytes resulted in decreased expression of hepatocyte gluconeogenic enzymes and accumulation of multiple gluconeogenic substrates. In addition, IL-13 neutralizing antibody treatment attenuated the effect of the decreased expression of gluconeogenic enzymes in hepatocytes. Transcription factor GATA3 complex analysis and GATA3-ChIPseq suggested binding of GATA3 of the AP-1 family (JunB) in liver ILC2s. Overexpression, knockdown, and scRNA-seq results suggest that AP1 may act in a GATA3-repressive manner in liver ILC2s. Discussion The functional characteristics of liver ILC2s, hepatocyte heterogeneity and subcluster were demonstrated by scRNA-seq, suggesting that liver ILC2s may directly suppress hepatocyte gluconeogenesis via IL-13. This may play a novel role in the homeostasis of hepatic glucose metabolism. Presentation: 6/1/2024

Microbial degradation of the waste jute fiber and sawdust fiber-based epoxy composites in drainage system

The non-biodegradable nature of polymers presents a considerable environmental hazard, mainly when they accumulate in drainage systems and pollute the water. The application of natural fiber composites has the potential to offer a feasible resolution to address this problem, as natural fibers possess inherent biodegradability. This study examined the degradation ability of epoxy composites made with 5 wt% waste jute fiber and 5 wt% waste sawdust fiber when subjected to drainage water for one year. The composites comprising jute fiber and sawdust demonstrated a reduction in tensile strength by 57 % and 40 %, respectively, because of biodegradation caused by microorganisms. The microorganism consumed the fiber for energy, resulting in significant weight and flexural strength loss. The weathered waste jute and sawdust fiber composite samples displayed an additional peak at a wavenumber of 1700 cm−1 for FTIR analysis, indicating the presence of the C=O group and reflecting CO2 production. The SEM image reveals the presence of clusters, biofilms, and colonies of microorganisms on the surface of the composites, indicating that the microbes were utilizing the fibers and matrix as a substrate for growth and multiplication. This research contributes to the understanding of the degradation mechanisms of sustainable composites and provides insight into the advancement of eco-friendly materials to reduce water pollution.

ATP-binding cassette transporter TaABCG2 contributes to Fusarium head blight resistance by mediating salicylic acid transport in wheat.

ATP-binding cassette (ABC) transporters hydrolyse ATP to transport various substrates. Previous studies have shown that ABC transporters are responsible for transporting plant hormones and heavy metals, thus contributing to plant immunity. Herein, we identified a wheat G-type ABC transporter, TaABCG2-5B, that responds to salicylic acid (SA) treatment and is induced by Fusarium graminearum, the primary pathogen causing Fusarium head blight (FHB). The loss-of-function mutation of TaABCG2-5B (ΔTaabcg2-5B) reduced SA accumulation and increased susceptibility to F. graminearum. Conversely, overexpression of TaABCG2-5B (OE-TaABCG2-5B) exerted the opposite effect. Quantification of intracellular SA in ΔTaabcg2-5B and OE-TaABCG2-5B protoplasts revealed that TaABCG2-5B acts as an importer, facilitating the transport of SA into the cytoplasm. This role was further confirmed by Cd2+ absorption experiments in wheat roots, indicating that TaABCG2-5B also participates in Cd2+ transport. Thus, TaABCG2-5B acts as an importer and is crucial for transporting multiple substrates. Notably, the homologous gene TaABCG2-5A also facilitated Cd2+ uptake in wheat roots but did not significantly influence SA accumulation or FHB resistance. Therefore, TaABCG2 could be a valuable target for enhancing wheat tolerance to Cd2+ and improving FHB resistance.

Revisiting the activity of two poly(vinyl chloride)- and polyethylene-degrading enzymes

Biocatalytic degradation of non-hydrolyzable plastics is a rapidly growing field of research, driven by the global accumulation of waste. Enzymes capable of cleaving the carbon-carbon bonds in synthetic polymers are highly sought-after as they may provide tools for environmentally friendly plastic recycling. Despite some reports of oxidative enzymes acting on non-hydrolyzable plastics, including polyethylene or poly(vinyl chloride), the notion that these materials are susceptible to efficient enzymatic degradation remains controversial, partly driven by a general lack of studies independently reproducing previous observations. Here, we attempt to replicate two recent studies reporting that deconstruction of polyethylene and poly(vinyl chloride) can be achieved using an insect hexamerin from Galleria mellonella (so-called “Ceres”) or a bacterial catalase-peroxidase from Klebsiella sp., respectively. Reproducing previously described experiments, we do not observe any activity on plastics using multiple reaction conditions and multiple substrate types. Digging deeper into the discrepancies between the previous data and our observations, we show how and why the original experimental results may have been misinterpreted.

Immunoprognostic analysis of indoleamine 2,3-dioxygenase 1 in patients with cervical cancer.

The incidence of cervical cancer is increasing. Immunotherapies show better patient outcomes than monotherapies; however, the mainstay treatment for cervical cancer remains surgery and chemotherapy. Indoleamine 2,3-dioxygenase 1 (IDO1) acts on multiple tryptophan substrates, exhibiting antitumor, immunomodulatory, and antioxidant activities. Despite the association of elevated IDO1 expression with unfavorable outcomes in various cancers, its precise function in cervical cancer remains ambiguous. Here, we explored the prognostic significance of IDO1 in cervical carcinoma. Gene expression datasets were obtained from The Cancer Genome Atlas. Gene Expression Omnibus datasets were used for differential expression and functional correlation analyses. Using Human Protein Atlas alongside Tumor-Immune System Interaction Database, we assessed the association of IDO1 with survival rates. Given the link between cervical cancer prognosis and immune invasion, CIBERSORT was used to assess the connection between immune cells and IDO1, while the percentage of tumor-penetrating immune cells based on IDO1 expression in cervical cancer patients was analyzed using Tumor-Immune System Interaction Database. Incorporating a clinicopathological characteristic-based risk score model with IDO1 risk score, we devised a nomogram to predict cervical cancer patient survival. The effects of IDO1 in immune regulation and its prognostic significance were validated using data from patients with cervical cancer obtained from The Cancer Imaging Archive database. Compared with that in normal cervical tissues, IDO1 expression was significantly upregulated in cervical cancer tissues and significantly correlated with cervical cancer progression and prognosis. IDO1 expression showed a positive association with monocyte and macrophage abundance, while exhibiting a negative correlation with that of endothelial cells and eosinophils. Cox regression analyses highlighted IDO1 as the core immune gene implicated in cervical cancer. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses revealed an association of IDO1 with the metabolic pathways of tryptophan, phenylalanine, and tyrosine. Univariate and multivariate analyses revealed that elevated IDO1 expression correlates markedly with cervical cancer outcomes, suggesting it as a promising therapeutic target. The Cancer Imaging Archive data analysis revealed that the impact of anti-PD1 and CTLA4 therapy is more pronounced in cervical cancer patients exhibiting elevated IDO1 expression. IDO1 is a potential target for immunotherapy for cervical cancer.

Nonconventional Fluorescent Non‐Isocyanate Polyurethane Foams for Multipurpose Sensing Applications

Fluorescent foams with interconnected pores are attractive for the detection and quantification of various products. However, many fluorescent probes are suffering from aggregation‐caused fluorescence quenching in their solid/aggregated state, are costly, and/or not straightforward to incorporate in foams, limiting their utility for this application. Herein, non‐isocyanate polyurethane foams, prepared by the simple water‐induced self‐blowing process, present a nonconventional fluorescence behaviour, i.e. they are intrinsically fluorescent with a multicolor emission without requiring ex‐situ traditional fluorescent probes. These foams demonstrate utility for capturing‐sensing gaseous formaldehyde (an emblematic indoor air pollutant), as well as for detecting and quantifying various metal ions (Fe2+, Cu2+, Fe3+, Hg2+). They are also able to selectively sense tetracycline antibiotic in a ratiometric way with a high sensitivity. By exploiting the unique multicolor photoluminescent foam properties, a smartphone‐compatible device is used for the facile antibiotic quantification. This nonconventional fluorescence behaviour is discussed experimentally and theoretically, and is mainly based on clusteroluminescence originating from multiple hydrogen bonding and hetero‐atomic sub‐luminophores, thus from aggregation‐induced emission luminogens that are naturally present in the foams. This work illustrates that easily accessible non‐conventional fluorescent NIPU foams characterized by a modular emission wavelength have an enormous potential for multiple substrates detection and quantification.

Nonconventional Fluorescent Non-Isocyanate Polyurethane Foams for Multipurpose Sensing Applications.

Fluorescent foams with interconnected pores are attractive for the detection and quantification of various products. However, many fluorescent probes are suffering from aggregation-caused fluorescence quenching in their solid/aggregated state, are costly, and/or not straightforward to incorporate in foams, limiting their utility for this application. Herein, non-isocyanate polyurethane foams, prepared by the simple water-induced self-blowing process, present a nonconventional fluorescence behaviour, i.e. they are intrinsically fluorescent with a multicolor emission without requiring ex situ traditional fluorescent probes. These foams demonstrate utility for capturing-sensing gaseous formaldehyde (an emblematic indoor air pollutant), as well as for detecting and quantifying various metal ions (Fe2+, Cu2+, Fe3+, Hg2+). They are also able to selectively sense tetracycline antibiotic in a ratiometric way with a high sensitivity. By exploiting the unique multicolor photoluminescent foam properties, a smartphone-compatible device is used for the facile antibiotic quantification. This nonconventional fluorescence behaviour is discussed experimentally and theoretically, and is mainly based on clusteroluminescence originating from multiple hydrogen bonding and hetero-atomic sub-luminophores, thus from aggregation-induced emission luminogens that are naturally present in the foams. This work illustrates that easily accessible non-conventional fluorescent NIPU foams characterized by a modular emission wavelength have an enormous potential for multiple substrates detection and quantification.