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Stimulator of interferon genes (STING) activation favors effective innate immune responses against viral infections. Its role in chronic rhinosinusitis with nasal polyps (CRSwNP) remains unknown. Our aim was to explore the expression, regulation, and function of STING in CRSwNP. STING expression in sinonasal mucosal samples was analyzed by means of quantitative RT-PCR, immunohistochemistry, flow cytometry, and Western blotting. Regulation and function of STING expression were explored by using cultured primary human nasal epithelial cells (HNECs) and cells of the line BEAS-2B in vitro. STING expression was reduced in eosinophilic nasal polyps compared with that in noneosinophilic nasal polyps and control tissues. STING was predominantly expressed by epithelial cells in nasal tissue and was downregulated by IL-4 and IL-13 in a signal transducer and activator of transcription 6 (STAT6)-dependent manner. HNECs derived from eosinophilic polyps displayed compromised STING-dependent type I interferon production but heightened IL-13–induced STAT6 activation and CCL26 production as compared with HNECs from noneosinophilic polyps and control tissues, which were rescued by exogenous STING overexpression. Knocking down or overexpressing STING decreased or enhanced expression of suppressor of cytokine signaling 1 (SOCS1) in BEAS-2B cells, respectively, independent of the canonic STING pathway elements TBK1 and IRF3. Knocking down SOCS1 abolished the inhibitory effect of STING on IL-13 signaling in BEAS-2B cells. STING expression was positively correlated with SOCS1 expression but negatively correlated with CCL26 expression in nasal epithelial cells from patients with CRSwNP. Reduced STING expression caused by the type 2 milieu not only impairs STING-dependent type I interferon production but also amplifies IL-13 signaling by decreasing SOCS1 expression in nasal epithelial cells in eosinophilic CRSwNP. [Display omitted] [ABSTRACT FROM AUTHOR]

[Display omitted] Chronic rhinosinusitis (CRS) is an upper airway inflammation disease associated with hypoxia-mediated inflammation. The effect of hypoxia-inducible factor 1α (HIF-1α) on NOD-like receptor family pyrin domain containing 3 (NLRP3) inflammasome activation in the pathogenesis of sinonasal mucosa is unclear. We investigated the effect and mechanism of HIF-1α on NLRP3 inflammasome activation in the primary human nasal epithelial cells (hNECs). We measured the expression levels of HIF-1α and the NLRP3 inflammasome in nasal biopsy samples and hNECs derived from negative controls (healthy) and patients with CRS with and without nasal polyps, then further analyzed the specific mechanism of HIF-1α regulation of the NLRP3 inflammasome and its effect on hNEC differentiation. Increased mRNA and protein expression levels of HIF-1α and the NLRP3 inflammasome were found in all CRS biopsy samples. HIF-1α enhanced expression of phosphorylated NLRP3 (S295) in both HEK293T cells and hNECs; it also promoted recruitment of caspase-1 and apoptotic speck-like protein containing caspase recruitment domain (aka ASC) by NLRP3. HIF-1α also improved NLRP3's stability by preventing NLRP3 degradation caused by hypoxia-mediated inflammation. In addition, HIF-1α could also increase expression of Mucin5AC and decrease expression of α-tubulin by promoting activation of the NLRP3 inflammasome in hNECs. In addition, HIF-1α could also directly promote P63 expression in hNECs. HIF-1α could potentially induce cilia loss and enhance the proliferation of goblet cells, possibly mediated by the regulation of NLRP3 phosphorylation in CRS inflammation. [ABSTRACT FROM AUTHOR]

Background Despite advances in our understanding of the mechanisms of influenza A virus (IAV) infection, the crucial virus-host interactions during the viral replication cycle still remain incomplete. Tetraspanin CD151 is highly expressed in the human respiratory tract, but its pathological role in IAV infection is unknown. Objectives We sought to characterize the functional role and mechanisms of action of CD151 in IAV infection of the upper and lower respiratory tracts with H1N1 and H3N2 strains. Methods We used CD151-null mice in an in vivo model of IAV infection and clinical donor samples of in vitro –differentiated human nasal epithelial cells cultured at air-liquid interface. Results As compared with wild-type infected mice, CD151-null infected mice exhibited a significant reduction in virus titer and improvement in survival that is associated with pronounced host antiviral response and inflammasome activation together with accelerated lung repair. Interestingly, we show that CD151 complexes newly synthesized viral proteins with host nuclear export proteins and stabilizes microtubule complexes, which are key processes necessary for the polarized trafficking of viral progeny to the host plasma membrane for assembly. Conclusions Our results provide new mechanistic insights into our understanding of IAV infection. We show that CD151 is a critical novel host factor of nuclear export signaling whereby the IAV nuclear export uses it to complement its own nuclear export proteins (a site not targeted by current therapy), making this regulation unique, and holds promise for the development of novel alternative/complementary strategies to reduce IAV severity. [ABSTRACT FROM AUTHOR]

This paper presents a comprehensive approach for evaluating agroecosystems based on an embodied cosmic exergy investigation. This novel methodology is applied to three distinctive systems: farmland-biogas (F-B), farmland-dairy (F-D) and farmland-dairy-biogas (F-D-B) systems. A comparison of renewability and sustainability among the F-B, F-D and F-D-B systems is conducted to demonstrate this framework. The results show that over 50% of the total cosmic exergy inputs for the F-D-B system can be ascribed to purchased and free renewable resources, which is much higher than the other two systems. The net present ecological value ( NPEV ) of the F-D-B system is approximately 6 times higher than that of the F-B and F-D systems. The sustainability of the F-D-B system is 2.76 and 2.08 times higher than that of the F-D and F-B systems, respectively. The economic benefit ( EB ) of the F-D-B system is the highest of all three systems. These results suggest that the F-D-B system is superior to the other two systems. This study contributes to providing a theoretical foundation for policy-making in the rural regions of China. [ABSTRACT FROM AUTHOR]

Objective Neuropeptide Y, a widely circulating neurotransmitter, plays a pivotal role in energy balance, immunomodulation and asthma, and several NPY polymorphisms are promising genetic risk factors for asthma and obesity. We explored the associations of candidate NPY gene polymorphisms with prevalent asthma and its relationship with obesity in young adult asthma patients free of other chronic medical morbidity. Methods Five common gene variants of NPY (rs16147 (− 399T/C), rs17149106 (− 602G/T), rs16140 (+ 1000C/G), rs5573 (+ 1201A/G), rs5574 (+ 5327C/T)) previously validated to account for most of the NPY expression in vitro and in vivo were investigated in 126 physician-diagnosed asthma patients without other chronic medical morbidity and 182 healthy controls (21–35 years). Plasma levels of NPY, adiponectin, and CRP were determined using ELISA, and IL-6 was measured by Luminex in a subgroup of 70 patients and 69 age- and sex-matched healthy controls. Results In logistic regression models controlling for gender and obesity, the CT genotype of rs5574 (OR = 0.54, 95%CI: 0.30–0.89) and the GT genotype of rs17149106 (OR = 5.58, 95%CI: 1.09–28.54) were significantly associated with asthma. No significant interaction between NPY SNP polymorphisms and obesity were detected. Plasma NPY level was correlated with adiponectin levels ( p < 0.05). Compared with the healthy controls, patients with asthma had higher BMI ( p < 0.001), adiponectin ( p < 0.05), IL-6 ( p = 0.001) and CRP ( p < 0.001), and lower NPY levels ( p < 0.01). Conclusions The CT genotype of rs5574 and the GT genotype of rs17149106 are significantly associated with prevalent asthma. [ABSTRACT FROM AUTHOR]

Objectives Asia-Pacific Burden of Respiratory Diseases is a cross-sectional, observational study examining the burden of disease in adults with respiratory diseases across six countries. The aim of this study was to describe health care resource use (HCRU), work impairment, cost burden, and health-related quality of life (HRQOL) associated with respiratory disease in the Asia-Pacific. Methods Consecutive participants aged 18 years or older with a primary diagnosis of asthma, allergic rhinitis, chronic obstructive pulmonary disease, or rhinosinusitis were enrolled. Participants completed a survey detailing respiratory symptoms, HCRU, work productivity and activity impairment, and HRQOL. Locally sourced unit costs for each country were used in the calculation of total costs. Results The study enrolled 5250 patients. Overall, the mean annual cost for patients with a respiratory disease was US $4191 (SGD 8489) per patient. For patients who reported impairment at work, the mean annual cost was US $7315 (SGD 10,244), with productivity loss being the highest cost component for all four diseases (US $6310 [SGD 9100]). On average, patients were impaired for one-third of their time at work and 5% of their work time missed because of respiratory disease, which resulted in a 36% reduction in productivity. Patients with a primary diagnosis of chronic obstructive pulmonary disease had the greatest impact on HRQOL. Conclusions In the Asia-Pacific, respiratory diseases have a significant impact on HCRU and associated costs, along with work productivity. Timely and effective management of these diseases has the potential to reduce disease burden and health care costs and improve work productivity and HRQOL. [ABSTRACT FROM AUTHOR]

Background Aberrant airway epithelial remodeling is one of the cardinal histopathologic features of inflammatory airway diseases, but whether it alters the mucociliary apparatus remains unknown. Objective We sought to investigate the morphologic pattern of motile cilia and ciliogenesis-associated makers in hyperplastic nasal epithelium from nasal polyps (NPs) both in vivo and in vitro . Methods Biopsy specimens obtained from patients with NPs (n = 44) and inferior turbinate from healthy control subjects (n = 38) were analyzed by using scanning electron microscopy, immunofluorescence staining, single-cell (cytospin) staining, quantitative real-time PCR, and human nasal epithelial stem/progenitor cell culture and differentiation. Results Abnormal cilia architecture (untidy, overly dense, and lengthened) was more commonly observed in patients with NPs by using scanning electron microscopy. Ectopic lengthened cilia were visualized by means of immunofluorescence (patients with NPs: 6.33 μm [5.51-7.43 μm] vs control subjects: 3.73 μm [3.50-4.27 μm], P < .0001), at the site of epithelial hyperplasia in isolated single cells (patients with NPs: 6.55 ± 0.23 μm vs control subjects 4.89 ± 0.24 μm, P < .0001), and in differentiated ciliated cells derived from human nasal epithelial stem/progenitor cells (patients with NPs: 9.20 ± 0.56 μm vs control subjects: 5.21 ± 0.37 μm, P < .0001). Ciliary beat frequency was found to be significantly slower in patients with NPs than control subjects in vitro . Both protein and mRNA levels of ciliogenesis-associated markers (centrosomal protein 110 [CP110], forkhead box J1 [Foxj1], and P73 isoform with an N-terminal transactivation domain [TAp73]) were significantly increased in patients with NPs versus those seen in control subjects and were positively correlated with cilia length. Conclusion For the first time, this study demonstrates for that motile cilia impairment is a co-condition of epithelial hyperplasia in patients with NPs, and this impairment of function is a likely cause of chronic mucosal inflammation or infection (eg, biofilm) observed in patients with chronic rhinosinusitis. [ABSTRACT FROM AUTHOR]

Background: Allergenic components from Blomia tropicalis are important triggers of allergies in the tropics. Objective: We sought to identify and characterize a novel allergen, Blo t 21, from B tropicalis. Methods: Blo t 21 was initially identified from an expressed sequence tag database generated from a B tropicalis cDNA library. Allergenicity of this antigen was examined by means of skin prick testing, ELISA, and IgE immuno-dot blotting. We evaluated whether Blo t 21 and Blo t 5 were cross-reactive by using IgE inhibition ELISAs. Results: Blo t 21, a 129-amino-acid protein sharing 39% identity with Blo t 5, is a product of a single-copy gene. It has an α-helical secondary structure and localizes to midgut and hindgut contents of B tropicalis, as well as fecal particles. Positive responses to Blo t 21 were shown in 93% (40/43) by means of ELISA and 95% (41/43) by means of skin prick testing when assayed in 43 adult patients with ongoing persistent allergic rhinitis. However, sera of 494 consecutive individuals attending outpatient allergy clinics over 1½ years showed 57.9% (286/494) had positive responses to Blo t 21. Although the majority (>75%) of sensitized individuals were cosensitized to both Blo t 5 and Blo t 21, these 2 allergens had a low-to-moderate degree of cross-reactivity. Conclusion: Blo t 21 is a major allergen in B tropicalis that is not highly cross-reactive to Blo t 5, despite sharing some sequence and structural identity. Clinical implications: Blo t 21, representing a new group of allergens, is an important B tropicalis allergen. [Copyright &y& Elsevier]

Background Allergic rhinitis (AR) and asthma are common allergic conditions with a shared genetic component to their cause. The 17q12-21 locus includes several genes that have been linked to asthma susceptibility, but the role of this locus in AR is unclear. Asthma and AR in adults of Chinese ethnicity in Singapore are predominately caused by sensitization against house dust mites with a nearly complete penetrance of the allergen, which presents a unique opportunity for accurately identifying genetic associations with allergic diseases. Objective We sought to define the functional role of 17q12-21 in patients with AR and allergic asthma. Methods We asked whether single nucleotide polymorphisms (SNPs) in the 17q12-21 locus were associated with AR or asthma in a cohort of 3460 ethnic Chinese subjects residing in Singapore (1435 in the discovery phase and 2025 in the validation phase). Full-blood mRNA gene expression data, plasma IgE levels, and immune cell frequencies in peripheral blood were tested against the tag SNP genotypes. Luciferase assays were used to measure the effect of putative promoter SNPs on expression of the asthma-associated orosomucoid-like 3 gene (ORMDL3) . Results Within 17q12-21, only the tag SNP rs8076131 was significantly associated with asthma ( P = 8.53 × 10 −10 ; odds ratio, 0.6715), and AR status was independent of SNPs in this region. C-A alleles at rs8076131 resulted in significantly increased ORMDL3 expression in HEK293 cells in vitro relative to T-G alleles. Moreover, subjects with the risk genotype AA exhibited significantly higher total IgE levels and higher blood eosinophil counts than those with the lower-risk genotypes. Conclusion The 17q12-21 locus has a strong genetic association with allergic asthma but not with AR. The polymorphic effect of this locus is attributed to the linkage set tagged by rs8076131, which affects the expression of ORMDL3 , protein phosphatase 1, regulatory inhibitor subunit 1B ( PPP1R1B ), zona pellucida binding protein 2 ( ZPBP2 ), and gasdermin B (GSDMB) and is correlated with high IgE levels and eosinophil counts in subjects bearing the risk genotype. [ABSTRACT FROM AUTHOR]

Background Nasal polyposis (NP) is recognized as aberrant epithelial remodeling, but the molecular mechanism underlying this process is poorly understood. Two important p53 homologues (p63 and p73) play a key role in orchestrating the epithelial development. Objective We intended to study whether p63 and p73 are involved in the epithelial remodeling seen in patients with NP and their response to oral glucocorticosteroid (GC) treatment. Methods Nasal polyp tissues were obtained from 65 patients, and inferior turbinates were obtained from 19 control subjects without NP. Among patients with NP, 20 were treated with oral prednisone, so that 2 sets of polyp biopsy specimens were taken before (GC naive) and after (GC treated) treatment. Immunohistochemistry and quantitative PCR were performed to determine the expression levels of p63 and p73. Results The increase in p63-positive cell numbers was significant in GC-naive NP epithelium (46%) compared with that seen in control epithelium (5%), and it was positively related to the epithelial hyperplasia in patients with NP. The increase in N-terminal transactivation domain p73–positive cell numbers was found in 27% of GC-naive patients with NP and 16% of control subjects, with no statistical difference. The mRNA expression of both p63 and p73 was significantly upregulated in GC-naive patients with NP versus control subjects, and a positive correlation between the p63 and p73 mRNAs was found in all nasal tissues. Furthermore, the improvement of epithelial structure and reduction of p63 mRNA/protein levels were found in patients with NP after GC treatment. Conclusions Our results suggest that the ectopic expression of p63 in multiple cell layers is an important pathologic phenomenon in the epithelial remodeling seen in chronically inflamed airway epithelium (eg, in patients with NP), and its aberrant expression can be suppressed with GC treatment. [ABSTRACT FROM AUTHOR]

Abstract: Two compound Chinese herbal medicinal ingredients (cCIs) were prepared respectively with epimedium polysaccharide (EPS) plus propolis flavone (PF) and astragalus polysaccharide (APS) plus ginsenoside (GS). Also, two compound Chinese herbal medicines (cCMs) with the same ingredient content as corresponding cCIs were made with the extracts of epimedium plus propolis and astragalus plus ginseng. In rabbit immune trial, two cCIs, physiological saline in the control, were respectively injected to the rabbits vaccinated with inactivated rabbit hemorrhagic disease vaccine. On Days 3, 7, 10, 14, 21, 28, 35 and 42 after vaccination, the dynamic changes of serum antibody titers were determined by hemagglutination inhibition (HI) test. In chicken immune trial, all of cCIs and cCMs were mixed respectively with inactivated Newcastle disease vaccine virus to vaccinate chickens, taking oil-adjuvant and non-adjuvant vaccine as controls. On Days 7, 14, 21, 28, 35 and 42 after vaccination, the dynamic changes of peripheral lymphocyte proliferation and serum antibody titers were tested respectively by MTT method and HI test method. The results showed that both cCIs could significantly raise antibody titer in rabbits, which the effect of compound Chinese herbal medicinal ingredients 1 (cCIs 1) was better than that of compound Chinese herbal medicinal ingredients 2 (cCIs 2). All of cCIs and cCMs could markedly promote lymphocyte proliferation and enhance antibody titer in chickens, which was similar to oil adjuvant, the immunologic enhancement of cCIs were slightly superior to that of the cCMs. [Copyright &y& Elsevier]

Objective: To investigate the effect of fluticasone propionate (FP) on the symptom of nasal obstruction and to assess the correlation between the subjective visual analogue score (VAS) and the objective acoustic rhinometry (AR) measurements. Methods: A prospective study of 45 consecutive patients, 30 males and 15 females with a mean age of 27 years (range: 16–59 years), with moderate/severe symptoms of perennial rhinitis who were treated by FP nasal spray for 4 weeks. AR and VAS were used to evaluate, compare and correlate the efficacy of FP nasal sprays. Results: There was a significant improvement in the VAS post-treatment (3.9) compared with pre-treatment (6.3). There was also a significant increase in the nasal volume (V) and minimum cross-sectional area (MCA) after intranasal FP. Good correlation between the total MCA and total V was noted. Subjective improvements in symptoms did not correlate well with objective measurements as the correlation between VAS and AR was poor. Conclusion: Our study provides subjective and objective evidence on the efficacy of intranasal FP in improving nasal obstruction in perennial rhinitis. AR also proved to be a useful instrument in monitoring the effectiveness of medical therapy for perennial rhinitis. [Copyright &y& Elsevier]

• Chemo-radiotherapy induces long-term defects in nasal epithelial barrier functions. • The defects in nasal epithelium cause sinonasal mucosal infection and inflammation. • Damage of nasal epithelial stem/progenitor cells were found in barrier dysfunction. • Promote nasal epithelial stem/progenitor cells may contribute to recover the barrier. Chronic and recurrent upper respiratory tract infection and inflammation is common in patients with nasopharyngeal carcinoma (NPC) post chemo-radiotherapy (CRT). Whether it is due to intrinsic (e.g., host-defense mechanisms of the epithelium), epigenetic or extrinsic factors is not fully understood. Tissue biopsies of the middle turbinate (MT) and inferior turbinate (IT) from NPC patients after CRT (mean of 3 years, n = 39) were compared with the IT biopsies from healthy subjects (n = 44). The epithelial ultrastructure was examined by transmission electron microscope (TEM). mRNA and protein expressions of epithelial stem/progenitor cells markers, as well markers of cell proliferation and differentiation markers was analyzed. Abnormal epithelial architecture was observed in all tissue samples of NPC patients. Significantly decreased expression levels of mRNA and protein levels for p63 (basal cells), Ki67 (cell proliferation), p63+/KRT5+ (epithelial stem/progenitor cells), MUC5AC and MUC5B (secretary proteins from goblet cells), alpha-tubulin, beta-tubulin and TAp73 (ciliated cells), DNAH5 and DNAI1 and RSPH4A (microtubule assemblies of motile cilia), FOXJ1 and CP110 (ciliogenesis-associated markers) were evident in MT and IT biopsies from NPC patients when compared to healthy controls. CRT causes long-term defects of epithelial barrier functions and increases the susceptibility of these patients to upper respiratory tract infection and inflammation. [ABSTRACT FROM AUTHOR]

Abstract: In this study, we report our findings as we evaluated the association of IL-13 SNP rs20541 to AR as reported in the meta-analysis (Ying, X-J et al., April, Gene 2013) in an Asian population of 1322 ethnic Chinese recruited in Singapore well defined and characterized for allergic rhinitis. The SNP was significantly associated with AR at an odds ratio of 1.57 for the homozygous genotype comparisons indicating a strong risk for AR. This highlights the importance of this mutation in Asian populations for risk towards allergic phenotypes and also warrants further functional work to characterize the mechanism behind this genetic predisposition. [Copyright &y& Elsevier]

Thirty-one compounds, including fourteen triterpenoids ( 1 – 14 ), seven coumarins ( 15 – 21 ), four lignans ( 22 – 25 ), and six diterpenes ( 26 – 31 ) were isolated from the aerial part of Euphorbia hirta . The structures were elucidated by spectroscopic methods and by comparison of their reported spectroscopic data. These compounds have shown the chemical relationships between this plant and other species from the genus Euphorbia . [ABSTRACT FROM AUTHOR]

Abstract: Eighteen compounds, including four hemiterpene glycosides (1–4), three triterpenoid saponins (5–7), four triterpenes (8–11), five sterols (12-16) and two monoterpene glucosides (17 and 18), were isolated from the leaves of Ilex urceolatus C. B. Shang, K. S. Tang et D. Q. Du, which was identified as a new species belonging to the genus Ilex. Among them, compounds 14–18 were firstly isolated from the genus Ilex, others were obtained from I. urceolatus for the first time. This work represented the initially phytochemical study on this plant. The isolated compounds have significant chemotaxonomic characteristics with the other species from this genus. [Copyright &y& Elsevier]

Highlights: [•] We modeled nasal and sinus airflow in a subject before and after targeted sinonasal surgery. [•] The operation changed nasal airflow patterns by altering airflow partitioning between the two airways, decreasing nasal resistance and changing airflow distribution. [•] Sinus airflow rate increased during inspiration after uncinectomy, while during expiration after balloon surgery. [•] The sinus airflow always entered natural ostium and exited from accessory ostium during both inspiration and expiration in both the left and right sinuses. [Copyright &y& Elsevier]

Abstract: We evaluated, by CFD simulation, effects of accessory ostium (AO) on maxillary sinus ventilation. A three-dimensional nasal model was constructed from an adult CT scan with two left maxillary AOs (sinus I) and one right AO (sinus II), then compared to an identical control model with all AOs sealed (sinuses III and IV). Transient simulations of quiet inspiration and expiration at 15L/min, and nasal blow at 48L/min, were calculated for both models using low-Reynolds-number turbulent analysis. At low flows, ventilation rates in sinuses with AOs (I≈0.46L/min, II≈0.54L/min), were both more than a magnitude higher than sinuses without AOs (III≈0.019L/min, IV≈0.020L/min). Absence of AO almost completely prevented sinus ventilation. Increased ventilation of sinuses with AOs is complex. Under high flow conditions mimicking nose blowing, in sinuses II, III, and IV, the sinus flow rate increased. In contrast, the airflow direction through sinus I reversed between inspiration and expiration, while it remained almost constant throughout the respiration cycle in sinus II. CFD simulation demonstrated that AOs markedly increase maxillary sinus airflow rates and alter sinus air circulation patterns. Whether these airflow changes impact maxillary sinus physiology or pathophysiology is unknown. [Copyright &y& Elsevier]

Abstract: Nasal airflow is one of the most important determinants for nasal physiology. During the long evolution of human beings, different races have developed their own attributes of nasal morphologies which result in variations of nasal airflow patterns and nasal functions. This study evaluated and compared the effects of differences of nasal morphology among three healthy male subjects from Caucasian, Chinese and Indian ethnic groups on nasal airflow patterns using computational fluid dynamics simulation. By examining the anterior nasal airway, the nasal indices and the nostril shapes of the three subjects were found to be similar to nasal cavities of respective ethnic groups. Computed tomography images of these three subjects were obtained to reconstruct 3-dimensional models of nasal cavities. To retain the flow characteristics around the nasal vestibules, a 40mm-radius semi sphere was assembled around the human face for the prescription of zero ambient gauge pressure. The results show that more airflow tends to pass through the middle passage of the nasal airway in the Caucasian model, and through the inferior portion in the Indian model. The Indian model was found with extremely low flow flux flowing through the olfactory region. The sizes of vortexes near the anterior cavity were found to be correlated with the angles between the upper nasal valve wall and the anterior head of the nasal cavity. [Copyright &y& Elsevier]

Abstract: Objective: In order to select the component drug in promoting blood circulation and removing blood stasis of Chinese herbal medicinal formula for dairy cow mastitis. Methods: 25 healthy rabbits were allocated randomly into five equal groups. The rabbits in four experimental groups were administered with decoctions of giant knotweed rhizome (GKR, rhizoma polygoni cuspidati), safflower (SF, flos carthami), red sage root (RSR, radix salviae miltiorrhizae) and chuanxiong rhizome (CXR, rhizoma Chuanxiong) by gastrogavage, respectively, in control group, physiological saline, once a day for seven successive days. After the last administration, all rabbits were intravenously injected with 10% macromolecular dextran to induce blood stasis. The blood samples of all rabbits were collected before the first administration, at 2h after the last administration and 1h after injection of dextran, respectively for determination of hemorheologic parameters by MVIS-2035 hemorheology auto-analyzing system. Results: The results showed that all of four kinds of herbs presented different degree of activating blood flow and removing blood stasis. Conclusion: Red sage root was the best especially in resisting blood stasis induced by dextran, and would be selected as main component drug of the prescription for dairy cow mastitis. [Copyright &y& Elsevier]

Rapid diagnostics of adventitious agents in biopharmaceutical/cell manufacturing release testing and the fight against viral infection have become critical. Quantitative real-time PCR and CRISPR-based methods rapidly detect DNA/RNA in 1 h but suffer from inter-site variability. Absolute quantification of DNA/RNA by methods such as digital PCR reduce this variability but are currently too slow for wider application. Here, we report a RApid DIgital Crispr Approach (RADICA) for absolute quantification of nucleic acids in 40-60 min. Using SARS-CoV-2 as a proof-of-concept target, RADICA allows for absolute quantification with a linear dynamic range of 0.6–2027 copies/μL (R2 value > 0.99), high accuracy and low variability, no cross-reactivity to similar targets, and high tolerance to human background DNA. RADICA's versatility is validated against other targets such as Epstein-Barr virus (EBV) from human B cells and patients' serum. RADICA can accurately detect and absolutely quantify EBV DNA with similar dynamic range of 0.5–2100 copies/μL (R2 value > 0.98) in 1 h without thermal cycling, providing a 4-fold faster alternative to digital PCR-based detection. RADICA therefore enables rapid and sensitive absolute quantification of nucleic acids which can be widely applied across clinical, research, and biomanufacturing areas. [ABSTRACT FROM AUTHOR]