CARD9S12N facilitates the production of IL-5 by alveolar macrophages for the induction of type 2 immune responses.

The adaptor CARD9 functions downstream of C-type lectin receptors (CLRs) for the sensing of microbial infection, which leads to responses by the TH1 and TH17 subsets of helper T cells. The single-nucleotide polymorphism rs4077515 at CARD9 in the human genome, which results in the substitution S12N (CARD9S12N), is associated with several autoimmune diseases. However, the function of CARD9S12N has remained unknown. Here we generated CARD9S12N knock-in mice and found that CARD9S12N facilitated the induction of type 2 immune responses after engagement of CLRs. Mechanistically, CARD9S12N mediated CLR-induced activation of the non-canonical transcription factor NF-κB subunit RelB, which initiated production of the cytokine IL-5 in alveolar macrophages for the recruitment of eosinophils to drive TH2 cell-mediated allergic responses. We identified the homozygous CARD9 mutation encoding S12N in patients with allergic bronchopulmonary aspergillosis and revealed activation of RelB and production of IL-5 in peripheral blood mononuclear cells from these patients. Our study provides genetic and functional evidence demonstrating that CARD9S12N can turn alveolar macrophages into IL-5-producing cells and facilitates TH2 cell-mediated pathologic responses.

[Correlation Between Initial Postoperative Hemoglobin Value and Prognosis in Non-Cardiac Surgery Patients Receiving Intraoperative Blood Transfusion].

Objective: To analyze the relationship between initial (within 24 hours) postoperative hemoglobin (Hb) value and prognosis in non-cardiac surgery patients receiving intraoperative blood transfusion, and to provide support for sensible blood use in surgery. Methods: A retrospective analysis was performed on all patients aged 18 or older who underwent non-cardiac surgeries and who received intraoperative blood transfusion at West China Hospital, Sichuan University from 2012 to 2018. According to their initial postoperative Hb levels, the patients were divided into 6 groups, including Hb<75 g/L, 75 g/L≤Hb<85 g/L, 85 g/L≤Hb<95 g/L, 95 g/L≤Hb<105 g/L, 105 g/L≤Hb<115 g/L, and Hb≥115 g/L goups. Multivariate linear regression was performed to examine the differences in the length-of-stay between the groups and binary logistic regression analysis was conducted to examine the differences between the groups in inpatient mortality, the rate of patient voluntary discharge against medical advice, incidence of acute ischemic injury, including acute kidney injury, myocardial infarction, and cerebral infarction, and length-of-stay longer than 28 days. In addition, the effects of multiple interactions between initial postoperative Hb and the types of surgery, the amount of intraoperative red blood cell infusion (red blood cell<8 U vs. red blood cell≥8 U), and preoperative anemia status (Hb<100 g/L vs. Hb≥100 g/L) on postoperative length-of-stay were analyzed. Results: A total of 7528 patients were included in this study. Compared to those of the reference group, the 95 g/L≤Hb<105 g/L group, the length-of-stay of patients with initial postoperative Hb<75 g/L increased and the mortality (odds ratio [ OR]=2.562) and the rate of voluntary discharge against medical advice ( OR=1.681) increased significantly. Patients in the 75 g/L≤Hb<85 g/L group had increased length-of-stay and increased incidence of acute ischemic injury ( OR=1.778) relative to the reference group. The interaction analysis showed that there was significant interaction between initial postoperative Hb and the types of surgery, which influenced the postoperative length-of-stay. Conclusion: In non-cardiac surgery patients who have receive blood transfusion, initial postoperative Hb<85 g/L is associated with poorer prognosis. However, those patients with higher initial postoperative Hb did not gain more benefits, suggesting that 85 g/L≤Hb<95 g/L may be the target Hb value for sensible intraoperative transfusion.

[Diterpenoids from Rabdosia flexicaulis].

The genus Rabdosia is famous for the abundance of diverse and novel ent-kaurane diterpenoids. However, only a few ent-kauranoids have been discovered from R. flexicaulis since the investigation on its chemical constituents is not systematic. To find novel bioactive diterpenoids, the ethyl acetate extract of the above ground part of R. flexicaulis in Daofu County, Sichuan Province was obtained by column chromatography. One new compound and five known ones were identified as flexicaulin E(1), forrestin B(2), inf-lexarabdonin D(3), 7α-hydroxydehydroabietic acid(4), 15-hydroxydehydroabietic acid(5), and pomiferin F(6) by spectral techniques. Compounds 1-3 were the ent-kaurane diterpenoids isolated from this species for the first time. Compounds 4-6, aromatic abie-tanoids, were isolated from the genus Rabdosia for the first time.

IL-4-Producing Dendritic Cells Induced during Schistosoma japonica Infection Promote Th2 Cells via IL-4-Dependent Pathway.

Although dendritic cells (DCs) have been widely demonstrated to play essential roles in initiation of Th2 responses in helminth infections and allergic reactions, the mechanisms remain uncertain largely because DCs do not produce IL-4. In present investigation, we have uncovered a novel subset of DCs from mice infected with Th2-provoking pathogens Schistosoma japonica, which independently promoted Th2 cells via IL-4-dependent pathway. These DCs contained similar levels of IL-4 mRNA and higher levels of IL-12p40 mRNA comparing to basophils, correlating to their Th2-promoting and Th1-promoting dual polarization capacities. Characterized by expression of FcεRI(+), these DCs were induced independent of T cells. Further investigations revealed that Th2-promoting FcεRI(+) DCs were monocyte-derived inflammatory DCs, which were sufficient to induce Th2 cells in vivo. Egg Ags together with GM-CSF or IL-3 alone were able to stimulate the generation of Th2-promoting FcεRI(+) DCs from bone marrow cells in vitro. To our knowledge, our data for the first time demonstrate that IL-4-producing DCs are induced under some Th2-provoking situations, and they should play important roles in initiation of Th2 response.

Interleukin-4- and NACHT, LRR and PYD domains-containing protein 3-independent mechanisms of alum enhanced T helper type 2 responses on basophils.

Aluminium hydroxide (alum), the most widely used adjuvant in human and animal vaccines, has long been known to promote T helper type 2 (Th2) responses and Th2-associated humoral responses, but the mechanisms have remained poorly understood. In this study, we explored whether alum is able to directly modulate antigen-presenting cells to enhance their potency for Th2 polarization. We found that alum treatment of dendritic cells failed to show any Th2-promoting activities. In contrast, alum was able to enhance the capacity of basophils to induce Th2 cells. When basophils from interleukin-4 (IL-4) knockout mice were examined, the intrinsic Th2-promoting activities by basophils were largely abrogated, but the alum-enhanced Th2-promoting activities on basophils were still detectable. More importantly, Th2-promoting adjuvant activities by alum found in IL-4 knockout mice were also largely reduced when basophils were depleted by antibody administration. Therefore, basophils can mediate Th2-promoting activities by alum both in vitro and in vivo through IL-4-independent mechanisms. Further studies revealed that secreted soluble molecules from alum-treated basophils were able to confer the Th2-promoting activities, and neutralization of thymic stromal lymphopoietin or IL-25 attenuated the IL-4-independent development of Th2 cells elicited by alum-treated basophils. Finally, alum was able to activate NACHT, LRR and PYD domains-containing protein 3 (NLRP3) inflammasome in murine basophils in the same way as alum in professional antigen-presenting cells, but NLRP3 was not required for Th2-promoting activities on basophils by alum in vitro. These results demonstrated that alum can enhance the capacities of basophils to polarize Th2 cells via IL-4- and NLRP3-independent pathways.

Psychological maladjustment of Asian and African peacekeepers in Liberia and its related factors.

This study aimed to investigate the maladjustment of Asian (Bangladeshi, Pakistani) and African (Nigerian, Namibian, Ghanaian) peacekeepers and its major influence factors. By random cluster sampling, 300 Asian peacekeepers and 271 African peacekeepers were administered the military psychological maladjustment scale (MPMS) and risk factors questionnaire. Investigation at Day 7 and Day 120 into the peacekeeping deployment period indicated that MPMS total score and factor scores of the Asian peacekeepers were significantly lower than those of the African peacekeepers (p < .01). The total score and each factor score of MPMS of the Asian peacekeepers significantly decreased (p < .01); for the African peacekeepers, only the factor score of emotional disorder of MPMS significantly decreased (p < .05). Stepwise regression analysis showed that the education duration was the influence factor for the emotional disorder factor score in the Asian peacekeepers, and the two factors were positively correlated. Age, military service duration, education duration and marital status were the major influence factors for the MPMS factors of the African peacekeepers, among which age was negatively correlated with the total score and each factor score, and military service duration, education duration and marital status were positively related. We conclude that the Asian peacekeepers are more adaptable and resilient than the African peacekeepers. Education duration was the major influence factor for Emotional Disorder in the Asian peacekeepers. The major influence factors for maladjustment in the African peacekeepers were age, military service duration, education duration and marital status.

[Research on Assessment Methods of Spectrum Data Quality of Core Scan].

Core scan is the instrument used for core spectrum and pictures detection that has been developed in recent years. Cores' data can be digitized with this equipment, then automatic core catalog can be achieved, which provides basis for geological research, mineral deposit study and peripheral deposit prospecting. Meanwhile, an online database of cores can be established by the means of core digitalization to solve the cost problem caused by core preservation and share resources. Quality of core data measurement directly affects the mineral identification, reliability of parameter inversion results. Therefore it's very important to quasi-manage the assessment of data quality with the instrument before cores' spectrum testing services. Combined with the independent R&D of CSD350A type core scan, and on the basis of spectroscopy basic theory, spectrum analysis methods, core spectrum analysis requirements, key issues such as data quality assessment methods, evaluation criteria and target parameters has been discussed in depth, and comprehensive assessment of independent R&D of core scan has been conducted, which indicates the reliability and validity of spectrum measurements of the instrument. Experimental tests show that the methods including test parameters and items can perfectly response the measurements of reflectance spectrum, wavelength accuracy, repeatability and signal to noise ratio with the instrument. Thus the quality of core scan data can be evaluated correctly, and the foundation of data quality for commercial services can be provided. In the case of the current lack of relevant assessment criteria, the method this study proposes for the assessment has great value in the work of core spectrum measurements.

Enantioselective synthesis of 3,3'-dihydropyrryl-spirooxindoles via an organocatalytic three-component reaction.

An organocatalytic three-component reaction of isatins, malononitrile and isocyanoacetates provided 3,3'-dihydropyrryl-spirooxindoles in excellent yields and enantioselectivities. The products could be readily converted to valuable 3,3'-pyrrolidinyl-spirooxindoles.

Organocatalytic conjugate addition of malononitrile to conformationally restricted dienones.

Organocatalytic conjugate addition of malononitrile to conformationally restricted dienones has been studied. A series of chiral primary and tertiary amine catalysts were screened. A piperidine-based thiourea-tertiary amine was found to be the efficient catalyst. Chiral pyran derivatives were obtained in excellent yields and enantioselectivities via a cascade conjugate addition-intramolecular cyclization pathway. The reaction is remarkably different for the corresponding reaction of conformationally flexible dienones.

Determination of the content of alkyl ketene dimer in its latex by an ionic-liquid assisted headspace gas chromatography.

This paper reports on an ionic-liquid assisted headspace gas chromatographic (HS-GC) for the determination of the content of alkyl ketene dimer (AKD) in its latex samples, in which the GC system was equipped with a thermal conductivity detector (TCD). The method was based on the AKD hydrolysis conducted in 1-butyl-3-methylimidazolium chloride (ionic-liquid) added medium at 100°C for 10min in a closed headspace sample vial, and the measured CO2 (the resulting product of the hydrolysis) by HS-GC. The results showed that the present method has a good measurement precision (RSD <2.3%) and accuracy (recoveries from 96 - 105%), and the limit of quantitation (LOQ) is 0.9%. The present method is very suitable to be used for the routine check of AKD content in its latex sample in mill applications. The study also showed that the content of AKD in the tested commercial latex samples were in the range of 3.5-12%.

Molecular visualizing and quantifying immune-associated peroxynitrite fluxes in phagocytes and mouse inflammation model.

Reactions of peroxynitrite (ONOO-) with biomolecules can lead to cytotoxic and cytoprotective events. Due to the difficulty of directly and unambiguously measuring its levels, most of the beneficial effects associated with ONOO- in vivo remain controversial or poorly characterized. Recently, optical imaging has served as a powerful noninvasive approach to studying ONOO- in living systems. However, ratiometric probes for ONOO- are currently lacking. Herein, we report the design, synthesis, and biological evaluation of F482, a novel fluorescence indicator that relies on ONOO--induced diene oxidation. The remarkable sensitivity, selectivity, and photostability of F482 enabled us to visualize basal ONOO- in immune-stimulated phagocyte cells and quantify its generation in phagosomes by high-throughput flow cytometry analysis. With the aid of in vivo ONOO- imaging in a mouse inflammation model assisted by F482, we envision that F482 will find widespread applications in the study of the ONOO- biology associated with physiological and pathological processes in vitro and in vivo.

Relationship between acute stress and sleep disorder in grass-root military personnel: mediating effect of social support.

BACKGROUND: Sleep disorder induced by acute stress has always been an important topic for study among the general population. However, the mediating effect of social support between acute stress and sleep disorder has rarely been reported before. METHODS: A total of 2,411 grass-root military personnel were randomly selected by cluster sampling, and administered the Chinese Military Personnel Sleep Disorder Scale, Military Acute Stress Scale and Social Support Rating Scale. RESULTS: The total score of acute stress scale was positively correlated with the total score and factor scores of sleep disorder scale (r = 0.209 ~ 0.465, P < 0.01); The total score of social support scale was positively correlated with the total score of acute stress scale and the total score and factor scores of sleep disorder scale (r = 0.356 ~ 0.537, P < 0.01). The analysis of mediating effects showed that lack of social support partially mediated between acute stress and the factors of sleep disorder. The analysis of structural equation model showed that acute stress not only had a direct effect on sleep disorder (the path coefficient was 0.29, P = 0.000), but also on lack of social support (the path coefficient was 0.39, P = 0.000); lack of social support had a direct effect on sleep disorder (the path coefficient was 0.48, P = 0.000). CONCLUSIONS: Acute stress and lack of social support are two significant factors of sleep disorder in grass-root military personnel. Well-established social support could alleviate sleep disorder induced by acute stress. Lack of social support was a partial mediator between acute stress and sleep disorder.

Scene-trait coping style of military rescuers in Wenchuan earthquake.

OBJECTIVE: This study aimed to explore the scene-trait coping style of military rescuers in Wenchuan earthquake in an effort to provide scientific evidences for mental intervention program for Chinese military personnel. METHODS: By cluster sampling, a total of 151 military rescuers and 331 control servicemen were administered the military personnel scene-trait coping style scale (MPSTCSS). RESULTS: All active coping factor scores, and passive coping factor scores of affection, health and economy in the rescuer group were significantly higher than those in control group (P < 0.05). The 21-above age subgroup, the 3-year plus service subgroup, and the officer subgroup had significantly higher active coping factor scores on military tasks, military experience and personal development than those of the 21-below age subgroup, 3-year minus service subgroup and the soldier subgroup, respectively (P < 0.05 or P < 0.01). CONCLUSION: The earthquake relief servicemen can cope with stressful situations better than control group by taking active coping style. The officers, servicemen older than 21 years, and servicemen with more service duration than 3 years could usually take active coping style.

Mental Health of Chinese Peacekeepers in Liberia

Background and Objectives: As part of UN peacekeeping operations in Liberia, China has sent a dozen of batches of peacekeeping force to Liberia for medical, engineering and transporting purposes from 2003 to 2012. This study aimed to explore the mental health of Chinese peacekeepers under the influence of stressful and traumatic events in Liberia. Methods: A total of 440 Chinese peacekeepers were selected by cluster sampling and surveyed by Chinese Military Mental Health Scale (CMMHS) before, during and after peacekeeping deployment. Results: The total CMMHS score (48.90 ± 21.15), depression factor (7.25 ± 3.43), interpersonal sensitivity (4.20 ± 2.15) of Chinese peacekeepers were significantly higher than the Chinese military norm (23.04 ± 14.70, 2.47 ± 2.46, 3.95 ± 2.97 respectively) (p<0.01). The total score and anxiety, somatization factor score of the transporting group were significantly higher than those of the medical group (P <0.05); All CMMHS factors in the transporting group and the medical group were higher than those of the engineering group (p<0.01). CMMHS factors score of the peacekeepers positively correlated with the age, military service duration, years of eudcation and military rank (r = 0.107 ~ 0.523, p<0.05); stepwise linear regression analysis revealed that years of eudcation was the main influence factor for peacekeepers' mental health (t = 2.288 ~ 4.358, p<0.05 ~ 0.01). Conclusions: The mental health status of Chinese peacekeepers was worse than average Chinese servicemen. Peacekeepers of different mission groups had different degree of mental damage, and the years of education was the main influence factor for peacekeepers' mental health, whereas age, military service duration as well as military rank were the secondary influence factors (AU)

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