In vivo evaluations of Lactobacillus-fermented Eucheuma spinosum polysaccharides on alleviating food allergy activity.

In order to explore the in vivo anti-food allergy activity of Lactobacillus sakei subsp. sakei-fermented Eucheuma spinosum polysaccharides F1-ESP-3, an ovalbumin (OVA)-induced food allergy mouse model was established by ascites immunization and gavage. The weight, temperature, incidence of diarrhea, levels of allergic mediators and inflammatory factors in the serum of mice were analyzed. We analyzed the differentiation of mouse spleen lymphocytes and the proportion of sensitized mast cells by flow cytometry. The intestinal barrier status of mice was analyzed by intestinal pathological tissue sections and microbiota sequencing. The results showed that F1-ESP-3 could alleviate the food allergy symptoms of mice, such as hypothermia and loose stool; levels of OVA-specific immunoglobulin E, mast cell protease and histamine in the serum of sensitized mice and the proportion of dendritic cells and mast cells in mouse spleen were significantly reduced; in addition, F1-ESP-3 may protect the intestinal barrier and further improve the intestinal microenvironment of food-allergic mice by regulating the abundance of Bacteroidetes and Firmicutes. F1-ESP-3 can further improve the intestinal microenvironment of food-allergic mice by upregulating the levels of Lachnospiraceae, and may affect the signal pathways such as NOD-like receptor, MAPK, I kappa B and antigen processing and presentation.

Wetting-enhanced adhesion of photo-polymerized supramolecular adhesives for both smooth and rough surfaces.

Efficient interactions between an adhesive and a substrate surface at the molecular level are the basis for the formation of robust adhesion, which substantially relies on interfacial wetting. However, strong adhesives usually improve cohesion but compromise interfacial properties. Herein, we have reported a kind of robust supramolecular adhesive based on the outstanding mobility and interfacial wettability of adhesive precursors. In situ fast photopolymerization endows supramolecular adhesives with more outstanding adhesion for both smooth and rough surfaces in air and underwater in contrast to their counterparts from thermal polymerization. In addition to their low viscosity and high monomer concentration, supramolecular adhesive precursors without any organic solvents possess well-defined hydrogen bonding interactions. These superior properties consistently contribute to the wetting of the substrate and the formation of adhesive polymers with high molecular weights. This work highlights that enhancing interfacial wetting between an adhesive and a substrate is a promising route to achieving robust adhesion.

Identification of neurological complications in childhood influenza: a random forest model.

BACKGROUND: Among the neurological complications of influenza in children, the most severe is acute necrotizing encephalopathy (ANE), with a high mortality rate and neurological sequelae. ANE is characterized by rapid progression to death within 1-2 days from onset. However, the knowledge about the early diagnosis of ANE is limited, which is often misdiagnosed as simple seizures/convulsions or mild acute influenza-associated encephalopathy (IAE). OBJECTIVE: To develop and validate an early prediction model to discriminate the ANE from two common neurological complications, seizures/convulsions and mild IAE in children with influenza. METHODS: This retrospective case-control study included patients with ANE (median age 3.8 (2.3,5.4) years), seizures/convulsions alone (median age 2.6 (1.7,4.3) years), or mild IAE (median age 2.8 (1.5,6.1) years) at a tertiary pediatric medical center in China between November 2012 to January 2020. The random forest algorithm was used to screen the characteristics and construct a prediction model. RESULTS: Of the 433 patients, 278 (64.2%) had seizures/convulsions alone, 106 (24.5%) had mild IAE, and 49 (11.3%) had ANE. The discrimination performance of the model was satisfactory, with an accuracy above 0.80 from both model development (84.2%) and internal validation (88.2%). Seizures/convulsions were less likely to be wrongly classified (3.7%, 2/54), but mild IAE (22.7%, 5/22) was prone to be misdiagnosed as seizures/convulsions, and a small proportion (4.5%, 1/22) of them was prone to be misdiagnosed as ANE. Of the children with ANE, 22.2% (2/9) were misdiagnosed as mild IAE, and none were misdiagnosed as seizures/convulsions. CONCLUSION: This model can distinguish the ANE from seizures/convulsions with high accuracy and from mild IAE close to 80% accuracy, providing valuable information for the early management of children with influenza.

Animal-derived food allergen: A review on the available crystal structure and new insights into structural epitope.

Immunoglobulin E (IgE)-mediated food allergy is a rapidly growing public health problem. The interaction between allergens and IgE is at the core of the allergic response. One of the best ways to understand this interaction is through structural characterization. This review focuses on animal-derived food allergens, overviews allergen structures determined by X-ray crystallography, presents an update on IgE conformational epitopes, and explores the structural features of these epitopes. The structural determinants of allergenicity and cross-reactivity are also discussed. Animal-derived food allergens are classified into limited protein families according to structural features, with the calcium-binding protein and actin-binding protein families dominating. Progress in epitope characterization has provided useful information on the structural properties of the IgE recognition region. The data reveals that epitopes are located in relatively protruding areas with negative surface electrostatic potential. Ligand binding and disulfide bonds are two intrinsic characteristics that influence protein structure and impact allergenicity. Shared structures, local motifs, and shared epitopes are factors that lead to cross-reactivity. The structural properties of epitope regions and structural determinants of allergenicity and cross-reactivity may provide directions for the prevention, diagnosis, and treatment of food allergies. Experimentally determined structure, especially that of antigen-antibody complexes, remains limited, and the identification of epitopes continues to be a bottleneck in the study of animal-derived food allergens. A combination of traditional immunological techniques and emerging bioinformatics technology will revolutionize how protein interactions are characterized.

Fermented Gracilaria lemaneiformis polysaccharides alleviate food allergy by regulating Treg cells and gut microbiota.

Food allergy has a significant impact on the health and well-being of individuals, affecting both their physical and mental states. Research on natural bioactive compounds, such as polysaccharides extracted from seaweeds, holds great promise in the treatment of food allergies. In this study, fermented Gracilaria lemaneiformis polysaccharides (F-GLSP) were prepared using probiotic fermentation. Probiotic fermentation of Gracilaria lemaneiformis reduces the particle size of polysaccharides. To compare the anti-allergic activity of F-GLSP with unfermented Gracilaria lemaneiformis polysaccharides (UF-GLSP), an OVA-induced mouse food allergy model was established. F-GLSP exhibited a significant reduction in OVA-specific IgE and mMCP levels in allergic mice. Moreover, it significantly inhibited Th2 differentiation and IL-4 production and significantly promoted Treg differentiation and IL-10 production in allergic mice. In contrast, UF-GLSP only reduced OVA-specific IgE and mMCP in the serum of allergic mice. Furthermore, F-GLSP demonstrated a more pronounced regulation of intestinal flora abundance compared to UF-GLSP, significantly influencing the populations of Firmicutes, Bacteroidetes, Lactobacillus, and Clostridiales in the intestines of mice with food allergy. These findings suggest that F-GLSP may regulate food allergies in mice through multiple pathways. In summary, this study has promoted further development of functional foods with anti-allergic properties based on red algae polysaccharides.

In utero and postnatal ivacaftor/lumacaftor therapy rescues multiorgan disease in CFTR-F508del ferrets.

Cystic fibrosis (CF) is caused by mutations in the CF transmembrane conductance regulator (CFTR) gene, with F508del being the most prevalent mutation. The combination of CFTR modulators (potentiator and correctors) has provided benefit to CF patients carrying the F508del mutation; however, the safety and effectiveness of in utero combination modulator therapy remains unclear. We created a F508del ferret model to test whether ivacaftor/lumacaftor (VX-770/VX-809) therapy can rescue in utero and postnatal pathologies associated with CF. Using primary intestinal organoids and air-liquid interface cultures of airway epithelia, we demonstrate that the F508del mutation in ferret CFTR results in a severe folding and trafficking defect, which can be partially restored by treatment with CFTR modulators. In utero treatment of pregnant jills with ivacaftor/lumacaftor prevented meconium ileus at birth in F508del kits and sustained postnatal treatment of CF offspring improved survival and partially protected from pancreatic insufficiency. Withdrawal of ivacaftor/lumacaftor treatment from juvenile CF ferrets reestablished pancreatic and lung diseases, with altered pulmonary mechanics. These findings suggest that in utero intervention with a combination of CFTR modulators may provide therapeutic benefits to individuals with F508del. This CFTR-F508del ferret model may be useful for testing therapies using clinically translatable endpoints.

Lead Optimization of Butyrolactone I as an Orally Bioavailable Antiallergic Agent Targeting FcγRIIB.

Food allergy (FA) poses a growing global food safety concern, yet no effective cure exists in clinics. Previously, we discovered a potent antifood allergy compound, butyrolactone I (BTL-I, 1), from the deep sea. Unfortunately, it has a very low exposure and poor pharmacokinetic (PK) profile in rats. Therefore, a series of structural optimizations toward the metabolic pathways of BTL-I were conducted to provide 18 derives (2-19). Among them, BTL-MK (19) showed superior antiallergic activity and favorable pharmacokinetics compared to BTL-I, being twice as potent with a clearance (CL) rate of only 0.5% that of BTL-I. By oral administration, Cmax and area under the concentration-time curve (AUC0-∞) were 565 and 204 times higher than those of BTL-I, respectively. These findings suggest that butyrolactone methyl ketone (BTL-BK) could serve as a drug candidate for the treatment of FAs and offer valuable insights into optimizing the druggability of lead compounds.

Culture-free detection of ß-lactamase-Producing bacteria in urinary tract infections using a paper sensor.

Developing simple, inexpensive, fast, sensitive, and specific probes for antibiotic-resistant bacteria is crucial for the management of urinary tract infections (UTIs). We here propose a paper-based sensor for the rapid detection of ß-lactamase-producing bacteria in the urine samples of UTI patients. By conjugating a strongly electronegative group -N+(CH3)3 with the core structures of cephalosporin and carbapenem antibiotics, two visual probes were achieved to respectively target the extended-spectrum/AmpC ß-lactamases (ESBL/AmpC) and carbapenemase, the two most prevalent factors causing antibiotic resistance. By integrating these probes into a portable paper sensor, we confirmed 10 and 8 cases out of 30 clinical urine samples as ESBL/AmpC- and carbapenemase-positive, respectively, demonstrating 100% clinical sensitivity and specificity. This paper sensor can be easily conducted on-site, without resorting to bacterial culture, providing a solution to the challenge of rapid detection of ß-lactamase-producing bacteria, particularly in resource-limited settings.

Comparative analysis of tropomyosin allergenicity in three different species of molluscs: insights into the role of amino acid composition in IgE epitopes.

Limited research has been conducted on the differences in allergenicity among Alectryonella plicatula tropomyosin (ATM), Haliotis discus hannai tropomyosin (HTM), and Mimachlamys nobilis tropomyosin (MTM) in molluscs. Our study aimed to comprehensively analyze and compare their immunoreactivity, sensitization, and allergenicity while simultaneously elucidating the underlying molecular mechanisms involved. We assessed the immune binding activity of TM utilizing 86 sera from allergic patients and evaluated sensitization and allergenicity through two different types of mouse models. The dot-blot and basophil activation test assays revealed strong immunoreactivity for HTM, ATM, and MTM, with HTM exhibiting significantly lower levels compared to ATM. In the BALB/c mouse sensitization model, all TM groups stimulated the production of specific antibodies, elicited IgE-mediated immediate hypersensitivity responses, and caused an imbalance in the IL-4/IFN-γ ratio. Similarly, in the BALB/c mouse model of food allergy, all TM variants induced IgE-mediated type I hypersensitivity responses, leading to the development of food allergies characterized by clinical symptoms and an imbalance in the IL-4/IFN-γ ratio. The stimulation ability of sensitization and the severity of food allergies consistently ranked as ATM > MTM > HTM. Through an in-depth analysis of non-polar amino acid frequency and polar hydrogen bonds, HTM exhibited higher frequencies of non-polar amino acids in its amino acid sequence and IgE epitopes, in comparison with ATM and MTM. Furthermore, HTM demonstrated a lower number of polar hydrogen bonds in IgE epitopes. Overall, HTM exhibited the lowest allergenic potential in both allergic patients and mouse models, likely due to its lower polarity in the amino acid sequence and IgE epitopes.

STING agonist, SMA-2, inhibits clear cell renal cell carcinoma through improving tumor microenvironment.

Clear cell renal cell carcinoma (ccRCC) is the most prevalent and lethal subtype of kidney cancer, patients with ccRCC usually have very poor prognosis and short survival. Therefore, it is urgent to develop more effective therapeutics or medications to suppress ccRCC progression. Here, we demonstrated that STING agonist, MSA-2 significantly inhibits tumor progress and prolongs the survival of ccRCC mice by promoting cytokines secretion. Moreover, MSA-2 triggered the trafficking and infiltration of CD8+ T cells, supported by the generation of a chemokine milieu that promoted recruitment and modulation of the immunosuppressive TME in ccRCC. These findings suggest that MSA-2 potentially serves an effective and preferable adjuvant immunotherapy of ccRCC.

Microfluidic Immunosensing Platform Based on a Rolling Circle Amplification-Assisted DNA Dendrimer Probe for Portable and Sensitive Detection of Allergen-Specific IgE.

The robust point-of-care platform for sensitive, multiplexed, and affordable detection of allergen-specific IgE (sIgE) is an urgent demand in component-resolved diagnostics. Here, we developed a microfluidic immunosensing platform based on a rolling circle amplification-assisted DNA dendrimer probe for sensitive detection of multiple sIgEs. The versatile multichannel microfluidic whole blood analytical device integrates cell filtration, recombinant antigen-modified magnetic enrichment, and DNA dendrimer probe-amplified signal transduction for portable on-chip analysis. Three sIgEs against common oyster allergens were simultaneously detected in blood samples by simple smartphone-based imaging without any pretreatment. The quantitative detection of multiple allergen-specific antibodies on the platform was achieved with limits of detection of less than 50 pg/mL, exhibiting superior sensitivity compared to most point-of-care testing. The detection results of 55 serum samples and 4 whole blood samples were 100% consistent with the ELISA results, confirming the accuracy and stability of our platform. Additionally, the reversible combination of hexahistidine6-tag and Ni-IMAC magbead was elegantly utilized on the immunosensing platform for desired reversibility. With the advantages of general applicability, high sensitivity, and reversibility, the DNA dendrimer-based microfluidic immunosensing platform provides great potential for the portable detection of immune proteins as a point-of-care platform in disease diagnostics and biological analysis.

Mutation of Disulfide Bond Sites Reduces the Immunoreactivity of Cra a 4 by Changing the Structural Characteristics.

Sarcoplasmic calcium-binding protein (Cra a 4) from Crassostrea angulata belongs to the EF-hand superfamily, and understanding of its structure-allergenicity relationship is still insufficient. In this study, chemical denaturants were used to destroy the structure of Cra a 4, showing that disruption of the structure reduced its IgG-/IgE-binding activity. To explore which critical amino acid site affects the allergenicity of Cra a 4, the mutants were obtained by site-directed mutations in the disulfide bonds site (C97), conformational epitopes (I105, D114), or Ca2+-binding region (D106, D110) and their IgG-/IgE-binding activity was reduced significantly using serological tests. Notably, C97A had the lowest immunoreactivity. In addition, two conformational epitopes of Cra 4 were verified. Meanwhile, the increase of the α-helical content, surface hydrophobicity, and surface electrostatic potential of C97A affected its allergenicity. Overall, the understanding of the structure-allergenicity relationship of Cra a 4 allowed the development of a hypoallergenic mutant.

Research on the Cold Rolling Process, Microstructure and Properties of 305 Austenitic Stainless Steel Thin Strips.

Austenitic stainless steel has high toughness and plasticity; however, it tends to exhibit low yield strength, which severely limits the widespread application of this steel. It can be strengthened by cold working; however, this will cause many defects in the structure. Therefore, annealing treatment must be carried out before use. In this paper, the effects of annealing treatment at different temperatures and times on the microstructure and mechanical properties of cold-rolled 305 stainless steel sheet were studied and the theoretical mechanism was further analyzed to provide better theoretical guidance for production and application. It was found that the microstructure grains obtained by annealing at 850 °C for 30 s were finer and more uniform, and the mechanical properties were also the best, which met the requirements of strong plasticity. Therefore, the rolling and annealing experiments could be carried out again under this annealing condition, and the requirements of the finished product could be finally obtained. At this time, the thickness of the plate was about 0.15 mm, the yield strength was 1238 MPa, and the permeability was below 1.02, which met the production requirements of the metal mask plate.

Intervention Efficacy of Slightly Processed Allergen/Meat in Oral Immunotherapy for Seafood Allergy: A Systematic Review, Meta-Analysis, and Meta-Regression Analysis in Mouse Models and Clinical Patients.

Background: Seafood allergy is a significant global health concern that greatly impacts a patient's quality of life. The intervention efficacy of oral immunotherapy (OIT), an emerging intervention strategy, for seafood allergy remains controversial. This study aimed to perform a systematic review and meta-analysis to evaluate the efficacy of slightly processed allergen/meat from fish and crustacea in OIT, both in mouse models and clinical patients. Methods: A comprehensive literature search was performed in four mainstream databases and the EBSCOhost database to identify all relevant case-control and cohort studies. The aim was to elucidate the intervention efficacy, encompassing various processing methods and assessing the efficacy of multiple major allergens in OIT. Results: The meta-analysis included five case-control studies on crustacean allergens in mouse models and 11 cohort studies on meat from fish and crustacea in clinical patients for final quantitative assessments. In mouse models, crustacean allergen substantially decreased the anaphylactic score after OIT treatment (mean difference (MD) = -1.30, p < 0.01). Subgroup analyses with low-level heterogeneities provided more reliable results for crab species (MD = -0.63, p < 0.01, I2 = 0), arginine kinase allergen (MD = -0.83, p < 0.01, I2 = 0), and Maillard reaction processing method (MD = -0.65, p < 0.01, I2 = 29%), respectively. In clinical patients, the main meta-analysis showed that the slightly processed meat significantly increased the incidence rate of oral tolerance (OT, incidence rate ratio (IRR) = 2.90, p < 0.01). Subgroup analyses for fish meat (IRR = 2.79, p < 0.01) and a simple cooking treatment (IRR = 2.36, p = 0.01) also demonstrated a substantial increase in the incidence rate of OT. Sensitivity and meta-regression analyses successfully identified specific studies contributing to heterogeneity in mouse models and clinical patients, although these studies did not impact the overall significant pooled effects. Conclusions: This meta-analysis provides preliminary evidence for the high intervention efficacy of slightly processed allergen/meat from fish and crustacea in OIT, both in mouse models and clinical patients. The Maillard reaction and cooking processing methods may emerge as potentially effective approaches to treating allergen/meat in OIT for clinical patients, offering a promising and specific treatment strategy for seafood allergy. However, these findings should be interpreted cautiously, and further supporting evidence is necessary.

Marine-Derived Alternariol Monomethyl Ether Alleviates Ovalbumin-Induced Food Allergy by Suppressing MAPK and NF-κB Signaling Pathways of Mast Cells.

The prevalence of food allergies has grown dramatically over the past decade. Recently, studies have shown the potential of marine substances to alleviate food allergies. We utilized a rat basophilic leukemia (RBL)-2H3 model to evaluate the antiallergic effects of alternariol monomethyl ether (AME) extracted from marine fungi Alternaria sp. Our results showed that AME attenuated food allergy symptoms in mice and reduced histamine release in serum. The population of mast cells in the spleen and mesenteric lymph nodes was considerably reduced. Moreover, in vitro assays also revealed that AME inhibited the release of ß-hexosaminidase and histamine. Transcriptomic analysis uncovered that AME regulated gene expression associated with mast cells. Additionally, Western blotting demonstrated that AME suppressed mast cell activation by modulating MAPK and NF-κB signaling pathways. Taken together, these findings provide a theoretical basis for the potential antiallergic use of marine-derived compounds in the development of functional foods.

Dichloroacetate ameliorates apoptosis, EMT and oxidative stress in diabetic cataract via inhibiting the IDO1-dependent p38 MAPK pathway.

As an oral antidiabetic agent, dichloroacetate (DCA) has been proven to improve diabetes and related complications. However, its functional role in diabetic cataract (DC) remains to be elucidated. This study was to define the role of DCA and its underlying molecular mechanism in DC in vitro and in vivo. In this study, it was shown that DCA dose-dependently ameliorated DC formation and development in DM rats. In addition, DCA significantly increased cell viability, reduced apoptosis, and inhibited EMT and oxidative stress of high glucose (HG)-treated SRA-01/04 cells in a concentration-dependent manner. Besides, it was revealed that Indoleamine 2,3-dioxygenase 1 (IDO1) expression was upregulated in lenses of DM rats and HG-treated SRA-01/04 cells, which was reversed by DCA. In addition, DCA abrogated the activation of the p38 MAPK signaling in the lenses of DM rats and HG-treated SRA-01/04 cells. Further experiments showed that IDO1 upregulation activated the p38 MAPK signaling in HG-challenged SRA-01/04 cells. Moreover, IDO1 overexpression partially reversed DCA-mediated inactivation of p38 MAPK signaling and suppression of HG-induced damage to SRA-01/04 cells. To sum up, our findings showed that DCA prevented DC-related apoptosis, EMT, and oxidative stress via inactivating IDO1-dependent p38 MAPK signaling.

Molecular epidemiological characteristics of carbapenem-resistant Pseudomonas aeruginosa clinical isolates in southeast Shanxi, China.

OBJECTIVES: Infection by carbapenem-resistant Pseudomonas aeruginosa (CRPA) is a serious clinical problem worldwide. However, the molecular epidemiology of the clinical isolates varies depending on the region. This study was conducted to analyse the resistance phenotype and clarify the genetic and epidemiological properties of CRPA clinical isolates from southeast Shanxi, China. METHODS: Fifty-seven isolates of CRPA were collected from a hospital in this region. These isolates were reidentified by MALDI-TOF and subjected to whole-genome sequencing by next-generation sequencing. Phylogenetic trees were constructed based on single nucleotide polymorphisms (SNPs), after which multilocus sequence typing (MLST) was performed and antimicrobial resistance genes were identified. RESULTS: All the 57 CRPA isolates carried at least one kind of gene encoding carbapenemase, such as blaIMP-1, blaIMP-10, blaOXA-10, blaOXA-395, blaOXA-396, blaOXA-485, blaOXA-486, blaOXA-488, blaOXA-494, and blaOXA-50. The isolates harboured AIM-1, CMY-51, mecD, and NmcR genes and carried one kind of Pseudomonas-derived cephalosporinase (PDC) ß-lactamase-encoding gene, such as blaPCD-1 to blaPCD-3, blaPCD-5, or blaPCD-7 to blaPCD-10. Two isolates were found to harbour the aminoglycoside-modifying enzyme genes aadA1 and aadA7; however, no isolates were found to harbour genes encoding 16S rRNA methylase or quinolone resistance-related genes. These CRPA isolates belonged to various sequence types (STs), two of which, namely, ST235 and ST277, were high-risk types. CONCLUSIONS: Our findings indicate that CRPA isolates carrying resistance genes with unique regional characteristics are spreading in this region, with a high diversity of STs, especially in high-risk clones. These findings highlight the necessity for further measures to prevent CRPA spread in Shanxi.

A systematic two-sample and bidirectional MR process highlights a unidirectional genetic causal effect of allergic diseases on COVID-19 infection/severity.

BACKGROUND: Allergic diseases (ADs) such as asthma are presumed risk factors for COVID-19 infection. However, recent observational studies suggest that the assumed correlation contradicts each other. We therefore systematically investigated the genetic causal correlations between various ADs and COVID-19 infection/severity. METHODS: We performed a two-sample, bidirectional Mendelian randomization (MR) study for five types of ADs and the latest round of COVID-19 GWAS meta-analysis datasets (critically ill, hospitalized, and infection cases). We also further validated the significant causal correlations and elucidated the potential underlying molecular mechanisms. RESULTS: With the most suitable MR method, asthma consistently demonstrated causal protective effects on critically ill and hospitalized COVID-19 cases (OR < 0.93, p < 2.01 × 10-2), which were further confirmed by another validated GWAS dataset (OR < 0.92, p < 4.22 × 10-3). In addition, our MR analyses also observed significant causal correlations of food allergies such as shrimp allergy with the risk of COVID-19 infection/severity. However, we did not find any significant causal effect of COVID-19 phenotypes on the risk of ADs. Regarding the underlying molecular mechanisms, not only multiple immune-related cells such as CD4+ T, CD8+ T and the ratio of CD4+/CD8+ T cells showed significant causal effects on COVID-19 phenotypes and various ADs, the hematology traits including monocytes were also significantly correlated with them. Conversely, various ADs such as asthma and shrimp allergy may be causally correlated with COVID-19 infection/severity by affecting multiple hematological traits and immune-related cells. CONCLUSIONS: Our systematic and bidirectional MR analyses suggest a unidirectional causal effect of various ADs, particularly of asthma on COVID-19 infection/severity, but the reverse is not true. The potential underlying molecular mechanisms of the causal effects call for more attention to clinical monitoring of hematological cells/traits and may be beneficial in developing effective therapeutic strategies for allergic patients following infection with COVID-19.

[Diagnostic yield of bronchoscopic rapid on-site evaluation in severe invasive bronchopulmonary aspergillosis].

OBJECTIVE: To explore the diagnostic yield of bronchoscopic rapid on-site evaluation (B-ROSE) in patients with severe invasive bronchopulmonary aspergillosis (IBPA) and provide evidence for starting antifungal treatment before microbiological results were available. METHODS: A prospective cohort study was conducted to select patients with severe pneumonia suspected of IBPA admitted to the respiratory intensive care unit (RICU) in the First Affiliated Hospital of Xinjiang Medical University from June 2014 to June 2022, and those who were primarily infected with other pathogens (such as bacteria, Mycobacterium tuberculosis) at admission were excluded. Whether the antifungal treatment was initiated or not on the basis of the bedside B-ROSE, the B-ROSE was administered as soon as possible within 24 hours after admission to RICU. The current international definition of invasive aspergillosis was used as the gold diagnostic standard, the diagnostic accordance rate, the sensitivity and specificity of B-ROSE were calculated respectively, and the receiver operator characteristic curve (ROC curve) was also plotted, to evaluate the predictive value in diagnosing IBPA. RESULTS: A total of 176 patients with severe pneumonia suspected of IBPA were included in the study. According to international diagnostic standards, there were 81 cases of IBPA and 95 cases of non-IBPA. According to the early diagnosis of B-ROSE, there were 89 cases of IBPA and 87 cases of non-IBPA. The diagnostic accordance rate of B-ROSE was 84.09% (148/176), the area under the ROC curve for B-ROSE in diagnosing severe IBPA was 0.844, the 95% confidence interval (95%CI) was 0.782-0.905, the sensitivity was 87.65%, the specificity was 81.05%, the positive predictive value was 79.78%, the negative predictive value was 88.51%, the rate of underdiagnosis was 12.35% (10/81), and the rate of misdiagnosis was 18.95% (18/95). Compared with the true negative group, the proportion of long-term (≥ 14 days) use of glucocorticoid [70.0% (7/10) vs. 9.1% (7/77), P < 0.01] and the proportion of cases with diabetes [40.0% (4/10) vs. 10.4% (8/77), P < 0.05] were significantly higher in the false negative group (underdiagnosis group). However, B-ROSE of both groups showed mucosal bleeding, congestion and edema [100.0% (10/10) vs. 94.8% (73/77), P > 0.05], indicating that acute mucosal inflammation was non-characteristic. Compared with the true positive group, the proportion of long-term (≥ 14 days) use of glucocorticoid in the false positive group (misdiagnosis group) was significantly reduced [33.3% (6/18) vs. 60.6% (43/71), P < 0.05]. The B-ROSE results showed the proportion of cases with mucosal white spots, black plaques and pseudomembrane was significantly reduced [16.7% (3/18) vs. 52.1% (37/71), P < 0.01] in the misdiagnosed group, which suggest that cases of long-term use of glucocorticoid and cases with B-ROSE showing mucosal white spots, black plaques and pseudomembrane were less likely to be misdiagnosed. The main diseases that were easily misdiagnosed as IBPA included pulmonary tuberculosis (38.9%, 7/18), inflammatory lung adenocarcinoma (27.8%, 5/18) and pulmonary vasculitis (16.7%, 3/18). CONCLUSIONS: Before obtaining microbiological evidence, B-ROSE can assist in decision-making of early anti-aspergillus treatment for severe IBPA. This method is prompt, simple, and has high accuracy and reliability. If B-ROSE lacks characteristic manifestations, especially for severe pneumonia in patients with long-term use of glucocorticoid or diabetes, attention should be paid to the underdiagnosis of IBPA. Diseases such as lung tuberculosis, inflammatory lung adenocarcinoma and lung vasculitis should be vigilant against misdiagnosis as IBPA.

Immunoglobulin E Epitope Mapping and Structure-Allergenicity Relationship Analysis of Crab Allergen Scy p 9.

Filamin C is an allergen of Scylla paramamosain (Scy p 9), and six IgE linear epitopes of the allergenic predominant region had previously been validated. However, the IgE epitope and structure-allergenicity relationship of Scy p 9 are unclear. In this study, a hydrophobic bond was found to be an important factor of conformation maintaining. The critical amino acids in the six predicted conformational epitopes were mutated, and the IgE-binding capacity and surface hydrophobicity of four mutants (E216A, T270A, Y699A, and V704A) were reduced compared to Scy p 9. Ten linear epitopes were verified with synthetic peptides, among which L-AA187-205 had the strongest IgE-binding capacity. In addition, IgE epitopes were mapped in the protruding surface of the tertiary structure, which were conducive to binding with IgE and exhibited high conservation among filamin genes. Overall, these data provided a basis for IgE epitope mapping and structure-allergenicity relationship of Scy p 9.