Search

Abstract Background Cobalt (Co) is a metal which is widely used in the industrial production. The previous studies found the toxic effects of environmental Co exposure on multiple organs. However, the correlation of blood Co concentration with lung function was inconsistent in patients with chronic obstructive pulmonary disease (COPD). Methods All 771 stable COPD patients were recruited. Peripheral blood and clinical information were collected. The levels of blood Co and serum CC16 were measured. Results Cross-sectional study suggested that the level of blood Co was inversely and dose-dependently related to lung function parameters. Each 1 ppm elevation of blood Co was related to 0.598 L decline in FVC, 0.465 L decline in FEV1, 6.540% decline in FEV1/FVC%, and 14.013% decline in FEV1%, respectively. Moreover, higher age, enrolled in winter, current-smoking, higher smoking amount, and inhaled corticosteroids prominently exacerbated the negative correlation between blood Co and lung function. Besides, serum CC16 content was gradually reduced with blood Co elevation in COPD patients. Besides, serum CC16 was positively correlated with lung function, and inversely related to blood Co. Additionally, decreased CC16 substantially mediated 11.45% and 6.37% Co-triggered downregulations in FEV1 and FEV1%, respectively. Conclusion Blood Co elevation is closely related to the reductions of pulmonary function and serum CC16. CC16 exerts a significantly mediating role of Co-related to pulmonary function decrease among COPD patients.

Abstract Background Prior studies in patients with chronic obstructive pulmonary disease (COPD) had indicated a potential correlation between cadmium (Cd) exposure and reduction in lung function. Nevertheless, the influence of Cd exposure on the progression of COPD remained unknown. Exploring the relationship between Cd exposure and the progression of COPD was the aim of this investigation. Methods Stable COPD patients were enrolled. Blood samples were collected and lung function was evaluated. Regular professional follow-ups were conducted through telephone communications, outpatient services, and patients' hospitalization records. Results Each additional unit of blood Cd was associated with upward trend in acute exacerbation, hospitalization, longer hospital stay, and death within 2 years. Even after adjusting for potential confounding factors, each 1 unit rise in blood Cd still correlated with a rise in the frequencies of acute exacerbation, longer hospital stay, and death. Moreover, COPD patients with less smoking amount, lower lung function and without comorbidities were more vulnerable to Cd-induced disease deterioration. Conclusion Patients with COPD who have higher blood Cd concentration are susceptible to worse disease progression. Graphical Abstract

Thinned unripe kiwifruits (TUK) are considered the major agro by-products in kiwifruit production. To promote their potential applications, polyphenols and biological effects of unripe fruits from nine commercial kiwifruit cultivars were compared. Our findings showed that TUK were rich in bioactive polyphenols, which varied greatly by different cultivars. Indeed, catechin, epicatechin, procyanidin PB1, procyanidin B2, protocatechuic acid, neochlorogenic acid, and gallic acid were measured as the major phenolic components in most TUK, with the highest levels observed in ‘Hongao’ and ‘Cuiyu’ cultivars. Furthermore, TUK exerted strong in vitro antioxidant capacities, inhibitory effects on digestive enzymes, and anti-inflammatory activities. Particularly, their stronger antioxidant effects and inhibitory effects on digestive enzymes were probably attributed to their higher contents of phenolic compounds, especially procyanidin B2. Collectively, our findings reveal that TUK are potential resources of valuable polyphenols, which can be exploited as natural antioxidants and natural inhibitors of α-glucosidase and α-amylase.

Discarded unripe kiwifruits (DUKs) are regarded as the major agro-byproducts in the production of kiwifruits, which have abundantly valuable secondary metabolites. Nevertheless, owing to the limited knowledge about the differences in phytochemicals and bioactivity between DUKs and mature kiwifruits, the utilization of DUKs in the food industry remains scarce. Hence, to promote their food applications, the phenolic compounds and bioactivity of discarded unripe, mature, and overripe fruits from three red-fleshed kiwifruit cultivars were studied and compared. The results revealed that the levels of total phenolics, total flavonoids, and total procyanidins in kiwifruits varied significantly by maturity stage. In addition, our findings demonstrated that DUKs possessed much higher contents of valuable phenolic compounds (e.g., chlorogenic acid (CHA), neochlorogenic acid (NCHA), gallic acid (GA), protocatechuic acid (PA), procyanidin B1 (ProcB1), procyanidin B2 (ProcB2), procyanidin C1 (ProcC1), quercetin 3-O-glucoside (QueG), and quercetin 3-O-rhamnoside (QueR)) than mature and overripe kiwifruits. Furthermore, DUKs exerted much stronger in vitro antioxidant capacity, inhibitory effects on α-glucosidase, and anti-inflammatory activity than mature and overripe kiwifruits, which were mainly attributed to their higher contents of total polyphenols and individual phenolic components, such as GA, CHA, NCHA, PA, ProcB1, ProcB2, ProcC1, and QueR. Overall, these findings provide sufficient evidence for the development and utilization of DUKs in the food/functional food industry.

Researchers are increasingly interested in discovering new pancreatic lipase inhibitors as anti-obesity ingredients. Medicine-and-food homology plants contain a diverse set of natural bioactive compounds with promising development potential. This study screened and identified potent pancreatic lipase inhibitors from 20 commonly consumed medicine-and-food homology plants using affinity ultrafiltration combined with spectroscopy and docking simulations. The results showed that turmeric exhibited the highest pancreatic lipase-inhibitory activity, and curcumin, demethoxycurcumin, and bisdemethoxycurcumin were discovered to be potent pancreatic lipase inhibitors within the turmeric extract, with IC50 values of 0.52 ± 0.04, 1.12 ± 0.05, and 3.30 ± 0.08 mg/mL, respectively. In addition, the enzymatic kinetics analyses demonstrated that the inhibition type of the three curcuminoids was the reversible competitive model, and curcumin exhibited a higher binding affinity and greater impact on the secondary structure of pancreatic lipase than found with demethoxycurcumin or bisdemethoxycurcumin, as observed through fluorescence spectroscopy and circular dichroism. Furthermore, docking simulations supported the above experimental findings, and revealed that the three curcuminoids might interact with amino acid residues in the binding pocket of pancreatic lipase through non-covalent actions, such as hydrogen bonding and π-π stacking, thereby inhibiting the pancreatic lipase. Collectively, these findings suggest that the bioactive compounds of turmeric, in particular curcumin, can be promising dietary pancreatic lipase inhibitors for the prevention and management of obesity.

ObjectivesRegarding increased nuchal translucency (NT), the cutoff values used are heterogeneous in clinical practice, this study aims to assess the efficacy of prenatal detection for chromosomal abnormalities and pregnancy outcomes in fetuses with varying NT thicknesses, in order to provide data that supports informed prenatal diagnosis and genetic counseling for such cases.MethodsWe included 2,272 pregnant women under 35 with singleton pregnancies who underwent invasive prenatal diagnosis between 2014 and 2022. The cohort comprised 2,010 fetuses with increased NT (≥2.5 mm) and 262 fetuses with normal NT but exhibiting a single soft marker. Prenatal diagnoses were supported by chromosomal microarray (CMA) and copy number variation sequencing (CNV-seq) analyses.ResultsThe detection rates of numerical chromosomal abnormalities were 15.4% (309/2,010) and 17.3% (297/1,717) in the NT ≥2.5 and ≥ 3.0 groups, respectively. Pathogenic/likely pathogenic CNV incidence increased with NT thickness (χ2 = 8.60, p 0.05). Fetuses with NT thickness between 2.5 and 2.9 mm combined with the presence of soft markers or non-lethal structural abnormalities exhibited a significantly higher chromosomal abnormality risk (19.0%) compared to fetuses with isolated increased NT ranging from 3.5 to 4.4 mm (13.0%). Pregnancy termination rates increased with NT thickness (χ2 = 435.18, p

To promote the potentially industrial applications of thinned unripe kiwifruits, two deep eutectic solvent-based methods, including deep eutectic solvent-assisted extraction (DAE) and microwave-assisted deep eutectic solvent extraction (MDE), were optimized for the extraction of polysaccharides from thinned unripe kiwifruits (YKP). Results showed that the yields of YKP-D prepared by DAE and YKP-DM prepared by MDE were extremely higher than YKP-H prepared by hot water extraction. Furthermore, YKP-H, YKP-D, and YKP-DM were mainly composed of pectic polysaccharides, including homogalacturonan (HG) and rhamnogalacturonan I (RG I) domains. Besides, both YKP-D and YKP-DM exhibited stronger antioxidant, anti-glycosylation, and immunomodulatory effects than those of YKP-H, and their higher contents of uronic acids and bound polyphenols as well as lower molecular weights could partially contribute to their bioactivities. Overall, these results revealed that the developed MDE method could be utilized as a promising method for highly efficient extraction of YKP with superior beneficial effects.

Background: Birth asphyxia causes hypoxia or inadequate perfusion to the organs of newborns, leading to metabolism dysfunctions including blood glucose disorders. Methods: Neonates with and without birth asphyxia were retrospectively recruited from 53 hospitals in Hubei Province from January 1 to December 31, 2018. In summary, 875, 1139, and 180 cases in the control group, the mild asphyxia group, and the severe asphyxia group were recruited, respectively. Neonatal blood glucose values at postnatal 1, 2, 6, and 12 h (time error within 0.5 h was allowed) were gathered from the medical records. Results: The incidence rates of hyperglycemia in the control group, the mild asphyxia group and the severe asphyxia group were 2.97%, 7.90%, and 23.33%, respectively (p

BackgroundThe effectiveness of acupuncture and tuina in treating knee osteoarthritis (KOA) is still controversial, which limits their clinical application in practice. This study aims to evaluate the short-term and long-term effectiveness of acupuncture and tuina on KOA.Methods/designThis parallel-group, multicenter randomized clinical trial (RCT) will be conducted at the outpatient clinic of five traditional Chinese medicine hospitals in China. Three hundred and thirty participants with KOA will be randomly assigned to acupuncture, tuina, or home-based exercise group with a ratio of 1:1:1. The primary outcome is the proportion of participants achieving a minimal clinically important improvement defined as a ≥ 12% reduction on the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain dimension on short term (week 8) and long term (week 26) compared with baseline. Secondary outcomes are knee joint conditions (pain, function, and stiffness), self-efficacy of arthritis, quality of life, and psychological conditions, which will be evaluated by the WOMAC score and the Patient Global Assessment (PGA), and in addition, the respondents index of OMERACT-OARSI, Short Form 12 Health Survey (SF-12), arthritis self-efficacy scale, and European five-dimensional health scale (EQ-5D). Adverse events will be collected by self-reported questionnaires predefined.Clinical trial registrationhttps://www.chictr.org.cn

Pu-erh tea is a famous tea worldwide, and identification of the geographical origin of Pu-erh tea can not only protect manufacture’s interests, but also boost consumers’ confidence. However, tree age may also influence the fingerprints of Pu-erh tea. In order to study the effects of the geographical origin and tree age on the interactions of stable isotopes and multi-elements of Pu-erh tea, 53 Pu-erh tea leaves with three different age stages from three different areas in Yunnan were collected in 2023. The δ13C, δ15N values and 25 elements were determined and analyzed. The results showed that δ13C, δ15N, Mg, Mn, Fe, Cu, Zn, Rb, Sr, Y, La, Pr, Nd, Sm, Eu, Gd, Tb, Dy, Ho, Er, Tm, Yb, and Lu had significant differences among different geographical origins (p < 0.05). Mn content was significantly influenced by region and tree age interaction. Based on multi-way analysis of variance, principal component analysis and step-wised discriminant analysis, 24 parameters were found to be closely related to the geographical origin rather than tree age, and the geographical origin of Pu-erh tea can be 100.0% discriminated in cross-validation with six parameters (δ13C, δ15N, Mn, Mg, La, and Tb). The study could provide references for the establishment of a database for the traceability of Pu-erh tea, and even the identification of tea sample regions with different tree ages.

IntroductionChina is one of the major producers and exporters of various kinds of citrus fruits. As one of China’s major citrus planting bases, Sichuan has a citrus planting area that exceeds 400,000 hectares. Meanwhile, citrus cultivation has become one of the important agricultural pillar industries in the region. Citrus fruits are reported to show various health-promoting effects, especially antioxidant activity. However, reports on the functional, nutritional and qualitative characteristics of different citrus varieties in Sichuan are still scarce.MethodsThe quality attributes (color parameters, shape, and size), juice properties (titratable acids and total soluble sugar), mineral elements, and health-promoting nutritional and functional components (protein, carbohydrates, fat, dietary fiber, ascorbic acid, phenolic acids, and flavonoids), as well as antioxidant properties of 10 typical citrus varieties cultivated in Sichuan, were systematically investigated and analyzed.Results and DiscussionSignificant differences among different citrus varieties were found. In particular, the total soluble sugar content of Mingrijian was higher than that of other citrus, suggesting its potential for fresh consumption and food processing. Moreover, a total of five flavonoids and nine phenolic acids were identified and quantified. Yuanhong, with higher contents of ascorbic acid and phenolic acids, was considered to be a valuable variety with excellent antioxidant capacity and can be used for value-added processing in the food industry. Principal component analysis and hierarchical cluster heatmap analysis suggested that there were significant differences among the 10 citrus varieties. Correlation analysis confirmed the significant contribution of ascorbic acid and phenolic acids to antioxidant capacity in citrus. The results can provide some references for the cultivation and selection of nutritious citrus fruits.

The cardioprotective effects of sodium-glucose cotransporter type 2 (SGLT2) inhibitors have been demonstrated in many studies. However, their benefits for end-stage kidney disease patients, particularly those on peritoneal dialysis, remain unclear. SGLT2 inhibition has shown peritoneal protective effects in some studies, but the mechanisms are still unknown. Herein, we investigated the peritoneal protective mechanisms of Canagliflozin in vitro by simulating hypoxia with CoCl2 in human peritoneal mesothelial cells (HPMCs) and rats by intraperitoneal injection of 4.25% peritoneal dialysate simulating chronic high glucose exposure. CoCl2 hypoxic intervention significantly increased HIF-1α abundance in HPMCs, activated TGF-β/p-Smad3 signaling, and promoted the production of fibrotic proteins (Fibronectin, COL1A2, and α-SMA). Meanwhile, Canagliflozin significantly improved the hypoxia of HPMCs, decreased HIF-1α abundance, inhibited TGF-β/p-Smad3 signaling, and decreased the expression of fibrotic proteins. Five-week intraperitoneal injection of 4.25% peritoneal dialysate remarkably increased peritoneal HIF-1α/TGF-β/p-Smad3 signaling and promoted peritoneal fibrosis and peritoneal thickening. At the same time, Canagliflozin significantly inhibited the HIF-1α/TGF-β/p-Smad3 signaling, prevented peritoneal fibrosis and peritoneal thickening, and improved peritoneal transportation and ultrafiltration. High glucose peritoneal dialysate increased the expression of peritoneal GLUT1, GLUT3 and SGLT2, all of which were inhibited by Canagliflozin. In conclusion, we showed that Canagliflozin could improve peritoneal fibrosis and function by ameliorating peritoneal hypoxia and inhibiting the HIF-1α/TGF-β/p-Smad3 signaling pathway, providing theoretical support for the clinical use of SGLT2 inhibitors in patients on peritoneal dialysis.

Riboflavin is an essential micronutrient for humans and must be obtained exogenously from foods or supplements. Numerous studies have suggested a major role of riboflavin in the prevention and treatment of various diseases. There are mainly three strategies for riboflavin synthesis, including total chemical synthesis, chemical semi-synthesis, and microbial fermentation, the latter being currently the most promising strategy. In recent years, flavinogenic microbes have attracted increasing attention. Fungi, including Eremothecium ashbyii and Ashbya gossypii, and bacteria, including Bacillus subtilis, Escherichia coli, and lactic acid bacteria, are ideal cell factories for riboflavin overproduction. Thus they are good candidates for enhancing the level of riboflavin in fermented foods or designing novel riboflavin bio-enriched foods with improved nutritional value and/or beneficial properties for human health. This review briefly describes the role of riboflavin in human health and the historical process of its industrial production, and then highlights riboflavin biosynthesis in bacteria and fungi, and finally summarizes the strategies for riboflavin overproduction based on both the optimization of fermentation conditions and the development of riboflavin-overproducing strains via chemical mutagenesis and metabolic engineering. Overall, this review provides an updated understanding of riboflavin biosynthesis and can promote the research and development of fermented food products rich in riboflavin.

Climate warming has been projected to enhance vegetation growth more strongly in higher latitudes than in lower latitudes, but different projections show distinct regional differences. By employing big data analysis (deep learning), we established gridded, global-scale, climate-driven vegetation growth models to project future changes in vegetation growth under SSP scenarios. We projected no substantial trends of vegetation growth change under the sustainable development scenario (SSP1-1.9) by the end of the 21st century. However, the increase of vegetation growth driven by climate warming shows distinct regional variability under the scenario representing high carbon emissions and severe warming (SSP5-8.5), especially in Northeast Asia where growth could increase by (6.00% ± 4.21%). This may be attributed to the high temperature sensitivities of the deciduous needleleaf forests and permanent wetlands in these regions. When the temperature sensitivity that is defined as permutation importance in deep learning is greater than 0.05, the increase in vegetation growth will be more prominent. In addition, an extreme temperature increase across grasslands, as well as changing land-use management in northern China may also influence the vegetation growth in the future. The results suggest that the sustainable development scenario can maintain stable vegetation growth, and it may be a reliable way to mitigate global warming due to potential climate feedbacks driven by vegetation changes in boreal regions. Deciduous needleleaf forests will be a centre of greening in the future, and it should become the focus of future vegetation dynamics modelling studies and projections.

Abstract Background Severe fever with thrombocytopenia syndrome (SFTS), caused by the SFTS virus (SFTSV), is an acute infectious disease transmitted by ticks that has recently been identified. There are no reports of epidemic serotypes in Liaoning Province, PR China. The aim of this study was, therefore, to identify genotypes of SFTSV in this province. Methods In 2019, quantitative PCR testing was performed on 17 patients suspected of being infected with SFTS in Liaoning Province and on 492 ticks from the counties and cities surrounding the patients’ residences. Four samples were subjected to virus isolation and whole-genome amplification. Results Molecular diagnostic results confirmed SFTSV infection in five of the 17 suspected cases of SFTS and in 12 of the 492 ticks, with a prevalence of 2.4%. Four strains of SFTSV were successfully isolated from patients’ blood and ticks. Phylogenetic analysis after whole-genome amplification and sequencing showed that they all belonged to genotype A of SFTSV. Conclusions This study is the first to determine the genotype of SFTSV in patients and ticks in Liaoning Province, PR China. The results deepen our understanding of the SFTS epidemic and provide information on the variability in mortality rate among genotypes. Graphical Abstract

Theabrownins (TBs) in dark tea have received increasing attention for their multiple health benefits. In this study, ultrasound assisted extraction with deep eutectic solvent (UAE-DES) was developed for the extraction of TBs from Kangzhuan dark tea (KZDT). The highest yield (12.59%) of TBs was obtained using UAE-choline (ChCl)/malic acid (MA) with a liquid to solid ratio of 20:1 (v/w), ultrasonic power of 577 W, ultrasonic time of 25 min, and water content of 30%. TBs were further eluded by silica gel to obtain six theabrownine fractions (TBFs), namely, TBFs1, TBFs2, TBFs3, TBFs4, TBFs5, and TBFs6. LC-MS/MS revealed that flavonoids, terpenes, phenolic acids, alkaloids, lipids, and amino acids are the leading components of TBFs. The TBFs4, with the DPPH, ABTS, and FRAP values of 45.08 ± 0.42 μM Ascorbic acid/g DW, 178.52 ± 0.29 μM Trolox/g DW, and 370.85 ± 6.00 μM Fe(II)/g DW, respectively, showed the highest antioxidant activity among all the TBFs. Overall, this study first provided the evidence that UAE-ChCl/MA combining with silica gel was effective to extract TBs from KZDT, and the 6,7-dihydroxycoumarin-6-glucoside and neohesperidin were found as the leading compounds in the TBFs, providing a guidance for the chemical research and further utilization of dark tea and its TBs.

Sprouts are recognized as nutritional and functional vegetables. In this study, 17 selected seeds were germinated simultaneously. The antioxidant capacity and total phenolic content (TPC) were determined for seeds and sprouts of all species. Both seed and sprout of white radish, with the highest antioxidant capacity, and TPC among all the 17 species, were further determined for phenolic metabolomics. Four phenolic classes with 316 phenolic metabolites were identified. 198 significantly different metabolites with 146 up-regulated and 52 down-regulated were confirmed, and high amounts of phenolic acids and flavonoids were found to be accumulated in the sprout. Several metabolism and biosynthesis, including phenylpropanoid, favone and flavonol, phenylalanine, and various secondary metabolites, were significantly activated. Significant correlations were found among FRAP, DPPH, ABTS, TPC, and phenolic profiles. Therefore, white radish sprout could be served as antioxidant and could be a good source of dietary polyphenols.

BackgroundCysteine-rich 61 (CYR61) is implicated in many pulmonary diseases. However, the relationship between CYR61 and community-acquired pneumonia (CAP) patients was unknown. This research aimed to estimate the correlations of serum CYR61 with severity and prognosis in CAP patients through a prospective cohort study.MethodsAll 541 CAP patients were enrolled in this study. Fasting venous blood was collected. Clinical characteristics and demographic information were obtained. CYR61 and inflammatory cytokines were detected in serum using ELISA.ResultsSerum CYR61 was gradually increased in parallel with severity scores in CAP patients. Correlative analysis indicated that serum CYR61 was strongly associated with many clinical parameters in CAP patients. Moreover, mixed logistic and linear regression models found that there were positive correlations between serum CYR61 and CAP severity scores after adjusted for age, BMI, and respiratory rate. Stratified analyses suggested that age affected the associations between serum CYR61 and severity scores. On admission, higher serum CYR61 levels elevated the risks of mechanical ventilation, vasoactive agent, ICU admission, death, and longer hospital stays during hospitalization. Moreover, serum CYR61 in combination with severity scores upregulated the predictive capacities for severity and death than single serum CYR61 or severity scores in CAP patients.ConclusionThere are significantly positive dose-response associations of serum CYR61 on admission with the severity and adverse prognostic outcomes, demonstrating that CYR61 is involved in the pathophysiology of CAP. Serum CYR61 may be used as a potential biomarker for the diagnosis and prognosis in CAP patients.

Fruit thinning is a common practice employed to enhance the quality and yield of kiwifruits during the growing period, and about 30–50% of unripe kiwifruits will be thinned and discarded. In fact, these unripe kiwifruits are rich in nutrients and bioactive compounds. Nevertheless, the applications of thinned young kiwifruits and related bioactive compounds in the food and functional food industry are still limited. Therefore, to promote the potential applications of thinned young kiwifruits as value-added health products, the extraction, characterization, and evaluation of beneficial effects of phenolic compounds from thinned young fruits of red-fleshed Actinidia chinensis cv ‘HY’ were examined in the present study. A green and efficient ultrasound-assisted deep eutectic solvent extraction (UADE) method for extracting phenolic compounds from thinned young kiwifruits was established. A maximum yield (105.37 ± 1.2 mg GAE/g DW) of total phenolics extracted from thinned young kiwifruits by UADE was obtained, which was significantly higher than those of conventional organic solvent extraction (CSE, about 14.51 ± 0.26 mg GAE/g DW) and ultrasound-assisted ethanol extraction (UAEE, about 43.85 ± 1.17 mg GAE/g DW). In addition, 29 compounds, e.g., gallic acid, chlorogenic acid, neochlorogenic acid, catechin, epicatechin, procyanidin B1, procyanidin B2, quercetin-3-rhamnoside, and quercetin-3-O-glucoside, were identified in the kiwifruit extract by UPLC-MS/MS. Furthermore, the contents of major phenolic compounds in different kiwifruit extracts prepared by conventional organic solvent extraction (EE), ultrasound-assisted ethanol extraction (UEE), and ultrasound-assisted deep eutectic solvent extraction (UDE) were compared by HPLC analysis. Results revealed that the content of major phenolics in UDE (about 15.067 mg/g DW) was significantly higher than that in EE (about 2.218 mg/g DW) and UEE (about 6.122 mg/g DW), suggesting that the UADE method was more efficient for extracting polyphenolics from thinned young kiwifruits. In addition, compared with EE and UEE, UDE exhibited much higher antioxidant and anti-inflammatory effects as well as inhibitory effects against α-glucosidase and pancreatic lipase, which were closely associated with its higher content of phenolic compounds. Collectively, the findings suggest that the UADE method can be applied as an efficient technique for the preparation of bioactive polyphenolics from thinned young kiwifruits, and the thinned young fruits of red-fleshed A. chinensis cv ‘HY’ have good potential to be developed and utilized as functional foods and nutraceuticals.

The increasing demand of hemp (Cannabis sativa L.) has attracted more interest in exploring its phytochemical profile and bioactivities, such as anti-inflammatory effect. In this study, the phytochemicals of different hemp leaves were investigated, with the content order: total saponins content (TSC) > total alkaloids content (TAC) > total phenolics content (TPC) > total flavonoids content (TFC) > cannabinoids. Hemp leaves from Shanxi accumulated higher flavonoids and cannabinoids (i.e., THC, CBD, and CBN), while phenolics were more abundant in those from Hunan. A lipopolysaccharide (LPS)-induced inflammatory Matin-Darby canine kidney (MDCK) cell model was established to evaluate the anti-inflammatory effects of hemp leaf extracts. Hemp leaf extracts, especially the D129 and c7, significantly increased cell viability of LPS-induced inflammatory MDCK cells, and D132 significantly decreased the secretion of pro-inflammatory cytokines (TNF-α and IL-6) and the lactate dehydrogenase (LDH) activity. Except for c12, other hemp leaf extracts obviously decreased the cell morphological damage of LPS-induced inflammatory MDCK cells. The correlation analysis revealed that cannabinol (CBN) and TPC showed the strongest correlation with anti-inflammatory activities, and hierarchical clustering analysis also showed that hemp germplasms from Shanxi might be good alternatives to the common cultivar Ym7 due to their better anti-inflammatory activities. These results indicated that hemp leaves were effective in LPS-induced inflammatory MDCK cells, and flavonoids and cannabinoids were potential geographical markers for distinguishing them, which can provide new insights into the anti-inflammatory effect of hemp leaves and facilitate the application of hemp leaves as functional ingredients against inflammatory-related disorders.

BackgroundFour-hydroxynonenal (4-HNE) exerts a central role in the pathophysiological process of pulmonary diseases. The aim of this project was to evaluate the correlations between serum 4-HNE with severity and prognosis in patients with community-acquired pneumonia (CAP) by a prospective cohort study.Materials and MethodsA total of 239 patients with CAP and healthy volunteers were recruited. Fasting blood was collected. Serum 4-HNE was measured with ELISA. Clinical characteristics and demographic information were obtained. The relationships between serum 4-HNE and clinical characteristics were evaluated through the Spearman or Pearson correlation coefficient. The associations of serum 4-HNE with severity and prognosis were estimated through logistic regression analysis.ResultsOn admission, serum 4-HNE was upregulated in patients with CAP compared with healthy volunteers. Serum 4-HNE was gradually increased in line with CAP scores. Additionally, elderly patients with CAP were more prone to suffer from 4-HNE elevation. Moreover, serum 4-HNE was positively correlated with CAP severity scores. Meanwhile, the poor prognostic outcomes were tracked among patients with CAP. Higher serum 4-HNE on admission increased the risks of mechanical ventilation, vasoactive agent usage, and death in patients with CAP during hospitalization. The predictive powers for severity and death were increased in serum 4-HNE compared with CAP severity scores and inflammatory cytokines.ConclusionSerum 4-HNE on admission is positively correlated with the severity and poor prognosis among patients with CAP, indicating that 4-HNE participates in the pathophysiology of CAP. Serum 4-HNE may be used as an earlier biomarker for diagnosis and prognosis in patients with CAP.

Abstract Background Previous studies found that S100A9 may involve in the pathophysiology of community-acquired pneumonia (CAP). However, the role of S100A9 was unclear in the CAP. The goal was to explore the correlations of serum S100A9 with the severity and prognosis of CAP patients based on a prospective cohort study. Methods A total of 220 CAP patients and 110 control subjects were recruited. Demographic and clinical data were collected. Serum S100A9 and inflammatory cytokines were measured. Results Serum S100A9 was elevated in CAP patients on admission. Serum S100A9 was gradually elevated parallelly with CAP severity scores. Additionally, inflammatory cytokines were increased and blood routine parameters were changed in CAP patients compared with control subjects. Correlation analysis found that serum S100A9 was positively associated with CAP severity scores, blood routine parameters (WBC, NLR and MON) and inflammatory cytokines. Further, logistic regression analysis demonstrated that there were positive associations between serum S100A9 and CAP severity scores. Besides, the prognosis of CAP was tracked. Serum higher S100A9 on the early stage elevated the death of risk and hospital stay among CAP patients. Conclusion Serum S100A9 is positively correlated with the severity of CAP. On admission, serum higher S100A9 elevates the risk of death and hospital stay in CAP patients, suggesting that S100A9 may exert a certain role in the pathophysiology of CAP and regard as a serum diagnostic and managing biomarker for CAP.

Tea (Camellia sinensis L.) is a very popular health drink and has attracted increasing attention in recent years due to its various bioactive substances. Among them, L-theanine, a unique free amino acid, is one of the most important substances in tea and endows tea with a special flavor. Moreover, L-theanine is also a bioactive compound with plenty of health benefits, including antioxidant, anti-inflammatory, neuroprotective, anticancer, metabolic regulatory, cardiovascular protective, liver and kidney protective, immune regulatory, and anti-obesity effects. Due to the unique characteristics and beneficial functions, L-theanine has potential applications in the development of functional foods. This review summarized the influencing factors of L-theanine content in teas, the main health benefits and related molecular mechanisms of L-theanine, and its applications in food, understanding of which can provide updated information for the further research of L-theanine.

BackgroundResistin is an endogenous ligand of Toll-like receptor 4 that activates several inflammatory signals. But the physiological function of resistin in community-acquired pneumonia (CAP) remains unknown. The goal of this research was to explore the associations between serum resistin and the severity and prognosis in CAP patients through a retrospective cohort study.MethodsAll 212 CAP patients and 106 healthy cases were enrolled. Demographic characteristics were extracted. Serum resistin was determined via enzyme-linked immunosorbent assay. The prognosis was tracked in CAP patients.ResultsSerum resistin on admission was raised in CAP patients compared with control cases. The level of resistin was gradually increased in parallel with CAP severity scores in CAP patients. Pearson and Spearman analyses revealed that serum resistin was positively correlated with CAP severity scores, white blood cells, urea nitrogen, creatinine, and inflammatory cytokines among CAP patients. There were negative relationships between resistin and hematocrit and albumin in CAP patients. Besides, linear and logistic regression analyses further indicated that serum resistin on admission was positively associated with CAP severity scores among CAP patients. Follow-up research revealed that serum resistin elevation on admission prolonged hospital stay in CAP patients.ConclusionSerum resistin on admission is positively correlated with the severity and hospital stay in CAP patients, indicating that resistin may be involved in the physiological process of CAP. Serum resistin may be a potential biomarker in the diagnosis and prognosis for CAP.

Heavy metal pollution is a global knotty problem and fungi hold promising potential for the remediation of wastewater containing heavy metals. Here, a new highly chromium-tolerance species, Penicillium janthinellum P1, is investigated. The genome of P1 was sequenced and assembled into 30 Mb genome size containing 10,955 predicted protein-coding genes with a GC content of 46.16% through an integrated method of Illumina short-read sequencing and single-molecule real-time Pacific Biosciences sequencing platforms. Through a phylogenetic analysis with model species of fungi, the evolutionary divergence time of Penicillium janthinellum P1 and Penicillium oxalicum 114-2 was estimated to be 74 MYA. 33 secondary metabolism gene clusters were identified via antiSMASH software, mainly including non-ribosomal peptide synthase genes and T1 polyketide synthase genes. 525 genes were annotated to encode enzymes that act on carbohydrates, involving 101 glucose-degrading enzymes and 24 polysaccharide synthase. By whole-genome sequence analysis, large numbers of metal resistance genes were found in strain P1. Especially ABC transporter and Superoxide dismutase ensure that the P1 fungus can survive in a chromium-polluted environment. ChrA and ChrR were also identified as key genes for chromium resistance. Analysis of their genetic loci revealed that the specific coding-gene arrangement may account for the fungus’s chromium resistance. Genetic information and comparative analysis of Penicillium janthinellum are valuable for further understanding the mechanism of high resistance to heavy metal chromium, and gene loci analysis provides a new perspective for identifying chromium-resistant strains.

Abstract. Background. Brachydactyly, a developmental disorder, refers to shortening of hands/feet due to small or missing metacarpals/metatarsals and/or phalanges. Isolated brachydactyly type E (BDE), characterized by shortened metacarpals and/or metatarsals, consists in a small proportion of patients with Homeobox D13 (HOXD13) or parathyroid-hormone-like hormone (PTHLH) mutations. BDE is often accompanied by other anomalies that are parts of many congenital syndromes. In this study, we investigated a Chinese family presented with BDE combined with pectus carinatum and short stature. Methods. A four-generation Chinese family was recruited in June 2016. After informed consent was obtained, venous blood was collected, and genomic DNA was extracted by standard procedures. Whole-exome sequencing was performed to screen pathogenic mutation, array comparative genomic hybridization (Array-CGH) analysis was used to analyze copy number variations, and quantitative real-time polymerase chain reaction (PCR), stride over breakpoint PCR (gap-PCR), and Sanger sequencing were performed to confirm the candidate variation. Results. A 3.06-Mb deletion (chr12:25473650–28536747) was identified and segregated with the phenotype in this family. The deletion region encompasses 23 annotated genes, one of which is PTHLH which has been reported to be causative to the BDE. PTHLH is an important regulator of endochondral bone development. The affected individuals showed bilateral, severe, and generalized brachydactyly with short stature, pectus carinatum, and prematurely fusion of epiphyses. The feature of pectus carinatum has not been described in the PTHLH-related BDE patients previously. Conclusions. The haploinsufficiency of PTHLH might be responsible for the disease in this family. This study has expanded the knowledge on the phenotypic presentation of PTHLH variation.

Sweet tea (Lithocarpus litseifolius [Hance] Chun) is a new resource for food raw materials, with plenty of health functions. This study aimed to investigate the preventive effect and potential mechanism of sweet tea extract (STE) against ulcerative colitis (UC). Briefly, BABL/c mice were treated with STE (100 and 400 mg/kg) for 2 weeks to prevent 3% dextran sulfate sodium (DSS)-induced UC. It was found that STE supplementation significantly prevented DSS-induced UC symptoms; suppressed the levels of pro-inflammatory mediators, such as myeloperoxidase and tumor necrosis factor-α; increased the levels of anti-inflammatory cytokines; and up-regulated the expression of tight junction proteins (Zonula occludens-1 and Occludin). STE also altered the gut microbiota profile of UC mice by increasing Bacteroidetes, Lactobacillus, Akkermansia, Lachnospiraceae_NK4A136_group, and Alistipes and inhibiting Firmicutes, Proteobacteria, and Helicobacter, accompanied by a significant increase in the content of butyric acid. Moreover, STE increased the expression of G-protein-coupled receptor (GPR) 43 and GPR109A and inhibited the expression of histone deacetylase 3 (HDAC3) and nuclear factor-κB p65 (NF-κB p65) in the colon. In conclusion, this study indicated that STE has a good preventive effect on UC by regulating gut microbiota to activate butyrate-GPR-mediated anti-inflammatory signaling and simultaneously inhibit HDAC3/NF-κB inflammatory signaling.

Abstract Background The congenital stationary night blindness (CSNB) affects the patients' dim light vision or dark adaption by impairing the normal function of retina. It is a clinically and genetically heterogeneous disorder and can be inherited in an X‐linked, autosomal dominant or autosomal recessive pattern. Several genetic alterations to the genes involved in visual signal transduction of photoreceptors and/or bipolar cells underlie its pathogenesis. Methods In this study, we used Sanger sequencing and next‐generation sequencing (NGS)‐based gene panel screening to investigate a family of three patients with CSNB inherited in an apparent autosomal dominant pattern. We expected to find out the disease‐causing gene defects carried by this family. Results We found that the patients in this family did not carry the RHO, GNAT1, or PDE6B mutation, but carried compound heterozygotes mutations of GRM6. Three deleterious GRM6 variants, p.Arg621Ter, p.Gly51Val, and p.Gly464Arg, were found to be co‐segregating with the disease, causing a pseudodominant inheritance of GRM6‐related autosomal recessive complete CSNB. Conclusion This study presents a rare case of autosomal recessive CSNB (arCSNB) pseudodominant inheritance, which potentially leads us to expand our gene candidate list in future genetic testing for apparent dominant pedigrees. The discovery of the two novel likely pathogenic variants p.Gly51Val and p.Gly464Arg could broaden our knowledge about the genetics of CSNB and provide insights into the structure and function of the GRM6 protein.

This study aims to investigate the effects of raw materials and drying methods on the phytochemical and antioxidant capacities of instant sweet tea powder. Four raw materials of sweet tea leave powders (STUT) were extracted and dried with two methods (freeze-drying and spray-drying). The antioxidant capacity, total phenolic content (TPC), total flavonoid content (TFC), and phlorizin and trilobatin contents of obtained instant sweet tea powders were compared. In addition, the single-factor experiments coupled with response surface methodology were used to study the influences of solvent-to-sample ratio, extraction temperature, extraction time, and their interactions on instant sweet tea yield. Results showed that the optimal conditions for extraction were the solvent-to-sample ratio of 19:1 mL/g, extraction temperature of 88 °C, and extraction time of 30 min. The TPC, TFC, antioxidant capacities, and phloridzin and trilobatin contents of instant sweet teas were higher than those of STUT, and the TPC and TFC of freeze-dried instant sweet teas were higher than those of spray-dried instant sweet teas. Significant correlations were found among TPC, TFC, and antioxidant capacities (p < 0.01). The freeze-dried instant sweet tea produced by young leaves (prepared by oven-drying) showed the highest TPC, TFC, and antioxidant capacities, compared with other raw materials and drying methods.

The whole mitochondrial genome sequence of Lepturichthys fimbriata was amplified by primer walking sequence method, and then the whole genome genetic map of mitochondrion was obtained and mapped. The mitochondrial genome of L. fimbriata is a double-strand ring-like molecule with a total length of 16,567bp. It contains 2 rRNA genes (12SrRNA and 16SrRNA), 13 protein-coding genes (COI, COII, COIII, ATP6, ATP8, ND1, ND2, ND3, ND4, ND4L, ND5, ND6, Cytb), 22 tRNA coding genes, and one non-coding control region (D-loop control region). The overall nucleotide composition was A: 30.4%, T: 24.4%, C: 28.7%, and G: 16.5%, exhibiting an A + T bias of 54.8%. Phylogeny showed the phylogenetic relationships of different genera in the family Balitoridae and found the genus Lepturichthys is clustered with the genus Jinshaia, which suggested the intergeneric hybridization has likely occurred in both lineages.

A fractional nonlinear differential system is studied to search for its periodic solution near the equilibrium. The release oscillation of silver ions from hollow fibers is used as an example to illustrate the importance of fractional order to the release frequency. The criterion for the periodic solution is obtained and it shows that the fractional order will greatly affect its periodic property.

In this study, the efficiency of microwave-assisted hydro-distillation (MAHD) to extract essential oil from Cinnamomum camphora leaf, and the recovery of polyphenols from extract fluid were investigated. The effects of microwave power, liquid-to-material ratio, and extraction time on the extraction efficiency were studied by a single factor test as well as the response surface methodology (RSM) based on the central composite design method. The optimal extraction conditions were a microwave power of 786.27 W, liquid-to-material ratio of 7.47:1 mL/g, and extraction time of 35.57 min. The yield of essential oil was 3.26 ± 0.05% (w/w), and the recovery of polyphenols was 4.97 ± 0.02 mg gallic acid equivalent/g dry weight under the optimal conditions. Furthermore, the comprehensive two-dimensional gas chromatography-time-of-flight mass spectrometry (GC×GC-TOFMS) was used to characterize the essential oils of fresh and fallen leaves, and 159 individual compounds were tentatively identified, accounting for more than 89.68 and 87.88% of the total contents, respectively. The main ingredients include sabinene, l-β-pinene, β-myrcene, α-terpineol, 3-heptanone, and β-thujene, as well as δ-terpineol and 3-heptanone, which were first identified in C. camphora essential oil. In conclusion, the MAHD method could extract essential oil from C. camphora with high efficiency, and the polyphenols could be obtained from the extract fluid at the same time, improving the utilization of C. camphora leaf.

The complete chloroplast genome from Cardiocrinum cathayanum (Liliaceae), an important herbaceous perennial species of the Liliaceae, is determined in this study. We characterized its whole plastid genome sequence using the Illumina sequencing platform. The whole plastid genome of C. cathayanum was a typical quadripartite circular molecule with 152,502 bp in length, comprised of a large single copy region of 82,517 bp, a small single copy region of 17,311 bp, and two inverted repeat regions of 26,337 bp. A total of 136 genes, 84 protein-coding genes, 38 tRNA, and 8 rRNA genes were identified. The GC content in the chloroplast genome, LSC region, SSC region, and IR region were 42.5, 34.9, 30.8, and 42.5%, respectively. Phylogenetic analysis suggested that C. cathayanum is more closely related with Allium cepa, Allium prattii, Amana edulis, and Erythronium sibiricum, these species were clustered into a clade with high bootstrap support.

Psathyrostachys huashanica Keng belongs to the genus Psathyrostachys within the Gramineae family, is a rare and endangered herb plant endemic to China. In the current work, we first developed its whole chloroplast (cp) genome sequence. The cp genome of P. huashanica is 136,632 bp in size, including a large single copy (LSC) region of 81,803 bp, a small single copy (SSC) region of 12,763 bp, and a pair of inverted repeats (IRs) of 21,033 bp. The genome contains 114 genes, including 78 protein-coding genes, 32 tRNA genes, and 4 rRNA genes. The GC content in cp genome, LSC, SSC, and IR regions were 38.5, 36.5, 32.6, and 38.5%, respectively. The phylogenetic analysis showed P. huashanica is closely related to Triticum genus.

OBJECTIVE:To investigate the awareness and use of the Systematic Review Center for Laboratory Animal Experimentation's (SYRCLE) risk-of-bias tool, the Animal Research: Reporting of In Vivo Experiments (ARRIVE) reporting guidelines, and Gold Standard Publication Checklist (GSPC) in China in basic medical researchers of animal experimental studies. METHODS:A national questionnaire-based survey targeting basic medical researchers was carried in China to investigate the basic information and awareness of SYRCLE's risk of bias tool, ARRIVE guidelines, GSPC, and animal experimental bias risk control factors. The EpiData3.1 software was used for data entry, and Microsoft Excel 2013 was used for statistical analysis in this study. The number of cases (n) and percentage (%) of classified information were statistically described, and the comparison between groups (i.e., current students vs. research staff) was performed using chi-square test. RESULTS:A total of 298 questionnaires were distributed, and 272 responses were received, which included 266 valid questionnaires (from 118 current students and 148 research staff). Among the 266 survey participants, only 15.8% was aware of the SYRCLE's risk of bias tool, with significant difference between the two groups (P = 0.003), and the awareness rates of ARRIVE guidelines and GSPC were only 9.4% and 9.0%, respectively; 58.6% survey participants believed that the reports of animal experimental studies in Chinese literature were inadequate, with significant difference between the two groups (P = 0.004). In addition, only approximately 1/3 of the survey participants had read systematic reviews and meta-analysis reports of animal experimental studies; only 16/266 (6.0%) had carried out/participated in and 11/266 (4.1%) had published systematic reviews/meta-analysis of animal experimental studies. CONCLUSIONS:The awareness and use rates of SYRCLE's risk-of-bias tool, the ARRIVE guidelines, and the GSPC were low among Chinese basic medical researchers. Therefore, specific measures are necessary to promote and popularize these standards and specifications and to introduce these standards into guidelines of Chinese domestic journals as soon as possible to raise awareness and increase use rates of researchers and journal editors, thereby improving the quality of animal experimental methods and reports.

Abies chensiensis Van Tiegh. (Pinaceae) is a rare and endangered endemic conifer in China. In this study, using the Illumina sequencing platform, we firstly characterized its whole plastid genome sequence. Our study revealed that A. chensiensis have a typical plastid genome of 121,498 bp in length, comprised of a large single copy region of 76,484 bp, a small single copy region of 42,654 bp and two inverted repeat regions of 1180 bp. A total of 113 genes, 74 protein-coding genes, 35 tRNA, and 4 rRNA genes were identified. The phylogenetic analysis indicated that A. chensiensis was placed as a sister to the congeneric A. sibirica.

Abscisic acid (ABA) plays a central role in the plant response to water deficit by inducing stomatal closure to conserve water when the soil dries. Exogenous ABA was applied at 45 days after sowing (DAS) as a soil drench, the physiological and seed yield response of soybean to exogenous ABA were examined as the soil was drying. Three experiments were conducted using the drought-tolerant soybean cultivar Jindou 19, grown in pots at the Yuzhong Experimental Station of Lanzhou University, China. In experiment 1, plants were exposed to progressive soil drying and leaf ABA concentration, leaf photosynthesis rate, leaf relative water content (RWC) and osmotic adjustment (OA) were measured. In experiment 2, plants were under progressive soil drying and lethal leaf water potential was measured. In experiment 3, flower production and abortion, and grain yield were measured in plants under well-watered (WW), moderate (MWD) and severe water deficits (SWD). Exogenous ABA application increased ABA accumulation in leaves and reduced the rate of soil drying. It also increased leaf photosynthetic rate, stomatal conductance and transpiration rate at 7−10 days after withholding water. The intrinsic and instantaneous water use efficiency (WUE) was consistently higher with exogenous ABA than without ABA as the soil dried. Exogenous ABA increased OA when the leaf relative water content (RWC) decreased at eight days after withholding water, lowering the lethal leaf water potential by 0.4 MPa. Exogenous ABA reduced water use, increased WUE for grain yield under WW and MWD, and had no effect on flower number, flower abortion or grain yield in any water treatment. We concluded that (1) exogenous ABA induced OA, improved leaf photosynthetic rate, leaf water relations and desiccant tolerance, but did not benefit grain yield in soybean under water deficits; (2) exogenous ABA improved the WUE at the leaf level as soil drying and WUE for grain yield under moderate water deficit.

Objective. We aim to investigate the long-term benefits of growth hormone (GH) therapy in short stature adolescents and adults with pituitary stalk interruption syndrome (PSIS), which would be beneficial for future clinical applications. Design and Methods. In this study, initial height, final height, total height gain, and GH treatment history were retrospectively investigated in 75 Chinese PSIS patients. We compared height gain between the GH treated cohort and untreated cohort and explored the impact of different GH therapy duration on height gain. Results. For GH treated patients, their final height (SDS) increased from -1.99±1.91 (−6.93~2.80) at bone age (BA) of 11.2 (5.0~17.0) years to -1.47±1.64 (−7.82~1.05) at BA of 16.6 (8.0~18.0) years (P=0.016). And GH treated patients had more height gain than the untreated patients (P

Improved ranging accuracy is obtained by the development of a novel ultrasonic sensor ranging algorithm, unlike the conventional ranging algorithm, which considers the divergence angle and the incidence angle of the ultrasonic sensor synchronously. An ultrasonic sensor scanning method is developed based on this algorithm for the recognition of an inclined plate and to obtain the localization of the ultrasonic sensor relative to the inclined plate reference frame. The ultrasonic sensor scanning method is then leveraged for the omni-directional localization of a mobile robot, where the ultrasonic sensors are installed on a mobile robot and follow the spin of the robot, the inclined plate is recognized and the position and posture of the robot are acquired with respect to the coordinate system of the inclined plate, realizing the localization of the robot. Finally, the localization method is implemented into an omni-directional scanning localization experiment with the independently researched and developed mobile robot. Localization accuracies of up to ±3.33 mm for the front, up to ±6.21 for the lateral and up to ±0.20° for the posture are obtained, verifying the correctness and effectiveness of the proposed localization method.

In the title compound, C17H14O5S, the coumarin ring system is nearly planar, with a maximum deviation of 0.034 (2) Å from the mean plane. The dihedral angle between the benzene ring and the coumarin ring system is 56.11 (6)°. The crystal packing is stabilized by C—H...O hydrogen bonding, which forms a three-dimensional framework.

The aim of this study was to examine the mechanisms of IFN induction and viral escape. In order to accomplish the goal we compared our new hepatoma cell line LH86, which has intact TLR3 and RIG-I expression and responds to HCV by inducing IFN, with Huh7.5 cells which lack those features.The initial interaction of LH86 cells, Huh7.5 cells or their transfected counter parts (LH86 siRIG-I, siTLR3 or siTLR7 and Huh7.5 RIG-I, TLR3 or TLR7) after infection with HCV (strain JFH-1) was studied by measuring the expression levels of IFNβ, TRAIL, DR4, DR5 and their correlation to viral replication.HCV replicating RNA induces IFN in LH86 cells. The IFN induction system is functional in LH86, and the expression of the RIG-I and TLR3 in LH86 is comparable to the primary hepatocytes. Both proteins appear to play important roles in suppression of viral replication. We found that innate immunity against HCV is associated with the induction of apoptosis by RIG-I through the TRAIL pathway and the establishment of an antiviral state by TLR3. HCV envelope proteins interfere with the expression of TLR3 and RIG-I.These findings correlate with the lower expression level of PRRs in HCV chronic patients and highlight the importance of the PRRs in the initial interaction of the virus and its host cells. This work represents a novel mechanism of viral pathogenesis for HCV and demonstrates the role of PRRs in viral infection.