A New Phase of Networking: The Molecular Composition and Regulatory Dynamics of Mammalian Stress Granules.

Stress granules (SGs) are cytosolic biomolecular condensates that form in response to cellular stress. Weak, multivalent interactions between their protein and RNA constituents drive their rapid, dynamic assembly through phase separation coupled to percolation. Though a consensus model of SG function has yet to be determined, their perceived implication in cytoprotective processes (e.g., antiviral responses and inhibition of apoptosis) and possible role in the pathogenesis of various neurodegenerative diseases (e.g., amyotrophic lateral sclerosis and frontotemporal dementia) have drawn great interest. Consequently, new studies using numerous cell biological, genetic, and proteomic methods have been performed to unravel the mechanisms underlying SG formation, organization, and function and, with them, a more clearly defined SG proteome. Here, we provide a consensus SG proteome through literature curation and an update of the user-friendly database RNAgranuleDB to version 2.0 (http://rnagranuledb.lunenfeld.ca/). With this updated SG proteome, we use next-generation phase separation prediction tools to assess the predisposition of SG proteins for phase separation and aggregation. Next, we analyze the primary sequence features of intrinsically disordered regions (IDRs) within SG-resident proteins. Finally, we review the protein- and RNA-level determinants, including post-translational modifications (PTMs), that regulate SG composition and assembly/disassembly dynamics.

Study protocol: infectious diseases consortium (I3D) for study on integrated and innovative approaches for management of respiratory infections: respiratory infections research and outcome study (RESPIRO).

BACKGROUND: Community-acquired respiratory infections are a leading cause of illness and death globally. The aetiologies of community-acquired pneumonia remain poorly defined. The RESPIRO study is an ongoing prospective observational cohort study aimed at developing pragmatic logistical and analytic platforms to accurately identify the causes of moderate-to-severe community-acquired pneumonia in adults and understand the factors influencing disease caused by individual pathogens. The study is currently underway in Singapore and has plans for expansion into the broader region. METHODS: RESPIRO is being conducted at three major tertiary hospitals in Singapore. Adults hospitalised with acute community-acquired pneumonia or lower respiratory tract infections, based on established clinical, laboratory and radiological criteria, will be recruited. Over the course of the illness, clinical data and biological samples will be collected longitudinally and stored in a biorepository for future analysis. DISCUSSION: The RESPIRO study is designed to be hypothesis generating, complementary to and easily integrated with other research projects and clinical trials. The detailed clinical database and biorepository will yield insights into the epidemiology and outcomes of community-acquired lower respiratory tract infections in Singapore and the surrounding region and offers the opportunity to deeply characterise the microbiology and immunopathology of community-acquired pneumonia.

Intestinal microbiota disturbance affects the occurrence of African swine fever.

Intestinal microbiota not only participates in the digestion and absorption of nutrients, but also plays an important role in regulating host metabolism and health. The current study aimed to explore the intestinal microbiota characteristics in pigs infected with African swine fever. Below the same term, fresh fecal samples of sick and healthy pigs were collected. Primers were designed and PCR was extracted based on the 16S rDNA gene of bacteria by Illumina NovaSeq sequencing platform. The results showed that the bacterial alpha diversity index of healthy pigs was significantly higher than that of sick pigs (p < 0.05). On the phylum taxa, dominant bacteria more than 98.5% in the two groups are composed of Firmicutes, Spirobacteria, and Bacteroides, of which the abundance of Firmicutes and Bacteroidetes decreased and Spiricobacteria increased extremely significant in sick pigs (p < 0.01). On the genus taxa, the relative abundance of Oscillospira, Streptococcus and Roseburia decreased significantly (p < 0.05). Most notably, Treponema performed excellently in distinguishing pigs infected with African swine fever with the abundance increased extremely significantly (p < 0.01). In conclusion, African swine fever could alter the abundance of dominant bacteria in pigs, and Treponema may be one of the important inducers for swine pathogenicity. HighlightsThe bacterial population composition in sick pigs and healthy pigs was basically similar, but the relative abundance of dominant bacteria was significantly difference.ASF could alter the abundance of dominant bacteria in pigs, and Treponema may be one of the important inducers for swine pathogenicity.These results will provide further evidence for the ASF infection in local pig farms and provide reference for their microecological control, which has important practical significance and social value for effective control of ASF, stability of pig production and guarantee of market supply.

Room-Temperature Macroscopic Coherence of Two Electron-Hole Plasmas in a Microcavity.

Macroscopic coherence of Bose condensates is a fundamental and practical phenomenon in many-body systems, such as the long-range correlation of exciton-polariton condensates with a dipole density typically below the exciton Mott-transition limit. Here we extend the macroscopic coherence of electron-hole-photon interacting systems to a new region in the phase diagram-the high-density plasma region, where long-range correlation is generally assumed to be broken due to the rapid dephasing. Nonetheless, a cooperative state of electron-hole plasma does emerge through the sharing of the superfluorescence field in an optical microcavity. In addition to the in situ coherence of e-h plasma, a long-range correlation is formed between two 8-µm-spaced plasma ensembles even at room temperature. Quantized and self-modulated correlation modes are generated for e-h ensembles in the plasma region. By controlling the distance between the two ensembles, multiple coupling regimes are revealed, from strong correlation to perturbative phase correlation and finally to an incoherent classical case, which has potential implications for tunable and high-temperature-compatible quantum devices.

Microbiota stratification and succession of amylase-producing Bacillus in traditional Chinese Jiuqu (fermentation starters).

BACKGROUND: Jiuqu are vital saccharifying and fermenting agents for Chinese fermented foods. Natural ventilation during Jiuqu fermentation causes changes in temperature, oxygen and moisture content, resulting in mass and heat gradients from the outer to inner areas of Jiuqu blocks. In the present study, microbiota stratification in Jiuqu was investigated by single molecule real-time sequencing and culture isolation. The contributors of Bacillus to amylase activity of Jiuqu and the dynamics of their biomass during Jiuqu fermentation were also analyzed. RESULTS: The dominant orders, genera and species between the inner and outer layers of Huangjiu qu (HJQ) were similar, although they displayed greater variance in two layers of Baijiu qu (BJQ). Bacillus possessed the highest diversity (including 27 species) in Jiuqu. Bacillus licheniformis, Bacillus altitudinis, Bacillus subtilis, Bacillus amyloliquefaciens and Bacillus megaterium were most prevalent in HJQ, whereas B. licheniformis, B. amyloliquefaciens and Bacillus cereus were dominant in BJQ. Isolates of B. amyloliquefaciens, B. subtilis and B. cereus exhibited high activities of amylase and glucoamylase. Quantification of Bacillus members possessing genes of α-amylase revealed that B. cereus and B. licheniformis were the most dominant microbes to secret α-amylase in Jiuqu and their biomass were increasing during Jiuqu fermentation. CONCLUSION: The present study demonstrates the microbial distribution in different layers of Jiuqu and clarifies the Bacillus species processing the activity of α-amylase. These results will help industries control the quality of Jiuqu by rationally selecting starters and optimizing their microbiota. © 2020 Society of Chemical Industry.

Remodeling of myocardial energy and metabolic homeostasis in a sheep model of persistent atrial fibrillation.

BACKGROUND: Atrial fibrillation (AF) is the most common progressive cardiac arrhythmia and is often associated with rapid contraction in both atria and ventricles. The role of atrial energy and metabolic homeostasis in AF progression is under-investigated. OBJECTIVES: To determine the remodeling of energy metabolism during persistent AF and the effect of eplerenone (EPL), an aldosterone inhibitor, on metabolic homeostasis. METHODS: A nonsustained atrial pacing sheep model was developed to simulate the progression of AF from paroxysmal to persistent. Metabolomic and proteomic analyses at termination of the experiment were used to analyze atrial tissues obtained from sheep in sham, sugar pill (SP) and EPL-treated groups. RESULTS: Proteomic analysis indicated that compared to the sham group, in SP group, fatty acid (FA) synthesis, FA oxidation, tricarboxylic acid (TCA) cycle processes and amino acids (AAs) transport and metabolism were reduced, while glycolytic processes were increased. In metabolomic analysis, the levels of intermediate metabolites of the glycolytic pathways, including 2-phosphoglyceric acid (2 PG), 1,3-bisphosphoglyceric acid (1,3 PG), and pyruvate, HBP (uridine diphosphate-N-acetylglucosamine, UDP-GlcNAc), TCA (citrate) and AAs were greater while the levels of the majority of lipid classes, including phosphatidic acid (PA), phosphatidylcholine (PC), phosphatidylglycerol (PG), glycerophosphoglycerophosphates (PGP), glycerophosphoinositols (PI) and glycerophosphoserines (PS), were decreased in the atria of SP group than in those of sham group. EPL-pretreatment decreased the expression of glut4 and increased the content of acylcarnitines and lipids, such as lyso phospholipids, phospholipids and neutral lipids. CONCLUSION: In the metabolic remodeling during AF, glucose and lipid metabolism were up- and down-regulated, respectively, to sustain TCA cycle anaplerosis. EPL partialy reversed the metabolic shifting.

Dicer1 dysfunction promotes stemness and aggression in endometrial carcinoma.

Endometrial carcinoma is one of the most common gynecological malignancies, but the molecular events involved in the development and progression of endometrial carcinoma remain unclear. Dicer1 and cancer stem cells play important roles in cell motility and survival. This study investigated the role of the let-7 family and Dicer1 in the stemness of endometrial carcinoma cells. We profiled Dicer1 expression in clinical samples and explored its relationship with stem cell-associated markers and clinical parameters. We showed that Dicer1 dysfunction leads to the enrichment of tumor stemness features and tumor aggression both in vitro and in vivo. We also identified the mechanism related to this potential tumor-predisposing phenotype: loss of Dicer1 induced abnormal expression of the let-7 family, which comprises well-known tumor suppressors, thus regulating stemness in endometrial carcinoma cells.

The ecological filter system for treatment of decentralized wastewater.

A vertical flow constructed wetland was combined with a biological aerated filter to develop an ecological filter, and to obtain the optimal operating parameters: The hydraulic loading was 1.55 m3/(m2·d), carbon-nitrogen ratio was 10, and gas-water ratio was 6. The experimental results demonstrated considerable removal efficiency of chemical oxygen demand (COD), ammonia nitrogen (NH4+-N), total nitrogen (TN), and total phosphorus (TP) in wastewater by the ecological filter, with average removal rates of 83.79%, 93.10%, 52.90%, and 79.07%, respectively. Concentration of NH4+-N after treatment met the level-A discharge standard of GB18918-2002. Compared with non-plant filter, the ecological filter improved average removal efficiency of COD, NH4+-N, TN, and TP by 13.03%, 25.30%, 14.80%, and 2.32%, respectively: thus, plants significantly contribute to the removal of organic pollutants and nitrogen. Through microporous aeration and O2 secretion of plants, the ecological filter formed an aerobic-anaerobic-aerobic alternating environment; thus aerobic and anaerobic microbes were active and effectively removed organic pollutants. Meanwhile, nitrogen and phosphorus were directly assimilated by plants and as nutrients of microorganisms. Meanwhile, pollutants were removed through nitrification, denitrification, filtration, adsorption, and interception by the filler. High removal rates of pollutants on the ecological filter proved that it is an effective wastewater-treatment technology for decentralized wastewater of mountainous towns.

The genetic basis of population fecundity prediction across multiple field populations of Nilaparvata lugens.

Identifying the molecular markers for complex quantitative traits in natural populations promises to provide novel insight into genetic mechanisms of adaptation and to aid in forecasting population dynamics. In this study, we investigated single nucleotide polymorphisms (SNPs) using candidate gene approach from high- and low-fecundity populations of the brown planthopper (BPH) Nilaparvata lugens Stål (Hemiptera: Delphacidae) divergently selected for fecundity. We also tested whether the population fecundity can be predicted by a few SNPs. Seven genes (ACE, fizzy, HMGCR, LpR, Sxl, Vg and VgR) were inspected for SNPs in N. lugens, which is a serious insect pest of rice. By direct sequencing of the complementary DNA and promoter sequences of these candidate genes, 1033 SNPs were discovered within high- and low-fecundity BPH populations. A panel of 121 candidate SNPs were selected and genotyped in 215 individuals from 2 laboratory populations (HFP and LFP) and 3 field populations (GZP, SGP and ZSP). Prior to association tests, population structure and linkage disequilibrium (LD) among the 3 field populations were analysed. The association results showed that 7 SNPs were significantly associated with population fecundity in BPH. These significant SNPs were used for constructing general liner models with stepwise regression. The best predictive model was composed of 2 SNPs (ACE-862 and VgR-816 ) with very good fitting degree. We found that 29% of the phenotypic variation in fecundity could be accounted for by only two markers. Using two laboratory populations and a complete independent field population, the predictive accuracy was 84.35-92.39%. The predictive model provides an efficient molecular method to predict BPH fecundity of field populations and provides novel insights for insect population management.

The TSC22D, WNK, and NRBP gene families exhibit functional buffering and evolved with Metazoa for cell volume regulation.

The ability to sense and respond to osmotic fluctuations is critical for the maintenance of cellular integrity. We used gene co-essentiality analysis to identify an unappreciated relationship between TSC22D2, WNK1, and NRBP1 in regulating cell volume homeostasis. All of these genes have paralogs and are functionally buffered for osmo-sensing and cell volume control. Within seconds of hyperosmotic stress, TSC22D, WNK, and NRBP family members physically associate into biomolecular condensates, a process that is dependent on intrinsically disordered regions (IDRs). A close examination of these protein families across metazoans revealed that TSC22D genes evolved alongside a domain in NRBPs that specifically binds to TSC22D proteins, which we have termed NbrT (NRBP binding region with TSC22D), and this co-evolution is accompanied by rapid IDR length expansion in WNK-family kinases. Our study reveals that TSC22D, WNK, and NRBP genes evolved in metazoans to co-regulate rapid cell volume changes in response to osmolarity.

[Seasonal Variations and Source Apportionment of Carbonaceous Components in Luoyang: Implication for Brown Carbon Contribution].

A total of 98 samples were collected to analyze the seasonal variation and source apportionment of carbonaceous components, especially brown carbon (BrC), of PM2.5in Luoyang during 2018-2019. The concentrations of organic carbon (OC) and elemental carbon (EC) ranged from (7.04±1.82) µg·m-3to(23.81±8.68) µg·m-3and (2.96±1.4) µg·m-3to (13.41±7.91) µg·m-3, respectively, showing the seasonal variation of being high in winter and low in summer; the carbonaceous fraction and secondary organic aerosol percentages were higher by 8.33%-141.03% and by 0.77%-63.14%, respectively, compared with that in 2015. The light absorption cross section (MAC) values showed different seasonal variations with the concentration of carbonaceous fraction, shown in descending order as autumn (7.67 m2·g-1)>winter (5.65 m2·g-1)>spring (5.13 m2·g-1)>summer (3.84 m2·g-1). The MAC values ranged from 3.84 to 7.67 m2·g-1 at 445 nm, which was lower than that in coal ash. Seasonal variation in light absorption and the contribution of BrC to total light absorption (babs,BrC,405 nm, babs,BrC,405 nm/babs,405 nm) in descending order was winter (31.57 Mm-1, 33%), autumn (11.40 Mm-1, 25%), spring (4.88 Mm-1, 23%), and summer (2.12 Mm-1, 21%). The proportion of carbonaceous components decreased as haze episodes evolved, whereas the contribution of light absorption of BrC increased, highlighting the important contribution of BrC to the total light absorption. The results of PMF and correlation coefficients of babs,BrC,405 nm and PM2.5 components indicated that motor vehicles and secondary nitrate contributed 27.7% and 24.0%, respectively. Our findings have significant scientific implications for the deep controlling of carbonaceous aerosol, especially for BrC, in Luoyang in the future.

Short-term effects of individual exposure to PM2.5 on hospital admissions for myocardial infarction and stroke: a population-based case-crossover study in Guangzhou, China.

Some studies have investigated the effects of PM2.5 on cardiovascular diseases based on the population-average exposure data from several monitoring stations. No one has explored the short-term effect of PM2.5 on cardiovascular hospitalizations using individual-level exposure data. We assessed the short-term effects of individual exposure to PM2.5 on hospitalizations for myocardial infarction (MI) and stroke in Guangzhou, China, during 2014-2019. The population-based data on cardio-cerebrovascular events were provided by Guangzhou Center for Disease Control and Prevention. Average annual percent changes (AAPCs) were used to describe trends in the hospitalization rates of MI and stroke. The conditional logistic regression model with a time-stratified case-crossover design was applied to estimate the effects of satellite-retrieved PM2.5 with 1-km resolution as individual-level exposure. Furthermore, we performed stratified analyses by demographic characteristics and season. There were 28,346 cases of MI, 188,611, and 36,850 cases of ischemic stroke (IS) and hemorrhagic stroke (HS), respectively, with an annual average hospitalization rate of 37.2, 247, and 48.4 per 100,000 people. Over the six-year study period, significant increasing trends in the hospitalization rates were observed with AAPCs of 12.3% (95% confidence interval [CI]: 7.24%, 17.6%), 13.1% (95% CI: 9.54%, 16.7%), and 9.57% (95% CI: 6.27%, 13.0%) for MI, IS, and HS, respectively. A 10 µg/m3 increase in PM2.5 was associated with an increase of 1.15% (95% CI: 0.308%, 1.99%) in MI hospitalization and 1.29% (95% CI: 0.882%, 1.70%) in IS hospitalization. A PM2.5-associated reduction of 1.17% (95% CI: 0.298%, 2.03%) was found for HS hospitalization. The impact of PM2.5 was greater in males than in females for MI hospitalization, and greater effects were observed in the elderly (≥ 65 years) and in cold seasons for IS hospitalization. Our study added important evidence on the adverse effect of PM2.5 based on satellite-retrieved individual-level exposure data.

Cone-beam computed tomography study of the incidence and characteristics of the second mesiobuccal canal in maxillary permanent molars.

Objective: This study aimed to review the characteristics of the second mesiobuccal canal (MB2) in the maxillary first and second permanent molars of 500 patients to analyze the incidence of MB2 and its connection with gender, age, tooth position, and mesiobuccal (MB) root length. The study also aimed to investigate the distribution of the root canal orifice on the pulp chamber floor to obtain an imaging reference for clinical practices related to maxillary molars in Fujian, China. Methods: In accordance with the enrollment criteria, cone-beam computed tomography images of the maxillofacial area were collected from 500 patients, including 1,000 maxillary first molars and 1,000 maxillary second molars. The patients were grouped according to gender and tooth position. The incidence of MB2 was observed, and the MB root length and distribution angle of the mesiobuccal-palatal-distobuccal root canal orifices were measured for statistical analysis. Results: The overall incidence of MB2 in maxillary first and second molars was 51.1% and 32.9%, respectively. The incidence of MB2 in maxillary molars was 50% in male patients and 35.45% in female patients, with a significant difference (p < 0.05). The incidence of MB2 in maxillary molars was significantly higher in subjects aged below 50 (especially in male patients) than those aged 50 and above. The MB root length of maxillary first and second molars with MB2 was longer than that without MB2, and the difference was statistically significant. An association was identified between the incidences of MB2 in contralateral molars of the same type and in ipsilateral adjacent molars. When MB2 occurred in the MB root of maxillary molars, the root canals were mostly classified as type IV, followed by type II. The angle formed by the MB-P-DB orifices on the pulp chamber floor in the maxillary first and second molars was (25.23 ± 5.20) and (20.17 ± 10.88)°respectively. Conclusion: The incidence of MB2 in maxillary molars is high in Fujian, China. The occurrence of MB2 is affected by gender, age, and length of MB root, and it occurs symmetrically in adjacent molars and in contralateral molars of the same type. In addition, the distribution law of the main root canal orifice at the pulp chamber floor is conducive to locating MB2, thereby guiding clinical operations.

Different Intestinal Microbiota with Growth Stages of Three-Breed Hybrid Pig.

The changes of intestinal microbiota are closely related to the growth and development of animals. The current study is aimed at exploring the composition of the microbial community of pigs at different growth stages. Fresh fecal samples of three-breed hybrid pigs at three developmental stages (60, 120, and 180 days of age) were collected. The microbial composition was analyzed based on the 16S rDNA gene of bacteria Illumina NovaSeq sequencing platform. The results showed that the intestinal microbiota of pigs was distributed in 22 phyla, 46 classes, 84 orders, 147 families, and 287 genera. Firmicutes, Bacteroides, Spirochaetae, Proteobacteria, and Actinobacteria were the dominant phyla. Lactobacillus, Streptococcus, SMB53, Oscillospira, and Prevotella were the dominant genera. Among them, the abundance of Lactobacillus and SMB53 increased first and then decreased, while the change of Oscillospira was opposite. In addition, the abundance of Streptococcus increased while that of Prevotella decreased gradually. Moreover, with the increase of time and body weight, the microbial diversity showed a decreasing trend. In conclusion, the intestinal microbial composition of the three-breed hybrid pigs was relatively stable during the fattening stage, but there were significant differences in abundance.

Individual exposure to ambient PM2.5 and hospital admissions for COPD in 110 hospitals: a case-crossover study in Guangzhou, China.

Few studies have evaluated the short-term association between hospital admissions and individual exposure to ambient particulate matter (PM2.5). Particularly, no studies focused on hospital admissions for chronic obstructive pulmonary disease (COPD) at the individual level. We assessed the short-term effects of PM2.5 on hospitalization admissions for COPD in Guangzhou, China, during 2014-2015, based on satellite-derived estimates of ambient PM2.5 concentrations at a 1-km resolution near the residential address as individual-level exposure for each patient. Around 40,002 patients with COPD admitted to 110 hospitals were included in this study. A time-stratified case-crossover design with conditional logistic regression models was applied to assess the effects of PM2.5 based on a 1-km grid data of aerosol optical depth provided by the National Aeronautics and Space Administration on hospital admissions for COPD. Further, we performed stratified analyses by individual demographic characteristics and season of hospital admission. Around 10 µg/m3 increase in individual-level PM2.5 was associated with an increase of 1.6% (95% confidence interval [CI]: 0.6%, 2.7%) in hospitalization for COPD at a lag of 0-5 days. The impact of PM2.5 on hospitalization for COPD was greater significantly in males and patients admitted in summer. Our study strengthened the evidence for the adverse effect of PM2.5 based on satellite-based individual-level exposure data.

Corrigendum: Detecting key functional components group and speculating the potential mechanism of Xiao-Xu-Ming decoction in treating stroke.

[This corrects the article DOI: 10.3389/fcell.2022.753425.].

Detecting Key Functional Components Group and Speculating the Potential Mechanism of Xiao-Xu-Ming Decoction in Treating Stroke.

Stroke is a cerebrovascular event with cerebral blood flow interruption which is caused by occlusion or bursting of cerebral vessels. At present, the main methods in treating stroke are surgical treatment, statins, and recombinant tissue-type plasminogen activator (rt-PA). Relatively, traditional Chinese medicine (TCM) has widely been used at clinical level in China and some countries in Asia. Xiao-Xu-Ming decoction (XXMD) is a classical and widely used prescription in treating stroke in China. However, the material basis of effect and the action principle of XXMD are still not clear. To solve this issue, we designed a new system pharmacology strategy that combined targets of XXMD and the pathogenetic genes of stroke to construct a functional response space (FRS). The effective proteins from this space were determined by using a novel node importance calculation method, and then the key functional components group (KFCG) that could mediate the effective proteins was selected based on the dynamic programming strategy. The results showed that enriched pathways of effective proteins selected from FRS could cover 99.10% of enriched pathways of reference targets, which were defined by overlapping of component targets and pathogenetic genes. Targets of optimized KFCG with 56 components can be enriched into 166 pathways that covered 80.43% of 138 pathways of 1,012 pathogenetic genes. A component potential effect score (PES) calculation model was constructed to calculate the comprehensive effective score of components in the components-targets-pathways (C-T-P) network of KFCGs, and showed that ferulic acid, zingerone, and vanillic acid had the highest PESs. Prediction and docking simulations show that these components can affect stroke synergistically through genes such as MEK, NFκB, and PI3K in PI3K-Akt, cAMP, and MAPK cascade signals. Finally, ferulic acid, zingerone, and vanillic acid were tested to be protective for PC12 cells and HT22 cells in increasing cell viabilities after oxygen and glucose deprivation (OGD). Our proposed strategy could improve the accuracy on decoding KFCGs of XXMD and provide a methodologic reference for the optimization, mechanism analysis, and secondary development of the formula in TCM.

Detecting Critical Functional Ingredients Group and Mechanism of Xuebijing Injection in Treating Sepsis.

Sepsis is a systemic inflammatory reaction caused by various infectious or noninfectious factors, which can lead to shock, multiple organ dysfunction syndrome, and death. It is one of the common complications and a main cause of death in critically ill patients. At present, the treatments of sepsis are mainly focused on the controlling of inflammatory response and reduction of various organ function damage, including anti-infection, hormones, mechanical ventilation, nutritional support, and traditional Chinese medicine (TCM). Among them, Xuebijing injection (XBJI) is an important derivative of TCM, which is widely used in clinical research. However, the molecular mechanism of XBJI on sepsis is still not clear. The mechanism of treatment of "bacteria, poison and inflammation" and the effects of multi-ingredient, multi-target, and multi-pathway have still not been clarified. For solving this issue, we designed a new systems pharmacology strategy which combines target genes of XBJI and the pathogenetic genes of sepsis to construct functional response space (FRS). The key response proteins in the FRS were determined by using a novel node importance calculation method and were condensed by a dynamic programming strategy to conduct the critical functional ingredients group (CFIG). The results showed that enriched pathways of key response proteins selected from FRS could cover 95.83% of the enriched pathways of reference targets, which were defined as the intersections of ingredient targets and pathogenetic genes. The targets of the optimized CFIG with 60 ingredients could be enriched into 182 pathways which covered 81.58% of 152 pathways of 1,606 pathogenetic genes. The prediction of CFIG targets showed that the CFIG of XBJI could affect sepsis synergistically through genes such as TAK1, TNF-α, IL-1ß, and MEK1 in the pathways of MAPK, NF-κB, PI3K-AKT, Toll-like receptor, and tumor necrosis factor signaling. Finally, the effects of apigenin, baicalein, and luteolin were evaluated by in vitro experiments and were proved to be effective in reducing the production of intracellular reactive oxygen species in lipopolysaccharide-stimulated RAW264.7 cells, significantly. These results indicate that the novel integrative model can promote reliability and accuracy on depicting the CFIGs in XBJI and figure out a methodological coordinate for simplicity, mechanism analysis, and secondary development of formulas in TCM.

Point-of-care test of heart-type fatty acid-binding protein for the diagnosis of early acute myocardial infarction.

AIM: To investigate the efficacies of point-of-care test of heart-type fatty-acid binding protein (H-FABP) and its combinations with the conventional biomarkers in the diagnosis of early acute myocardial infarction (AMI). METHODS: 227 patients suspected of AMI were consecutively recruited in two centers. Biomarkers including H-FABP, myoglobin (MYO), creatine kinase-myocardial band (CK-MB) and cardiac troponin T (cTnT) were determined simultaneously at admission. AMI was defined according to the universal definition of myocardial infarction. Chi-Square test was adopted for the analysis. RESULTS: In patients presenting within 12 h of symptom onset, the sensitivity of H-FABP[93.0% (95% CI: 86.6%-96.9%)] was significantly higher than that of initial CK-MB [67.5% (95% CI: 58.1%-76.0%), P<0.0001], cTnT [69.3% (95%CI: 60.0%-77.6%), P<0.0001] and MYO [68.6% (95% CI: 54.1%-80.9%), P<0.05]. The negative predictive value of H-FABP [92.8% (95%CI: 86.3%-96.8%)] was significantly higher than that of initial CK-MB [74.7% (95% CI: 66.8%-81.5%), P<0.001] and cTnT [75.9% (95% CI: 68.1%-82.6%), P<0.001]. The sensitivity of H-FABP+cTnT combination [94.7% (95% CI: 88.9%-98.0%)] was significantly higher than that of admission cTnT [69.3% (95% CI: 60.0%-77.6%), P<0.0001], CK-MB+cTnT [75.4% (95% CI: 66.5%-83.0%), P<0.0001] and MYO+CK-MB+cTnT [74.5% (95% CI: 60.4%-85.7%), P<0.05]. The negative predictive value of H-FABP+cTnT [94.5% (95% CI: 88.4%-98.0%] was significantly higher than that of initial cTnT [75.9% (95% CI: 68.1%-82.6%), P<0.001] and CK-MB+cTnT [79.1% (95% CI: 71.2%-85.6%), P<0.001]. Subgroup analysis showed that the superiorities of both the sensitivities and the negative predictive values of H-FABP and H-FABP+cTnT combination occurred only in patients who presented within 6 h of the symptom onset. CONCLUSION: Point-of-care test of H-FABP can be used as a valuable biomarker to detect or exclude an early-stage AMI. Combining H-FABP and cTnT provides the best performance for early AMI diagnosis.

Plasmodium yoelii: influence of immune modulators on the development of the liver stage.

Plasmodium sporozoites suppress the respiratory burst and antigen presentation of Kupffer cells, which are regarded as the portal of invasion into hepatocytes. It is not known whether immune modulation of Kupffer cells can affect the liver stage. In the present study, we found that sporozoites inoculated into Wistar rats could be detected in the liver, spleen, and lung; however, most sporozoites were arrested in the liver. Sporozoites were captured by Kupffer cells lined with endothelial cells in the liver sinusoid before hepatocyte invasion. Pretreatment with TLR3 agonist poly(I:C) and TLR2 agonist BCG primarily activated Kupffer cells, inhibiting the sporozoite development into the exoerythrocytic form, whereas Kupffer cell antagonists dexamethasone and cyclophosphamide promoted development of the liver stage. Our data suggests that sporozoite development into its exoerythrocytic form may be associated with Kupffer cell functional status. Immune modulation of Kupffer cells could be a promising strategy to prevent malaria parasite infection.