A case report of IgG4-related hepatic inflammatory pseudotumor in a 3-year old boy.

Background: Hepatic Inflammatory Pseudotumor (IPT) is an infrequent condition often masquerading as a malignant tumor, resulting in misdiagnosis and unnecessary surgical resection. The emerging concept of IgG4-related diseases (IgG4-RD) has gained widespread recognition, encompassing entities like IgG4-related hepatic IPT. Clinically and radiologically, corticosteroids and immunosuppressive therapies have proven effective in managing this condition. Case Presentation: A 3-year-old Chinese boy presented to the clinic with an 11-month history of anemia, fever of unknown origin, and a tender hepatic mass. Blood examinations revealed chronic anemia (Hb: 6.4 g/L, MCV: 68.6 fl, MCH: 19.5 pg, reticulocytes: 1.7%) accompanied by an inflammatory reaction and an elevated serum IgG4 level (1542.2 mg/L). Abdominal contrast-enhanced computed tomography unveiled a 7.6 cm low-density mass in the right lateral lobe, while magnetic resonance imaging demonstrated slight hypointensity on T1-weighted images and slight hyperintensity on T2-weighted images, prompting suspicion of hepatic malignancy. A subsequent liver biopsy revealed a mass characterized by fibrous stroma and dense lymphoplasmacytic infiltration. Immunohistochemical analysis confirmed the presence of IgG4-positive plasma cells, leading to the diagnosis of IgG4-related hepatic IPT. Swift resolution occurred upon initiation of corticosteroid and mycophenolate mofetil therapies. Conclusion: This study underscores the diagnostic approach to hepatic IPT, utilizing histopathology, immunostaining, imaging, serology, organ involvement, and therapeutic response. Early histological examination plays a pivotal role in clinical guidance, averting misdiagnosis as a liver tumor and unnecessary surgical interventions.

Construction of a novel fluorescent probe for sensitive determination of glyphosate in food and imaging living cells.

Glyphosate is a widely used broad-spectrum herbicide in agriculture and horticulture to control a variety of weeds and undesirable plants. However, the excessive use of glyphosate has raised a number of environmental and human health concerns. It is urgent to develop tools to detect glyphosate. Herein, a novel dual-signal probe CCU-Cu2+ was designed and synthesized on the basis of CCU. CCU exhibited excellent selectivity and great sensitivity for Cu2+ which were based on both fluorescence "turn-off" reaction and comparative color visualisation methods. Due to the strong chelating ability of glyphosate on Cu2+, the CCU-Cu2+ complex was applied to glyphosate detection in practical samples. The experimental results in vitro showed that the CCU-Cu2+ complex was highly selective and rapid, with a low detection limit (1.6 µM), and could be recognised by the naked eye in the detection of glyphosate. Based on the excellent properties of the CCU-Cu2+ complex, we also constructed a smartphone-assisted detection sensing system for glyphosate detection, which has the advantages of precision, sensitivity, and high interference immunity. Moreover, the CCU-Cu2+ complex was also successfully employed for exogenous glyphosate imaging in living cells. These characteristics demonstrated that CCU-Cu2+ holds significant potential for detection and imaging of glyphosate in bio-systems.

Histopathology and molecular pathology confirmed a diagnosis of atypical Caroli's syndrome: a case report.

Caroli's syndrome is a congenital disease characterized by dilation of intrahepatic bile ducts and congenital hepatic fibrosis. It is a rare condition in clinical work. Typically, the diagnosis of this disease is confirmed through medical imaging. Here, we report a case of atypical Caroli's syndrome in a patient who presented with recurrent upper gastrointestinal tract bleeding. The patient underwent imaging examinations, liver biopsy and whole exome sequencing. The results of the imaging examination were non-specific. However, with the aid of pathological examination, the patient was diagnosed with Caroli's syndrome. In conclusion, for cases where the imaging presentation of Caroli's syndrome is inconclusive, an accurate diagnosis should rely on pathology. By discussing this specific case, our aim is to enhance readers' understanding of this disease, provide valuable information that can aid in the early detection and appropriate management of Caroli's syndrome, ultimately improving patient outcomes.

The hepatoprotective effect of aspirin on carbon tetrachloride­induced hepatic fibrosis via inhibition of TGFß­1 pathway and pro­inflammatory cytokines IL­1ß and COX­2 in rats.

Aspirin decreases liver fibrosis index and inflammation levels. However, the exact mechanism underlying the effects of aspirin are yet to be elucidated. The aim of the study was to investigate the potential protective effects of aspirin on carbon tetrachloride (CCl4)-induced hepatic fibrosis in Sprague-Dawley rats. Rats were divided into four groups, including healthy and CCl4 control and low-(aspirin 10 mg/kg + CCl4) and high-dose aspirin group (aspirin 300 mg/kg + CCl4). After 8 weeks treatment, the histopathological examinations of hepatocyte fibrosis in liver and serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), IL-1ß, transforming growth factor-ß1 (TGF-ß1), hyaluronic acid (HA), laminin (LN) and type IV collagen (IV.C) were determined. Histopathological examination suggested that aspirin decreased CCl4-induced hepatic fibrosis and liver inflammation. The high-dose aspirin group significantly decreased the serum levels of ALT, AST, HA and LN compared with the CCl4 control group. High-dose aspirin group significantly decreased the levels of pro-inflammatory cytokines IL-1ß compared with CCl4 group. The high-dose aspirin group significantly inhibited the expression of TGFß-1 protein compared with CCl4 group. Overall, the present study indicated that aspirin exhibited potent protective effects against CCl4-induced hepatic fibrosis via inhibition of the TGFß-1 pathway and pro-inflammatory cytokine IL-1ß.

A ratiometric SERS aptasensor array for human DNA glycosylaseat single-cell sensitivity/resolution.

Human 8-oxoguanine DNA glycosylase (hOGG1) is involved in the cellular genomic 8-oxoguanine (8-oxoG) excision repair to maintain genome stability. Accurate detection of hOGG1 activity is essential for clinical diagnosis and treatment of various human pathology. Yet, the quantitative detection of hOGG1 remains challenging for existing methods due to poor reproducibility and portability. Herein, we propose a ratiometric array-based SERS point-of-care testing method for hOGG1 activity. A kind of reproducible, uniform and stable plasmonic multi-microarray reaction cells was constructed by assembling AuNPs on the substrate modified by aminosilane and segmented by silica gel gasket, which greatly improved the sensitivity, portability and repeatability of SERS measurement. Based on this, the ratiometric method is further used to effectively overcome the instability of single SERS signal intensity, which allows signal rationing and provides built-in correction for environment effects. In specific, we designed two different Raman-labeled probes for the detection of hOGG1, a thiol- and Cy3-labeled aptamer as an internal standard and a Rox-labeled 8-oxoG-modified complementary aptamer as a signal probe. The ratio value between Cy3 and Rox SERS intensity is well linear with the hOGG1 activity on logarithmic scales in the range from 5 × 10-5 to 5 × 10-3 U/mL, and the limit of detection reaches 3.3 × 10-5 U/mL. Moreover, this strategy can be applied for the screening of inhibitors and the monitoring of cellular hOGG1 activity fluctuation at single-cell levels, providing a flexible and adaptive tool for clinical diagnosis, biochemical processes and drug discovery.

APOA4 as a novel predictor of prognosis in Stevens-Johnson syndrome/toxic epidermal necrolysis: A proteomics analysis from two prospective cohorts.

BACKGROUND: Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are rare but life-threatening adverse drug reactions. Conventional systemic therapies are of limited efficacy and often exhibit strong side effects. OBJECTIVE: To assess the efficacy and safety of the combination treatment with a tumor necrosis factor-α antagonist adalimumab and delineate the underlying mechanisms. METHODS: We evaluated the efficacy and safety of the combination therapy with adalimumab by comparing 2 treatment cohorts of SJS/TEN patients. Patient plasma samples were collected for proteomics analysis. RESULTS: The combination therapy with adalimumab significantly shortened the time to mucocutaneous re-epithelization and healing, with reduced side effects caused by corticosteroids. Plasma proteomic profiling showed that apolipoprotein A-IV (APOA4) was one of the most significant differentially expressed proteins. Multivariate regression analysis revealed that APOA4 level was significantly associated with prognosis parameter of SJS/TEN (P = .004), but not with disease severity score (severity-of-illness score for toxic epidermal necrolysis [SCORTEN]) (P = .118). Thus further research will be helpful to effectively incorporate APOA4 into current SCORTEN-driven protocols. LIMITATIONS: The cohort size is relatively small. Both cohorts had low overall SCORTEN scores. CONCLUSION: Adalimumab in combination with corticosteroids demonstrates significant clinical benefits over corticosteroids alone in SJS/TEN patients. Moreover, APOA4 may serve as a novel prognostic marker of SJS/TEN.

Optical Sensing Strategies for Probing Single-Cell Secretion.

Measuring cell secretion events is crucial to understand the fundamental cell biology that underlies cell-cell communication, migration, proliferation, and differentiation. Although strategies targeting cell populations have provided significant information about live cell secretion, they yield ensemble profiles that obscure intrinsic cell-to-cell variations. Innovation in single-cell analysis has made breakthroughs allowing accurate sensing of a wide variety of secretions and their release dynamics with high spatiotemporal resolution. This perspective focuses on the power of single-cell protocols to revolutionize cell-secretion analysis by allowing real-time and real-space measurements on single live cell resolution. We begin by discussing recent progress on single-cell bioanalytical techniques, specifically optical sensing strategies such as fluorescence-, surface plasmon resonance-, and surface-enhanced Raman scattering-based strategies, capable of in situ real-time monitoring of single-cell released ions, metabolites, proteins, and vesicles. Single-cell sensing platforms which allow for high-throughput high-resolution analysis with enough accuracy are highlighted. Furthermore, we discuss remaining challenges that should be addressed to get a more comprehensive understanding of secretion biology. Finally, future opportunities and potential breakthroughs in secretome analysis that will arise as a result of further development of single-cell sensing approaches are discussed.

In situ ratiometric SERS imaging of intracellular protease activity for subtype discrimination of human breast cancer.

Accurate discrimination between different cells at the molecular level is of fundamental importance for disease diagnosis. Endogenous proteases are such molecular candidates for cancer cell subtype study. But in situ probing their activity in live cells remains challenging for surface-enhanced Raman scattering (SERS). Here, we present a sensitive ratio-type SERS nanoprobe for imaging of matrix metalloproteinase-2 (MMP-2) in different cancer cells subtypes. The nanoprobe contained three components: a plasmon-active gold nanoparticle as the SERS enhancing matrix, Raman dye rhodamine B (Rh B)-labelled substrate peptides as the specific MMP-2 recognizer, and 2-naphthalenethiol (2-NT) as the internal standard. MMP-2-responsive cleavage of peptides from the nanoprobe surface results in decrease or even disappearance of SERS emission of Rh B, which was ratioed over the emission of 2-NT for the quantification of MMP-2 activity. Both in-tube assay and in-cell imaging results show that the MMP-responsive nanoprobe can work and serve to differentiate the normal breast cells from the tumorous ones, to differentiate two breast cancer cell subtypes with a different degree of malignancy. We believe that this SERS nanoprobe could find a wide application in the fields of tumor biology and accurate disease diagnosis.

Monodispersed silver-gold nanorods controllable etching for ultrasensitive SERS detection of hydrogen peroxide-involved metabolites.

Hydrogen peroxide (H2O2)-involved metabolites are widely engaged in cellular metabolism, and play significant roles in cell proliferation, cell growth, and signaling transduction. It is highly desirable to establish a method for the detection of H2O2-involved metabolites for applications ranging from chemical sensing to biomedical diagnosis. Herein, monodispersed sandwich Au@4-MBN@Ag@PEG nanorods (referred to as AMPRs) with bright Raman emission were developed to serve as a universal platform for detecting H2O2-involved metabolites (4-mercaptobenzonitrile is abbreviated to 4-MBN as the Raman reporter and PEG is polyethylene glycol). The system detects metabolites through changes in the surface-enhanced Raman scattering (SERS) spectrum, resulting from the controllable etching of the silver layer by the H2O2 produced by the metabolites. The integrative nanoplatform was successfully used to quantify the levels of glucose, lactate, and choline in aqueous solutions by exploiting the close linear relationship between the intensity of a SERS band and the logarithmic concentration of H2O2. The presented SERS nanoplatform demonstrated considerable practicability for the detection of glucose in cerebrospinal fluid samples (with a limit of detection (LOD) of 1.76 µM), and was capable of distinguishing infected from uninfected individuals. Therefore, the SERS sensor provides a new platform for the detection of H2O2-involved metabolites in biological fluids, and has potential for use in metabolite analysis and biomedical diagnostics.

A Rational Designed Bioorthogonal Surface-Enhanced Raman Scattering Nanoprobe for Quantitatively Visualizing Endogenous Hydrogen Sulfide in Single Living Cells.

Understanding the biology of gasotransmitters in living cells is of significance but remains challenging due to largely a lack of robust molecular probes. Here, we present the facile design and synthesis of a bioorthogonal Raman probe, 4-azidobenzenethiol (4-ABT), for endogenous hydrogen sulfide (H2S) imaging in single live cells by surface-enhanced Raman scattering (SERS). 4-ABT bears a thiol group and an azido group in the benzene ring, thus affording a bifunction to firmly bind to the gold nanoparticle surface and specifically respond to H2S. Moreover, the 4-ABT-based SERS nanoprobe shows a dose-dependent spectral change in the cellular Raman-silent region upon reacting with H2S, allowing ratiometric quantitative detection and visualization of intracellular H2S status without bio-interference. The ease of fabrication and superior performance of the novel SERS nanoprobe demonstrate its promising application in studies of H2S-related signaling networks.

Highly efficient sub-nanometer RuxCuyP2 nanoclusters designed for hydrogen evolution under alkaline media.

Design of highly active and stable non-precious electrocatalysts towards hydrogen evolution reaction (HER) is a hot research topic in low cost, clean and sustainable hydrogen energy field, yet remaining the important challenge caused by the sluggish reaction kinetics for water-alkali electrolyzers. Herein, a robust electrocatalyst is proposed by designing a novel sub-nanometer of copper and ruthenium bimetallic phosphide nanoclusters (RuxCuyP2) supported on a graphited carbon nanofibers (CNF). Uniform RuxCuyP2 (~1.90 nm) on the surface of CNF are obtained by introducing the dispersed Ru, thereby improving the intrinsic activity for HER. On optimizing the Ru ratio, the (x = y = 1) RuCuP2/CNF catalyst exhibits an excellent HER electroactivity with an overpotential of 10 mV in 1.0 M NaOH electrolyte to produce 10 mA cm-2 current density, which is lower than commercial 20% Pt/C in alkaline solution. Moreover, the kinetic study demonstrated that electrochemical activation energies for HER of RuCuP2/CNF is 20.7 kJ mol-1 highest among different ratio bimetallic phosphide. This simple, cost-effective, and environmentally friendly methodology can pave the way for exploitation of bimetallic phosphide nanoclusters for catalyst design.

SIRT1/IGFBPrP1/TGF ß1 axis involved in cucurbitacin B ameliorating concanavalin A-induced mice liver fibrosis.

The present study investigated the improving effect of cucurbitacin B on liver fibrosis induced by concanavalin A in mice and explored its possible mechanism. AST, ALT and TB were detected by kits. ELISA was performed to detect the levels of IL 5, IL 6, IL 13 and TNF-α in serum. Haematoxylin-eosin (HE) staining and Masson's trichrome staining were used to evaluate pathological changes. Western blotting was performed to observe expression levels of sirtuin (SIRT) 1, insulin-like growth factor binding protein-related protein 1 (IGFBPrP1) and TGF ß1. The activity of SIRT 1 also was detected. Results showed that cucurbitacin B could effectively improve the abnormal liver function, inhibit liver fibrosis and suppress releases of inflammatory factors in mice induced by concanavalin A. Furthermore, cucurbitacin B could down-regulate the expressions of TGF ß1 and IGFBPrP1, increase the expression and activity of SIRT 1. Interestingly, when SIRT1 activity was inhibited by EX 527, a selective inhibitor of SIRT 1, the preventive effect of cucurbitacin B was significantly attenuated. Taken together, the above results showed that cucurbitacin B could significantly suppress releases of inflammatory cytokines and improve liver fibrosis induced by concanavalin A in mice, and those may be achieved through SIRT1/IGFBPrP1/TGF ß1 axis.

Colorimetric enzymatic determination of glucose based on etching of gold nanorods by iodine and using carbon quantum dots as peroxidase mimics.

Carbon quantum dots (CQDs) with peroxidase-mimicking activity were successfully prepared from litchi rind. A colorimetric method for glucose determination was developed based on etching of gold nanorods (GNRs) using CQDs as peroxidase mimetic. The glucose oxidase-catalyzed oxidation of glucose leads to the generation of H2O2 which oxidizes added iodide under formation of elemental iodine under the catalytic action of CQDs. Iodine then etches the GNRs along the longitudinal direction due to the higher reaction activities at the tips of GNRs. This results in a stepwise decrease in the maximum absorption wavelength of the GNRs, from initially 953 nm to finally 645 nm. Under the optimized conditions, the shift in the maximum absorption wavelength decreases linearly in the 0.01-2.0 mM glucose concentration range, and the detection limit is 3.0 µM. Importantly, this method was applied to the determination of glucose in human serum. It is perceived that the CQDs are valuable peroxidase mimics due to their ease of preparation, low costs and stable catalytic activity. Graphical abstract Carbon quantum dots were prepared from litchi rind. They can induce the oxidation of gold nanorods in the presence of I- ions and H2O2. This finding was applied to design a colorimetric assay for glucose.

Remediation of cadmium, lead and zinc in contaminated soil with CETSA and MA/AA.

Soil washing, which is used to remove heavy metals from soil, is dependent on suitable washing agents. However, there is still a lack of economical, environmentally friendly washing agents with high removal efficiency. In this study, three washing agents, carboxyalkylthiosuccinic acid (CETSA), copolymer of maleic and acrylic acid (MA/AA) and ethylenediamine tetra acetic acid (EDTA), were used to remove heavy metals from contaminated soil. The influence of washing solution concentration, pH and washing time on heavy metals removal was also investigated. The cadmium (Cd), lead (Pb), and zinc (Zn) removal efficiencies increased as washing solution concentrations increased from 0 to 60 g L-1, while they declined as pH increased from 3 to 8. Despite fluctuations between 90 and 120 min, heavy metal removal efficiencies increased continuously from 10 to 90 min. The three agents also effectively reduced the potential risks of Cd, Pb, and Zn in contaminated soil, but only CETSA and MA/AA produced no significant changes in chemical properties. Fourier transform infrared spectroscopy revealed that the hydroxyl, carboxyl, carbonyl, methoxyl, and sulfur groups were related to the heavy metal ions from the soil colloids. Thus, CETSA and MA/AA were suitable washing agents for remediation of heavy metals contaminated soil.

Colorimetric detection of hydrogen peroxide and glucose by exploiting the peroxidase-like activity of papain.

Papain, a natural plant protease that exists in the latex of Carica papaya, catalyzes the hydrolysis of peptide, ester and amide bonds. In this work, we found that papain displayed peroxidase-like activity and catalyzed the oxidation of 3,3',5',5'-tetramethylbenzidine (TMB) in the presence of H2O2. This results in the formation of a blue colored product with an absorption maximum at 652 nm. The effects of experimental parameters including pH and reaction temperature on catalytic activity of papain were investigated. The increase of absorbance induced by the catalytic effect of papain offers accurate detection of H2O2 in the range of 5.00-90.0 µM, along with a detection limit of 2.10 µM. A facile colorimetric method for glucose detection was also proposed by combining the glucose oxidase (GOx)-catalyzed glucose oxidation and papain-catalyzed TMB oxidation, which exhibited a linear response in the range of 0.05-0.50 mM with a detection limit of 0.025 mM. The method proposed here displayed excellent selectivity, indicating that common coexisting substances (urea, uric acid, ascorbic acid, maltose, lactose and fructose) in urine did not interfere with detection of glucose. More importantly, the suggested method was successfully used to precisely detect the glucose concentration in human urine samples with recoveries over 96.0%.