Latent profiles of academic resilience in undergraduate nursing students and their association with resilience and self-efficacy.

AIM: This study aimed to investigate the heterogeneity of academic resilience among nursing students using latent profile analysis and its associated influencing factors. BACKGROUND: Nursing students experience higher levels of stress compared to their peers in other professions, and the cultivation of academic resilience plays a pivotal role in their ability to effectively cope with this stress. Academic resilience not only facilitates success in the face of academic adversity but also contributes to the promotion of mental well-being among nursing students. However, the current research on the academic resilience of nursing students has predominantly focused on a scale-centered total score approach, disregarding individual variability, and hindering the development to inform personalized interventions for enhancing academic resilience. DESIGN: A cross-sectional study. METHODS: A convenience sampling method was used to collect a total of 644 nursing students from two medical schools in Guangzhou City. The participants were recruited through an online survey conducted from January to March 2023. The questionnaires consisted of a general information form, the Chinese version of the Academic Resilience Scale-30 (C-ARS-30), the 10-item Connor Davidson Resilience Scale (CD-RISC-10), and the General Self-Efficacy Scale (GSES). Latent profile analysis was used to identify distinct categories of academic resilience among nursing students, and influencing factors were examined through ordinal logistic regression analysis. RESULTS: The academic resilience levels of nursing students can be divided into three potential categories: 'low academic resilience' (13.0%), 'moderate academic resilience' (70.0%), and 'high academic resilience' (17.0%). Level of grade, GPA, self-reported physical health level, resilience and self-efficacy were significantly influenced the different categories of academic resilience of nursing students (P<0.05). CONCLUSIONS: The majority of undergraduate nursing students were placed in the moderate academic resilience group, however, educational institutions should pay special attention to nursing students demonstrating low levels. Regular assessments of academic resilience are recommended, and personalized interventions should be tailored to address specific academic resilience characteristics across different grades of nursing students. Strategies aimed at enhancing academic resilience among nursing students may include improvements in GPA performance, attention to physical health, and the reinforcement of resilience and self-efficacy.

Latent profiles of nurses' subjective well-being and its association with social support and professional self-concept.

AIM: To identify latent profiles of nurses' subjective well-being (SWB) and explore its association with social support and professional self-concept. DESIGN: This study used an online survey and cross-sectional latent profile analysis design. METHODS: A total of 1009 nurses from 30 hospitals in Guangdong Province, China, were selected using convenience sampling. An online questionnaire survey comprising the following scales was distributed: Index of Well-Being, Nurses' Professional Self-concept Questionnaire and Multidimensional Scale of Perceived Social Support. Nurses' SWB was examined and categorized into profiles using nine Index of Well-being items as explicit variables and ordinal logistic regression analysis was performed to explore factors related to the distinct categories. RESULTS: Nurses' SWB was divided into four latent profiles: extremely low, low, moderate and high. Regression analysis showed that social support and professional self-concept influenced SWB. There were statistically significant differences in age, title, working years, social support and professional self-concept among nurses in the different well-being categories. Ordered logistic regression analysis showed that social support and professional self-concept are associated with different SWB profiles.

Communication between the stem cell niche and an adjacent differentiation niche through miRNA and EGFR signaling orchestrates exit from the stem cell state in the Drosophila ovary.

The signaling environment, or niche, often governs the initial difference in behavior of an adult stem cell and a derivative that initiates a path towards differentiation. The transition between an instructive stem cell niche and differentiation niche must generally have single-cell resolution, suggesting that multiple mechanisms might be necessary to sharpen the transition. Here, we examined the Drosophila ovary and found that Cap cells, which are key constituents of the germline stem cell (GSC) niche, express a conserved microRNA (miR-124). Surprisingly, loss of miR-124 activity in Cap cells leads to a defect in differentiation of GSC derivatives. We present evidence that the direct functional target of miR-124 in Cap cells is the epidermal growth factor receptor (EGFR) and that failure to limit EGFR expression leads to the ectopic expression of a key anti-differentiation BMP signal in neighboring somatic escort cells (ECs), which constitute a differentiation niche. We further found that Notch signaling connects EFGR activity in Cap cells to BMP expression in ECs. We deduce that the stem cell niche communicates with the differentiation niche through a mechanism that begins with the selective expression of a specific microRNA and culminates in the suppression of the major anti-differentiation signal in neighboring cells, with the functionally important overall role of sharpening the spatial distinction between self-renewal and differentiation environments.

Genomic profiling of pediatric hematologic malignancies and diagnosis of cancer predisposition syndromes: tumor-only versus paired tumor-normal sequencing.

Not available.

Unveiling Dynamic Changes and Regulatory Mechanisms of T Cell Subsets in Sepsis Pathogenesis.

Purpose: The pathogenesis of T cell subsets in sepsis during the body's resistance to infection is currently unknown. We aimed to investigate the dynamics and molecular mechanisms of T cells during the development of sepsis. Patients and Methods: Perform single-cell data analysis on peripheral blood mononuclear cells (PBMCs) specimen samples from seven healthy controls, five early-stage sepsis patients, and four late sepsis patients, and the atlas were mapped and analyzed using reference mapping to identify the T cell subpopulations specific to early sepsis. Expression network upstream to investigate the changes of regulatory transcription factors and pathways by pySCENIC. Results: Twenty-two CD4+ T-cell subpopulations and 10 CD8+ T-cell subpopulations were identified by mapping analysis. At the early stage of sepsis, we observed altered ratios of multiple immune cells in PBMCs. Three cell types CD4 Tn cells, CD8 (GZMK+ early Tem), and CD8 (ZNF683+CXCR6- Tm) showed an upward trend (p < 0.05) in the early stages of sepsis compared to normal and returned to normal levels after two weeks. In addition, we found the presence of four sepsis-specific transcription factors (MXI1, CHD1, ARID5A, KLF9) in these three types of cells, which were validated in two external datasets. The differentially expressed genes in CD4 Tn cells, CD8 (GZMK+ early Tem), and CD8 (ZNF683+CXCR6- Tm) cells between the healthy group and the early-stage sepsis group are commonly enriched in the allograft rejection pathway. In addition, it was found that CD8 cells exhibit a trend towards differentiation into CD8 Temra cells in sepsis. Conclusion: We successfully depicted the dynamic changes of T cell subsets during sepsis onset and progression, which provides important clues for an in-depth understanding of T cells' function and regulatory mechanisms during sepsis pathogenesis.

Lipocalin-2 promotes neutrophilic inflammation in nasal polyps and its value as biomarker.

BACKGROUND: Chronic rhinosinusitis with nasal polyps (CRSwNP) is a common chronic inflammatory disease of the nasal cavity and paranasal sinuses. The role of neutrophils in the pathogenesis of CRSwNP has attracted more attention in recent years, due to its association with more severe disease and reduced steroid responsiveness. Lipocalin-2 (LCN2) has been found to modulate neutrophils infiltration in other neutrophilic inflammation including inflammatory bowel disease, rheumatoid arthritis, and psoriasis. The aim was to evaluate the expression and regulator role of LCN2 in neutrophilic inflammation in CRSwNP, and its role as a potential biomarker predicting non-eosinophilic CRSwNP (neCRSwNP). METHODS: Bioinformatic analysis, immunostainings, real-time PCR and ELISA were used to analyze the expression and location of LCN2 in nasal tissues. The expression of proinflammatory mediators were assessed in nasal tissues and secretions. LCN2 production in human nasal epithelial cells (HNECs) and neutrophils, as well as its role in neutrophilic inflammation was evaluated by in vitro experiments. RESULTS: LCN2 was mainly located in neutrophils and HNECs of nasal polyps. LCN2 expression was also significantly higher in the polyp tissue and nasal secretions from patients with neCRSwNP. The LCN2 levels were positively correlated with type 3 inflammation markers, including G-CSF, IL-8, and IL-17. LCN2 expression could be upregulated by IL-17 A and TNF-α in HNECs, and LCN2 could also promote the expression of IL-8 in dispersed polyp cells and HNECs. CONCLUSIONS: LCN2 could serve as a novel biomarker predicting patients with neCRSwNP, and the increased expression of LCN2 may participate in the pathogenesis of neCRSwNP.

Uncovering the Genetic Etiology of Inherited Bone Marrow Failure Syndromes Using a Custom-Designed Next-Generation Sequencing Panel.

Inherited bone marrow failure syndromes (IBMFS) are a group of heterogeneous disorders that account for ∼30% of pediatric cases of bone marrow failure and are often associated with developmental abnormalities and cancer predisposition. This article reports the laboratory validation and clinical utility of a large-scale, custom-designed next-generation sequencing panel, Children's Hospital of Philadelphia (CHOP) IBMFS panel, for the diagnosis of IBMFS in a cohort of pediatric patients. This panel demonstrated excellent analytic accuracy, with 100% sensitivity, ≥99.99% specificity, and 100% reproducibility on validation samples. In 269 patients with suspected IBMFS, this next-generation sequencing panel was used for identifying single-nucleotide variants, small insertions/deletions, and copy number variations in mosaic or nonmosaic status. Sixty-one pathogenic/likely pathogenic variants (54 single-nucleotide variants/insertions/deletions and 7 copy number variations) and 24 hypomorphic variants were identified, resulting in the molecular diagnosis of IBMFS in 21 cases (7.8%) and exclusion of IBMFS with a diagnosis of a blood disorder in 10 cases (3.7%). Secondary findings, including evidence of early hematologic malignancies and other hereditary cancer-predisposition syndromes, were observed in 9 cases (3.3%). The CHOP IBMFS panel was highly sensitive and specific, with a significant increase in the diagnostic yield of IBMFS. These findings suggest that next-generation sequencing-based panel testing should be a part of routine diagnostics in patients with suspected IBMFS.

Long head of biceps tendon transposition for massive and irreparable rotator cuff tears: A systematic review and meta-analysis.

BACKGROUND: Superior capsular reconstruction (SCR) with long head of biceps tendon (LHBT) transposition was developed to massive and irreparable rotator cuff tears (MIRCTs); however, the outcomes of this technique remain unclear. AIM: To perform a systematic review of biomechanical outcomes and a meta-analysis of clinical outcomes after LHBT transposition for MIRCTs. METHODS: We performed a systematic electronic database search on PubMed, EMBASE, and Cochrane Library. Studies of SCR with LHBT transposition were included according to the inclusion and exclusion criteria. Biomechanical studies were assessed for main results and conclusions. Included clinical studies were evaluated for quality of methodology. Data including study characteristics, cohort demographics, and outcomes were extracted. A meta-analysis was conducted of the clinical outcomes. RESULTS: According to our inclusion and exclusion criteria, a total of six biomechanical studies were identified and reported an overall improvement in subacromial contact pressures and prevention of superior humeral migration without limiting range of motion (ROM) after LHBT transposition for MIRCTs. A total of five clinical studies were included in the meta-analysis of LHBT transposition outcomes, consisting of 253 patients. The results indicated that compared to other surgical methods for MIRCTs, LHBT transposition had advantages of more significant improvement in ROM (forward flexion mean difference [MD] = 6.54, 95% confidence interval [CI]: 3.07-10.01; external rotation [MD = 5.15, 95%CI: 1.59-8.17]; the acromiohumeral distance [AHD] [MD = 0.90, 95%CI: 0.21-1.59]) and reducing retear rate (odds ratio = 0.27, 95%CI: 0.15-0.48). No significant difference in American Shoulder and Elbow Surgeons score, visual analogue scale score, and University of California at Los Angles score was demonstrated between these two groups for MIRCTs. CONCLUSION: In general, SCR with LHBT transposition was a reliable and economical technique for treating MIRCTs, both in terms of biomechanical and clinical outcomes, with comparable clinical outcomes, improved ROM, AHD, and reduced the retear rates compared to conventional SCR and other established techniques. More high-quality randomized controlled studies on the long-term outcomes of SCR with LHBT transposition are required to further assess.

Role of mitochondrial fusion proteins MFN2 and OPA1 on lung cellular senescence in chronic obstructive pulmonary disease.

BACKGROUND: Mitochondrial dysfunction and lung cellular senescence are significant features involved in the pathogenesis of chronic obstructive pulmonary disease (COPD). Cigarette smoke (CS) stands as the primary contributing factor to COPD. This study examined mitochondrial dynamics, mitophagy and lung cellular senescence in COPD patients and investigated the effects of modulation of mitochondrial fusion [mitofusin2 (MFN2) and Optic atrophy 1 (OPA1)] on CS extract (CSE)-induced lung cellular senescence. METHODS: Senescence-associated secretory phenotype (SASP) component mRNAs (IL-1ß, IL-6, CXCL1 and CXCL8), mitochondrial morphology, mitophagy and mitochondria-related proteins (including phosphorylated-DRP1(p-DRP1), DRP1, MFF, MNF2, OPA1, PINK1, PARK2, SQSTM1/p62 and LC3b) and senescence-related proteins (including P16, H2A.X and Klotho) were measured in lung tissues or primary alveolar type II (ATII) cells of non-smokers, smokers and COPD patients. Alveolar epithelial (A549) cells were exposed to CSE with either pharmacologic inducer (leflunomide and BGP15) or genetic induction of MFN2 and OPA1 respectively. RESULTS: There were increases in mitochondrial number, and decreases in mitochondrial size and activity in lung tissues from COPD patients. SASP-related mRNAs, DRP1 phosphorylation, DRP1, MFF, PARK2, SQSTM1/p62, LC3B II/LC3B I, P16 and H2A.X protein levels were increased, while MFN2, OPA1, PINK1 and Klotho protein levels were decreased in lung tissues from COPD patients. Some similar results were identified in primary ATII cells of COPD patients. CSE induced increases in oxidative stress, SASP-related mRNAs, mitochondrial damage and dysfunction, mitophagy and cellular senescence in A549 cells, which were ameliorated by both pharmacological inducers and genetic overexpression of MFN2 and OPA1. CONCLUSIONS: Impaired mitochondrial fusion, enhanced mitophagy and lung cellular senescence are observed in the lung of COPD patients. Up-regulation of MFN2 and OPA1 attenuates oxidative stress, mitophagy and lung cellular senescence, offering potential innovative therapeutic targets for COPD therapy.

Chinese cross-cultural adaptation and validation of the Well-being Numerical Rating Scales.

Introduction: Well-being is a multi-domain concept that involves measuring physical, psychological, social, and spiritual domains. However, there are currently few multi-domain and comprehensive well-being instruments available. In addition, measures that do exist customarily contain a vast number of items that may lead to boredom or fatigue in participants. The Well-being Numerical Rating Scales (WB-NRSs) offer a concise, multi-domain well-being scale. This study aimed to perform the translation, adaptation, and validation of the Chinese version of WB-NRSs (WBNRSs-CV). Methods: A total of 639 clinical participants and 542 community participants completed the WB-NRSs-CV, the Single-item Self-report Subjective Well-being Scale (SISRSWBS), the World Health Organization Five-item Well-Being Index (WHO-5), the 10-item Perceived Stress Scale (PSS-10), and the Kessler Psychological Distress Scale (K10). Results: High internal consistency and test-retest reliability were obtained for both samples. Additionally, WB-NRSs-CV was positively associated with SISRSWBS and WHO-5 and negatively associated with PSS-10 and K10. In the item response theory analysis, the model fit was adequate with the discrimination parameters ranging from 2.73 to 3.56. The diffculty parameters ranged from -3.40 to 1.71 and were evenly spaced along the trait, attesting to the appropriateness of the response categories. The invariance tests demonstrated that there was no difference in WB-NRSs-CV across groups by gender or age. Discussion: The WB-NRSs-CV was translated appropriately and cross-culturally adapted in China. It can be used as a rapid and relevant instrument to assess well-being in both clinical and non-clinical settings, with its utility for well-being measurement and management among the Chinese people.

Chinese adaptation and validation of the chronic rhinosinusitis-patient-reported outcome: Assessment of health-related quality-of-life.

BACKGROUND: The chronic rhinosinusitis patient-reported outcome (CRS-PRO) is a recently published disease-specific questionnaire designed for CRS patients, with fewer entries and ease of completion. This study aimed to translate the CRS-PRO questionnaire into Chinese and assess its reliability, validity, and responsiveness to provide Chinese patients with a more concise and efficient subjective assessment instrument. METHODS: The Chinese version of the CRS-PRO was created through forward-backward translations and cultural adaptation. Here, 168 CRS patients (118 patients CRS with nasal polyps [CRSwNP] and 50 patients with CRS without nasal polyps [CRSsNP]) and 43 healthy individuals were enrolled. All participants completed the CRS-PRO, 22-item Sinonasal Outcome Test (SNOT-22), and EuroQol five dimensions questionnaire (EQ-5D) questionnaires preoperatively as well as 3 and 6 months after surgery. RESULTS: The Chinese version of the CRS-PRO demonstrated good internal consistency, with a Cronbach's α of 0.813. It also exhibited a higher criterion validity (r = 0.65, p < 0.05) than the SNOT-22. A moderate association was found between the CRS-PRO and objective indicators such as the Lund-Mackay and endoscopic scores. Furthermore, the CRS-PRO, like the SNOT-22, could clearly distinguish CRS patients from healthy subjects (p < 0.01), as well as between the CRSwNP and CRSsNP subtypes (p < 0.01). Additionally, changes in the CRS-PRO exhibited a larger effect size compared to changes in the SNOT-22 (Cohen's d = 1.05 and 0.93 vs. 0.71 and 0.90 for 3 and 6 months, respectively, all p < 0.01). CONCLUSIONS: The Chinese version of the CRS-PRO is a concise, reliable, and responsive instrument that can be utilized as a novel subjective evaluation tool for future clinical practice.

Effects of metalloprotease ADAMTS12 on cervical cancer cell phenotype and its potential mechanism.

ADAMTS12 is a gene widely expressed in human tissues. We studied the expression level of ADAMTS12 in cervical cancer tissue and its relationship with clinicopathological features. We also explored the function of ADAMTS12 in cervical cancer cells and its underlying mechanisms. We found the higher expression level of ADAMTS12 in cancer tissues, which was associated with the worse overall survival rate. The immunofluorescence assay showed that the cytoplasm of cervical cancer cells is the main expression site of ADAMTS12. Overexpression of ADAMTS12 in HeLa and CaSki cells prominently promoted the cell proliferation, migration and invasion. We found that 2032 genes were correlated with ADAMTS12, which was mainly related to extracellular matrix, TGF-ß signaling pathway. The phosphorylation levels of mTOR and 4E-BP1 were upregulated in ADAMTS12-overexpressing cells. Co-Immunoprecipitation combined with protein mass spectrometry showed that TGF-ß signaling pathway-related proteins interacting with ADAMTS12 were screened from HeLa cells with ADAMTS12 overexpression. Therefore, we concluded that ADAMTS12 may affect the mTOR signaling pathway through the interacting with TGF-ß1, and then affect the biological function of cervical cancer cells.

Palladium-Catalyzed Decarbonylative Annulation of 2-Arylbenzoic Acids with Internal Alkynes toward Phenanthrenes.

A palladium-catalyzed decarbonylative annulation of 2-arylbenzoic acids with internal alkynes via C(sp2)-H activation has been developed. A series of phenanthrenes were produced in moderate to good yield with good functional group tolerance. The mechanism study indicated that the C(sp2)-H activation should be the rate-determining step during the reaction.

Comprehensive Gene Panel Testing for Hearing Loss in Children: Understanding Factors Influencing Diagnostic Yield.

OBJECTIVE: To evaluate factors influencing the diagnostic yield of comprehensive gene panel testing (CGPT) for hearing loss (HL) in children and to understand the characteristics of undiagnosed probands. STUDY DESIGN: This was a retrospective cohort study of 474 probands with childhood-onset HL who underwent CGPT between 2016 and 2020 at a single center. Main outcomes and measures included the association between clinical variables and diagnostic yield and the genetic and clinical characteristics of undiagnosed probands. RESULTS: The overall diagnostic yield was 44% (209/474) with causative variants involving 41 genes. While the diagnostic yield was high in the probands with congenital, bilateral, and severe HL, it was low in those with unilateral, noncongenital, or mild HL; cochlear nerve deficiency; preterm birth; neonatal intensive care unit admittance; certain ancestry; and developmental delay. Follow-up studies on 49 probands with initially inconclusive CGPT results changed the diagnostic status to likely positive or negative outcomes in 39 of them (80%). Reflex to exome sequencing on 128 undiagnosed probands by CGPT revealed diagnostic findings in 8 individuals, 5 of whom had developmental delays. The remaining 255 probands were undiagnosed, with 173 (173/255) having only a single variant in the gene(s) associated with autosomal recessive HL and 28% (48/173) having a matched phenotype. CONCLUSION: CGPT efficiently identifies the genetic etiologies of HL in children. CGPT-undiagnosed probands may benefit from follow-up studies or expanded testing.

Comparative short-term efficacy of endoscopic sinus surgery and biological therapies in chronic rhinosinusitis with nasal polyps: A network meta-analysis.

BACKGROUND: To compare the safety and efficacy between endoscopic sinus surgery and different biologics in treating chronic rhinosinusitis with nasal polyps in adults by reviewing the existing clinical trials. METHODS: Data extraction and risk of bias assessment were conducted by 2 independent reviewers according to the PRISMA recommendations and any disagreement was resolved by a third investigator. Outcomes were measured through a random-effects model. We searched Embase, Web of Science, MEDLINE, Cochrane, and other relevant sources from its inception to April 30, 2022. We included randomized controlled trials(RCTs) involving endoscopic sinus surgery (ESS) or biologics in treating adult patients with chronic rhinosinusitis with nasal polyps. Studies involving other miscellaneous diseases, non-RCT design, and insufficient participants or follow-up were excluded. RESULTS: In this systematic review, five RCTs and 1748 patients were included. All the biologics, as well as ESS, could significantly improve key nasal outcomes in CRSwNP both at 6 months and 1 year. Dupilumab exhibited better efficacy than ESS in improving SNOT-22 scores at one year. However, ESS showed superiority over three biologics in improving nasal congestion scores (NCS) at two various time points, except for better efficacy of Dupilumab at 1 year. For the loss of smell scores, a greater improvement was observed in the Dupilumab cohort compared with other biologics and even ESS counterparts. Safety analysis showed no significant difference between the ESS cohort and biologic treatment. CONCLUSIONS: In summary, ESS showed comparable improvement in quality of life and symptoms to Omalizumab, Mepolizumab, and Benralizumab. Dupilumab seems to be more effective than ESS in selected items, whereas head-to-head trials and real-world studies are urgent to compare their efficacy. Our findings also showed that biologics could be applied as alternative or adjuvant therapy for uncontrolled severe CRSwNP.

The species coalescent indicates possible bat and pangolin origins of the COVID-19 pandemic.

A consensus species tree is reconstructed from 11 gene trees for human, bat, and pangolin beta coronaviruses from samples taken early in the pandemic (prior to April 1, 2020). Using coalescent theory, the shallow (short branches relative to the hosts) consensus species tree provides evidence of recent gene flow events between bat and pangolin beta coronaviruses predating the zoonotic transfer to humans. The consensus species tree was also used to reconstruct the ancestral sequence of human SARS-CoV-2, which was 2 nucleotides different from the Wuhan sequence. The time to most recent common ancestor was estimated to be Dec 8, 2019 with a bat origin. Some human, bat, and pangolin coronavirus lineages found in China are phylogenetically distinct, a rare example of a class II phylogeography pattern (Avise et al. in Ann Rev Eco Syst 18:489-422, 1987). The consensus species tree is a product of evolutionary factors, providing evidence of repeated zoonotic transfers between bat and pangolin as a reservoir for future zoonotic transfers to humans.

Metabolomics Provides New Insights into Host Manipulation Strategies by Asobara japonica (Hymenoptera: Braconidae), a Fruit Fly Parasitoid.

Asobara japonica (Hymenoptera: Braconidae) is an endoparasitoid wasp that can successfully parasitize a wide range of host species across the Drosophila genus, including the invasive crop pest Drosophila suzukii. Parasitoids are capable of regulating the host metabolism to produce the nutritional metabolites for the survival of their offspring. Here, we intend to investigate the metabolic changes in D. melanogaster hosts after parasitization by A. japonica, using the non-targeted LC-MS (liquid chromatography-mass spectrometry) metabolomics analysis. In total, 3043 metabolites were identified, most of which were not affected by A. japonica parasitization. About 205 metabolites were significantly affected in parasitized hosts in comparison to non-parasitized hosts. The changed metabolites were divided into 10 distinct biochemical groups. Among them, most of the lipid metabolic substances were significantly decreased in parasitized hosts. On the contrary, most of metabolites associated with the metabolism of amino acids and sugars showed a higher abundance of parasitized hosts, and were enriched for a wide range of pathways. In addition, eight neuromodulatory-related substances were upregulated in hosts post A. japonica parasitization. Our results reveal that the metabolites are greatly changed in parasitized hosts, which might help uncover the underlying mechanisms of host manipulation that will advance our understanding of host-parasitoid coevolution.

The vitellogenin receptor gene contributes to mating and host-searching behaviors in parasitoid wasps.

Vitellogenin receptor (VgR) is essential to vitellogenin uptaking and dominates ovary maturation in insects. However, the function of VgR in parasitoid wasps is largely unknown. Here, we applied the Drosophila parasitoid Leptopilina boulardi as a study model to investigate the function of VgR in parasitoids. Despite the conserved sequence characteristics with other insect VgRs, we found L. boulardi VgR (LbVgR) gene was highly expressed in head but lower in ovary. In addition, we found that LbVgR had no effects on ovary development, but participated in host-searching behavior of female L. boulardi and mating behavior of male L. boulardi. Comparative transcriptome analysis further revealed LbVgR might play crucial roles in regulating the expression of some important chemoreception genes to adjust the parasitoid behaviors. These results will broaden our knowledge of the function of VgR in insects, and contribute to develop advanced pest management strategies using parasitoids as biocontrol agents.

Subjective symptoms as predictors for eosinophilic chronic rhinosinusitis with nasal polyps in the Chinese population.

PURPOSE: To evaluate the putative association between subjective symptoms and eosinophilic inflammation in patients with chronic rhinosinusitis with nasal polyps (CRSwNP). METHODS: A total of 102 patients with CRSwNP who underwent endoscopic sinus surgery were prospectively enrolled. The Sinonasal Outcomes Test-22 scores (SNOT-22), EuroQol 5-dimensional Questionnaire scores (ED-5D), and Lund-Mackay scores by computed tomography (CT) were obtained. Patients were grouped as eosinophilic CRSwNP (eCRSwNP) and non-eosinophilic CRSwNP (neCRSwNP). ECRSwNP was defined if tissue eosinophils of nasal polyps were greater than or equal to 8/HPF according to positive major basic protein (MBP) staining, and neCRSwNP otherwise. RESULTS: Thirty neCRSwNP and 72 eCRSwNP patients were included. ECRSwNP patients had higher incidences of asthma (p = 0.001), allergic rhinitis (p = 0.001), and ethmoid-to-maxillary opacification ratio on CT scans (p < 0.001), whereas the proportion of purulent discharge (p < 0.001) and maxillary sinus score (p = 0.002) was higher in the neCRSwNP patients. There were no significant differences between patients on the mains of the EQ-5D health utility values and total SNOT-22 score. However, eCRSwNP patients had higher SNOT-22 scores of sneezing (p = 0.006), runny nose (p < 0.001), and ear/facial domain (p = 0.012), and lower scores of thick nasal discharge (p = 0.015) and blockage (p = 0.042). Sneezing, thick nasal discharge, and blockage/congestion of nose were recognized as independent factors of CRSwNP. CONCLUSION: Sneezing was an independent predictor of eCRSwNP, and thick nasal discharge and blockage/congestion of nose were independent predictors of neCRSwNP.

In vitro and in vivo analyses on anti-NSCLC activity of apatinib: rediscovery of a new drug target V600E mutation.

BACKGROUND: Apatinib (YN968D1) is the first small-molecule-targeting drug with anti-tumor activity created in China for the treatment of advanced gastric cancer (GC) and hepatocellular carcinoma (HCC). It showed significant variation in the efficacy for treating cancers, including advanced non-squamous non-small-cell lung cancer (NSCLC). Whether its efficacy could be optimized by subgrouping patients with certain genetic variation remains elusive. METHODS: Here, we firstly used kinase screening to identify any possible target of apatinib against 138 kinases. The effects of apatinib on proliferation rates, cell cycle, cell apoptosis, and cell migration on cancer cell lines were analyzed; the in vitro potential pathways of apatinib on cancer cell lines were screened. The effect of apatinib on mouse cancer models in vivo was also analyzed. RESULTS: Based on HCC364 cells with BRAF V600E mutation, we have shown that apatinib could inhibit their growth, migration, cell cycle, and induce their apoptosis. Based on mice with transplanted HCC364 cells, we have also shown that apatinib could inhibit the tumor growth. Based on immunohistochemistry, we have demonstrated that apatinib could suppress the phosphorylation of mitogen-activated protein kinase/extracellular signal-regulated kinase and extracellular regulated protein kinases. This may account at least part of the apatinib's inhibitory effect on HCC364 cancer cells. CONCLUSIONS: BRAF V600E protein kinase is a target of apatinib by kinase screening. We have demonstrated that apatinib can effectively inhibit tumor cells with BRAF V600E mutation by in vitro and in vivo experiments. Our results have demonstrated that targeting BRAF V600E mutation, apatinib appears to be effective and safe for treating NSCLC and possibly other cancers with the same mutation.