Ascorbate peroxidase catalyses synthesis of protocatechualdehyde from p-hydroxybenzaldehyde in Lycoris aurea.

Protocatechualdehyde is a plant natural phenolic aldehyde and an active ingredient with important bioactivities in traditional Chinese medicine. Protocatechualdehyde is also a key intermediate in the synthesis of Amaryllidaceae alkaloids for supplying the C6-C1 skeleton. However, the biosynthesis of protocatechualdehyde in plants remains obscure. In this study, we measured the protocatechualdehyde contents in the root, bulb, scape and flower of the Amaryllidaceae plant Lycoris aurea (L'Hér.) Herb., and performed the correlation analysis between the protocatechualdehyde contents and the transcriptional levels of the phenolic oxidization candidate protein encoding genes. We found that a novel ascorbate peroxidase encoded by the contig_24999 in the L. aurea transcriptome database had potential role in the biosynthesis of protocatechualdehyde. The LauAPX_24999 gene was then cloned from the cDNA of the scape of L. aurea. The transient expression of LauAPX_24999 protein in Arabidopsis protoplasts demonstrated that LauAPX_24999 protein was localized in the cytoplasm, thus belonging to Class II L-ascorbate peroxidase. Subsequently, LauAPX_24999 protein was heterogenously expressed in Escherichia coli, and identified that LauAPX_24999 biosynthesized protocatechualdehyde from p-hydroxybenzaldehyde using L-ascorbic acid as the electron donor. The protein structure modelling and molecular docking indicated that p-hydroxybenzaldehyde could access to the active pocket of LauAPX_24999 protein, and reside at the δ-edge of the heme group while L-ascorbic acid binds at the γ-heme edge. To our knowledge, LauAPX_24999 is the first enzyme discovered in plants able to biosynthesize protocatechualdehyde from p-hydroxybenzaldehyde, and offers a competent enzyme resource for the biosynthesis of Amaryllidaceae alkaloids via synthetic biology.

An update on the use of antihistamines in managing chronic urticaria.

INTRODUCTION: Urticaria, a mast cell-mediated skin disease, manifests as acute or chronic, with the latter divided into spontaneous and inducible types and requires individualized management, including identifying triggers and comorbidities. Antihistamines, particularly the second generation group, form the mainstay of primary treatment plans consisting of dosage adjustments and/or in combination with other treatment modalities depending on underlying disease control. AREAS COVERED: A literature search was conducted using 'antihistamines,' 'urticaria,' 'pharmacogenomics,' 'genomics,' 'biomarkers' and 'treatment response' as key words. In this review, we focus on the comprehensive understanding and application of antihistamines in managing adult and adolescent patients with chronic urticaria. EXPERT OPINION: Using antihistamines to treat urticaria is set to change significantly, focusing more on personalized medicine and identifying key biomarkers to enhance treatment response prediction. These changes aim to make treatments more specific and cost-effective by avoiding unnecessary tests. Applying new approaches in everyday clinical care faces challenges like proving the biomarkers' reliability, updating current guidelines, and incorporating individualized treatments into standard procedures. Efforts should now concentrate on finding easy-to-use biomarkers, improving access to pharmacogenomics, understanding why some patients are resistant to treatment, and creating more specific treatment options based on patient needs.

The evaluation of cystatin protein vaccines based on the stress response of ticks triggered by low-temperature and toxin stress in Haemaphysalis doenitzi.

BACKGROUND: Ticks, which are obligate blood-feeding parasites, transmit a wide range of pathogens during their hematophagic process. Certain enzymes and macromolecules play a crucial role in inhibition of several tick physiological processes, including digestion and reproduction. In the present study, genes encoding type 2 cystatin were cloned and characterized from Haemaphysalis doenitzi, and the potential role of cystatin in tick control was further assessed. RESULTS: Two cystatin genes, HDcyst-1 and HDcyst-2, were successfully cloned from the tick H. doenitzi. Their open reading frames are 390 and 426 base pairs, and the number of coding amino acids are 129 and 141, respectively. In the midgut, salivary glands, Malpighian tubules and ovaries of ticks, the relative expression of HDcyst-1 was higher in the midgut and Malpighian tubules, and HDcyst-2 was higher in the salivary glands of H. doenitzi, respectively. Lipopolysaccharide (LPS) injection and low-temperature stress elevated cystatin expression in ticks. Enzyme-linked immunosorbent assay showed that both rHDcyst-1 and rHDcyst-2 protein vaccines increased antibody levels in immunized rabbits. A vaccination trial in rabbits infected with H. doenitzi showed that both recombinant cystatin proteins significantly reduced tick engorgement weights and egg mass weight, in particular, rHDcyst-1 significantly prolonged tick engorgement time by 1 day and reduced egg hatching rates by 16.9%. In total, rHDcyst-1 and rHDcyst-2 protein vaccinations provided 64.1% and 51.8% protection to adult female ticks, respectively. CONCLUSION: This is the first report on the immunological characterization of the cystatin protein and sequencing of the cystatin gene in H. doenitzi. Cystatin proteins are promising antigens that have the potential to be used as vaccines for infestation of H. doenitzi control. © 2024 Society of Chemical Industry.

Autoreactive IgE: Pathogenic role and therapeutic target in autoimmune diseases.

Autoimmunity is the break of tolerance to self-antigens that leads to organ-specific or systemic diseases often characterized by the presence of pathogenic autoreactive antibodies (AAb) produced by plasmablast and/or plasma cells. AAb are prevalent in the general population and not systematically associated with clinical symptoms. In contrast, in some individuals, these AAb are pathogenic and drive the development of signs and symptoms of antibody-mediated autoimmune diseases (AbAID). AAb production, isotype profiles, and glycosylations are promoted by pro-inflammatory triggers linked to genetic, environmental, and hormonal parameters. Recent evidence supports a role for pathogenic AAb of the IgE isotype in a number of AbAID. Autoreactive IgE can drive the activation of mast cells, basophils, and other types of FcεRI-bearing cells and may play a role in promoting autoantibody production and other pro-inflammatory pathways. In this review, we discuss the current knowledge on the pathogenicity of autoreactive IgE in AbAID and their status as therapeutic targets. We also highlight unresolved issues including the need for assays that reproducibly quantify IgE AAbs, to validate their diagnostic and prognostic value, and to further study their pathophysiological contributions to AbAID.

Simultaneous partial nitrification, denitrification, and phosphorus removal in sequencing batch reactors via controlled reduced aeration and short-term sludge retention time decrease.

Simultaneous bio-treatment processes of organic carbon (C)-, nitrogen (N)-, and phosphorus (P)-containing wastewater are challenged by insufficient carbon sources in the effluent. In the present study, two parallel anaerobic/aerobic sequencing batch reactors (R-1 and R-2) treating low C/N (≤4) wastewater were employed using different partial nitrification start-up strategies, controlled reduced aeration, and decreased sludge retention time. Advanced removal efficiencies for NH4+-N (≥96%), total nitrogen (TN, ≥86%), PO43--P (≥95%), and CODintra (≥91%) were realized, with TN and PO43--P effluent concentrations of 10.0 ± 3.5 and 0.11 ± 0.3 mg/L in R-1 and 9.28 ± 4.0 and 0.11 ± 0.1 mg/L in R-2, respectively. Higher nitrite accumulation rate (nearly 100%) and TN (121.1 ± 0.7 mg TN/g VSS·d) and P (12.5 ± 0.6 mg PO43--P/g VSS·d) removal loadings were obtained in R-2 by a thorough elimination of nitrite-oxidizing bacteria. Moreover, different microbial structures and nutrient removal pathways were identified. Denitrifying glycogen-accumulating organisms (Candidatus Competibacter) and phosphorus-accumulating organisms (PAOs) (Tetrasphaera) removed N and P with partial nitrification-endogenous denitrification pathways and aerobic P removal in R-1. In R-2, aerobic denitrifying bacteria (Psychrobacter) and PAOs ensured N and P removal through the partial nitrification-aerobic denitrification and aerobic P removal pathways. Compared to R-1, R-2 offers greater efficiency, convenience, and scope to further reduce carbon-source demand.

Chronic spontaneous urticaria: new evidences on the role of autoimmunity.

PURPOSE OF REVIEW: The purpose of this review is to provide an overview of the recent advancements and relevance of the autoimmune theories in chronic spontaneous urticaria (CSU). RECENT FINDINGS: Two primary types of autoimmunity, Type I and Type IIb, have emerged as major contributors to CSU, characterized by immunoglobulin E (IgE) and immunoglobulin G (IgG) autoantibodies, respectively. Genetic evidence supports the notion that CSU shares more similarities with other autoimmune diseases rather than atopic diseases. Novel autoallergens such as FcεRI and tissue transglutaminase have been identified, contributed to our understanding of autoimmune mechanisms. Furthermore, the potential overlap between Type I and Type IIb autoimmunity has been recognized. Evaluating the autoimmune status of CSU patients through biomarkers and understanding their clinical implications is vital for effective management. For instance, CSU patients with Type IIb autoimmunity, with or without coexisting Type I autoimmunity, may exhibit resistance to H1-antihistamines and omalizumab treatment but could potentially respond well to cyclosporine or Bruton's tyrosine kinase inhibitors. SUMMARY: Further investigations are needed to explore new autoallergens and autoantibodies in CSU, establishing their connection to the development of autoimmunity. The efficacy of novel drugs targeting different mechanisms should be examined to determine their responses in both autoimmune CSU and nonautoimmunity-related CSU.

Above management: Scale development and empirical testing for public opinion monitoring of marine pollution.

The marine eco-environment is receiving increasing attention globally, and the rapid development of network technology has enabled individuals to express their dissatisfaction and appeals for marine pollution through public engagement measures, particularly on network platforms. As a result, chaotic public opinions and information dissemination on marine pollution are becoming more prevalent. Previous studies have mainly focused on practical measures of marine pollution management, with limited exploration of how to prioritize the monitoring of public opinions on marine pollution. This study aims to develop a comprehensive and scientific measurement scale for public opinion monitoring on marine pollution by defining its implications and dimensions, verifying its reliability, validity, and predictive validity. The research defines the implications of public opinion monitoring regarding marine pollution based on previous literature and experience, using empathy theory as an entry point. The study uses text analysis to explore the internal laws of topic data on social media sites (n = 12,653), forming a theoretical conception of public opinion monitoring composed of three Level 1 dimensions (empathy arousal, empathy experience, and empathy memory). Based on research conclusions and related measurement scales, the study compiles the measurement items to develop the initial scale. Finally, the study verifies the scale reliability and validity (n1 = 435, n2 = 465) and predictive validity (n = 257). Results show that the public opinion monitoring scale has good reliability and validity, and the three Level 1 dimensions have a high level of interpretation for public opinion monitoring and good predictive validity. This research expands the application scope of public opinion monitoring theory and emphasizes the significance of public opinion management on the basis of traditional management research, increasing marine pollution managers' attention to the public domain of the network. Furthermore, it provides public opinion monitoring instruments for marine pollution through scale development and empirical research, reducing the occurrence of public trust crises and creating a stable and harmonious network environment.

Positive Basophil Tests Are Linked to High Disease Activity and Other Features of Autoimmune Chronic Spontaneous Urticaria: A Systematic Review.

BACKGROUND: Chronic spontaneous urticaria (CSU) is believed to be Autoimmune (aiCSU) (type IIb CSU) in at least 8% of patients, associated with mast cell-activating IgG autoantibodies. Basophil tests such as the basophil activation test (BAT) and basophil histamine release assay (BHRA) are considered the best single tests for an aiCSU diagnosis. To date, the strength of associations among a positive BAT and/or BHRA (BAT/BHRA+) and CSU features, patient demographics, and response to treatment remains poorly characterized. OBJECTIVE: To evaluate the strength of current evidence on basophil tests as parameters for CSU characteristics. METHODS: We performed a systematic literature search and review to assess the relationship between BAT/BHRA+ and clinical and laboratory parameters of CSU. Of 1,058 records found in the search, 94 studies were reviewed by experts in urticaria and 42 were included in the analysis. RESULTS: In CSU patients, BAT/BHRA+ showed a strong level of evidence for an association with high disease activity and low levels of total IgE. A weak level of evidence was shown for the association of BAT/BHRA+ and the presence of angioedema, and basopenia. CONCLUSIONS: Our results suggest that aiCSU defined by BAT/BHRA+ is more active or severe and is linked to other aiCSU markers such as low total IgE/basopenia. Basophil tests should be standardized and implemented in routine clinical care to improve the diagnosis and treatment of patients with aiCSU.

Effects of oral immunonutritional supplement on 3-year disease-free survival in gastric cancer patients with pathological stage III after total gastrectomy (CRUCIAL): study protocol of a multicentre, randomised clinical trial.

INTRODUCTION: The nutritional status of patients with gastric cancer (GC) after total gastrectomy continues to deteriorate and lasts a long time after discharge, which is an independent risk factor for mortality. Recent guidelines have recommended appropriate nutritional support after discharge for cancer surgery patients with malnutrition or nutritional risk. The evidence on the efficacy of oral immunonutritional supplement (INS) and its effect on long-term disease-free survival (DFS) in patients with GC is limited. This study was designed to test the hypothesis that oral INS compared to diet alone may improve 3-year DFS of GC patients with pathological stage III after total gastrectomy (Nutrition Risk Screening 2002 score ≥3 at discharge). METHODS AND ANALYSIS: This is a pragmatic, open-label, multicentre, randomised controlled study. 696 eligible GC patients with pathological stage III after total gastrectomy will be randomised in a 1:1 ratio to oral INS group or normal diet group for 6 months. The primary endpoint is 3-year DFS after discharge. The following secondary endpoints will be evaluated: 3-year overall survival; unplanned readmission rate at 3 and 6 months after discharge; quality of life, body mass index and haematological index at 3, 6 and 12 months after discharge; incidence of sarcopenia at 6 and 12 months after discharge; and the tolerance to chemotherapy. The adverse events of oral INS will also be evaluated during the intervention. ETHICS AND DISSEMINATION: This study was approved by the ethics committee of Jinling Hospital, Nanjing University (number 2021NZKY-069-01). The present study may validate the effectiveness of oral immunonutritional therapy in improving 3-year DFS for GC patients with pathological stage III after total gastrectomy for the first time. The results of this trial will be disseminated in peer-reviewed journals and at scientific conferences. TRIAL REGISTRATION NUMBER: NCT05253716.

Recent findings on miR­370 expression, regulation and functions in cancer (Review).

MicroRNAs (miRNAs/miRs) are a group of small non­coding RNAs that serve as post­transcriptional gene modulators. miRNAs have been demonstrated to serve a pivotal role in carcinogenesis and the dysregulated expression of miRNAs is a well­understood characteristic of cancer. In recent years, miR­370 has been established as a key miRNA in various cancers. The expression of miR­370 is dysregulated in various types of cancer and varies markedly across different tumor types. miR­370 can regulate multiple biological processes, including cell proliferation, apoptosis, migration, invasion, as well as cell cycle progression and cell stemness. Moreover, it has been reported that miR­370 affects the response of tumor cells to anticancer treatments. Additionally, the expression of miR­370 is modulated by multiple factors. The present review summarizes the role and mechanism of miR­370 in tumors, and demonstrates its potential as a molecular marker for cancer diagnosis and prognosis.

Most Patients With Autoimmune Chronic Spontaneous Urticaria Also Have Autoallergic Urticaria, but Not ViceVersa.

BACKGROUND: Two endotypes of chronic spontaneous urticaria (CSU) associated with mast cell-activating autoantibodies are described, namely autoallergic chronic spontaneous urticaria (aaCSU; with immunoglobulin E [IgE]-anti-autoallergens) and autoimmune chronic spontaneous urticaria (aiCSU; with IgG-anti-high-affinity receptor for the Fc region of immunoglobulin E [FcεRI]/IgE). OBJECTIVE: To investigate the rates of CSU patients with aaCSU and aiCSU. METHODS: We analyzed 111 CSU patients for aaCSU (ie, IgE to thyroid peroxidase, interleukin 24) and for aiCSU (ie, a positive autologous serum skin and Basophil Activation Test plus immunoglobulin G [IgG]-anti-FcεRI/IgE). Clinical and laboratory parameters were compared in patients with aaCSU, aiCSU, and both. RESULTS: Across 111 patients with CSU, 64 (58%) had aaCSU and 9 (8%) had aiCSU. Eight of the 9 aiCSU patients had aaCSU, but only 8 of 64 patients with aaCSU had aiCSU. In total, 7% (8 of 111) of patients had both aiCSU and aaCSU, 41% (46 of 111) had neither, and 16% (18 of 111) tested negative for all markers of aaCSU and aiCSU assessed. Patients with aaCSU or aiCSU are different from those without: patients with stand-alone aaCSU tend to be younger than non-aaCSU patients, aiCSU, and aaCSU/aiCSU overlapping subpopulations. In contrast, patients with aiCSU, with or without aaCSU coexistence, are more often female, have higher levels of thyroid peroxidase autoantibodies (both IgG and IgE), and show more severe quality of life impairment. CONCLUSIONS: Our novel finding that aiCSU coexisting with aaCSU needs to be confirmed in bigger cohorts and multicenter studies. Autoimmunity driven by autoreactive IgE and/or IgG in CSU needs further investigation for better understanding of the pathophysiology.

Appeal of word of mouth: Influences of public opinions and sentiment on ports in corporate choice of import and export trade in the post-COVID-19 era.

With the advent of the post-COVID-19 era, corporate managers of import and export trade are now more sensitive in their daily work, and their decisions are more likely to be influenced by the emotional bias of public opinions, especially regarding cooperation with trade ports of frequent circulation. Therefore, how to manage public opinion and sentiment in the post-COVID-19 era will be a new opportunity and challenge for the marketing management of ports. For the above considerations, through the same frequency verification between public opinions and sentiment on ports and corporate choice of import and export trade, and through analysis of the influence mechanism, the present study demonstrates the positive effects of public opinions and sentiment on ports in corporate choice of import and export trade in the post-COVID-19 era, verifies the significance of shaping word of mouth in port management, puts forward the great role of public opinions and sentiment in the cognitive and emotional empathy in the choice of import and export trade, and provides theoretical guidance for port managers' strategic choices in the post-COVID-19 era.

Autoimmune chronic spontaneous urticaria.

Chronic spontaneous urticaria (CSU) is a debilitating mast cell-driven disease characterized by recurrent wheals and/or angioedema. Substantial progress has been made in dissecting the 2 main autoimmune mechanisms that drive the pathogenesis of CSU. Type I autoimmune (autoallergic) CSU is associated with IgE antibodies against autoantigens, for example, thyroid peroxidase and IL-24. Type IIb autoimmune CSU is mediated by autoantibodies that activate mast cells, for example, via IgE and FcεRI, and is present in less than 10% of patients with CSU when strict criteria are used, that is, triple positivity of autologous serum skin test, immunoassays for IgG autoantibodies, and basophil activation tests. A subpopulation of patients with CSU has both types. Type IIb autoimmune CSU is characterized by higher disease severity, concomitant autoimmune diseases, low levels of total IgE, elevated levels of IgG-anti-thyroid peroxidase, basopenia, eosinopenia, poor response to antihistamines and to omalizumab, and a good response to cyclosporine. Novel targeted therapies for CSU are under development such as ligelizumab, an anti-IgE, fenebrutinib and remibrutinib, Bruton's tyrosine kinase inhibitors, and dupilumab, an anti-IL-4Rα. Further studies should investigate the overlap between autoallergic and type IIb autoimmune CSU, optimize the diagnosis of both autoimmune endotypes using easy-to-perform, noninvasive, and inexpensive markers, and assess differences in response to therapy.

The Mediating Role of Empathy in the Internal Mechanism of Film-Induced Tourism.

With the advent of the information age and advancement of digital technology, film and television tourism is developing rapidly under the joint action of the film industry and tourism industry, and has become a crucial form of cultural and entertainment consumption for individuals to pursue a better life in the new age. This study designs three experiments from the perspectives of identity conversion, motivation transfer, and demand change to conduct an empirical study on the mediating role of empathy for further exploring the internal mechanism of film-induced tourism in film and television tourism. The findings suggest that the three mediation hypotheses are all valid, indicating that film-induced tourism involves identity conversion from audiences to visitors, motivation transfer from watching to traveling, and demand change from interest to expectation through emotional media.

Sustainable Development for Film-Induced Tourism: From the Perspective of Value Perception.

The tourism economy has become a new driving force for economic growth, and film-induced tourism in particular has been widely proven to promote economic and cultural development. Few studies focus on analyzing the inherent characteristics of the economic and cultural effects of film-induced tourism, and the research on the dynamic mechanism of the sustainable development of film-induced tourism is relatively limited. Therefore, from the perspective of the integration of culture and industry, the research explores the dynamic mechanism of sustainable development between film-induced culture and film-induced industry through a questionnaire survey of 1,054 tourism management personnel, combined with quantitative empirical methods. The conclusion shows that the degree of integration of culture and tourism is an important mediating role that affects the dynamic mechanism of sustainable development of film-induced tourism, and the development of film-induced tourism depends on the integration of culture and industry. Constructing a diversified industrial integration model according to local conditions and determining the development path of resource, technology, market, product integration, and administrative management can become the general trend of the future development of film-induced tourism.

Nonlinear state estimation by Extended Parallelotope Set-Membership Filter.

In this paper, we propose a state estimation method called the Extended Parallelotope Set-Membership Filter that provides a higher estimation accuracy than existing methods for discrete-time nonlinear systems. The Extended Parallelotope Set-Membership Filter is motivated by the fact that the iteration operations in existing methods generate much redundancy, and will deteriorate the accuracy of the state estimation. To account for this issue, an innovative parallelotope envelope method is proposed for the purpose of reducing the redundancy arising from the process of the noise envelope. In addition, a cofactor separation method is designed for nonlinear systems to obtain a tight envelope of the parallelotope set. Furthermore, we develop a novel parallelotope intersection method suitable for the parallelotope envelope to update the state set. The simulation results verified the effectiveness of the proposed method as well as its superiority over conventional methods in terms of both the maximum and average accuracies of the state estimation.