Investigating the value of urinary biomarkers in relation to lupus nephritis histopathology: present insights and future prospects.

Lupus nephritis (LN), a leading cause of death in Systemic Lupus Erythematosus (SLE) patients, presents significant diagnostic and prognostic challenges. Although renal pathology offers critical insights regarding the diagnosis, classification, and therapy for LN, its clinical utility is constrained by the invasive nature and limited reproducibility of renal biopsies. Moreover, the continuous monitoring of renal pathological changes through repeated biopsies is impractical. Consequently, there is a growing interest in exploring urine as a non-invasive, easily accessible, and dynamic "liquid biopsy" alternative to guide clinical management. This paper examines novel urinary biomarkers from a renal pathology perspective, encompassing cellular components, cytokines, adhesion molecules, auto-antibodies, soluble leukocyte markers, light chain fragments, proteins, small-molecule peptides, metabolomics, urinary exosomes, and ribonucleic acids. We also discuss the application of combined models comprising multiple biomarkers in assessing lupus activity. These innovative biomarkers and models offer insights into LN disease activity, acute and chronic renal indices, fibrosis, thrombotic microangiopathy, podocyte injury, and other pathological changes, potentially improving the diagnosis, management, and prognosis of LN. These urinary biomarkers or combined models may serve as viable alternatives to traditional renal pathology, potentially revolutionizing the method for future LN diagnosis and observation.

Research progress of T cell autophagy in autoimmune diseases.

T cells, as a major lymphocyte population involved in the adaptive immune response, play an important immunomodulatory role in the early stages of autoimmune diseases. Autophagy is a cellular catabolism mediated by lysosomes. Autophagy maintains cell homeostasis by recycling degraded cytoplasmic components and damaged organelles. Autophagy has a protective effect on cells and plays an important role in regulating T cell development, activation, proliferation and differentiation. Autophagy mediates the participation of T cells in the acquired immune response and plays a key role in antigen processing as well as in the maintenance of T cell homeostasis. In autoimmune diseases, dysregulated autophagy of T cells largely influences the pathological changes. Therefore, it is of great significance to study how T cells play a role in the immune mechanism of autoimmune diseases through autophagy pathway to guide the clinical treatment of diseases.

Bibliometric and visualization analysis of the application of inorganic nanomaterials to autoimmune diseases.

Objective: To conduct bibliometric analysis of the application of inorganic nanomaterials to autoimmune diseases to characterize current research trends and to visualize past and emerging trends in this field in the past 15 years. Methods: The evolution and thematic trends of the application of inorganic nanomaterials to autoimmune diseases from January 1, 1985, to March 15, 2024, were analyzed by bibliometric analysis of data retrieved and extracted from the Web of Science Core Collection (WoSCC) database. A total of 734 relevant reports in the literature were evaluated according to specific characteristics such as year of publication, journal, institution, country/region, references, and keywords. VOSviewer was used to build co-authorship analysis, co-occurrence analysis, co-citation analysis, and network visualization. Some important subtopics identified by bibliometric characterization are further discussed and reviewed. Result: From 2009 to 2024, annual publications worldwide increased from 11 to 95, an increase of 764%. ACS Nano published the most papers (14) with the most citations (1372). China (230 papers, 4922 citations) and the Chinese Academy of Sciences (36 papers, 718 citations) are the most productive and influential country and institution, respectively. The first 100 keywords were co-clustered to form four clusters: (1) the application of inorganic nanomaterials in drug delivery, (2) the application of inorganic nano-biosensing to autoimmune diseases, (3) the use of inorganic nanomaterials for imaging applied to autoimmune diseases, and (4) the application of inorganic nanomaterials in the treatment of autoimmune diseases. Combination therapy, microvesicles, photothermal therapy (PTT), targeting, diagnostics, transdermal, microneedling, silver nanoparticles, psoriasis, and inflammatory cytokines are the latest high-frequency keywords, marking the emerging frontier of inorganic nanomaterials in the field of autoimmune diseases. Sub-topics were further discussed to help researchers determine the scope of research topics and plan research directions. Conclusion: Over the past 39 years, the application of inorganic nanotechnology to the field of autoimmune diseases shows extensive cooperation between countries and institutions, showing a continuous increase in the number of reports in the literature, and has clinical translation prospects. Future research should further improve the safety of inorganic nanomaterials, clarify the mechanism of action of nanomaterials, establish a standardized nanomaterial preparation and performance evaluation system, and ultimately achieve the goal of early detection and precise treatment of autoimmune diseases.

High-performance colorimetric sensor based on PtRu bimetallic nanozyme for xanthine analysis.

The identification and quantification of xanthine are crucial for assessing the freshness and quality of food products, particularly in the seafood industry. Herein, a new approach was developed, involving the in-situ controllable growth of Pt91Ru9 nanoparticles on graphitic carbon nitride to yield Pt91Ru9@C3N4 catalytic materials. By integrating Pt91Ru9@C3N4 with the xanthine/xanthine oxidase (XOD) enzyme catalytic system, a nanozyme-enzyme tandem platform was obtained for the quantification analysis of xanthine. Under the catalytic oxidation of xanthine by XOD in the presence O2, H2O2 was generated. Upon the addition of peroxidase-like activity of Pt91Ru9@C3N4, H2O2 can be decomposed into •OH and 1O2, which can further catalyze the oxidation of TMB to its oxidation product oxTMB with an absorption peak at 652 nm. This smartphone-assisted portable colorimetric sensor for visual monitoring xanthine with a low detection limit of 8.92 nmol L-1, and successfully applied to detect xanthine in grass carp and serum samples.

Large-scale CRISPR screen reveals context-specific genetic regulation of retinal ganglion cell regeneration.

Many genes are known to regulate retinal regeneration following widespread tissue damage. Conversely, genes controlling regeneration following limited cell loss, per degenerative diseases, are undefined. As stem/progenitor cell responses scale to injury levels, understanding how the extent and specificity of cell loss impact regenerative processes is important. Here, transgenic zebrafish enabling selective retinal ganglion cell (RGC) ablation were used to identify genes that regulate RGC regeneration. A single cell multiomics-informed screen of 101 genes identified seven knockouts that inhibited and eleven that promoted RGC regeneration. Surprisingly, 35 of 36 genes known/implicated as being required for regeneration following widespread retinal damage were not required for RGC regeneration, and seven even enhanced regeneration kinetics, including proneural factors neurog1, olig2, and ascl1a. Mechanistic analyses revealed ascl1a disruption increased the propensity of progenitor cells to produce RGCs; i.e., increased "fate bias". These data demonstrate plasticity in how Müller glia can convert to a stem-like state and context-specificity in how genes function during regeneration. Increased understanding of how the regeneration of disease-relevant cell types is specifically controlled will support the development of disease-tailored regenerative therapeutics.

Evaluation of oxaliplatin and tigio combination therapy in locally advanced gastric cancer.

BACKGROUND: Locally advanced gastric cancer (LAGC) is a common malignant tumor. In recent years, neoadjuvant chemotherapy has gradually become popular for the treatment of LAGC. AIM: To investigate the efficacy of oxaliplatin combined with a tigio neoadjuvant chemotherapy regimen vs a conventional chemotherapy regimen for LAGC. METHODS: Ninety patients with LAGC were selected and randomly divided into control and study groups with 45 patients in each group, according to the numerical table method. The control group was treated with conventional chemotherapy, and the study group was treated with oxaliplatin combined with tigio-neoadjuvant chemotherapy. The primary outcome measures were the clinical objective response rate (ORR) and surgical resection rate (SRR), whereas the secondary outcome measures were safety and Karnofsky Performance Status score. RESULTS: The ORR in the study group was 80.00%, which was significantly higher than that of the control group (57.78%). In the study group, SRR was 75.56%, which was significantly higher than that of the control group (57.78%). There were 15.56% adverse reactions in the study group and 35.56% in the control group. These differences were statistically significant between the two groups. CONCLUSION: The combination of oxaliplatin and tigio before surgery as neoadjuvant chemotherapy for patients with LAGC can effectively improve the ORR and SRR and is safe.

Outcomes of a dexamethasone-prednisone combination treatment course for status asthmaticus.

OBJECTIVES: Dexamethasone has become the standard of care for pediatric patients with status asthmaticus in the emergency department (ED) setting. Inpatient providers often must decide between continuing the second dose of dexamethasone or transitioning to prednisone. The effectiveness of receiving dexamethasone followed by prednisone (combination therapy) compared to only prednisone or dexamethasone remains unclear. This study compares patient characteristics and ED reutilization/hospital readmission outcomes of dexamethasone, prednisone, and combination therapy for inpatient asthma management. METHODS: A retrospective study was conducted at our tertiary children's hospital of children aged 2 to 18 years hospitalized between March 2016 and December 2018 with a primary discharge diagnosis of asthma, reactive airway disease, or bronchospasm. The differences between steroid groups were compared using Fisher's exact or Chi-square tests for categorical variables, and a Kruskal-Wallis test for continuous variables. A multivariable logistic regression was performed to analyze ED reutilization and hospital readmission rates. RESULTS: 1697 subjects met inclusion criteria. 115 (6.8%) patients received dexamethasone, 597 (35.2%) received prednisone, and 985 (58.0%) received combination therapy. Patients prescribed combination therapy had a lower exacerbation severity than patients prescribed prednisone, but higher severity than patients prescribed dexamethasone (p < .001, p = .001, respectively). Dexamethasone and combination therapy were not associated with increased 30-day ED reutilization/hospital readmissions compared to prednisone (p > .05). CONCLUSIONS: In our study, most patients hospitalized for status asthmaticus received combination therapy. Despite the differences in severity between steroid groups, outcomes of combination therapy and dexamethasone monotherapy, as measured by frequency of ED reutilizations/hospital readmissions, are comparable to prednisone monotherapy.

Integrative transcriptomic profiling of ncRNAs and mRNAs in developing mouse lens.

In recent years, burgeoning research has underscored the pivotal role of non-coding RNA in orchestrating the growth, development, and pathogenesis of various diseases across organisms. However, despite these advances, our understanding of the specific contributions of long non-coding RNAs (lncRNAs) and circular RNAs (circRNAs) to lens development remains notably limited. Clarifying the intricate gene regulatory networks is imperative for unraveling the molecular underpinnings of lens-related disorders. In this study, we aimed to address this gap by conducting a comprehensive analysis of the expression profiles of messenger RNAs (mRNAs), lncRNAs, and circRNAs at critical developmental time points of the mouse lens, encompassing both embryonic (E10.5, E12.5, and E16.5) and postnatal stages (P0.5, P10.5, and P60). Leveraging RNA-sequencing technology, we identified key transcripts pivotal to lens development. Our analysis revealed differentially expressed (DE) mRNAs, lncRNAs, and circRNAs across various developmental stages. Particularly noteworthy, there were 1831 co-differentially expressed (CO-DE) mRNAs, 150 CO-DE lncRNAs, and 13 CO-DE circRNAs identified during embryonic stages. Gene Ontology (GO) enrichment analysis unveiled associations primarily related to lens development, DNA conformational changes, and angiogenesis among DE mRNAs and lncRNAs. Furthermore, employing protein-protein interaction networks, mRNA-lncRNA co-expression networks, and circRNA-microRNA-mRNA networks, we predicted candidate key molecules implicated in lens development. Our findings underscore the pivotal roles of lncRNAs and circRNAs in this process, offering fresh insights into the pathogenesis of lens-related disorders and paving the way for future exploration in this field.

Nanocluster-agminated amorphous cobalt nanofilms for highly selective electroreduction of nitrate to ammonia.

Developing highly-efficient electrocatalysts for the nitrate reduction reaction (NITRR) is a persistent challenge. Here, we present the successful synthesis of 14 amorphous/low crystallinity metal nanofilms on three-dimensional carbon fibers (M-NFs/CP), including Al, Ti, Mn, Fe, Co, Ni, Cu, Zn, Ag, In, Sn, Pb, Au, or Bi, using rapid thermal evaporation. Among these samples, our study identifies the amorphous Co nanofilm with fine agglomerated Co clusters as the optimal electrocatalyst for NITRR in a neutral medium. The resulting Co-NFs/CP exhibits a remarkable Faradaic efficiency (FENH3) of 91.15 % at - 0.9 V vs RHE, surpassing commercial Co foil (39 %) and Co powder (20 %), despite sharing the same metal composition. Furthermore, during the electrochemical NITRR, the key intermediates on the surface of the Co-NFs/CP catalyst were detected by in situ Fourier-transform infrared (FTIR) spectroscopy, and the possible reaction ways were probed by Density functional theory (DFT) calculations. Theoretical calculations illustrate that the abundant low-coordinate Co atoms of Co-NFs/CP could enhances the adsorption of *NO3 intermediates compared to crystalline Co. Additionally, the amorphous Co structure lowers the energy barrier for the rate-determining step (*NH2→*NH3). This work opens a new avenue for the controllable synthesis of amorphous/low crystallinity metal nano-catalysts for various electrocatalysis reaction applications.

Multimodal Assessment and Intramodal Comparison of Imaging Techniques for Pediatric Pulmonary Vein Stenosis with Pulmonary Hypertension.

Pulmonary vein stenosis (PVS) is a rare, serious, and progressive disease in the pediatric population. Evaluation is complex and involves multimodality imaging. Diagnosis is important as early treatment to prevent progressive pulmonary hypertension and right ventricular dysfunction is essential. Adult studies have shown good correlation between various imaging modalities; however, there are limited data in children. This is a single-center retrospective pilot study to determine the reliability of measurement of pulmonary vein stenosis and pulmonary hypertension across different imaging modalities-computed tomography angiography (CTA), echocardiography (echo), lung perfusion scan (LPS), and cardiac catheterization (cath). PVS was defined as > 2 mmHg by echo and cath and/or 50% reduction in diameter by CTA. Patients had to have an echo, CTA and cath performed within a 1-month timeframe of one another to be included in the study, with LPS data included if testing was completed at initial evaluation. Fifteen total patients were enrolled; 87% were categorized as primary PVS; a condition not directly related to direct injury or prior surgical intervention. Twenty-seven total stenotic pulmonary veins were identified (mean 1.8, range 1-4). CTA had a slightly better agreement with cath than echo in identifying PVS in different vein locations except in the LLPV. Additionally, echo and CTA had excellent sensitivity (91%) and specificity (100%) compared to cath for diagnosis of PH. We conclude that non-invasive imaging of echo and CTA has an acceptable correlation to cardiac catheterization for screening and initial evaluation of PVS and PH, as directly related to PVS, in pediatrics.

Ratio-fluorescence sensor based on carbon dots and PtRu/CN nanozyme for efficient detection of melatonin in tablet.

The identification and quantification of melatonin (MT) are crucial for early diagnosis of disorders associated with circadian rhythm disruption. Herein, novel blue-emissive carbon dots (BCDs) were synthesized through an improved hydrothermal treatment using serine and malic acid as reductant and carbon source. The excellent optical properties of the as-obtained BCDs were used for ratiometric sensing by strategically constructing a MT sensing system integrating BCDs with C3N4 nanosheets loaded with platinum/ruthenium nanoparticles (PtRu/CN). In this system, H2O2 activated the peroxidase-like activity of PtRu/CN to generate •OH and 1O2 for oxidizing the colorless o-phenylenediamine (OPD) into yellow 2,3-diaminophenazine (DAP) with fluorescence emission at 565 nm. Concurrently, the fluorescence emission of BCDs at 439 nm was quenched by the generated DAP via the static quenching and inner filter effect (IFE) process. However, MT rapidly scavenged the generated free radicals to reverse the ratio fluorescence signal. The developed BCDs/PtRu/CN/OPD/H2O2 sensing platform enabled quantitative analysis of MT at concentrations ranging from 0.06 to 600 µmol/L with a low detection limit of 23.56 nmol/L. Moreover, smartphone-based RGB sensing of MT was successfully developed for rapid visualization and portable processing. More broadly, novel insights into the preparation of carbon dots with sensitive fluorescence sensing properties were presented, promising for future considerations.

Electrochemical Sensor for the Detection and Accurate Early Diagnosis of Ovarian Cancer.

Ovarian cancer (OC) has the highest mortality rate among malignant tumors, primarily because it is difficult to diagnose early. Exosomes, a type of extracellular vesicle rich in parental information, have garnered significant attention in the field of cancer diagnosis and treatment. They play an important regulatory role in the occurrence, development, and metastasis of OC. Consequently, exosomes have emerged as noninvasive biomarkers for early cancer detection. Therefore, identifying cancer-derived exosomes may offer a novel biomarker for the early detection of OC. In this study, we developed a metal-organic frameworks assembled "double hook"-type aptamer electrochemical sensor, which enables accurate early diagnosis of OC. Under optimal experimental conditions, electrochemical impedance spectroscopy technology demonstrated a good linear relationship within the concentration range of 31-3.1 × 106 particles per microliter, with a detection limit as low as 12 particles per microliter. The universal exosome detection platform is constructed, and this platform can not only differentiate between high-grade serous ovarian cancer (HGSOC) patients and healthy individuals but also distinguish between HGSOC patients and nonhigh-grade serous OC (non-HGSOC). Consequently, it provides a novel strategy for the early diagnosis of OC and holds great significance in clinical differential diagnosis.

Plasmid size determines adsorption to clay and breakthrough in a saturated sand column.

Horizontal gene transfer (HGT) is a major factor in the spread of antibiotic resistant genes (ARG). Transformation, one mode of HGT, involves the acquisition and expression of extracellular DNA (eDNA). eDNA in soils is degraded rapidly by extracellular nucleases. However, if bound to a clay particle, eDNA can persist for long periods of time without losing its transformation ability. To better understand the mechanism of eDNA persistence in soil, this experiment assessed the effects of 1) clay mineralogy, 2) mixed salt solution, 3) plasmid size on DNA adsorption to clay and 4) breakthrough behavior of three differently sized plasmids in an environmentally relevant solution. Batch test methods were used to determine adsorption trends of three differently sized DNA plasmids, pUC19, pBR322, and pTYB21, to several pure clay minerals, goethite (α-FeOOH), illite, and kaolinite, and one environmental soil sample. Results show not all sorbents have equal adsorption capacity based on surface area with adsorption capacities decreasing from goethite > illite = kaolinite > bulk soil, and low ionic strength solutions will likely not significantly alter sorption trends. Additionally, plasmid DNA size (i.e., length) was shown to be a significant predictor of adsorption efficiency and that size affects DNA breakthrough, with breakthroughs occurring later with larger plasmids. Given that DNA persistence is linked to its adsorption to soil constituents and breakthrough, eDNA size is likely an important contributor to the spread of ARG within natural microbial communities.

Silibinin attenuates TGF-ß2-induced fibrogenic changes in human trabecular meshwork cells by targeting JAK2/STAT3 and PI3K/AKT signaling pathways.

Transforming growth factor-ß2 (TGF-ß2) induced fibrogenic changes in human trabecular meshwork (HTM) cells have been implicated in trabecular meshwork (TM) damage and intraocular pressure (IOP) elevation in primary open-angle glaucoma (POAG) patients. Silibinin (SIL) exhibited anti-fibrotic properties in various organs and tissues. This study aimed to assess the effects of SIL on the TGF-ß2-treated HTM cells and to elucidate the underlying mechanisms. Our study found that SIL effectively inhibited HTM cell proliferation, attenuated TGF-ß2-induced cell migration, and mitigated TGF-ß2-induced reorganization of both actin and vimentin filaments. Moreover, SIL suppressed the expressions of fibronectin (FN), collagen type I alpha 1 chain (COL1A1), and alpha-smooth muscle actin (α-SMA) in the TGF-ß2-treated HTM cells. RNA sequencing indicated that SIL interfered with the phosphoinositide 3-kinase (PI3K)/protein kinase B (PKB, also known as AKT) signaling pathway, extracellular matrix (ECM)-receptor interaction, and focal adhesion in the TGF-ß2-treated HTM cells. Western blotting demonstrated SIL inhibited the activation of Janus kinase 2 (JAK2)/signal transducers and activators of transcription 3 (STAT3) and the downstream PI3K/AKT signaling pathways induced by TGF-ß2, potentially contributing to its inhibitory effects on ECM protein production in the TGF-ß2-treated HTM cells. Our study demonstrated the ability of SIL to inhibit TGF-ß2-induced fibrogenic changes in HTM cells. SIL could be a potential IOP-lowering agent by reducing the fibrotic changes in the TM tissue of POAG patients, which warrants further investigation through additional animal and clinical studies.

Characteristics of Volatile Organic Compounds Emitted from Airport Sources and Their Effects on Ozone Production.

In recent years, commercial air transport has increased considerably. However, the compositions and source profiles of volatile organic compounds (VOCs) emitted from aircraft are still not clear. In this study, the characteristics of VOCs (including oxygenated VOCs (OVOCs)) emitted from airport sources were measured at Shenzhen Bao'an International Airport. The results showed that the compositions and proportions of VOC species showed significant differences as the aircraft operating state changed. OVOCs were the dominant species and accounted for 63.17%, 58.44%, and 51.60% of the total VOC mass concentration during the taxiing, approach, and take-off stages. Propionaldehyde and acetone were the main OVOCs, and dichloromethane and 1,2-dichloroethane were the main halohydrocarbons. Propane had the highest proportion among all alkanes, while toluene and benzene were the predominant aromatic hydrocarbons. Compared with the source profiles of VOCs from construction machinery, the proportions of halogenated hydrocarbons and alkanes emitted from aircraft were significantly higher, as were those of propionaldehyde and acetone. OVOCs were still the dominant VOC species in aircraft emissions, and their calculated ozone formation potential (OFP) was much higher than that of other VOC species at all stages of aircraft operations. Acetone, propionaldehyde, formaldehyde, acetaldehyde, and ethylene were the greatest contributors to ozone production. This study comprehensively measured the distribution characteristics of VOCs, and its results will aid in the construction of a source profile inventory of VOCs emitted from aircraft sources in real atmospheric environments.

Review on strategies for improving the added value and expanding the scope of CO2 electroreduction products.

The electrochemical reduction of CO2 into value-added chemicals has been explored as a promising solution to realize carbon neutrality and inhibit global warming. This involves utilizing the electrochemical CO2 reduction reaction (CO2RR) to produce a variety of single-carbon (C1) and multi-carbon (C2+) products. Additionally, the electrolyte solution in the CO2RR system can be enriched with nitrogen sources (such as NO3-, NO2-, N2, or NO) to enable the synthesis of organonitrogen compounds via C-N coupling reactions. However, the electrochemical conversion of CO2 into valuable chemicals still faces challenges in terms of low product yield, poor faradaic efficiency (FE), and unclear understanding of the reaction mechanism. This review summarizes the promising strategies aimed at achieving selective production of diverse carbon-containing products, including CO, formate, hydrocarbons, alcohols, and organonitrogen compounds. These approaches involve the rational design of electrocatalysts and the construction of coupled electrocatalytic reaction systems. Moreover, this review presents the underlying reaction mechanisms, identifies the existing challenges, and highlights the prospects of the electrosynthesis processes. The aim is to offer valuable insights and guidance for future research on the electrocatalytic conversion of CO2 into carbon-containing products of enhanced value-added potential.

Accuracy of Early Neuroprognostication in Pediatric Severe Traumatic Brain Injury.

BACKGROUND: Children with severe traumatic brain injury (sTBI) are at risk for neurological sequelae impacting function. Clinicians are tasked with neuroprognostication to assist in decision-making. We describe a single-center study assessing clinicians' neuroprognostication accuracy. METHODS: Clinicians of various specialties caring for children with sTBI were asked to predict their patients' functioning three to six months postinjury. Clinicians were asked to participate in the study if their patient had survived but not returned to baseline between day 4 and 7 postinjury. The outcome tool utilized was the functional status scale (FSS), ranging from 6 to 30 (best-worst function). Predicted scores were compared with actual scores three to six months postinjury. Lin concordance correlation coefficients were used to estimate agreement between predicted and actual FSS. Outcome was dichotomized as good (FSS 6 to 8) or poor (FSS ≥9). Positive and negative predictive values for poor outcome were calculated. Pessimistic prognostic prediction was defined as predicted worse outcome by ≥3 FSS points. Demographic and clinical variables were collected. RESULTS: A total of 107 surveys were collected on 24 patients. Two children died. Fifteen children had complete (FSS = 6) or near-complete (FSS = 7) recovery. Mean predicted and actual FSS scores were 10.8 (S.D. 5.6) and 8.6 (S.D. 4.1), respectively. Predicted FSS scores were higher than actual scores (P < 0.001). Eight children had collective pessimistic prognostic prediction. CONCLUSIONS: Clinicians predicted worse functional outcomes, despite high percentage of patients with near-normal function at follow-up clinic. Certain patient and provider factors were noted to impact accuracy and need to be studied in larger cohorts.

Visualization of polarity changes in endoplasmic reticulum (ER) autophagy and rheumatoid arthritis mice with near-infrared ER-targeted fluorescent probe.

The crucial cellular activities for maintaining normal cell functions heavily rely on the polarity of the endoplasmic reticulum (ER). Understanding how the polarity shifts, particularly in the context of ER autophagy (ER-phagy), holds significant promise for advancing knowledge of disorders associated with ER stress. Herein, a polarity-sensitive fluorescent probe CDI was easily synthesized from the condensation reaction of coumarin and dicyanoisophorone. CDI was composed of coumarin as the electron-donating moiety (D), ethylene and phenyl ring as the π-conjugation bridge, and malononitrile as the electron-accepting moiety (A), forming a typical D-π-A molecular configuration that recognition in the near-infrared (NIR) region. The findings suggested that as the polarity increased, the fluorescence intensity of CDI decreased, and it was accompanied by a redshift of emission wavelength at the excitation wavelength of 524 nm, shifting from 641 nm to 721 nm. Significantly, CDI exhibited a notable ability to effectively target ER and enabled real-time monitoring of ER-phagy induced by starvation or drugs. Most importantly, alterations in polarity can be discerned through in vivo imaging in mice model of rheumatoid arthritis (RA). CDI has been proven effective in evaluating the therapeutic efficacy of drugs for RA. ER fluorescent probe CDI can be optically activated in lysosomes, providing a sensitive tool for studying ER-phagy in biology and diseases.

Development of a CRISPR/Cas12a-mediated aptasensor for Mpox virus antigen detection.

The emergence and rapid spread of Mpox (formerly monkeypox) have caused significant societal challenges. Adequate and appropriate diagnostics procedures are an urgent necessity. Herein, we discover a pair of aptamers through the systematic evolution of ligands by exponential enrichment (SELEX) that exhibit high affinity and bind to different sites towards the A29 protein of the Mpox virus. Subsequently, we propose a facile, sensitive, convenient CRISPR/Cas12a-mediated aptasensor for detecting the A29 antigen. The procedure employs the bivalent aptamers recognition, which induces the formation of a proximity switch probe and initiates subsequent cascade strand displacement reactions, then triggers CRISPR/Cas12a DNA trans-cleavage to achieve the sensitive detection of Mpox. Our method enables selective and ultrasensitive evaluation of the A29 protein within the range of 1 ng mL-1 to 1 µg mL-1, with a limit of detection (LOD) at 0.28 ng mL-1. Moreover, spiked A29 protein recovery exceeds 96.9%, while the detection activity remains above 91.9% after six months of storage at 4 °C. This aptasensor provides a novel avenue for exploring clinical diagnosis in cases involving Mpox as facilitating development in various analyte sensors.