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Objective To study the efficacy and safety of secukinumab in the treatment of moderate and severe plaque psoriasis in children. Methods A total of 10 children with psoriasis were enrolled at Yongcheng Central Hospital from November 2021 to November 2022. All patients were treated with subcutaneous injection of secukinumab and followed up for 52 weeks. The psoriasis area and severity index (PASI) and childrens' dermatology life quality index(CDLQI) were evaluated, and adverse reactions were observed. Results After 4 weeks of the treatment, 8 patients achieved PASI 75, among which 7 patients achieved PASI 90 and PASI 100 was observed in 5 patients. After 8 weeks of the treatment, all 10 patients reached PASI 75, including 8 patients with PASI 100. After 12 weeks, all 10 patients achieved PASI 100. By 52 weeks, 9 patients reached PASI 75, including 8 patients with PASI 90 and 7 patients with PASI 100. After 4 weeks of the treatment, CDLQI scores were significantly decreased and declined to 0 by 52 weeks. No adverse reactions were observed in all patients. Conclusions Secukinumab can rapidly improve moderate to severe plaque psoriasis in children and exhibits long-lasting benefit. It is safe and can quickly improve the quality of life of the children.

In order to identify the pathogen that caused rust of Bletilla striata in Guangxi Zhuang Autonomous Region and to screen resistance resources for B. striata, the rust pathogen was isolated from infected leaves of B. striata and identified using morphology and molecular methods. At the same time, the resistance of 23 B. striata from different regions was evaluated by artificial inoculation of pathogen. The results were as follows: (1) The urediopores of strain X2 isolated from diseased leaves in B. striata were golden yellow, oval, (21.43-30.95) μm × (13.10-19.05) μm. The teleutospores were golden yellow, obovate or clavate, (17.25-30) μm × (5.5-6.65) μm. (2) The length of ITS sequence of strain X2(OQ826009) was 689 bp, which were compared with other ITS sequences in the GenBank, and the similarity reached 95.86% compared with Coleosporium sp. (KY783686.1). But the phylogenetic tree showed that the sequence was clustered together with two sequences of Coleosporium bletiae (MN108161.1, OP363680.1). The strain X2 was identified as Coleosporium bletiae by combining morphology and molecular methods. (3) After 14 days of artificial inoculation with strain X2, the disease index of 23 Bletilla striata ranged from 0 to 70.7. And the resistance of strain X2 from 23 B. striata were divided into six different levels according to the disease index. Among them, one immune materials was identified for the disease index was 0. Four highly resistant materials were identified for the disease index was 1.7-4.7. Six disease-resistant materials were identified for the disease index was 5.6-9.4. Five medium-resistant materials were identified for the disease index was 12.7-18.3. Five susceptible materials were identified for the disease index was 32.0-49.1 and two highly susceptible materials were identified for the disease index was 62.2-70.7. In conclusion, five materials (one immune material and four highly resistant materials) of B. striata from different places (Honghe City in Yunnan Province, Gongcheng County and Baise City in Guangxi Zhuang Autonomous Region, Zunyi City in Guizhou Province and Yichang City in Hubei Province, respectively) can be promoted directly or applied as parent materials for creating excellent germplasm to resist the rust in B. striata for they express immune or highly resistance. This study provides the basis for further research on pathogenesis and control of rust in B. striata.

In order to identify the pathogens that caused tuber rot in Bletilla striata and study the inhibiting effects of herbal extracts on pathogens, the pathogens that caused tuber rot of B. striata were isolated using usual tissue isolation the strains were identified by morphological and molecular biological techniques, and inhibiting effects of seven traditional Chinese medicine extracts on pathogen were observed. The results were as follows:(1) A total of fourteen fungi and four bacteria were isolated from diseased leaves, leaf sheaths and tubers. But only strain GF-1 caused disease, whose symptoms consistent with those in the field. The incidences of GF-1 disease reinoculated in the field and laboratory were both 100％. (2) GF-1 was identified as a member of Epicoccum, and its colonial morphology was a circular form, with white mycelium, prostrate on the medium, aerial, diaphragms and branches. There were conidia and chlamydospores. (3) At last, the sequence of internal transcribed spacer (ITS) region of GF-1 were analyzed, the length was 522 bp. The sequence was compared with other species in the GenBank and reached 99.62% similarity to Epicoccum sorghinum (MN493119.1) isolated form Sorghum, which was closer than others, including Epicoccum sorghinum (MF948994.1) isolated form leaves of Bletilla striata. (4) GF-1 could be fully inhibited when the medium contained 0.1-0.2 g·mL-1 extracts that extracted from seven traditional Chinese medicines, respectively. It also could be fully inhibited by 0.05 g·mL-1 of Cinnamomum cassia or Syringa oblate. In summary, the pathogen that caused tuber rot in Bletilla striata was identified as Epicoccum sorghinum. And GF-1 could be fully inhibited cultivated on the medium which contained 0.1-0.2 g·mL-1 herbal extracts, e.g.: Cinnamomum cassia, Syringa oblate, Cyclocarya paliurus, Bletilla striata, Houpoea officinalis, Illicium verum or Cnidium monnieri. The results provide theoretical references for the control of tuber rot of Bletilla striata.

Abstract Background C-type lectin domain family 1 member B (CLEC1B, encoding the CLEC-2 protein), a member of the C-type lectin superfamily, is a type II transmembrane receptor involved in platelet activation, angiogenesis, and immune and inflammatory responses. However, data regarding its function and clinical prognostic value in hepatocellular carcinoma (HCC) remain scarce. Methods The expression of CLEC1B was explored using The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. RT-qPCR, western blot, and immunohistochemistry assays were employed to validate the downregulation of CLEC1B. Univariate Cox regression and survival analyses were used to evaluate the prognostic value of CLEC1B. Gene Set Enrichment Analysis (GSEA) was conducted to investigate the potential association between cancer hallmarks and CLEC1B expression. The TISIDB database was applied to search for the correlation between immune cell infiltration levels and CLEC1B expression. The association between CLEC1B and immunomodulators was conducted by Spearman correlation analysis based on the Sangerbox platform. Annexin V-FITC/PI apoptosis kit was used for the detection of cell apoptosis. Results The expression of CLEC1B was low in various tumors and exhibited a promising clinical prognostic value for HCC patients. The expression level of CLEC1B was tightly associated with the infiltration of various immune cells in the HCC tumor microenvironment (TME) and positively correlated with a bulk of immunomodulators. In addition, CLEC1B and its related genes or interacting proteins are implicated in multiple immune-related processes and signaling pathways. Moreover, overexpression of CLEC1B significantly influenced the treatment effects of sorafenib on HCC cells. Conclusions Our results reveal that CLEC1B could serve as a potential prognostic biomarker and may be a novel immunoregulator for HCC. However, its function in immune regulation should be further explored.

Allergic rhinitis (AR) is a common inflammation that affects many people globally. Quercetin has anti-allergic biological activity in AR. Here, we aimed to explore the effects of quercetin on type 1 helper T (Th1)/Th2 and regulatory T cells (Treg)/Th17 balance. We established an ovalbumin (OVA)-induced mouse model and orally administered 20, 35, and 50 mg/kg/day quercetin. The nasal symptoms of mice were observed. The immunoglobulin levels, Treg/Th17-related factors, and pro-inflammatory factors were examined by ELISA. The differentiated inflammation cells were visualized using the diff-quick staining assay. The nasal histopathology was evaluated using H&E, periodic acid Schiff (PAS), and Giemsa staining assay. The results showed that quercetin attenuated OVA-induced rubbing and sneezing. Quercetin reduced IgE, IgG1, histamine, and increased IgG2 in serum. The number of differentiated inflammation cells and goblet cells in tissues that elevated by OVA was reduced by quercetin. Moreover, OVA increased the Treg cell percentage, the levels of IL-17, TGF-β, IL-6, TNF-α, and decreased Th17 cell percentage, IL-10 and FOXP3 levels, while quercetin abrogated their levels induced by OVA. Additionally, quercetin inactivated the NF-κB pathway. Taken together, quercetin attenuated AR symptoms by balancing the Th1/Th2, Treg/Th17 ratios, and inactivating the NF-κB pathway. The results suggested that quercetin may use for AR treatment.

Background: T-helper 17 (Th17) cell response is engaged in the onset of allergic rhinitis (AR). Moreover, interleukin (IL)-38 is thought to be involved in inhibiting cytokine secretion in the Th17 pathway.Objective: To evaluate the regulatory function of IL-38 on abnormal Th17 responses in Chinese patients with AR.Methods: Forty-five participants, divided into an AR group (n=25) and a control group (n=20), were recruited for the study. In addition, the expression of IL-38 and Th17-related cytokines was measured as well as the Th17 cell count in participants. By implementing recombinant IL-38 (rIL-38), the intervention of human peripheral blood mononuclear cells (PBMCs) was performed. Then, flow cytometry, polymerase chain reaction (PCR), and enzyme-linked immunosorbent assay (ELISA) were used to detect theTh17 milieu.Results: The expression of IL-38 in the AR group notably reduced compared with that in the control, whereas Th17 cell frequency and the expression levels of its transcription factor (RORC) and cytokines (IL-17A and IL-23) increased. The differentiation and immune function of Th17 cells in PBMCs were inhibited by rIL-38.Conclusion: Th17 responses are inhibited by IL-38 in patients with AR. Therefore, the obtained findings indicate that IL-38 is a potential therapeutic target for Chinese patients with AR.

Abstract Background Type 2 innate lymphoid cells (ILC2) are upregulated in childhood allergic rhinitis (AR) and are associated with AR severity. This study aimed to investigate changes in the ILC2 milieu in pediatric patients with AR after sublingual immunotherapy (SLIT). Methods Forty- pediatric patients with AR received house dust mite (HDM) allergen extract for SLIT group and thirty pediatric patients received placebo in the study, respectively. The levels of ILC2, ILC2-related cytokines (IL-5/IL-13) and their transcription factors (GATA binding protein 3, retinoic acid-related orphan receptor α) in the circulation were assessed after 1- and 2-year SLIT. Moreover, peripheral blood mononuclear cells (PBMCs) in patients were prepared and stimulated by recombinant thymic stromal lymphopoietin, IL-25, and IL-33 after 2-year SLIT. Subsequently, the levels of ILC2, IL-5, and IL-13 were tested. Results The frequency of ILC2 and the levels of their transcription factors in the circulation were significantly decreased after SLIT in the SLIT group. The levels of ILC2-related cytokines in the SLIT group showed the same trend. The frequency of ILC2 was positively correlated with transcription factors and cytokines after SLIT. SLIT was observed to reduce the ability of HDM sensitization to generate the ILC2 milieu in PBMCs. Conclusions Changes in the ILC2 milieu may be correlated with the curative effect and immune regulation function of SLIT. Our results suggested that the regulatory effect on ILC2 is part of the therapeutic mechanism of SLIT.

Abstract Background Chronic rhinosinusitis with nasal polyps (CRSwNP) was potentially due to the epithelial barrier injury. YES‐associated protein (YAP) is a multifunctional transcriptional factor and plays versatile roles in the regulation and maintenance of epithelial barrier in different organs and tissues. The purpose of this study is to elucidate possible effect and mechanism of YAP on the epithelial barrier of CRSwNP. Methods Patients were divided into CRSwNP group (n = 12) and control group (n = 9). The location of YAP, PDZ‐binding transcriptional co‐activator (TAZ), and Smad7 were estimated by immunohistochemistry and immunofluorescence. Meanwhile, the expression of YAP, TAZ, Zona occludens‐1 (ZO‐1), E‐cadherin, and transforming growth factor‐beta1 (TGF‐β1) were detected by Western blot. After primary human nasal epithelial cells were treated with YAP inhibitor, the expression level of YAP, TAZ, ZO‐1, E‐cadherin, TGF‐β1, and Smad7 were measured by Western blot. Results Compared with the control group, the protein levels of YAP, TAZ, and Smad7 were significantly upregulated, while TGF‐β1, ZO‐1, and E‐cadherin were downregulated in CRSwNP. YAP and Smad7 demonstrated lower levels, while the expression of ZO‐1, E‐cadherin, and TGF‐β1 rose slightly after YAP inhibitor treatment in primary nasal epithelial cells. Conclusions Higher level of YAP may lead to CRSwNP epithelial barrier injury via the TGF‐β1 signaling pathway, and the inhibition of YAP can partially reverse epithelial barrier function.

Gastric cancer (GC) is one of the most common neoplastic malignancies, which permutes a fourth of cancer-related mortality globally. RNA modification plays a significant role in tumorigenesis, the underlying molecular mechanism of how different RNA modifications directly affect the tumor microenvironment (TME) in GC is unclear. Here, we profiled the genetic and transcriptional alterations of RNA modification genes (RMGs) in GC samples from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) cohorts. Through the unsupervised clustering algorithm, we identified three distinct RNA modification clusters and found that they participate in different biological pathways and starkly correlate with the clinicopathological characteristics, immune cell infiltration, and prognosis of GC patients. Subsequently, univariate Cox regression analysis unveiled 298 of 684 subtype-related differentially expressed genes (DEGs) are tightly interwoven to prognosis. In addition, we conducted the principal component analysis to develop the RM_Score system, which was used to quantify and predict the prognostic value of RNA modification in GC. Our analysis indicated that patients with high RM_Score were characterized by higher tumor mutational burden, mutation frequency, and microsatellite instability which were more susceptible to immunotherapy and had a favorable prognosis. Altogether, our study uncovered RNA modification signatures that may have a potential role in the TME and prediction of clinicopathological characteristics. Identification of these RNA modifications may provide a new understanding of immunotherapy strategies for gastric cancer.

The article in the Journal of Fluid Mechanics delves into flow patterns and energy spectra in forced quasi-two-dimensional turbulence, examining how system size and damping rate influence these phenomena. It uncovers that larger system sizes display streamers while smaller sizes exhibit coherent vortices, and the damping rate impacts the energy spectrum transition. The study proposes the dimensionless Taylor microscale as a diagnostic tool for spectral transition. Overall, the research sheds light on the intricate dynamics of turbulence and challenges current theories in the field. [Extracted from the article]