Enhanced Electrochemical Performance and Cycling Stability of the (NH4)8[VIV12VV7O41(OH)9]·11H2O Cathode in Aqueous Zinc Ion Batteries.

Although vanadium-based compounds possess several advantageous characteristics, such as multivalency, open structure, and high theoretical specific capacity, which render them highly promising candidates for cathode materials in aqueous zinc ion batteries (AZIBs), their large-scale application still necessitates addressing the challenges posed by slow kinetics resulting from low conductivity and capacity degradation caused by material dissolution. Therefore, we have successfully synthesized high-purity mixed multivalent (NH4)8[VIV12VV7O41(OH)9]·11H2O (NVO) crystalline materials via a liquid-phase precipitation modulation method and employed it as an innovative AZIB cathode material for the first time. It exhibits a remarkable reversible specific capacity of 240 and 102.2 mAh g-1 after undergoing 1000 cycles at current densities of 1 and 5 A g-1, respectively, highlighting its exceptional cycling stability and electrochemical performance. The results from cyclic voltammetry (CV) and GITT tests demonstrate that the dominant factor influencing the charge storage is the pseudocapacitive behavior, which is accompanied by an exceptionally high diffusion coefficient of Zn2+ at a rate of 10-10 cm2 s-1. The highly reversible intercalation-deintercalation of Zn2+ in NVO/Zn cells is demonstrated through ex-situ TEM, XRD, and XPS analyses. This work provides a benchmark for the development of high-performance POV electrode materials.

Microenvironment-Responsive Antibacterial, Anti-Inflammatory, and Antioxidant Pickering Emulsion Stabilized by Curcumin-Loaded Tea Polyphenol Particles for Accelerating Infected Wound Healing.

Multiphase Pickering emulsions, including two or more active agents, are of great importance to effectively manage complicated wounds. However, current strategies based on Pickering emulsions are still unsatisfying since they involve only stabilization by inactive particles and encapsulation of the hydrophobic drugs in the oil phase. Herein, thyme essential oil (TEO) was encapsulated in the shell of functional tea polyphenol (TP)-curcumin (Cur) nanoparticles (TC NPs) to exemplarily develop a novel Pickering emulsion (TEO/TC PE). Hydrophobic Cur was loaded with hydrophilic TP to obtain TC NPs, and under homogenization, these TC NPs adsorbed on the surface of TEO droplets to form a stable core-shell structure. Owing to such an oil-in-water (O/W) structure, the sequential release of the first Cur from pH-responsive disintegrated TC NPs and then the leaked TEO from the emulsion yielded synergetic functions of TEO/TC PE, leading to enhanced antibacterial, biofilm elimination, antioxidant, and anti-inflammatory activities. This injectable TEO/TC PE was applied to treat the infected full-thickness skin defects, and satisfactory wound healing effects were achieved with rapid angiogenesis, collagen deposition, and skin regeneration. The present TEO/TC PE constituted entirely of plant-sourced active products is biosafe and expected to spearhead the future development of novel wound dressings.

Cinquefoil Knot Possessing Dynamic and Tunable Metal Coordination.

While the majority of knots are made from the metal-template approach, the use of entangled, constrained knotted loops to modulate the coordination of the metal ions remains inadequately elucidated. Here, we report on the coordination chemistry of a 140-atom-long cinquefoil knotted strand comprising five tridentate and five bidentate chelating vacancies. The knotted loop is prepared through the self-assembly of asymmetric "3 + 2" dentate ligands with copper(II) ions that favor five-coordination geometry. The formation of the copper(II) pentameric helicate is confirmed by X-ray crystallography, while the corresponding copper(II) knot is characterized by XPS and LR-/HR ESI-MS. Upon removal of the original template, the knotted ligand facilitates zinc(II) ions, which typically form four- or six-coordination geometries, resulting in the formation of an otherwise inaccessible zinc(II) metallic knot with coordinatively unsaturated metal centers. The coordination numbers and geometries of the zinc(II) cations are undoubtedly determined by X-ray crystallography. Despite the kinetically labile nature and high reversibility of the zinc(II) complex preventing the detection of 5-to-6 coordination equilibrium in solution, the effects on metal-ion coordination induced by knotting hold promise for fine-tuning the coordination of metal complexes.

Functional black phosphorus-based sensors for food safety applications: A review.

Food safety has garnered global attention, necessitating advanced methods for the quick and accurate detection of contaminants. Sensors, notable for their ease of use, high sensitivity, and fast analysis, are prominent. Two-dimensional (2D) nanomaterials have been employed to improve sensor performance. Particularly, black phosphorus (BP) stands out with its multifunctional capabilities, attributed to unique layered structure, ultra-high charge mobility, easy surface functionalization, enhanced optical absorption, and tunable direct bandgap. These characteristics suggest that BP could significantly enhance sensor selectivity, sensitivity, and response speed for contaminant detection. Despite numerous studies on BP-based sensors in food safety, few reviews have been comprehensively summarized. Moreover, challenges in BP's preparation and stability restrict its wider use. This paper reviews recent research on BP's role in food safety, covering preparation, passivation, and applications. Through analysis of challenges and prospects, this review aims to provide insightful guidance for upcoming research in this area.

Effect of Additives on the Morphology of γ-Aminobutyric Acid Crystals.

The effect of surfactant, polymer, and tailor-made additives on the crystallization of γ-aminobutyric acid (GABA) was studied in this work. Cooling crystallization of GABA in water yielded plate-like crystals. In the presence of sodium stearate, polyhedral block-like crystals of GABA were obtained. Hydroxyethyl cellulose (HEC) led to rod-like crystals, in which the morphology was associated with additive concentrations. Six kinds of amino acids were used as tailor-made additives, and they exhibit different influences on crystal shape and size. The induction time of GABA was determined in the absence and presence of additives. The results showed that sodium stearate promoted nucleation, while HEC, l-Lysine, l-histidine, and l-tyrosine inhibited nucleation. Crystal face indexing, Hirshfeld surface analysis, and molecular dynamics (MD) simulation in aqueous solution-crystal systems were carried out to investigate the affecting factors of different crystal faces. The polymer additive was selected as an example during MD simulation to calculate intermolecular interactions between the crystal face and solvent or additive. The effect of the additive on the mobility of the solute in solution was also evaluated by mean-square displacement. The additive offers an effective approach for changing crystal morphology and particle size and adapting it to different production requirements.

Genome-Wide Identification and Expression Analysis of ADK Gene Family Members in Cotton under Abiotic Stress.

Adenosine kinase (ADK) is a key enzyme widely distributed in plants, playing an important role in maintaining cellular energy homeostasis and regulating plant growth, development, and responses to environmental stresses. However, research on ADK genes in cotton (Gossypium hirsutum), an economically significant crop, has been limited. This study identified 92 ADK genes from four cotton species (G. arboreum, G. raimondii, G. hirsutum, and G. barbadense) using HMMER and Local BLASTP methods and classified them into six groups. Chromosomal localization revealed a random distribution of ADK genes in G. hirsutum, with 13 genes located on the At subgenome and 14 genes on the Dt subgenome. Gene structure analysis showed consistency in exon-intron organization within subgroups, while conserved motif analysis identified subgroup-specific motifs, indicating functional diversity. Synteny and collinearity mapping analysis revealed that the primary expansion mechanisms of the ADK gene family in cotton are polyploidy and segmental duplication. Cis-regulatory elements in GhADK promoters were classified into light response, hormone response, developmental regulation, and stress response. We also analyzed the expression patterns of GhADK genes under a low temperature (4 °C) and drought conditions. Most GhADK genes responded to cold stress with different expression patterns, indicating their roles in rapid response and long-term cold adaptation. Under drought stress, expression patterns varied, with some genes showing sustained high expression levels. The qRT-PCR validation of transcriptomic data confirmed the stress-induced expression patterns of selected GhADK genes. Functional analysis through the VIGS silencing of GhADK25 demonstrated its importance in cold and drought stress responses, with silencing resulting in poor growth under stress, highlighting its significance in stress tolerance. This study provides a basis for further understanding the evolutionary relationships and functions of the cotton ADK gene family.

Highly Stable Polyimide Composite Nanofiber Membranes with Spectrally Selective for Passive Daytime Radiative Cooling.

Passive radiative cooling technology without electric consumption is an emerging sustainability technology that plays a key role in advancing sustainable development. However, most radiative cooling materials are vulnerable to outdoor contamination and thermal/UV exposure, which leads to decreased performance. Herein, we report a hierarchically structured polyimide/zinc oxide (PINF/ZnO) composite membrane that integrates sunlight reflectance of 91.4% in the main thermal effect of the solar spectrum (0.78-1.1 µm), the mid-infrared emissivity of 90.0% (8-13 µm), UV shielding performance, thermal resistance, and ideal hydrophobicity. The comprehensive performance enables the composite membrane to yield a temperature drop of ∼9.3 °C, compared to the air temperature, under the peak solar irradiance of ∼800 W m-2. In addition, the temperature drop of as-obtained composite membranes after heating at 200 °C for 6 h in a nitrogen/air atmosphere can be well maintained at ∼9.0 °C, demonstrating their ideal radiative cooling effect in a high-temperature environment. Additionally, the PINF/ZnO composite membrane shows excellent chemical durability after exposure to the outdoor environment. This work provides a new strategy to integrate chemical durability and thermal resistance with radiative cooling, presenting great potential for passive radiative cooling materials toward practical applications in harsh environments.

Simultaneous Hg2+ and Pb2+ detection in water samples using an electrochemical aptasensor with dual signal amplification by exonuclease III and metal-organic frameworks.

Heavy metal pollution in the environment has become a significant global concern due to its detrimental effects on human health and the environment. In this study, we report an electrochemical aptasensor for the simultaneous detection of Hg2+ and Pb2+. Gold nanoflower/polyethyleneimine-reduced graphene oxide (AuNFs/PEI-rGO) was introduced on the surface of a gold electrode to improve sensing performance. The aptasensor is based on the formation of a T-Hg2+-T mismatch structure and specific cleavage of the Pb2+-dependent DNAzyme, resulting in a dual signal generated by the Exo III specific digestion of methylene blue (MB) labeled at the 3' end of probe DNA-1 and the reduction of the substrate ascorbic acid (AA) catalyzed by the signal label. The decrease of MB signal and the increase of AA oxidation peak was used to indicate the content of Hg2+ and Pb2+, respectively, with detection limits of 0.11 pM (Hg2+) and 0.093 pM (Pb2+). The aptasensor was also used for detecting Hg2+ and Pb2+ in water samples with good recoveries. Overall, this electrochemical aptasensor shows promising potential for sensitive and selective detection of heavy metals in environmental samples.

Consensus clustering and novel risk score model construction based on m6A methylation regulators to evaluate the prognosis and tumor immune microenvironment of early-stage lung adenocarcinoma.

BACKGROUND: The aim of this study was to investigate the correlation between m6A methylation regulators and cell infiltration characteristics in tumor immune microenvironment (TIME), so as to help understand the immune mechanism of early-stage lung adenocarcinoma (LUAD). METHODS: The expression and consensus cluster analyses of m6A methylation regulators in early-stage LUAD were performed. The clinicopathological features, immune cell infiltration, survival and functional enrichment in different subtypes were analyzed. We also constructed a prognostic model. Clinical tissue samples were used to validate the expression of model genes through real-time polymerase chain reaction (RT-PCR). In addition, cell scratch assay and Transwell assay were also performed. RESULTS: Expression of m6A methylation regulators was abnormal in early-stage LUAD. According to the consensus clustering of m6A methylation regulators, patients with early-stage LUAD were divided into two subtypes. Two subtypes showed different infiltration levels of immune cell and survival time. A prognostic model consisting of HNRNPC, IGF2BP1 and IGF2BP3 could be used to predict the survival of early-stage LUAD. RT-PCR results showed that HNRNPC, IGF2BP1 and IGF2BP3 were significantly up-regulated in early-stage LUAD tissues. The results of cell scratch assay and Transwell assay showed that overexpression of HNRNPC promotes the migration and invasion of NCI-H1299 cells, while knockdown HNRNPC inhibits the migration and invasion of NCI-H1299 cells. CONCLUSIONS: This work reveals that m6A methylation regulators may be potential biomarkers for prognosis in patients with early-stage LUAD. Our prognostic model may be of great value in predicting the prognosis of early-stage LUAD.

The Study of Associated Factors for Non-Tuberculous Mycobacterial Pulmonary Disease Compared to Pulmonary Tuberculosis: A Propensity Score Matching Analysis.

Objective: Investigate the differences in clinical manifestations, imaging features, and associated inflammatory markers between Nontuberculous Mycobacterial Pulmonary Disease (NTM-PD) and Pulmonary Tuberculosis (PTB), identify potential risk factors for NTM-PD, and establish a logistic regression model to evaluate its diagnostic value. Methods: Baseline data were collected from 145 patients with NTM-PD and 206 patients with PTB. Propensity score matching (PSM) was utilized to achieve a 1:1 match between the two groups, resulting in 103 matched pairs. The differences in comorbidities, imaging features, and inflammatory markers were compared between the two groups. Multivariate binary logistic regression analysis was conducted to identify independent influencing factors, and the diagnostic value of the established model was evaluated. Results: After matching, significant differences were observed between the NTM-PD group and the PTB group in terms of diabetes, bronchiectasis, chronic obstructive pulmonary disease(COPD), cystic and columnar changes, lung cavity presentation, and monocyte percentage (MONO%), lymphocyte count (LYMPH#), platelet-to-lymphocyte ratio (PLR), and lymphocyte-to-monocyte ratio (LMR) (P<0.05). Logistic regression analysis confirmed that diabetes, bronchiectasis, COPD, and lung cavities were risk factors for NTM-PD. The established regression analysis model was analyzed by the Receiver Operating Characteristic (ROC) curve, the Area Under the Curve (AUC) was obtained as 0.795 (P<0.001, 95% CI 0.734-0.857). At a Youden index of 0.505, the sensitivity was 84.5% and the specificity was 66.6%. The Hosmer-Lemeshow test was used to evaluate the model's calibration, with a chi-square value of 11.023 and P=0.200>0.05, indicating no significant difference between predicted and observed values. Conclusion: For patients without diabetes but with bronchiectasis, COPD, and imaging characteristics of lung cavities, a high level of vigilance and active differential diagnosis for NTM-PD should be exercised. Given that the clinical manifestations of NTM-PD are similar to those of PTB, a detailed differential diagnosis is necessary during the diagnostic process to avoid misdiagnosis.

Understanding the relationship between sequences and kinetics of DNA strand displacements.

Precisely modulating the kinetics of toehold-mediated DNA strand displacements (TMSD) is essential for its application in DNA nanotechnology. The sequence in the toehold region significantly influences the kinetics of TMSD. However, due to the large sample space resulting from various arrangements of base sequences and the resulted complex secondary structures, such a correlation is not intuitive. Herein, machine learning was employed to reveal the relationship between the kinetics of TMSD and the toehold sequence as well as the correlated secondary structure of invader strands. Key factors that influence the rate constant of TMSD were identified, such as the number of free hydrogen bonding sites in the invader, the number of free bases in the toehold, and the number of hydrogen bonds in intermediates. Moreover, a predictive model was constructed, which successfully achieved semi-quantitative prediction of rate constants of TMSD even with subtle distinctions in toehold sequence.

Isoreticular Covalent Organic Pillars: Engineered Nanotubular Hosts for Tailored Molecular Recognition.

In the realm of nanoscale materials design, achieving precise control over the dimensions of nanotubular architectures poses a substantial challenge. In our ongoing pursuit, we have successfully engineered a novel class of single-molecule nanotubes─isoreticular covalent organic pillars (iCOPs)─by stacking formylated macrocycles through multiple dynamic covalent imine bonds, guided by principles of reticular chemistry. Our strategic selection of rigid diamine linkers has facilitated the synthesis of a diverse array of iCOPs, each retaining a homologous structure yet offering distinct cavity shapes influenced by the linker choice. Notably, three of these iCOP variants feature continuous one-dimensional channels, exhibiting length-dependent host-guest interactions with α,ω-dibromoalkanes, and each presenting a distinct critical guest alkyl chain length threshold for efficient guest encapsulation. This newfound capability not only provides a platform for tailoring nanotubular structures with precision, but also opens new avenues for innovative applications in molecular recognition and the purification of complex mixtures.

Investigating the proliferative inhibition of HepG2 cells by exosome-like nanovesicles derived from Centella asiatica extract through metabolomics.

Nano-particles demonstrating excellent anticancer properties have gradually found application in cancer therapy. However, their widespread use is impeded by their potential toxicity, high cost, and the complexity of the preparation process. In this study, we achieved exosome-like Centella asiatica-derived nanovesicles (ADNVs) through a straightforward juicing and high-speed centrifugation process. We employed transmission electron microscopy and nanoparticle flow cytometry to characterize the morphology, diameter, and stability of the ADNVs. We evaluated the in vitro anticancer effects of ADNVs using Cell Counting Kit-8 and apoptosis assays. Through sequencing and bicinchoninic acid protein analysis, we discovered the abundant presence of proteins and microRNAs in ADNVs. These microRNAs can target various diseases such as cancer and infection. Furthermore, we demonstrated the effective internalization of ADNVs by HepG2 cells, resulting in an increase in reactive oxygen species levels, mitochondrial damage, cell cycle arrest at the G1 phase, and apoptosis. Finally, we analyzed changes in cellular metabolites post-treatment using cell metabolomics techniques. Our findings indicated that ADNVs primarily influence metabolic pathways such as amino acid metabolism and lipid biosynthesis, which are closely associated with HepG2 treatment. Our results demonstrate the potential utility of ADNVs as anticancer agents.

Remotely sensed estimates of long-term biochemical oxygen demand over Hong Kong marine waters using machine learning enhanced by imbalanced label optimisation.

In many coastal cities around the world, continuing water degradation threatens the living environment of humans and aquatic organisms. To assess and control the water pollution situation, this study estimated the Biochemical Oxygen Demand (BOD) concentration of Hong Kong's marine waters using remote sensing and an improved machine learning (ML) method. The scheme was derived from four ML algorithms (RBF, SVR, RF, XGB) and calibrated using a large amount (N > 1000) of in-situ BOD5 data. Based on labeled datasets with different preprocessing, i.e., the original BOD5, the log10(BOD5), and label distribution smoothing (LDS), three types of models were trained and evaluated. The results highlight the superior potential of the LDS-based model to improve BOD5 estimate by dealing with imbalanced training dataset. Additionally, XGB and RF outperformed RBF and SVR when the model was developed using log10(BOD5) or LDS(BOD5). Over two decades, the BOD5 concentration of Hong Kong marine waters in the autumn (Sep. to Nov.) shows a downward trend, with significant decreases in Deep Bay, Western Buffer, Victoria Harbour, Eastern Buffer, Junk Bay, Port Shelter, and the Tolo Harbour and Channel. Principal component analysis revealed that nutrient levels emerged as the predominant factor in Victoria Harbour and the interior of Deep Bay, while chlorophyll-related and physical parameters were dominant in Southern, Mirs Bay, Northwestern, and the outlet of Deep Bay. LDS provides a new perspective to improve ML-based water quality estimation by alleviating the imbalance in the labeled dataset. Overall, the remotely sensed BOD5 can offer insight into the spatial-temporal distribution of organic matter in Hong Kong coastal waters and valuable guidance for the pollution control.

Potential-Regulated Design for Direct Recycling of Degraded LiFePO4 Cathode.

The rapid proliferation of power sources equipped with lithium-ion batteries poses significant challenges in terms of post-scrap recycling and environmental impacts, necessitating urgent attention to the development of sustainable solutions. The cathode direct regeneration technologies present an optimal solution for the disposal of degraded cathodes, aiming to non-destructively re-lithiate and straightforwardly reuse degraded cathode materials with reasonable profits and excellent efficiency. Herein, a potential-regulated strategy is proposed for the direct recycling of degraded LiFePO4 cathodes, utilizing low-cost Na2SO3 as a reductant with lower redox potential in the alkaline systems. The aqueous re-lithiation approach, as a viable alternative, not only enables the re-lithiation of degraded cathode while ignoring variation in Li loss among different feedstocks but also utilizes the rapid sintering process to restore the cathode microstructure with desirable stoichiometry and crystallinity. The regenerated LiFePO4 exhibits enhanced electrochemical performance with a capacity of 144 mA h g-1 at 1 C and a high retention of 98% after 500 cycles at 5 C. Furthermore, this present work offers considerable prospects for the industrial implementation of directly recycled materials from lithium-ion batteries, resulting in improved economic benefits compared to conventional leaching methods.

Enzymatic mechanism of MlrB for catalyzing linearized microcystins by Sphingopyxis sp. USTB-05.

Microcystins (MCs) are the most widespread cyanobacterial toxins in eutrophic water body. As high toxic intermediate metabolites, linearized MCs are further catalyzed by linearized microcystinase (MlrB) of Sphingopyxis sp. USTB-05. Here MlrB structure was studied by comprizing with a model representative of the penicillin-recognizing enzyme family via homology modeling. The key active sites of MlrB were predicted by molecular docking, and further verified by site-directed mutagenesis. A comprehensive enzymatic mechanism for linearized MCs biodegradation by MlrB was proposed: S77 transferred a proton to H307 to promote a nucleophilic attack on the peptide bond (Ala-Leu in MC-LR or Ala-Arg in MC-RR) of linearized MCs to form the amide intermediate. Then water was involved to break the peptide bond and produced the tetrapeptide as product. Meanwhile, four amino acid residues (K80, Y171, N173 and D245) acted synergistically to stabilize the substrate and intermediate transition states. This study firstly revealed the enzymatic mechanism of MlrB for biodegrading linearized MCs with both computer simulation and experimental verification.

Ultrasensitive label-free electrochemical aptasensor for Pb2+ detection exploiting Exo III amplification and AgPt/GO nanocomposite-enhanced transduction.

Lead ion pollution has become a serious public health concern worldwide. Therefore, sensitive detection of Pb2+ is critical to control lead pollution, assess risks, and safeguard the health of vulnerable populations. This study reports a highly sensitive labelling-free electrochemical aptasensor for Pb2+ detection. The aptasensor employs silver-platinum nanoparticles/graphene oxide (AgPt/GO) and Exonuclease III (Exo III) for signal amplification. GO provides high surface area and conductivity for immobilizing AgPt NPs, facilitating the immobilization of aptamer (Apt) probes on the electrode surface. Exo III enzymatically cleaves DNA strands on the electrode surface, releasing DNA segments to amplify the signal further. The synergistic amplification by AgPt/GO and ExoIII enables an extremely wide linear detection range of 0.05 pM-5 nM for Pb2+, with a low detection limit of 0.019 pM. Additionally, the G-quadruplex structure ensures excellent selectivity for Pb2+ detection, resulting in high reproducibility and stability of the aptasensor. The aptasensor was successfully applied to detect spiked Pb2+ in tap water samples, achieving recovery rates ranging from 96 to 108.4 %. By integrating nanomaterials, aptamers and enzymatic amplification, the aptasensor facilitates highly sensitive and selective detection of Pb2+, demonstrating potential for practical applications in environmental monitoring.

Soft yet mechanically robust injectable alginate hydrogels with processing versatility based on alginate/hydroxyapatite hybridization.

The salient gelling feature of alginate via forming the egg-box structure with calcium ions has received extensive interests for different applications. Owing to the interfacial incompatibility of rigid inorganic solids with soft polymers, the requirement of overall stereocomplexation with calcium released from uniformly distributed solids in alginate remains a challenge. In this study, a novel alginate-incorporated calcium source was proposed to tackle the intractable dispersion for the preparation of injectable alginate hydrogels. Calcium phosphate synthesis in alginate solution yielded CaP-alginate hybrids as a calcium source. The physicochemical characterization confirmed the CaP-alginate hybrid was a nano-scale alginate-hydroxyapatite complex. The colloidally stable CaP-alginate hybrids were uniformly dispersed in alginate solutions even under centrifugation. The calcium-induced gelling of the CaP-alginate hybrids-loaded alginate solutions formed soft yet tough hydrogels including transparent sheets and knittable threads, confirming the homogeneous gelation of the hydrogel. The gelation time, injectability and mechanical properties of the hydrogels could be adjusted by changing preparation parameters. The prepared hydrogels showed uniform porous structure, excellent swelling, wetting properties and cytocompatibility, showing a great potential for applications in different fields. The present strategy with organic/inorganic hybridization could be exemplarily followed in the future development of functional hydrogels especially associated with the interface integration.

Multidimensional biomarker approach integrating tumor markers, inflammatory indicators, and disease activity indicators may improve prediction of rheumatoid arthritis-associated interstitial lung disease.

INTRODUCTION: Rheumatoid arthritis (RA) often leads to interstitial lung disease (ILD), significantly affecting patient outcomes. This study explored the diagnostic accuracy of a multi-biomarker approach to offer a more efficient and accessible diagnostic strategy for RA-associated ILD (RA-ILD). METHODS: Patients diagnosed with RA, with or without ILD, at Beijing Tiantan Hospital from October 2019 to October 2023 were analyzed. A total of 125 RA patients were included, with 76 diagnosed with RA-ILD. The study focused on three categories of indicators: tumor markers, inflammatory indicators, and disease activity measures. The heatmap correlation analysis was employed to analyze the correlation among these indicators. Logistic regression was used to determine odds ratios (OR) for indicators linked to RA-ILD risk. Receiver-operating characteristic (ROC) curve analysis was employed to evaluate the diagnostic potential of these indicators for RA-ILD. RESULTS: The results of logistic regression analysis showed that tumor markers (carbohydrate antigen 19-9 (CA19-9), carbohydrate antigen 125 (CA125), and cytokeratin 19 fragment (CYFRA21-1)), as well as inflammatory indicators (neutrophil, neutrophil-to-lymphocyte ratio (NLR), platelet, C-reactive protein (CRP)) and disease activity measures (disease activity score-28-CRP (DAS28-CRP), rheumatoid factor (RF), and anti-cyclic peptide containing citrulline (anti-CCP)), were significantly associated with RA-ILD. The correlation coefficients among these indicators were relatively low. Notably, the combination indicator 4, which integrated the aforementioned three categories of biomarkers, demonstrated improved diagnostic accuracy with an AUC of 0.857. CONCLUSION: The study demonstrated that combining tumor markers, inflammatory indicators, and disease activity measures significantly enhanced the prediction of RA-ILD. Key Points • Multidimensional strategy: Integrated tumor markers, inflammatory indicators, and disease activity measures to enhance early detection of rheumatoid arthritis-associated interstitial lung disease (RA-ILD). • Diagnostic accuracy: Employed heatmap correlation and logistic regression, identifying significant associations and improving diagnostic accuracy with a multidimensional biomarker combination. • Superior performance: The combined multidimensional biomarker strategy demonstrated higher diagnostic precision compared to individual or dual-category indicators. • Clinical relevance: Offers a promising, accessible approach for early detection of RA-ILD in clinical settings, potentially improving patient outcomes.

Effectiveness of tofacitinib monotherapy for patients with IgG4-RD or idiopathic retroperitoneal fibrosis.

OBJECTIVES: To explore the effectiveness of tofacitinib for immunoglobulin G4-related disease (IgG4-RD) and idiopathic retroperitoneal fibrosis (IRF), and investigate the expression of JAKs in the lesion of these diseases. METHODS: Clinical data of patients with IgG4-RD or IRF who were administered with tofacitinib monotherapy were collected. IgG4-RD responder index (IgG4-RD RI) was assessed. The expression of JAK1, JAK2, JAK3, and TYK2 were analysed with immunohistochemistry staining in three salivary glands specimens of IgG4-RD and one retroperitoneal tissue of IRF. RESULTS: Two patients with IRF and two patients with IgG4-RD used tofacitinib monotherapy. Two patients with IRF achieved complete remission with diminished retroperitoneal mass and decreased CRP, as IgG4-RD RI decreased from 6 to 1 in both of them. One with IgG4-RD achieved complete remission with alleviated enlargement of pancreas and IgG4 level decreased from 13.7 g/L to 2.4 g/L, as IgG4-RD RI decreased from 12 to 1. One with IgG4-RD achieved partial response with IgG4 level decreased from 77.1g/L to 25.8g/L as IgG4-RD RI from 18 to 6. JAK1, JAK2, JAK3, and TYK2 expression were detected in biopsy tissues. The staining intensity of the JAK family on the lesion from one IRF patient was similar to those from IgG4-RD patients. CONCLUSIONS: Tofacitinib is a potentially effective treatment for IgG4-RD and IRF and it is reasonable to conduct clinical trial to validate its efficacy. The JAKs were expressed in the inflammatory lesions of IgG4-RD and IRF and they may share a common pathogenesis pathway that is independent of IgG4 production.