Chelicerata sDscam isoforms combine homophilic specificities to define unique cell recognition.

Thousands of Down syndrome cell adhesion molecule (Dscam1) isoforms and ∼60 clustered protocadhrein (cPcdh) proteins are required for establishing neural circuits in insects and vertebrates, respectively. The strict homophilic specificity exhibited by these proteins has been extensively studied and is thought to be critical for their function in neuronal self-avoidance. In contrast, significantly less is known about the Dscam1-related family of ∼100 shortened Dscam (sDscam) proteins in Chelicerata. We report that Chelicerata sDscamα and some sDscamß protein trans interactions are strictly homophilic, and that the trans interaction is meditated via the first Ig domain through an antiparallel interface. Additionally, different sDscam isoforms interact promiscuously in cis via membrane proximate fibronectin-type III domains. We report that cell-cell interactions depend on the combined identity of all sDscam isoforms expressed. A single mismatched sDscam isoform can interfere with the interactions of cells that otherwise express an identical set of isoforms. Thus, our data support a model by which sDscam association in cis and trans generates a vast repertoire of combinatorial homophilic recognition specificities. We propose that in Chelicerata, sDscam combinatorial specificity is sufficient to provide each neuron with a unique identity for self-nonself discrimination. Surprisingly, while sDscams are related to Drosophila Dscam1, our results mirror the findings reported for the structurally unrelated vertebrate cPcdh. Thus, our findings suggest a remarkable example of convergent evolution for the process of neuronal self-avoidance and provide insight into the basic principles and evolution of metazoan self-avoidance and self-nonself discrimination.

Characterizing Fibrosis and Inflammation in a Partial Bile Duct Ligation Mouse Model by Multiparametric Magnetic Resonance Imaging.

BACKGROUND: Partial bile duct ligation (PBDL) model is a reliable cholestatic fibrosis experimental model that showed complex histopathological changes. Magnetic resonance imaging (MRI) features of PBDL have not been well characterized. PURPOSE: To investigate the potential of MRI parameters in assessing fibrosis in PBDL and explore the relationships between MRI and pathological features. ANIMAL MODEL: Established PBDL models. POPULATION: Fifty-four mice were randomly divided into four timepoints PBDL groups and one sham group. FIELD STRENGTH/SEQUENCE: 3.0 T; MRI sequences included T1-weighted fast spin-echo (FSE), T2-weighted single shot FSE, variable flip angle T1 mapping, multi-echo SE T2 mapping, multi-echo gradient-echo T2* mapping, and multi-b-value diffusion-weighted imaging. ASSESSMENT: MRI examination was performed at the corresponding timepoints after surgery. Native T1, ΔT1 (T1native-T1post), T2, T2*, apparent diffusion coefficient (ADC) values, histogram parameters (skewness and kurtosis), intravoxel incoherent motion parameters (f, D, and D* ) within the entire ligated (PBDL), non-ligated liver (PBDL), and whole liver (sham) were obtained. Fibrosis and inflammation were assessed in Masson and H&E staining slices using the Metavir and activity scoring system. STATISTICAL TESTS: One-way ANOVA, Spearman's rank correlation, and receiver operating characteristic curves were performed. P < 0.05 was considered statistically significant. RESULTS: Fibrosis and inflammation were finally staged as F3 and A3 in ligated livers but were not observed in non-ligated or sham livers. Ligated livers displayed significantly elevated native T1, ΔT1, T2, and reduced ADC and T2* than other livers. Spearman's correlation showed better correlation with inflammation (r = 0.809) than fibrosis (r = 0.635) in T2 and both ΔT1 and ADC showed stronger correlation with fibrosis (r = 0.704 and r = -0.718) than inflammation (r = 0.564 and r = -0.550). Area under the curve (AUC) for ΔT1 performed the highest (0.896). When combined with all relative parameters, AUC increased to 0.956. DATA CONCLUSION: Multiparametric MRI can evaluate and differentiate pathological changes in PBDL. ΔT1 and ADC better correlated with fibrosis while T2 stronger with inflammation. LEVEL OF EVIDENCE: 1 TECHNICAL EFFICACY: Stage 2.

Synergistic Effect between Zr-MOF and Phosphomolybdic Acid with the Promotion of TiF4 Template.

Metal-Organic Framework (MOF) materials are often modified or functionalized, and then the crystal size and morphology of MOF materials are changed. In the process of preparing UiO-66 confined phosphomolybdic acid (PMA) composites (PU), the TiF4-modified PU (PMA + UiO-66) composite catalyst (TiF4-PU) was successfully synthesized by adding titanium tetrafluoride, and the catalytic desulfurization activity was excellent. Similarly, the reaction mechanism was investigated by means of infrared spectroscopy, Raman spectroscopy, XPS, and UV/Vis spectroscopy. The results show that the addition of TiF4 not only changes the appearance and color of the catalyst, but also changes the valence distribution of the elements in the catalyst. The number of oxygen vacancies in the MOF increases due to the addition of TiF4, and more electrons are transferred from the Zr-MOF to PMA to form more Mo5+, which improved the performance of oxidative desulfurization in comparison. Thus, a stronger strong metal-support interaction (SMSI) effect is observed for TiF4-modified PU catalysts. In addition, the quenching experiment of free radicals shows that ·OH radical is the main active substance in the oxidative desulfurization reaction over TiF4-PU catalyst.

[Spectral characterization for capsanthin molecule with in vitro oxidative defense reaction].

The changes of UV-Vis and FTIR spectroscopic properties for capsanthin before and after reaction with exogenous superoxide anion (*O2(-)), hydrogen peroxide (H2O2) and hydroxyl radical (*OH), catalase (CAT), peroxidase (POD) and lipoxygenase (LOX) were explored. The results showed that, the UV-Vis spectral absorption of capsanthin treated with reactive oxygen species had a blue-shift. At the same time, the FTIR spectra changed significantly. The number of FTIR spectral peaks reduced and theFTIR strength weakened for capsanthin molecule treated with *O2(-) and *OH. The characteristic and strong peaks moved to shorter wavelengths when treated with H2O2. And LOX caused breakage of capsanthin molecule and reduction of peak number or groups without carbonyl. Exogenous H2O2 + CAT or H2O2 + POD treatment could not affect the UV-Vis and FTIR spectra significantly. So ROS could cause oxidative degradation of capsanthin and destroy chromophoric groups such as carbon-carbon double bond and carbonyl, then grow colorless alcohols. Hence ROS and LOX should transforms the conjugate system of capsanthin molecules, while CAT and POD could protect the capsanthin.

FOXP4-AS1 promotes CD8+ T cell exhaustion and esophageal cancer immune escape through USP10-stabilized PD-L1.

Esophageal cancer (EC) is the 9th most frequently diagnosed malignancy globally with unfavorable prognosis. Immune escape is one of the principal factors leading to poor survival, however, the mechanism underlying immune escape remains largely uninvestigated. The xenograft mouse model and EC cell-CD8+ cytotoxic T lymphocytes (CTLs) co-culture system were established. Immunohistochemistry, qRT-PCR or western blot were employed to detect the levels of long non-coding RNA (lncRNA) FOXP4-AS1, PD-L1, USP10 and other molecules. The abundance of T cells, cytokine production and cell apoptosis were monitored by flow cytometry. The viability of CTLs was assessed by Trypan blue staining. The binding between FOXP4-AS1 and USP10 was validated by RNA pull-down assay, and the interaction between USP10 and PD-L1, as well as the ubiquitination of PD-L1, were detected by co-immunoprecipitation. The elevation of FOXP4-AS1 in EC was associated with decreased CTL abundance, and upregulated PD-L1 facilitated CTL apoptosis in EC. FOXP4-AS1 accelerated EC tumor growth by decreasing the abundance of tumor infiltrating CTLs in vivo. FOXP4-AS1 inhibited the viability of CTLs and facilitated the cytotoxicity and exhaustion of CTLs. In Kyse 450 cell-CTL co-culture system, FOXP4-AS1 suppressed the viability and abundance of CTLs, and inhibited EC cell apoptosis via PD-L1. Mechanistically, FOXP4-AS1 regulated the ubiquitination of PD-L1 through deubiquitinating enzyme USP10. FOXP4-AS1 promoted CTL exhaustion and EC immune escape through USP10-stabilized PD-L1. HIGHLIGHTS: PD-L1 facilitated CD8+ T cell apoptosis in EC. Upregulated FOXP4-AS1 promoted EC tumor growth by inhibiting the viability and facilitating the cytotoxicity and exhaustion of tumor infiltrating CD8+ T cells. FOXP4-AS1 suppressed the viability and abundance of CD8+ T cells through USP10-mediated deubiquitination of PD-L1.

ß-amyloid peptide binds and regulates ectopic ATP synthase α-chain on neural surface.

Accumulation of the amyloid ß protein (Aß) in the brain is an important step in the pathogenesis of Alzheimer's disease. Many molecules could bind with Aß, among which some molecules mediate Aß neuronal toxicity. Thus, it is of interest to study the binding proteins of Aß, and the functions that might be affected by Aß. In the present study, we observed that accumulation of α-subunit of ATP synthase is associated with aggregates of Aß proteins in amyloid plaques of amyloid precursor protein/presennillin-1 transgenic mice, and identified the α-subunit of ATP synthase as one of the Aß binding proteins on the plasma membrane of neural cells by Western blot and mass spectrometry. In order to evaluate the consequences of the interaction between Aß and surface α-subunit of ATP synthase, the extracellular ATP generation was analyzed, which showed that aggregated Aß partially inhibited the extracellular generation of ATP, but was unable to significantly induce a decrease in cell surface ATP synthase α on neurons. These results suggest that the cell surface ATP synthase α is a binding protein for Aß on neural cells, the functional inhibition of surface ATP synthase might be involved in machinery of brain malfunction in Aß-mediated pathogenesis of Alzheimer's disease.

[To investigate the strategy of Chinese medicine for prevention and treatment of atherosclerosis based on vascular aging].

Atherosclerosis, a chronic degenerative disease mainly attacks the middle-aged and the aged population as they grow old. Anti-angiocellular aging has gradually become a new strategy for atherosclerosis. In the process of atherosclerosis developing, endothelial cell renewing is speeding. Various biological function disorders that induce blood vessel aging emerge, which leads to changes of the telomere and telomerase, resulting in aged endothelial cells and dysfunction. Telomere and telomerase may play key roles in the etiological factors such as inflammation and AS plaque. In our previous work we have found that Chinese compounds with Shen invigorating effects could not only obviously ameliorate the symptoms and functions of the senility, but also show significant effects on restraining atherosclerosis. We should actively study the mechanisms of Chinese medicine for treating atherosclerosis from Shen, and the mechanisms of Shen invigorating compounds for regulating angiocellular aging through the telomere pathway, thus providing evidence for establishing vascular cell aging based atherosclerosis prevention and treatment strategies by Chinese medicine.

[Dynamic proteomic analysis of liver tissue in the carbon tetrachloride-induced liver fibrosis rat model].

OBJECTIVE: To elucidate the dynamic physiopathologic mechanisms of liver fibrosis by investigating the differential proteome of liver tissue during progression of liver fibrosis in a chemically induced rat model. METHODS: Following treatment with carbon tetrachloride (CCl4), livers were harvested from rats at various time points. The respective total protein extracts were resolved by two-dimensional gel electrophoresis (2-DE) and compared to identify differentially expressed protein spots, which were then analyzed by matrix-assisted laser desorption/ionization two-stage time-of-flight mass spectrometry (MALDI-TOF/TOF-MS) and identified by database querying. The differential expression of selected proteins was validated by Western blotting and immunohistochemical methods. Statistical analyses were carried out by the least significant difference method of one-way ANOVA for parametric data or by the H test for non-parametric data. RESULTS: The severity scores of liver fibrosis increased in a time-dependent manner following CCl4 exposure (post-induction weeks: 3 less than 6 less than 9). Forty-four protein spots were different on the 2-DE maps for the different time points, among which the CK8 and CK18 proteins were identified and verified as significantly differentially expressed as liver fibrosis progressed. Protein expressions of CK8/CK18 were enhanced upon CCl4 exposure and increased over time (untreated controls: 0.113 ± 0.005/0.170 ± 0.030; CCl4-induced rats at week 3: 0.473 ± 0.046/0.530 ± 0.070, at week 6: 0.682 ± 0.087/0.780 ± 0.080, and at week 9: 0.837 ± 0.096/1.390 ± 0.130). Moreover, the rate of "a" determinant mutations for CK8/CK18 was also significantly differently between weeks 3, 6, and 9 (F = 196.085/74.088, 13.870/16.115, and 75.800/75.900, P less than 0.01). CONCLUSION: Dynamic proteomic analysis of liver tissue can indicate physiopathologic changes in protein expressions that are related to liver fibrosis induced by CCl4. Proteins with differential expression in CCl4-damaged fibrotic liver are associated with cell growth, development and differentiation, cell proliferation and apoptosis, angiogenesis or reconstitution, oxidative stress, substance metabolism and transport, and signal transduction.

Influence of Anhydrite on the Properties and Microstructure of Aluminophosphate Cement.

Aluminophosphate cement (APC) is a new type of hydraulic cementitious material with many potential functions. Microscopic analysis techniques were used to study the effect of anhydrite on the performance and hydration process of APC under standard curing conditions. The results show that adding an appropriate amount of anhydrite promotes the hydration of APC. The highest compressive strength is reached at an anhydrite content of 15 wt.%. As the anhydrite content increases, the APC's compressive strength decreases. The microscopic analysis of the hydration product morphology shows that the incorporation of anhydrite produces ettringite and other hydration products, improving the microstructure of the cement paste. The mercury intrusion porosimetry results show that the total porosity of the hardened APC paste decreases, and the microstructure becomes denser with an increase in the curing age, resulting in an increase in the compressive strength over time.

Multiparameter magnetic resonance imaging of liver fibrosis in a bile duct ligation mouse model.

BACKGROUND: Bile duct ligation (BDL) in animals is a classical method for mimicking cholestatic fibrosis. Although different surgical techniques have been described in rats and rabbits, mouse models can be more cost-effective and reproducible for investigating cholestatic fibrosis. Magnetic resonance imaging (MRI) has made great advances for noninvasive assessment of liver fibrosis. More comprehensive liver fibrotic features of BDL on MRI are important. However, the utility of multiparameter MRI to detect liver fibrosis in a BDL mouse model has not been assessed. AIM: To evaluate the correlation between the pathological changes and multiparameter MRI characteristics of liver fibrosis in a BDL mouse model. METHODS: Twenty-eight healthy adult male balb/c mice were randomly divided into four groups: sham, week 2 BDL, week 4 BDL, and week 6 BDL. Multiparameter MRI sequences, included magnetic resonance cholangiopancreatography, T1-weighted, T2-weighted, T2 mapping, and pre- and post-enhanced T1 mapping, were performed after sham and BDL surgery. Peripheral blood and liver tissue were collected after MRI. For statistical analysis, Student's t-test and Pearson's correlation coefficient were used. RESULTS: Four mice died after BDL surgery; seven, six, five and six mice were included separately from the four groups. Signal intensities of liver parenchyma showed no difference on TI- and T2-weighted images. Bile duct volume, ΔT1 value, T2 value, and the rate of liver fibrosis increased steadily in week 2 BDL, week 4 BDL and week 6 BDL groups compared with those in the sham group (P < 0.01). Alanine aminotransferase and aspartate transaminase levels initially surged after surgery, followed by a gradual decline over time. Strong correlations were found between bile duct volume (r = 0.84), T2 value (r = 0.78), ΔT1 value (r = 0.62), and hepatic fibrosis rate (all P < 0.01) in the BDL groups. CONCLUSION: The BDL mouse model induces changes that can be observed on MRI. The MRI parameters correlate with the hepatic fibrosis rate and allow for detection of cholestatic fibrosis.

Symptoms Based on Deficiency Syndrome in Traditional Chinese Medicine Might Be Predictor of Frailty in Elderly Community Dwellers.

BACKGROUND: The most widely used frailty phenotype and frailty indexes are either time-consuming or complicated, thus restricting their generalization in clinical practice; and therefore, an easier and faster screening tool is needed to be developed. OBJECTIVE: To select sensitive symptoms in traditional Chinese medicine (TCM) and study whether they can improve the risk prediction of frailty. METHODS: This is a cross-sectional study enrolling 2249 Chinese elderly community dwellers. Data were collected via face-to-face inquiries, anthropometric measurements, laboratory tests, and community health files. Frailty was the main outcome measure, and it was evaluated by Fried's frailty phenotype (FP). The ordinal logistic regression model was used to identify the factors associated with frailty. The risk assessment plot was used to compare the discriminative ability for frailty among models with and without TCM symptoms. RESULTS: The identified sensitive influential factors for frailty included age, education level, dietary habits, chronic obstructive pulmonary disease, diabetes, cerebral infarction, osteoporosis, cold limbs, lethargy and laziness in speaking and moving, weakness of lower limbs, slow movement, dry mouth and throat, and glazed expression. The risk prediction for "frailty cumulative components ≥1" was not significantly increased, while for "frailty cumulative components ≥2", a new model developed with the above selected TCM symptoms had a higher AUC than the baseline model without it (0.79 VS 0.81, P=0.002). And the NRI and IDI for the new model were 41.4% (P=0.016) and 0.024% (P=0.041), respectively. CONCLUSION: This research might provide an easier and faster way for early identification and risk prediction of frailty in elderly community dwellers.

[Mechanism of hepatocytes transdifferentiation to bile duct epithelial cells and intervention of huangqi decoction].

OBJECTIVE: To investigate the mechanism of hepatocytes transdifferentiation to bile duct epithelial cells (BECs) and intervention of Huangqi decoction (HQD) on hepatic fibrosis formation in rats with secondary cholestasis. METHODS: Seventy-five SD male rats were made into cholestatic hepatic fibrosis model animals by bile duct ligation, and randomized into the control group (n = 50) and the HQD group (n = 15). Starting from one week after modeling, they were administered orally with saline and HQD respectively for four weeks. Besides, a sham-operated group was set up with 10 rats operated by choledochus segregating only and administered after then with saline. Rats were killed in batches at different time points, i.e. each five from the control group and sham-operated group at the end of the 1st week, five from the control group for each time at the end of the 2nd, 3rd and 4th week, and all the remaining rats at the end of the 5th week. Their liver tissues were taken for histological change examination, content of hydroxyproline (Hyp) determination; protein expression of BECs marker cytokeratin 7 (CK7) and the hepatocyte specific antigen HepPar detection by Western blot, and CK7-Hep Par co-localization by laser confocal microscopy. Then IPP software was used to analyze Sirius red stained positive areas of CK7 and Hep Par, as well as the average IOD of CK7/Hep Par co-localization. RESULTS: Hepatocytes in hepatic tissues (Hep Par positive cell) in the model rats decreased gradually along was time went by after modeling (Sham > M1w > M2w > M3w > M4w > M5w), which was in parallel with the increase of BECs (CK7 positive cells), degree of fibrosis, Hyp content and CK7 protein expression. Increasing of co-localized positive cells of CK7/Hep Par began at 1 week and reached the peak 3 weeks after modeling, then it decreased gradually. The Hep Par protein expression was negatively correlated with that of CK7; the Hep Par positive cell expression was negatively correlated with CK7 positive cell expression and collagen deposition; while the CK7 positive cell expression was positively correlated with the collagen deposition in the liver tissue. Compared with the model control group, the mortality, CK7/Hep Par co-localized positive cells, fibrosis degree, Hyp content and CK7 protein expression were lesser obviously (P < 0.01), while Hep Par positive cell and protein expressions were higher significantly in the HQD group. CONCLUSIONS: Hepatocytes transdifferentiation to BECs might be a key pathological element for secondary cholestatic hepatic fibrosis formation; the restraining action of HQD is possibly a major action mechanism of HQD for effectively intervening and treating secondary cholestasis hepatic fibrosis.

[Effects of Yiguanjian Decoction on liver cirrhosis formation:a differential proteomics study in rats].

OBJECTIVE: To investigate the effects of Yiguanjian Decoction, a compound traditional Chinese herbal medicine, on rats with cirrhosis based on the method of differential proteomics. METHODS: Wistar male rats (n=48) were randomly divided into normal control group (n=12) and model-making group (n=36). Rat cirrhosis model was established by intraperitoneal injection of 50% carbon tetrachloride (CCl4) plus olive oil solution (1 mL/kg, twice weekly for 9 weeks). After 3- and 6-week injection, 6 rats each time were sacrificed for dynamic observation before medicine intervention, and the 24 remained rats were randomly divided into untreated group (n=12) and Yiguanjian Decoction group (n=12) at the first day of the 7th week. All animals were sacrificed by the end of the 9th week, and total protein of liver tissue was isolated by two-dimensional gel electrophoresis (2-DE); some differentially expressed protein spots were analyzed and identified by matrix-assisted laser desorption/ionization two-stage time-of-flight mass spectrometry (MALDI-TOF/TOF-MS) and database querying. Protein expressions of Cu/Zn superoxide dismutase (Cu/Zn SOD) and DJ-1 were validated by Western blot and immunohistochemical methods. RESULTS: 2-DE maps with high resolution and good repeatability were obtained. In all 50 protein spots identified by MALDI-TOF/TOF-MS and database querying, there were 5 protein spots related to oxidative stress named Cu/Zn SOD, DJ-1, glutathione synthetase, glutathione S-transferase Yb-1 subunit and aldo-keto reductase family 7, A2 respectively. Compared with the normal control group, expressions of Cu/Zn SOD, DJ-1, glutathione S-transferase Yb-1 subunit and aldo-keto reductase family 7, A2 in the untreated group were decreased significantly. Expressions of Cu/Zn SOD and aldo-keto reductase family 7, A2 were decreased time-dependently. Compared with the untreated group in 9th week, protein expressions of Cu/Zn SOD, DJ-1, glutathione S-transferase Yb-1 subunit and aldo-keto reductase family 7, A2 in the Yiguanjian Decoction groups were increased significantly while expression of glutathione synthetase was decreased notably. Western blot and immunohistochemical results of Cu/Zn SOD and DJ-1 expressions coincided with proteomics results. CONCLUSION: Anti-oxidative depression is a key pathological change of cirrhosis induced by CCl4 in rats, and increasing expression of proteins related to anti-oxidative stress may be a major mechanism of Yiguanjian Decoction in treating cirrhosis induced by CCl4 effectively.

Nano-MOF@defected film C3N4 Z-scheme composite for visible-light photocatalytic nitrogen fixation.

Photocatalytic nitrogen fixation has attracted extensive attention in recent years. Studies have shown that catalytic materials with O, N and other defects can effectively reduce the bond energy of N[triple bond, length as m-dash]N triple bond when N2 is adsorbed on the defects. As an outstanding non-metallic catalyst, g-C3N4 has been widely studied in the field of photocatalytic catalysis, and the nitrogen-defected C3N4 shows promoted photocatalytic activity. Herein, nano-size MOF-74 particles (<20 nm) was dispersed on nitrogen-defected C3N4 thin film (∼4 nm) via a simple sol-gel method. The combination of Nano-MOF and defected film C3N4 could effectively improve the photocatalytic activity of nitrogen fixation through Z-scheme mechanism compared with pure defected film C3N4.

Effect of Quercetin on Atherosclerosis Based on Expressions of ABCA1, LXR-α and PCSK9 in ApoE-/- Mice.

OBJECTIVE: To investigate the effect of quercetin on ATP binding cassette transporter A1 (ABCA1), liver X receptor (LXR), and proprotein convertase subtilisin/kexin type 9 (PCSK9) expressions in apoE-knockout (ApoE-/-) mice. METHODS: The high-fat diet-induced atherosclerosis (AS) in ApoE-/- mice was established. Thirty-six mice were divided into 3 groups using random number table method: model group (n=12), quercetin group (n=12), and atorvastatin group (n=12), with C57BL/6J mice of the same strain and age as the control group (n=12). Quercetin group and atorvastatin group were administrated with quercetin and atorvastatin by oral gavage, with doses of 12.5 and 4 mg/(kg•d), respectively. Animals in the control and model groups were given an equal volume of distilled water by oral gavage once per day for a total of 12 weeks. Western blot and immunohistochemical methods were employed to determine the aortic ABCA1, LXR-α and PCSK9 protein expression. Enzyme linked immunosorbent assay method was used to detect the expression of serum total cholesterol (TC), triglyceride (TG), high density lipoprotein-cholesterol (HDL-C), low density lipoprotein-cholesterol (LDL-C), tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and IL-10, combined with tissue pathological examination. RESULTS: ApoE-/- mice fed with a high-fat diet had notable atherosclerosis lesions, with reduced ABCA1, LXR-α and IL-10 levels (all P<0.01), elevated PCSK9, TNF-α and IL-6 expression, and increased TC and LDL-C contents (all P<0.01). After quercetin intervention, the areas of AS plaques and the expressions of PCSK9, TNF-α and IL-6 were significantly reduced (all P<0.01), while the expressions of ABCA1 and LXR-α were increased significantly (all P<0.01). CONCLUSION: Quercetin effectively interfered with AS development by regulating the expressions of ABCA1, LXR- α and PCSK9 in ApoE-/- mice.

[Progress and challenges of global malaria elimination].

Recently, the global malaria control has achieved remarkable results, and the epidemic map of malaria has gradually shrinked. However, in the past two years, the number of malaria deaths remained at a high level, and the incidence of malaria has even risen, leading to the stagnant of malaria elimination. The main reasons include lacking of the well monitoring and response system, sensitivity declining of antimalarial drugs, the spread of insecticide resistance, and the reduction of financial support. This paper introduces the progress and challenges of global malaria elimination, summarizes the current strategies and major interventions, and provides the corresponding response.

Tiaoxin Recipe, a Chinese herbal formula, inhibits microRNA-34a expression in the APPswe/PS1ΔE9 mouse model of Alzheimer's disease.

OBJECTIVE: To investigate the effect and underlying mechanisms of Tiaoxin Recipe (a Chinese herbal formula) treatment on Alzheimer's disease (AD). METHODS: Twelve-week-old APPswe/PS1ΔE9 (APP/PS1) double transgenic mice were used as a model of AD-afflicted mice. One group of mice was treated with Tiaoxin Recipe by gastrogavage for 12 weeks, while two other groups were given intraperitoneal injections of nicotinamide adenine dinucleotide or FK866 for 4 weeks. Morris water maze and thioflavin S staining tests were performed to evaluate cognitive impairment and amyloid plaque deposition, respectively. Serum amyloid-ß1-42 (Aß1-42) content was detected using an enzyme-linked immunosorbent assay, and quantitative reverse transcription-polymerase chain reaction was performed to examine the expression levels of microRNA-34a (miR-34a) in cortex and hippocampus samples of the study mice. RESULTS: Compared with the normal control group, the memory and learning abilities of the APP/PS1 model group were found to be impaired (P < 0.01), as shown by the increased levels of senile plaque deposition in cortex and hippocampus (P < 0.01), miR-34a expression (P < 0.01) and serum Aß1-42 content (P < 0.01). Treatment with Tiaoxin Recipe significantly reduced memory impairment (P < 0.01) by reducing amyloid plaque accumulation in cortex and hippocampus (P < 0.01), miR-34a expression (P < 0.01) and serum Aß1-42 content (P < 0.01) in APP/PS1 mice. CONCLUSION: Tiaoxin Recipe is a viable complementary or alternative therapeutic treatment that is capable of delaying the development of early-stage AD by inhibiting the expression of miR-34a.

[Epidemiological analysis of malaria prevalence in Jiangsu Province in 2017].

OBJECTIVE: To understand the malaria epidemic situation and characteristics in Jiangsu Province in 2017, so as to provide the evidence for formulating the targeted strategy of malaria elimination. METHODS: The data of malaria cases in Jiangsu Province in 2016 were collected from China's Routine Diseases Surveillance Information System (CRDSIS). RESULTS: Totally, 239 imported malaria cases were reported in Jiangsu Province in 2017, and the cases decreased by 22.40% compared to 308 cases in 2015. Except 2 malaria case caused by blood transfusion, the rest patients were all imported. Among them, there were 163 falciparum malaria cases, 21 vivax malaria cases, 11 quartan malaria cases, 43 ovale malaria cases, and 1 mixed infection case (Plasmodium falciparum and P. ovale). The numbers of imported cases of Nantong (39 cases, 16.32%), Suzhou (26 cases, 10.88%), Taizhou (25 cases, 10.46%), Huai'an (24 cases, 10.04%), and Lianyungang (22 cases, 9.21%) ranked in the top 5 cities across Jiangsu Province, the malaria cases in the five cities accounted for 56.90% (136/239). The infection source areas of the imported malaria cases included Africa (225 cases), Asia (8 cases), Oceania (2 cases), and South America (2 cases). CONCLUSIONS: Jiangsu Province has no local malaria cases for 6 consecutive years. Despite the imported cases in 2017 decreased some-what compared to that in 2016, it is still necessary to strengthen the surveillance of imported malaria cases and improve malaria diagnosis and treatment in the whole province.

New constructions of one- and two-stage pooling designs.

The study of gene functions requires a DNA library of high quality, such a library is obtained from a large mount of testing and screening. Pooling design is a very helpful tool for reducing the number of tests for DNA library screening. In this paper, we present new one- and two-stage pooling designs, together with new probabilistic pooling designs. The approach in this paper works for both error-free and error-tolerance scenarios.

A target role for mast cell in the prevention and therapy of hepatic fibrosis.

Hepatic fibrosis is a common pathological process of chronic hepatic disease. Despite the extensive studies, the pathophysiological mechanisms in hepatic fibrosis remain unclear. Mast cell has a variety of physiological and pathological functions through the production of heparin, histamine, neutrophil chemoattractants, immunoregulatory cytokines, and mast cell-specific serine proteases tryptase and chymase. The survival and proliferation of mast cell are dependent upon stem cell factor. More recently, the data have suggested that mast cell has been associated with hepatic fibrosis in many chronic liver diseases. However, to what extent the mast cell effects the hepatic fibrosis remains to be clarified. Several therapeutic approaches to inhibit mast cell activation have already demonstrated some clinical utility in tissue fibrosis or inflammatory diseases such as the use of mast cell stabilizers, inhibitors of tryptase or chymase, blockade of stem cell factor and anti-IgE therapy. The article introduces the hypothesis that mast cell has a central role when it is affected by its activation state in the progression of hepatic fibrosis, thus new therapeutic strategies for treatment of hepatic fibrosis are suggested by this hypothesis. Considering the important role of mast cell and the development of these tangible therapeutic approaches in hepatic fibrosis will enable us to target any types of chronic liver diseases, which appears to be a more reasonable or a promising strategy.