Exploration of the combined role of immune checkpoints and immune cells in the diagnosis and treatment of ankylosing spondylitis: a preliminary study immune checkpoints in ankylosing spondylitis.

OBJECTIVE: Immune checkpoints have emerged as promising therapeutic targets for autoimmune diseases. However, the specific roles of immune checkpoints in the pathophysiology of ankylosing spondylitis (AS) remain unclear. METHODS: Hip ligament samples were obtained from two patient groups: those with AS and femoral head deformity, and those with femoral head necrosis but without AS, undergoing hip arthroplasty. Label-Free Quantification (LFQ) Protein Park Analysis was used to identify the protein composition of the ligaments. Peripheral blood samples of 104 AS patients from public database were used to validate the expression of key proteins. KEGG, GO, and GSVA were employed to explore potential pathways regulated by immune checkpoints in AS progression. xCell was used to calculate cell infiltration levels, LASSO regression was applied to select key cells, and the correlation between immune checkpoints and immune cells was analyzed. Drug sensitivity analysis was conducted to identify potential therapeutic drugs targeting immune checkpoints in AS. The expression of key genes was validated through immunohistochemistry (IHC). RESULTS: HLA-DMB and HLA-DPA1 were downregulated in the ligaments of AS and this has been validated through peripheral blood datasets and IHC. Significant differences in expression were observed in CD8 + Tcm, CD8 + T cells, CD8 + Tem, osteoblasts, Th1 cells, and CD8 + naive T cells in AS. The infiltration levels of CD8 + Tcm and CD8 + naive T cells were significantly positively correlated with the expression levels of HLA-DMB and HLA-DPA1. Immune cell selection using LASSO regression showed good predictive ability for AS, with AUC values of 0.98, 0.81, and 0.75 for the three prediction models, respectively. Furthermore, this study found that HLA-DMB and HLA-DPA1 are involved in Th17 cell differentiation, and both Th17 cell differentiation and the NF-kappa B signaling pathway are activated in the AS group. Drug sensitivity analysis showed that AS patients are more sensitive to drugs such as doramapimod and GSK269962A. CONCLUSION: Immune checkpoints and immune cells could serve as avenues for exploring diagnostic and therapeutic strategies for AS.

Rational Design of Amorphous Carbon-Coated Laminar-Structured Wood for Integrating Repeatable Early Fire Detection and High-Temperature Affordable Flexible Pressure Sensing in One System.

High-temperature affordable flexible polymer-based pressure sensors integrated with repeatable early fire warning service are strongly desired for harsh environmental applications, yet their creation remains challenging. This work proposed an approach for preparing such advanced integrated sensors based on silver nanoparticles and an ammonium polyphosphate (APP)-modified laminar-structured bulk wood sponge (APP/Ag@WS). Such integrated sensors demonstrated excellent fire warning performance, including a short response time (minimum of 0.44 s), a long-lasting alarm time (>750 s), and reliable repeatability. Moreover, it achieved high-temperature affordable flexible pressure sensing that exhibited an almost unimpaired working range of 0-7.5 kPa and a higher sensitivity (in the low-pressure range, maximum to 226.03 kPa-1) after fire. The high stability was attributed to reliable structural elasticity, and the wood-derived amorphous carbon is capable of repeatable fire warnings. Finally, a Ag@APP/WS-based wireless fire alarm system that realized reliable house fire accident detection was demonstrated, showing great promise for smart firefighting application.

A C-Type Lectin, RfCTL27, Activates the Immune Defense in the Red Palm Weevil Rhynchophorus ferrugineus (A.G. Olivier, 1791) (Coleoptera: Curculionidae: Dryophthorinae) by the Recognition of Gram-Negative Bacteria.

Red palm weevil, Rhynchophorus ferrugineus (Olivier), is a palm tree insect pest that causes significant damage in the many countries from the Indian sub-continent and southeast Asia into date palm-growing countries of Africa, the Middle East, and the Mediterranean Basin. This study is aimed at determining the role of a C-type lectin, RfCTL27, in the immune defense of RPW larvae. RfCTL27 is a secreted protein that possesses a QPD motif, being integral for the discrimination of Gram-negative bacteria. The abundance of RfCTL27 transcripts in the gut and fat body was significantly higher than that in other tissues. Six hours after injection of Escherichia coli, the expression level of RfCTL27 in the gut of RPW larvae was significantly elevated compared with other groups. At 12 h after injection of E. coli, the expression of RfCTL27 in fat body was dramatically induced in contrast with other treatments. More interestingly, the ability of RPW larvae to clear the pathogenic bacteria in the body cavity and gut was markedly impaired by the silencing of RfCTL27. Additionally, the expression levels of two antimicrobial peptide genes, RfCecropin in the gut and RfDefensin in fat body of RPW larvae, were significantly decreased. Taken together, these data suggested that RfCTL27 can recognize the Gram-negative bacterium and activate the expression of antimicrobial peptides to remove the invaded bacterial pathogens. This study provides a new scientific basis for improving the control efficiency of pathogenic microorganisms against red palm weevils in production practice.

An Important Role in Novel Immune Mechanism and Diagnostic Model of Ankylosing Spondylitis: The CeRNA-ADRB2 Network.

Objective: The mechanism of ankylosing spondylitis (AS) remains unclear, and clinical diagnosis still pose challenges. This study aims to explore potential regulatory mechanisms underlying AS and develop a novel diagnostic model. Methods: Interspinous ligament (ISL) tissues were collected from control samples and ankylosing spondylitis with kyphotic deformity (AS-KD) samples during surgery, followed by high-throughput sequencing. By integrating gene expression profiles from publicly available AS peripheral blood (PB) samples, differentially expressed immune genes (DEIRGs) were identified. Through gene set enrichment analysis(GSEA), gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses, the regulatory mechanisms of the immune gene family in AS were explored. A diagnostic model for AS were constructed and validated it externally. Additionally, a competing endogenous RNA(ceRNA)-protein regulatory network was built for key immune genes. Results: Adrenergic receptor beta 2 (ADRB2) was downregulated in both ISL and PB samples. It was enriched in common pathways, including natural killer cell-mediated cytotoxicity, B cell receptor signaling pathway, Th1 and Th2 cell differentiation. Using the LASSO algorithm, 12 DEIRGs were identified, including the downregulated ADRB2. Based on the DEIRGs family, a novel diagnostic model was constructed with an AUC of 0.87 for the validation set and 0.7 for the test set. The AUC for ADRB2 alone was 0.75. Subgrouping AS based on these immune genes revealed a close association with neutrophils. GSEA and KEGG analysis of ISL, PB, and subgrouping of AS showed that ADRB2 may be involved in regulating the T cell receptor signaling pathway. Immune infiltration analysis indicated a decrease in CD8+ T cell infiltration, which was positively correlated with ADRB2. ADRB2 in AS-KD was regulated by multiple ceRNA-protein (lncRNA-[hsa-miR-513a-5p]-mRNA-protein). Conclusion: The immune gene family, especially ADRB2, participates in the mechanism and contributes to the diagnosis of AS.

Reconstruction of Cellulose Intermolecular Interactions from Hydrogen Bonds to Dynamic Covalent Networks Enables a Thermo-processable Cellulosic Plastic with Tunable Strength and Toughness.

Its excellent renewability and biodegradability make cellulose an attractive resource to prepare fossil-based plastic alternatives. However, cellulose itself exhibits strong intermolecular hydrogen bond (H-bond) interactions, significantly restricting the mobility of cellulose chains, thus leading to poor thermo-processing performance. Here, we reconstructed the intermolecular interactions of cellulose chains via replacing the original H-bonds with dynamic covalent bonds. By this, cellulose can be easily thermo-processed into a cellulosic plastic under mild conditions (70 °C). Through adjusting the chemical structure of dynamic covalent networks, the cellulosic plastic shows tunable mechanical strength (3.0-33.5 MPa) and toughness (43-321 kJ m-2). The cellulosic plastic also exhibits excellent resistance to water, organic solvent, acid solution, alkali solution, and high temperature (>400 °C). Moreover, it owns good chemical and biological degradability and recyclability. This work provides an effective method to develop high-performance cellulosic plastics for fossil-based plastic substitution.

Clinical model of pulmonary metastasis in patients with osteosarcoma: A new multiple machine learning-based risk prediction.

BACKGROUND: Metastasis is one of the most significant prognostic factors in osteosarcoma (OS). The goal of this study was to construct a clinical prediction model for OS patients in a population cohort and to evaluate the factors influencing the occurrence of pulmonary metastasis. METHODS: We collected data from 612 patients with osteosarcoma (OS), and 103 clinical indicators were collected. After the data were filtered, the patients were randomly divided into training and validation cohorts by using random sampling. The training cohort included 191 patients with pulmonary metastasis in OS and 126 patients with non-pulmonary metastasis, and the validation cohort included 50 patients with pulmonary metastasis in OS and 57 patients with non-pulmonary metastasis. Univariate logistics regression analysis, LASSO regression analysis and multivariate logistic regression analysis were performed to identify potential risk factors for pulmonary metastasis in patients with osteosarcoma. A nomogram was developed that included risk influencing variables selected by multivariable analysis, and used the concordance index (C-index) and calibration curve to validate the model. Receiver operating characteristic curve (ROC), decision analysis curve (DCA) and clinical impact curve (CIC) were employed to assess the model. In addition, we used a predictive model on the validation cohort. RESULTS: Logistic regression analysis was used to identify independent predictors [N Stage + Alkaline phosphatase (ALP)+Thyroid stimulating hormone (TSH)+Free triiodothyronine (FT3)]. A nomogram was constructed to predict the risk of pulmonary metastasis in patients with osteosarcoma. The performance was evaluated by the concordance index (C-index) and calibration curve. The ROC curve provides the predictive power of the nomogram (AUC = 0.701 in the training cohort, AUC = 0.786 in the training cohort). Decision curve analysis (DCA) and clinical impact curve (CIC) demonstrated the clinical value of the nomogram and higher overall net benefits. CONCLUSIONS: Our study can help clinicians effectively predict the risk of lung metastases in osteosarcoma with more readily available clinical indicators, provide more personalized diagnosis and treatment guidance, and improve the prognosis of patients. MINI ABSTRACT: A new risk model was constructed to predict the pulmonary metastasis in patients with osteosarcoma based on multiple machine learning.

A Biodegradable, Waterproof, and Thermally Processable Cellulosic Bioplastic Enabled by Dynamic Covalent Modification.

The growing environmental concern over petrochemical-based plastics continuously promotes the exploration of green and sustainable substitute materials. Compared with petrochemical products, cellulose has overwhelming superiority in terms of availability, cost, and biodegradability; however, cellulose's dense hydrogen-bonding network and highly ordered crystalline structure make it hard to be thermoformed. A strategy to realize the partial disassociation of hydrogen bonds in cellulose and the reassembly of cellulose chains via constructing a dynamic covalent network, thereby endowing cellulose with thermal processability as indicated by the observation of a moderate glass transition temperature (Tg  = 240 °C), is proposed. Moreover, the cellulosic bioplastic delivers a high tensile strength of 67 MPa, as well as excellent moisture and solvent resistance, good recyclability, and biodegradability in nature. With these advantageous features, the developed cellulosic bioplastic represents a promising alternative to traditional plastics.

A peptidoglycan recognition protein regulates the immune response of Rhynchophorus ferrugineus Olivier (Coleoptera: Dryophthoridae) during exposure to pathogenic Gram-positive bacteria and fungi.

Red palm weevil (RPW), Rhynchophorus ferrugineus Olivier, is a tremendously destructive insect pest of palm trees worldwide. Although some biological agents have been used to fight against RPW larvae, the control efficiency is still dissatisfactory. This study aimed to determine the role of a peptidoglycan recognition protein (PGRP), RfPGRP-S3, in RPW immunity. RfPGRP-S3 is a secreted protein with a DF (Asp85-Phe86) motif, implying that it can discriminate Gram-positive bacteria. The abundance of RfPGRP-S3 transcripts in the hemolymph was significantly higher than that in other tissues. The expression of RfPGRP-S3 can be markedly induced by challenge with Staphylococcus aureus and Beauveria bassiana. After RfPGRP-S3 was silenced, the ability of individuals to clear the pathogenic bacteria in the body cavity and gut was significantly compromised. Furthermore, silencing RfPGRP-S3 dramatically impaired the survival rate of RPW larvae upon challenge with S. aureus. RT‒qPCR revealed that the expression levels of RfDefensin in the fat body and gut were decreased by RfPGRP-S3 silencing. Taken together, these results demonstrated that RfPGRP-S3 acts as a circulating receptor to promote the expression of the antimicrobial peptide gene upon the discrimination of pathogenic microbes.

Supramolecular structure of microwave treated bamboo for production of lignin-containing nanocellulose by oxalic acid dihydrate.

Supramolecular structure of cellulosic materials from microwave treatment were throughly investigated for production of lignin-containing nanocellulose. The results revealed that both the intermolecular and intramolecular hydrogen bonds were altered by microwave irradiation. Cellulose Iß was the main component in microwave treated bamboo (MTB) with smaller interplanar spacing, and the cellulose molecules were loosely connected resulting in a loose structure. Thereafter, MTB was used to produce lignin-containing nanocellulose by using oxalic acid dihydrate (OAD) to test the feasibility on its efficiency. The chemical consumed for the preparation of lignin-containing nanocellulose (LCN) with a comparable yield (68.08-82.33 %) from MTB was merely 1/10 that from conventional cellulosic materials, indicating the supramolecular structural changes of bamboo cellulose induced by microwave treatment provided suitable conditions for the subsequent hydrolysis of OAD to prepare LCN. The LCN was further added into the polyvinyl alcohol (PVA) matrix endowed excellent UV shielding property and thermal stability for the PVA/LCN films. This study was aimed to provide an environmentally friendly method on the production and application of LCN from bamboo by employing microwave treatment from the perspective of supramolecular level.

Synthesis of cellulose II-based spherical nanoparticle microcluster adsorbent for removal of toxic hexavalent chromium.

Since natural cellulose is mostly cellulose I and has a fibrous form, most cellulose-based adsorbents are fibrous/rod-shaped and exhibit the cellulose I crystal structure. This study reports a cellulose II-based spherical nanoparticle microcluster adsorbent (SNMA), synthesized from biomass by a bottom-up approach, for removing toxic hexavalent chromium (Cr(VI)). The basic structure of SNMA was investigated. Notably, the prepared adsorbent was a microcluster composed of spherical nanoparticles, while exhibiting cellulose II crystal structure, resulting in higher thermal stability and significantly enhanced adsorption performance. The adsorption process and mechanism of SNMA on Cr(VI) were studied in detail. The SNMA achieved a high adsorption capacity (225.94 mg/g) and receptor site density. The SNMA is expected to be used as a bio-based spherical nanoparticle microcluster adsorbent platform for the adsorption of different toxic substances by changing the surface functional groups of its components, spherical nanoparticles.

Thermo-processable chitosan-based plastic substitute with self-adaptiveness and closed-loop recyclability.

The increasing environmental burden generated by disposable plastic wastes makes the development of sustainable substitute materials an emergent task. As one of the most abundant bioresources, chitosan (CS) has been considered as a potential candidate for plastic substitution. Conventionally, CS-based materials are fabricated through a solution-processing procedure due to the high crystallinity of CS. Herein, we designed a CS-based material via integrating CS into the network of polyimine (PI), which shows thermomechanical processability similar to plastics. Strong interactions were achieved through dynamic imine bond and hydrogen bond and thus formed a thermo-processable dynamic composite network. These CS-based plastic substitutes exhibit exceptional mechanical performances, excellent thermal/chemical stability, and a series of self-adaptiveness, including re-healing, reprocessing and multi-layer laminating. Notably, CPs can be easily degraded and 100% recycled for the production of next-generation materials. This work provides an alternative route to produce green and sustainable biomass materials as a plastic substitute.

Current understanding and perspectives on the potential mechanisms of immune priming in beetles.

Beetles are the most diverse group of insects in Insecta which can be found in almost every habitat and environment on Earth. The possessing of the rapid and effective immune defenses is one of the important factors for their success. It is generally recognized that beetles only rely on the non-specific innate immune defense, without immunological memory, to fight against pathogens. However, there was cumulative evidence for the innate immune memory in invertebrates, including beetles, over the last decades, implying that insect innate immunity is more complex and has more features than previously thought. In beetles, it has been well documented that the specific or nonspecific enhanced immunocompetence can persist throughout development within generations and can even be transferred to the descendents in the next generation. Although insect immune priming might be shaped by epigenetic modifications and transferring effectors, mRNA and microbial signals, the solid experimental evidence to support the causal relationship between any of them and immune priming is still scarce. The combined usage of 'omics' approaches and CRISPR/Cas9 in the appropriate insect models with well-known genetic background, Tribolium castaneum and Tenebrio molitor, will help us to decipher the molecular mechanisms by which immune priming occurs in beetles in depth.

The Effect of Gut Bacteria on the Physiology of Red Palm Weevil, Rhynchophorus ferrugineus Olivier and Their Potential for the Control of This Pest.

Red Palm Weevil (RPW), Rhynchophorus ferrugineus Olivier, is a notorious pest, which infests palm trees and has caused great economic losses worldwide. At present, insecticide applications are still the main way to control this pest. However, pesticide resistance has been detected in the field populations of RPW. Thus, future management strategies based on the novel association biological control need be developed. Recent studies have shown that the intestinal tract of RPW is often colonized by multiple microbial species as mammals and model insects, and gut bacteria have been found to promote the growth, development and immune activity of RPW larvae by modulating nutrient metabolism. Furthermore, two peptidoglycan recognition proteins (PGRPs), PGRP-LB and PGRP-S1, can act as the negative regulators to modulate the intestinal immunity to maintain the homeostasis of gut bacteria in RPW larvae. Here, we summarized the current knowledge on the gut bacterial composition of RPW and their impact on the physiological traits of RPW larvae. In contrast with metazoans, it is much easier to make genetic engineered microbes to produce some active molecules against pests. From this perspective, because of the profound effects of gut bacteria on host phenotypes, it is promising to dissect the molecular mechanisms behind their effect on host physiology and facilitate the development of microbial resource-based management methods for pest control.

A Truxenone-based Covalent Organic Framework as an All-Solid-State Lithium-Ion Battery Cathode with High Capacity.

All-solid-state lithium ion batteries (LIBs) are ideal for energy storage given their safety and long-term stability. However, there is a limited availability of viable electrode active materials. Herein, we report a truxenone-based covalent organic framework (COF-TRO) as cathode materials for all-solid-state LIBs. The high-density carbonyl groups combined with the ordered crystalline COF structure greatly facilitate lithium ion storage via reversible redox reactions. As a result, a high specific capacity of 268 mAh g-1 , almost 97.5 % of the calculated theoretical capacity was achieved. To the best of our knowledge, this is the highest capacity among all COF-based cathode materials for all-solid-state LIBs reported so far. Moreover, the excellent cycling stability (99.9 % capacity retention after 100 cycles at 0.1 C rate) shown by COF-TRO suggests such truxenone-based COFs have great potential in energy storage applications.

All-Biomass Fluorescent Hydrogels Based on Biomass Carbon Dots and Alginate/Nanocellulose for Biosensing.

This work describes an all-biomass fluorescent hydrogel fabricated by functionalizing alginate (ALg) and cellulose nanofibers (CNF) hydrogels with fluorescent biomass carbon dots (CQDs) derived from glucose, xylose, and glucosamine. The biomass CQDs played dual functions in the composite hydrogels: first, endowing hydrogels with good fluorescent characters; second, enhancing the mechanical properties of hydrogels because of the cross-linking effect of the abundant oxygen-containing groups or amino groups on surface with ALg or CNF. The elastic modulus of ALg hydrogel and CNF hydrogel was increased by 4.7 times and 1.5 times, respectively, by the adding CQDs. As a proof of concept, ALg/CQDs-3 hydrogel and CNF/CQDs-3 hydrogel were used to detect Fe3+ ions and gold nanoparticle (AuNPs) in aqueous solution, showing high sensitivity. The prepared all-biomass fluorescent hydrogels hold great potential in biological imaging, biosensing, and biological monitoring fields.