Incidence, severity, and risk factors for white spot lesions in adolescent patients treated with clear aligners.

OBJECTIVES: This study was aimed to clarify the incidence, severity, and clinical risk factors for white spot lesions (WSLs) in adolescent patients treated with clear aligners. METHODS: Pre-treatment and post-treatment intraoral photographs of 203 adolescent patients undergoing clear aligner therapy were retrospectively evaluated to assess the occurrence and severity of WSLs. Information on patients' general oral condition and orthodontic treatment was collected from clinical medical documents, retrospective questionnaires, and ClinCheck® software. Independent risk factors and model performance were determined by multivariate logistic regression and receiver operating characteristic curve analysis. RESULTS: Thirty-five percent of adolescent patients developed WSLs during clear aligner treatment. Logistic regression analysis revealed that the presence of WSLs before treatment (OR 2.484, 95% CI 1.245-4.957), frequency of drinking carbonated beverages (OR 1.508, 95% CI 1.045-2.177), and number of anterior attachments (OR 2.192, 95% CI 1.502-3.198) were risk factors for the occurrence of WSLs in adolescent patients treated with clear aligners (P < .05), whereas the number of times they brushed each day (OR 0.656, 95% CI 0.454-0.947) and frequency of aligner cleaning after eating while wearing them (OR 0.611, 95% CI 0.433-0.861) were protective factors against WSLs (P < .05). CONCLUSIONS: The incidence of WSLs was high in adolescent patients treated with clear aligners. Few brushings each day, pre-treatment WSLs, a high frequency of drinking carbonated beverages, a low frequency of aligner cleaning after eating while wearing them, and a high number of anterior attachments are strongly associated with the development of WSLs in adolescent patients treated with clear aligners.

Carboxylated Hexagonal Boron Nitride/Graphene Configuration for Electrosynthesis of High-Concentration Neutral Hydrogen Peroxide.

The electrosynthesis of hydrogen peroxide (H2 O2 ) via two-electron (2e- ) oxygen (O2 ) reduction reaction (ORR) has great potential to replace the traditional energy-intensive anthraquinone process, but the design of low-cost and highly active and selective catalysts is greatly challenging for the long-term H2 O2 production under industrial relevant current density, especially under neutral electrolytes. To address this issue, this work constructed a carboxylated hexagonal boron nitride/graphene (h-BN/G) heterojunction on the commercial activated carbon through the coupling of B, N co-doping with surface oxygen groups functionalization. The champion catalyst exhibited a high 2e- ORR selectivity (>95 %), production rate (up to 13.4 mol g-1 h-1 ), and Faradaic efficiency (FE, >95 %). The long-term H2 O2 production under the high current density of 100 mA cm-2 caused the cumulative concentration as high as 2.1 wt %. The combination of in situ Raman spectra and theoretical calculation indicated that the carboxylated h-BN/G configuration promotes the adsorption of O2 and the stabilization of the key intermediates, allowing a low energy barrier for the rate-determining step of HOOH* release from the active site and thus improving the 2e- ORR performance. The fast dye degradation by using this electrochemical synthesized H2 O2 further illustrated the promising practical application.

CCL3 aggravates intestinal damage in NEC by promoting macrophage chemotaxis and M1 macrophage polarization.

BACKGROUND: NEC is a life-threatening gastrointestinal disease in neonates, the pathogenesis of which remains poorly understood. METHODS: CCL3 levels in intestinal tissue of mice were measured and analyzed. HE staining was used to assess pathological changes in intestinal tissue. FCM was used to detect the proportion and phenotype of macrophages. RNA-seq and RT-PCR were used to evaluate the effect of CCL3 on macrophages. RESULTS: CCL3 was highly expressed in the intestinal tissues of mice with NEC and induced macrophage infiltration. Transcriptome data showed that CCL3 strongly induced a transition in the phenotype of macrophages into a proinflammatory one. Mechanistically, in vivo experiments confirmed that CCL3 induced M1 macrophage polarization in NEC intestinal tissue, thereby aggravating inflammatory injury of intestinal tissue, which was alleviated by anti-CCL3 treatment. In addition, in vitro experiments showed that CCL3 significantly enhances the expression of M1-related genes in both PMφ and BMDM while inhibiting the expression of M2-related genes, which was also alleviated by anti-CCl3 treatment. CONCLUSIONS: Our data elucidated the involvement of CCL3 in the pathogenesis of NEC, in which upregulated CCL3 expression exacerbated inflammatory intestinal damage by regulating macrophage chemotaxis and M1 phenotype polarization, suggesting that blocking CCL3 may be a potential strategy for effective intervention in NEC. IMPACT: Our study represents an important conceptual advancement that CCL3 may be one of the key culprits of intestinal tissue damage in patients with NEC. CCL3 aggravates inflammatory intestinal injury and intestinal mucosal barrier imbalance by regulating the chemotaxis, polarization, and function of macrophages. Blocking CCL3 significantly reduced NEC-mediated intestinal injury, suggesting a new potential therapeutic strategy.

Correlation between salivary cytokine profiles and white spot lesions in adolescent patients receiving clear aligner orthodontic treatment.

BACKGROUND: To explore the relationship between changes in salivary cytokine levels and the occurrence of white spot lesions in adolescents receiving clear aligner orthodontic treatment and investigate the predictive value of various factors for lesion occurrence. METHODS: We retrospectively analyzed sixthy eight adolescent in the permanent dentition period, who received clear aligner orthodontics in our hospital were randomly divided into two groups according to the occurrence or aggravation of white spot lesions after treatment. The general condition of the oral cavity was analyzed, saliva was collected, and inflammation-related cytokines with varying transcription levels between groups were screened by transcriptome analysis. The expression levels of inflammatory cytokines in the saliva of the patients in the two groups were measured, and the risk factors for white spot lesions were screened by correlation analysis and binary logistic regression analysis. The value of the independent and combined application of risk factors for predicting the occurrence of white spot lesions in adolescent patients after invisible orthodontic treatment was analyzed by receiver operating characteristic (ROC) curve analysis. RESULTS: Transcriptome and GO and KEGG pathway analyses showed that there were differences in the transcription levels of inflammatory cytokines such as CXCL1, CXCL2, CXCL8, CCL3, CCL4, IL-1ß and IL-2 between groups. The levels of CXCL8, CCL3, CCL4, IL-1ß and IL-2 in the saliva of patients with white spot lesions were significantly higher in patients after invisible orthodontic treatment (P < 0.05). Correlation analysis and binary logistic regression analysis showed that elevated levels of CXCL8, IL-1ß and IL-2 were independent risk factors for the occurrence of white spot lesions (P < 0.05). CXCL8 had the highest independent predictive value for the occurrence of white spot lesions (AUC = 0.773, P < 0.05), and the combination of IL-1ß and IL-2 was also of high value in predicting the occurrence of white spot lesions. CONCLUSION: After invisible orthodontic treatment, the oral microenvironment, including inflammatory cytokine levels, in adolescent patients changes; in particular, the levels of inflammatory cytokines such as CXCLs and ILs change. CXCL8 expression is significantly associated with the occurrence of white spot lesions and is an important potential target for the prevention and treatment of white spot lesions in the future.

Floral organ transcriptome in Camellia sasanqua provided insight into stamen petaloid.

BACKGROUND: The cultivated Camellia sasanqua forms a divergent double flower pattern, and the stamen petaloid is a vital factor in the phenomenon. However, the regulation mechanism remains largely unclear. RESULTS: Here, a comprehensive comparative transcriptome analysis of the wild-type, "semi-double", "peony double", and "rose double" was performed. The cluster analysis of global gene expression level showed petal and stamen difficulty separable in double flower. The crucial pathway and genes related to double flower patterns regulation were identified by pairwise comparisons and weighted gene coexpression network (WGCNA). Divergent genes expression, such as AUX1 and AHP, are involved in plant hormone signaling and photosynthesis, and secondary metabolites play an important role. Notably, the diversity of a petal-specific model exhibits a similar molecular signature to the stamen, containing extensin protein and PSBO1, supporting the stamen petaloid point. Moreover, the expansion of class A gene activity influenced the double flower formation, showing that the key function of gene expression was probably demolished. CONCLUSIONS: Overall, this work confirmed the ABCE model and provided new insights for elucidating the molecular signature of double formation.

Identifying Prokineticin2 as a Novel Immunomodulatory Factor in Diagnosis and Treatment of Sepsis.

OBJECTIVES: Sepsis remains a highly lethal disease, whereas the precise reasons for death remain poorly understood. Prokineticin2 is a secreted protein that regulates diverse biological processes. Whether prokineticin2 is beneficial or deleterious to sepsis and the underlying mechanisms remain unknown. DESIGN: Prospective randomized animal investigation and in vitro studies. SETTING: Research laboratory at a medical university hospital. SUBJECTS: Prokineticin2 deficiency and wild-type C57BL/6 mice were used for in vivo studies; sepsis patients by Sepsis-3 definitions, patient controls, and healthy controls were used to obtain blood for in vitro studies. INTERVENTIONS: Prokineticin2 concentrations were measured and analyzed in human septic patients, patient controls, and healthy individuals. The effects of prokineticin2 on sepsis-related survival, bacterial burden, organ injury, and inflammation were assessed in an animal model of cecal ligation and puncture-induced polymicrobial sepsis. In vitro cell models were also used to study the role of prokineticin2 on antibacterial response of macrophages. MEASUREMENTS AND MAIN RESULTS: Prokineticin2 concentration is dramatically decreased in the patients with sepsis and septic shock compared with those of patient controls and healthy controls. Furthermore, the prokineticin2 concentration in these patients died of sepsis or septic shock is significantly lower than those survival patients with sepsis or septic shock, indicating the potential value of prokineticin2 in the diagnosis of sepsis and septic shock, as well as the potential value in predicting mortality in adult patients with sepsis and septic shock. In animal model, recombinant prokineticin2 administration protected against sepsis-related deaths in both heterozygous prokineticin2 deficient mice and wild-type mice and alleviated sepsis-induced multiple organ damage. In in vitro cell models, prokineticin2 enhanced the phagocytic and bactericidal functions of macrophage through signal transducers and activators of transcription 3 pathway which could be abolished by signal transducers and activators of transcription 3 inhibitors S3I-201. Depletion of macrophages reversed prokineticin2-mediated protection against polymicrobial sepsis. CONCLUSIONS: This study elucidated a previously unrecognized role of prokineticin2 in clinical diagnosis and treatment of sepsis. The proof-of-concept study determined a central role of prokineticin2 in alleviating sepsis-induced death by regulation of macrophage function, which presents a new strategy for sepsis immunotherapy.

Correlation between exopolysaccharide biosynthesis and gastrointestinal tolerance of Lactiplantibacillus plantarum.

AIM: This study aimed to investigate the correlation between the level of exopolysaccharide (EPS) biosynthesis and gastrointestinal tolerance of 12 Lactiplantibacillus plantarum strains. METHODS AND RESULTS: In this study, the EPS production and survival rate of 12 strains of L. plantarum under gastrointestinal stress were determined. Results showed that the EPS biosynthesis level of L. plantarum in semi-defined medium ranged from 9.84 to 26.05 mg/L. The survival rates of all strains in simulated gastric juice at pH 3.0 ranged from 43.52% to 112.73%. Among them, eight strains were higher than 90%, while only one strain was lower than 50%. The survival rates of all strains in simulated intestinal juice ranged from 50.36% to 125.39%, among which eight strains were higher than 80%. The survival rates of all strains under 0.1% bile salt stress ranged from 3.39% to 109.34%, among which four strains were higher than 80% and three strains were lower than 60%. Besides, the survival rates of all strains under 0.5% bile salt stress ranged from 0.42% to 95.34%. The results indicated that the 12 L. plantarum strains had good tolerance to simulated gastric juice at pH 3.0, simulated intestinal juice and 0.1% bile salt. Notably, it was observed that the survival rates of L. plantarum strains under simulated gastric juice at pH 3.0 and simulated intestinal juice were significantly positively correlated with EPS biosynthesis (p < 0.01). CONCLUSION: The yield of EPS of L. plantarum was related to simulated gastric juice and simulated intestinal juice environment. SIGNIFICANCE AND IMPACT OF STUDY: It was speculated that the production of EPS may be one of the strategies for L. plantarum to adapt to the part of gastrointestinal environment. In the future, we could analyse the protection mechanism of EPS from the gene level.

Molybdenum contamination dispersion from mining site to a reservoir.

This study was conducted to assess heavy metals in the overlying water and sediments of Luhun Reservoir, Henan Province, China, which is positioned downstream from a molybdenum (Mo) mining area. The pollution indexes indicated that deposition of all metals may have been affected by the mining area. The single element pollution factor (Pi) of Mo was the highest among all heavy metals, with a mean value of 2.05. However, the sediments were subject to long-term accumulation of metals, particularly Mo, Cd, Pb, and Zn, which originated from anthropogenic sources. The mean individual element potential ecological risk index values for Cd were above 385, while the mean value comprehensive potential ecological risk index was 465, which indicates a high ecological risk. Moreover, the enriched heavy metals had different spatial distributions in the Luhun Reservoir sediments. Finally, Pearson correlation analysis indicated that the Pb was mainly affected by different anthropogenic sources and had no relationship with other metals, which suggests that the influence of mining area on heavy metal concentrations in the reservoir is difficult to disentangle.

Spatial and temporal distribution of Mo in the overlying water of a reservoir downstream from mining area.

This study aimed to evaluate the spatial and temporal variations of molybdenum (Mo) in the downstream water body of a Mo mine during three hydrologic periods (wet, dry and medium seasons). The physical properties in Luhun Reservoir reflected seasonal variations in different hydrological periods. The redox potential (ORP) and dissolved oxygen (DO) increased in the dry season. The concomitant decrease in temperature (T), conductivity (COND) and total dissolved solids (TDS) were lowest in the wet season. The pH value did not change significantly during the three hydrologic periods. The distribution of Mo in the dry season was high in upstream and low in downstream areas, which was significantly different from that of the wet and medium seasons. The total Mo concentration in wet (150.1 µg/L) and medium season (148.2 µg/L) was higher than that in the dry season, but the TDS (288.3 mg/L) and the percentage dissolved Mo (81.3%) in overlying water was lowest in the wet season. There was no significant relationship between the dissolved Mo and the total Mo with TDS. In the dry season, the mean total Mo concentration was 116.3 µg/L, which was higher than the standard limit value (70 µg/L) for drinking water (US EPA-United States Environmental Protection Agency recommended value 40 µg/L). Non-point source pollution is the main characteristic of mining area pollution, which was closely related to rainfall. Thus, the Luhun Reservoir contains substantial Mo pollution, which was a significant concern given that it is used as a source of drinking and irrigation water.

Progranulin as a novel biomarker in diagnosis of early-onset neonatal sepsis.

BACKGROUND: Infections are leading causes of morbidity and mortality in neonates and may also have severe long-term consequences. As early diagnosis of neonatal sepsis improves prognosis, identification of new or complementary biomarkers is of great importance. In this study, we have evaluated the diagnostic value of progranulin (PGRN) in early-onset neonatal sepsis (EOS) and compare its effectiveness with other commonly used biomarkers, such as procalcitonin (PCT) and C-reactive protein (CRP). METHODS: A total of 121 infants with gestational age of >34 weeks admitted with suspected EOS were included in this study. Before initiating therapy, blood samples for whole blood count, CRP, PCT and PGRN were obtained from all neonates. Receiver-operating characteristic (ROC) curve and multivariate logistic regression analyses were performed. RESULTS: Serum PGRN level of infected group was significantly higher than uninfected group (median 47.72 vs. 37.86 ng/ml, respectively; Mann-Whitney p < 0.0001). The ROC area under the curve (AUC) was 0.786 [95% confidence interval (CI) 0.706-0.867; p < 0.0001] for PGRN, 0.699 (95% CI 0.601-0.797; p = 0.0001) for age adjusted PCT, and 0.673 (95% CI 0.573-0.773; p = 0.0007) for CRP. With a cut-off value of 37.89 ng/ml, the diagnostic sensitivity and negative predictive value of PGRN were 94.34% and 91.7%, respectively. PGRN could significantly predict EOS independently of PCT (p < 0.0001), and the combined use of PGRN and PCT could significantly improve diagnostic performance for EOS (0.806; 95% CI 0.73-0.88; p < 0.0001), with a specificity of 89.06% and a positive predictive value of 81.10%. CONCLUSIONS: PGRN may be used as a promising biomarker for the diagnosis of EOS, and the combined use of PGRN and PCT could improve the diagnosis of sepsis.

Determining cadmium bioavailability in sediment profiles using diffusive gradients in thin films.

Cadmium (Cd) uptake by plants or benthic organisms largely depends on its bioavailability in sediments, so it is necessary to understand Cd bioavailability for determining its ecological risks in riverine sediments. Pore water is easily disturbed during sample collection, indicating that there was a shortage of traditional methods for investigating Cd bioavailability. Here, sediment cores were collected from rivers, after which sequential extraction and diffusive gradients in thin films (DGT) method were employed to determine Cd potential bioavailability in the sediments and pore water. We found that Cd concentrations measured by DGT were lower than that in pore water profiles, and Cd distribution in various fractions changed remarkably. Pearson correlation analysis showed significant positive correlations between Cd concentrations measured by DGT and total Cd concentrations (r2 = 0.76), exchangeable and weak acid soluble fraction (r2 = 0.68), ferromanganese fraction (r2 = 0.72) and bound organic matter or oxidizable fraction (r2 = 0.54). However, the correlation was relatively low between Cd concentrations measured by DGT and that in pore water profiles (r2 = 0.26). These results demonstrated that DGT method could provide more accurate information of Cd bioavailability in sediment profiles than traditional methods.

Interleukin-34 Ameliorates Survival and Bacterial Clearance in Polymicrobial Sepsis.

OBJECTIVES: Sepsis is a devastating condition with a high mortality rate and limited treatments. Sepsis is characterized by a failed host immune response to contain the infection, resulting in organ dysfunction. Interleukin-34 is new cytokine involved in infection and immunity. Whether interleukin-34 is beneficial or deleterious to sepsis and the underlying mechanisms remains unknown. DESIGN: Prospective randomized animal investigation and in vitro studies. SETTING: Research laboratory at a university hospital. SUBJECTS: Wild-type C57BL/6 mice were used for in vivo studies, and septic human patients and healthy human subjects were used to obtain blood for in vitro studies. INTERVENTIONS: Interleukin-34 concentrations were measured in human sepsis patients and healthy individuals. The effects of interleukin-34 administration on survival, bacterial burden, organ injury, and inflammatory response were assessed in a murine model of cecal ligation and puncture-induced polymicrobial sepsis. MEASUREMENTS AND MAIN RESULTS: Interleukin-34 levels were significantly elevated in human sepsis and cecal ligation and puncture-induced experimental sepsis. Interleukin-34 administration improved survival and bacterial clearance, although suppressed vascular leakage and organ injury after cecal ligation and puncture-induced polymicrobial sepsis. Neutralization of interleukin-34 increased mortality rate and decreased bacterial clearance in septic mice. An increased neutrophil and macrophage influx were developed in interleukin-34-treated mice at the site of infection, accompanied by elevated production of neutrophil chemokine chemokine (C-X-C motif) ligand 1 and macrophage chemokine C-C motif chemokine ligand 2 in the peritoneal cavity. Depletion of neutrophils or macrophages reversed interleukin-34-mediated protection against polymicrobial sepsis. CONCLUSIONS: We reported for the first time a potential therapeutic role for interleukin-34 in sepsis and suggested that interleukin-34 is a novel target for the development of therapeutic agents against sepsis.

Evaluation of a new hemoglobin A1c analyzer for point-of-care testing.

BACKGROUND: There has been an increasing desire for the use of point-of-care testing (POCT) by both primary care clinicians and patients. This study aimed to evaluate the performance of a new POCT analyzer for hemoglobin A1c (HbA1c) testing. METHODS: We assessed the accuracy, precision, and linearity of the POCT HbA1c analyzer (A1C EZ 2.0) with the Tosoh G8 Analyzer as comparative instrument, following the Clinical and Laboratory Standards Institute (CLSI) protocols. We evaluated sensitivity and specificity of the A1C EZ 2.0 in the clinical diagnosis of diabetes among 842 subjects from 79 communities in Beijing, China. RESULTS: Using regression analysis, the slope of the A1C EZ 2.0 vs the Tosoh G8 Analyzer was 0.9938, with an intercept of 0.0964 and a concordance correlation coefficient of 0.978. For precision, the reproducibility of CV (CVT ) were 3.7% and 2.7% at a lower (36 mmol/mol (5.4%)) and higher (107 mmol/mol (11.9%)) level of HbA1c respectively. The area under the receiver operating characteristic (ROC) curve for clinical diagnosis of diabetes was 0.911 with the HbA1c cut-off value of 44 mmol/mol (6.14%). At the HbA1c level of 48 mmol/mol (6.5%), the sensitivity and specificity were76.1% and 86.6%. CONCLUSION: The A1C EZ 2.0 has a high accuracy and precision, with a wide range of linearity, compared to a comparative laboratory instrument. It met analytical quality specifications and could be suitable for the clinical management of diabetes mellitus.

Contribution of Progranulin to Protective Lung Immunity During Bacterial Pneumonia.

Background: Progranulin (PGRN) is an important immunomodulatory factor in a variety of inflammatory diseases. However, its role in pulmonary immunity against bacterial infection remains unknown. Methods: Pneumonia was induced in PGRN-deficient and normal wild-type mice using Pseudomonas aeruginosa or Staphylococcus aureus, and we assessed the effects of PGRN on survival, bacterial burden, cytokine and chemokine production, and pulmonary leukocyte recruitment after bacterial pneumonia. Results: Patients with community-acquired pneumonia displayed elevated PGRN levels. Likewise, mice with Gram-negative and Gram-positive pneumonia had increased PGRN production in the lung and circulation. Progranulin deficiency led to increased bacterial growth and dissemination accompanied by enhanced lung injury and mortality in bacterial pneumonia, which was associated with impaired recruitment of macrophages and neutrophils in the lung. The reduced number of pulmonary macrophages and neutrophils observed in PGRN-deficient mice was related to a reduction of CCL2 and CXCL1 in the lungs after bacterial pneumonia. Importantly, therapeutic administration of PGRN improved mortality in severe bacterial pneumonia. Conclusions: This study supports a novel role for PGRN in pulmonary immunity and suggests that treatment with PGRN may be a viable therapy for bacterial pneumonia.

Interleukin 36α Attenuates Sepsis by Enhancing Antibacterial Functions of Macrophages.

Background: Sepsis is newly defined as life-threatening organ dysfunction caused by a dysregulated host response to infection with a high mortality rate and limited effective treatments. The role of interleukin 36α (IL-36α) in host response during sepsis remains unknown. Methods: An experimental sepsis model of cecal ligation and puncture was established to investigate the effects of IL-36α on host response to sepsis. Results: IL-36α production was significantly up-regulated during sepsis. IL-36α treatment reduced the mortality rate in mice with severe sepsis by cecal ligation and puncture. IL-36α-treated mice had more efficient bacterial clearance, inhibited tissue inflammation, improved organ injury, and reduced immune cell apoptosis. The therapeutic implication of these observations was also highlighted by the finding that specific blockade of IL-36α led to an increased mortality rate in mice with nonsevere sepsis. Furthermore, we found that IL-36α enhanced bacterial phagocytosis and killing by macrophages, thereby allowing local and systemic bacterial clearance. Importantly, macrophage depletion before the onset of sepsis eliminated IL-36α-mediated protection against sepsis. Conclusions: Our results demonstrate that IL-36α plays an important role in the host defense response to sepsis and suggest a potential therapeutic role for IL-36α in sepsis.

Purified Streptococcus pneumoniae Endopeptidase O (PepO) Enhances Particle Uptake by Macrophages in a Toll-Like Receptor 2- and miR-155-Dependent Manner.

Insights into the host-microbial virulence factor interaction, especially the immune signaling mechanisms, could provide novel prevention and treatment options for pneumococcal diseases. Streptococcus pneumoniae endopeptidase O (PepO) is a newly discovered and ubiquitously expressed pneumococcal virulence protein. A PepO-mutant strain showed impaired adherence to and invasion of host cells compared with the isogenic wild-type strain. It is still unknown whether PepO is involved in the host defense response to pneumococcal infection. Here, we demonstrated that PepO could enhance phagocytosis of Streptococcus pneumoniae and Staphylococcus aureus by peritoneal exudate macrophages (PEMs). Further studies showed that PepO stimulation upregulated the expression of microRNA-155 (miR-155) in PEMs in a time- and dose-dependent manner. PepO-induced enhanced phagocytosis was decreased in cells transfected with an inhibitor of miR-155, while it was increased in cells transfected with a mimic of miR-155. We also revealed that PepO-induced upregulation of miR-155 in PEMs was mediated by Toll-like receptor 2 (TLR2)-NF-κB signaling and that the increased expression of miR-155 downregulated expression of SHIP1. Taken together, these results indicate that PepO induces upregulation of miR-155 in PEMs, contributing to enhanced phagocytosis and host defense response to pneumococci and Staphylococcus aureus.

Progranulin Plays a Central Role in Host Defense during Sepsis by Promoting Macrophage Recruitment.

RATIONALE: Progranulin, a widely expressed protein, has multiple physiological functions. The functional role of progranulin in the host response to sepsis remains unknown. OBJECTIVES: To assess the role of progranulin in the host response to sepsis. METHODS: Effects of progranulin on host response to sepsis were determined. MEASUREMENTS AND MAIN RESULTS: Progranulin concentrations were significantly elevated in adult (n = 74) and pediatric (n = 26) patients with sepsis relative to corresponding healthy adult (n = 36) and pediatric (n = 17) control subjects, respectively. By using a low-lethality model of nonsevere sepsis, we observed that progranulin deficiency not only increased mortality but also decreased bacterial clearance during sepsis. The decreased host defense to sepsis in progranulin-deficient mice was associated with reduced macrophage recruitment, with correspondingly impaired chemokine CC receptor ligand 2 (CCL2) production in peritoneal lavages during the early phase of sepsis. Progranulin derived from hematopoietic cells contributed to host defense in sepsis. Therapeutic administration of recombinant progranulin not only rescued impaired host defense in progranulin-deficient mice after nonsevere sepsis but also protected wild-type mice against a high-lethality model of severe sepsis. Progranulin-mediated protection against sepsis was closely linked to improved peritoneal macrophage recruitment. In addition, CCL2 treatment of progranulin-deficient mice improved survival and decreased peritoneal bacterial loads during sepsis, at least in part through promotion of peritoneal macrophage recruitment. CONCLUSIONS: This proof-of-concept study supports a central role of progranulin-dependent macrophage recruitment in host defense to sepsis, opening new opportunities to host-directed therapeutic strategy that manipulate host immune response in the treatment of sepsis.

Will heavy metals in the soils of newly submerged areas threaten the water quality of Danjiangkou Reservoir, China?

Soil heavy metal contents were measured in newly submerged areas of the Danjiangkou Reservoir, China. We aimed to determine the heavy metal distribution in this area and the associated ecological risk. Most of these heavy metal contents (except Pb and Mn) suggest enrichment compared with the background values of soils from Henan Province, especially As and Cd with mean geo-accumulation index (Igeo) values of 0.84 and 0.54. The spatial analysis results indicated that the highest heavy metal contents were distributed in the arable soils above 160m elevation, whereas low heavy metal contents were observed under other land-use types above 160m elevation. According to Igeo and EF values, Cd was the major heavy metal contaminant in the newly submerged area, Cr, Pb and Mn mainly originated from natural geochemical sources. In contrast, Ni, Cd, As, Cu, and Zn mainly originated from anthropogenic sources. Evaluation using the potential ecological risk (PER) method indicated that PER of individual elements were low in the studied soils, and the comprehensive PER index was at a moderate level, indicating heavy metals in the soils of newly submerged areas may not threaten the water quality of Danjiangkou Reservoir, especially in winter.

Modified HPLC-ESI-MS Method for Glycated Hemoglobin Quantification Based on the IFCC Reference Measurement Procedure and Its Application for Quantitative Analyses in Clinical Laboratories of China.

BACKGROUND: The level of glycated hemoglobin (HbA1c ) has been recognized as an important indicator of long-term glycemic control. However, the HbA1c measurement is not currently included as a diagnostic determinant in China. Current study aims to assess a candidate modified International Federation of Clinical Chemistry reference method for the forthcoming standardization of HbA1c measurements in China. METHODS: The HbA1c concentration was measured using a modified high-performance liquid chromatography-electrospray ionization-mass spectrometry (HPLC-ESI-MS) method. The modified method replaces the propylcyanide column with a C18 reversed-phase column, which has a lower cost and is more commonly used in China, and uses 0.1% (26.5 mmol/l) formic acid instead of trifluoroacetic acid. Moreover, in order to minimize matrix interference and reduce the running time, a solid-phase extraction was employed. The discrepancies between HbA1c measurements using conventional methods and the HPLC-ESI-MS method were clarified in clinical samples from healthy people and diabetic patients. Corresponding samples were distributed to 89 hospitals in Beijing for external quality assessment. RESULTS: The linearity, reliability, and accuracy of the modified HPLC-ESI-MS method with a shortened running time of 6 min were successfully validated. Out of 89 hospitals evaluated, the relative biases of HbA1c concentrations were < 8% for 74 hospitals and < 5% for 60 hospitals. Compared with other conventional methods, HbA1c concentrations determined by HPLC methods were similar to the values obtained from the current HPLC-ESI-MS method. CONCLUSION: The HPLC-ESI-MS method represents an improvement over existing methods and provides a simple, stable, and rapid HbA1c measurement with strong signal intensities and reduced ion suppression.