Group 3 innate lymphoid cells secret neutrophil chemoattractants and are insensitive to glucocorticoid via aberrant GR phosphorylation.

BACKGROUND: Patients with neutrophil-mediated asthma have poor response to glucocorticoids. The roles and mechanisms of group 3 innate lymphoid cells (ILC3s) in inducing neutrophilic airway inflammation and glucocorticoid resistance in asthma have not been fully clarified. METHODS: ILC3s in peripheral blood were measured by flow cytometry in patients with eosinophilic asthma (EA) and non-eosinophilic asthma (NEA). ILC3s were sorted and cultured in vitro for RNA sequencing. Cytokines production and signaling pathways in ILC3s after IL-1ß stimulation and dexamethasone treatment were determined by real-time PCR, flow cytometry, ELISA and western blot. RESULTS: The percentage and numbers of ILC3s in peripheral blood was higher in patients with NEA compared with EA, and negatively correlated with blood eosinophils. IL-1ß stimulation significantly enhanced CXCL8 and CXCL1 production in ILC3s via activation of p65 NF-κB and p38/JNK MAPK signaling pathways. The expression of neutrophil chemoattractants from ILC3s was insensitive to dexamethasone treatment. Dexamethasone significantly increased phosphorylation of glucocorticoid receptor (GR) at Ser226 but only with a weak induction at Ser211 residues in ILC3s. Compared to human bronchial epithelial cell line (16HBE cells), the ratio of p-GR S226 to p-GR S211 (p-GR S226/S211) was significantly higher in ILC3s at baseline and after dexamethasone treatment. In addition, IL-1ß could induce Ser226 phosphorylation and had a crosstalk effect to dexamethasone via NF-κB pathway. CONCLUSIONS: ILC3s were elevated in patients with NEA, and associated with neutrophil inflammation by release of neutrophil chemoattractants and were glucocorticoid (GC) resistant. This paper provides a novel cellular and molecular mechanisms of neutrophil inflammation and GC-resistance in asthma. Trial registration The study has been prospectively registered in the World Health Organization International Clinical Trials Registry Platform (ChiCTR1900027125).

Chemical comparison and discrimination of two plant sources of Angelicae dahuricae Radix, Angelica dahurica and Angelica dahurica var. formosana, by HPLC-Q/TOF-MS and quantitative analysis of multiple components by a single marker.

INTRODUCTION: Angelica dahurica(BZ) and Angelica dahurica var. formosana(HBZ) are two plant sources of Angelicae dahuricae Radix. Although BZ and HBZ are commonly used herbal medicines with great medicinal and dietary values, study on their phytochemicals and bioactive compositions is limited. OBJECTIVE: To compare the chemical compositions of BZ and HBZ and find the chemical makers for discrimination and quality evaluation of the two botanical origins of Angelicae dahuricae Radix. METHODOLOGY: A high-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry method was established for chemical profiling of BZ and HBZ. Then, a quantitative analysis of multiple components by a single marker method was developed for simultaneous determination of nine bioactive coumarins (xanthotoxol, oxypeucedanin hydrate, byakangelicin, xanthotoxin, bergapten, oxypeucedanin, phellopterin, imperatorin and isoimperatorin). Moreover, chemometrics were performed to compare and discriminate BZ and HBZ samples. RESULTS: A total of 30 coumarins compounds were identified, and the chemical compositions in BZ and HBZ were quite similar. The quantitative analysis showed that there were significant differences in the contents of bioactive coumarins, and the chemometric analysis indicated five coumarins (xanthotoxol, xanthotoxin, bergapten, phellopterin and isoimperatorin) were responsible for the significant differences between BZ and HBZ, which could be used as chemical markers to distinguish the two original plant sources of Angelicae dahuricae Radix. CONCLUSION: The present work provided useful information for understanding the chemical differences between BZ and HBZ and also provided feasible methods for quality evaluation and discrimination of herbal medicines originating from multiple botanical sources.

MiR-124-3p targeting PDE4B attenuates LPS-induced ALI through the TLR4/NF-κB signaling pathway.

BACKGROUND: A large number of studies have found that microRNAs (miRNAs) and phosphodiesterase 4 (PDE4) are crucial regulators of inflammatory responses in acute lung injury (ALI). OBJECTIVE: This study will explore the protective effect of miR-124-3p on ALI and its related mechanism. METHODS: The ALI mouse model was established by intratracheal administration of lipopolysaccharide (LPS) and evaluated by haematoxylin and eosin (HE) staining, lung injury score, inflammation factors, polymorphonuclear leukocyte (PMN) count, total protein and lung wet weight/dry weight (W/D) ratio. MiR-124-3p was overexpressed in vivo by intratracheal administration of miR-agomir, and PDE4B was expressed at low level in vivo by intratracheal administration of a PDE4B inhibitor. The mRNA expression level was detected by qRT-PCR, and the protein expression level was detected by Western blot. The relationship between miR-124-3p and PDE4B was detected by dual-luciferase activity assay. RESULTS: We found that miR-124-3p was downregulated in LPS-induced ALI. Overexpression of miR-124-3p alleviated lung injury by inhibiting the Toll-like receptor 4 (TLR4)/nuclear factor-kappa B (NF-κB) signaling pathway. Furthermore, we confirmed that miR-124-3p suppressed the TLR4/NF-κB signaling pathway by directly targeting PDE4B. CONCLUSION: miR-124-3p targeting PDE4B had a protective effect on LPS-induced ALI by inhibiting the TLR4/NF-κB signaling pathway.

Clinical characteristics and postoperative outcomes of systemic artery-to-pulmonary vessel fistula in hemoptysis patients.

OBJECTIVES: To investigate the clinical characteristics and outcomes on the success of bronchial arterial embolization (BAE) in patients with and without systemic artery-to-pulmonary vessel fistula (SA-PF) and to evaluate the feasibility of CTA in the assessment of SA-PF. METHODS: We retrospectively enrolled 420 consecutive patients that underwent BAE for hemoptysis control in our hospital from September 2011 to May 2019. The clinical characteristics, preprocedural CTA findings, BAE procedural findings, and follow-up outcomes were collected. Patients were divided into two groups according to DSA findings: patients with SA-PF and those without. RESULTS: A total of 184 (43.7%) patients presented with SA-PF. Pneumonia was less likely to be the concomitant condition in patients with SA-PF (p < 0.001). The mean number of culprit arteries per patient was significantly higher in patients with SA-PF compared to that in patients without SA-PF (p = 0.017). The SA-PF patients saw a greater probability of recurrence (HR: 2.782, 95% CI: 1.617-4.784, p < 0.001). SA-pulmonary venous fistula (SA-PVF) favored lower hemoptysis recurrence rate (HR: 0.199, 95%CI: 0.052-0.765, p = 0.019). SA-pulmonary artery fistula (SA-PAF) can be detected by optimized CTA protocol with a detection rate of 65.3% (49/75). CONCLUSIONS: The presence of SA-PF is an independent risk factor predicting early recurrence of hemoptysis after BAE. SA-PVF seems to be a protective factor for longer hemoptysis control compared to SA-PAF. Optimized preprocedural CTA is a reliable examination to identify SA-PAF. KEY POINTS: • The appearance of SA-PF is associated with a greater probability of early recurrent hemoptysis after bronchial artery embolization. • The presence of SA-PVF seems to be a protective factor for longer hemoptysis control after BAE compared to SA-PAF. • Optimized CTA protocol seems to be a promising auxiliary examination to detect SA-PAF.

Long-Term Wu Qin Xi Exercise on Response Inhibition and Cortical Connectivity in Parkinson's Disease: Design and Implementation of a Randomized Controlled Clinical Trial.

Background: Motor symptom disorders in patients with Parkinson disease (PD) are closely related to reduced inhibitory ability. Although exercise has been shown to improve this ability in patients with PD, its effects on proactive and reactive inhibition have not been determined. Most previous studies of inhibitory control disorder in people with PD have been behavioral, and little attention has been paid to functional cortical connectivity. Wu Qin Xi, a low-medium-intensity qigong exercise that is safe and easy to do for elderly individuals, can support physical well-being and help prevent and alleviate disease. In this study, our aims were to explore the effects of a long-term Wu Qin Xi intervention on response inhibition and to examine how improved inhibition control relates to cortical connectivity using dual-site paired-pulse transcranial magnetic stimulation (ppTMS), in patients with mild-moderate PD. Methods: A single-blind randomized controlled trial will be conducted. A total of 90 elderly subjects will be recruited and allocated randomly to Wu Qin Xi, balance exercise, and healthy control groups. The exercise interventions will be implemented in three 90-min sessions per week for 24 weeks; the healthy control group will receive no intervention. The primary assessments will be response inhibition metrics and task-based ppTMS. The secondary outcomes will include motor symptom severity, mobility, balance, emotional state, and quality of life. Assessments will be conducted at baseline, at the conclusion of the intervention period (week 24), and a few months after the intervention (week 36 follow-up). Discussion: This study is designed to provide insights into the effects of practicing Wu Qin Xi on response inhibition function in people with PD. The results will provide evidence on the value of traditional Chinese exercise as a therapeutic rehabilitation option for these patients. They will also provide data addressing how brain function-related cortical connectivity is related to reactive vs. proactive inhibition in people with PD participating in an exercise intervention. Clinical Trial Registration: This study has been registered prospectively in the Chinese Clinical Trial Registry (ChiCTR2000038517, 18 January 2021).

Efficacy and safety of docetaxel and prednisolone chemotherapy in very elderly men with metastatic castration-resistant prostate cancer (mCRPC) in real world: a single institute experience.

BACKGROUND: Prostate cancer is the most common type of malignancy in elderly men. Although elderly patients are commonly encountered in clinical practice, few studies have focused on the value of chemotherapy in elderly patients. In this study, we reviewed the use of docetaxel with prednisolone in elderly men (aged ≥80 years) with metastatic castration-resistant prostate cancer (mCRPC) at Ningbo First Hospital with a focus on efficacy and toxicity. METHODS: A retrospective study including a series of men aged ≥80 years with mCRPC and received docetaxel plus prednisone chemotherapy between August 2011 and May 2019. All these cases were selected from the Ningbo First Hospital prostate cancer database located in Zhejiang Province, China. RESULTS: Sixteen patients were identified, with a mean age of 82 years (range, 80 to 87 years). All patients have received a median of four and half cycles (range, 1-10) of 3-week (60-75 mg/m2 ) docetaxel regimens and 5 mg prednisone twice per day. Seven (43.75%) patients completed more than six cycles. Ten (62.50%) patients had a good prostate-specific antigen (PSA) response of ≥50% decline. Eight (50.00%) patients had ostealgia before receiving docetaxel treatment and six of them (75.00%) experienced reduced pain after the treatment. Hematologic toxicity was observed in six (37.50%) patients with neutropenia, one of which was diagnosed with agranulocytosis and had to be admitted for the same reason. Other adverse reactions such as fever, debilitation, and alopecia were also observed. CONCLUSIONS: Very elderly patients (aged ≥80 years) with mCRPC are easy to be neglected and infrequently involved in clinical trials. Our study demonstrates that docetaxel chemotherapy plus prednisone is tolerable and effective among Chinese elderly patients (≥80 years) with mCRPC. Docetaxel chemotherapy may be given under careful surveillance even in frail elderly patients.

Genome-wide characterization, expression analyses, and functional prediction of the NPF family in Brassica napus.

BACKGROUND: NITRATE TRANSPORTER 1/PEPTIDE TRANSPORTER (NRT1/PTR) family (NPF) members are essential transporters for many substrates in plants, including nitrate, hormones, peptides, and secondary metabolites. Here, we report the global characterization of NPF in the important oil crop Brassica napus, including that for phylogeny, gene/protein structures, duplications, and expression patterns. RESULTS: A total of 199 B. napus (BnaNPFs) NPF-coding genes were identified. Phylogenetic analyses categorized these genes into 11 subfamilies, including three new ones. Sequence feature analysis revealed that members of each subfamily contain conserved gene and protein structures. Many hormone-/abiotic stress-responsive cis-acting elements and transcription factor binding sites were identified in BnaNPF promoter regions. Chromosome distribution analysis indicated that BnaNPFs within a subfamily tend to cluster on one chromosome. Syntenic relationship analysis showed that allotetraploid creation by its ancestors (Brassica rapa and Brassica oleracea) (57.89%) and small-scale duplication events (39.85%) contributed to rapid BnaNPF expansion in B. napus. A genome-wide spatiotemporal expression survey showed that NPF genes of each Arabidopsis and B. napus subfamily have preferential expression patterns across developmental stages, most of them are expressed in a few organs. RNA-seq analysis showed that many BnaNPFs (32.66%) have wide exogenous hormone-inductive profiles, suggesting important hormone-mediated patterns in diverse bioprocesses. Homologs in a clade or branch within a given subfamily have conserved organ/spatiotemporal and hormone-inductive profiles, indicating functional conservation during evolution. qRT-PCR-based comparative expression analysis of the 12 BnaNPFs in the NPF2-1 subfamily between high- and low-glucosinolate (GLS) content B. napus varieties revealed that homologs of AtNPF2.9 (BnaNPF2.12, BnaNPF2.13, and BnaNPF2.14), AtNPF2.10 (BnaNPF2.19 and BnaNPF2.20), and AtNPF2.11 (BnaNPF2.26 and BnaNPF2.28) might be involved in GLS transport. qRT-PCR further confirmed the hormone-responsive expression profiles of these putative GLS transporter genes. CONCLUSION: We identified 199 B. napus BnaNPFs; these were divided into 11 subfamilies. Allopolyploidy and small-scale duplication events contributed to the immense expansion of BnaNPFs in B. napus. The BnaNPFs had preferential expression patterns in different tissues/organs and wide hormone-induced expression profiles. Four BnaNPFs in the NPF2-1 subfamily may be involved in GLS transport. Our results provide an abundant gene resource for further functional analysis of BnaNPFs.

Genome-Wide Survey and Expression Analysis of the KT/HAK/KUP Family in Brassica napus and Its Potential Roles in the Response to K+ Deficiency.

The KT/HAK/KUP (HAK) family is the largest potassium (K+) transporter family in plants, which plays key roles in K+ uptake and homeostasis, stress resistance, and root and embryo development. However, the HAK family has not yet been characterized in Brassica napus. In this study, 40 putative B. napus HAK genes (BnaHAKs) are identified and divided into four groups (Groups I-III and V) on the basis of phylogenetic analysis. Gene structure analysis revealed 10 conserved intron insertion sites across different groups. Collinearity analysis demonstrated that both allopolyploidization and small-scale duplication events contributed to the large expansion of BnaHAKs. Transcription factor (TF)-binding network construction, cis-element analysis, and microRNA prediction revealed that the expression of BnaHAKs is regulated by multiple factors. Analysis of RNA-sequencing data further revealed extensive expression profiles of the BnaHAKs in groups II, III, and V, with limited expression in group I. Compared with group I, most of the BnaHAKs in groups II, III, and V were more upregulated by hormone induction based on RNA-sequencing data. Reverse transcription-quantitative polymerase reaction analysis revealed that the expression of eight BnaHAKs of groups I and V was markedly upregulated under K+-deficiency treatment. Collectively, our results provide valuable information and key candidate genes for further functional studies of BnaHAKs.

Modulation of hand motor skill performance induced by motor practice combined with matched or mismatched hand posture motor imagery.

Motor imagery (MI), the mental rehearsal of a movement without muscle activation, combined with motor practice (MP) improves the performance of athletes and promotes rehabilitation of motor function among patients with brain injury. The actual hand posture influences the mental simulation of hand movements such that the ability of MI to affect corticospinal excitability is enhanced when the actual hand posture is consistent with the imagined movement of the hand. However, how MP combined with matched or mismatched hand posture MI modulates hand motor skill performance and the underlying neural mechanisms remain unclear. Thus, we first investigated whether MI hand posture that was compatible or incompatible with the actual MP influenced motor performance and corticospinal excitability induced by MI combined with MP. Twenty-eight healthy young adults repeatedly imagined either (1) closing their right hand into a fist with the thumb on top of the fingers and then opening the hand before actually performing that exact motor action or (2) performing the same motor skill but first imagining the right thumb touching the little finger before opening the hand . Changes in the peak acceleration of the hand grasp were measured to assess motor performance. The amplitudes of motor-evoked potentials (MEPs) in a target muscle were obtained using transcranial magnetic stimulation to assess corticospinal activation, a measure of primary cortex stimulation, before, immediately after, and 20 min after the performance. When the results of two-way repeated-measures analyses of variance assessing the effects of the protocols and time on the various measurements were found to be significant, post hoc paired t tests with Bonferroni corrections for multiple comparisons were applied. The results showed that both peak grasp acceleration and corticospinal excitability significantly increased immediately and 20 min after task completion (p < 0.05 for all) only when the MI hand posture matched with that of the actual MP. We then determined whether this increased corticospinal activity was associated with decreased short-interval intracortical inhibition, as measured using paired-pulse transcranial magnetic stimulation. Similar to our previous results, we found that short-interval intracortical inhibition was significantly decreased immediately and 20 min after task completion (p < 0.05 for both) only when MI matched MP. We concluded that the increased motor performance and corticospinal excitability induced by MI and MP depended on the match between the hand posture in the MI and MP, and that this increased corticospinal excitability was associated with disinhibition of the primary motor cortex activity.

[Correlation analysis of main agronomic traits and contents of diterpene lactones of Andrographis paniculata].

In order to study the correlation between the traits of Andrographis paniculata. The main agronomic traits and the content of four kinds of diterpene lactons were measured by the seedlings and the unmutagenized seeds carried by the spacecraft,and multiple comparisons,correlations and principal component analysis were carried out. The results showed that the agronomic traits of A. paniculata have different degrees of difference after being carried by space. The contents of diterpene lactones were quite different. The variation coefficients of deoxyandrographolide content,fresh weight,leaf dry weight,dehydrated andrographolide content,dry weight,neoandrographolide content and andrographolide content were all over 35%. There was a significant correlation between multiple traits,and the leaf weight ratio was significantly positively correlated with the number of primary tillers,leaf dry weight and dry weight,and was significantly negatively correlated with the content of deoxyandrographolide. Andrographolide content was a significantly negatively correlated with the number of leaves and the number of primary tillers,and positively correlated with the other three lactones. Five principal components were extracted from principal component analysis,and the cumulative contribution rate was 83. 127%,which were yield factor,plant type factor,leaf type factor,component factor and seed weight factor. Among the traits affecting the quality of A. paniculata,the yield factor for reliability of the selection of A. paniculata is higher than other factors. There are abundant variations among the traits of A. paniculata,carried in space which increase the genetic diversity. The principal component analysis method can be used to select the principal component factors according to the breeding requirements,which provides a theoretical basis for the breeding of high-yield and high-quality A. paniculata and the high-yield and stable cultivation of A. paniculata.

Twining Poly(polyoxometalate) Chains into Nanoropes.

Organic polymers and inorganic clusters belong to two different disciplines and have completely different properties and structures. When a cluster is attached to the backbone of a polymer as a pendant, the resultant hybrid polymers (polyclusters) exhibit unique behaviours totally different from those of conventional polymers owing to the nanoscale size of the cluster and its particular interactions. Herein, the aggregation of a poly(polyoxometalate)-a polynorbornene backbone with inorganic polyoxometalate cluster pendants-upon addition of a non-solvent to its dilute solution is reported. A three-dimensional network of tangled and snake-like nanothreads was observed. Direct visualisation of individual nanoscale clusters enabled identification of single chains within the nanothreads. These observations suggest that during the process of aggregation, the hybrid polymer forms curved or extended chains as a consequence of an armouring effect in which the collapsed cluster pendants wrap around the backbone. The collapse occurs because they become less soluble in the solvent/non-solvent mixture. The extended chains then become entwined and form nanoropes consisting of multiple chains wound around each other. This study provides a deeper understanding of the nature of polyclusters and should also prove useful for their future development and application.

Reproductive Biology of Johnius taiwanensis (Perciformes: Sciaenidae) in Fujian Waters, Southern China.

Johnius taiwanensis is a newly described species from the Family Sciaenidae (Perciformes). The species is commonly found in shallow coastal waters along both sides of the Taiwan Strait, on the west sides of Zhejiang, Fujian, Guangdong and Hong Kong and east side of Taiwan, and has been misidentified for decades. We studied the reproductive biology of J. taiwanensis from Fujian coastal waters, southern China, using gonadosomatic index (GSI) and gonad histology analyses. Monthly sampling from July 2016 to October 2017 was conducted and a total of 638 specimens were collected, ranging from 7.3 to 19.0 cm standard length (SL). Gonad histology suggested that the spawning activity of J. taiwanensis females and males lasted from April to October, and the peak spawning months for females was July to September. Mature females and males were 12.5 and 11.8 cm SL, respectively, while the estimated sizes at 50% maturity were 12.0 cm and 10.9 cm SL, respectively. Vitellogenic stage oocytes (O3) and post-ovulatory follicles (POF) or hydrated oocytes (HO) were observed, and POF and O3 in ovaries indicated that J. taiwanensis spawns multiple times each spawning season. HO or both HO and POF were observed in ovaries collected from one same location in May 2017 and August 2016.

[Synthesis and identification of artificial antigen of spinosin].

Immunogenic antigen (spinosin-BSA) and coating antigen (spinosin-OVA) of spinosin were synthesized by sodium periodate oxidation method. UV scanning analysis method showed that these two spinosins were successfully conjugated with carrier protein and the coupling ratio was 17 and 13.7, respectively. Meanwhile, when immunized by spinosin-BSA，the mice can produce anti-spinosin antibodies with the high titer (1:32 000),specificity (IC50 211.6 µg·L⁻¹) and low cross-reaction rate measured by ELISA tests. The artificial antigen of spinosin was successfully synthesized, which can be applied for preparation of monoclonal antibodies and establishment of appropriate immune method.

Expertise-Level-Dependent Functionally Plastic Changes During Motor Imagery in Basketball Players.

Motor imagery is the mental process of rehearsing or simulating a given action without overt movements. The aim of the present study is to examine plastic changes in relevant brain areas during motor imagery with increasing expertise level. Subjects (novices, intermediate and elite players) performed motor imagery of basketball throws under two experimental conditions (with-ball and without-ball). We found that all basketball players exhibited better temporal congruence (between motor imagery and motor execution) and higher vividness of motor imagery than novices. The vividness of motor imagery was higher for the with-ball than for the without-ball conditions in all three subject groups. The results from functional magnetic resonance imaging (fMRI) showed three different patterns of cortical activation. Activation in the left middle frontal gyrus increased and that in the left supplementary motor area decreased with increasing levels of motor expertise. Importantly, brain activation in the left postcentral gyrus was the highest in the intermediate players compared to both novices and elite players. For the elite group, these three areas showed higher activation in the without-ball condition than the with-ball condition, while the opposite trend was found in intermediate players. Our findings suggest that the level of motor expertise may be related to high-order brain functions that are linked to different activation patterns in different brain areas.

Identification of significant biomarkers and pathways associated with gastric carcinogenesis by whole genome-wide expression profiling analysis.

The incidence of gastric cancer (GC) is extremely high in East Asia. GC is also one of the most common and lethal forms of cancer from a global perspective. However, to date, we have not been able to determine one or several genes as biomarkers in the diagnosis of GC and have also been unable to identify the genes which are important in the therapy of GC. In this study, we analyzed all genome-wide expression profiling arrays uploaded onto the Gene Expression Omnibus (GEO) database to filtrate the differentially expressed genes (DEGs) between normal stomach tissues and GC tissues. GSE13911, GSE19826 and GSE79973 were based on the GPL570 platform, and GSE29272 was based on the GPL96 platform. We screened out the DEGs from the two platforms and by selecting the intersection of these two platforms, we identified the common DEGs in the sequencing data from different laboratories. Finally, we obtained 3 upregulated and 34 downregulated DEGs in GC from 384 samples. As the number of downregulated DEGs was greater than that of the upregulated DEGs, functional analysis and pathway enrichment analysis were performed on the downregulated DEGs. Through our analysis, we identified the most significant genes associated with GC, such as secreted phosphoprotein 1 (SPP1), sulfatase 1 (SULF1), thrombospondin 2 (THBS2), ATPase H+/K+ transporting beta subunit (ATP4B), gastric intrinsic factor (GIF) and gastrokine 1 (GKN1). The prognostic power of these genes was corroborated in the Oncomine database and by Kaplan-Meier plotter (KM-plotter) analysis. Moreover, gastric acid secretion, collecting duct acid secretion, nitrogen metabolism and drug metabolism were significantly related to GC. Thus, these genes and pathways may be potential targets for improving the diagnosis and clinical effects in patients with GC.